Variability of Pinus halepensis Mill. Essential Oils and Their Antioxidant Activities Depending on the Stage of Growth During Vegetative Cycle.

PubMed

Djerrad, Zineb; Djouahri, Abderrahmane; Kadik, Leila

2017-04-01

The impact of growth stages during vegetative cycle (B 0  - B 5 ) on chemical composition and antioxidant activities of Pinus halepensis Mill. needles essential oils was investigated for the first time. GC and GC/MS analyses pointed to a quantitative variability of components; terpene hydrocarbons derivatives, represented by α-pinene (8.5 - 12.9%), myrcene (17.5 - 21.6%), p-cymene (7.9 - 11.9%) and (Z)-β-caryophyllene (17.3 - 21.2%) as major components, decreased from 88.9% at B 0 growth stage to 66.9% at B 5 growth stage, whereas oxygenated derivatives, represented by caryophyllene oxide (5.4 - 12.6%) and terpinen-4-ol (0.4 - 3.3%) as major components, increased from 7% at B 0 growth stage to 28.4% at B 5 growth stage. Furthermore, our findings showed that essential oil of P. halepensis needles collected at B 5 growth stage possess higher antioxidant activities by four different testing systems than those collected at B 0  - B 4 growth stages. This highlighted variability led to conclude that we should select essential oils to be investigated carefully depending on growth stage, in order to have the highest effectiveness of essential oil in terms of biological activities for human health purposes. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

HRV Analysis to Identify Stages of Home-based Telerehabilitation Exercise.

PubMed

Jeong, In Cheol; Finkelstein, Joseph

2014-01-01

Spectral analysis of heart rate variability (HRV) has been widely used to investigate activity of autonomous nervous system. Previous studies demonstrated potential of analysis of short-term sequences of heart rate data in a time domain for continuous monitoring of levels of physiological stress however the value of HRV parameters in frequency domain for monitoring cycling exercise has not been established. The goal of this study was to assess whether HRV parameters in frequency domain differ depending on a stage of cycling exercise. We compared major HRV parameters in high, low and very low frequency ranges during rest, height of exercise, and recovery during cycling exercise. Our results indicated responsiveness of frequency-domain indices to different phases of cycling exercise program and their potential in monitoring autonomic balance and stress levels as a part of a tailored home-based telerehabilitation program.

Age, stage and senescence in plants

PubMed Central

Caswell, Hal; Salguero-Gómez, Roberto

2013-01-01

1. Senescence (an increase in the mortality rate or force of mortality, or a decrease in fertility, with increasing age) is a widespread phenomenon. Theories about the evolution of senescence have long focused on the age trajectories of the selection gradients on mortality and fertility. In purely age-classified models, these selection gradients are non-increasing with age, implying that traits expressed early in life have a greater impact on fitness than traits expressed later in life. This pattern leads inevitably to the evolution of senescence if there are trade-offs between early and late performance. 2. It has long been suspected that the stage- or size-dependent demography typical of plants might change these conclusions. In this paper, we develop a model that includes both stage- and age-dependence and derive the age-dependent, stage-dependent and age×stage-dependent selection gradients on mortality and fertility. 3. We applied this model to stage-classified population projection matrices for 36 species of plants, from a wide variety of growth forms (from mosses to trees) and habitats. 4. We found that the age-specific selection gradients within a life cycle stage can exhibit increases with age (we call these contra-senescent selection gradients). In later stages, often large size classes in plant demography, the duration of these contra-senescent gradients can exceed the life expectancy by several fold. 5. Synthesis. The interaction of age- and stage-dependence in plants leads to selection pressures on senescence fundamentally different from those found in previous, age-classified theories. This result may explain the observation that large plants seem less subject to senescence than most kinds of animals. The methods presented here can lead to improved analysis of both age-dependent and stage-dependent demographic properties of plant populations. PMID:23741075

An interferon signature identified by RNA-sequencing of mammary tissues varies across the estrous cycle and is predictive of metastasis-free survival

DOE PAGES

Snijders, Antoine M.; Langley, Sasha; Mao, Jian-Hua; ...

2014-06-30

The concept that a breast cancer patient's menstrual stage at the time of tumor surgery influences risk of metastases remains controversial. The scarcity of comprehensive molecular studies of menstrual stage-dependent fluctuations in the breast provides little insight. To gain a deeper understanding of the biological changes in mammary tissue and blood during the menstrual cycle and to determine the influence of environmental exposures, such as low-dose ionizing radiation (LDIR), we used the mouse to characterize estrous-cycle variations in mammary gene transcripts by RNA-sequencing, peripheral white blood cell (WBC) counts and plasma cytokine levels. We identified an estrous-variable and hormone-dependent genemore » cluster enriched for Type-1 interferon genes. Cox regression identified a 117-gene signature of interferon-associated genes, which correlated with lower frequencies of metastasis in breast cancer patients. LDIR (10cGy) exposure had no detectable effect on mammary transcripts. However, peripheral WBC counts varied across the estrous cycle and LDIR exposure reduced lymphocyte counts and cytokine levels in tumor-susceptible mice. Our finding of variations in mammary Type-1 interferon and immune functions across the estrous cycle provides a mechanism by which timing of breast tumor surgery during the menstrual cycle may have clinical relevance to a patient's risk for distant metastases.« less

An interferon signature identified by RNA-sequencing of mammary tissues varies across the estrous cycle and is predictive of metastasis-free survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Snijders, Antoine M.; Langley, Sasha; Mao, Jian-Hua

The concept that a breast cancer patient's menstrual stage at the time of tumor surgery influences risk of metastases remains controversial. The scarcity of comprehensive molecular studies of menstrual stage-dependent fluctuations in the breast provides little insight. To gain a deeper understanding of the biological changes in mammary tissue and blood during the menstrual cycle and to determine the influence of environmental exposures, such as low-dose ionizing radiation (LDIR), we used the mouse to characterize estrous-cycle variations in mammary gene transcripts by RNA-sequencing, peripheral white blood cell (WBC) counts and plasma cytokine levels. We identified an estrous-variable and hormone-dependent genemore » cluster enriched for Type-1 interferon genes. Cox regression identified a 117-gene signature of interferon-associated genes, which correlated with lower frequencies of metastasis in breast cancer patients. LDIR (10cGy) exposure had no detectable effect on mammary transcripts. However, peripheral WBC counts varied across the estrous cycle and LDIR exposure reduced lymphocyte counts and cytokine levels in tumor-susceptible mice. Our finding of variations in mammary Type-1 interferon and immune functions across the estrous cycle provides a mechanism by which timing of breast tumor surgery during the menstrual cycle may have clinical relevance to a patient's risk for distant metastases.« less

Using a spatially structured life cycle model to assess the influence of multiple stressors on an exploited coastal-nursery-dependent population

NASA Astrophysics Data System (ADS)

Archambault, B.; Rivot, E.; Savina, M.; Le Pape, O.

2018-02-01

Exploited coastal-nursery-dependent fish species are subject to various stressors occurring at specific stages of the life cycle: climate-driven variability in hydrography determines the success of the first eggs/larvae stages; coastal nursery habitat suitability controls juvenile growth and survival; and fisheries target mostly adults. A life cycle approach was used to quantify the relative influence of these stressors on the Eastern English Channel (EEC) population of the common sole (Solea solea), a coastal-nursery-dependent flatfish population which sustains important fisheries. The common sole has a complex life cycle: after eggs hatch, larvae spend several weeks drifting in open water. Survivors go on to metamorphose into benthic fish. Juveniles spend the first two years of their life in coastal and estuarine nurseries. Close to maturation, they migrate to deeper areas, where different subpopulations supplied by different nurseries reproduce and are exploited by fisheries. A spatially structured age-and stage-based hierarchical Bayesian model integrating various aspects of ecological knowledge, data sources and expert knowledge was built to quantitatively describe this complex life cycle. The model included the low connectivity among three subpopulations in the EEC, the influence of hydrographic variability, the availability of suitable juvenile habitat and fisheries. Scenarios were designed to quantify the effects of interacting stressors on population renewal. Results emphasized the importance of coastal nursery habitat availability and quality for the population renewal. Realistic restoration scenarios of the highly degraded Seine estuary produced a two-third increase in catch potential for the adjacent subpopulation. Fisheries, however, remained the main source of population depletion. Setting fishing mortality to the maximum sustainable yield led to substantial increases in biomass (+100%) and catch (+33%) at the EEC scale. The approach also showed how climate-driven variability in hydrography is likely to interact with human pressures, e.g., overfishing increased the sensitivity to unfavourable conditions. Our results provided insights into the dynamics of numerous exploited coastal-nursery-dependent species while paving the way toward more robust advice for sustainable management of these resources.

Effects of menstrual cycle phase on cocaine self-administration in rhesus macaques.

PubMed

Cooper, Ziva D; Foltin, Richard W; Evans, Suzette M

2013-01-01

Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates. Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine's reinforcing effects than males, with estrous cycle stage as a key determinant of this effect. The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans. Dose-dependent intravenous cocaine self-administration (0.0125, 0.0250, and 0.0500 mg/kg/infusion) using a progressive-ratio schedule of reinforcement was determined across the menstrual cycle. The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone. Dependent variables including number of infusions self-administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase. Analysis of plasma hormone levels verified phase-dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase. Progressive ratio breakpoint, infusions self-administered, and cocaine intake did not consistently vary based on menstrual cycle phase. These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques. Copyright © 2012 Elsevier Inc. All rights reserved.

Stage-dependent piRNAs in chicken implicated roles in modulating male germ cell development.

PubMed

Chang, Kai-Wei; Tseng, Yen-Tzu; Chen, Yi-Chen; Yu, Chih-Yun; Liao, Hung-Fu; Chen, Yi-Chun; Tu, Yu-Fan Evan; Wu, Shinn-Chih; Liu, I-Hsuan; Pinskaya, Marina; Morillon, Antonin; Pain, Bertrand; Lin, Shau-Ping

2018-06-01

The PIWI/piRNA pathway is a conserved machinery important for germ cell development and fertility. This piRNA-guided molecular machinery is best known for repressing derepressed transposable elements (TE) during epigenomic reprogramming. The extent to which piRNAs are involved in modulating transcripts beyond TEs still need to be clarified, and it may be a stage-dependent event. We chose chicken germline as a study model because of the significantly lower TE complexity in the chicken genome compared to mammalian species. We generated high-confidence piRNA candidates in various stages across chicken germline development by 3'-end-methylation-enriched small RNA sequencing and in-house bioinformatics analysis. We observed a significant developmental stage-dependent loss of TE association and a shifting of the ping-pong cycle signatures. Moreover, the stage-dependent reciprocal abundance of LINE retrotransposons, CR1-C, and its associated piRNAs implicated the developmental stage-dependent role of piRNA machinery. The stage dependency of piRNA expression and its potential functions can be better addressed by analyzing the piRNA precursors/clusters. Interestingly, the new piRNA clusters identified from embryonic chicken testes revealed evolutionary conservation between chickens and mammals, which was previously thought to not exist. In this report, we provided an original chicken RNA resource and proposed an analytical methodology that can be used to investigate stage-dependent changes in piRNA compositions and their potential roles in TE regulation and beyond, and also revealed possible conserved functions of piRNAs in developing germ cells.

The Malaria Parasite Cyclin H Homolog PfCyc1 Is Required for Efficient Cytokinesis in Blood-Stage Plasmodium falciparum.

PubMed

Robbins, Jonathan A; Absalon, Sabrina; Streva, Vincent A; Dvorin, Jeffrey D

2017-06-13

All well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs), and these protein kinase complexes are viable drug targets. The regulatory control of the Plasmodium falciparum cell division cycle remains poorly understood, and the roles of the various CDKs and cyclins remain unclear. The P. falciparum genome contains multiple CDKs, but surprisingly, it does not contain any sequence-identifiable G 1 -, S-, or M-phase cyclins. We demonstrate that P. falciparum Cyc1 (PfCyc1) complements a G 1 cyclin-depleted Saccharomyces cerevisiae strain and confirm that other identified malaria parasite cyclins do not complement this strain. PfCyc1, which has the highest sequence similarity to the conserved cyclin H, cannot complement a temperature-sensitive yeast cyclin H mutant. Coimmunoprecipitation of PfCyc1 from P. falciparum parasites identifies PfMAT1 and PfMRK as specific interaction partners and does not identify PfPK5 or other CDKs. We then generate an endogenous conditional allele of PfCyc1 in blood-stage P. falciparum using a destabilization domain (DD) approach and find that PfCyc1 is essential for blood-stage proliferation. PfCyc1 knockdown does not impede nuclear division, but it prevents proper cytokinesis. Thus, we demonstrate that PfCyc1 has a functional divergence from bioinformatic predictions, suggesting that the malaria parasite cell division cycle has evolved to use evolutionarily conserved proteins in functionally novel ways. IMPORTANCE Human infection by the eukaryotic parasite Plasmodium falciparum causes malaria. Most well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs) to promote essential cell division processes. Remarkably, there are no identifiable cyclins that are predicted to control the cell cycle in the malaria parasite genome. Thus, our knowledge regarding the basic mechanisms of the malaria parasite cell cycle remains unsatisfactory. We demonstrate that P. falciparum Cyc1 (PfCyc1), a transcriptional cyclin homolog, complements a cell cycle cyclin-deficient yeast strain but not a transcriptional cyclin-deficient strain. We show that PfCyc1 forms a complex in the parasite with PfMRK and the P. falciparum MAT1 homolog. PfCyc1 is essential and nonredundant in blood-stage P. falciparum PfCyc1 knockdown causes a stage-specific arrest after nuclear division, demonstrating morphologically aberrant cytokinesis. This work demonstrates a conserved PfCyc1/PfMAT1/PfMRK complex in malaria and suggests that it functions as a schizont stage-specific regulator of the P. falciparum life cycle. Copyright © 2017 Robbins et al.

Optimality of cycle time and inventory decisions in a two echelon inventory system with exponential price dependent demand under credit period

NASA Astrophysics Data System (ADS)

Krugon, Seelam; Nagaraju, Dega

2017-05-01

This work describes and proposes an two echelon inventory system under supply chain, where the manufacturer offers credit period to the retailer with exponential price dependent demand. The model is framed as demand is expressed as exponential function of retailer’s unit selling price. Mathematical model is framed to demonstrate the optimality of cycle time, retailer replenishment quantity, number of shipments, and total relevant cost of the supply chain. The major objective of the paper is to provide trade credit concept from the manufacturer to the retailer with exponential price dependent demand. The retailer would like to delay the payments of the manufacturer. At the first stage retailer and manufacturer expressions are expressed with the functions of ordering cost, carrying cost, transportation cost. In second stage combining of the manufacturer and retailer expressions are expressed. A MATLAB program is written to derive the optimality of cycle time, retailer replenishment quantity, number of shipments, and total relevant cost of the supply chain. From the optimality criteria derived managerial insights can be made. From the research findings, it is evident that the total cost of the supply chain is decreased with the increase in credit period under exponential price dependent demand. To analyse the influence of the model parameters, parametric analysis is also done by taking with help of numerical example.

NeoPalAna: Neoadjuvant palbociclib, a cyclin-dependent kinase 4/6 inhibitor, and anastrozole for clinical stage 2 or 3 estrogen receptor positive breast cancer

PubMed Central

Ma, Cynthia X.; Gao, Feng; Luo, Jingqin; Northfelt, Donald W.; Goetz, Matthew; Forero, Andres; Hoog, Jeremy; Naughton, Michael; Ademuyiwa, Foluso; Suresh, Rama; Anderson, Karen S.; Margenthaler, Julie; Aft, Rebecca; Hobday, Timothy; Moynihan, Timothy; Gillanders, William; Cyr, Amy; Eberlein, Timothy J.; Hieken, Tina; Krontiras, Helen; Guo, Zhanfang; Lee, Michelle V.; Spies, Nicholas C.; Skidmore, Zachary L.; Griffith, Obi L.; Griffith, Malachi; Thomas, Shana; Bumb, Caroline; Vij, Kiran; Bartlett, Cynthia Huang; Koehler, Maria; Al-Kateb, Hussam; Sanati, Souzan; Ellis, Matthew J.

2017-01-01

Purpose Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the anti-proliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. Experimental Design Eligible patients with clinical stage II/III ER+/HER2- breast cancer received anastrozole 1mg daily for 4 weeks (cycle 0) (with goserelin if premenopausal), followed by adding palbociclib (125mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67>10%, in which case patients went off study due to inadequately response. Anastrozole was continued until surgery, which occurred 3-5 weeks post palbociclib exposure. Later patients received additional 10-12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression and mutation profiles. The primary endpoint was Complete Cell Cycle Arrest (CCCA: central Ki67<2.7%). Results Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs C1D1 26%, p<0.001). Palbociclib enhanced cell cycle control over anastrozole monotherapy regardless of luminal subtype (A vs B) and PIK3CA status with activity observed across a broad range of clinicopathological and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with non-luminal subtypes and persistent E2F-target gene expression. Conclusions Palbociclib is an active anti-proliferative agent for early-stage breast cancer resistant to anastrozole, however, prolonged administration may be necessary to maintain its effect. PMID:28270497

Predicting responses to climate change requires all life-history stages.

PubMed

Zeigler, Sara

2013-01-01

In Focus: Radchuk, V., Turlure, C. & Schtickzelle, N. (2013) Each life stage matters: the importance of assessing response to climate change over the complete life cycle in butterflies. Journal of Animal Ecology, 82, 275-285. Population-level responses to climate change depend on many factors, including unexpected interactions among life history attributes; however, few studies examine climate change impacts over complete life cycles of focal species. Radchuk, Turlure & Schtickzelle () used experimental and modelling approaches to predict population dynamics for the bog fritillary butterfly under warming scenarios. Although they found that warming improved fertility and survival of all stages with one exception, populations were predicted to decline because overwintering larvae, whose survival declined with warming, were disproportionately important contributors to population growth. This underscores the importance of considering all life history stages in analyses of climate change's effects on population dynamics. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

Evaluation of innovative rocket engines for single-stage earth-to-orbit vehicles

NASA Astrophysics Data System (ADS)

Manski, Detlef; Martin, James A.

1988-07-01

Computer models of rocket engines and single-stage-to-orbit vehicles that were developed by the authors at DFVLR and NASA have been combined. The resulting code consists of engine mass, performance, trajectory and vehicle sizing models. The engine mass model includes equations for each subsystem and describes their dependences on various propulsion parameters. The engine performance model consists of multidimensional sets of theoretical propulsion properties and a complete thermodynamic analysis of the engine cycle. The vehicle analyses include an optimized trajectory analysis, mass estimation, and vehicle sizing. A vertical-takeoff, horizontal-landing, single-stage, winged, manned, fully reusable vehicle with a payload capability of 13.6 Mg (30,000 lb) to low earth orbit was selected. Hydrogen, methane, propane, and dual-fuel engines were studied with staged-combustion, gas-generator, dual bell, and the dual-expander cycles. Mixture ratio, chamber pressure, nozzle exit pressure liftoff acceleration, and dual fuel propulsive parameters were optimized.

Evaluation of innovative rocket engines for single-stage earth-to-orbit vehicles

NASA Technical Reports Server (NTRS)

Manski, Detlef; Martin, James A.

1988-01-01

Computer models of rocket engines and single-stage-to-orbit vehicles that were developed by the authors at DFVLR and NASA have been combined. The resulting code consists of engine mass, performance, trajectory and vehicle sizing models. The engine mass model includes equations for each subsystem and describes their dependences on various propulsion parameters. The engine performance model consists of multidimensional sets of theoretical propulsion properties and a complete thermodynamic analysis of the engine cycle. The vehicle analyses include an optimized trajectory analysis, mass estimation, and vehicle sizing. A vertical-takeoff, horizontal-landing, single-stage, winged, manned, fully reusable vehicle with a payload capability of 13.6 Mg (30,000 lb) to low earth orbit was selected. Hydrogen, methane, propane, and dual-fuel engines were studied with staged-combustion, gas-generator, dual bell, and the dual-expander cycles. Mixture ratio, chamber pressure, nozzle exit pressure liftoff acceleration, and dual fuel propulsive parameters were optimized.

Complex life cycles and density dependence: assessing the contribution of egg mortality to amphibian declines.

PubMed

Vonesh, James R; De la Cruz, Omar

2002-11-01

In the last decade there has been increasing evidence of amphibian declines from relatively pristine areas. Some declines are hypothesized to be the result of egg mortality caused by factors such as elevated solar UV-B irradiation, chemical pollutants, pathogenic fungi, and climate change. However, the population-level consequences of egg mortality have not been examined explicitly, and may be complicated by density dependence in intervening life-history stages. Here we develop a demographic model for two amphibians with contrasting life-history strategies, Bufo boreas and Ambystoma macrodactylum. We then use the complementary approaches of elasticity and limitation to examine the relationships among stage-specific survival rates, larval-stage density dependence and amphibian population dynamics. Elasticity analyses showed that for a range of density dependence scenarios both species were more sensitive to changes in post-embryonic survival parameters, particularly juvenile survival, than to egg survival, suggesting that mortality of later stages may play an important role in driving declines. Limitation analyses revealed that larval density dependence can dramatically alter the consequences of early mortality, reducing or even reversing the expected population-level effects of egg mortality. Thus, greater focus on later life stages and density dependence is called for to accurately assess how stressors are likely to affect amphibian populations of conservation concern.

The cyclin-dependent kinase inhibitor p57Kip2 regulates cell cycle exit, differentiation, and migration of embryonic cerebral cortical precursors.

PubMed

Tury, Anna; Mairet-Coello, Georges; DiCicco-Bloom, Emanuel

2011-08-01

Mounting evidence indicates cyclin-dependent kinase (CDK) inhibitors (CKIs) of the Cip/Kip family, including p57(Kip2) and p27(Kip1), control not only cell cycle exit but also corticogenesis. Nevertheless, distinct activities of p57(Kip2) remain poorly defined. Using in vivo and culture approaches, we show p57(Kip2) overexpression at E14.5-15.5 elicits precursor cell cycle exit, promotes transition from proliferation to neuronal differentiation, and enhances process outgrowth, while opposite effects occur in p57(Kip2)-deficient precursors. Studies at later ages indicate p57(Kip2) overexpression also induces precocious glial differentiation, suggesting stage-dependent effects. In embryonic cortex, p57(Kip2) overexpression advances cell radial migration and alters postnatal laminar positioning. While both CKIs induce differentiation, p57(Kip2) was twice as effective as p27(Kip1) in inducing neuronal differentiation and was not permissive to astrogliogenic effects of ciliary neurotrophic factor, suggesting that the CKIs differentially modulate cell fate decisions. At molecular levels, although highly conserved N-terminal regions of both CKIs elicit cycle withdrawal and differentiation, the C-terminal region of p57(Kip2) alone inhibits in vivo migration. Furthermore, p57(Kip2) effects on neurogenesis and gliogenesis require the N-terminal cyclin/CDK binding/inhibitory domains, while previous p27(Kip1) studies report cell cycle-independent functions. These observations suggest p57(Kip2) coordinates multiple stages of corticogenesis and exhibits distinct and common activities compared with related family member p27(Kip1).

Magnetocaloric cycle with six stages: Possible application of graphene at low temperature

NASA Astrophysics Data System (ADS)

Reis, M. S.

2015-09-01

The present work proposes a thermodynamic hexacycle based on the magnetocaloric oscillations of graphene, which has either a positive or negative adiabatic temperature change depending on the final value of the magnetic field change. For instance, for graphenes at 25 K, an applied field of 2.06 T/1.87 T promotes a temperature change of ca. -25 K/+3 K. The hexacycle is based on the Brayton cycle and instead of the usual four steps, it has six stages, taking advantage of the extra cooling provided by the inverse adiabatic temperature change. This proposal opens doors for magnetic cooling applications at low temperatures.

Effects of copper oxide nanomaterials (CuONMs) are life stage dependent - full life cycle in Enchytraeus crypticus.

PubMed

Bicho, Rita C; Santos, Fátima C F; Scott-Fordsmand, Janeck J; Amorim, Mónica J B

2017-05-01

Copper oxide nanomaterials (CuONMs) have various applications in industry and enter the terrestrial environment, e.g. via sewage sludge. The effects of CuONMs and copper chloride (CuCl 2 ) were studied comparing the standard enchytraeid reproduction test (ERT) and the full life cycle test (FLCt) with Enchytraeus crypticus. CuONMs mainly affected growth or juveniles' development, whereas CuCl 2 mainly affected embryo development and/or hatching success and adults survival. Compared to the ERT, the FLCt allowed discrimination of effects between life stages and provided indication of the underlying mechanisms; further, the FLCt showed increased sensitivity, e.g. reproductive effects for CuONMs: EC 10  = 8 mg Cu/kg and EC 10  = 421 mg Cu/kg for the FLCt and the ERT respectively. The performance of the FLCt is preferred to the ERT and we recommend it as a good alternative to assess hazard of NMs. Effects of CuONMs and CuCl 2 are life stage dependent and are different between Cu forms. Copyright © 2017 Elsevier Ltd. All rights reserved.

The plurennial life cycles of the European Tettigoniidae (Insecta: Orthoptera) : 1. The effect of temperature on embryonic development and hatching.

PubMed

Ingrisch, Sigfrid

1986-11-01

The effect of temperature on embryonic development, voltinism, and hatching was studied in the laboratory in eggs of 21 Central and Southeastern European Tettigoniidae species. In most species, the embryo has to arrive at a postkatatrepsis stage prior to the onset of cold to be able to hatch in the following spring. The rate of embryonic development differs: quickly developing species need 4 weeks at 24°C (prior to cold) and almost all eggs hatch after the first cold treatment, slowly developing species would need 8-12 weeks to do the same. In Central Europe, warmth is not enough for the slowly developing species to have an univoltine life cycle, but they could have it in southern Europe. Most species make use of a dormancy sequence to pass successive winters as follows: an initial embryonic dormancy (either quiscence or diapause in embryonic stage 4) and a final diapause in embryonic stage 23/24. Additionally, 3 forms of aestivation or summer dormancy were observed facultatively: an initial diapause in embryonic stage 4 (induced and terminated at 30°C), a median dormancy shortly before or after katatrepsis (at 30°C), and a penultimate diapause in embryonic stage 20 (at 24°C).The life cycles of the European Tettigoniidae species can follow one of 3 types: 1. annual life cycle (no initial embryonic dormancy); 2. annual or biennial depending on whether laid early or late; 3. biennial or many year life cycle (up to 8 years due to a prolonged initial diapause).

The life cycle of thunderstorm gust fronts as viewed with Doppler radar and rawinsonde data

NASA Technical Reports Server (NTRS)

Wakimoto, R. M.

1982-01-01

This paper presents the time-dependent analysis of the thunderstorm gust front with the use of Project NIMROD data. RHI cross sections of reflectivity and Doppler velocity are constructed to determine the entire vertical structure. The life cycle of the gust front is divided into four stages: (1) the formative stage; (2) the early mature stage; (3) the late mature stage; and (4) the dissipation stage. A new finding is a horizontal roll detected in the reflectivity pattern resulting from airflow that is deflected upward by the ground, while carrying some of the smaller precipitation ahead of the main echo core of the squall line. This feature is called a 'precipitation roll'. As determined from rawinsonde data, the cold air behind the gust front accounts for the observed surface pressure rise. Calculations confirm that the collision of two fluids produce a nonhydrostatic pressure at the leading edge of the outflow. The equation governing the propagation speed of a density current accurately predicts the movement of the gust front.

Cyclin-dependent kinase inhibitor p20 controls circadian cell-cycle timing

PubMed Central

Laranjeiro, Ricardo; Tamai, T. Katherine; Peyric, Elodie; Krusche, Peter; Ott, Sascha; Whitmore, David

2013-01-01

Specific stages of the cell cycle are often restricted to particular times of day because of regulation by the circadian clock. In zebrafish, both mitosis (M phase) and DNA synthesis (S phase) are clock-controlled in cell lines and during embryo development. Despite the ubiquitousness of this phenomenon, relatively little is known about the underlying mechanism linking the clock to the cell cycle. In this study, we describe an evolutionarily conserved cell-cycle regulator, cyclin-dependent kinase inhibitor 1d (20 kDa protein, p20), which along with p21, is a strongly rhythmic gene and directly clock-controlled. Both p20 and p21 regulate the G1/S transition of the cell cycle. However, their expression patterns differ, with p20 predominant in developing brain and peak expression occurring 6 h earlier than p21. p20 expression is also p53-independent in contrast to p21 regulation. Such differences provide a unique mechanism whereby S phase is set to different times of day in a tissue-specific manner, depending on the balance of these two inhibitors. PMID:23569261

Cyclin-dependent kinase inhibitor p20 controls circadian cell-cycle timing.

PubMed

Laranjeiro, Ricardo; Tamai, T Katherine; Peyric, Elodie; Krusche, Peter; Ott, Sascha; Whitmore, David

2013-04-23

Specific stages of the cell cycle are often restricted to particular times of day because of regulation by the circadian clock. In zebrafish, both mitosis (M phase) and DNA synthesis (S phase) are clock-controlled in cell lines and during embryo development. Despite the ubiquitousness of this phenomenon, relatively little is known about the underlying mechanism linking the clock to the cell cycle. In this study, we describe an evolutionarily conserved cell-cycle regulator, cyclin-dependent kinase inhibitor 1d (20 kDa protein, p20), which along with p21, is a strongly rhythmic gene and directly clock-controlled. Both p20 and p21 regulate the G1/S transition of the cell cycle. However, their expression patterns differ, with p20 predominant in developing brain and peak expression occurring 6 h earlier than p21. p20 expression is also p53-independent in contrast to p21 regulation. Such differences provide a unique mechanism whereby S phase is set to different times of day in a tissue-specific manner, depending on the balance of these two inhibitors.

Expression of the proliferation marker Ki-67 during early mouse development.

PubMed

Winking, H; Gerdes, J; Traut, W

2004-01-01

In somatic tissues, the mouse Ki-67 protein (pKi-67) is expressed in proliferating cells only. Depending on the stage of the cell cycle, pKi-67 is associated with different nuclear domains: with euchromatin as part of the perichromosomal layer, with centromeric heterochromatin, and with the nucleolus. In gametes, sex-specific expression is evident. Mature MII oocytes contain pKi-67, whereas pKi-67 is not detectable in mature sperm. We investigated the re-establishment of the cell cycle-dependent distribution of pKi-67 during early mouse development. After fertilization, male and female pronuclei exhibited very little or no pKi-67, while polar bodies were pKi-67 positive. Towards the end of the first cell cycle, prophase chromosomes of male and female pronuclei simultaneously got decorated with pKi-67. In 2-cell embryos, the distribution pattern changed, presumably depending on the progress of development of the embryo, from a distribution all over the nucleus to a preferential location in the nucleolus precursor bodies (NPBs). From the 4-cell stage onwards, pKi-67 showed the regular nuclear relocations known from somatic tissues: during mitosis the protein was found covering the chromosome arms as a constituent of the perichromosomal layer, in early G1 it was distributed in the whole nucleus, and for the rest of the cell cycle it was associated with NPBs or with the nucleolus. Copyright 2004 S. Karger AG, Basel

Life histories of microalgal species causing harmful blooms: Haploids, diploids and the relevance of benthic stages.

PubMed

Figueroa, Rosa Isabel; Estrada, Marta; Garcés, Esther

2018-03-01

In coastal and offshore waters, Harmful Algal Blooms (HABs) currently threaten the well-being of coastal countries. These events, which can be localized or involve wide-ranging areas, pose risks to human health, marine ecosystems, and economic resources, such as tourism, fisheries, and aquaculture. Dynamics of HABs vary from one site to another, depending on the hydrographic and ecological conditions. The challenge in investigating HABs is that they are caused by organisms from multiple algal classes, each with its own unique features, including different life histories. The complete algal life cycle has been determined in <1% of the described species, although elucidation of the life cycles of bloom-forming species is essential in developing preventative measures. The knowledge obtained thus far has confirmed the complexity of the algal life cycle, which is composed of discrete life stages whose morphology, ecological niche (plankton/benthos), function, and lifespan vary. The factors that trigger transitions between the different stages in nature are mostly unknown, but it is clear that an understanding of this process provides the key to effectively forecasting bloom recurrence, maintenance, and decline. Planktonic stages constitute an ephemeral phase of the life cycle of most species whereas resistant, benthic stages enable a species to withstand adverse conditions for prolonged periods, thus providing dormant reservoirs for eventual blooms and facilitating organismal dispersal. Here we review current knowledge of the life cycle strategies of major groups of HAB producers in marine and brackish waters. Rather than providing a comprehensive discussion, the objective was to highlight several of the research milestones that have changed our understanding of the plasticity and frequency of the different life cycle stages as well as the transitions between them. We also discuss the relevance of benthic and planktonic forms and their implications for HAB dynamics. Copyright © 2018. Published by Elsevier B.V.

Keratin 17 modulates hair follicle cycling in a TNFα-dependent fashion

PubMed Central

Tong, Xuemei; Coulombe, Pierre A.

2006-01-01

Mammalian hair follicles cycle between stages of rapid growth (anagen) and metabolic quiescence (telogen) throughout life. Transition from anagen to telogen involves an intermediate stage, catagen, consisting of a swift, apoptosis-driven involution of the lower half of the follicle. How catagen is coordinated, and spares the progenitor cells needed for anagen re-entry, is poorly understood. Keratin 17 (K17)-null mice develop alopecia in the first week post-birth, correlating with hair shaft fragility and untimely apoptosis in the hair bulb. Here we show that this abnormal apoptosis reflects premature entry into catagen. Of the proapoptotic challenges tested, K17-null skin keratinocytes in primary culture are selectively more sensitive to TNFα. K17 interacts with TNF receptor 1 (TNFR1)-associated death domain protein (TRADD), a death adaptor essential for TNFR1-dependent signal relay, suggesting a functional link between this keratin and TNFα signaling. The activity of NF-κB, a downstream target of TNFα, is increased in K17-null skin. We also find that TNFα is required for a timely anagen–catagen transition in mouse pelage follicles, and that its ablation partially rescues the hair cycling defect of K17-null mice. These findings identify K17 and TNFα as two novel and interdependent regulators of hair cycling. PMID:16702408

Magnetocaloric cycle with six stages: Possible application of graphene at low temperature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reis, M. S., E-mail: marior@if.uff.br

2015-09-07

The present work proposes a thermodynamic hexacycle based on the magnetocaloric oscillations of graphene, which has either a positive or negative adiabatic temperature change depending on the final value of the magnetic field change. For instance, for graphenes at 25 K, an applied field of 2.06 T/1.87 T promotes a temperature change of ca. −25 K/+3 K. The hexacycle is based on the Brayton cycle and instead of the usual four steps, it has six stages, taking advantage of the extra cooling provided by the inverse adiabatic temperature change. This proposal opens doors for magnetic cooling applications at low temperatures.

Stable Density and Dynamics of Dendritic Spines of Cortical Neurons Across the Estrous Cycle While Expressing Differential Levels of Sensory-Evoked Plasticity.

PubMed

Alexander, Bailin H; Barnes, Heather M; Trimmer, Emma; Davidson, Andrew M; Ogola, Benard O; Lindsey, Sarah H; Mostany, Ricardo

2018-01-01

Periodic oscillations of gonadal hormone levels during the estrous cycle exert effects on the female brain, impacting cognition and behavior. While previous research suggests that changes in hormone levels across the cycle affect dendritic spine dynamics in the hippocampus, little is known about the effects on cortical dendritic spines and previous studies showed contradictory results. In this in vivo imaging study, we investigated the impact of the estrous cycle on the density and dynamics of dendritic spines of pyramidal neurons in the primary somatosensory cortex of mice. We also examined if the induction of synaptic plasticity during proestrus, estrus, and metestrus/diestrus had differential effects on the degree of remodeling of synapses in this brain area. We used chronic two-photon excitation (2PE) microscopy during steady-state conditions and after evoking synaptic plasticity by whisker stimulation at the different stages of the cycle. We imaged apical dendritic tufts of layer 5 pyramidal neurons of naturally cycling virgin young female mice. Spine density, turnover rate (TOR), survival fraction, morphology, and volume of mushroom spines remained unaltered across the estrous cycle, and the values of these parameters were comparable with those of young male mice. However, while whisker stimulation of female mice during proestrus and estrus resulted in increases in the TOR of spines (74.2 ± 14.9% and 75.1 ± 12.7% vs. baseline, respectively), sensory-evoked plasticity was significantly lower during metestrus/diestrus (32.3 ± 12.8%). In males, whisker stimulation produced 46.5 ± 20% increase in TOR compared with baseline-not significantly different from female mice at any stage of the cycle. These results indicate that, while steady-state density and dynamics of dendritic spines of layer 5 pyramidal neurons in the primary somatosensory cortex of female mice are constant during the estrous cycle, the susceptibility of these neurons to sensory-evoked structural plasticity may be dependent on the stage of the cycle. Since dendritic spines are more plastic during proestrus and estrus than during metestrus/diestrus, certain stages of the cycle could be more suitable for forms of memory requiring de novo formation and elimination of spines and other stages for forms of memory where retention and/or repurposing of already existing synaptic connections is more pertinent.

Stable Density and Dynamics of Dendritic Spines of Cortical Neurons Across the Estrous Cycle While Expressing Differential Levels of Sensory-Evoked Plasticity

PubMed Central

Alexander, Bailin H.; Barnes, Heather M.; Trimmer, Emma; Davidson, Andrew M.; Ogola, Benard O.; Lindsey, Sarah H.; Mostany, Ricardo

2018-01-01

Periodic oscillations of gonadal hormone levels during the estrous cycle exert effects on the female brain, impacting cognition and behavior. While previous research suggests that changes in hormone levels across the cycle affect dendritic spine dynamics in the hippocampus, little is known about the effects on cortical dendritic spines and previous studies showed contradictory results. In this in vivo imaging study, we investigated the impact of the estrous cycle on the density and dynamics of dendritic spines of pyramidal neurons in the primary somatosensory cortex of mice. We also examined if the induction of synaptic plasticity during proestrus, estrus, and metestrus/diestrus had differential effects on the degree of remodeling of synapses in this brain area. We used chronic two-photon excitation (2PE) microscopy during steady-state conditions and after evoking synaptic plasticity by whisker stimulation at the different stages of the cycle. We imaged apical dendritic tufts of layer 5 pyramidal neurons of naturally cycling virgin young female mice. Spine density, turnover rate (TOR), survival fraction, morphology, and volume of mushroom spines remained unaltered across the estrous cycle, and the values of these parameters were comparable with those of young male mice. However, while whisker stimulation of female mice during proestrus and estrus resulted in increases in the TOR of spines (74.2 ± 14.9% and 75.1 ± 12.7% vs. baseline, respectively), sensory-evoked plasticity was significantly lower during metestrus/diestrus (32.3 ± 12.8%). In males, whisker stimulation produced 46.5 ± 20% increase in TOR compared with baseline—not significantly different from female mice at any stage of the cycle. These results indicate that, while steady-state density and dynamics of dendritic spines of layer 5 pyramidal neurons in the primary somatosensory cortex of female mice are constant during the estrous cycle, the susceptibility of these neurons to sensory-evoked structural plasticity may be dependent on the stage of the cycle. Since dendritic spines are more plastic during proestrus and estrus than during metestrus/diestrus, certain stages of the cycle could be more suitable for forms of memory requiring de novo formation and elimination of spines and other stages for forms of memory where retention and/or repurposing of already existing synaptic connections is more pertinent. PMID:29615867

Modelling Pseudocalanus elongatus stage-structured population dynamics embedded in a water column ecosystem model for the northern North Sea

NASA Astrophysics Data System (ADS)

Moll, Andreas; Stegert, Christoph

2007-01-01

This paper outlines an approach to couple a structured zooplankton population model with state variables for eggs, nauplii, two copepodites stages and adults adapted to Pseudocalanus elongatus into the complex marine ecosystem model ECOHAM2 with 13 state variables resolving the carbon and nitrogen cycle. Different temperature and food scenarios derived from laboratory culture studies were examined to improve the process parameterisation for copepod stage dependent development processes. To study annual cycles under realistic weather and hydrographic conditions, the coupled ecosystem-zooplankton model is applied to a water column in the northern North Sea. The main ecosystem state variables were validated against observed monthly mean values. Then vertical profiles of selected state variables were compared to the physical forcing to study differences between zooplankton as one biomass state variable or partitioned into five population state variables. Simulated generation times are more affected by temperature than food conditions except during the spring phytoplankton bloom. Up to six generations within the annual cycle can be discerned in the simulation.

How can mortality increase population size? A test of two mechanistic hypotheses.

PubMed

McIntire, Kristina M; Juliano, Steven A

2018-05-03

Overcompensation occurs when added mortality increases survival to the next life-cycle stage. Overcompensation can contribute to the Hydra Effect, wherein added mortality increases equilibrium population size. One hypothesis for overcompensation is that added mortality eases density-dependence, increasing survival to adulthood ("temporal separation of mortality and density dependence"). Mortality early in the life cycle is therefore predicted to cause overcompensation, whereas mortality later in the life cycle is not. Another hypothesis for overcompensation is that threat of mortality (e.g., from predation) causes behavioral changes that reduce overexploitation of resources, allowing resource recovery, and increasing production of adults ("prudent resource exploitation"). Behaviorally active predation cues alone are therefore predicted to cause overcompensation. We tested these predictions in two experiments with larvae of two species of Aedes. As predicted, early mortality yielded greater production of adults, and of adult females, and greater estimated rate of population increase than did later mortality. Addition of water-borne predation cues usually reduced browsing on surfaces in late-stage larvae, but contrary to prediction, resulted in neither significantly greater production of adult mosquitoes nor significantly greater estimated rate of increase. Thus we have strong evidence that timing of mortality contributes to overcompensation and the Hydra effect in mosquitoes. Evidence that predation cues alone can result in overcompensation via prudent resource exploitation is lacking. We expect the overcompensation in response to early mortality will be common in organisms with complex life cycles, density dependence among juveniles, and developmental control of populations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Triple effect absorption cycles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erickson, D.C.; Potnis, S.V.; Tang, J.

1996-12-31

Triple effect absorption chillers can achieve 50% COP improvement over double-effect systems. However, to translate this potential into cost-effective hardware, the most promising embodiments must be identified. In this study, 12 generic triple effect cycles and 76 possible hermetic loop arrangements of those 12 generic cycles were identified. The generic triple effect cycles were screened based on their pressure and solubility field requirements, generic COPs, risk involved in the component design, and number of components in a high corrosive environment. This screening identified four promising arrangements: Alkitrate Topping cycle, Pressure Staged Envelope cycle, High Pressure Overlap cycle, and Dual Loopmore » cycle. All of these arrangements have a very high COP ({approximately} 1.8), however the development risk and cost involved is different for each arrangement. Therefore, the selection of a particular arrangement will depend upon the specific situation under consideration.« less

Modeling metabolism and stage-specific growth of Plasmodium falciparum HB3 during the intraerythrocytic developmental cycle.

PubMed

Fang, Xin; Reifman, Jaques; Wallqvist, Anders

2014-10-01

The human malaria parasite Plasmodium falciparum goes through a complex life cycle, including a roughly 48-hour-long intraerythrocytic developmental cycle (IDC) in human red blood cells. A better understanding of the metabolic processes required during the asexual blood-stage reproduction will enhance our basic knowledge of P. falciparum and help identify critical metabolic reactions and pathways associated with blood-stage malaria. We developed a metabolic network model that mechanistically links time-dependent gene expression, metabolism, and stage-specific growth, allowing us to predict the metabolic fluxes, the biomass production rates, and the timing of production of the different biomass components during the IDC. We predicted time- and stage-specific production of precursors and macromolecules for P. falciparum (strain HB3), allowing us to link specific metabolites to specific physiological functions. For example, we hypothesized that coenzyme A might be involved in late-IDC DNA replication and cell division. Moreover, the predicted ATP metabolism indicated that energy was mainly produced from glycolysis and utilized for non-metabolic processes. Finally, we used the model to classify the entire tricarboxylic acid cycle into segments, each with a distinct function, such as superoxide detoxification, glutamate/glutamine processing, and metabolism of fumarate as a byproduct of purine biosynthesis. By capturing the normal metabolic and growth progression in P. falciparum during the IDC, our model provides a starting point for further elucidation of strain-specific metabolic activity, host-parasite interactions, stress-induced metabolic responses, and metabolic responses to antimalarial drugs and drug candidates.

Assessing Marine Species Exposure to Ocean Acidification

NASA Astrophysics Data System (ADS)

Jewett, E.; Busch, S.; McElhany, P.; Gledhill, D. K.; Milke, L. M.; Wieczorek, D.

2016-02-01

Assessing the vulnerability of society to ocean acidification (OA) demands an understanding of both the sensitivity of economically important species together with an organism's exposure to potentially harmful carbonate chemistry conditions. However, research has revealed that sensitivity to OA is frequently life-stage dependent and the environmental conditions experienced by a marine organism often vary with life-stage. Enhancing the development of a National Ocean Acidification Observing Network (NOA-ON) and establishing appropriate treatment conditions for experimental studies requires careful consideration of where the vulnerable life-stages of an organism reside in space (e.g., estuary versus oceanic), depth (e.g., surface mixed layer versus benthos), and time (e.g., diel vertical migration, seasonality of the chemical environment within the context of an organism life cycle). Few studies have explicitly attempted to document carbonate chemistry dynamics specific to a given organism's life-cycle. Here we estimate carbonate dynamics in terms of aragonite saturation state range and variability within the U.S. Northeast and West Coast through the application of NOAA's NOA-ON assets mapped out with respect to the life stages of economically important species within those regions. Two economically important species will be considered for which the life-cycles are well known along with the sensitivities to OA for early life-stages: Atlantic Surf Clam in the northeast and Dungeness Crab of the northwest coast of the U.S. Other species may also be considered.

Cell cycle progression is an essential regulatory component of phospholipid metabolism and membrane homeostasis

PubMed Central

Sanchez-Alvarez, Miguel; Zhang, Qifeng; Finger, Fabian; Wakelam, Michael J. O.; Bakal, Chris

2015-01-01

We show that phospholipid anabolism does not occur uniformly during the metazoan cell cycle. Transition to S-phase is required for optimal mobilization of lipid precursors, synthesis of specific phospholipid species and endoplasmic reticulum (ER) homeostasis. Average changes observed in whole-cell phospholipid composition, and total ER lipid content, upon stimulation of cell growth can be explained by the cell cycle distribution of the population. TORC1 promotes phospholipid anabolism by slowing S/G2 progression. The cell cycle stage-specific nature of lipid biogenesis is dependent on p53. We propose that coupling lipid metabolism to cell cycle progression is a means by which cells have evolved to coordinate proliferation with cell and organelle growth. PMID:26333836

Cell cycle progression is an essential regulatory component of phospholipid metabolism and membrane homeostasis.

PubMed

Sanchez-Alvarez, Miguel; Zhang, Qifeng; Finger, Fabian; Wakelam, Michael J O; Bakal, Chris

2015-09-01

We show that phospholipid anabolism does not occur uniformly during the metazoan cell cycle. Transition to S-phase is required for optimal mobilization of lipid precursors, synthesis of specific phospholipid species and endoplasmic reticulum (ER) homeostasis. Average changes observed in whole-cell phospholipid composition, and total ER lipid content, upon stimulation of cell growth can be explained by the cell cycle distribution of the population. TORC1 promotes phospholipid anabolism by slowing S/G2 progression. The cell cycle stage-specific nature of lipid biogenesis is dependent on p53. We propose that coupling lipid metabolism to cell cycle progression is a means by which cells have evolved to coordinate proliferation with cell and organelle growth. © 2015 The Authors.

Impact of Life-Cycle Stage and Gender on the Ability to Balance Work and Family Responsibilities.

ERIC Educational Resources Information Center

Higgins, Christopher; And Others

1994-01-01

Examined impact of gender and life-cycle stage on three components of work-family conflict using sample of 3,616 respondents. For men, levels of work-family conflict were moderately lower in each successive life-cycle stage. For women, levels were similar in two early life-cycle stages but were significantly lower in later life-cycle stage.…

Assessing the greenhouse gas emissions of Brazilian soybean biodiesel production.

PubMed

Cerri, Carlos Eduardo Pellegrino; You, Xin; Cherubin, Maurício Roberto; Moreira, Cindy Silva; Raucci, Guilherme Silva; Castigioni, Bruno de Almeida; Alves, Priscila Aparecida; Cerri, Domingos Guilherme Pellegrino; Mello, Francisco Fujita de Castro; Cerri, Carlos Clemente

2017-01-01

Soybean biodiesel (B100) has been playing an important role in Brazilian energy matrix towards the national bio-based economy. Greenhouse gas (GHG) emissions is the most widely used indicator for assessing the environmental sustainability of biodiesels and received particular attention among decision makers in business and politics, as well as consumers. Former studies have been mainly focused on the GHG emissions from the soybean cultivation, excluding other stages of the biodiesel production. Here, we present a holistic view of the total GHG emissions in four life cycle stages for soybean biodiesel. The aim of this study was to assess the GHG emissions of Brazilian soybean biodiesel production system with an integrated life cycle approach of four stages: agriculture, extraction, production and distribution. Allocation of mass and energy was applied and special attention was paid to the integrated and non-integrated industrial production chain. The results indicated that the largest source of GHG emissions, among four life cycle stages, is the agricultural stage (42-51%) for B100 produced in integrated systems and the production stage (46-52%) for B100 produced in non-integrated systems. Integration of industrial units resulted in significant reduction in life cycle GHG emissions. Without the consideration of LUC and assuming biogenic CO2 emissions is carbon neutral in our study, the calculated life cycle GHG emissions for domestic soybean biodiesel varied from 23.1 to 25.8 gCO2eq. MJ-1 B100 and those for soybean biodiesel exported to EU ranged from 26.5 to 29.2 gCO2eq. MJ-1 B100, which represent reductions by 65% up to 72% (depending on the delivery route) of GHG emissions compared with the EU benchmark for diesel fuel. Our findings from a life cycle perspective contributed to identify the major GHG sources in Brazilian soybean biodiesel production system and they can be used to guide mitigation priority for policy and decision-making. Projected scenarios in this study would be taken as references for accounting the environmental sustainability of soybean biodiesel within a domestic and global level.

Assessing the greenhouse gas emissions of Brazilian soybean biodiesel production

PubMed Central

You, Xin; Cherubin, Maurício Roberto; Moreira, Cindy Silva; Raucci, Guilherme Silva; Castigioni, Bruno de Almeida; Alves, Priscila Aparecida; Cerri, Domingos Guilherme Pellegrino; Mello, Francisco Fujita de Castro; Cerri, Carlos Clemente

2017-01-01

Soybean biodiesel (B100) has been playing an important role in Brazilian energy matrix towards the national bio-based economy. Greenhouse gas (GHG) emissions is the most widely used indicator for assessing the environmental sustainability of biodiesels and received particular attention among decision makers in business and politics, as well as consumers. Former studies have been mainly focused on the GHG emissions from the soybean cultivation, excluding other stages of the biodiesel production. Here, we present a holistic view of the total GHG emissions in four life cycle stages for soybean biodiesel. The aim of this study was to assess the GHG emissions of Brazilian soybean biodiesel production system with an integrated life cycle approach of four stages: agriculture, extraction, production and distribution. Allocation of mass and energy was applied and special attention was paid to the integrated and non-integrated industrial production chain. The results indicated that the largest source of GHG emissions, among four life cycle stages, is the agricultural stage (42–51%) for B100 produced in integrated systems and the production stage (46–52%) for B100 produced in non-integrated systems. Integration of industrial units resulted in significant reduction in life cycle GHG emissions. Without the consideration of LUC and assuming biogenic CO2 emissions is carbon neutral in our study, the calculated life cycle GHG emissions for domestic soybean biodiesel varied from 23.1 to 25.8 gCO2eq. MJ-1 B100 and those for soybean biodiesel exported to EU ranged from 26.5 to 29.2 gCO2eq. MJ-1 B100, which represent reductions by 65% up to 72% (depending on the delivery route) of GHG emissions compared with the EU benchmark for diesel fuel. Our findings from a life cycle perspective contributed to identify the major GHG sources in Brazilian soybean biodiesel production system and they can be used to guide mitigation priority for policy and decision-making. Projected scenarios in this study would be taken as references for accounting the environmental sustainability of soybean biodiesel within a domestic and global level. PMID:28493965

Reinforcing properties of an intermittent, low dose of ketamine in rats: effects of sex and cycle.

PubMed

Wright, Katherine N; Strong, Caroline E; Addonizio, Marjorie N; Brownstein, Naomi C; Kabbaj, Mohamed

2017-02-01

Repeated intermittent exposure to ketamine has rapid and long-lasting antidepressant effects, but the abuse potential has only been assessed at high doses. Furthermore, while females are more susceptible to depression and more sensitive to ketamine's antidepressant-like effects, the abuse potential for ketamine in females is unknown. The objectives of this study are to determine the reinforcing properties of low-dose intermittent ketamine in adult rats of both sexes and determine whether cycling gonadal hormones influence females' response to ketamine. In male rats, we also aimed to determine whether reinstatement to intermittent ketamine is comparable to intermittent cocaine. Male rats intravenously self-administered cocaine (0.75 mg/kg/infusion) or ketamine (0.1 mg/kg/infusion) once every fourth day, while intact cycling female rats self-administered ketamine only during preidentified stages of their 4-day estrus cycle, when gonadal hormones are either high (proestrus) or low (diestrus). After acquiring self-administration, rats underwent daily extinction training followed by cue-primed and drug-primed reinstatement to assess drug-seeking behavior. Diestrus-trained females fail to maintain ketamine self-administration and did not display reinstatement to ketamine-paired cues. Males and proestrus-trained females reinstated to ketamine-paired cues. Ketamine-primed reinstatement was dependent on simultaneous cue presentation. Male rats reinstated to cocaine priming independent of cue presentation. These findings indicate that females's responsivity to this dose of ketamine depends on stage of cycle, as only proestrus-trained females and males respond to ketamine's reinforcing effects under this treatment paradigm.

Molecular identification of PpHDAC1, the first histone deacetylase fron the slime mold Physarum polycephalum.

PubMed

Brandtner, Eva-Maria; Lechner, Thomas; Loidl, Peter; Lusser, Alexandra

2002-01-01

The dynamic state of post-translational acetylation of eukaryotic histones is maintained by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs and HDACs have been shown to be components of various regulatory protein complexes in the cell. Their enzymatic activities, intracellular localization and substrate specificities are regulated in a complex, cell cycle related manner. In the myxomycete Physarum polycephalum multiple HATs and HDACs can be distinguished in biochemical terms and they exhibit dynamic activity patterns depending on the cell cycle stage. Here we report on the cloning of the first P. polycephalum HDAC (PpHDAC1) related to the S. cerevisiae Rpd3 protein. The expression pattern of PpHDAC1 mRNA was analysed at different time points of the cell cycle and found to be largely constant. Treatment of macroplasmodia with the HDAC inhibitor trichostatin A at several cell cycle stages resulted in a significant delay in entry into mitosis of treated versus untreated plasmodia. No effect of TSA treatment could be observed on PpHDAC1 expression itself.

Expression of Progesterone Receptor Membrane Component-2 Within the Immature Rat Ovary and Its Role in Regulating Mitosis and Apoptosis of Spontaneously Immortalized Granulosa Cells1

PubMed Central

Griffin, Daniel; Liu, Xiufang; Pru, Cindy; Pru, James K.; Peluso, John J.

2014-01-01

ABSTRACT Progesterone receptor membrane component 2 (Pgrmc2) mRNA was detected in the immature rat ovary. By 48 h after eCG, Pgrmc2 mRNA levels decreased by 40% and were maintained at 48 h post-hCG. Immunohistochemical studies detected PGRMC2 in oocytes and ovarian surface epithelial, interstitial, thecal, granulosa, and luteal cells. PGRMC2 was also present in spontaneously immortalized granulosa cells, localizing to the cytoplasm of interphase cells and apparently to the mitotic spindle of cells in metaphase. Interestingly, PGRMC2 levels appeared to decrease during the G1 stage of the cell cycle. Moreover, overexpression of PGRMC2 suppressed entry into the cell cycle, possibly by binding the p58 form of cyclin dependent kinase 11b. Conversely, Pgrmc2 small interfering RNA (siRNA) treatment increased the percentage of cells in G1 and M stage but did not increase the number of cells, which was likely due to an increase in apoptosis. Depleting PGRMC2 did not inhibit cellular 3H-progesterone binding, but attenuated the ability of progesterone to suppress mitosis and apoptosis. Taken together these studies suggest that PGRMC2 affects granulosa cell mitosis by acting at two specific stages of the cell cycle. First, PGRMC2 regulates the progression from the G0 into the G1 stage of the cell cycle. Second, PGRMC2 appears to localize to the mitotic spindle, where it likely promotes the final stages of mitosis. Finally, siRNA knockdown studies indicate that PGRMC2 is required for progesterone to slow the rate of granulosa cell mitosis and apoptosis. These findings support a role for PGRMC2 in ovarian follicle development. PMID:24990806

How compliant are in vitro fertilization member clinics in following embryo transfer guidelines? An analysis of 59,689 fresh first in vitro fertilization autologous cycles from 2011 to 2012.

PubMed

Keyhan, Sanaz; Acharya, Kelly S; Acharya, Chaitanya R; Yeh, Jason S; Provost, Meredith P; Goldfarb, James M; Muasher, Suheil J

2016-09-01

To determine whether IVF clinics are compliant with American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) (ASRM/SART) guidelines and assess the multiple pregnancy outcomes according to the number of embryos transferred. Retrospective cohort study. Not applicable. Data from 59,689 fresh first autologous IVF cycles from the 2011-2012 SART registry. None. Percentage of compliant cycles, multiple pregnancy rate (PR). Between 2011 and 2012, a total of 59,689 fresh first autologous cycles were analyzed. Among cleavage-stage ET cycles, the noncompliance rate ranged from 10%-27.4% depending on the age group. The multiple PR was significantly increased in noncompliant cycles involving patients <35 years (38.1% vs. 28.7%) and 35-37 years (35.4% vs. 24.5%) compared with compliant cycles. Among blastocyst-stage ET cycles, the highest rate of noncompliance was seen in patients <35 years old (71%), which resulted in a statistically higher multiple PR (48.3% vs. 2.8%) compared with compliant cycles. Far fewer cycles were noncompliant in patients 35-40 years of age. In a subanalysis of compliant cycles, transferring two blastocyst embryos in patients 35-37 years and 38-40 years resulted in a higher live birth rate compared with the transfer of one embryo (50.4% vs. 40.9% and 42.1% vs. 30.0%, respectively) but the multiple PR was also significantly higher (40.5% vs. 1.7% and 34.0% vs. 2.0%, respectively). Most first fresh autologous IVF cycles performed from 2011-2012 were compliant with ASRM/SART guidelines, except those that involved a blastocyst ET in patients <35 years. Despite compliance, cycles that involved the transfer of >1 embryo resulted in a high multiple PR, whereas noncompliant cycles resulted in an even more remarkable multiple PR for both cleavage and blastocyst-stage embryos. Clinics need to be more compliant with ET limits and ASRM/SART need to consider revising their guidelines to limit the number of blastocyst transfer to one in patients ≤40 years of age undergoing their first IVF cycle. Furthermore, decreasing the number of cleavage-stage embryos transferred in patients ≤40 years of age should also be considered. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Complex life cycles and the responses of insects to climate change.

PubMed

Kingsolver, Joel G; Woods, H Arthur; Buckley, Lauren B; Potter, Kristen A; MacLean, Heidi J; Higgins, Jessica K

2011-11-01

Many organisms have complex life cycles with distinct life stages that experience different environmental conditions. How does the complexity of life cycles affect the ecological and evolutionary responses of organisms to climate change? We address this question by exploring several recent case studies and synthetic analyses of insects. First, different life stages may inhabit different microhabitats, and may differ in their thermal sensitivities and other traits that are important for responses to climate. For example, the life stages of Manduca experience different patterns of thermal and hydric variability, and differ in tolerance to high temperatures. Second, life stages may differ in their mechanisms for adaptation to local climatic conditions. For example, in Colias, larvae in different geographic populations and species adapt to local climate via differences in optimal and maximal temperatures for feeding and growth, whereas adults adapt via differences in melanin of the wings and in other morphological traits. Third, we extend a recent analysis of the temperature-dependence of insect population growth to demonstrate how changes in temperature can differently impact juvenile survival and adult reproduction. In both temperate and tropical regions, high rates of adult reproduction in a given environment may not be realized if occasional, high temperatures prevent survival to maturity. This suggests that considering the differing responses of multiple life stages is essential to understand the ecological and evolutionary consequences of climate change. © The Author 2011. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved.

Therapeutic Cell-Cycle-Decoy Efficacy of a Telomerase-Dependent Adenovirus in an Orthotopic Model of Chemotherapy-Resistant Human Stomach Carcinomatosis Peritonitis Visualized With FUCCI Imaging.

PubMed

Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

2017-11-01

We have established an orthotopic nude-mouse model of gastric cancer carcinomatosis peritonitis, a recalcitrant disease in human patients. Human MKN45 poorly-differentiated human gastric cancer cells developed carcinomatosis peritonitis upon orthotopic transplantation in nude mice. The MKN45 cells expressed the fluorescent ubiquitination-based cell cycle indicator (FUCCI) that color codes the phases of the cell cycle. The intra-peritoneal tumors and ascites contained mostly quiescent G 1 /G o cancer cells visualized as red by FUCCI imaging. Cisplatinum (CDDP) treatment did not reduce bloody ascites, and larger tumors formed in the peritoneal cavity after CDDP treatment in an early-stage carcinomatosis peritonitis orthotopic mouse model. Paclitaxel-treated mice had reduced ascites, but also had large tumor masses in the peritonium after treatment with cancer cells mostly in G 0 /G 1 , visualized by FUCCI red. In contrast, OBP-301 telomerase-dependent adenovirus-treated mice had no ascites and only small tumor nodules consisting of cancer cells mostly in S/G 2 phases in the early-stage carcinomatosis peritonitis model, visualized by FUCCI green. Furthermore, OBP-301 significantly reduced the size of tumors (P < 0.01) and ascites even in a late-stage carcinomatosis peritonitis model. These results suggest that quiescent peritoneally-disseminated gastric cancer cells are resistant to conventional chemotherapy, but OBP-301 significantly reduced the weight of the tumors and increased survival, suggesting clinical potential. J. Cell. Biochem. 118: 3635-3642, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The influence of the oestrous cycle on the radiation response of solid tumours

NASA Astrophysics Data System (ADS)

Swann, Patricia R.

Oestrogen increases the transcription of nitric oxide synthase, thus increasing nitric oxide production, which can result in vasodilation of blood vessels. Fluctuating levels of oestrogen throughout the menstrual cycle has the potential to affect tumour blood flow. Variations of blood supply to a solid tumour can influence tumour oxygenation and subsequently the percentage of hypoxic cells. As hypoxic cells are more resistant to radiation than well-oxygenated cells, this could potentially affect the radiation response of the tumour. This project evaluated the impact of the oestrous stage on the radiation response of BCHT, RIF-1 and SCCvii tumours in syngeneic C3H mice. The oestrous cycle consists of the following stages, pro-oestrus, oestrus, metoestrus and dioestrus and each stage can be determined by the cellular composition of vaginal smears. The peak of oestrogen occurs in the ovulatory phase and a second smaller peak occurs in dioestrus. Subcutaneous tumour were treated at a volume of 200 - 250 mm3 with local irradiation of 10 Gy ionising radiation at different stages of the oestrous cycle. Tumours were excised either immediately or 24 hours after irradiation and disaggregated into a single cell suspension. Tumour cell survival was assessed by clonogenic assay of the excised tumour relative to untreated tumours excised at the corresponding oestrous stage. Tumours irradiated in oestrus consistently produced the lowest surviving fraction after immediate and delayed excision. Tumours irradiated in pro-oestrus and excised immediately after irradiation, showed a two-fold increase in surviving fraction compared to tumours irradiated in oestrus. The surviving fractions of tumours excised 24 hours after irradiation were less than for tumours excised immediately after irradiation. Surviving fractions of irradiated, clamped KHT tumours were independent of oestrous stage. To confirm that these oestrous stage dependent changes were due to changes in tumour perfusion, the degree of transient perfusion in the tumours was assessed. This used a fluorescent double-staining technique by intravenous injection of the fluorescent dyes Hoechst 33342 and diheptyloxacarbocyanine with a 20 minute interval between dye administrations. These dyes stain functional blood vessels and can be viewed under the fluorescent microscope. Regions of vasculature stained with both dyes indicate constant perfusion throughout the experiment, whereas only one dye indicates mismatch or transient perfusion. Tumour vasculature that experiences intermittent perfusion will result in areas of acute hypoxia that can impact on the radiation response of the tumour. The results shows that in oestrus, KHT and RIF-1 tumours showed the lowest proportion of transient perfusion, where as this oestrous stage produced the most mismatch perfusion in the SCCvii tumour. The metastatic spread of KHT tumour cells was influenced by the oestrous cycle. Fractionated irradiation of a primary tumour during metoestrus and dioestrus showed less tumour control by radiation when compared to tumours irradiated in oestrus. The intravenous injection of KHT tumour cells in oestrus and dioestrus also produced a less metastatic burden to the lungs than cells injected in pro-oestrus and metoestrus. The results of this project suggest that there are oestrous stage dependent effects that could alter the radiation response of tumours.

Embryonic development rates of northern grasshoppers (Orthoptera: Acrididae): implications for climate change and habitat management

USDA-ARS?s Scientific Manuscript database

Temperature-dependent rates of embryonic development are a primary determinant of the life cycle of many species of grasshoppers which, in cold climates, spend two winters in the egg stage. Knowledge of embryonic developmental rates is important for an assessment of the effects of climate change and...

Ocean acidification affects redox-balance and ion-homeostasis in the life-cycle stages of Emiliania huxleyi.

PubMed

Rokitta, Sebastian D; John, Uwe; Rost, Björn

2012-01-01

Ocean Acidification (OA) has been shown to affect photosynthesis and calcification in the coccolithophore Emiliania huxleyi, a cosmopolitan calcifier that significantly contributes to the regulation of the biological carbon pumps. Its non-calcifying, haploid life-cycle stage was found to be relatively unaffected by OA with respect to biomass production. Deeper insights into physiological key processes and their dependence on environmental factors are lacking, but are required to understand and possibly estimate the dynamics of carbon cycling in present and future oceans. Therefore, calcifying diploid and non-calcifying haploid cells were acclimated to present and future CO(2) partial pressures (pCO(2); 38.5 Pa vs. 101.3 Pa CO(2)) under low and high light (50 vs. 300 µmol photons m(-2) s(-1)). Comparative microarray-based transcriptome profiling was used to screen for the underlying cellular processes and allowed to follow up interpretations derived from physiological data. In the diplont, the observed increases in biomass production under OA are likely caused by stimulated production of glycoconjugates and lipids. The observed lowered calcification under OA can be attributed to impaired signal-transduction and ion-transport. The haplont utilizes distinct genes and metabolic pathways, reflecting the stage-specific usage of certain portions of the genome. With respect to functionality and energy-dependence, however, the transcriptomic OA-responses resemble those of the diplont. In both life-cycle stages, OA affects the cellular redox-state as a master regulator and thereby causes a metabolic shift from oxidative towards reductive pathways, which involves a reconstellation of carbon flux networks within and across compartments. Whereas signal transduction and ion-homeostasis appear equally OA-sensitive under both light intensities, the effects on carbon metabolism and light physiology are clearly modulated by light availability. These interactive effects can be attributed to the influence of OA and light on the redox equilibria of NAD and NADP, which function as major sensors for energization and stress. This generic mode of action of OA may therefore provoke similar cell-physiological responses in other protists.

Performance evaluation of two-stage fuel cycle from SFR to PWR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fei, T.; Hoffman, E.A.; Kim, T.K.

2013-07-01

One potential fuel cycle option being considered is a two-stage fuel cycle system involving the continuous recycle of transuranics in a fast reactor and the use of bred plutonium in a thermal reactor. The first stage is a Sodium-cooled Fast Reactor (SFR) fuel cycle with metallic U-TRU-Zr fuel. The SFRs need to have a breeding ratio greater than 1.0 in order to produce fissile material for use in the second stage. The second stage is a PWR fuel cycle with uranium and plutonium mixed oxide fuel based on the design and performance of the current state-of-the-art commercial PWRs with anmore » average discharge burnup of 50 MWd/kgHM. This paper evaluates the possibility of this fuel cycle option and discusses its fuel cycle performance characteristics. The study focuses on an equilibrium stage of the fuel cycle. Results indicate that, in order to avoid a positive coolant void reactivity feedback in the stage-2 PWR, the reactor requires high quality of plutonium from the first stage and minor actinides in the discharge fuel of the PWR needs to be separated and sent back to the stage-1 SFR. The electricity-sharing ratio between the 2 stages is 87.0% (SFR) to 13.0% (PWR) for a TRU inventory ratio (the mass of TRU in the discharge fuel divided by the mass of TRU in the fresh fuel) of 1.06. A sensitivity study indicated that by increasing the TRU inventory ratio to 1.13, The electricity generation fraction of stage-2 PWR is increased to 28.9%. The two-stage fuel cycle system considered in this study was found to provide a high uranium utilization (>80%). (authors)« less

Autonomy and integration in complex parasite life cycles.

PubMed

Benesh, Daniel P

2016-12-01

Complex life cycles are common in free-living and parasitic organisms alike. The adaptive decoupling hypothesis postulates that separate life cycle stages have a degree of developmental and genetic autonomy, allowing them to be independently optimized for dissimilar, competing tasks. That is, complex life cycles evolved to facilitate functional specialization. Here, I review the connections between the different stages in parasite life cycles. I first examine evolutionary connections between life stages, such as the genetic coupling of parasite performance in consecutive hosts, the interspecific correlations between traits expressed in different hosts, and the developmental and functional obstacles to stage loss. Then, I evaluate how environmental factors link life stages through carryover effects, where stressful larval conditions impact parasites even after transmission to a new host. There is evidence for both autonomy and integration across stages, so the relevant question becomes how integrated are parasite life cycles and through what mechanisms? By highlighting how genetics, development, selection and the environment can lead to interdependencies among successive life stages, I wish to promote a holistic approach to studying complex life cycle parasites and emphasize that what happens in one stage is potentially highly relevant for later stages.

Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control

PubMed Central

Chávez, Santiago; Eastman, Guillermo; Smircich, Pablo; Becco, Lorena Lourdes; Oliveira-Rizzo, Carolina; Fort, Rafael; Potenza, Mariana; Garat, Beatriz; Sotelo-Silveira, José Roberto

2017-01-01

Trypanosoma cruzi is the protozoan parasite causing American trypanosomiasis or Chagas disease, a neglected parasitosis with important human health impact in Latin America. The efficacy of current therapy is limited, and its toxicity is high. Since parasite proliferation is a fundamental target for rational drug design, we sought to progress into its understanding by applying a genome-wide approach. Treating a TcI linage strain with hydroxyurea, we isolated epimastigotes in late G1, S and G2/M cell cycle stages at 70% purity. The sequencing of each phase identified 305 stage-specific transcripts (1.5-fold change, p≤0.01), coding for conserved cell cycle regulated proteins and numerous proteins whose cell cycle dependence has not been recognized before. Comparisons with the parasite T. brucei and the human host reveal important differences. The meta-analysis of T. cruzi transcriptomic and ribonomic data indicates that cell cycle regulated mRNAs are subject to sub-cellular compartmentalization. Compositional and structural biases of these genes- including CAI, GC content, UTR length, and polycistron position- may contribute to their regulation. To discover nucleotide motifs responsible for the co-regulation of cell cycle regulated genes, we looked for overrepresented motifs at their UTRs and found a variant of the cell cycle sequence motif at the 3' UTR of most of the S and G2 stage genes. We additionally identified hairpin structures at the 5' UTRs of a high proportion of the transcripts, suggesting that periodic gene expression might also rely on translation initiation in T. cruzi. In summary, we report a comprehensive list of T. cruzi cell cycle regulated genes, including many previously unstudied proteins, we show evidence favoring a multi-step control of their expression, and we identify mRNA motifs that may mediate their regulation. Our results provide novel information of the T. cruzi proliferative proteins and the integrated levels of their gene expression control. PMID:29182646

Translational Science Project Team Managers: Qualitative Insights and Implications from Current and Previous Postdoctoral Experiences.

PubMed

Wooten, Kevin C; Dann, Sara M; Finnerty, Celeste C; Kotarba, Joseph A

2014-07-01

The development of leadership and project management skills is increasingly important to the evolution of translational science and team-based endeavors. Team science is dependent upon individuals at various stages in their careers, inclusive of postdocs. Data from case histories, as well as from interviews with current and former postdocs, and those supervising postdocs, indicate six essential tasks required of project managers in multidisciplinary translational teams, along with eight skill-related themes critical to their success. To optimize the opportunities available and to ensure sequential development of team project management skills, a life cycle model for the development of translational team skills is proposed, ranging from graduate trainees, postdocs, assistant professors, and finally to mature scientists. Specific goals, challenges and project management roles and tasks are recommended for each stage for the life cycle.

Translational Science Project Team Managers: Qualitative Insights and Implications from Current and Previous Postdoctoral Experiences

PubMed Central

Wooten, Kevin C.; Dann, Sara M.; Finnerty, Celeste C.; Kotarba, Joseph A.

2015-01-01

The development of leadership and project management skills is increasingly important to the evolution of translational science and team-based endeavors. Team science is dependent upon individuals at various stages in their careers, inclusive of postdocs. Data from case histories, as well as from interviews with current and former postdocs, and those supervising postdocs, indicate six essential tasks required of project managers in multidisciplinary translational teams, along with eight skill-related themes critical to their success. To optimize the opportunities available and to ensure sequential development of team project management skills, a life cycle model for the development of translational team skills is proposed, ranging from graduate trainees, postdocs, assistant professors, and finally to mature scientists. Specific goals, challenges and project management roles and tasks are recommended for each stage for the life cycle. PMID:25621288

The impact of female education on fertility desires in Bangladesh.

PubMed

Matin, K A

1985-01-01

The objective of this study is to determine whether in Bangladesh a wife's educational level significantly affects her desire for more children, or whether Bangladesh has not yet reached the threshold of socioeconomic development where education has any effect on the number of additional children desired. The analysis was carried out in a rural-urban context and also at different stages in the woman's life cycle, as defined by parity at time of interview. 2-3 live births were considered early stage, and 4 or more were defined as later stage. The analysis was carried out on 2791 women selected from the Bangladesh Fertility Survey of 1975-76 who at the time of interview met the criteria of being married, fecund, parity of 2 or more, and having a husband present in the household. The method used to perform the analysis was the Maximum Likelihood estimation method for the truncated dependent variable developed by J. Tobin. The method is a hybrid of probit analysis and classical regression and was chosen because the dependent variable, number of additional children desired, had a clustering of values at the lower limit of O. Separate regressions were run by life cycle stage (parity) and rural-urban background. The effect of variables such as the education of the husband, age, age at first marriage, work status of wife, number of living male children, and infant mortality were held constant in order to find the impact of education on desired fertility. The study found that the number of additional children desired by rural wives was greater than that desired by urban wives at all stages of the life cycle. The mean number of additional children desired by a rural wife at the early stage of the life cycle was .57 and in the later stage .15. For urban women the corresponding values were .29 and .12. The study found that the educational level of both the wife and the husband and the age of the wife at first marriage were not significant. The age of the woman was not significant in urban areas but was negatively significant.in rural areas. The percent of dead children was positively significant in both urban and rural areas for early stage women but for later stage women only in rural areas. In rural areas also the number of living male children was positively significant. The author concludes that Bangladesh is not at the developmental level where education has a significant effect on desire for additional children and that desired fertility is more influenced by antecedent factors such as income, infant mortality, and preference for male children. He recommends that measures be taken to improve socioeconomic levels and provide employment opportunities for women. He also suggests that additional analysis be done to identify the factors important in determining fertility decisions in urban areas and that separate policies be adopted for rural and urban areas.

Comparative life cycle assessment of battery storage systems for stationary applications.

PubMed

Hiremath, Mitavachan; Derendorf, Karen; Vogt, Thomas

2015-04-21

This paper presents a comparative life cycle assessment of cumulative energy demand (CED) and global warming potential (GWP) of four stationary battery technologies: lithium-ion, lead-acid, sodium-sulfur, and vanadium-redox-flow. The analyses were carried out for a complete utilization of their cycle life and for six different stationary applications. Due to its lower CED and GWP impacts, a qualitative analysis of lithium-ion was carried out to assess the impacts of its process chains on 17 midpoint impact categories using ReCiPe-2008 methodology. It was found that in general the use stage of batteries dominates their life cycle impacts significantly. It is therefore misleading to compare the environmental performance of batteries only on a mass or capacity basis at the manufacturing outlet ("cradle-to-gate analyses") while neglecting their use stage impacts, especially when they have different characteristic parameters. Furthermore, the relative ranking of batteries does not show a significant dependency on the investigated stationary application scenarios in most cases. Based on the results obtained, the authors go on to recommend the deployment of batteries with higher round-trip efficiency, such as lithium-ion, for stationary grid operation in the first instance.

STAGE-DEPENDENCE, SEASONAL CHANGES AND EFFECTS OF CADMIUM ON CELL CYCLE AND APOPTOTIC ACTIVITIES DURING THE SPERMATOGENIC PROGRESSION IN THE DOGFISH SHARK (SQUALUS ACANTHIAS). (R825434)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Small-molecule histone methyltransferase inhibitors display rapid antimalarial activity against all blood stage forms in Plasmodium falciparum

PubMed Central

Malmquist, Nicholas A.; Moss, Thomas A.; Mecheri, Salah; Scherf, Artur; Fuchter, Matthew J.

2012-01-01

Epigenetic factors such as histone methylation control the developmental progression of malaria parasites during the complex life cycle in the human host. We investigated Plasmodium falciparum histone lysine methyltransferases as a potential target class for the development of novel antimalarials. We synthesized a compound library based upon a known specific inhibitor (BIX-01294) of the human G9a histone methyltransferase. Two compounds, BIX-01294 and its derivative TM2-115, inhibited P. falciparum 3D7 parasites in culture with IC50 values of ∼100 nM, values at least 22-fold more potent than their apparent IC50 toward two human cell lines and one mouse cell line. These compounds irreversibly arrested parasite growth at all stages of the intraerythrocytic life cycle. Decrease in parasite viability (>40%) was seen after a 3-h incubation with 1 µM BIX-01294 and resulted in complete parasite killing after a 12-h incubation. Additionally, mice with patent Plasmodium berghei ANKA strain infection treated with a single dose (40 mg/kg) of TM2-115 had 18-fold reduced parasitemia the following day. Importantly, treatment of P. falciparum parasites in culture with BIX-01294 or TM2-115 resulted in significant reductions in histone H3K4me3 levels in a concentration-dependent and exposure time-dependent manner. Together, these results suggest that BIX-01294 and TM2-115 inhibit malaria parasite histone methyltransferases, resulting in rapid and irreversible parasite death. Our data position histone lysine methyltransferases as a previously unrecognized target class, and BIX-01294 as a promising lead compound, in a presently unexploited avenue for antimalarial drug discovery targeting multiple life-cycle stages. PMID:23011794

The Expression of Glyceraldehyde-3-Phosphate Dehydrogenase Associated Cell Cycle (GACC) Genes Correlates with Cancer Stage and Poor Survival in Patients with Solid Tumors

PubMed Central

Wang, Dunrui; Moothart, Daniel R.; Lowy, Douglas R.; Qian, Xiaolan

2013-01-01

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is often used as a stable housekeeping marker for constant gene expression. However, the transcriptional levels of GAPDH may be highly up-regulated in some cancers, including non-small cell lung cancers (NSCLC). Using a publically available microarray database, we identified a group of genes whose expression levels in some cancers are highly correlated with GAPDH up-regulation. The majority of the identified genes are cell cycle-dependent (GAPDH Associated Cell Cycle, or GACC). The up-regulation pattern of GAPDH positively associated genes in NSCLC is similar to that observed in cultured fibroblasts grown under conditions that induce anti-senescence. Data analysis demonstrated that up-regulated GAPDH levels are correlated with aberrant gene expression related to both glycolysis and gluconeogenesis pathways. Down-regulation of fructose-1,6-bisphosphatase (FBP1) in gluconeogenesis in conjunction with up-regulation of most glycolytic genes is closely related to high expression of GAPDH in the tumors. The data presented demonstrate that up-regulation of GAPDH positively associated genes is proportional to the malignant stage of various tumors and is associated with an unfavourable prognosis. Thus, this work suggests that GACC genes represent a potential new signature for cancer stage identification and disease prognosis. PMID:23620736

DEVELOPMENTAL NEUROTOXICITY OF ORGANOPHOSPHATES TARGETS CELL CYCLE AND APOPTOSIS, REVEALED BY TRANSCRIPTIONAL PROFILES IN VIVO AND IN VITRO

PubMed Central

Slotkin, Theodore A.; Seidler, Frederic J.

2012-01-01

Developmental organophosphate exposure reduces the numbers of neural cells, contributing to neurobehavioral deficits. We administered chlorpyrifos or diazinon to newborn rats on postnatal days 1–4, in doses straddling the threshold for barely-detectable cholinesterase, and evaluated gene expression in the cell cycle and apoptosis pathways on postnatal day 5. Both organophosphates evoked transcriptional changes in 20–25% of the genes in each category; chlorpyrifos and diazinon targeted the same genes, with similar magnitudes of change, as evidenced by high concordance. Furthermore, the same effects were obtained with doses above or below the threshold for cholinesterase inhibition, indicating a mechanism unrelated to anticholinesterase actions. We then evaluated the effects of chlorpyrifos in undifferentiated and differentiating PC12 cells and found even greater targeting of cell cycle and apoptosis genes, affecting up to 40% of all genes in the pathways. Notably, the genes affected in undifferentiated cells were not concordant with those in differentiating cells, pointing to dissimilar outcomes dependent on developmental stage. The in vitro model successfully identified 60–70% of the genes affected by chlorpyrifos in vivo, indicating that the effects are exerted directly on developing neural cells. Our results show that organophosphates target the genes regulating the cell cycle and apoptosis in the developing brain and in neuronotypic cells in culture, with the pattern of vulnerability dependent on the specific stage of development. Equally important, these effects do not reflect actions on cholinesterase and operate at exposures below the threshold for any detectable inhibition of this enzyme. PMID:22222554

Developmental neurotoxicity of organophosphates targets cell cycle and apoptosis, revealed by transcriptional profiles in vivo and in vitro.

PubMed

Slotkin, Theodore A; Seidler, Frederic J

2012-03-01

Developmental organophosphate exposure reduces the numbers of neural cells, contributing to neurobehavioral deficits. We administered chlorpyrifos or diazinon to newborn rats on postnatal days 1-4, in doses straddling the threshold for barely-detectable cholinesterase inhibition, and evaluated gene expression in the cell cycle and apoptosis pathways on postnatal day 5. Both organophosphates evoked transcriptional changes in 20-25% of the genes in each category; chlorpyrifos and diazinon targeted the same genes, with similar magnitudes of change, as evidenced by high concordance. Furthermore, the same effects were obtained with doses above or below the threshold for cholinesterase inhibition, indicating a mechanism unrelated to anticholinesterase actions. We then evaluated the effects of chlorpyrifos in undifferentiated and differentiating PC12 cells and found even greater targeting of cell cycle and apoptosis genes, affecting up to 40% of all genes in the pathways. Notably, the genes affected in undifferentiated cells were not concordant with those in differentiating cells, pointing to dissimilar outcomes dependent on developmental stage. The in vitro model successfully identified 60-70% of the genes affected by chlorpyrifos in vivo, indicating that the effects are exerted directly on developing neural cells. Our results show that organophosphates target the genes regulating the cell cycle and apoptosis in the developing brain and in neuronotypic cells in culture, with the pattern of vulnerability dependent on the specific stage of development. Equally important, these effects do not reflect actions on cholinesterase and operate at exposures below the threshold for any detectable inhibition of this enzyme. Copyright © 2011 Elsevier Inc. All rights reserved.

Co-relation of estrous cycle phases with uterine bacterial and fungal flora in non-pregnant female laboratory rabbits

PubMed Central

Mogheiseh, A.; Derakhshandeh, A.; Batebi, E.; Golestani, N.; Moshiri, A.

2017-01-01

This study was designed to investigate the relationship between the estrous cycle phases with uterine bacterial and fungal flora in non-pregnant female rabbits. Thirty laboratory mature multiparous rabbits were used for this purpose. Samples from uterine lavage for culture of bacteria and fungi were collected at different stages of estrous cycle (based on vaginal cytology), and histopathological observations were evaluated based on the scoring system used for defining the infection of the uterus. Various types of bacteria and fungi were isolated from rabbits at all stages of estrous cycle. The widest variety of bacteria and fungi was isolated at Di-estrous stage and the lowest variety was detected at estrous stage. Klebsiella oxytoca as well as yeast have been isolated at all stages of estrous cycle. This study showed that infection with K. oxytoca and yeast had no relationship with different stages of estrous cycle but other bacteria and fungus were associated with one or more stages of the estrous cycle in rabbits. PMID:28775754

Comparison of geothermal power conversion cycles

NASA Technical Reports Server (NTRS)

Elliott, D. G.

1976-01-01

Geothermal power conversion cycles are compared with respect to recovery of the available wellhead power. The cycles compared are flash steam, in which steam turbines are driven by steam separated from one or more flash stages; binary, in which heat is transferred from the brine to an organic turbine cycle; flash binary, in which heat is transferred from flashed steam to an organic turbine cycle; and dual steam, in which two-phase expanders are driven by the flashing steam-brine mixture and steam turbines by the separated steam. Expander efficiencies assumed are 0.7 for steam turbines, 0.8 for organic turbines, and 0.6 for two-phase expanders. The fraction of available wellhead power delivered by each cycle is found to be about the same at all brine temperatures: 0.65 with one stage and 0.7 with four stages for dual stream; 0.4 with one stage and 0.6 with four stages for flash steam; 0.5 for binary; and 0.3 with one stage and 0.5 with four stages for flash binary.

Mechanisms underlying regulation of cell cycle and apoptosis by hnRNP B1 in human lung adenocarcinoma A549 cells.

PubMed

Han, Juan; Tang, Feng-ming; Pu, Dan; Xu, Dan; Wang, Tao; Li, Weimin

2014-01-01

Overexpression of heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1), a nuclear RNA binding protein, has been reported to occur in early-stage lung cancer and in premalignant lesions. DNA-dependent protein kinase (DNA-PK) is known to be involved in the repair of double-strand DNA breaks. Reduced capacity to repair DNA has been associated with the risk of lung cancer. We investigated a link between hnRNP B1 and DNA-PK and their effects on proliferation, cell cycle, and apoptosis in the human lung adenocarcinoma cell line A549. We found that hnRNP B1 and DNA-PK interact with each other in a complex fashion. Reducing hnRNP B1 expression in A549 cells with the use of RNAi led to upregulation of p53 activity through upregulation of DNA-PK activity but without inducing p53 expression. Further, suppression of hnRNP B1 in A549 cells slowed cell proliferation, promoted apoptosis, and induced cell cycle arrest at the G1 stage. The presence of NU7026 reduced the arrest of cells at the G1 stage and reduced the apoptosis rate while promoting cell growth. Taken together, our results demonstrate that by regulating DNA-PK activity, hnRNP B1 can affect p53-mediated cell cycle progression and apoptosis, resulting in greater cell survival and subsequent proliferation.

Electron-microscopic characteristics of neuroendocrine neurons in the amygdaloid body of the brain in male rats and female rats at different stages of the estral cycle.

PubMed

Akhmadeev, A V; Kalimullina, L B

2008-01-01

The ultrastructural features of neuroendocrine neurons in the dorsomedial nucleus (DMN) of the amygdaloid body of the brain - one of the major zones of sexual dimorphism - in 12 Wistar rats weighing 250-300 g were studied in three males and nine females at different stages of the estral cycle. On the basis of ultrastructural characteristics, analysis of the functional states of an average of 50 DMN neurons were studied in each animal. A morphofunctional classification reflecting hormone-dependent variations in neuron activity is proposed. DMN neurons were found to be in different structural-functional states, which could be classified as the states of rest, moderate activity, elevated activity, tension (maximal activity), decreased activity (types 1 and 2, depending on prior history), return to the initial state, and apoptosis. At the estrus stage, there was a predominance of neurons in the states of elevated activity (40% of all cells) and maximal activity (26%). At the metestrus stage, neurons in the state of decreased activity type 1 (with increased nuclear heterochromatin content) predominated (30% of cells), while 25% and 20% of cells were in the states of maximal activity and elevated activity respectively. In diestrus, neurons in the resting state, in moderate and elevated activity, in maximal activity, and in decreased activity type 1 were present in essentially identical proportions (18%, 21%, 18%, 20%, and 16% respectively). In males, 35% and 22% of neurons were in the states of elevated and maximal activity respectively. Neuron death was seen only in males.

Distinct mechanisms act in concert to mediate cell cycle arrest.

PubMed

Toettcher, Jared E; Loewer, Alexander; Ostheimer, Gerard J; Yaffe, Michael B; Tidor, Bruce; Lahav, Galit

2009-01-20

In response to DNA damage, cells arrest at specific stages in the cell cycle. This arrest must fulfill at least 3 requirements: it must be activated promptly; it must be sustained as long as damage is present to prevent loss of genomic information; and after the arrest, cells must re-enter into the appropriate cell cycle phase to ensure proper ploidy. Multiple molecular mechanisms capable of arresting the cell cycle have been identified in mammalian cells; however, it is unknown whether each mechanism meets all 3 requirements or whether they act together to confer specific functions to the arrest. To address this question, we integrated mathematical models describing the cell cycle and the DNA damage signaling networks and tested the contributions of each mechanism to cell cycle arrest and re-entry. Predictions from this model were then tested with quantitative experiments to identify the combined action of arrest mechanisms in irradiated cells. We find that different arrest mechanisms serve indispensable roles in the proper cellular response to DNA damage over time: p53-independent cyclin inactivation confers immediate arrest, whereas p53-dependent cyclin downregulation allows this arrest to be sustained. Additionally, p21-mediated inhibition of cyclin-dependent kinase activity is indispensable for preventing improper cell cycle re-entry and endoreduplication. This work shows that in a complex signaling network, seemingly redundant mechanisms, acting in a concerted fashion, can achieve a specific cellular outcome.

Influence of biological soil crusts at different successional stages in the implantation of biogeochemical cycles in arid and semiarid zones

NASA Astrophysics Data System (ADS)

Gil-Sotres, F.; Miralles, I.; Canton-Castilla, Y.; Domingo, F.; Leiros, M. C.; Trasar-Cepeda, C.

2012-04-01

Influence of biological soil crusts at different successional stages in the implantation of biogeochemical cycles in arid and semiarid zones I. Miralles1, F. Gil-Sotres2, Y. Cantón-Castilla3, F. Domingo1, M.C. Leirós2, C. Trasar-Cepeda4 1 Experimental Estation of Arid Zones (CSIC), E-04230 La Cañada de San Urbano, Almería, Spain. 2 Departamento Edafología y Química Agrícola, Grupo de Evaluación de la Calidad del Suelo, Unidad Asociada CSIC, Facultad de Farmacia, Universidad de Santiago de Compostela, E-15782 Santiago de Compostela, Spain. 3 University of Almería, Departamento de Edafología y Química Agrícola, E-04230-La Cañada de San Urbano, Almería, Spain. 4 Departamento Bioquímica del Suelo, IIAG-CSIC, Apartado 122, E-15708 Santiago de Compostela, Spain. Crusts (BSCs) are formed by a close association between soil particles and cyanobacteria, algae, lichens, bryophytes and microfungi in varying proportions. Their habitat is within or immediately on top of the uppermost millimetres of the soil and are the predominant surface cover in arid and semiarid zones. Among the diverse functions developed by BSCs in the ecosystem (hydrology, erosion, soil properties, etc.), one of the most important is its role in nutrient cycling. Within arid and semiarid environments, BSCs have been termed 'mantles of fertility' being considered hotspots of biogeochemical inputs, fixing C, N and P above- and below-ground. However, there are differences in N and C fixation rates between BSCs types. Early successional BSCs, dominated by cyanobacterial species, fix lower quantities of C and N than mature BSCs dominated by lichens. Although the positive effects of BSCs on biogeochemical soil cycles are widely accepted, no previous studies have evaluated the activities of the enzymes involved in C, N and P cycles of BSCs and how they are affected by the successional stage of the BSC. In this work, performed in the Tabernas desert (SE Spain), we studied the hydrolase enzymes involved in C (invertase, CM-cellulase, β-glucosidase), N (urease, BAA-protease, casein-protease) and P (phosphomonoesterase) cycles in BSCs at different successional stages (cyanobacteria represents the first successional stage, lichen Diploschistes diacapsis in an intermediate state and lichen Lepraria crassissima, with the greatest successional state). Our results show that BSCs at lower successional stage enriched the surface geological substrate in hydrolase enzymes to a lesser extent than mature BSCs (Lepraria crassissima), which show the highest values in all enzymatic activities. In contrast, the specific enzyme activities (activity values expressed per unit of carbon) were higher in the BSCs at lower successional stage, decreasing in the direction: cyanobacteria > Diploschistes diacapsis-lichen > Lepraria crassissima-lichen. These results suggest a different role of BSCs depending on their successional stage with regard to the implantation of biogeochemical cycles during the surface substrate colonization. Our conclusions are highly relevant to improve the knowledge of biogeochemical cycles in arid and semiarid areas. Keywords: Biological Soil Crusts, arid ecosystems, hydrolytic enzymes, biochemical activity

CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs?

PubMed

Lolli, Graziano; Johnson, Louise N

2005-04-01

The Cyclin-dependent kinase (CDK) Activating Kinase (CAK) is responsible for the activating phosphorylation of CDK1, CDK2, CDK4 and CDK6 and regulation of the cell cycle. The kinase is composed of three subunits: CDK7, Cyclin H and MAT1 (ménage a trois). Together with six other subunits, CAK is also part of the general transcription factor TFIIH where it is involved in promoter clearance and progression of transcription from the preinitiation to the initiation stage. CAK is required for cell cycle progression, which suggests that CDK7 could be a target for cancer therapy. However its role in transcription and its ubiquitous presence raise sensible concerns about possible toxicity of its inhibitors. The recently determined structure of CDK7 allows the design of inhibitors with differential specificity for the different CDKs. We review the role of CAK in different biological processes and evaluate the biological evidence for CDK7 as a possible pharmacological target.

Two stage sorption type cryogenic refrigerator including heat regeneration system

NASA Technical Reports Server (NTRS)

Jones, Jack A. (Inventor); Wen, Liang-Chi (Inventor); Bard, Steven (Inventor)

1989-01-01

A lower stage chemisorption refrigeration system physically and functionally coupled to an upper stage physical adsorption refrigeration system is disclosed. Waste heat generated by the lower stage cycle is regenerated to fuel the upper stage cycle thereby greatly improving the energy efficiency of a two-stage sorption refrigerator. The two stages are joined by disposing a first pressurization chamber providing a high pressure flow of a first refrigerant for the lower stage refrigeration cycle within a second pressurization chamber providing a high pressure flow of a second refrigerant for the upper stage refrigeration cycle. The first pressurization chamber is separated from the second pressurization chamber by a gas-gap thermal switch which at times is filled with a thermoconductive fluid to allow conduction of heat from the first pressurization chamber to the second pressurization chamber.

Hormone-dependence of sarin lethality in rats: Sex differences and stage of the estrous cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Carl D., E-mail: carl.d.smith179.mil@mail.mil; Wright, Linnzi K.M.; Garcia, Gregory E.

Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was tomore » determine the 24-hour median lethal dose (LD{sub 50}) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD{sub 50} of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD{sub 50}s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity. - Highlights: • The LD{sub 50} of sarin was determined in female rats throughout the stages of the estrous cycle. • Females in proestrus had a significantly higher LD{sub 50} compared to estrous or ovariectomized females. • No sex differences were observed between male and female rats. • It is unlikely that plasma esterase activity underlies the observed differences in LD{sub 50}s.« less

Materials, Processes and Manufacturing in Ares 1 Upper Stage: Integration with Systems Design and Development

NASA Technical Reports Server (NTRS)

Bhat, Biliyar N.

2008-01-01

Ares I Crew Launch Vehicle Upper Stage is designed and developed based on sound systems engineering principles. Systems Engineering starts with Concept of Operations and Mission requirements, which in turn determine the launch system architecture and its performance requirements. The Ares I-Upper Stage is designed and developed to meet these requirements. Designers depend on the support from materials, processes and manufacturing during the design, development and verification of subsystems and components. The requirements relative to reliability, safety, operability and availability are also dependent on materials availability, characterization, process maturation and vendor support. This paper discusses the roles and responsibilities of materials and manufacturing engineering during the various phases of Ares IUS development, including design and analysis, hardware development, test and verification. Emphasis is placed how materials, processes and manufacturing support is integrated over the Upper Stage Project, both horizontally and vertically. In addition, the paper describes the approach used to ensure compliance with materials, processes, and manufacturing requirements during the project cycle, with focus on hardware systems design and development.

Expression of progesterone receptor membrane component-2 within the immature rat ovary and its role in regulating mitosis and apoptosis of spontaneously immortalized granulosa cells.

PubMed

Griffin, Daniel; Liu, Xiufang; Pru, Cindy; Pru, James K; Peluso, John J

2014-08-01

Progesterone receptor membrane component 2 (Pgrmc2) mRNA was detected in the immature rat ovary. By 48 h after eCG, Pgrmc2 mRNA levels decreased by 40% and were maintained at 48 h post-hCG. Immunohistochemical studies detected PGRMC2 in oocytes and ovarian surface epithelial, interstitial, thecal, granulosa, and luteal cells. PGRMC2 was also present in spontaneously immortalized granulosa cells, localizing to the cytoplasm of interphase cells and apparently to the mitotic spindle of cells in metaphase. Interestingly, PGRMC2 levels appeared to decrease during the G1 stage of the cell cycle. Moreover, overexpression of PGRMC2 suppressed entry into the cell cycle, possibly by binding the p58 form of cyclin dependent kinase 11b. Conversely, Pgrmc2 small interfering RNA (siRNA) treatment increased the percentage of cells in G1 and M stage but did not increase the number of cells, which was likely due to an increase in apoptosis. Depleting PGRMC2 did not inhibit cellular (3)H-progesterone binding, but attenuated the ability of progesterone to suppress mitosis and apoptosis. Taken together these studies suggest that PGRMC2 affects granulosa cell mitosis by acting at two specific stages of the cell cycle. First, PGRMC2 regulates the progression from the G0 into the G1 stage of the cell cycle. Second, PGRMC2 appears to localize to the mitotic spindle, where it likely promotes the final stages of mitosis. Finally, siRNA knockdown studies indicate that PGRMC2 is required for progesterone to slow the rate of granulosa cell mitosis and apoptosis. These findings support a role for PGRMC2 in ovarian follicle development. © 2014 by the Society for the Study of Reproduction, Inc.

Two-statge sorption type cryogenic refrigerator including heat regeneration system

NASA Technical Reports Server (NTRS)

Jones, Jack A. (Inventor); Wen, Liang-Chi (Inventor); Bard, Steven (Inventor)

1989-01-01

A lower stage chemisorption refrigeration system physically and functionally coupled to an upper stage physical adsorption refrigeration system. Waste heat generated by the lower stage cycle is regenerated to fuel the upper stage cycle thereby greatly improving the energy efficiency of a two-stage sorption refrigerator. The two stages are joined by disposing a first pressurization chamber providing a high pressure flow of a first refrigerant for the lower stage refrigeration cycle within a second pressurization chamber providing a high pressure flow of a second refrigerant for the upper stage refrigeration cycle. The first pressurization chamber is separated from the second pressurization chamber by a gas-gap thermal switch which at times is filled with a thermoconductive fluid to allow conduction of heat from the first pressurization chamber to the second pressurization chamber.

Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host

PubMed Central

Goulielmaki, Evi; Chalari, Anna; Withers-Martinez, Chrislaine; Siden-Kiamos, Inga; Matuschewski, Kai

2017-01-01

Site-2 proteases (S2P) belong to the M50 family of metalloproteases, which typically perform essential roles by mediating activation of membrane–bound transcription factors through regulated intramembrane proteolysis (RIP). Protease-dependent liberation of dormant transcription factors triggers diverse cellular responses, such as sterol regulation, Notch signalling and the unfolded protein response. Plasmodium parasites rely on regulated proteolysis for controlling essential pathways throughout the life cycle. In this study we examine the Plasmodium-encoded S2P in a murine malaria model and show that it is expressed in all stages of Plasmodium development. Localisation studies by endogenous gene tagging revealed that in all invasive stages the protein is in close proximity to the nucleus. Ablation of PbS2P by reverse genetics leads to reduced growth rates during liver and blood infection and, hence, virulence attenuation. Strikingly, absence of PbS2P was compatible with parasite life cycle progression in the mosquito and mammalian hosts under physiological conditions, suggesting redundant or dispensable roles in vivo. PMID:28107409

Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host.

PubMed

Koussis, Konstantinos; Goulielmaki, Evi; Chalari, Anna; Withers-Martinez, Chrislaine; Siden-Kiamos, Inga; Matuschewski, Kai; Loukeris, Thanasis G

2017-01-01

Site-2 proteases (S2P) belong to the M50 family of metalloproteases, which typically perform essential roles by mediating activation of membrane-bound transcription factors through regulated intramembrane proteolysis (RIP). Protease-dependent liberation of dormant transcription factors triggers diverse cellular responses, such as sterol regulation, Notch signalling and the unfolded protein response. Plasmodium parasites rely on regulated proteolysis for controlling essential pathways throughout the life cycle. In this study we examine the Plasmodium-encoded S2P in a murine malaria model and show that it is expressed in all stages of Plasmodium development. Localisation studies by endogenous gene tagging revealed that in all invasive stages the protein is in close proximity to the nucleus. Ablation of PbS2P by reverse genetics leads to reduced growth rates during liver and blood infection and, hence, virulence attenuation. Strikingly, absence of PbS2P was compatible with parasite life cycle progression in the mosquito and mammalian hosts under physiological conditions, suggesting redundant or dispensable roles in vivo.

Effect of Temperature on the Biotic Potential of Honeybee Microsporidia▿

PubMed Central

Martín-Hernández, Raquel; Meana, Aránzazu; García-Palencia, Pilar; Marín, Pilar; Botías, Cristina; Garrido-Bailón, Encarna; Barrios, Laura; Higes, Mariano

2009-01-01

The biological cycle of Nosema spp. in honeybees depends on temperature. When expressed as total spore counts per day after infection, the biotic potentials of Nosema apis and N. ceranae at 33°C were similar, but a higher proportion of immature stages of N. ceranae than of N. apis were seen. At 25 and 37°C, the biotic potential of N. ceranae was higher than that of N. apis. The better adaptation of N. ceranae to complete its endogenous cycle at different temperatures clearly supports the observation of the different epidemiological patterns. PMID:19233948

Effect of temperature on the biotic potential of honeybee microsporidia.

PubMed

Martín-Hernández, Raquel; Meana, Aránzazu; García-Palencia, Pilar; Marín, Pilar; Botías, Cristina; Garrido-Bailón, Encarna; Barrios, Laura; Higes, Mariano

2009-04-01

The biological cycle of Nosema spp. in honeybees depends on temperature. When expressed as total spore counts per day after infection, the biotic potentials of Nosema apis and N. ceranae at 33 degrees C were similar, but a higher proportion of immature stages of N. ceranae than of N. apis were seen. At 25 and 37 degrees C, the biotic potential of N. ceranae was higher than that of N. apis. The better adaptation of N. ceranae to complete its endogenous cycle at different temperatures clearly supports the observation of the different epidemiological patterns.

Cellular localization and changes in expression of prolactin receptor isoforms in sheep ovary throughout the estrous cycle.

PubMed

Picazo, R A; García Ruiz, J P; Santiago Moreno, J; González de Bulnes, A; Muñoz, J; Silván, G; Lorenzo, P L; Illera, J C

2004-11-01

The actions of prolactin (PRL) on target cells depend on the type of prolactin receptor (PRLr) predominantly expressed, particularly whether the long PRLr isoform is expressed. The aims of this study were to determine the cellular localization and the changes in expression of long and short PRLr isoforms in sheep ovary throughout the estrous cycle. Long and short PRLrs were localized mostly in the same ovarian cells. Maximum signal intensity, particularly for long PRLrs, was found in stromal cells surrounding primordial and primary follicles, and, for both PRLrs, in granulosa cells of preantral follicles and in luteal cells. Moderate signal intensity for PRLrs was found in theca cells of preantral to ovulatory follicles, and in granulosa cells of antral follicles up to the gonadotropin-dependent stage. Decreasing immunoreactivity to PRLrs was found in granulosa cells of gonadotropin-dependent to ovulatory follicles. For long PRLrs in particular, no signal was found in mural granulosa cells of gonadotropin-dependent follicles; for both isoforms, no signal was found in most granulosa cells of ovulatory follicles. In primordial to gonadotropin-dependent follicles, cellular localization of PRLr was similar on days 0, 10 and 15 of the cycle. Oocytes consistently showed positive immunostaining for PRLrs. Comparative RT-PCR analysis of long and short PRLr expression showed that the short isoform is evenly expressed throughout the estrous cycle, whereas the expression of the long form increases at the time of estrus and decreases at mid-luteal phase and at the onset of the follicular phase. Expression of long PRLrs was greater than that of short PRLrs on day 0 of cycle; expression of both isoforms was similar on day 10 and on day 15, long PRLrs expression was lower than that of short PRLrs. Our results indicate that in sheep ovary, the maximum responsiveness to PRL might occur during the preovulatory phase of the estrous cycle.

Eddy current sensing of intermetallic composite consolidation

NASA Technical Reports Server (NTRS)

Dharmasena, Kumar P.; Wadley, Haydn N. G.

1991-01-01

A finite element method is used to explore the feasibility and optimization of a probe-type eddy current sensor for determining the thickness of plate specimens during a hot isostatic pressing cycle. The dependence of the sensor's impedance upon sample-sensor separation in the high frequency limit is calculated, and factors that maximize sensitivity to the final stages of densification are identified.

Complex life cycles and offspring provisioning in marine invertebrates.

PubMed

Marshall, Dustin J; Keough, Michael J

2006-10-01

Offspring size can have pervasive effects throughout an organism's life history. Mothers can make either a few large or many small offspring, and the balance between these extremes is determined by the relationship between offspring size and performance. This relationship in turn is thought to be determined by the offspring's environment. Recently, it has become clear that events in one life-history stage can strongly affect performance in another. Given these strong carryover effects, we asked whether events in the larval phase can change the relationship between offspring size and performance in the adult phase. We manipulated the length of the larval period in the bryozoan Bugula neritina and then examined the relationship between offspring size and various parameters of adult performance under field conditions. We found that despite the adult stage being outplanted into identical conditions, different offspring sizes were predicted to be optimal, depending on the experience of those adults as larvae. This work highlights the fact that the strong phenotypic links between life-history stages may result in optimal offspring size being highly unpredictable for organisms with complex life cycles.

Lactic Acid Bacteria in Durum Wheat Flour Are Endophytic Components of the Plant during Its Entire Life Cycle.

PubMed

Minervini, Fabio; Celano, Giuseppe; Lattanzi, Anna; Tedone, Luigi; De Mastro, Giuseppe; Gobbetti, Marco; De Angelis, Maria

2015-10-01

This study aimed at assessing the dynamics of lactic acid bacteria and other Firmicutes associated with durum wheat organs and processed products. 16S rRNA gene-based high-throughput sequencing showed that Lactobacillus, Streptococcus, Enterococcus, and Lactococcus were the main epiphytic and endophytic genera among lactic acid bacteria. Bacillus, Exiguobacterium, Paenibacillus, and Staphylococcus completed the picture of the core genus microbiome. The relative abundance of each lactic acid bacterium genus was affected by cultivars, phenological stages, other Firmicutes genera, environmental temperature, and water activity (aw) of plant organs. Lactobacilli, showing the highest sensitivity to aw, markedly decreased during milk development (Odisseo) and physiological maturity (Saragolla). At these stages, Lactobacillus was mainly replaced by Streptococcus, Lactococcus, and Enterococcus. However, a key sourdough species, Lactobacillus plantarum, was associated with plant organs during the life cycle of Odisseo and Saragolla wheat. The composition of the sourdough microbiota and the overall quality of leavened baked goods are also determined throughout the phenological stages of wheat cultivation, with variations depending on environmental and agronomic factors. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Lactic Acid Bacteria in Durum Wheat Flour Are Endophytic Components of the Plant during Its Entire Life Cycle

PubMed Central

Minervini, Fabio; Celano, Giuseppe; Lattanzi, Anna; Tedone, Luigi; De Mastro, Giuseppe; De Angelis, Maria

2015-01-01

This study aimed at assessing the dynamics of lactic acid bacteria and other Firmicutes associated with durum wheat organs and processed products. 16S rRNA gene-based high-throughput sequencing showed that Lactobacillus, Streptococcus, Enterococcus, and Lactococcus were the main epiphytic and endophytic genera among lactic acid bacteria. Bacillus, Exiguobacterium, Paenibacillus, and Staphylococcus completed the picture of the core genus microbiome. The relative abundance of each lactic acid bacterium genus was affected by cultivars, phenological stages, other Firmicutes genera, environmental temperature, and water activity (aw) of plant organs. Lactobacilli, showing the highest sensitivity to aw, markedly decreased during milk development (Odisseo) and physiological maturity (Saragolla). At these stages, Lactobacillus was mainly replaced by Streptococcus, Lactococcus, and Enterococcus. However, a key sourdough species, Lactobacillus plantarum, was associated with plant organs during the life cycle of Odisseo and Saragolla wheat. The composition of the sourdough microbiota and the overall quality of leavened baked goods are also determined throughout the phenological stages of wheat cultivation, with variations depending on environmental and agronomic factors. PMID:26187970

Analysis of uncultured extremophilic snow algae by non-invasive single cell Raman spectroscopy

NASA Astrophysics Data System (ADS)

Beer, Thomas; Tanaka, Zuki; Netzter, Nathan; Rothschild, Lynn J.; Chen, Bin

2011-10-01

The study of life in extreme environments is a critical component of Astrobiology. But many of the so-called "extremophiles" are not readily cultivatable and therefore difficult to study under laboratory conditions. An example of such an extremophile is the snow alga Chlamydomonas cd. nivalis which expresses still unstudied secondary metabolites within its life cycle. In this paper, we present the first time the non-invasive single cell Raman spectroscopy of the life cycle dependent metabolite composition of C. nivalis. These secondary metabolites are likely related to the adaptation of C. nivalis to various stress factors. Normalized carotenoid Raman spectra intensities reveal characteristic ratio differences that allow identification of life cycle stages and putative secondary metabolites.

Detection of density dependence requires density manipulations and calculation of lambda.

PubMed

Fowler, N L; Overath, R Deborah; Pease, Craig M

2006-03-01

To investigate density-dependent population regulation in the perennial bunchgrass Bouteloua rigidiseta, we experimentally manipulated density by removing adults or adding seeds to replicate quadrats in a natural population for three annual intervals. We monitored the adjacent control quadrats for 14 annual intervals. We constructed a population projection matrix for each quadrat in each interval, calculated lambda, and did a life table response experiment (LTRE) analysis. We tested the effects of density upon lambda by comparing experimental and control quadrats, and by an analysis of the 15-year observational data set. As measured by effects on lambda and on N(t+1/Nt in the experimental treatments, negative density dependence was strong: the population was being effectively regulated. The relative contributions of different matrix elements to treatment effect on lambda differed among years and treatments; overall the pattern was one of small contributions by many different life cycle stages. In contrast, density dependence could not be detected using only the observational (control quadrats) data, even though this data set covered a much longer time span. Nor did experimental effects on separate matrix elements reach statistical significance. These results suggest that ecologists may fail to detect density dependence when it is present if they have only descriptive, not experimental, data, do not have data for the entire life cycle, or analyze life cycle components separately.

TRANSCRIPTOME ANALYSES REVEAL DIFFERENTIAL GENE EXPRESSION PATTERNS BETWEEN THE LIFE-CYCLE STAGES OF EMILIANIA HUXLEYI (HAPTOPHYTA) AND REFLECT SPECIALIZATION TO DIFFERENT ECOLOGICAL NICHES(1).

PubMed

Rokitta, Sebastian D; de Nooijer, Lennart J; Trimborn, Scarlett; de Vargas, Colomban; Rost, Björn; John, Uwe

2011-08-01

Coccolithophores, especially the abundant, cosmopolitan species Emiliania huxleyi (Lohmann) W. W. Hay et H. P. Mohler, are one of the main driving forces of the oceanic carbonate pump and contribute significantly to global carbon cycling, due to their ability to calcify. A recent study indicates that termination of diploid blooms by viral infection induces life-cycle transition, and speculation has arisen about the role of the haploid, noncalcifying stage in coccolithophore ecology. To explore gene expression patterns in both life-cycle stages, haploid and diploid cells of E. huxleyi (RCC 1217 and RCC 1216) were acclimated to limiting and saturating photon flux densities. Transcriptome analyses were performed to assess differential genomic expression related to different ploidy levels and acclimation light intensities. Analyses indicated that life-cycle stages exhibit different properties of regulating genome expression (e.g., pronounced gene activation and gene silencing in the diploid stage), proteome maintenance (e.g., increased turnover of proteins in the haploid stage), as well as metabolic processing (e.g., pronounced primary metabolism and motility in the haploid stage and calcification in the diploid stage). Furthermore, higher abundances of transcripts related to endocytotic and digestive machinery were observed in the diploid stage. A qualitative feeding experiment indicated that both life-cycle stages are capable of particle uptake (0.5 μm diameter) in late-stationary growth phase. Results showed that the two life-cycle stages represent functionally distinct entities that are evolutionarily shaped to thrive in the environment they typically inhabit. © 2011 Phycological Society of America.

Effects of exogenous hormones on spermatogenesis in the male prairie dog (Cynomys ludovicianus).

PubMed

Foreman, D

1998-01-01

Male prairie dogs (Cynomys ludovicianus) breed anually and have complete testicular regression. Changes in the seminiferous tubules during the annual cycle have been described recently (Foreman, 1997). This is the first description of spermatogenesis in such a species. The definition of tubular stages during the cycle allows for evaluation of the effects of exogenous hormones, hemicastration, and hemicryptorchidism on spermatogenesis during the annual cycle. Hemicastration was performed during stages of the annual cycle to determine effects of exogenous hormones on remaining testes. Hemicryptorchidism was also done during stages of the annual cycle. FSH, LH, and testosterone were given in high and low doses for short- or long-term treatment periods during stages of the annual cycle. Testicular weights and counts of cell types in tubules of control and treated testes were made on testis tissues. Hemicastration during the out-of-season period does not cause compensatory hypertrophy of the remaining testis, but during recrudescence, hypertrophy of the remaining testis occurs. Hemicastration does not prevent loss of weight by the remaining testis during regression. The seminiferous epithelium of hemicryptorchid prairie dog testes shows damage during spermatogenic activity but not during testicular inactivity. Similarly, hemicryptorchid 15-day-old rat testes do not show damage from hemicryptorchidism. Long-term treatment with FSH preparations during testicular inactivity increased testis weights, spermatogonial proliferation, and spermatocyte differentiation in conjunction with Sertoli cell differentiation. Short-term treatments with low doses increased spermatogonial proliferation and abnormal meiotic activity. Both long- and short-term treatments with LH caused increased sloughing of germ cells and stimulated Leydig and Sertoli cells. Testosterone propionate injections stimulated Sertoli secretions but not Leydig cell activity. Hemicastration during inactivity does not stimulate gonadotropin secretion. Hemicryptorchidism does not affect tubular morphology during inactivity in either rats or prairie dogs. Prompt responses to FSH depend on scrotal location of the testis. FSH has its major effects on germ cell proliferation and differentiation, both directly and through activation of Sertoli cells, whereas LH affects Sertoli and Leydig cell activation but has no effect on germ cell activity. Testosterone activates Sertoli cells.

Energy Dissipation-Based Method for Fatigue Life Prediction of Rock Salt

NASA Astrophysics Data System (ADS)

He, Mingming; Huang, Bingqian; Zhu, Caihui; Chen, Yunsheng; Li, Ning

2018-05-01

The fatigue test for rock salt is conducted under different stress amplitudes, loading frequencies, confining pressures and loading rates, from which the evaluation rule of the dissipated energy is revealed and analysed. The evolution of energy dissipation under fatigue loading is divided into three stages: the initial stage, the second stage and the acceleration stage. In the second stage, the energy dissipation per cycle remains stable and shows an exponential relation with the stress amplitude; the failure dissipated energy only depends on the mechanical behaviour of the rock salt and confining pressure, but it is immune to the loading conditions. The energy dissipation of fatigued rock salt is discussed, and a novel model for fatigue life prediction is proposed on the basis of energy dissipation. A simple model for evolution of the accumulative dissipated energy is established. Its prediction results are compared with the test results, and the proposed model is validated.

The role of cGMP signalling in regulating life cycle progression of Plasmodium.

PubMed

Hopp, Christine S; Bowyer, Paul W; Baker, David A

2012-08-01

The 3'-5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue in ookinete differentiation and motility, and liver stage schizont development. The current views on potential effector proteins downstream of PKG and the mechanisms that may regulate cyclic nucleotide levels are presented. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Differential effects of insulin-like growth factor I and growth hormone on developmental stages of rat growth plate chondrocytes in vivo.

PubMed Central

Hunziker, E B; Wagner, J; Zapf, J

1994-01-01

Skeletal growth depends upon enchondral ossification in growth plate cartilage, within which chondrocytes undergo well defined stages of maturation. We infused IGF-I or growth hormone (GH), two key regulators of skeletal growth, into hypophysectomized rats and compared their effects on growth plate chondrocyte differentiation using qualitative and quantitative autoradiography, stereology, and incident light fluorescence microscopy. Stem cell cycle time was shortened from 50 to 15 and 8 d after treatment with IGF-I and GH, respectively. Proliferating cell cycle time decreased from 11 to 4.5 and 3 d, and duration of the hypertrophic phase decreased from 6 to 4 and 2.8 d. Average matrix volume per cell at each differentiation stage was similar for normal, hormone-treated, and untreated hypophysectomized groups. Mean cell volume and cell height were significantly reduced by hypophysectomy at the proliferative and hypertrophic stages, but were restored to physiological values by IGF-I and GH. In contrast, cell productivity, i.e., increases in cell volume, height, and matrix production per unit of time, did not reach normal values with either IGF-I or GH, and this parameter was inversely proportional to cell cycle time or phase duration. IGF-I and GH are thus capable of stimulating growth plate chondrocytes at all stages of differentiation, albeit to variable degrees with respect to individual cell activities. Although it is generally accepted that GH acts at both the stem and proliferating phases of chondrocyte differentiation, our data represent the first evidence in vivo that IGF-I is also capable of stimulating stem cells. Images PMID:8132746

Whole-genome analysis of mRNA decay in Plasmodium falciparum reveals a global lengthening of mRNA half-life during the intra-erythrocytic development cycle.

PubMed

Shock, Jennifer L; Fischer, Kael F; DeRisi, Joseph L

2007-01-01

The rate of mRNA decay is an essential element of post-transcriptional regulation in all organisms. Previously, studies in several organisms found that the specific half-life of each mRNA is precisely related to its physiologic role, and plays an important role in determining levels of gene expression. We used a genome-wide approach to characterize mRNA decay in Plasmodium falciparum. We found that, globally, rates of mRNA decay increase dramatically during the asexual intra-erythrocytic developmental cycle. During the ring stage of the cycle, the average mRNA half-life was 9.5 min, but this was extended to an average of 65 min during the late schizont stage of development. Thus, a major determinant of mRNA decay rate appears to be linked to the stage of intra-erythrocytic development. Furthermore, we found specific variations in decay patterns superimposed upon the dominant trend of progressive half-life lengthening. These variations in decay pattern were frequently enriched for genes with specific cellular functions or processes. Elucidation of Plasmodium mRNA decay rates provides a key element for deciphering mechanisms of genetic control in this parasite, by complementing and extending previous mRNA abundance studies. Our results indicate that progressive stage-dependent decreases in mRNA decay rate function are a major determinant of mRNA accumulation during the schizont stage of intra-erythrocytic development. This type of genome-wide change in mRNA decay rate has not been observed in any other organism to date, and indicates that post-transcriptional regulation may be the dominant mechanism of gene regulation in P. falciparum.

The impact of p53 on the early stage replication of retrovirus.

PubMed

Kinnetz, Michaela; Alghamdi, Faris; Racz, Michael; Hu, Wenwei; Shi, Binshan

2017-08-09

The function of p53 in cancer biology has been studied extensively, but its role in anti-retrovirus infection has been elusive for many years. The restriction of retrovirus early stage replication by p53 was investigated in this study. VSV-G pseudotyped retrovirus with GFP reporter gene was used to infect both HCT116 p53 +/+ cells and its isogenic p53 knockout HCT116 p53 -/- cells. The infection was detected by flow cytometry. Reverse transcription products were quantified by real time PCR. Mutation analysis was performed after 1-LTR cycle and 2-LTR cycle DNA were amplified and PCR products were sequenced. Transcription and translation of cyclin-dependent kinase inhibitor 1 (p21 Cip1 ) and SAM domain and HD domain-containing protein 1 (SAMHD1) were analyzed by TaqMan PCR and Western blot experiments. siRNA experiment was applied to study the role of p53 downstream gene p21 Cip1 in the restriction of retrovirus infection. It was found that the block of retrovirus infection in non-cycling cells was significantly attenuated in HCT116 p53 -/- cells when compared to HCT116 p53 +/+ cells. It was found that both late reverse transcription products and viral 2-LTR cycle DNA were significantly increased in infected non-cycling HCT116 p53 -/- cells. Furthermore, the mutation frequency detected in 1-LTR DNA from HCT116 p53 +/+ cells were significantly decreased in comparison to HCT116 p53 -/- cells. A higher number of insertion and deletion mutations were detected in the joint region of 2-LTR cycle DNA in infected p53 +/+ cells. Cell cycle analysis showed retrovirus infection promoted host cell replication. Higher levels of mRNA and protein of p21 Cip1 were found in HCT116 p53 +/+ cells in comparison to the HCT116 p53 -/- cells. Furthermore, knockdown of p21 Cip1 in non-cycling HCT116 p53 +/+ cells significantly increased the infection. The results of this study showed that p53 is an important restriction factor that interferes with retrovirus infection in its early stage of replication. Our results suggested that p53 mediates the inhibition of retrovirus infection in non-cycling cells through it downstream gene p21 Cip1 , and p53 also functions to influence formation of 1-LTR cycle and 2-LTR cycle DNA.

Carbohydrate dependence during prolonged simulated cycling time trials.

PubMed

Torrens, Samuel L; Areta, José L; Parr, Evelyn B; Hawley, John A

2016-04-01

We determined the effect of suppressing lipolysis via administration of Nicotinic acid (NA) and pre-exercise feeding on rates of whole-body substrate utilisation and cycling time trial (TT) performance. In a randomised, single-blind, crossover design, eight trained male cyclists/triathletes completed two series of TTs in which they performed a predetermined amount of work calculated to last ~60, 90 and 120 min. TTs were undertaken after a standardised breakfast (2 g kg(-1) BM of carbohydrate (CHO)) and ingestion of capsules containing either NA or placebo (PL). Plasma [free fatty acids] were suppressed with NA, but increased in the later stages of TT90 and TT120 with PL (p < 0.05). There was no treatment effect on time to complete TT60 (60.4 ± 4.1 vs. 59.3 ± 3.4 min) or TT90 (90.4 ± 9.1 vs. 89.5 ± 6.6 min) for NA and PL, respectively. However, TT120 was slower with NA (123.1 ± 5.7 vs. 120.1 ± 8.7 min, p < 0.001), which coincided with a decline in plasma [glucose] during the later stages of this ride (p < 0.05). For TTs of the same duration, the rates of whole-body CHO oxidation were unaffected by NA, but decreased with increasing TT time (p < 0.05). CHO was the predominant substrate for all TTs contributing between 83 and 94 % to total energy expenditure, although there was a small use of lipid-based fuels for all rides. (1) NA impaired cycling TT performance lasting 120 min, (2) cycling TTs lasting from 60 to 120 min are CHO dependent, and (3) there is an obligatory use of lipid-based fuels in TTs lasting 1-2 h.

Life Cycle of a Pencil.

ERIC Educational Resources Information Center

Reeske, Mike

2000-01-01

Explains a project called "Life Cycle of a Pencil" which was developed by the National Science Teachers Association (NSTA) and the U.S. Environmental Protection Agency (USEPA). Describes the life cycle of a pencil in stages starting from the first stage of design to the sixth stage of product disposal. (YDS)

Impact of hot events at different developmental stages of a moth: the closer to adult stage, the less reproductive output

PubMed Central

Zhang, Wei; Chang, Xiang-Qian; Hoffmann, AryA.; Zhang, Shu; Ma, Chun-Sen

2015-01-01

Hot days in summer (involving a few hours at particularly high temperatures) are expected to become more common under climate change. How such events at different life stages affect survival and reproduction remains unclear in most organisms. Here, we investigated how an exposure to 40 °C at different life stages in the global insect pest, Plutella xylostella, affects immediate survival, subsequent survival and reproductive output. First-instar larvae showed the lowest survival under heat stress, whereas 3rd-instar larvae were relatively heat resistant. Heat exposure at the 1st-instar or egg stage did not influence subsequent maturation success, while exposure at the 3rd-instar larval stage did have an effect. We found that heat stress at developmental stages closer to adult stage caused greater detrimental effects on reproduction than heat stress experienced at earlier life stages. The effects of hot events on insect populations can therefore depend critically on the timing of the event relative to an organism’s life-cycle. PMID:26000790

The Septins Function in G1 Pathways that Influence the Pattern of Cell Growth in Budding Yeast

PubMed Central

Egelhofer, Thea A.; Villén, Judit; McCusker, Derek; Gygi, Steven P.; Kellogg, Douglas R.

2008-01-01

The septins are a conserved family of proteins that have been proposed to carry out diverse functions. In budding yeast, the septins become localized to the site of bud emergence in G1 but have not been thought to carry out important functions at this stage of the cell cycle. We show here that the septins function in redundant mechanisms that are required for formation of the bud neck and for the normal pattern of cell growth early in the cell cycle. The Shs1 septin shows strong genetic interactions with G1 cyclins and is directly phosphorylated by G1 cyclin-dependent kinases, consistent with a role in early cell cycle events. However, Shs1 phosphorylation site mutants do not show genetic interactions with the G1 cyclins or obvious defects early in the cell cycle. Rather, they cause an increased cell size and aberrant cell morphology that are dependent upon inhibitory phosphorylation of Cdk1 at the G2/M transition. Shs1 phosphorylation mutants also show defects in interaction with the Gin4 kinase, which associates with the septins during G2/M and plays a role in regulating inhibitory phosphorylation of Cdk1. Phosphorylation of Shs1 by G1 cyclin-dependent kinases plays a role in events that influence Cdk1 inhibitory phosphorylation. PMID:18431499

Modulation of flagellum attachment zone protein FLAM3 and regulation of the cell shape in Trypanosoma brucei life cycle transitions

PubMed Central

Sunter, Jack D.; Benz, Corinna; Andre, Jane; Whipple, Sarah; McKean, Paul G.; Gull, Keith; Ginger, Michael L.; Lukeš, Julius

2015-01-01

ABSTRACT The cell shape of Trypanosoma brucei is influenced by flagellum-to-cell-body attachment through a specialised structure – the flagellum attachment zone (FAZ). T. brucei exhibits numerous morphological forms during its life cycle and, at each stage, the FAZ length varies. We have analysed FLAM3, a large protein that localises to the FAZ region within the old and new flagellum. Ablation of FLAM3 expression causes a reduction in FAZ length; however, this has remarkably different consequences in the tsetse procyclic form versus the mammalian bloodstream form. In procyclic form cells FLAM3 RNAi results in the transition to an epimastigote-like shape, whereas in bloodstream form cells a severe cytokinesis defect associated with flagellum detachment is observed. Moreover, we demonstrate that the amount of FLAM3 and its localisation is dependent on ClpGM6 expression and vice versa. This evidence demonstrates that FAZ is a key regulator of trypanosome shape, with experimental perturbations being life cycle form dependent. An evolutionary cell biology explanation suggests that these differences are a reflection of the division process, the cytoskeleton and intrinsic structural plasticity of particular life cycle forms. PMID:26148511

Metabolites Identified during Varied Doses of Aspergillus Species in Zea mays Grains, and Their Correlation with Aflatoxin Levels

PubMed Central

Chrysanthopoulos, Panagiotis K.; Hodson, Mark P.; Darnell, Ross; Korie, Sam

2018-01-01

Aflatoxin contamination is associated with the development of aflatoxigenic fungi such as Aspergillus flavus and A. parasiticus on food grains. This study was aimed at investigating metabolites produced during fungal development on maize and their correlation with aflatoxin levels. Maize cobs were harvested at R3 (milk), R4 (dough), and R5 (dent) stages of maturity. Individual kernels were inoculated in petri dishes with four doses of fungal spores. Fungal colonisation, metabolite profile, and aflatoxin levels were examined. Grain colonisation decreased with kernel maturity: milk-, dough-, and dent-stage kernels by approximately 100%, 60%, and 30% respectively. Aflatoxin levels increased with dose at dough and dent stages. Polar metabolites including alanine, proline, serine, valine, inositol, iso-leucine, sucrose, fructose, trehalose, turanose, mannitol, glycerol, arabitol, inositol, myo-inositol, and some intermediates of the tricarboxylic acid cycle (TCA—also known as citric acid or Krebs cycle) were important for dose classification. Important non-polar metabolites included arachidic, palmitic, stearic, 3,4-xylylic, and margaric acids. Aflatoxin levels correlated with levels of several polar metabolites. The strongest positive and negative correlations were with arabitol (R = 0.48) and turanose and (R = −0.53), respectively. Several metabolites were interconnected with the TCA; interconnections of the metabolites with the TCA cycle varied depending upon the grain maturity. PMID:29735944

Metabolites Identified during Varied Doses of Aspergillus Species in Zea mays Grains, and Their Correlation with Aflatoxin Levels.

PubMed

Falade, Titilayo D O; Chrysanthopoulos, Panagiotis K; Hodson, Mark P; Sultanbawa, Yasmina; Fletcher, Mary; Darnell, Ross; Korie, Sam; Fox, Glen

2018-05-07

Aflatoxin contamination is associated with the development of aflatoxigenic fungi such as Aspergillus flavus and A. parasiticus on food grains. This study was aimed at investigating metabolites produced during fungal development on maize and their correlation with aflatoxin levels. Maize cobs were harvested at R3 (milk), R4 (dough), and R5 (dent) stages of maturity. Individual kernels were inoculated in petri dishes with four doses of fungal spores. Fungal colonisation, metabolite profile, and aflatoxin levels were examined. Grain colonisation decreased with kernel maturity: milk-, dough-, and dent-stage kernels by approximately 100%, 60%, and 30% respectively. Aflatoxin levels increased with dose at dough and dent stages. Polar metabolites including alanine, proline, serine, valine, inositol, iso-leucine, sucrose, fructose, trehalose, turanose, mannitol, glycerol, arabitol, inositol, myo-inositol, and some intermediates of the tricarboxylic acid cycle (TCA—also known as citric acid or Krebs cycle) were important for dose classification. Important non-polar metabolites included arachidic, palmitic, stearic, 3,4-xylylic, and margaric acids. Aflatoxin levels correlated with levels of several polar metabolites. The strongest positive and negative correlations were with arabitol ( R = 0.48) and turanose and ( R = −0.53), respectively. Several metabolites were interconnected with the TCA; interconnections of the metabolites with the TCA cycle varied depending upon the grain maturity.

Cellular and functional characterization of buffalo (Bubalus bubalis) corpus luteum during the estrous cycle and pregnancy.

PubMed

Baithalu, Rubina Kumari; Singh, S K; Gupta, Chhavi; Raja, Anuj K; Saxena, Abhishake; Kumar, Yogendra; Singh, R; Agarwal, S K

2013-08-01

In the present paper, cellular composition of buffalo corpus luteum (CL) with its functional characterization based on 3β-HSD and progesterone secretory ability at different stages of estrous cycle and pregnancy was studied. Buffalo uteri along with ovaries bearing CL were collected from the local slaughter house. These were classified into different stages of estrous cycle (Stage I, II, III and IV) and pregnancy (Stage I, II and III) based on morphological appearance of CL, surface follicles on the ovary and crown rump length of conceptus. Luteal cell population, progesterone content and steroidogenic properties were studied by dispersion of luteal cells using collagenase type I enzyme, RIA and 3β-HSD activity, respectively. Large luteal cells (LLC) appeared as polyhedral or spherical in shape with a centrally placed large round nucleus and an abundance of cytoplasmic lipid droplets. However, small luteal cells (SLC) appeared to be spindle shaped with an eccentrically placed irregular nucleus and there was paucity of cytoplasmic lipid droplets. The size of SLC (range 12-23μm) and LLC (range 25-55μm) increased (P<0.01) with the advancement of stage of estrous cycle and pregnancy. The mean progesterone concentration per gram and per CL increased (P<0.01) from Stage I to III of estrous cycle with maximum concentration at Stage III of estrous cycle and pregnancy. The progesterone concentration decreased at Stage IV (day 17-20) of estrous cycle coinciding with CL regression. Total luteal cell number (LLC and SLC) also increased (P<0.01) from Stage I to III of estrous cycle and decreased (P<0.05), thereafter, at Stage IV indicating degeneration of luteal cells and regression of the CL. Total luteal cell population during pregnancy also increased (P<0.01) from Stage I to II and thereafter decreased (P>0.05) indicating cessation of mitosis. Increased (P<0.05) large luteal cell numbers from Stage I to III of estrous cycle and pregnancy coincided with the increased progesterone secretion and 3β-HSD activity of CL. Thus, proportionate increases of large compared with small luteal cells were primarily responsible for increased progesterone secretion during the advanced stages of the estrous cycle and pregnancy. Total luteal cells and progesterone content per CL during the mid-luteal stage in buffalo as observed in the present study seem to be less than with cattle suggesting inherent luteal deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Mechanisms of biotic resistance across complex life cycles.

PubMed

Rius, Marc; Potter, Elaine E; Aguirre, J David; Stachowicz, John J

2014-01-01

Biotic resistance is the ability of communities to inhibit the establishment, spread or impact of novel species. However, the interactions that underlie biotic resistance depend heavily on the contexts in which species interact. Consequently, studies of biotic resistance that consider single processes, patches, species or life-history stages may provide an incomplete picture of the capacity for communities to resist invasion. Many organisms have multiphasic life cycles, where individuals can occupy distinct niches at different stages of the life history. Generally, studies of biotic resistance focus on interactions within a single life-history stage, and interactions at other life-history stages are overlooked. Here, we demonstrate that different mechanisms of biotic resistance occur across the life history and together limit the invasion success of an introduced marine invertebrate (Ciona intestinalis) in Northern California. We tested the role of interactions (competition and predation) with the resident community in limiting the abundance of Ciona through experiments conducted on fertilization, larval survival, settlement, early postsettlement survival, and the survival of juveniles and adults. Under some circumstances, Ciona became abundant in mid-successional stages and showed more rapid growth rates than a morphologically similar native species, Ascidia ceratodes. However, predators reduced Ciona abundance much more than that of Ascidia at several life stages. Furthermore, Ciona appeared to be a weaker competitor at the adult stage. Early life-history interactions with other sessile species at the fertilization, larval and recruit stages had modest to no effects on Ciona abundance. The presence of biotic resistance mechanisms acting at multiple life stages, and potentially under different conditions, suggests that different components of biotic resistance interact to enhance the resident community's resistance to invasion. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

Hippocampal GABAA Receptor and Pain Sensitivity during Estrous Cycle in the Rat

PubMed Central

Taherianfard, Mahnaz; Mosavi, Mahnaz

2011-01-01

Background: Estradiol and progesterone as well as hippocampal GABAA receptors are believed to play a role in the modulation of pain. The aim of present study was to investigate the effect of intrahippocampal injections of GABAA receptor agonist (muscimol) and GABAA receptor antagonist (picrotoxin) on pain sensitivity during estrous cycle. Methods: Pain sensitivity was evaluated in rats by formalin test during all stages of estrous cycle. Animals were divided into five groups including; 1- control (intact animal); 2- sham 1 receiving 0.75 µl artificial cerebrospinal fluids (ACSF); 3- sham 2 receiving 0.75 µl alcoholic ACSF; 4- experimental 1 receiving 250 or 500 µg/rat of muscimol in 0.75 µl vehicle, and 5- experimental 2 receiving 20 or 30 µg/rat picrotoxin in 0.75 µl vehicle. Data were analyzed by Kruskal-Wallis followed by Tucky's test for pairwise comparisons using a P value of ≤0.50 for statistical significance. Results: Muscimol significantly (P<0.05) decreased pain sensitivity in all stages of estrous cycle, and the analgesic effect was higher during proestrus and estrus stages of estrous cycle than that during metestrus and diestrus stages. Picrotoxin significantly (P<0.05) increased pain sensitivity in all stages of estrous cycle, and such a hyperalgesic effect was lower during proestrus and estrus stages of estrous cycle than that during metestrus and diestrus stages. Conclusion: The findings of the present study indicate that the role of hippocampal GABAA receptor in the control of the pain sensitivity can be modulated by variation in gonadal steroids during different stages of the estrous cycle. PMID:23115414

The changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men.

PubMed

Huang, Rui; Zhu, Wei-Jie; Li, Jing; Gu, Yi-Qun

2014-12-01

To evaluate the changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men. Point counting method was used to analyze the stereological parameters of Leydig cells. The stage number of seminiferous epithelium cycle was calculated in the same testicular tissue samples which were used for Leydig cell stereological analysis. The aging group had shown more severe pathological changes as well as higher pathologic scores than the young group. Compared with the control group, the volume density (VV) and surface density (NA) of Leydig cells in the aging group were increased significantly. The stage number of seminiferous epithelium cycle in the aging group was decreased coincidently compared to the young group. Leydig cell Vv in the young group has a positive relationship with stages I, II, III, V and VI of seminiferous epithelium cycle, and Leydig cell NA and numerical density (NV) were positively related to stage IV. However, only the correlation between NV and stage II was found in the aging group. The stage number of seminiferous epithelium cycle was decreased in aging testes. Changes in the stage distribution in aging testes were related to the Leydig cell stereological parameters which presented as a sign of morphological changes. Copyright © 2014 Elsevier GmbH. All rights reserved.

From metamorphosis to maturity in complex life cycles: equal performance of different juvenile life history pathways.

PubMed

Schmidt, Benedikt R; Hödl, Walter; Schaub, Michael

2012-03-01

Performance in one stage of a complex life cycle may affect performance in the subsequent stage. Animals that start a new stage at a smaller size than conspecifics may either always remain smaller or they may be able to "catch up" through plasticity, usually elevated growth rates. We study how size at and date of metamorphosis affected subsequent performance in the terrestrial juvenile stage and lifetime fitness of spadefoot toads (Pelobates fuscus). We analyzed capture-recapture data of > 3000 individuals sampled during nine years with mark-recapture models to estimate first-year juvenile survival probabilities and age-specific first-time breeding probabilities of toads, followed by model selection to assess whether these probabilities were correlated with size at and date of metamorphosis. Males attained maturity after two years, whereas females reached maturity 2-4 years after metamorphosis. Age at maturity was weakly correlated with metamorphic traits. In both sexes, first-year juvenile survival depended positively on date of metamorphosis and, in males, also negatively on size at metamorphosis. In males, toads that metamorphosed early at a small size had the highest probability to reach maturity. However, because very few toadlets metamorphosed early, the vast majority of male metamorphs had a very similar probability to reach maturity. A matrix projection model constructed for females showed that different juvenile life history pathways resulted in similar lifetime fitness. We found that the effects of date of and size at metamorphosis on different juvenile traits cancelled each other out such that toads that were small or large at metamorphosis had equal performance. Because the costs and benefits of juvenile life history pathways may also depend on population fluctuations, ample phenotypic variation in life history traits may be maintained.

Is there a chronic sleep stage-dependent linear and nonlinear cardiac autonomic impairment in obstructive sleep apnea?

PubMed

Trimer, R; Mendes, R G; Costa, F S M; Sampaio, L M M; Delfino, A; Arena, R; Aletti, F; Ferrario, M; Borghi-Silva, A

2014-05-01

Obstructive sleep apnea (OSA) is a respiratory disorder that has the potential to negatively impact heart rate variability (HRV) during the sleep cycle. However, it is uncertain whether there is a chronic sleep stage-dependent linear and nonlinear cardiac autonomic impairment in OSA. The aim of this study was to perform HRV analysis in apnea-free samples as well as during stage 2 and rapid eye movement (REM) sleep in mild and moderate OSA (MiOSA and MOSA, respectively) subjects as well as health controls (NonOSA). This study included 20 MiOSA (37 ± 14 years), 20 MOSA (39 ± 8 years), and 18 NonOSA (36 ± 8 years) subjects. Subjects underwent in-laboratory overnight polysomnography with electrocardiography recording. HRV indices were obtained by analyzing the R-R intervals (RRis) in 5-min apnea-free samples by the linear frequency domain [low frequency (LF), high frequency (HF) and LF/HF], Poincaré plot [standard deviation (SD1) and (SD2)], recurrence plot [mean line length (Lmean)], recurrence rate (REC), determinism (DET), and Shannon entropy (ShanEn). The MOSA group presented with higher LF, LF/HF, and DET indices compared to NonOSA as well as a lower parasympathetic index (HF), suggesting sympathetic hyperactivity in MOSA subjects. Interestingly, MiOSA subjects failed to show the expected linear HRV difference between sleep stages, as observed in NonOSA, which may represent an early onset of autonomic impairment at this stage of OSA. In OSA patients, there is a chronic sleep stage-dependent impairment of linear and nonlinear cardiac autonomic modulation. Interestingly, this impairment may be identifiable during the early stages of the disease.

The Life Cycle Completed. Extended Version with New Chapters on the Ninth Stage of Development by Joan M. Erikson.

ERIC Educational Resources Information Center

Erikson, Erik H.

This expanded edition of a 1982 book by Erik Erikson summarizes his work on the stages of the human life cycle, including chapters on psychosexuality and the cycle of generations, major stages in psychosocial development, and ego and ethos. An additional chapter on the ninth stage sets forth his philosophy on old age--i.e. the 80s and 90s--and how…

Cell cycle-related metabolism and mitochondrial dynamics in a replication-competent pancreatic beta-cell line.

PubMed

Montemurro, Chiara; Vadrevu, Suryakiran; Gurlo, Tatyana; Butler, Alexandra E; Vongbunyong, Kenny E; Petcherski, Anton; Shirihai, Orian S; Satin, Leslie S; Braas, Daniel; Butler, Peter C; Tudzarova, Slavica

2017-01-01

Cell replication is a fundamental attribute of growth and repair in multicellular organisms. Pancreatic beta-cells in adults rarely enter cell cycle, hindering the capacity for regeneration in diabetes. Efforts to drive beta-cells into cell cycle have so far largely focused on regulatory molecules such as cyclins and cyclin-dependent kinases (CDKs). Investigations in cancer biology have uncovered that adaptive changes in metabolism, the mitochondrial network, and cellular Ca 2+ are critical for permitting cells to progress through the cell cycle. Here, we investigated these parameters in the replication-competent beta-cell line INS 832/13. Cell cycle synchronization of this line permitted evaluation of cell metabolism, mitochondrial network, and cellular Ca 2+ compartmentalization at key cell cycle stages. The mitochondrial network is interconnected and filamentous at G1/S but fragments during the S and G2/M phases, presumably to permit sorting to daughter cells. Pyruvate anaplerosis peaks at G1/S, consistent with generation of biomass for daughter cells, whereas mitochondrial Ca 2+ and respiration increase during S and G2/M, consistent with increased energy requirements for DNA and lipid synthesis. This synchronization approach may be of value to investigators performing live cell imaging of Ca 2+ or mitochondrial dynamics commonly undertaken in INS cell lines because without synchrony widely disparate data from cell to cell would be expected depending on position within cell cycle. Our findings also offer insight into why replicating beta-cells are relatively nonfunctional secreting insulin in response to glucose. They also provide guidance on metabolic requirements of beta-cells for the transition through the cell cycle that may complement the efforts currently restricted to manipulating cell cycle to drive beta-cells through cell cycle.

A guide to studying human hair follicle cycling in vivo

PubMed Central

Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A.; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan

2015-01-01

Hair follicles (HFs) undergo life-long cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative “quiescence” (telogen). Since HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. While available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. Here, we present such a guide, which uses objective, well-defined, and reproducible criteria and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in sub-optimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field. PMID:26763421

Porcine epidemic diarrhea virus through p53-dependent pathway causes cell cycle arrest in the G0/G1 phase.

PubMed

Sun, Pei; Wu, Haoyang; Huang, Jiali; Xu, Ying; Yang, Feng; Zhang, Qi; Xu, Xingang

2018-05-22

Porcine epidemic diarrhea virus (PEDV), an enteropathogenic Alphacoronavirus, has caused enormous economic losses in the swine industry. p53 protein exists in a wide variety of animal cells, which is involved in cell cycle regulation, apoptosis, cell differentiation and other biological functions. In this study, we investigated the effects of PEDV infection on the cell cycle of Vero cells and p53 activation. The results demonstrated that PEDV infection induces cell cycle arrest at G0/G1 phase in Vero cells, while UV-inactivated PEDV does not cause cell cycle arrest. PEDV infection up-regulates the levels of p21, cdc2, cdk2, cdk4, Cyclin A protein and down-regulates Cyclin E protein. Further research results showed that inhibition of p53 signaling pathway can reverse the cell cycle arrest in G0/G1 phase induced by PEDV infection and cancel out the up-regulation of p21 and corresponding Cyclin/cdk mentioned above. In addition, PEDV infection of the cells synchronized in various stages of cell cycle showed that viral subgenomic RNA and virus titer were higher in the cells released from G0/G1 phase synchronized cells than that in the cells released from the G1/S phase and G2/M phase synchronized or asynchronous cells after 18 h p.i.. This is the first report to demonstrate that the p53-dependent pathway plays an important role in PEDV induced cell cycle arrest and beneficially contributes to viral infection. Copyright © 2018 Elsevier B.V. All rights reserved.

Earthquake cycles and physical modeling of the process leading up to a large earthquake

NASA Astrophysics Data System (ADS)

Ohnaka, Mitiyasu

2004-08-01

A thorough discussion is made on what the rational constitutive law for earthquake ruptures ought to be from the standpoint of the physics of rock friction and fracture on the basis of solid facts observed in the laboratory. From this standpoint, it is concluded that the constitutive law should be a slip-dependent law with parameters that may depend on slip rate or time. With the long-term goal of establishing a rational methodology of forecasting large earthquakes, the entire process of one cycle for a typical, large earthquake is modeled, and a comprehensive scenario that unifies individual models for intermediate-and short-term (immediate) forecasts is presented within the framework based on the slip-dependent constitutive law and the earthquake cycle model. The earthquake cycle includes the phase of accumulation of elastic strain energy with tectonic loading (phase II), and the phase of rupture nucleation at the critical stage where an adequate amount of the elastic strain energy has been stored (phase III). Phase II plays a critical role in physical modeling of intermediate-term forecasting, and phase III in physical modeling of short-term (immediate) forecasting. The seismogenic layer and individual faults therein are inhomogeneous, and some of the physical quantities inherent in earthquake ruptures exhibit scale-dependence. It is therefore critically important to incorporate the properties of inhomogeneity and physical scaling, in order to construct realistic, unified scenarios with predictive capability. The scenario presented may be significant and useful as a necessary first step for establishing the methodology for forecasting large earthquakes.

Construction of Joule Thomson inversion curves for mixtures using equation of state

NASA Astrophysics Data System (ADS)

Patankar, A. S.; Atrey, M. D.

2017-02-01

The Joule-Thomson effect is at the heart of Joule-Thomson cryocoolers and gas liquefaction cycles. The effective harnessing of this phenomenon necessitates the knowledge of Joule-Thomson coefficient and the inversion curve. When the working fluid is a mixture, (in mix refrigerant Joule-Thomson cryocooler, MRJT) the phase diagrams, equations of state and inversion curves of multi-component systems become important. The lowest temperature attainable by such a cryocooler depends on the inversion characteristics of the mixture used. In this work the construction of differential Joule-Thomson inversion curves of mixtures using Redlich-Kwong, Soave-Redlich-Kwong and Peng-Robinson equations of state is investigated assuming single phase. It is demonstrated that inversion curves constructed for pure fluids can be improved by choosing an appropriate value of acentric factor. Inversion curves are used to predict maximum inversion temperatures of multicomponent systems. An application where this information is critical is a two-stage J-T cryocooler using a mixture as the working fluid, especially for the second stage. The pre-cooling temperature that the first stage is required to generate depends on the maximum inversion temperature of the second stage working fluid.

Turbine blade unsteady aerodynamic loading and heat transfer

NASA Astrophysics Data System (ADS)

Johnston, David Alan

Stator indexing to minimize the unsteady aerodynamic loading of closely spaced airfoil rows in turbomachinery is a new technique for the passive control of flow-induced vibrations. This technique, along with the effects of steady blade loading, were studied by means of experiments performed in a two-stage low-speed research turbine. With the second vane row fixed, the inlet vane row was indexed to six positions over one vane-pitch cycle for a range of stage loadings. The aerodynamic forcing function to the first-stage rotor was measured in the rotating reference frame, with the resulting rotor blade unsteady aerodynamic response quantified by rotor blades instrumented with dynamic pressure transducers. Reductions in the unsteady lift magnitude were achieved at all turbine operating conditions, with attenuation ranging from 37% to 74% of the maximum unsteady lift. Additionally, in complementary experiments, the effects of stator indexing and steady blade loading on the unsteady heat transfer of the first- and second-stage rotors was studied for the design and highest blade loading conditions using platinum-film heat gages. The attenuation of unsteady heat transfer coefficient was blade-loading dependent and location dependent along the chord and span, ranging 10% to 90% of maximum. Due to the high degree of location dependence of attenuation, stator indexing is therefore best suited to minimize unsteady heat transfer in local hot spots of the blade rather than the blade as a whole.

Effect of neoadjuvant chemotherapy on resectability of stage III and IV hepatoblastoma.

PubMed

Venkatramani, R; Stein, J E; Sapra, A; Genyk, Y; Jhaveri, V; Malogolowkin, M; Mascarenhas, L

2015-01-01

The potential for surgical resection of primary hepatoblastoma tumours was assessed at diagnosis, and after two and four cycles of neoadjuvant chemotherapy. Available radiographic images for patients with stage III and IV hepatoblastoma diagnosed between 1991 and 2008 were reviewed. The extent of disease was determined at diagnosis using the PRETEXT staging system, and after two and four cycles of therapy by POST-TEXT staging. Tumour resectability based on radiographic studies was assessed independently by two surgeons with expertise in hepatic surgery who were blinded to treatment and clinical outcome. Radiographic images from 20 patients with hepatoblastoma were reviewed. Six of 20 tumours were downstaged after two cycles, and three additional tumours were downstaged following four cycles. All PRETEXT stage III and IV tumours were determined to be surgically unresectable at diagnosis. The number of tumours considered unresectable decreased from 16 of 20 at diagnosis to seven of 20 after two cycles, and to four of 20 after four cycles. Five of the seven tumours that were unresectable after two cycles, and all four tumours that were unresectable after four cycles would have qualified for liver transplant based on radiographic studies. The majority of stage III and IV hepatoblastomas achieved radiographic resectability after two cycles of chemotherapy. There may be an opportunity for earlier surgical intervention and potential for a reduction in chemotherapy in a considerable number of patients. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Afferent control of central pattern generators: experimental analysis of scratching in the decerebrate cat.

PubMed

Baev, K V; Esipenko, V B; Shimansky, Y P

1991-01-01

Systematic quantitative analysis of changes in the spinal scratching generator motor activity evoked by tonic and phasic peripheral afferent signals during "fictitious" scratching was carried out in the cat. Correlations between the kinematics of hindlimb scratching movement, sensory inflow, and primary afferent depolarization were investigated. Reliable correlations between the parameters of generator motor activity during fictitious scratching were revealed: they depended on tonic peripheral afferent inflow. The functional role of these dependencies consists of providing stability for aiming the hindlimb to the itch site. It was shown that scratching generator reaction to a phasic sensory signal depended significantly on afferent input, signal intensity, and its arrival phase in the cycle of motor activity. Phase correction of "scratching" rhythm was performed by inhibition of the current stage of "scratching" cycle, the inhibition magnitude depending on the intensity of a sensory signal run along high threshold afferent fibers. The moments in the scratching cycle, in which the afferent signal caused no rearrangement in scratching generator activity, were discovered for all investigated afferent inputs. These moments corresponded to the transitions from one scratching cycle phase to another. Integral afferent activity was distributed unevenly in the cycle during real scratching. The main part of it was observed just in that scratching cycle part which included the above mentioned no rearrangement phase points. The data obtained allowed us to conclude that the scratching generator should be considered as a working program for the motor optimal control system containing the intrinsic model of the controlled object dynamics (e.g. hindlimb scratching movement dynamics), which produces an inner analog of peripheral flow. This inner flow interacts with peripheral afferent inflow just as one of the latter components. Centrally originated modulation of primary afferent depolarization is a result of affecting the depolarization generating system by this inner "sensory" activity. It is the model, with the aid of which the generator can work after deafferentation. The functional organization of a central pattern generator is considered.

A transgenic Plasmodium falciparum NF54 strain that expresses GFP-luciferase throughout the parasite life cycle.

PubMed

Vaughan, Ashley M; Mikolajczak, Sebastian A; Camargo, Nelly; Lakshmanan, Viswanathan; Kennedy, Mark; Lindner, Scott E; Miller, Jessica L; Hume, Jen C C; Kappe, Stefan H I

2012-12-01

Plasmodium falciparum is the pathogenic agent of the most lethal of human malarias. Transgenic P. falciparum parasites expressing luciferase have been created to study drug interventions of both asexual and sexual blood stages but luciferase-expressing mosquito stage and liver stage parasites have not been created which has prevented the easy quantification of mosquito stage development (e.g. for transmission blocking interventions) and liver stage development (for interventions that prevent infection). To overcome this obstacle, we have created a transgenic P. falciparum NF54 parasite that expresses a GFP-luciferase transgene throughout the life cycle. Luciferase expression is robust and measurable at all life cycle stages, including midgut oocyst, salivary gland sporozoites and liver stages, where in vivo development is easily measurable using humanized mouse infections in conjunction with an in vivo imaging system. This parasite reporter strain will accelerate testing of interventions against pre-erythrocytic life cycle stages. Copyright © 2012 Elsevier B.V. All rights reserved.

Passive margin evolution, initiation of subduction and the Wilson cycle

NASA Astrophysics Data System (ADS)

Cloetingh, S. A. P. L.; Wortel, M. J. R.; Vlaar, N. J.

1984-10-01

We have constructed finite element models at various stages of passive margin evolution, in which we have incorporated the system of forces acting on the margin, depth-dependent rheological properties and lateral variations across the margin. We have studied the interrelations between age-dependent forces, geometry and rheology, to decipher their net effect on the state of stress at passive margins. Lithospheric flexure induced by sediment loading dominates the state of stress at passive margins. This study has shown that if after a short evolution of the margin (time span a few tens of million years) subduction has not yet started, continued aging of the passive margin alone does not result in conditions more favourable for transformation into an active margin. Although much geological evidence is available in support of the key role small ocean basins play in orogeny and ophiolite emplacement, evolutionary frameworks of the Wilson cycle usually are cast in terms of opening and closing of wide ocean basins. We propose a more limited role for large oceans in the Wilson cycle concept.

Evaluation of Giga-cycle Fatigue Properties of Austenitic Stainless Steels Using Ultrasonic Fatigue Test

NASA Astrophysics Data System (ADS)

Takahashi, Kyouhei; Ogawa, Takeshi

Ultrasonic fatigue tests have been performed in austenitic stainless steel, SUS316NG, in order to investigate giga-cycle fatigue strength of pre-strained materials, i.e. 5, 10 and 20% tensile pre-strains and -20% compressive pre-strain. The pre-strains were applied before specimen machining. The austenitic stainless steels are known to exhibit remarkable self-heating during the fatigue experiment. Therefore, heat radiation method was established by setting fatigue specimens in a low temperature chamber at about -100°C. The self-heating was controlled by intermittent loading condition, which enabled us to maintain the test section of the specimens at about room temperature. The results revealed that the fatigue strength increased with increasing pre-strain levels. Fish-eye fracture was observed for -20% pre-strained specimen fractured at 4.11×107 cycles, while the other specimens exhibited ordinary fatigue fracture surface originated from stage I facet on the specimen surface. The increase in fatigue limit was predicted by Vickers hardness, HV, which depended on the size of indented region. The prediction was successful using HV values obtained by the size of the indented region similar to those of the stage I facets.

Time-Lapse Cinemicrographic Studies of X-Irradiated HeLa S3 Cells

PubMed Central

Hurwitz, Camilla; Tolmach, L. J.

1969-01-01

Analysis of time-lapse cinemicrographs of X-irradiated HeLa S3 cells has shown that the incidence of cell fusion was increased from 0.9% (following 1267 divisions) in control cells to an average of 22% (following 655 divisions) in cells irradiated with 500 rad doses of 220 kv X-rays. The incidence depended on the stage of the generation cycle at which the parent cells were irradiated. It was nearly constant in the first three postirradiation generations. Fusion occurred at all stages of the generation cycle, but preferentially during the first 20%. Cells undergoing fusion progressed more slowly through the generation cycle and had a higher probability of disintegrating than did irradiated cells that did not fuse. The occurrence of fusion was clonally distributed in the population. It took place only between sister (or closely related) cells. Protoplasmic bridges were often visible between sister cells prior to fusion. Giant cells arose only as a result of fusion. The incidence of multipolar divisions, though higher than in unirradiated cells, was only 5.5% in cultures irradiated with 500 rads. Fusion occurred following 85% of the multipolar divisions and was often followed by a multipolar division. ImagesFigure 1 PMID:5807221

Evolution of crystal structure during the initial stages of ZnO atomic layer deposition

DOE PAGES

Boichot, R.; Tian, L.; Richard, M. -I.; ...

2016-01-05

In this study, a complementary suite of in situ synchrotron X-ray techniques is used to investigate both structural and chemical evolution during ZnO growth by atomic layer deposition. Focusing on the first 10 cycles of growth, we observe that the structure formed during the coalescence stage largely determines the overall microstructure of the film. Furthermore, by comparing ZnO growth on silicon with a native oxide with that on Al 2O 3(001), we find that even with lattice-mismatched substrates and low deposition temperatures, the crystalline texture of the films depend strongly on the nature of the interfacial bonds.

Phospho-Rb mediating cell cycle reentry induces early apoptosis following oxygen-glucose deprivation in rat cortical neurons.

PubMed

Yu, Ying; Ren, Qing-Guo; Zhang, Zhao-Hui; Zhou, Ke; Yu, Zhi-Yuan; Luo, Xiang; Wang, Wei

2012-03-01

The aim of this study was to investigate the relationship between cell cycle reentry and apoptosis in cultured cortical neurons following oxygen-glucose deprivation (OGD). We found that the percentage of neurons with BrdU uptake, TUNEL staining, and colocalized BrdU uptake and TUNEL staining was increased relative to control 6, 12 and 24 h after 1 h of OGD. The number of neurons with colocalized BrdU and TUNEL staining was decreased relative to the number of TUNEL-positive neurons at 24 h. The expression of phosphorylated retinoblastoma protein (phospho-Rb) was significantly increased 6, 12 and 24 h after OGD, parallel with the changes in BrdU uptake. Phospho-Rb and TUNEL staining were colocalized in neurons 6 and 12 h after OGD. This colocalization was strikingly decreased 24 h after OGD. Treatment with the cyclin-dependent kinase inhibitor roscovitine (100 μM) decreased the expression of phospho-Rb and reduced neuronal apoptosis in vitro. These results demonstrated that attempted cell cycle reentry with phosphorylation of Rb induce early apoptosis in neurons after OGD and there must be other mechanisms involved in the later stages of neuronal apoptosis besides cell cycle reentry. Phosphoralated Rb may be an important factor which closely associates aberrant cell cycle reentry with the early stages of neuronal apoptosis following ischemia/hypoxia in vitro, and pharmacological interventions for neuroprotection may be useful directed at this keypoint.

The oak woodland bird conservation plan: a strategy for protecting and managing oak woodland habitats and associated birds in California

Treesearch

Steve Zack; Mary K. Chase; Geoffrey R. Geupel

2002-01-01

Over 330 species of birds, mammals, reptiles, and amphibians depend on oak woodlands in California at some stage in their life cycle. California oak woodlands may rank among the top three habitat types in North America for bird richness. Oak woodlands are able to sustain such abundant wildlife primarily because they produce acorns, a high quality and frequently copious...

The Oak Woodland Bird Conservation Plan: A Strategy for Protecting and Managing Oak Woodland Habitats and Associated Birds in California

Treesearch

Steve Zack; Mary K. Chase; Geoffrey R. Geupel; Diana Stralberg

2005-01-01

Over 330 species of birds, mammals, reptiles, and amphibians depend on oak woodlands in California (fig. 1) at some stage in their life cycle (Barrett 1980; Verner 1980; Block and Morrison 1998). These woodlands are able to sustain such abundant wildlife primarily because they produce acorns, a high quality and frequently copious food supply. The birds of California?s...

Ion regulation in the different life stages of Trypanosoma cruzi.

PubMed

Gil, J R; Soler, A; Azzouz, S; Osuna, A

2003-07-01

Different ion and pH regulation mechanisms have been detected in the three main life stages of Trypanosoma cruzi: epimastigote, metacyclic trypomastigote and amastigote. Treatment with amiloride showed that the Na(+)/H(+) exchanger participated in all three forms. The Na(+)/K(+) ATPase exchanger appeared to be more active in the epimastigote than in the other forms. V-H(+)-ATPase inhibitors revealed the activity of this regulatory mechanism in the amastigote and epimastigote forms, while treatment with oligomycin only affected the amastigotes. The HCO(-)(3)/Cl(-) exchanger was found in all stages as well as in the intracellular pH-regulatory mechanism after abrupt basification. We deduce that ion regulation in T. cruzi is a complex process and depends upon the precise stage of the cell cycle of the parasite. It would seem to be an important mechanism, allowing the parasite to adapt to the changing environmental conditions within which it develops.

p57KIP2 regulates radial glia and intermediate precursor cell cycle dynamics and lower layer neurogenesis in developing cerebral cortex

PubMed Central

Mairet-Coello, Georges; Tury, Anna; Van Buskirk, Elise; Robinson, Kelsey; Genestine, Matthieu; DiCicco-Bloom, Emanuel

2012-01-01

During cerebral cortex development, precise control of precursor cell cycle length and cell cycle exit is required for balanced precursor pool expansion and layer-specific neurogenesis. Here, we defined the roles of cyclin-dependent kinase inhibitor (CKI) p57KIP2, an important regulator of G1 phase, using deletion mutant mice. Mutant mice displayed macroencephaly associated with cortical hyperplasia during late embryogenesis and postnatal development. Embryonically, proliferation of radial glial cells (RGC) and intermediate precursors (IPC) was increased, expanding both populations, with greater effect on IPCs. Furthermore, cell cycle re-entry was increased during early corticogenesis, whereas cell cycle exit was augmented at middle stage. Consequently, neurogenesis was reduced early, whereas it was enhanced during later development. In agreement, the timetable of early neurogenesis, indicated by birthdating analysis, was delayed. Cell cycle dynamics analyses in mutants indicated that p57KIP2 regulates cell cycle length in both RGCs and IPCs. By contrast, related CKI p27KIP1 controlled IPC proliferation exclusively. Furthermore, p57KIP2 deficiency markedly increased RGC and IPC divisions at E14.5, whereas p27KIP1 increased IPC proliferation at E16.5. Consequently, loss of p57KIP2 increased primarily layer 5-6 neuron production, whereas loss of p27KIP1 increased neurons specifically in layers 2-5. In conclusion, our observations suggest that p57KIP2 and p27KIP1 control neuronal output for distinct cortical layers by regulating different stages of precursor proliferation, and support a model in which IPCs contribute to both lower and upper layer neuron generation. PMID:22223678

Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunther, Jillian R.; Fanale, Michelle A.; Reddy, Jay P.

Purpose: The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). Methods and Materials: We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicitiesmore » were evaluated. Results: The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Conclusions: Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease.« less

Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation.

PubMed

Gunther, Jillian R; Fanale, Michelle A; Reddy, Jay P; Akhtari, Mani; Smith, Grace L; Pinnix, Chelsea C; Milgrom, Sarah A; Yehia, Zeinab Abou; Allen, Pamela K; Osborne, Eleanor M; Mawlawi, Osama; Dabaja, Bouthaina S

2016-09-01

The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicities were evaluated. The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Cell cycle gene expression under clinorotation

NASA Astrophysics Data System (ADS)

Artemenko, Olga

2016-07-01

Cyclins and cyclin-dependent kinase (CDK) are main regulators of the cell cycle of eukaryotes. It's assumes a significant change of their level in cells under microgravity conditions and by other physical factors actions. The clinorotation use enables to determine the influence of gravity on simulated events in the cell during the cell cycle - exit from the state of quiet stage and promotion presynthetic phase (G1) and DNA synthesis phase (S) of the cell cycle. For the clinorotation effect study on cell proliferation activity is the necessary studies of molecular mechanisms of cell cycle regulation and development of plants under altered gravity condition. The activity of cyclin D, which is responsible for the events of the cell cycle in presynthetic phase can be controlled by the action of endogenous as well as exogenous factors, but clinorotation is one of the factors that influence on genes expression that regulate the cell cycle.These data can be used as a model for further research of cyclin - CDK complex for study of molecular mechanisms regulation of growth and proliferation. In this investigation we tried to summarize and analyze known literature and own data we obtained relatively the main regulators of the cell cycle in altered gravity condition.

Selection of components for the IDEALHY preferred cycle for the large scale liquefaction of hydrogen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quack, H.; Seemann, I.; Klaus, M.

2014-01-29

In a future energy scenario, in which storage and transport of liquid hydrogen in large quantities will be used, the efficiency of the liquefaction of hydrogen will be of utmost importance. The goal of the IDEALHY working party is to identify the most promising process for a 50 t/d plant and to select the components, with which such a process can be realized. In the first stage the team has compared several processes, which have been proposed or realized in the past. Based on this information a process has been selected, which is thermodynamically most promising and for which itmore » could be assumed that good components already exist or can be developed in the foreseeable future. Main features of the selected process are the compression of the feed stream to a relatively high pressure level, o-p conversion inside plate-fin heat exchangers and expansion turbines in the supercritical region. Precooling to a temperature between 150 and 100 K will be obtained from a mixed refrigerant cycle similar to the systems used successfully in natural gas liquefaction plants. The final cooling will be produced by two Brayton cycles, both having several expansion turbines in series. The selected overall process has still a number of parameters, which can be varied. The optimum, i.e. the final choice will depend mainly on the quality of the available components. Key components are the expansion turbines of the two Brayton cycles and the main recycle compressor, which may be common to both Brayton cycles. A six-stage turbo-compressor with intercooling between the stages is expected to be the optimum choice here. Each stage may consist of several wheels in series. To make such a high efficient and cost-effective compressor feasible, one has to choose a refrigerant, which has a higher molecular weight than helium. The present preferred choice is a mixture of helium and neon with a molecular weight of about 8 kg/kmol. Such an expensive refrigerant requires that the whole refrigeration loop is extremely tight.« less

A putative homologue of CDC20/CDH1 in the malaria parasite is essential for male gamete development.

PubMed

Guttery, David S; Ferguson, David J P; Poulin, Benoit; Xu, Zhengyao; Straschil, Ursula; Klop, Onny; Solyakov, Lev; Sandrini, Sara M; Brady, Declan; Nieduszynski, Conrad A; Janse, Chris J; Holder, Anthony A; Tobin, Andrew B; Tewari, Rita

2012-02-01

Cell-cycle progression is governed by a series of essential regulatory proteins. Two major regulators are cell-division cycle protein 20 (CDC20) and its homologue, CDC20 homologue 1 (CDH1), which activate the anaphase-promoting complex/cyclosome (APC/C) in mitosis, and facilitate degradation of mitotic APC/C substrates. The malaria parasite, Plasmodium, is a haploid organism which, during its life-cycle undergoes two stages of mitosis; one associated with asexual multiplication and the other with male gametogenesis. Cell-cycle regulation and DNA replication in Plasmodium was recently shown to be dependent on the activity of a number of protein kinases. However, the function of cell division cycle proteins that are also involved in this process, such as CDC20 and CDH1 is totally unknown. Here we examine the role of a putative CDC20/CDH1 in the rodent malaria Plasmodium berghei (Pb) using reverse genetics. Phylogenetic analysis identified a single putative Plasmodium CDC20/CDH1 homologue (termed CDC20 for simplicity) suggesting that Plasmodium APC/C has only one regulator. In our genetic approach to delete the endogenous cdc20 gene of P. berghei, we demonstrate that PbCDC20 plays a vital role in male gametogenesis, but is not essential for mitosis in the asexual blood stage. Furthermore, qRT-PCR analysis in parasite lines with deletions of two kinase genes involved in male sexual development (map2 and cdpk4), showed a significant increase in cdc20 transcription in activated gametocytes. DNA replication and ultra structural analyses of cdc20 and map2 mutants showed similar blockage of nuclear division at the nuclear spindle/kinetochore stage. CDC20 was phosphorylated in asexual and sexual stages, but the level of modification was higher in activated gametocytes and ookinetes. Changes in global protein phosphorylation patterns in the Δcdc20 mutant parasites were largely different from those observed in the Δmap2 mutant. This suggests that CDC20 and MAP2 are both likely to play independent but vital roles in male gametogenesis.

A Putative Homologue of CDC20/CDH1 in the Malaria Parasite Is Essential for Male Gamete Development

PubMed Central

Guttery, David S.; Ferguson, David J. P.; Poulin, Benoit; Xu, Zhengyao; Straschil, Ursula; Klop, Onny; Solyakov, Lev; Sandrini, Sara M.; Brady, Declan; Nieduszynski, Conrad A.; Janse, Chris J.; Holder, Anthony A.; Tobin, Andrew B.; Tewari, Rita

2012-01-01

Cell-cycle progression is governed by a series of essential regulatory proteins. Two major regulators are cell-division cycle protein 20 (CDC20) and its homologue, CDC20 homologue 1 (CDH1), which activate the anaphase-promoting complex/cyclosome (APC/C) in mitosis, and facilitate degradation of mitotic APC/C substrates. The malaria parasite, Plasmodium, is a haploid organism which, during its life-cycle undergoes two stages of mitosis; one associated with asexual multiplication and the other with male gametogenesis. Cell-cycle regulation and DNA replication in Plasmodium was recently shown to be dependent on the activity of a number of protein kinases. However, the function of cell division cycle proteins that are also involved in this process, such as CDC20 and CDH1 is totally unknown. Here we examine the role of a putative CDC20/CDH1 in the rodent malaria Plasmodium berghei (Pb) using reverse genetics. Phylogenetic analysis identified a single putative Plasmodium CDC20/CDH1 homologue (termed CDC20 for simplicity) suggesting that Plasmodium APC/C has only one regulator. In our genetic approach to delete the endogenous cdc20 gene of P. berghei, we demonstrate that PbCDC20 plays a vital role in male gametogenesis, but is not essential for mitosis in the asexual blood stage. Furthermore, qRT-PCR analysis in parasite lines with deletions of two kinase genes involved in male sexual development (map2 and cdpk4), showed a significant increase in cdc20 transcription in activated gametocytes. DNA replication and ultra structural analyses of cdc20 and map2 mutants showed similar blockage of nuclear division at the nuclear spindle/kinetochore stage. CDC20 was phosphorylated in asexual and sexual stages, but the level of modification was higher in activated gametocytes and ookinetes. Changes in global protein phosphorylation patterns in the Δcdc20 mutant parasites were largely different from those observed in the Δmap2 mutant. This suggests that CDC20 and MAP2 are both likely to play independent but vital roles in male gametogenesis. PMID:22383885

Strong shift from HCO3 (-) to CO 2 uptake in Emiliania huxleyi with acidification: new approach unravels acclimation versus short-term pH effects.

PubMed

Kottmeier, Dorothee M; Rokitta, Sebastian D; Tortell, Philippe D; Rost, Björn

2014-09-01

Effects of ocean acidification on Emiliania huxleyi strain RCC 1216 (calcifying, diploid life-cycle stage) and RCC 1217 (non-calcifying, haploid life-cycle stage) were investigated by measuring growth, elemental composition, and production rates under different pCO2 levels (380 and 950 μatm). In these differently acclimated cells, the photosynthetic carbon source was assessed by a (14)C disequilibrium assay, conducted over a range of ecologically relevant pH values (7.9-8.7). In agreement with previous studies, we observed decreased calcification and stimulated biomass production in diploid cells under high pCO2, but no CO2-dependent changes in biomass production for haploid cells. In both life-cycle stages, the relative contributions of CO2 and HCO3 (-) uptake depended strongly on the assay pH. At pH values ≤ 8.1, cells preferentially used CO2 (≥ 90 % CO2), whereas at pH values ≥ 8.3, cells progressively increased the fraction of HCO3 (-) uptake (~45 % CO2 at pH 8.7 in diploid cells; ~55 % CO2 at pH 8.5 in haploid cells). In contrast to the short-term effect of the assay pH, the pCO2 acclimation history had no significant effect on the carbon uptake behavior. A numerical sensitivity study confirmed that the pH-modification in the (14)C disequilibrium method yields reliable results, provided that model parameters (e.g., pH, temperature) are kept within typical measurement uncertainties. Our results demonstrate a high plasticity of E. huxleyi to rapidly adjust carbon acquisition to the external carbon supply and/or pH, and provide an explanation for the paradoxical observation of high CO2 sensitivity despite the apparently high HCO3 (-) usage seen in previous studies.

Merits of full flow vs. conventional staged combustion cycles for reusable launch vehicle propulsion

NASA Astrophysics Data System (ADS)

Peery, Steven D.; Parsley, Randy C.

1996-03-01

This paper provides a comparison between full-flow and conventional staged combustion thermodynamic O2/H2 rocket engine cycles for Reusable Launch Vehicle, RLV, single-stage-to-orbit applications. The impact of the cycle thermodynamics, component configuration, and component operating parameters on engine performance and weight for the two approaches is presented. Both cycles were modeled with equivalent technology turbomachinery and chamber/nozzle RLV life requirements. The first order impact of cycle selection, pump exit pressure, and turbine temperature on the empty weight of an SSTO Reusable Launch Vehicle is presented.

Simplified Helium Refrigerator Cycle Analysis Using the `Carnot Step'

DOE Office of Scientific and Technical Information (OSTI.GOV)

P. Knudsen; V. Ganni

2006-05-01

An analysis of the Claude form of an idealized helium liquefier for the minimum input work reveals the ''Carnot Step'' for helium refrigerator cycles. As the ''Carnot Step'' for a multi-stage polytropic compression process consists of equal pressure ratio stages; similarly for an idealized helium liquefier the ''Carnot Step'' consists of equal temperature ratio stages for a given number of expansion stages. This paper presents the analytical basis and some useful equations for the preliminary examination of existing and new Claude helium refrigeration cycles.

The chemosensitivity of labellar sugar receptor in female Phormia regina is paralleled with ovary maturation: Effects of serotonin.

PubMed

Solari, Paolo; Stoffolano, John G; De Rose, Francescaelena; Barbarossa, Iole Tomassini; Liscia, Anna

2015-11-01

Oogenesis in most adult insects is a nutrient-dependent process involving ingestion of both proteins and carbohydrates that ultimately depends on peripheral input from chemoreceptors. The main goal of this study was to characterize, in the female blowfly Phormia regina, the responsive changes of the labellar chemoreceptors to carbohydrates and proteins in relation to four different stages along the ovarian cycle: (1) immature ovaries, (2) mid-mature ovaries, (3) mature ovaries and ready for egg-laying and (4) post egg-laying ovaries. Then, the possible effects exerted by exogenous serotonin on the chemoreceptor sensitivity profiles were investigated. Our results show that ovary length, width and contraction rate progressively increase from stage 1 to 3, when all these parameters reach their maximum values, before declining in the next stage 4. The sensitivity of the labellar "sugar" chemoreceptors to both sucrose and proteins varies during the ovarian maturation stages, reaching a minimum for sucrose in stage 3, while that to proteins begins. Exogenous 5-HT supply specifically increases the chemoreceptor sensitivity to sugar at the stages 3 and 4, while it does not affect that to proteins. In conclusion, our results provide evidence that in female blowflies the cyclic variations in the sensitivity of the labellar chemosensilla to sugars and proteins are time-related to ovarian development and that during the stages 3 and 4 the responsiveness of the sugar cell to sucrose is under serotonergic control. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis of the occupational, consumer and environmental exposure to engineered nanomaterials used in 10 technology sectors.

PubMed

Nowack, Bernd; Brouwer, Connie; Geertsma, Robert E; Heugens, Evelyn H W; Ross, Bryony L; Toufektsian, Marie-Claire; Wijnhoven, Susan W P; Aitken, Robert J

2013-09-01

Humans and the environment can come into contact with nanomaterials through a wide range of applications during all stages of the life cycle of nanoproducts. The aim of this commentary is to present an assessment of the potential for exposure and thus identify possible environmental, health and safety (EHS) issues for nanomaterials used in 10 technology sectors. We analysed all life cycle stages with regard to potential for exposure of workers, consumers/patients, and the environment. A wide variety of nanomaterials are used of which many have negligible potential for exposure, while others have medium or even high potential for exposure. Based on the likelihood of exposure, it appears that in general most attention should be paid to the agrifood, chemistry/materials, textiles and health sectors; and less to the information and communication technology (ICT), security and energy sectors. Toxicity and exposure are both important; however, the EHS impact of nanomaterials is always dependent on their particular use.

Toxoplasma gondii influences aversive behaviors of female rats in an estrus cycle dependent manner.

PubMed

Golcu, Doruk; Gebre, Rahiwa Z; Sapolsky, Robert M

2014-08-01

The protozoan Toxoplasma gondii (T. gondii) manipulates the behavior of its rodent intermediate host to facilitate its passage to its feline definitive host. This is accomplished by a reduction of the aversive response that rodents show towards cat odors, which likely increases the predation risk. Females on average show similar changes as males. However, behaviors that relate to aversion and attraction are usually strongly influenced by the estrus cycle. In this study, we replicated behavioral effects of T. gondii in female rats, as well as expanded it to two novel behavioral paradigms. We also characterized the role of the estrus cycle in the behavioral effects of T. gondii on female rats. Uninfected females preferred to spend more time in proximity to rabbit rather than bobcat urine, and in a dark chamber rather than a lit chamber. Infected females lost both of these preferences, and also spent more time investigating social novelty (foreign bedding in their environment). Taken together, these data suggest that infection makes females less risk averse and more exploratory. Furthermore, this effect was influenced by the estrus cycle. Uninfected rats preferred rabbit urine to bobcat urine throughout the cycle except at estrus and metestrus. In contrast, infected rats lost this preference at every stage of the cycle except estrus. Commensurate with the possibility that this was a hormone-dependent effect, infected rats had elevated levels of circulating progesterone, a known anxiolytic. Copyright © 2014 Elsevier Inc. All rights reserved.

Toxoplasma gondii influences aversive behaviors of female rats in an estrus cycle dependent manner

PubMed Central

Golcu, Doruk; Gebre, Rahiwa Z.; Sapolsky, Robert M.

2016-01-01

The protozoan Toxoplasma gondii (T. gondii) manipulates the behavior of its rodent intermediate host to facilitate its passage to its feline definitive host. This is accomplished by a reduction of the aversive response that rodents show towards cat odors, which likely increases the predation risk. Females on average show similar changes as males. However, behaviors that relate to aversion and attraction are usually strongly influenced by the estrus cycle. In this study, we replicated behavioral effects of T. gondii in female rats, as well as expanded it to two novel behavioral paradigms. We also characterized the role of the estrus cycle in the behavioral effects of T. gondii on female rats. Uninfected females preferred to spend more time in proximity to rabbit rather than bobcat urine, and in a dark chamber rather than a lit chamber. Infected females lost both of these preferences, and also spent more time investigating social novelty (foreign bedding in their environment). Taken together, these data suggest that infection makes females less risk averse and more exploratory. Furthermore, this effect was influenced by the estrus cycle. Uninfected rats preferred rabbit urine to bobcat urine throughout the cycle except at estrus and metestrus. In contrast, infected rats lost this preference at every stage of the cycle except estrus. Commensurate with the possibility that this was a hormone-dependent effect, infected rats had elevated levels of circulating progesterone, a known anxiolytic. PMID:24907696

Modeling the influence of genetic and environmental variation on the expression of plant life cycles across landscapes.

PubMed

Burghardt, Liana T; Metcalf, C Jessica E; Wilczek, Amity M; Schmitt, Johanna; Donohue, Kathleen

2015-02-01

Organisms develop through multiple life stages that differ in environmental tolerances. The seasonal timing, or phenology, of life-stage transitions determines the environmental conditions to which each life stage is exposed and the length of time required to complete a generation. Both environmental and genetic factors contribute to phenological variation, yet predicting their combined effect on life cycles across a geographic range remains a challenge. We linked submodels of the plasticity of individual life stages to create an integrated model that predicts life-cycle phenology in complex environments. We parameterized the model for Arabidopsis thaliana and simulated life cycles in four locations. We compared multiple "genotypes" by varying two parameters associated with natural genetic variation in phenology: seed dormancy and floral repression. The model predicted variation in life cycles across locations that qualitatively matches observed natural phenology. Seed dormancy had larger effects on life-cycle length than floral repression, and results suggest that a genetic cline in dormancy maintains a life-cycle length of 1 year across the geographic range of this species. By integrating across life stages, this approach demonstrates how genetic variation in one transition can influence subsequent transitions and the geographic distribution of life cycles more generally.

A Guide to Studying Human Hair Follicle Cycling In Vivo.

PubMed

Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan; Kim, Moonkyu; Paus, Ralf; Plikus, Maksim V

2016-01-01

Hair follicles (HFs) undergo lifelong cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative "quiescence" (telogen). Given that HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. Although available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. In this article, we present such a guide, which uses objective, well-defined, and reproducible criteria, and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in suboptimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Residential Preferences and Moving Behavior: A Family Life Cycle Analysis.

ERIC Educational Resources Information Center

McAuley, William J.; Nutty, Cheri L.

The relationship of family life cycle changes to housing preferences and residential mobility is examined. Two residential decision-making issues are explored in detail--how family life cycle stages influence what people view as important to their choice of residential setting and what individuals at different family life cycle stages view as the…

The caligid life cycle: new evidence from Lepeophtheirus elegans reconciles the cycles of Caligus and Lepeophtheirus (Copepoda: Caligidae)

PubMed Central

Venmathi Maran, Balu Alagar; Moon, Seong Yong; Ohtsuka, Susumu; Oh, Sung-Yong; Soh, Ho Young; Myoung, Jung-Goo; Iglikowska, Anna; Boxshall, Geoffrey Allan

2013-01-01

The developmental stages of the sea louse Lepeophtheirus elegans (Copepoda: Caligidae) are described from material collected from marine ranched Korean rockfish, Sebastes schlegelii. In L. elegans, setal number on the proximal segment of the antennule increases from 3 in the copepodid to 27 in the adult. Using the number of setae as a stage marker supports the inference that the post-naupliar phase of the life cycle comprises six stages: copepodid, chalimus I, chalimus II, pre-adult I, pre-adult II, and the adult. We observed variation in body length in both of the chalimus stages which we consider represents an early expression of sexual size dimorphism. We interpret the larger specimens of chalimus I as putative females, and the smaller as putative males; similarly with chalimus II, larger specimens are putative females and the smaller are males. Two patterns of life cycle are currently recognized within the Caligidae but the evidence presented here reconciles the two. We conclude that the typical caligid life cycle comprises only eight stages: two naupliar, one copepodid, and four chalimus stages preceding the adult in Caligus, but with the four chalimus stages represented by two chalimus and two pre-adult stages in Lepeophtheirus. This is a profound change with significant implications for the aquaculture industry, given that lice monitoring protocols include counts of chalimus stages and use temperature to predict when they will moult into the more pathogenic, mobile pre-adults. Lice management strategies must be tailored to the precise life cycle of the parasite. PMID:23647664

Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells.

PubMed

Dasiram, Jade Dhananjay; Ganesan, Ramamoorthi; Kannan, Janani; Kotteeswaran, Venkatesan; Sivalingam, Nageswaran

2017-02-01

Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa, have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes' type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Final Report on Two-Stage Fast Spectrum Fuel Cycle Options

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Won Sik; Lin, C. S.; Hader, J. S.

2016-01-30

This report presents the performance characteristics of two “two-stage” fast spectrum fuel cycle options proposed to enhance uranium resource utilization and to reduce nuclear waste generation. One is a two-stage fast spectrum fuel cycle option of continuous recycle of plutonium (Pu) in a fast reactor (FR) and subsequent burning of minor actinides (MAs) in an accelerator-driven system (ADS). The first stage is a sodium-cooled FR fuel cycle starting with low-enriched uranium (LEU) fuel; at the equilibrium cycle, the FR is operated using the recovered Pu and natural uranium without supporting LEU. Pu and uranium (U) are co-extracted from the dischargedmore » fuel and recycled in the first stage, and the recovered MAs are sent to the second stage. The second stage is a sodium-cooled ADS in which MAs are burned in an inert matrix fuel form. The discharged fuel of ADS is reprocessed, and all the recovered heavy metals (HMs) are recycled into the ADS. The other is a two-stage FR/ADS fuel cycle option with MA targets loaded in the FR. The recovered MAs are not directly sent to ADS, but partially incinerated in the FR in order to reduce the amount of MAs to be sent to the ADS. This is a heterogeneous recycling option of transuranic (TRU) elements« less

The Developmental Cycle: Teachings on the Eight Stages of Growth of a Human Being.

ERIC Educational Resources Information Center

Coyhis, Don

1997-01-01

Ties Native American Medicine Wheel teachings on the cycle of life to Eric Erickson's work on the eight developmental stages: trust, autonomy, initiative, accomplishment, identity, intimacy, generativity, and integrity. To have healthy communities, people need to move successfully through these stages. Knowing about these stages can help a person…

Monoclonal Antibodies to Intracellular Stages of Cryptosporidium parvum Define Life Cycle Progression In Vitro.

PubMed

Wilke, Georgia; Ravindran, Soumya; Funkhouser-Jones, Lisa; Barks, Jennifer; Wang, Qiuling; VanDussen, Kelli L; Stappenbeck, Thaddeus S; Kuhlenschmidt, Theresa B; Kuhlenschmidt, Mark S; Sibley, L David

2018-06-27

Among the obstacles hindering Cryptosporidium research is the lack of an in vitro culture system that supports complete life development and propagation. This major barrier has led to a shortage of widely available anti- Cryptosporidium antibodies and a lack of markers for staging developmental progression. Previously developed antibodies against Cryptosporidium were raised against extracellular stages or recombinant proteins, leading to antibodies with limited reactivity across the parasite life cycle. Here we sought to create antibodies that recognize novel epitopes that could be used to define intracellular development. We identified a mouse epithelial cell line that supported C. parvum growth, enabling immunization of mice with infected cells to create a bank of monoclonal antibodies (MAbs) against intracellular parasite stages while avoiding the development of host-specific antibodies. From this bank, we identified 12 antibodies with a range of reactivities across the parasite life cycle. Importantly, we identified specific MAbs that can distinguish different life cycle stages, such as trophozoites, merozoites, type I versus II meronts, and macrogamonts. These MAbs provide valuable tools for the Cryptosporidium research community and will facilitate future investigation into parasite biology. IMPORTANCE Cryptosporidium is a protozoan parasite that causes gastrointestinal disease in humans and animals. Currently, there is a limited array of antibodies available against the parasite, which hinders imaging studies and makes it difficult to visualize the parasite life cycle in different culture systems. In order to alleviate this reagent gap, we created a library of novel antibodies against the intracellular life cycle stages of Cryptosporidium We identified antibodies that recognize specific life cycle stages in distinctive ways, enabling unambiguous description of the parasite life cycle. These MAbs will aid future investigation into Cryptosporidium biology and help illuminate growth differences between various culture platforms. Copyright © 2018 Wilke et al.

A NGS approach to the encrusting Mediterranean sponge Crella elegans (Porifera, Demospongiae, Poecilosclerida): transcriptome sequencing, characterization and overview of the gene expression along three life cycle stages.

PubMed

Pérez-Porro, A R; Navarro-Gómez, D; Uriz, M J; Giribet, G

2013-05-01

Sponges can be dominant organisms in many marine and freshwater habitats where they play essential ecological roles. They also represent a key group to address important questions in early metazoan evolution. Recent approaches for improving knowledge on sponge biological and ecological functions as well as on animal evolution have focused on the genetic toolkits involved in ecological responses to environmental changes (biotic and abiotic), development and reproduction. These approaches are possible thanks to newly available, massive sequencing technologies-such as the Illumina platform, which facilitate genome and transcriptome sequencing in a cost-effective manner. Here we present the first NGS (next-generation sequencing) approach to understanding the life cycle of an encrusting marine sponge. For this we sequenced libraries of three different life cycle stages of the Mediterranean sponge Crella elegans and generated de novo transcriptome assemblies. Three assemblies were based on sponge tissue of a particular life cycle stage, including non-reproductive tissue, tissue with sperm cysts and tissue with larvae. The fourth assembly pooled the data from all three stages. By aggregating data from all the different life cycle stages we obtained a higher total number of contigs, contigs with blast hit and annotated contigs than from one stage-based assemblies. In that multi-stage assembly we obtained a larger number of the developmental regulatory genes known for metazoans than in any other assembly. We also advance the differential expression of selected genes in the three life cycle stages to explore the potential of RNA-seq for improving knowledge on functional processes along the sponge life cycle. © 2013 Blackwell Publishing Ltd.

Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors.

PubMed

Lu, Zhimin; Hunter, Tony

2010-06-15

The expression levels of the p21(Cip1) family CDK inhibitors (CKIs), p21(Cip1), p27(Kip1) and p57(Kip2), play a pivotal role in the precise regulation of cyclin-dependent kinase (CDK) activity, which is instrumental to proper cell cycle progression. The stabilities of p21(Cip1), p27(Kip1) and p57(Kip2) are all tightly and differentially regulated by ubiquitylation and proteasome-mediated degradation during various stages of the cell cycle, either in steady state or in response to extracellular stimuli, which often elicit site-specific phosphorylation of CKIs triggering their degradation.

Kinetic Model of Growth of Arthropoda Populations

NASA Astrophysics Data System (ADS)

Ershov, Yu. A.; Kuznetsov, M. A.

2018-05-01

Kinetic equations were derived for calculating the growth of crustacean populations ( Crustacea) based on the biological growth model suggested earlier using shrimp ( Caridea) populations as an example. The development cycle of successive stages for populations can be represented in the form of quasi-chemical equations. The kinetic equations that describe the development cycle of crustaceans allow quantitative prediction of the development of populations depending on conditions. In contrast to extrapolation-simulation models, in the developed kinetic model of biological growth the kinetic parameters are the experimental characteristics of population growth. Verification and parametric identification of the developed model on the basis of the experimental data showed agreement with experiment within the error of the measurement technique.

Cycle of charge carrier states with formation and extinction of a floating gate in an ambipolar tetracyanoquaterthienoquinoid-based field-effect transistor

NASA Astrophysics Data System (ADS)

Itoh, Takuro; Toyota, Taro; Higuchi, Hiroyuki; Matsushita, Michio M.; Suzuki, Kentaro; Sugawara, Tadashi

2017-03-01

A tetracyanoquaterthienoquinoid (TCT4Q)-based field effect transistor is characterized by the ambipolar transfer characteristics and the facile shift of the threshold voltage induced by the bias stress. The trapping and detrapping kinetics of charge carriers was investigated in detail by the temperature dependence of the decay of source-drain current (ISD). We found a repeatable formation of a molecular floating gate is derived from a 'charge carrier-and-gate' cycle comprising four stages, trapping of mobile carriers, formation of a floating gate, induction of oppositely charged mobile carriers, and recombination between mobile and trapped carriers to restore the initial state.

Life Cycle Cost Assessments for Military Transatmospheric Vehicles,

DTIC Science & Technology

1997-01-01

earth orbit (GEO) that fall within the Titan-IV heavy launch vehicle (HLV) class are outside the practical design limits for a marketable RLV SSTO ...information is from the RAND-hosted TAV Workshop. Three SSTO concepts for X-33 were proposed during Phase I, all with either different takeoff or landing...1996 indicated some observed general differences in vehicles depending on the launch and landing modes:4 • Single stage to orbit ( SSTO ) TAVs for

THE COMPONENTS OF KIN COMPETITION

PubMed Central

Van Dyken, J. David

2011-01-01

It is well known that competition among kin alters the rate and often the direction of evolution in subdivided populations. Yet much remains unclear about the ecological and demographic causes of kin competition, or what role life cycle plays in promoting or ameliorating its effects. Using the multilevel Price equation, I derive a general equation for evolution in structured populations under an arbitrary intensity of kin competition. This equation partitions the effects of selection and demography, and recovers numerous previous models as special cases. I quantify the degree of kin competition, α, which explicitly depends on life cycle. I show how life cycle and demographic assumptions can be incorporated into kin selection models via α, revealing life cycles that are more or less permissive of altruism. As an example, I give closed-form results for Hamilton’s rule in a three-stage life cycle. Although results are sensitive to life cycle in general, I identify three demographic conditions that give life cycle invariant results. Under the infinite island model, α is a function of the scale of density regulation and dispersal rate, effectively disentangling these two phenomena. Population viscosity per se does not impede kin selection. PMID:20482610

DOE Office of Scientific and Technical Information (OSTI.GOV)

Preez-Coll, C.S.; Herkovits, J.

Over the last several years, environmental contamination with cadmium has significantly increased because of its extensive use In anthropogenic activities. This heavy metal is a very toxic xenobiotic producing reproductive and developmental impairments in a wide spectrum of organisms. Within the life cycle of organisms, the embryo is the most sensitive period to adverse conditions. Moreover, stage-dependent susceptibilities to toxic agents in amphibian embryos treated with lead, cadmium and aluminium were described. In the case of cadmium, this differential sensitivity could be related to changes in the metal accumulation through development or in the induction of defense mechanisms against cadmiummore » toxicity, such as metallothionein (Mt) synthesis, which seems to be developmentally regulated. In the case of the toad Bufo arenarum, susceptibility to cadmium seems to follow a biphasic pattern during embryonic development. From the two-cell stage to the neurula stage an increase in susceptibility occurs, whereas from the last stage onwards a gradual increase in the resistance against this heavy metal seems to be achieved. This stage reports the uptake profile of cadmium at different post-hatching stages. 20 refs., 3 figs.« less

Educational Focuses in Organisational Life Cycles.

ERIC Educational Resources Information Center

Miller, Harry G.

1985-01-01

Presents four stages frequently associated with the stages of an organization's life cycle: experimentation, growth, maturity, and decline or stability. The author also demonstrates that the impact of employment and thus training related to organizational life cycles suggests a need for understanding the technical preparation required for…

Reduced and Compressed Cisplatin-Based Chemotherapy in Children and Adolescents With Intermediate-Risk Extracranial Malignant Germ Cell Tumors: A Report From the Children’s Oncology Group

PubMed Central

Cullen, John W.; Olson, Thomas A.; Pashankar, Farzana; Malogolowkin, Marcio H.; Amatruda, James F.; Villaluna, Doojduen; Krailo, Mark; Billmire, Deborah F.; Rescorla, Frederick J.; Egler, Rachel A.; Dicken, Bryan J.; Ross, Jonathan H.; Schlatter, Marc; Rodriguez-Galindo, Carlos; Frazier, A. Lindsay

2017-01-01

Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92%. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS4) rate was 89% (95% confidence interval, 83% to 92%), which was significantly lower than the 92% threshold of the comparison model (P = .08). Among 181 newly diagnosed patients, the EFS4 rate was 87%, compared with 92% for 92 comparable children in the historical cohort (P = .15). The EFS4 rate was significantly associated with stage (stage I, 100%; stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted. PMID:28240974

Specific aspects of contemporary triathlon: implications for physiological analysis and performance.

PubMed

Bentley, David J; Millet, Grégoire P; Vleck, Verónica E; McNaughton, Lars R

2002-01-01

Triathlon competitions are performed over markedly different distances and under a variety of technical constraints. In 'standard-distance' triathlons involving 1.5km swim, 40km cycling and 10km running, a World Cup series as well as a World Championship race is available for 'elite' competitors. In contrast, 'age-group' triathletes may compete in 5-year age categories at a World Championship level, but not against the elite competitors. The difference between elite and age-group races is that during the cycle stage elite competitors may 'draft' or cycle in a sheltered position; age-group athletes complete the cycle stage as an individual time trial. Within triathlons there are a number of specific aspects that make the physiological demands different from the individual sports of swimming, cycling and running. The physiological demands of the cycle stage in elite races may also differ compared with the age-group format. This in turn may influence performance during the cycle leg and subsequent running stage. Wetsuit use and drafting during swimming (in both elite and age-group races) result in improved buoyancy and a reduction in frontal resistance, respectively. Both of these factors will result in improved performance and efficiency relative to normal pool-based swimming efforts. Overall cycling performance after swimming in a triathlon is not typically affected. However, it is possible that during the initial stages of the cycle leg the ability of an athlete to generate the high power outputs necessary for tactical position changes may be impeded. Drafting during cycling results in a reduction in frontal resistance and reduced energy cost at a given submaximal intensity. The reduced energy expenditure during the cycle stage results in an improvement in running, so an athlete may exercise at a higher percentage of maximal oxygen uptake. In elite triathlon races, the cycle courses offer specific physiological demands that may result in different fatigue responses when compared with standard time-trial courses. Furthermore, it is possible that different physical and physiological characteristics may make some athletes more suited to races where the cycle course is either flat or has undulating sections. An athlete's ability to perform running activity after cycling, during a triathlon, may be influenced by the pedalling frequency and also the physiological demands of the cycle stage. The technical features of elite and age-group triathlons together with the physiological demands of longer distance events should be considered in experimental design, training practice and also performance diagnosis of triathletes.

HIV-1 Vif's Capacity To Manipulate the Cell Cycle Is Species Specific.

PubMed

Evans, Edward L; Becker, Jordan T; Fricke, Stephanie L; Patel, Kishan; Sherer, Nathan M

2018-04-01

Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production, reflecting species-specific incompatibilities between viral Tat and Rev proteins and essential host factors cyclin T1 (CCNT1) and exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell blocks other than CCNT1 and XPO1 affect HIV's postintegration stages, we studied HIV-1 NL4-3 gene expression in mouse NIH 3T3 cells modified to constitutively express HIV-1-compatible versions of CCNT1 and XPO1 (3T3.CX cells). 3T3.CX cells supported both Rev-independent and Rev-dependent viral gene expression and produced relatively robust levels of virus particles, confirming that CCNT1 and XPO1 represent the predominant blocks to these stages. Unexpectedly, however, 3T3.CX cells were remarkably resistant to virus-induced cytopathic effects observed in human cell lines, which we mapped to the viral protein Vif and its apparent species-specific capacity to induce G 2 /M cell cycle arrest. Vif was able to mediate rapid degradation of human APOBEC3G and the PPP2R5D regulatory B56 subunit of the PP2A phosphatase holoenzyme in mouse cells, thus demonstrating that Vif NL4-3 's modulation of the cell cycle can be functionally uncoupled from some of its other defined roles in CUL5-dependent protein degradation. Vif was also unable to induce G 2 /M cell cycle arrest in other nonhuman cell types, including cells derived from nonhuman primates, leading us to propose that one or more human-specific cofactors underpin Vif's ability to modulate the cell cycle. IMPORTANCE Cells derived from mice and other rodents exhibit profound blocks to HIV-1 replication, thus hindering the development of a low-cost small-animal model for studying HIV/AIDS. Here, we engineered otherwise-nonpermissive mouse cells to express HIV-1-compatible versions of two species-specific host dependency factors, cyclin T1 (CCNT1) and exportin-1 (XPO1) (3T3.CX cells). We show that 3T3.CX cells rescue HIV-1 particle production but, unexpectedly, are completely resistant to virus-induced cytopathic effects. We mapped these effects to the viral accessory protein Vif, which induces a prolonged G 2 /M cell cycle arrest followed by apoptosis in human cells. Combined, our results indicate that one or more additional human-specific cofactors govern HIV-1's capacity to modulate the cell cycle, with potential relevance to viral pathogenesis in people and existing animal models. Copyright © 2018 American Society for Microbiology.

Identification of She3 as an SCFGrr1 Substrate in Budding Yeast

PubMed Central

Wang, Ruiwen; Solomon, Mark J.

2012-01-01

The highly orchestrated progression of the cell cycle depends on the degradation of many regulatory proteins at different cell cycle stages. One of the key cell cycle ubiquitin ligases is the Skp1-cullin-F-box (SCF) complex. Acting in concert with the substrate-binding F-box protein Grr1, SCFGrr1 promotes the degradation of cell cycle regulators as well as various metabolic enzymes. Using a yeast two-hybrid assay with a Grr1 derivative as the bait, we identified She3, which is an adaptor protein in the asymmetric mRNA transport system, as a novel Grr1 substrate. We generated stabilized She3 mutants, which no longer bound to Grr1, and found that the degradation of She3 is not required for regulating asymmetric mRNA transport. However, She3 stabilization leads to slower growth compared to wild-type cells in a co-culture assay, demonstrating that the degradation of She3 by Grr1 is required for optimal cell growth. PMID:23144720

Solution for Direct Solar Impingement Problem on Landsat-7 ETM+ Cooler Door During Cooler Outgas in Flight

NASA Technical Reports Server (NTRS)

Choi, Michael K.

1999-01-01

There was a thermal anomaly of the Landsat-7 Enhanced Thematic Mapper Plus (ETM+) radiative cooler cold stage during the cooler outgas phase in flight. With the cooler door in the outgas position and the outgas heaters enabled, the cold stage temperature increased to a maximum of 323 K when the spacecraft was in the sunlight, which was warmer than the 316.3 K upper set point of the outgas heater controller on the cold stage. Also, the outgas heater cycled off when the cold stage was warming up to 323 K. A corrective action was taken before the attitude of the spacecraft was changed during the first week in flight. One orbit before the attitude was changed, the outgas heaters were disabled to cool off the cold stage. The cold stage temperature increase was strongly dependent on the spacecraft roll and yaw. It provided evidence that direct solar radiation entered the gap between the cooler door and cooler shroud. There was a concern that the direct solar radiation could cause polymerization of hydrocarbons, which could contaminate the cooler and lead to a thermal short. After outgas with the cooler door in the outgas position for seven days, the cooler door was changed to the fully open position. With the cooler door fully open, the maximum cold stage temperature was 316.3 K when the spacecraft was in the sunlight, and the duty cycle of the outgas heater in the eclipse was the same as that in the sunlight. It provided more evidence that direct solar radiation had entered the gap between the cooler door and cooler shroud. Cooler outgas continued for seven more days, with the cooler door fully open. The corrective actions had prevented overheating of the cold stage and cold focal plane array (CFPA), which could damage these two components. They also minimized the risk of contamination on the cold stage, which could lead to a thermal short.

Measuring cell cycle progression kinetics with metabolic labeling and flow cytometry.

PubMed

Fleisig, Helen; Wong, Judy

2012-05-22

Precise control of the initiation and subsequent progression through the various phases of the cell cycle are of paramount importance in proliferating cells. Cell cycle division is an integral part of growth and reproduction and deregulation of key cell cycle components have been implicated in the precipitating events of carcinogenesis. Molecular agents in anti-cancer therapies frequently target biological pathways responsible for the regulation and coordination of cell cycle division. Although cell cycle kinetics tend to vary according to cell type, the distribution of cells amongst the four stages of the cell cycle is rather consistent within a particular cell line due to the consistent pattern of mitogen and growth factor expression. Genotoxic events and other cellular stressors can result in a temporary block of cell cycle progression, resulting in arrest or a temporary pause in a particular cell cycle phase to allow for instigation of the appropriate response mechanism. The ability to experimentally observe the behavior of a cell population with reference to their cell cycle progression stage is an important advance in cell biology. Common procedures such as mitotic shake off, differential centrifugation or flow cytometry-based sorting are used to isolate cells at specific stages of the cell cycle. These fractionated, cell cycle phase-enriched populations are then subjected to experimental treatments. Yield, purity and viability of the separated fractions can often be compromised using these physical separation methods. As well, the time lapse between separation of the cell populations and the start of experimental treatment, whereby the fractionated cells can progress from the selected cell cycle stage, can pose significant challenges in the successful implementation and interpretation of these experiments. Other approaches to study cell cycle stages include the use of chemicals to synchronize cells. Treatment of cells with chemical inhibitors of key metabolic processes for each cell cycle stage are useful in blocking the progression of the cell cycle to the next stage. For example, the ribonucleotide reductase inhibitor hydroxyurea halts cells at the G1/S juncture by limiting the supply of deoxynucleotides, the building blocks of DNA. Other notable chemicals include treatment with aphidicolin, a polymerase alpha inhibitor for G1 arrest, treatment with colchicine and nocodazole, both of which interfere with mitotic spindle formation to halt cells in M phase and finally, treatment with the DNA chain terminator 5-fluorodeoxyridine to initiate S phase arrest. Treatment with these chemicals is an effective means of synchronizing an entire population of cells at a particular phase. With removal of the chemical, cells rejoin the cell cycle in unison. Treatment of the test agent following release from the cell cycle blocking chemical ensures that the drug response elicited is from a uniform, cell cycle stage-specific population. However, since many of the chemical synchronizers are known genotoxic compounds, teasing apart the participation of various response pathways (to the synchronizers vs. the test agents) is challenging. Here we describe a metabolic labeling method for following a subpopulation of actively cycling cells through their progression from the DNA replication phase, through to the division and separation of their daughter cells. Coupled with flow cytometry quantification, this protocol enables for measurement of kinetic progression of the cell cycle in the absence of either mechanically- or chemically- induced cellular stresses commonly associated with other cell cycle synchronization methodologies. In the following sections we will discuss the methodology, as well as some of its applications in biomedical research.

Cell-cycle synchronisation of bloodstream forms of Trypanosoma brucei using Vybrant DyeCycle Violet-based sorting.

PubMed

Kabani, Sarah; Waterfall, Martin; Matthews, Keith R

2010-01-01

Studies on the cell-cycle of Trypanosoma brucei have revealed several unusual characteristics that differ from the model eukaryotic organisms. However, the inability to isolate homogenous populations of parasites in distinct cell-cycle stages has limited the analysis of trypanosome cell division and complicated the understanding of mutant phenotypes with possible impact on cell-cycle related events. Although hydroxyurea-induced cell-cycle arrest in procyclic and bloodstream forms has been applied recently with success, such block-release protocols can complicate the analysis of cell-cycle regulated events and have the potential to disrupt important cell-cycle checkpoints. An alternative approach based on flow cytometry of parasites stained with Vybrant DyeCycle Orange circumvents this problem, but is restricted to procyclic form parasites. Here, we apply Vybrant Dyecycle Violet staining coupled with flow cytometry to effectively select different cell-cycle stages of bloodstream form trypanosomes. Moreover, the sorted parasites remain viable, although synchrony is rapidly lost. This method enables cell-cycle enrichment of populations of trypanosomes in their mammal infective stage, particularly at the G1 phase.

Cell-cycle synchronisation of bloodstream forms of Trypanosoma brucei using Vybrant DyeCycle Violet-based sorting

PubMed Central

Kabani, Sarah; Waterfall, Martin; Matthews, Keith R.

2010-01-01

Studies on the cell-cycle of Trypanosoma brucei have revealed several unusual characteristics that differ from the model eukaryotic organisms. However, the inability to isolate homogenous populations of parasites in distinct cell-cycle stages has limited the analysis of trypanosome cell division and complicated the understanding of mutant phenotypes with possible impact on cell-cycle related events. Although hydroxyurea-induced cell-cycle arrest in procyclic and bloodstream forms has been applied recently with success, such block-release protocols can complicate the analysis of cell-cycle regulated events and have the potential to disrupt important cell-cycle checkpoints. An alternative approach based on flow cytometry of parasites stained with Vybrant DyeCycle Orange circumvents this problem, but is restricted to procyclic form parasites. Here, we apply Vybrant Dyecycle Violet staining coupled with flow cytometry to effectively select different cell-cycle stages of bloodstream form trypanosomes. Moreover, the sorted parasites remain viable, although synchrony is rapidly lost. This method enables cell-cycle enrichment of populations of trypanosomes in their mammal infective stage, particularly at the G1 phase. PMID:19729042

Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation

PubMed Central

Ankers, John M; Awais, Raheela; Jones, Nicholas A; Boyd, James; Ryan, Sheila; Adamson, Antony D; Harper, Claire V; Bridge, Lloyd; Spiller, David G; Jackson, Dean A; Paszek, Pawel; Sée, Violaine; White, Michael RH

2016-01-01

Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-κB) signalling and the cell cycle are prioritised differently depending on the timing of an inflammatory signal. Using iterative experimental and computational analyses, we show physical and functional interactions between NF-κB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. These interactions modulate the NF-κB response. In S-phase, the NF-κB response was delayed or repressed, while cell cycle progression was unimpeded. By contrast, activation of NF-κB at the G1/S boundary resulted in a longer cell cycle and more synchronous initial NF-κB responses between cells. These data identify new mechanisms by which the cellular response to stress is differentially controlled at different stages of the cell cycle. DOI: http://dx.doi.org/10.7554/eLife.10473.001 PMID:27185527

Comparative proteomics of two life cycle stages of stable isotope-labeled Trypanosoma brucei reveals novel components of the parasite's host adaptation machinery.

PubMed

Butter, Falk; Bucerius, Ferdinand; Michel, Margaux; Cicova, Zdenka; Mann, Matthias; Janzen, Christian J

2013-01-01

Trypanosoma brucei developed a sophisticated life cycle to adapt to different host environments. Although developmental differentiation of T. brucei has been the topic of intensive research for decades, the mechanisms responsible for adaptation to different host environments are not well understood. We developed stable isotope labeling by amino acids in cell culture in trypanosomes to compare the proteomes of two different life cycle stages. Quantitative comparison of 4364 protein groups identified many proteins previously not known to be stage-specifically expressed. The identification of stage-specific proteins helps to understand how parasites adapt to different hosts and provides new insights into differences in metabolism, gene regulation, and cell architecture. A DEAD-box RNA helicase, which is highly up-regulated in the bloodstream form of this parasite and which is essential for viability and proper cell cycle progression in this stage is described as an example.

Thermo-mechanical Properties of Upper Jurassic (Malm) Carbonate Rock Under Drained Conditions

NASA Astrophysics Data System (ADS)

Pei, Liang; Blöcher, Guido; Milsch, Harald; Zimmermann, Günter; Sass, Ingo; Huenges, Ernst

2018-01-01

The present study aims to quantify the thermo-mechanical properties of Neuburger Bankkalk limestone, an outcrop analog of the Upper Jurassic carbonate formation (Germany), and to provide a reference for reservoir rock deformation within future enhanced geothermal systems located in the Southern German Molasse Basin. Experiments deriving the drained bulk compressibility C were performed by cycling confining pressure p c between 2 and 50 MPa at a constant pore pressure p p of 0.5 MPa after heating the samples to defined temperatures between 30 and 90 °C. Creep strain was then measured after each loading and unloading stage, and permeability k was obtained after each creep strain measurement. The drained bulk compressibility increased with increasing temperature and decreased with increasing differential pressure p d = p c - p p showing hysteresis between the loading and unloading stages above 30 °C. The apparent values of the indirectly calculated Biot coefficient α ind containing contributions from inelastic deformation displayed the same temperature and pressure dependencies. The permeability k increased immediately after heating and the creep rates were also temperature dependent. It is inferred that the alteration of the void space caused by temperature changes leads to the variation of rock properties measured under isothermal conditions while the load cycles applied under isothermal conditions yield additional changes in pore space microstructure. The experimental results were applied to a geothermal fluid production scenario to constrain drawdown and time-dependent effects on the reservoir, overall, to provide a reference for the hydromechanical behavior of geothermal systems in carbonate, and more specifically, in Upper Jurassic lithologies.

Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells

PubMed Central

Janzer, Andreas; German, Natalie J.; Gonzalez-Herrera, Karina N.; Asara, John M.; Haigis, Marcia C.; Struhl, Kevin

2014-01-01

Metformin, a first-line diabetes drug linked to cancer prevention in retrospective clinical analyses, inhibits cellular transformation and selectively kills breast cancer stem cells (CSCs). Although a few metabolic effects of metformin and the related biguanide phenformin have been investigated in established cancer cell lines, the global metabolic impact of biguanides during the process of neoplastic transformation and in CSCs is unknown. Here, we use LC/MS/MS metabolomics (>200 metabolites) to assess metabolic changes induced by metformin and phenformin in an Src-inducible model of cellular transformation and in mammosphere-derived breast CSCs. Although phenformin is the more potent biguanide in both systems, the metabolic profiles of these drugs are remarkably similar, although not identical. During the process of cellular transformation, biguanide treatment prevents the boost in glycolytic intermediates at a specific stage of the pathway and coordinately decreases tricarboxylic acid (TCA) cycle intermediates. In contrast, in breast CSCs, biguanides have a modest effect on glycolytic and TCA cycle intermediates, but they strongly deplete nucleotide triphosphates and may impede nucleotide synthesis. These metabolic profiles are consistent with the idea that biguanides inhibit mitochondrial complex 1, but they indicate that their metabolic effects differ depending on the stage of cellular transformation. PMID:25002509

Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells.

PubMed

Janzer, Andreas; German, Natalie J; Gonzalez-Herrera, Karina N; Asara, John M; Haigis, Marcia C; Struhl, Kevin

2014-07-22

Metformin, a first-line diabetes drug linked to cancer prevention in retrospective clinical analyses, inhibits cellular transformation and selectively kills breast cancer stem cells (CSCs). Although a few metabolic effects of metformin and the related biguanide phenformin have been investigated in established cancer cell lines, the global metabolic impact of biguanides during the process of neoplastic transformation and in CSCs is unknown. Here, we use LC/MS/MS metabolomics (>200 metabolites) to assess metabolic changes induced by metformin and phenformin in an Src-inducible model of cellular transformation and in mammosphere-derived breast CSCs. Although phenformin is the more potent biguanide in both systems, the metabolic profiles of these drugs are remarkably similar, although not identical. During the process of cellular transformation, biguanide treatment prevents the boost in glycolytic intermediates at a specific stage of the pathway and coordinately decreases tricarboxylic acid (TCA) cycle intermediates. In contrast, in breast CSCs, biguanides have a modest effect on glycolytic and TCA cycle intermediates, but they strongly deplete nucleotide triphosphates and may impede nucleotide synthesis. These metabolic profiles are consistent with the idea that biguanides inhibit mitochondrial complex 1, but they indicate that their metabolic effects differ depending on the stage of cellular transformation.

Putting one step before the other: distinct activation pathways for Cdk1 and Cdk2 bring order to the mammalian cell cycle

PubMed Central

Merrick, Karl A.; Fisher, Robert P.

2010-01-01

Eukaryotic cell division is controlled by the activity of cyclin-dependent kinases (CDKs). Cdk1 and Cdk2, which function at different stages of the mammalian cell cycle, both require cyclin-binding and phosphorylation of the activation (T-) loop for full activity, but differ with respect to the order in which the two steps occur in vivo. To form stable complexes with either of its partners—cyclins A and B—Cdk1 must be phosphorylated on its T-loop, but that phosphorylation in turn depends on the presence of cyclin. Cdk2 can follow a kinetically distinct path to activation in which T-loop phosphorylation precedes cyclin-binding, and thereby out-compete the more abundant Cdk1 for limiting amounts of cyclin A. Mathematical modeling suggests this could be a principal basis for the temporal ordering of CDK activation during S phase, which may dictate the sequence in which replication origins fire. Still to be determined are how: 1) the activation machinery discriminates between closely related CDKs, and 2) coordination of the cell cycle is affected when this mechanism of pathway insulation breaks down. PMID:20139727

Characterisation of the nucleolar organising regions during the cell cycle in two varieties of Petunia hybrida as visualised by fluorescence in situ hybridisation and silver staining.

PubMed

Montijn, M B; ten Hoopen, R; Fransz, P F; Oud, J L; Nanninga, N

1998-05-01

The cell cycle-dependent spatial position, morphology and activity of the four nucleolar organising regions (NORs) of the Petunia hybrida cultivar Mitchell and the inbred line V26 have been analysed. Application of the silver staining technique and fluorescence in situ hybridisation on fixed root-tip material revealed that these interspecific hybrids possess four NORs of which only those of chromosome 2 are active during interphase, which implies that the NOR activity is not of parental origin. However, at the end of mitosis, activity of all NOR regions could be detected, suggesting that the high demand for ribosomes at this stage of the cell cycle requires temporal activity of all NORs. Using actin DNA probes as markers in fluorescence in situ hybridisation experiments enabled the identification of the individual petunia chromosomes.

DEVELOPMENT OF COLD CLIMATE HEAT PUMP USING TWO-STAGE COMPRESSION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Bo; Rice, C Keith; Abdelaziz, Omar

2015-01-01

This paper uses a well-regarded, hardware based heat pump system model to investigate a two-stage economizing cycle for cold climate heat pump applications. The two-stage compression cycle has two variable-speed compressors. The high stage compressor was modelled using a compressor map, and the low stage compressor was experimentally studied using calorimeter testing. A single-stage heat pump system was modelled as the baseline. The system performance predictions are compared between the two-stage and single-stage systems. Special considerations for designing a cold climate heat pump are addressed at both the system and component levels.

Induction of Phase Variation Events in the Life Cycle of the Marine Coccolithophorid Emiliania huxleyi

PubMed Central

Laguna, Richard; Romo, Jesus; Read, Betsy A.; Wahlund, Thomas M.

2001-01-01

Emiliania huxleyi is a unicellular marine alga that is considered to be the world's major producer of calcite. The life cycle of this alga is complex and is distinguished by its ability to synthesize exquisitely sculptured calcium carbonate cell coverings known as coccoliths. These structures have been targeted by materials scientists for applications relating to the chemistry of biomedical materials, robust membranes for high-temperature separation technology, lightweight ceramics, and semiconductor design. To date, however, the molecular and biochemical events controlling coccolith production have not been determined. In addition, little is known about the life cycle of E. huxleyi and the environmental and physiological signals triggering phase switching between the diploid and haploid life cycle stages. We have developed laboratory methods for inducing phase variation between the haploid (S-cell) and diploid (C-cell) life cycle stages of E. huxleyi. Plating E. huxleyi C cells on solid media was shown to induce phase switching from the C-cell to the S-cell life cycle stage, the latter of which has been maintained for over 2 years under these conditions. Pure cultures of S cells were obtained for the first time. Laboratory conditions for inducing phase switching from the haploid stage to the diploid stage were also established. Regeneration of the C-cell stage from pure cultures of S cells followed a predictable pattern involving formation of large aggregations of S cells and the subsequent production of cultures consisting predominantly of diploid C cells. These results demonstrate the ability to manipulate the life cycle of E. huxleyi under controlled laboratory conditions, providing us with powerful tools for the development of genetic techniques for analysis of coccolithogenesis and for investigating the complex life cycle of this important marine alga. PMID:11525973

Disentangling Facilitation Along the Life Cycle: Impacts of Plant-Plant Interactions at Vegetative and Reproductive Stages in a Mediterranean Forb.

PubMed

García-Cervigón, Ana I; Iriondo, José M; Linares, Juan C; Olano, José M

2016-01-01

Facilitation enables plants to improve their fitness in stressful environments. The overall impact of plant-plant interactions on the population dynamics of protégées is the net result of both positive and negative effects that may act simultaneously along the plant life cycle, and depends on the environmental context. This study evaluates the impact of the nurse plant Juniperus sabina on different stages of the life cycle of the forb Helleborus foetidus. Growth, number of leaves, flowers, carpels, and seeds per flower were compared for 240 individuals collected under nurse canopies and in open areas at two sites with contrasting stress levels. Spatial associations with nurse plants and age structures were also checked. A structural equation model was built to test the effect of facilitation on fecundity, accounting for sequential steps from flowering to seed production. The net impact of nurse plants depended on a combination of positive and negative effects on vegetative and reproductive variables. Although nurse plants caused a decrease in flower production at the low-stress site, their net impact there was neutral. In contrast, at the high-stress site the net outcome of plant-plant interactions was positive due to an increase in effective recruitment, plant density, number of viable carpels per flower, and fruit set under nurse canopies. The naturally lower rates of secondary growth and flower production at the high-stress site were compensated by the net positive impact of nurse plants here. Our results emphasize the need to evaluate entire processes and not only final outcomes when studying plant-plant interactions.

Growing population causes of unemployment.

PubMed

1995-01-01

At the March, 1995, International Meeting on Population and Social Development in Copenhagen, during the session on unemployment, underemployment, and population it was stated that the problem of employment was the extent to which a nation's labor supply was not matched by labor demand or job opportunities. Population was thus a supply factor, and the country's economic situation was a demand factor. The demographic variables that were considered important in the supply of labor were: a) the size and rate of growth of the population, which was a function of the birth rate, the death rate, and migration; and b) the age structure of the population, which was also a product of the rate of growth of the population and its distribution. An imbalance between the supply of labor and the demand for it gave rise to unemployment and underemployment. The vicious cycle generated by a high dependency burden associated with a young age-structure led to low savings and investments, which in turn led to low economic growth and a low standard of living. This produced high fertility rates, which in turn heightened the dependency burden perpetuating the cycle. This vicious cycle could be broken at only two points: at the high fertility stage, primarily by introducing family planning programs; and at the stage of low economic growth, by adopting policies to accelerate economic growth. To be successful, however, both actions had to be pursued simultaneously. Numerous participants emphasized the global nature of the issue of unemployment and underemployment; the effects of international competition and restrictive trade policies on employment opportunities. The growing disparity between North and South had created a social injustice between countries. Several participants called for more humane policies that favored democracy and promoted human development, and asked for assistance to help create an enabling environment for social and economic development.

Diel variation of ichthyoplankton recruitment in a wind-dominated temperate coastal lagoon (Argentina)

NASA Astrophysics Data System (ADS)

Bruno, Daniel O.; Delpiani, Sergio M.; Acha, Eduardo M.

2018-05-01

This study aimed to assess the diel changes of ichthyoplankton occurrence, during a known recruitment period, to a wind-dominated coastal lagoon (Argentina). We collected plankton samples at three sites of the lagoon's inlet area every 3 h during four 24 h cycles in mid austral summer. For each early-life history stage (eggs, yolk sac, preflexion larvae, postflexion larvae and early juveniles), the relationship between the abundance and possible combinations of the time of sampling, the wind effect, the wave period and the tidal state was evaluated by fitting generalized linear mix-effects models (GLMM). The wind effects depending on the time of sampling mainly affected fish abundance in all developmental stages. Overall, the highest abundances were collected at nocturnal hours when low-speed offshore winds blew. In addition, higher abundances of eggs, yolk sac and preflexion larvae were related to the incoming flood tide; whereas higher abundances of postflexion larvae and early juveniles were related to longer wave periods. We argued that the daily variation in the abundance of early-life history stages of fishes is related to the sea-land breeze cycle. Therefore, a conceptual framework of the recruitment process of eggs, larvae and early juveniles of fishes into this estuarine system considering the daily effect of winds is proposed.

Modulatory effect of phytoglycoprotein (38 kDa) on cyclin D1/CDK4 in BNL CL.2 cells induced by N-methyl-N'-nitro-N-nitrosoguanidine.

PubMed

Lee, Jin; Lim, Kye-Taek

2012-02-01

In the developmental stages of cancer, cell transformation occurs after the promotion stage and is a marker of cancer progression. This cell transformation is related to abnormal proliferation during the cancer initiation stage. The purpose of this study was to evaluate the effect of Styrax japonica Siebold et al. Zuccarin (SJSZ) glycoprotein on cell transformation in murine embryonic liver cells (BNL CL.2) following N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment. To determine abnormal proliferation during the initiation stage, intracellular reactive oxygen species (ROS), phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), activities of cell cycle-related factors [cyclin D1/cyclin dependent kinase (CDK) 4], cell cycle inhibitors (p53, p21, and p27), nuclear factor (NF)-κB, and proliferating cell nuclear antigen (PCNA) were evaluated using Western blot analysis and real-time PCR. Our study demonstrated that SJSZ glycoprotein (50 μg/ml) reduces foci formation with combined treatment [MNNG and 12-O-tetradecanoyl phorbol-13-acetate] of BNL CL.2 cells. With regard to proliferation-related signals, our finding indicated that SJSZ glycoprotein (50 μg/ml) diminished the production of intracellular ROS, activity of phosphorylated ERK, p38 MAPK, NF-κB (p50 and p65), PCNA, and cyclin D1/CDK4 in MNNG-induced BNL CL.2 cells. Taken together, these results lead us to speculate that SJSZ glycoprotein can inhibit abnormal cell proliferation at the initiation stage of hepatocarcinogenesis.

Do donor oocyte cycles comply with ASRM/SART embryo transfer guidelines? An analysis of 13,393 donor cycles from the SART registry.

PubMed

Acharya, Kelly S; Keyhan, Sanaz; Acharya, Chaitanya R; Yeh, Jason S; Provost, Meredith P; Goldfarb, James M; Muasher, Suheil J

2016-09-01

To analyze donor oocyte cycles in the Society for Assisted Reproductive Technology (SART) registry to determine: 1) how many cycles complied with the 2009 American Society for Reproductive Medicine/SART embryo transfer guidelines; and 2) cycle outcomes according to the number of embryos transferred. For donor oocyte IVF with donor age <35 years, the consideration of single-embryo transfer was strongly recommended. Retrospective cohort study of United States national registry information. Not applicable. A total of 13,393 donor-recipient cycles from 2011 to 2012. Embryos transferred in donor IVF cycles. Percentage of compliant cycles, multiple pregnancy rate. There were 3,157 donor cleavage-stage transfers and 10,236 donor blastocyst transfers. In the cleavage-stage cycles, 88% met compliance criteria. The multiple pregnancy rate (MPR) was significantly higher in the noncompliant cycles. In a subanalysis of compliant cleavage-stage cycles, 91% transferred two embryos and only 9% single embryos. In those patients transferring two embryos, the MPR was significantly higher (33% vs. 1%). In blastocyst transfers, only 28% of the cycles met compliance criteria. The MPR was significantly higher in the noncompliant blastocyst cohort at 53% (compared with 2% in compliant cycles). The majority of donor cleavage-stage transfers are compliant with current guidelines, but the transfer of two embryos results in a significantly higher MPR compared with single-embryo transfer. The majority of donor blastocyst cycles are noncompliant, which appears to be driving an unacceptably high MPR in these cycles. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The SnSAG merozoite surface antigens of Sarcocystis neurona are expressed differentially during the bradyzoite and sporozoite life cycle stages.

PubMed

Gautam, A; Dubey, J P; Saville, W J; Howe, D K

2011-12-29

Sarcocystis neurona is a two-host coccidian parasite whose complex life cycle progresses through multiple developmental stages differing at morphological and molecular levels. The S. neurona merozoite surface is covered by multiple, related glycosylphosphatidylinositol-linked proteins, which are orthologous to the surface antigen (SAG)/SAG1-related sequence (SRS) gene family of Toxoplasma gondii. Expression of the SAG/SRS proteins in T. gondii and another related parasite Neospora caninum is life-cycle stage specific and seems necessary for parasite transmission and persistence of infection. In the present study, the expression of S. neurona merozoite surface antigens (SnSAGs) was evaluated in the sporozoite and bradyzoite stages. Western blot analysis was used to compare SnSAG expression in merozoites versus sporozoites, while immunocytochemistry was performed to examine expression of the SnSAGs in merozoites versus bradyzoites. These analyses revealed that SnSAG2, SnSAG3 and SnSAG4 are expressed in sporozoites, while SnSAG5 was appeared to be downregulated in this life cycle stage. In S. neurona bradyzoites, it was found that SnSAG2, SnSAG3, SnSAG4 and SnSAG5 were either absent or expression was greatly reduced. As shown for T. gondii, stage-specific expression of the SnSAGs may be important for the parasite to progress through its developmental stages and complete its life cycle successfully. Thus, it is possible that the SAG switching mechanism by these parasites could be exploited as a point of intervention. As well, the alterations in surface antigen expression during different life cycle stages may need to be considered when designing prospective approaches for protective vaccination. Copyright © 2011 Elsevier B.V. All rights reserved.

Sulforaphane inhibits mitotic clonal expansion during adipogenesis through cell cycle arrest.

PubMed

Choi, Kyeong-Mi; Lee, Youn-Sun; Sin, Dong-Mi; Lee, Seunghyun; Lee, Mi Kyeong; Lee, Yong-Moon; Hong, Jin-Tae; Yun, Yeo-Pyo; Yoo, Hwan-Soo

2012-07-01

Obesity is a risk factor for numerous metabolic disorders such as type 2 diabetes, hypertension, and coronary heart disease. Adipocyte differentiation is triggered by adipocyte hyperplasia, which leads to obesity. In this study, the inhibitory effect of sulforaphane, an isothiocyanate, on adipogenesis in 3T3-L1 cells was investigated. Sulforaphane decreased the accumulation of lipid droplets stained with Oil Red O and inhibited the elevation of triglycerides in the adipocytes (half-maximal inhibitory concentration = 7.3 µmol/l). The expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), major transcription factors for adipocyte differentiation, was significantly reduced by sulforaphane. The major effects of sulforaphane on the inhibition of adipocyte differentiation occurred during the early stage of adipogenesis. Thus, the expression of C/EBPβ, an early-stage biomarker of adipogenesis, decreased in a concentration-dependent manner when the adipocytes were exposed to sulforaphane (0, 5, 10, and 20 µmol/l). The proliferation of adipocytes treated with 20 µmol/l sulforaphane for 24 and 48 h was also suppressed. These results indicate that sulforaphane may specifically affect mitotic clonal expansion to inhibit adipocyte differentiation. Sulforaphane arrested the cell cycle at the G(0)/G(1) phase, increased p27 expression, and decreased retinoblastoma (Rb) phosphorylation. Additionally, sulforaphane modestly decreased the phosphorylation of ERK1/2 and Akt. Our results indicate that the inhibition of early-stage adipocyte differentiation by sulforaphane may be associated with cell cycle arrest at the G(0)/G(1) phase through upregulation of p27 expression.

Predicting ecosystem shifts requires new approaches that integrate the effects of climate change across entire systems

PubMed Central

Russell, Bayden D.; Harley, Christopher D. G.; Wernberg, Thomas; Mieszkowska, Nova; Widdicombe, Stephen; Hall-Spencer, Jason M.; Connell, Sean D.

2012-01-01

Most studies that forecast the ecological consequences of climate change target a single species and a single life stage. Depending on climatic impacts on other life stages and on interacting species, however, the results from simple experiments may not translate into accurate predictions of future ecological change. Research needs to move beyond simple experimental studies and environmental envelope projections for single species towards identifying where ecosystem change is likely to occur and the drivers for this change. For this to happen, we advocate research directions that (i) identify the critical species within the target ecosystem, and the life stage(s) most susceptible to changing conditions and (ii) the key interactions between these species and components of their broader ecosystem. A combined approach using macroecology, experimentally derived data and modelling that incorporates energy budgets in life cycle models may identify critical abiotic conditions that disproportionately alter important ecological processes under forecasted climates. PMID:21900317

Fetal bovine serum simultaneously stimulates apoptosis and DNA synthesis in premeiotic stages of spermatogenesis in spiny dogfish (Squalus acanthias) in vitro: modulation by androgen and spermatogenic activity status.

PubMed

McClusky, Leon Mendel

2008-05-01

Using the simple cystic spermatogenesis in the shark testis as a model, we previously reported the relative resistance of immature spermatogonia (stem cell and early-stage spermatogonia) to apoptosis in the normal testis and after spermatoxicant exposure in vivo. Apoptosis was monitored by fluorescence image analysis of living cysts, using the validated acridine orange (AO) vital staining technique. Findings show that FBS simultaneously stimulates both apoptosis and [(3)H]thymidine incorporation in immature spermatogonial clones in a concentration-dependent manner in vitro. Furthermore, androgen inhibits apoptosis and increases cyst viability, more so with 10% FBS than with 1% FBS. All the effects were as a function of spermatogenic activity status but were distinct in early-stage spermatogonial cysts isolated from testes awakening from the previous winter spermatogenic arrest period. Results are discussed in the context of the alternating germ-Sertoli cell population kinetics of early-stage spermatogonial cysts in Squalus acanthias's protracted testicular cycle.

Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division.

PubMed

Grob, Alice; Colleran, Christine; McStay, Brian

2014-02-01

Human cell nuclei are functionally organized into structurally stable yet dynamic bodies whose cell cycle inheritance is poorly understood. Here, we investigate the biogenesis and propagation of nucleoli, sites of ribosome biogenesis and key regulators of cellular growth. Nucleolar and cell cycles are intimately connected. Nucleoli disappear during mitosis, reforming around prominent uncharacterized chromosomal features, nucleolar organizer regions (NORs). By examining the effects of UBF depletion on both endogenous NORs and synthetic pseudo-NORs, we reveal its essential role in maintaining competency and establishing a bookmark on mitotic NORs. Furthermore, we demonstrate that neo-NORs, UBF-binding site arrays coupled with rDNA transcription units, direct the de novo biogenesis of functional compartmentalized neonucleoli irrespective of their site of chromosomal integration. For the first time, we establish the sequence requirements for nucleolar biogenesis and provide proof that this is a staged process where UBF-dependent mitotic bookmarking precedes function-dependent nucleolar assembly.

Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division

PubMed Central

Grob, Alice; Colleran, Christine; McStay, Brian

2014-01-01

Human cell nuclei are functionally organized into structurally stable yet dynamic bodies whose cell cycle inheritance is poorly understood. Here, we investigate the biogenesis and propagation of nucleoli, sites of ribosome biogenesis and key regulators of cellular growth. Nucleolar and cell cycles are intimately connected. Nucleoli disappear during mitosis, reforming around prominent uncharacterized chromosomal features, nucleolar organizer regions (NORs). By examining the effects of UBF depletion on both endogenous NORs and synthetic pseudo-NORs, we reveal its essential role in maintaining competency and establishing a bookmark on mitotic NORs. Furthermore, we demonstrate that neo-NORs, UBF-binding site arrays coupled with rDNA transcription units, direct the de novo biogenesis of functional compartmentalized neonucleoli irrespective of their site of chromosomal integration. For the first time, we establish the sequence requirements for nucleolar biogenesis and provide proof that this is a staged process where UBF-dependent mitotic bookmarking precedes function-dependent nucleolar assembly. PMID:24449107

Evolution of periodicity in periodical cicadas.

PubMed

Ito, Hiromu; Kakishima, Satoshi; Uehara, Takashi; Morita, Satoru; Koyama, Takuya; Sota, Teiji; Cooley, John R; Yoshimura, Jin

2015-09-14

Periodical cicadas (Magicicada spp.) in the USA are famous for their unique prime-numbered life cycles of 13 and 17 years and their nearly perfectly synchronized mass emergences. Because almost all known species of cicada are non-periodical, periodicity is assumed to be a derived state. A leading hypothesis for the evolution of periodicity in Magicicada implicates the decline in average temperature during glacial periods. During the evolution of periodicity, the determinant of maturation in ancestral cicadas is hypothesized to have switched from size dependence to time (period) dependence. The selection for the prime-numbered cycles should have taken place only after the fixation of periodicity. Here, we build an individual-based model of cicadas under conditions of climatic cooling to explore the fixation of periodicity. In our model, under cold environments, extremely long juvenile stages lead to extremely low adult densities, limiting mating opportunities and favouring the evolution of synchronized emergence. Our results indicate that these changes, which were triggered by glacial cooling, could have led to the fixation of periodicity in the non-periodical ancestors.

Building a pseudo-atomic model of the anaphase-promoting complex.

PubMed

Kulkarni, Kiran; Zhang, Ziguo; Chang, Leifu; Yang, Jing; da Fonseca, Paula C A; Barford, David

2013-11-01

The anaphase-promoting complex (APC/C) is a large E3 ubiquitin ligase that regulates progression through specific stages of the cell cycle by coordinating the ubiquitin-dependent degradation of cell-cycle regulatory proteins. Depending on the species, the active form of the APC/C consists of 14-15 different proteins that assemble into a 20-subunit complex with a mass of approximately 1.3 MDa. A hybrid approach of single-particle electron microscopy and protein crystallography of individual APC/C subunits has been applied to generate pseudo-atomic models of various functional states of the complex. Three approaches for assigning regions of the EM-derived APC/C density map to specific APC/C subunits are described. This information was used to dock atomic models of APC/C subunits, determined either by protein crystallography or homology modelling, to specific regions of the APC/C EM map, allowing the generation of a pseudo-atomic model corresponding to 80% of the entire complex.

Aggregation of Ribosomal Protein S6 at Nucleolus Is Cell Cycle-Controlled and Its Function in Pre-rRNA Processing Is Phosphorylation Dependent.

PubMed

Zhang, Duo; Chen, Hui-Peng; Duan, Hai-Feng; Gao, Li-Hua; Shao, Yong; Chen, Ke-Yan; Wang, You-Liang; Lan, Feng-Hua; Hu, Xian-Wen

2016-07-01

Ribosomal protein S6 (rpS6) has long been regarded as one of the primary r-proteins that functions in the early stage of 40S subunit assembly, but its actual role is still obscure. The correct forming of 18S rRNA is a key step in the nuclear synthesis of 40S subunit. In this study, we demonstrate that rpS6 participates in the processing of 30S pre-rRNA to 18S rRNA only when its C-terminal five serines are phosphorylated, however, the process of entering the nucleus and then targeting the nucleolus does not dependent its phosphorylation. Remarkably, we also find that the aggregation of rpS6 at the nucleolus correlates to the phasing of cell cycle, beginning to concentrate in the nucleolus at later S phase and disaggregate at M phase. J. Cell. Biochem. 117: 1649-1657, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Final Technical Report on Quantifying Dependability Attributes of Software Based Safety Critical Instrumentation and Control Systems in Nuclear Power Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smidts, Carol; Huang, Funqun; Li, Boyuan

With the current transition from analog to digital instrumentation and control systems in nuclear power plants, the number and variety of software-based systems have significantly increased. The sophisticated nature and increasing complexity of software raises trust in these systems as a significant challenge. The trust placed in a software system is typically termed software dependability. Software dependability analysis faces uncommon challenges since software systems’ characteristics differ from those of hardware systems. The lack of systematic science-based methods for quantifying the dependability attributes in software-based instrumentation as well as control systems in safety critical applications has proved itself to be amore » significant inhibitor to the expanded use of modern digital technology in the nuclear industry. Dependability refers to the ability of a system to deliver a service that can be trusted. Dependability is commonly considered as a general concept that encompasses different attributes, e.g., reliability, safety, security, availability and maintainability. Dependability research has progressed significantly over the last few decades. For example, various assessment models and/or design approaches have been proposed for software reliability, software availability and software maintainability. Advances have also been made to integrate multiple dependability attributes, e.g., integrating security with other dependability attributes, measuring availability and maintainability, modeling reliability and availability, quantifying reliability and security, exploring the dependencies between security and safety and developing integrated analysis models. However, there is still a lack of understanding of the dependencies between various dependability attributes as a whole and of how such dependencies are formed. To address the need for quantification and give a more objective basis to the review process -- therefore reducing regulatory uncertainty -- measures and methods are needed to assess dependability attributes early on, as well as throughout the life-cycle process of software development. In this research, extensive expert opinion elicitation is used to identify the measures and methods for assessing software dependability. Semi-structured questionnaires were designed to elicit expert knowledge. A new notation system, Causal Mechanism Graphing, was developed to extract and represent such knowledge. The Causal Mechanism Graphs were merged, thus, obtaining the consensus knowledge shared by the domain experts. In this report, we focus on how software contributes to dependability. However, software dependability is not discussed separately from the context of systems or socio-technical systems. Specifically, this report focuses on software dependability, reliability, safety, security, availability, and maintainability. Our research was conducted in the sequence of stages found below. Each stage is further examined in its corresponding chapter. Stage 1 (Chapter 2): Elicitation of causal maps describing the dependencies between dependability attributes. These causal maps were constructed using expert opinion elicitation. This chapter describes the expert opinion elicitation process, the questionnaire design, the causal map construction method and the causal maps obtained. Stage 2 (Chapter 3): Elicitation of the causal map describing the occurrence of the event of interest for each dependability attribute. The causal mechanisms for the “event of interest” were extracted for each of the software dependability attributes. The “event of interest” for a dependability attribute is generally considered to be the “attribute failure”, e.g. security failure. The extraction was based on the analysis of expert elicitation results obtained in Stage 1. Stage 3 (Chapter 4): Identification of relevant measurements. Measures for the “events of interest” and their causal mechanisms were obtained from expert opinion elicitation for each of the software dependability attributes. The measures extracted are presented in this chapter. Stage 4 (Chapter 5): Assessment of the coverage of the causal maps via measures. Coverage was assessed to determine whether the measures obtained were sufficient to quantify software dependability, and what measures are further required. Stage 5 (Chapter 6): Identification of “missing” measures and measurement approaches for concepts not covered. New measures, for concepts that had not been covered sufficiently as determined in Stage 4, were identified using supplementary expert opinion elicitation as well as literature reviews. Stage 6 (Chapter 7): Building of a detailed quantification model based on the causal maps and measurements obtained. Ability to derive such a quantification model shows that the causal models and measurements derived from the previous stages (Stage 1 to Stage 5) can form the technical basis for developing dependability quantification models. Scope restrictions have led us to prioritize this demonstration effort. The demonstration was focused on a critical system, i.e. the reactor protection system. For this system, a ranking of the software dependability attributes by nuclear stakeholders was developed. As expected for this application, the stakeholder ranking identified safety as the most critical attribute to be quantified. A safety quantification model limited to the requirements phase of development was built. Two case studies were conducted for verification. A preliminary control gate for software safety for the requirements stage was proposed and applied to the first case study. The control gate allows a cost effective selection of the duration of the requirements phase.« less

An optimal policy for deteriorating items with time-proportional deterioration rate and constant and time-dependent linear demand rate

NASA Astrophysics Data System (ADS)

Singh, Trailokyanath; Mishra, Pandit Jagatananda; Pattanayak, Hadibandhu

2017-12-01

In this paper, an economic order quantity (EOQ) inventory model for a deteriorating item is developed with the following characteristics: (i) The demand rate is deterministic and two-staged, i.e., it is constant in first part of the cycle and linear function of time in the second part. (ii) Deterioration rate is time-proportional. (iii) Shortages are not allowed to occur. The optimal cycle time and the optimal order quantity have been derived by minimizing the total average cost. A simple solution procedure is provided to illustrate the proposed model. The article concludes with a numerical example and sensitivity analysis of various parameters as illustrations of the theoretical results.

In Vitro Alterations Do Not Reflect a Requirement for Host Cell Cycle Progression during Plasmodium Liver Stage Infection

PubMed Central

Hanson, Kirsten K.; March, Sandra; Ng, Shengyong; Bhatia, Sangeeta N.

2014-01-01

Prior to invading nonreplicative erythrocytes, Plasmodium parasites undergo their first obligate step in the mammalian host inside hepatocytes, where each sporozoite replicates to generate thousands of merozoites. While normally quiescent, hepatocytes retain proliferative capacity and can readily reenter the cell cycle in response to diverse stimuli. Many intracellular pathogens, including protozoan parasites, manipulate the cell cycle progression of their host cells for their own benefit, but it is not known whether the hepatocyte cell cycle plays a role during Plasmodium liver stage infection. Here, we show that Plasmodium parasites can be observed in mitotic hepatoma cells throughout liver stage development, where they initially reduce the likelihood of mitosis and ultimately lead to significant acquisition of a binucleate phenotype. However, hepatoma cells pharmacologically arrested in S phase still support robust and complete Plasmodium liver stage development, which thus does not require cell cycle progression in the infected cell in vitro. Furthermore, murine hepatocytes remain quiescent throughout in vivo infection with either Plasmodium berghei or Plasmodium yoelii, as do Plasmodium falciparum-infected primary human hepatocytes, demonstrating that the rapid and prodigious growth of liver stage parasites is accomplished independent of host hepatocyte cell cycle progression during natural infection. PMID:25416236

The steady-state level and stability of TLS polymerase eta are cell cycle dependent in the yeast S. cerevisiae.

PubMed

Plachta, Michal; Halas, Agnieszka; McIntyre, Justyna; Sledziewska-Gojska, Ewa

2015-05-01

Polymerase eta (Pol eta) is a ubiquitous translesion DNA polymerase that is capable of bypassing UV-induced pyrimidine dimers in an error-free manner. However, this specialized polymerase is error prone when synthesizing through an undamaged DNA template. In Saccharomyces cerevisiae, both depletion and overproduction of Pol eta result in mutator phenotypes. Therefore, regulation of the cellular abundance of this enzyme is of particular interest. However, based on the investigation of variously tagged forms of Pol eta, mutually contradictory conclusions have been reached regarding the stability of this polymerase in yeast. Here, we optimized a protocol for the detection of untagged yeast Pol eta and established that the half-life of the native enzyme is 80 ± 14 min in asynchronously growing cultures. Experiments with synchronized cells indicated that the cellular abundance of this translesion polymerase changes throughout the cell cycle. Accordingly, we show that the stability of Pol eta, but not its mRNA level, is cell cycle stage dependent. The half-life of the polymerase is more than fourfold shorter in G1-arrested cells than in those at G2/M. Our results, in concert with previous data for Rev1, indicate that cell cycle regulation is a general property of Y family TLS polymerases in S. cerevisiae. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of cyclin-dependent kinases and Cdc2/Cdc28 kinase subunits in Trichomonas vaginalis.

PubMed

Amador, Erick; López-Pacheco, Karla; Morales, Nataly; Coria, Roberto; López-Villaseñor, Imelda

2017-04-01

Cyclin-dependent kinases (CDKs) have important roles in regulating key checkpoints between stages of the cell cycle. Their activity is tightly regulated through a variety of mechanisms, including through binding with cyclin proteins and the Cdc2/Cdc28 kinase subunit (CKS), and their phosphorylation at specific amino acids. Studies of the components involved in cell cycle control in parasitic protozoa are limited. Trichomonas vaginalis is the causative agent of trichomoniasis in humans and is therefore important in public health; however, some of the basic biological processes used by this organism have not been defined. Here, we characterized proteins potentially involved in cell cycle regulation in T. vaginalis. Three genes encoding protein kinases were identified in the T. vaginalis genome, and the corresponding recombinant proteins (TvCRK1, TvCRK2, TvCRK5) were studied. These proteins displayed similar sequence features to CDKs. Two genes encoding CKSs were also identified, and the corresponding recombinant proteins were found to interact with TvCRK1 and TvCRK2 by a yeast two-hybrid system. One putative cyclin B protein from T. vaginalis was found to bind to and activate the kinase activities of TvCRK1 and TvCRK5, but not TvCRK2. This work is the first characterization of proteins involved in cell cycle control in T. vaginalis.

Dbf4-dependent kinase and the Rtt107 scaffold promote Mus81-Mms4 resolvase activation during mitosis.

PubMed

Princz, Lissa N; Wild, Philipp; Bittmann, Julia; Aguado, F Javier; Blanco, Miguel G; Matos, Joao; Pfander, Boris

2017-03-01

DNA repair by homologous recombination is under stringent cell cycle control. This includes the last step of the reaction, disentanglement of DNA joint molecules (JMs). Previous work has established that JM resolving nucleases are activated specifically at the onset of mitosis. In case of budding yeast Mus81-Mms4, this cell cycle stage-specific activation is known to depend on phosphorylation by CDK and Cdc5 kinases. Here, we show that a third cell cycle kinase, Cdc7-Dbf4 (DDK), targets Mus81-Mms4 in conjunction with Cdc5-both kinases bind to as well as phosphorylate Mus81-Mms4 in an interdependent manner. Moreover, DDK-mediated phosphorylation of Mms4 is strictly required for Mus81 activation in mitosis, establishing DDK as a novel regulator of homologous recombination. The scaffold protein Rtt107, which binds the Mus81-Mms4 complex, interacts with Cdc7 and thereby targets DDK and Cdc5 to the complex enabling full Mus81 activation. Therefore, Mus81 activation in mitosis involves at least three cell cycle kinases, CDK, Cdc5 and DDK Furthermore, tethering of the kinases in a stable complex with Mus81 is critical for efficient JM resolution. © 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Exploring the universal ecological responses to climate change in a univoltine butterfly.

PubMed

Fenberg, Phillip B; Self, Angela; Stewart, John R; Wilson, Rebecca J; Brooks, Stephen J

2016-05-01

Animals with distinct life stages are often exposed to different temperatures during each stage. Thus, how temperature affects these life stages should be considered for broadly understanding the ecological consequences of climate warming on such species. For example, temperature variation during particular life stages may affect respective change in body size, phenology and geographic range, which have been identified as the "universal" ecological responses to climate change. While each of these responses has been separately documented across a number of species, it is not known whether each response occurs together within a species. The influence of temperature during particular life stages may help explain each of these ecological responses to climate change. Our goal was to determine if monthly temperature variation during particular life stages of a butterfly species can predict respective changes in body size and phenology. We also refer to the literature to assess if temperature variability during the adult stage influences range change over time. Using historical museum collections paired with monthly temperature records, we show that changes in body size and phenology of the univoltine butterfly, Hesperia comma, are partly dependent upon temporal variation in summer temperatures during key stages of their life cycle. June temperatures, which are likely to affect growth rate of the final larval instar, are important for predicting adult body size (for males only; showing a positive relationship with temperature). July temperatures, which are likely to influence the pupal stage, are important for predicting the timing of adult emergence (showing a negative relationship with temperature). Previous studies show that August temperatures, which act on the adult stage, are linked to range change. Our study highlights the importance of considering temperature variation during each life stage over historic time-scales for understanding intraspecific response to climate change. Range edge studies of ectothermic species that have annual life cycles, long time-series occurrence data, and associated temperature records (ideally at monthly resolutions) could be useful model systems for intraspecific tests of the universal ecological responses to climate change and for exploring interactive effects. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Framework for Multidisciplinary Analysis, Design, and Optimization with High-Fidelity Analysis Tools

NASA Technical Reports Server (NTRS)

Orr, Stanley A.; Narducci, Robert P.

2009-01-01

A plan is presented for the development of a high fidelity multidisciplinary optimization process for rotorcraft. The plan formulates individual disciplinary design problems, identifies practical high-fidelity tools and processes that can be incorporated in an automated optimization environment, and establishes statements of the multidisciplinary design problem including objectives, constraints, design variables, and cross-disciplinary dependencies. Five key disciplinary areas are selected in the development plan. These are rotor aerodynamics, rotor structures and dynamics, fuselage aerodynamics, fuselage structures, and propulsion / drive system. Flying qualities and noise are included as ancillary areas. Consistency across engineering disciplines is maintained with a central geometry engine that supports all multidisciplinary analysis. The multidisciplinary optimization process targets the preliminary design cycle where gross elements of the helicopter have been defined. These might include number of rotors and rotor configuration (tandem, coaxial, etc.). It is at this stage that sufficient configuration information is defined to perform high-fidelity analysis. At the same time there is enough design freedom to influence a design. The rotorcraft multidisciplinary optimization tool is built and substantiated throughout its development cycle in a staged approach by incorporating disciplines sequentially.

Efficiency improvement of technological preparation of power equipment manufacturing

NASA Astrophysics Data System (ADS)

Milukov, I. A.; Rogalev, A. N.; Sokolov, V. P.; Shevchenko, I. V.

2017-11-01

Competitiveness of power equipment primarily depends on speeding-up the development and mastering of new equipment samples and technologies, enhancement of organisation and management of design, manufacturing and operation. Actual political, technological and economic conditions cause the acute need in changing the strategy and tactics of process planning. At that the issues of maintenance of equipment with simultaneous improvement of its efficiency and compatibility to domestically produced components are considering. In order to solve these problems, using the systems of computer-aided process planning for process design at all stages of power equipment life cycle is economically viable. Computer-aided process planning is developed for the purpose of improvement of process planning by using mathematical methods and optimisation of design and management processes on the basis of CALS technologies, which allows for simultaneous process design, process planning organisation and management based on mathematical and physical modelling of interrelated design objects and production system. An integration of computer-aided systems providing the interaction of informative and material processes at all stages of product life cycle is proposed as effective solution to the challenges in new equipment design and process planning.

Cycle Commuting and Perceptions of Barriers: Stages of Change, Gender and Occupation

ERIC Educational Resources Information Center

van Bekkum, Jennifer E.; Williams, Joanne M.; Morris, Paul Graham

2011-01-01

Purpose: The aim of this study is to investigate perceptions of cycle commuting barriers in relation to stage of change, gender and occupational role. Stage of change is a key construct of the transtheoretical model of behaviour change that defines behavioural readiness (intentions and actions) into five distinct categories.…

Teacher Career Stages: Implications for Staff Development. Fastback 214.

ERIC Educational Resources Information Center

Burke, Peter J.; And Others

Literature on adult life stages and career development is synthesized and placed within the perspective of a career cycle model for teachers as adult learners. The teacher career cycle is viewed as a progression affected by personal and environmental factors. The stages a teacher's career proceeds through (e.g., preservice, entry, growing, stable,…

Transient thermal stresses analysis and thermal fatigue damage evaluation for skirt attachment of coke drum

NASA Astrophysics Data System (ADS)

Ambarita, H.; Siahaan, A. S.; Kawai, H.; Daimaruya, M.

2018-02-01

In the last decade, the demand for delayed coking capacity has been steadily increasing. The trend in the past 15 to 20 years has been for operators to try to maximize the output of their units by reducing cycle times. This mode of operation can result in very large temperature gradients within the drums during preheating stage and even more so during the quench cycle. This research provide the optimization estimation of fatigue life due to each for the absence of preheating stage and cutting stage. In the absence of preheating stage the decreasing of fatigue life is around 19% and the increasing of maximum stress in point 5 of shell-to-skirt junction is around 97 MPa. However for the absence of cutting stage it was found that is more severe compare to normal cycle. In this adjustment fatigue life reduce around 39% and maximum stress is increased around 154 MPa. It can concluded that for cycle optimization, eliminating preheating stage possibly can become an option due to the increasing demand of delayed coking process.

A novel multiple-stage antimalarial agent that inhibits protein synthesis.

PubMed

Baragaña, Beatriz; Hallyburton, Irene; Lee, Marcus C S; Norcross, Neil R; Grimaldi, Raffaella; Otto, Thomas D; Proto, William R; Blagborough, Andrew M; Meister, Stephan; Wirjanata, Grennady; Ruecker, Andrea; Upton, Leanna M; Abraham, Tara S; Almeida, Mariana J; Pradhan, Anupam; Porzelle, Achim; Luksch, Torsten; Martínez, María Santos; Luksch, Torsten; Bolscher, Judith M; Woodland, Andrew; Norval, Suzanne; Zuccotto, Fabio; Thomas, John; Simeons, Frederick; Stojanovski, Laste; Osuna-Cabello, Maria; Brock, Paddy M; Churcher, Tom S; Sala, Katarzyna A; Zakutansky, Sara E; Jiménez-Díaz, María Belén; Sanz, Laura Maria; Riley, Jennifer; Basak, Rajshekhar; Campbell, Michael; Avery, Vicky M; Sauerwein, Robert W; Dechering, Koen J; Noviyanti, Rintis; Campo, Brice; Frearson, Julie A; Angulo-Barturen, Iñigo; Ferrer-Bazaga, Santiago; Gamo, Francisco Javier; Wyatt, Paul G; Leroy, Didier; Siegl, Peter; Delves, Michael J; Kyle, Dennis E; Wittlin, Sergio; Marfurt, Jutta; Price, Ric N; Sinden, Robert E; Winzeler, Elizabeth A; Charman, Susan A; Bebrevska, Lidiya; Gray, David W; Campbell, Simon; Fairlamb, Alan H; Willis, Paul A; Rayner, Julian C; Fidock, David A; Read, Kevin D; Gilbert, Ian H

2015-06-18

There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.

A novel multiple-stage antimalarial agent that inhibits protein synthesis

NASA Astrophysics Data System (ADS)

Baragaña, Beatriz; Hallyburton, Irene; Lee, Marcus C. S.; Norcross, Neil R.; Grimaldi, Raffaella; Otto, Thomas D.; Proto, William R.; Blagborough, Andrew M.; Meister, Stephan; Wirjanata, Grennady; Ruecker, Andrea; Upton, Leanna M.; Abraham, Tara S.; Almeida, Mariana J.; Pradhan, Anupam; Porzelle, Achim; Martínez, María Santos; Bolscher, Judith M.; Woodland, Andrew; Norval, Suzanne; Zuccotto, Fabio; Thomas, John; Simeons, Frederick; Stojanovski, Laste; Osuna-Cabello, Maria; Brock, Paddy M.; Churcher, Tom S.; Sala, Katarzyna A.; Zakutansky, Sara E.; Jiménez-Díaz, María Belén; Sanz, Laura Maria; Riley, Jennifer; Basak, Rajshekhar; Campbell, Michael; Avery, Vicky M.; Sauerwein, Robert W.; Dechering, Koen J.; Noviyanti, Rintis; Campo, Brice; Frearson, Julie A.; Angulo-Barturen, Iñigo; Ferrer-Bazaga, Santiago; Gamo, Francisco Javier; Wyatt, Paul G.; Leroy, Didier; Siegl, Peter; Delves, Michael J.; Kyle, Dennis E.; Wittlin, Sergio; Marfurt, Jutta; Price, Ric N.; Sinden, Robert E.; Winzeler, Elizabeth A.; Charman, Susan A.; Bebrevska, Lidiya; Gray, David W.; Campbell, Simon; Fairlamb, Alan H.; Willis, Paul A.; Rayner, Julian C.; Fidock, David A.; Read, Kevin D.; Gilbert, Ian H.

2015-06-01

There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.

Distinct Prominent Roles for Enzymes of Plasmodium berghei Heme Biosynthesis in Sporozoite and Liver Stage Maturation

PubMed Central

Matuschewski, Kai; Haussig, Joana M.

2016-01-01

Malarial parasites have evolved complex regulation of heme supply and disposal to adjust to heme-rich and -deprived host environments. In addition to its own pathway for heme biosynthesis, Plasmodium likely harbors mechanisms for heme scavenging from host erythrocytes. Elaborate compartmentalization of de novo heme synthesis into three subcellular locations, including the vestigial plastid organelle, indicates critical roles in life cycle progression. In this study, we systematically profile the essentiality of heme biosynthesis by targeted gene deletion of enzymes in early steps of this pathway. We show that disruption of endogenous heme biosynthesis leads to a first detectable defect in oocyst maturation and sporogony in the Anopheles vector, whereas blood stage propagation, colonization of mosquito midguts, or initiation of oocyst development occurs indistinguishably from that of wild-type parasites. Although sporozoites are produced by parasites lacking an intact pathway for heme biosynthesis, they are absent from mosquito salivary glands, indicative of a vital role for heme biosynthesis only in sporozoite maturation. Rescue of the first defect in sporogony permitted analysis of potential roles in liver stages. We show that liver stage parasites benefit from but do not strictly depend upon their own aminolevulinic acid synthase and that they can scavenge aminolevulinic acid from the host environment. Together, our experimental genetics analysis of Plasmodium enzymes for heme biosynthesis exemplifies remarkable shifts between the use of endogenous and host resources during life cycle progression. PMID:27600503

Investigation of the environmental implications of the CNT switch through its life cycle

NASA Astrophysics Data System (ADS)

Dahlben, Lindsay Johanna

Carbon nanotubes (CNTs) are unique allotropes of carbon that have high tensile strength, a high Young's modulus, good thermal conductivity, and depending on the CNT chirality can be metallic or semiconducting. These mechanical, thermal, and electrical properties make CNTs an attractive element in electronic applications such as conductive films, photovoltaics, non-volatile memory devices, batteries, sensors, and displays. Although commercialization of CNT-enabled products is increasing, there remains a significant lack of information regarding the health effects and environmental impacts of CNTs. Some studies have even shown that the behavior, toxicity, and persistence of CNTs may differ from bulk heterogeneous carbon. Given these uncertainties, it is prudent to assess the environmental attributes of CNT products and processes now to discover and potentially prevent adverse effects. This study investigates the environmental implications of a non-volatile bi-stable electromechanical CNT switch through its life cycle. Life cycle assessment (LCA) methodology is used to track the environmental impacts of the CNT switch through its fabrication and expected use and end-of-life (EOL) stages. Process parameters, energy consumption, input materials, output emissions, and yield efficiencies are determined for the laboratory and full-scale manufacture environments. The Ecoinvent(TM) inventory database and Eco-indicator 1999(TM) method are utilized for the impact assessment. Results for the fabrication stage are reported for highest contributions to environmental impact such as airborne inorganics, land use, and fossil fuels due to Au refining processes and electricity consumption. Extension of the LCA scope is evaluated for the potential replacement of CNT switches to current field-effect transistors (FETs) in flash memory for a cellular phone application. First-order predictions are made for the functionality and performance of the CNT switch during the use stage through an environmental perspective. Existing cellular phone EOL management options including recycling and direct disposal to landfill and incineration are evaluated for potential limitations, concerns, and environmental releases that may occur from the assimilation of CNT switch-enabled phones into the waste stream. In this manner, potential environmental effects of the CNT switch throughout its life cycle stages can be addressed alongside its technological development to ensure safe, sustainable, and successful CNT products.

The components of kin competition.

PubMed

Van Dyken, J David

2010-10-01

It is well known that competition among kin alters the rate and often the direction of evolution in subdivided populations. Yet much remains unclear about the ecological and demographic causes of kin competition, or what role life cycle plays in promoting or ameliorating its effects. Using the multilevel Price equation, I derive a general equation for evolution in structured populations under an arbitrary intensity of kin competition. This equation partitions the effects of selection and demography, and recovers numerous previous models as special cases. I quantify the degree of kin competition, α, which explicitly depends on life cycle. I show how life cycle and demographic assumptions can be incorporated into kin selection models via α, revealing life cycles that are more or less permissive of altruism. As an example, I give closed-form results for Hamilton's rule in a three-stage life cycle. Although results are sensitive to life cycle in general, I identify three demographic conditions that give life cycle invariant results. Under the infinite island model, α is a function of the scale of density regulation and dispersal rate, effectively disentangling these two phenomena. Population viscosity per se does not impede kin selection. © 2010 The Author(s). Journal compilation © 2010 The Society for the Study of Evolution.

Natural variability of biochemical biomarkers in the macro-zoobenthos: Dependence on life stage and environmental factors.

PubMed

Scarduelli, Lucia; Giacchini, Roberto; Parenti, Paolo; Migliorati, Sonia; Di Brisco, Agnese Maria; Vighi, Marco

2017-11-01

Biomarkers are widely used in ecotoxicology as indicators of exposure to toxicants. However, their ability to provide ecologically relevant information remains controversial. One of the major problems is understanding whether the measured responses are determined by stress factors or lie within the natural variability range. In a previous work, the natural variability of enzymatic levels in invertebrates sampled in pristine rivers was proven to be relevant across both space and time. In the present study, the experimental design was improved by considering different life stages of the selected taxa and by measuring more environmental parameters. The experimental design considered sampling sites in 2 different rivers, 8 sampling dates covering the whole seasonal cycle, 4 species from 3 different taxonomic groups (Plecoptera, Perla grandis; Ephemeroptera, Baetis alpinus and Epeorus alpicula; Tricoptera, Hydropsyche pellucidula), different life stages for each species, and 4 enzymes (acetylcholinesterase, glutathione S-transferase, alkaline phosphatase, and catalase). Biomarker levels were related to environmental (physicochemical) parameters to verify any kind of dependence. Data were statistically elaborated using hierarchical multilevel Bayesian models. Natural variability was found to be relevant across both space and time. The results of the present study proved that care should be paid when interpreting biomarker results. Further research is needed to better understand the dependence of the natural variability on environmental parameters. Environ Toxicol Chem 2017;36:3158-3167. © 2017 SETAC. © 2017 SETAC.

Hormone-Dependence of Sarin Lethality in Rats: Sex Differences and Stage of the Estrous Cycle

DTIC Science & Technology

2015-06-12

that causes numerous physiological events including miosis, salivation , respiratory failure, tremors, seizures, and death. Treatment regimens that...into 96-well plates. The reactions were initiated by the addition of 290 μL of 50 mM sodium phosphate buffer ( pH 8.0) containing one of the following...buffer containing 50mMHEPES pH 7.4 in a total volume of 280 μL. Treat- ed samples were loaded into a 96-microtiter plate well, and the reaction was

Training for Content Teachers of English Language Learners: Using Experiential Learning to Improve Instruction

ERIC Educational Resources Information Center

Bohon, Leslie L.; McKelvey, Susan; Rhodes, Joan A.; Robnolt, Valerie J.

2017-01-01

Experiential learning theory places experience at the center of learning. Kolb's four-stage cycle of experiential learning suggests that effective learners must engage fully in each stage of the cycle--feeling, reflection, thinking, and action. This research assesses the alignment of Kolb's experiential learning cycle with the week-long Summer…

Alternative Approaches to the Family Life Cycle in the Analysis of Housing Consumption.

ERIC Educational Resources Information Center

McLeod, P. B.; Ellis, J. R.

1983-01-01

Used loan-approval data to analyze the effects of life-cycle stage on housing consumption. The detailed typologies were not generally superior to the more simplified approaches, except for per capita consumption. For per capita consumption, price, and quality, clear evidence is found for structural nonhomogeneity across life-cycle stages. (JAC)

An ongoing process: a qualitative study of how the alcohol-dependent free themselves of addiction through progressive abstinence.

PubMed

Yeh, Mei-Yu; Che, Hui-Lian; Wu, Shu-Mei

2009-11-24

Most people being treated for alcoholism are unable to successfully quit drinking within their treatment programs. In few cases do we know the full picture of how abstinence is achieved in Taiwan. We tracked processes of abstinence in alcohol-dependency disorders, based on study evidence and results. This research explores the process of recovery from the viewpoint of the alcohol-dependent. Semi-structured interviews were conducted in two different settings, using purpose sampling, during 2003-2004. The data were analyzed using content analysis. Participants were 32 adults, purposefully selected from an Alcoholics Anonymous group and a psychiatric hospital in North Taiwan. We found that the abstinence process is an ongoing process, in which the alcohol-dependent free themselves of addiction progressively. This process never ends or resolves in complete recovery. We have identified three stages in the struggle against alcoholism: the Indulgence, Ambivalence and Attempt (IAA) cycle, in which the sufferer is trapped in a cycle of attempting to give up and failing; the Turning Point, in which a Personal Nadir is reached, and the Ongoing Process of abstinence, in which a constant effort is made to remain sober through willpower and with the help of support groups. We also discuss Influencing Factors that can derail abstinence attempts, pushing the sufferer back into the IAA cycle. This study provides important points of reference for alcohol and drug service workers and community healthcare professionals in Taiwan, casting light on the abstinence process and providing a basis for intervention or rehabilitation services.

ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage

PubMed Central

Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

2014-01-01

The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein–protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage. PMID:24675884

ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage.

PubMed

Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

2014-01-01

The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein-protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage.

An ongoing process: A qualitative study of how the alcohol-dependent free themselves of addiction through progressive abstinence

PubMed Central

2009-01-01

Background Most people being treated for alcoholism are unable to successfully quit drinking within their treatment programs. In few cases do we know the full picture of how abstinence is achieved in Taiwan. We tracked processes of abstinence in alcohol-dependency disorders, based on study evidence and results. This research explores the process of recovery from the viewpoint of the alcohol-dependent. Methods Semi-structured interviews were conducted in two different settings, using purpose sampling, during 2003-2004. The data were analyzed using content analysis. Participants were 32 adults, purposefully selected from an Alcoholics Anonymous group and a psychiatric hospital in North Taiwan. Results We found that the abstinence process is an ongoing process, in which the alcohol-dependent free themselves of addiction progressively. This process never ends or resolves in complete recovery. We have identified three stages in the struggle against alcoholism: the Indulgence, Ambivalence and Attempt (IAA) cycle, in which the sufferer is trapped in a cycle of attempting to give up and failing; the Turning Point, in which a Personal Nadir is reached, and the Ongoing Process of abstinence, in which a constant effort is made to remain sober through willpower and with the help of support groups. We also discuss Influencing Factors that can derail abstinence attempts, pushing the sufferer back into the IAA cycle. Conclusion This study provides important points of reference for alcohol and drug service workers and community healthcare professionals in Taiwan, casting light on the abstinence process and providing a basis for intervention or rehabilitation services. PMID:19930698

The genetic covariance between life cycle stages separated by metamorphosis

PubMed Central

Aguirre, J. David; Blows, Mark W.; Marshall, Dustin J.

2014-01-01

Metamorphosis is common in animals, yet the genetic associations between life cycle stages are poorly understood. Given the radical changes that occur at metamorphosis, selection may differ before and after metamorphosis, and the extent that genetic associations between pre- and post-metamorphic traits constrain evolutionary change is a subject of considerable interest. In some instances, metamorphosis may allow the genetic decoupling of life cycle stages, whereas in others, metamorphosis could allow complementary responses to selection across the life cycle. Using a diallel breeding design, we measured viability at four ontogenetic stages (embryo, larval, juvenile and adult viability), in the ascidian Ciona intestinalis and examined the orientation of additive genetic variation with respect to the metamorphic boundary. We found support for one eigenvector of G (gobsmax), which contrasted larval viability against embryo viability and juvenile viability. Target matrix rotation confirmed that while gobsmax shows genetic associations can extend beyond metamorphosis, there is still considerable scope for decoupled phenotypic evolution. Therefore, although genetic associations across metamorphosis could limit that range of phenotypes that are attainable, traits on either side of the metamorphic boundary are capable of some independent evolutionary change in response to the divergent conditions encountered during each life cycle stage. PMID:24966319

Functions of the Type 1 BMP Receptor Acvr1 (Alk2) in Lens Development: Cell Proliferation, Terminal Differentiation, and Survival

PubMed Central

Rajagopal, Ramya; Dattilo, Lisa K.; Kaartinen, Vesa; Deng, Chu-Xia; Umans, Lieve; Zwijsen, An; Roberts, Anita B.; Bottinger, Erwin P.; Beebe, David C.

2009-01-01

Purpose Bone morphogenetic protein (BMP) signaling is essential for the induction and subsequent development of the lens. The purpose of this study was to analyze the function(s) of the type 1 BMP receptor, Acvr1, in lens development. Methods Acvr1 was deleted from the surface ectoderm of mouse embryos on embryonic day 9 using the Cre-loxP method. Cell proliferation, cell cycle exit, and apoptosis were measured in tissue sections by immunohistochemistry, immunofluorescence, and TUNEL staining. Results Lenses formed in the absence of Acvr1. However, Acvr1CKO (conditional knockout) lenses were small. Acvr1 signaling promoted proliferation at early stages of lens formation but inhibited proliferation at later stages. Inhibition of cell proliferation by Acvr1 was necessary for the proper regionalization of the lens epithelium and promoted the withdrawal of lens fiber cells from the cell cycle. In spite of the failure of all Acvr1CKO fiber cells to withdraw from the cell cycle, they expressed proteins characteristic of differentiated fiber cells. Although the stimulation of proliferation was Smad independent, the ability of Acvr1 to promote cell cycle exit later in development depended on classical R-Smad-Smad4 signaling. Loss of Acvr1 led to an increase in apoptosis of lens epithelial and fiber cells. Increased cell death, together with the initial decrease in proliferation, appeared to account for the smaller sizes of the Acvr1CKO lenses. Conclusions This study revealed a novel switch in the functions of Acvr1 in regulating lens cell proliferation. Previously unknown functions mediated by this receptor included regionalization of the lens epithelium and cell cycle exit during fiber cell differentiation. PMID:18566469

Carbon footprint of forest and tree utilization technologies in life cycle approach

NASA Astrophysics Data System (ADS)

Polgár, András; Pécsinger, Judit

2017-04-01

In our research project a suitable method has been developed related the technological aspect of the environmental assessment of land use changes caused by climate change. We have prepared an eco-balance (environmental inventory) to the environmental effects classification in life-cycle approach in connection with the typical agricultural / forest and tree utilization technologies. The use of balances and environmental classification makes possible to compare land-use technologies and their environmental effects per common functional unit. In order to test our environmental analysis model, we carried out surveys in sample of forest stands. We set up an eco-balance of the working systems of intermediate cutting and final harvest in the stands of beech, oak, spruce, acacia, poplar and short rotation energy plantations (willow, poplar). We set up the life-cycle plan of the surveyed working systems by using the GaBi 6.0 Professional software and carried out midpoint and endpoint impact assessment. Out of the results, we applied the values of CML 2001 - Global Warming Potential (GWP 100 years) [kg CO2-Equiv.] and Eco-Indicator 99 - Human health, Climate Change [DALY]. On the basis of the values we set up a ranking of technology. By this, we received the environmental impact classification of the technologies based on carbon footprint. The working systems had the greatest impact on global warming (GWP 100 years) throughout their whole life cycle. This is explained by the amount of carbon dioxide releasing to the atmosphere resulting from the fuel of the technologies. Abiotic depletion (ADP foss) and marine aquatic ecotoxicity (MAETP) emerged also as significant impact categories. These impact categories can be explained by the share of input of fuel and lube. On the basis of the most significant environmental impact category (carbon footprint), we perform the relative life cycle contribution and ranking of each technologies. The technological life cycle stages examined in the stands are the followings: Stage 1. cleaning cutting Stage 2. selection thinning Stage 3. increment thinning Stage 4. final harvest In these priority impact categories, the life cycle contribution of technologies varied according to the life cycle stages. • The spruce stand showed the smallest contribution in the stages 1, 2, 3 alike. • After the large contribution of beech stand at the beginning (stage 1), it continues representing a moderate level in stage 2 and 3, and it shares the smallest rate in final harvest (stage 4). • The oak stand showed the largest contribution in the stages 2, 3, 4 alike. • In the case of acacia and poplar, we have got the same results as in the case of oak stands. • In the case of short rotation energy plantations (willow, poplar), we got the results typical on stage 4 of spruce stands. We can conclude, that in case of the stage of final harvest, which represents the most significant environmental impact, the ranking of working systems showes the increasing order of „energy plantations - beech - spruce - acacia - poplar - oak". The environmental assessment of technological aspects of land use and land use change represent an important added value to the climate research. Acknowledgement: This research has been supported by the Agroclimate.2 VKSZ_12-1- 2013-0034 project. Keywords: life-cycle assessment / forest utilization technology / carbon footprint / life-cycle thinking

Regeneration experiments below 10K in a regenerative-cycle cryocooler

NASA Technical Reports Server (NTRS)

Sager, R. E.; Paulson, D. N.

1983-01-01

At temperatures below 10K, regenerative cycle cryocoolers are limited by regeneration losses in the helium working fluid which result from the decreasing heat capacity of the regenerating material and the increasing density of helium. Experiments examining several approaches to improving the low-temperature regeneration in a four-stage regenerative cycle cooler constructed primarily of fiberglass materials are discussed. Using an interchangeable fourth stage, the experiments included configurations with multiple regeneration passages, and a static helium volume for increased heat capacity. Experiments using helium-3 as the working fluid and a Malone stage are planned. Results indicate that, using these techniques, it should be possible to construct a regenerative cycle cooler which will operate below 6K.

A life cycle database for parasitic acanthocephalans, cestodes, and nematodes

USGS Publications Warehouse

Benesh, Daniel P.; Lafferty, Kevin D.; Kuris, Armand

2017-01-01

Parasitologists have worked out many complex life cycles over the last ~150 years, yet there have been few efforts to synthesize this information to facilitate comparisons among taxa. Most existing host-parasite databases focus on particular host taxa, do not distinguish final from intermediate hosts, and lack parasite life-history information. We summarized the known life cycles of trophically transmitted parasitic acanthocephalans, cestodes, and nematodes. For 973 parasite species, we gathered information from the literature on the hosts infected at each stage of the parasite life cycle (8510 host-parasite species associations), what parasite stage is in each host, and whether parasites need to infect certain hosts to complete the life cycle. We also collected life-history data for these parasites at each life cycle stage, including 2313 development time measurements and 7660 body size measurements. The result is the most comprehensive data summary available for these parasite taxa. In addition to identifying gaps in our knowledge of parasite life cycles, these data can be used to test hypotheses about life cycle evolution, host specificity, parasite life-history strategies, and the roles of parasites in food webs.

Endocrine and ultrasonographic aspects of the oestrous cycle of the mule.

PubMed

Volpe, P; Russo, M; Ianetti, L; Izzo, B

2005-12-03

The blood serum concentrations of progesterone and estradiol-17beta were measured at various stages of the oestrous cycle of seven female mules, and their reproductive tracts were examined ultrasonographically at the same stages.

A Multiplexed High-Content Screening Approach Using the Chromobody Technology to Identify Cell Cycle Modulators in Living Cells.

PubMed

Schorpp, Kenji; Rothenaigner, Ina; Maier, Julia; Traenkle, Bjoern; Rothbauer, Ulrich; Hadian, Kamyar

2016-10-01

Many screening hits show relatively poor quality regarding later efficacy and safety. Therefore, small-molecule screening efforts shift toward high-content analysis providing more detailed information. Here, we describe a novel screening approach to identify cell cycle modulators with low toxicity by combining the Cell Cycle Chromobody (CCC) technology with the CytoTox-Glo (CTG) cytotoxicity assay. The CCC technology employs intracellularly functional single-domain antibodies coupled to a fluorescent protein (chromobodies) to visualize the cell cycle-dependent redistribution of the proliferating cell nuclear antigen (PCNA) in living cells. This image-based cell cycle analysis was combined with determination of dead-cell protease activity in cell culture supernatants by the CTG assay. We adopted this multiplex approach to high-throughput format and screened 960 Food and Drug Administration (FDA)-approved drugs. By this, we identified nontoxic compounds, which modulate different cell cycle stages, and validated selected hits in diverse cell lines stably expressing CCC. Additionally, we independently validated these hits by flow cytometry as the current state-of-the-art format for cell cycle analysis. This study demonstrates that CCC imaging is a versatile high-content screening approach to identify cell cycle modulators, which can be multiplexed with cytotoxicity assays for early elimination of toxic compounds during screening. © 2016 Society for Laboratory Automation and Screening.

Redox Changes During the Cell Cycle in the Embryonic Root Meristem of Arabidopsis thaliana.

PubMed

de Simone, Ambra; Hubbard, Rachel; de la Torre, Natanael Viñegra; Velappan, Yazhini; Wilson, Michael; Considine, Michael J; Soppe, Wim J J; Foyer, Christine H

2017-12-20

The aim of this study was to characterize redox changes in the nuclei and cytosol occurring during the mitotic cell cycle in the embryonic roots of germinating Arabidopsis seedlings, and to determine how redox cycling was modified in mutants with a decreased capacity for ascorbate synthesis. Using an in vivo reduction-oxidation (redox) reporter (roGFP2), we show that transient oxidation of the cytosol and the nuclei occurred at G1 in the synchronized dividing cells of the Arabidopsis root apical meristem, with reduction at G2 and mitosis. This redox cycle was absent from low ascorbate mutants in which nuclei were significantly more oxidized than controls. The cell cycle-dependent increase in nuclear size was impaired in the ascorbate-deficient mutants, which had fewer cells per unit area in the root proliferation zone. The transcript profile of the dry seeds and size of the imbibed seeds was strongly influenced by low ascorbate but germination, dormancy release and seed aging characteristics were unaffected. These data demonstrate the presence of a redox cycle within the plant cell cycle and that the redox state of the nuclei is an important factor in cell cycle progression. Controlled oxidation is a key feature of the early stages of the plant cell cycle. However, sustained mild oxidation restricts nuclear functions and impairs progression through the cell cycle leading to fewer cells in the root apical meristem. Antioxid. Redox Signal. 27, 1505-1519.

Influence of cryopreservation on perinatal outcome after blastocyst- vs cleavage-stage embryo transfer: systematic review and meta-analysis.

PubMed

Alviggi, C; Conforti, A; Carbone, I F; Borrelli, R; de Placido, G; Guerriero, S

2018-01-01

To compare the perinatal outcomes of singleton pregnancies resulting from blastocyst- vs cleavage-stage embryo transfer and to assess whether they differ between fresh and frozen embryo transfer cycles. A systematic review of the literature was carried out using the Scopus, MEDLINE and ISI Web of Science databases with no time restriction. We included only peer-reviewed articles involving humans, in which perinatal outcomes of singleton pregnancies after blastocyst-stage embryo transfer were compared with those after cleavage-stage embryo transfer. Primary outcomes were preterm birth before 37 weeks and low birth weight (< 2500 g). Secondary outcomes were very preterm birth before 32 weeks, very low birth weight (< 1500 g), small-for-gestational-age (SGA), large-for-gestational-age (LGA), perinatal mortality and congenital anomaly. A meta-analysis was performed using a random-effects model. Three subgroups were evaluated: fresh only, frozen only and fresh plus frozen embryo transfer cycles. From a total of 3928 articles identified, 14 were selected for qualitative/quantitative analysis. Significantly higher incidences of preterm birth < 37 weeks (11 studies, n = 106 629 participants; risk ratio (RR), 1.15 (95% CI, 1.05 - 1.25); P = 0.002) and very preterm birth < 32 weeks (seven studies, n = 103 742; RR, 1.16 (95% CI, 1.02-1.31); P = 0.03) were observed after blastocyst- than after cleavage-stage embryo transfer in fresh cycles. However, the risk of preterm and very preterm birth was similar after blastocyst- and cleavage-stage transfers in frozen and fresh plus frozen cycles. Overall effect size analysis revealed fewer SGA deliveries after blastocyst- compared with cleavage-stage transfer in fresh cycles but a similar number in frozen cycles. Conversely, more LGA deliveries were observed after blastocyst- compared with cleavage-stage transfer in frozen cycles (two studies, n = 39 044; RR, 1.18 (95% CI, 1.09-1.27); P < 0.0001) and no differences between the two groups in fresh cycles (four studies, n = 42 982; RR, 1.14 (95% CI, 0.97-1.35); P = 0.11). There were no differences with respect to low birth weight, very low birth weight or congenital anomalies between blastocyst- and cleavage-stage transfers irrespective of the cryopreservation method employed. Only one study reported a higher incidence of perinatal mortality after blastocyst- vs cleavage-stage embryo transfer in frozen cycles, while no differences were found in fresh cycles. Our results suggest that cryopreservation of embryos can influence outcome of pregnancy conceived following blastocyst- vs cleavage-stage embryo transfer in terms of preterm birth, very preterm birth, LGA, SGA and perinatal mortality. Caution should be exercised in interpreting these findings given the low level of evidence and wide heterogeneity of the studies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Terrestrial cosmogenic nuclide surface exposure dating of the oldest glacial successions in the Himalayan orogen: Ladakh Range, northern India

USGS Publications Warehouse

Owen, L.A.; Caffee, M.W.; Bovard, K.R.; Finkel, R.C.; Sharma, M.C.

2006-01-01

Terrestrial cosmogenic nuclide surface exposure dating of moraine boulders and alluvial fan sediments define the timing of five glacial advances over at least the last five glacial cycles in the Ladakh Range of the Transhimalaya. The glacial stages that have been identified are: the Indus Valley glacial stage, dated at older than 430 ka; the Leh glacial stage occurring in the penultimate glacial cycle or older; the Karglacial stage, occurring during the early part of the last glacial cycle; the Bazgo glacial stage, at its maximum during the middle of the last glacial cycle; and the early Holocene Khalling glacial stage. The exposure ages of the Indus Valley moraines are the oldest observed to date throughout the Himalayan orogen. We observe a pattern of progressively more restricted glaciation during the last five glacial cycles, likely indicating a progressive reduction in the moisture supply necessary to sustain glaciation. A possible explanation is that uplift of Himalayan ranges to the south and/or of the Karakoram Mountains to the west of the region may have effectively blocked moisture supply by the south Asian summer monsoon and mid-latitude westerlies, respectively. Alternatively, this pattern of glaciation may reflect a trend of progressively less extensive glaciation in mountain regions that has been observed globally throughout the Pleistocene. ?? 2006 Geological Society of America.

Endoreduplication intensity as a marker of seed developmental stage in the Fabaceae.

PubMed

Rewers, Monika; Sliwinska, Elwira

2012-12-01

Flow cytometry (FCM) can be used to study cell cycle activity in developing, mature and germinating seeds. It provides information about a seed's physiological state and therefore can be used by seed growers for assessing optimal harvest times and presowing treatments. Because an augmented proportion of 4C nuclei usually is indicative of high mitotic activity, the 4C/2C ratio is commonly used to follow the progress of seed development and germination. However, its usefulness for polysomatic (i.e., containing cells with different DNA content) seeds is questioned. Changes in cell cycle/endoreduplication activity in developing seeds of five members of the Fabaceae were studied to determine a more suitable marker of seed developmental stages for polysomatic species based on FCM measurements. Seeds of Phaseolus vulgaris, Medicago sativa, Pisum sativum, Vicia sativa, and Vicia faba var. minor were collected 20, 30, 40, 50, and 60 days after flowering (DAF), embryos were isolated and the proportion of nuclei with different DNA contents in the embryo axis and cotyledon was established. The ratios 4C/2C and (Σ>2C)/2C were calculated. Dried seeds were subjected to laboratory germination tests following international seed testing association (ISTA) rules. Additionally, the absolute nuclear DNA content was estimated in the leaves of the studied species. During seed development nuclei with DNA contents from 2C to 128C were detected; the endopolyploidy pattern depended on the species, seed organ and developmental stage. The cell cycle/endoreduplication parameters correlated negatively with genome size. The (Σ>2C)/2C ratio in the cotyledons reflected the seed developmental stage and corresponded with seed germinability. Therefore, this ratio is recommended as a marker in polysomatic seed research and production instead of the 4C/2C ratio, which does not consider the occurrence of endopolyploid cells. Copyright © 2012 International Society for Advancement of Cytometry.

Mapping the global journey of anthropogenic aluminum: a trade-linked multilevel material flow analysis.

PubMed

Liu, Gang; Müller, Daniel B

2013-10-15

Material cycles have become increasingly coupled and interconnected in a globalizing era. While material flow analysis (MFA) has been widely used to characterize stocks and flows along technological life cycle within a specific geographical area, trade networks among individual cycles have remained largely unexplored. Here we developed a trade-linked multilevel MFA model to map the contemporary global journey of anthropogenic aluminum. We demonstrate that the anthropogenic aluminum cycle depends substantially on international trade of aluminum in all forms and becomes highly interconnected in nature. While the Southern hemisphere is the main primary resource supplier, aluminum production and consumption concentrate in the Northern hemisphere, where we also find the largest potential for recycling. The more developed countries tend to have a substantial and increasing presence throughout the stages after bauxite refining and possess highly consumption-based cycles, thus maintaining advantages both economically and environmentally. A small group of countries plays a key role in the global redistribution of aluminum and in the connectivity of the network, which may render some countries vulnerable to supply disruption. The model provides potential insights to inform government and industry policies in resource criticality, supply chain security, value chain management, and cross-boundary environmental impacts mitigation.

Further evidences for sleep instability and impaired spindle-delta dynamics in schizophrenia: a whole-night polysomnography study with neuroloop-gain and sleep-cycle analysis.

PubMed

Sasidharan, Arun; Kumar, Sunil; Nair, Ajay Kumar; Lukose, Ammu; Marigowda, Vrinda; John, John P; Kutty, Bindu M

2017-10-01

Sleep offers a unique window into the brain dysfunctions in schizophrenia. Many past sleep studies have reported abnormalities in both macro-sleep architecture (like increased awakenings) as well as micro-sleep-architecture (like spindle deficits) in patients with schizophrenia (PSZ). The present study attempts to replicate previous reports of macro- and micro-sleep-architectural abnormalities in schizophrenia. In addition, the study also examined sleep-stage changes and spindle-delta dynamics across sleep-cycles to provide further evidence in support of the dysfunctional thalamocortical mechanisms causing sleep instability and poor sleep maintenance associated with schizophrenia pathophysiology. Whole-night polysomnography was carried out among 45 PSZ and 39 age- and gender-matched healthy control subjects. Sleep-stage dynamics were assessed across sleep-cycles using a customized software algorithm. Spindle-delta dynamics across sleep-cycles were determined using neuroloop-gain analysis. PSZ showed macro-sleep architecture abnormalities such as prolonged sleeplessness, increased intermittent-awakenings, long sleep-onset latency, reduced non-rapid eye movement (NREM) stage 2 sleep, increased stage transitions, and poor sleep efficiency. They also showed reduced spindle density (sigma neuroloop-gain) but comparable slow wave density (delta neuroloop-gain) throughout the sleep. Sleep-cycle-wise analysis revealed transient features of sleep instability due to significantly increased intermittent awakenings especially in the first and third sleep-cycles, and unstable and recurrent stage transitions in both NREM (first sleep-cycle) and rapid eye movement (REM) sleep-periods (second sleep-cycle). Spindle deficits were persistent across the first three cycles and were positively correlated with sleep disruption during the subsequent REM sleep. In addition to replicating previously reported sleep deficits in PSZ, the current study showed subtle deficits in NREM-REM alterations across whole-night polysomnography. These results point towards a possible maladaptive interplay between unstable thalamocortical networks, resulting in sleep-cycle-specific instability patterns associated with schizophrenia pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.

Roles of α- and β-estrogen receptors in mouse social recognition memory: effects of gender and the estrous cycle.

PubMed

Sánchez-Andrade, G; Kendrick, K M

2011-01-01

Establishing clear effects of gender and natural hormonal changes during female ovarian cycles on cognitive function has often proved difficult. Here we have investigated such effects on the formation and long-term (24 h) maintenance of social recognition memory in mice together with the respective involvement of α- and β-estrogen receptors using α- and β-estrogen receptor knockout mice and wildtype controls. Results in wildtype animals showed that while females successfully formed a memory in the context of a habituation/dishabituation paradigm at all stages of their ovarian cycle, only when learning occurred during proestrus (when estrogen levels are highest) was it retained after 24 h. In α-receptor knockout mice (which showed no ovarian cycles) both formation and maintenance of this social recognition memory were impaired, whereas β-receptor knockouts showed no significant deficits and exhibited the same proestrus-dependent retention of memory at 24 h. To investigate possible sex differences, male α- and β-estrogen receptor knockout mice were also tested and showed similar effects to females excepting that α-receptor knockouts had normal memory formation and only exhibited a 24 h retention deficit. This indicates a greater dependence in females on α-receptor expression for memory formation in this task. Since non-specific motivational and attentional aspects of the task were unaffected, our findings suggest a general α-receptor dependent facilitation of memory formation by estrogen as well as an enhanced long-term retention during proestrus. Results are discussed in terms of the differential roles of the two estrogen receptors, the neural substrates involved and putative interactions with oxytocin. Copyright © 2010 Elsevier Inc. All rights reserved.

Sensory role of actin in auxin-dependent responses of tobacco BY-2.

PubMed

Huang, Xiang; Maisch, Jan; Nick, Peter

2017-11-01

Polar auxin transport depends on the polar localization of auxin-efflux carriers. The cycling of these carriers between cell interior and plasma membrane depends on actin. The dynamic of actin not only affects auxin transport, but also changes the auxin-responsiveness. To study the potential link between auxin responsiveness and actin dynamics, we investigated developmental responses of the non-transformed BY-2 (Nicotiana tabacum L. cv Bright Yellow 2) cell line and the transgenic BY-2 strain GF11 (stably transformed BY-2 cells with a GFP-fimbrin actin-binding domain 2 construct). The developmental process was divided into three distinct stages: cell cycling, cell elongation and file disintegration. Several phenotypes were measured to monitor the cellular responses to different concentrations of exogenous natural auxin (Indole-3-acetic acid, IAA). We found that auxin stimulated and prolonged the mitotic activity, and delayed the exit from the proliferation phase. However, both responses were suppressed in the GF11 line. At the stationary phase of the cultivation cycle, auxin strongly accelerated the cell file disintegration. Interestingly, it was not suppressed but progressed to a more complete disintegration in the GF11 line. During the cultivation cycle, we also followed the organization of actin in the GF11 line and did not detect any significant difference in actin organization from untreated control or exogenous IAA treatment. Therefore, our findings indicate that the specific differences observed in the GF11 line must be linked with a function of actin that is not structural. It means that there is a sensory role of actin for auxin signaling. Copyright © 2017 Elsevier GmbH. All rights reserved.

Identification by Random Mutagenesis of Functional Domains in KREPB5 That Differentially Affect RNA Editing between Life Cycle Stages of Trypanosoma brucei

PubMed Central

McDermott, Suzanne M.; Carnes, Jason

2015-01-01

KREPB5 is an essential component of ∼20S editosomes in Trypanosoma brucei which contains a degenerate, noncatalytic RNase III domain. To explore the function of this protein, we used a novel approach to make and screen numerous conditional null T. brucei bloodstream form cell lines that express randomly mutagenized KREPB5 alleles. We identified nine single amino acid substitutions that could not complement the conditional loss of wild-type KREPB5. Seven of these were within the RNase III domain, and two were in the C-terminal region that has no homology to known motifs. Exclusive expression of these mutated KREPB5 alleles in the absence of wild-type allele expression resulted in growth inhibition, the loss of ∼20S editosomes, and inhibition of RNA editing in BF cells. Eight of these mutations were lethal in bloodstream form parasites but not in procyclic-form parasites, showing that multiple domains function in a life cycle-dependent manner. Amino acid changes at a substantial number of positions, including up to 7 per allele, allowed complementation and thus did not block KREPB5 function. Hence, the degenerate RNase III domain and a newly identified domain are critical for KREPB5 function and have differential effects between the life cycle stages of T. brucei that differentially edit mRNAs. PMID:26370513

Mosquito Life Cycle

EPA Pesticide Factsheets

Knowing the stages of the mosquito's life will help you prevent mosquitoes around your home and help you choose the right pesticides for your needs, if you decide to use them. All mosquito species go through four distinct stages during their live cycle.

Development and infectious disease in hosts with complex life cycles.

PubMed

Searle, Catherine L; Xie, Gisselle Yang; Blaustein, Andrew R

2013-01-01

Metamorphosis is often characterized by profound changes in morphology and physiology that can affect the dynamics of species interactions. For example, the interaction between a pathogen and its host may differ depending on the life stage of the host or pathogen. One pathogen that infects hosts with complex life cycles is the emerging fungal pathogen of amphibians, Batrachochytrium dendrobatidis (Bd). We sought to determine how conditions at the larval stage can affect variation in development and patterns of Bd infection across amphibian life stages. We used outdoor experimental mesocosms to simulate natural pond habitats and manipulated the presence of Bd, the larval density, and the number of host species in larvae of two co-occurring amphibian species (Rana cascadae and Pseudacris regilla). We found that infection differed between species throughout development; P. regilla consistently had higher infection severity compared to R. cascadae. Additionally, while up to 100% of larvae were infected, only 18.2% of R. cascadae and 81.5% of P. regilla were infected after metamorphosis. This indicates that amphibians have the ability to recover from Bd infection as they undergo metamorphosis. Higher larval densities in P. regilla led to a shorter larval period, and individuals with a shorter larval period had lower infection severity. This led to a trend where P. regilla larvae reared at high densities tended to have lower infection prevalence after metamorphosis. We also found that exposure to Bd increased larval mortality and prolonged the larval period in P. regilla, indicating that P. regilla are susceptible to the negative effects of Bd as larvae. This study demonstrates that host density, species composition, and pathogen exposure may all interact to influence development and infection in hosts with complex life cycles.

Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility

PubMed Central

Green, Judith L.; Wall, Richard J.; Vahokoski, Juha; Yusuf, Noor A.; Ridzuan, Mohd A. Mohd; Stanway, Rebecca R.; Stock, Jessica; Knuepfer, Ellen; Brady, Declan; Martin, Stephen R.; Howell, Steven A.; Pires, Isa P.; Moon, Robert W.; Molloy, Justin E.; Kursula, Inari; Tewari, Rita

2017-01-01

Myosin A (MyoA) is a Class XIV myosin implicated in gliding motility and host cell and tissue invasion by malaria parasites. MyoA is part of a membrane-associated protein complex called the glideosome, which is essential for parasite motility and includes the MyoA light chain myosin tail domain–interacting protein (MTIP) and several glideosome-associated proteins (GAPs). However, most studies of MyoA have focused on single stages of the parasite life cycle. We examined MyoA expression throughout the Plasmodium berghei life cycle in both mammalian and insect hosts. In extracellular ookinetes, sporozoites, and merozoites, MyoA was located at the parasite periphery. In the sexual stages, zygote formation and initial ookinete differentiation precede MyoA synthesis and deposition, which occurred only in the developing protuberance. In developing intracellular asexual blood stages, MyoA was synthesized in mature schizonts and was located at the periphery of segmenting merozoites, where it remained throughout maturation, merozoite egress, and host cell invasion. Besides the known GAPs in the malaria parasite, the complex included GAP40, an additional myosin light chain designated essential light chain (ELC), and several other candidate components. This ELC bound the MyoA neck region adjacent to the MTIP-binding site, and both myosin light chains co-located to the glideosome. Co-expression of MyoA with its two light chains revealed that the presence of both light chains enhances MyoA-dependent actin motility. In conclusion, we have established a system to study the interplay and function of the three glideosome components, enabling the assessment of inhibitors that target this motor complex to block host cell invasion. PMID:28893907

Perturbation of host-cell membrane is a primary mechanism of HIV cytopathology.

PubMed

Cloyd, M W; Lynn, W S

1991-04-01

Cytopathic viruses injure cells by a number of different mechanisms. The mechanism by which HIV-1 injures T cells was studied by temporally examining host-cell macromolecular syntheses, stages of the cell cycle, and membrane permeability following acute infection. T cells cytopathically infected at an m.o.i. of 1-5 grew normally for 24-72 hr, depending on the cell line, followed by the first manifestation of cell injury, slowing of cell division. At that time significant amounts of unintegrated HIV DNA and p24 core protein became detectable, and acridine orange flow cytometric cell cycle studies demonstrated the presence of fewer cells in the G2/M stage of the cell cycle. There was no change in the frequency of cells in the S-stage, and metabolic pulsing with radioactive precursors demonstrated that host-cell DNA, RNA, and protein syntheses were normal at that time and normal up to the time cells started to die (approximately 24 hr later), when all three decreased. Cellular lipid synthesis, however, was perturbed when cell multiplication slowed, with phospholipid synthesis reduced and neutral lipid synthesis enhanced. Permeability of the host-cell membrane to small molecules, such as Ca2+ and sucrose, was slightly enhanced early postinfection, and by the time of slowing of cell division, host membrane permeability was greatly increased to both Ca2+ and sucrose (Stokes radius 5.2 A) but not to inulin (Stokes radium 20 A). These changes in host-cell membrane permeability and phospholipid synthesis were not observed in acutely infected H9 cells, which are not susceptible to HIV cytopathology. Thus, HIV-1 appeared to predominantly injure T cells by perturbing host-cell membrane permeability and lipid synthesis, which is similar to the cytopathic mechanisms of paramyxoviruses.

The dynamics of resource allocation and costs of reproduction in a sexually dimorphic, wind-pollinated dioecious plant.

PubMed

Teitel, Z; Pickup, M; Field, D L; Barrett, S C H

2016-01-01

Sexual dimorphism in resource allocation is expected to change during the life cycle of dioecious plants because of temporal differences between the sexes in reproductive investment. Given the potential for sex-specific differences in reproductive costs, resource availability may contribute to variation in reproductive allocation in females and males. Here, we used Rumex hastatulus, a dioecious, wind-pollinated annual plant, to investigate whether sexual dimorphism varies with life-history stage and nutrient availability, and determine whether allocation patterns differ depending on reproductive commitment. To examine if the costs of reproduction varied between the sexes, reproduction was either allowed or prevented through bud removal, and biomass allocation was measured at maturity. In a second experiment to assess variation in sexual dimorphism across the life cycle, and whether this varied with resource availability, plants were grown in high and low nutrients and allocation to roots, aboveground vegetative growth and reproduction were measured at three developmental stages. Males prevented from reproducing compensated with increased above- and belowground allocation to a much larger degree than females, suggesting that male reproductive costs reduce vegetative growth. The proportional allocation to roots, reproductive structures and aboveground vegetative growth varied between the sexes and among life-cycle stages, but not with nutrient treatment. Females allocated proportionally more resources to roots than males at peak flowering, but this pattern was reversed at reproductive maturity under low-nutrient conditions. Our study illustrates the importance of temporal dynamics in sex-specific resource allocation and provides support for high male reproductive costs in wind-pollinated plants. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

Cell cycle synchronization of leukemia inhibitory factor (LIF)-dependent porcine-induced pluripotent stem cells and the generation of cloned embryos.

PubMed

Yuan, Ye; Lee, Kiho; Park, Kwang-Wook; Spate, Lee D; Prather, Randall S; Wells, Kevin D; Roberts, R Michael

2014-01-01

Nuclear transfer (NT) from porcine iPSC to create cloned piglets is unusually inefficient. Here we examined whether such failure might be related to the cell cycle stage of donor nuclei. Porcine iPSC, derived here from the inner cell mass of blastocysts, have a prolonged S phase and are highly sensitive to drugs normally used for synchronization. However, a double-blocking procedure with 0.3 μM aphidicolin for 10 h followed by 20 ng/ml nocodazole for 4 h arrested 94.3% of the cells at G2/M and, after release from the block, provided 70.1% cells in the subsequent G1 phase without causing any significant loss of cell viability or pluripotent phenotype. Nuclei from different cell cycle stages were used as donors for NT to in vitro-matured metaphase II oocytes. G2/M nuclei were more efficient than either G1 and S stage nuclei in undergoing first cleavage and in producing blastocysts, but all groups had a high incidence of chromosomal/nuclear abnormalities at 2 h and 6 h compared with non-synchronized NT controls from fetal fibroblasts. Many G2 embryos extruded a pseudo-second polar body soon after NT and, at blastocyst, tended to be either polyploid or diploid. By contrast, the few G1 blastocysts that developed were usually mosaic or aneuploid. The poor developmental potential of G1 nuclei may relate to lack of a G1/S check point, as the cells become active in DNA synthesis shortly after exit from mitosis. Together, these data provide at least a partial explanation for the almost complete failure to produce cloned piglets from piPSC.

The Life Cycle Stages of Pneumocystis murina Have Opposing Effects on the Immune Response to This Opportunistic Fungal Pathogen

PubMed Central

Evans, Heather M.; Bryant, Grady L.

2016-01-01

The cell wall β-glucans of Pneumocystis cysts have been shown to stimulate immune responses in lung epithelial cells, dendritic cells, and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with these innate immune cells. Here we report differences in the responses of both neonatal and adult mice to the trophic and cystic life cycle stages of Pneumocystis murina. The adult and neonatal immune responses to infection with Pneumocystis murina trophic forms were less robust than the responses to infection with a physiologically normal mixture of cysts and trophic forms. Cysts promoted the recruitment of nonresident innate immune cells and T and B cells into the lungs. Cysts, but not trophic forms, stimulated increased concentrations of the cytokine gamma interferon (IFN-γ) in the alveolar spaces and an increase in the percentage of CD4+ T cells that produce IFN-γ. In vitro, bone marrow-derived dendritic cells (BMDCs) stimulated with cysts produced the proinflammatory cytokines interleukin 1β (IL-1β) and IL-6. In contrast, trophic forms suppressed antigen presentation to CD4+ T cells, as well as the β-glucan-, lipoteichoic acid (LTA)-, and lipopolysaccharide (LPS)-induced production of interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) by BMDCs. The negative effects of trophic forms were not due to ligation of mannose receptor. Our results indicate that optimal innate and adaptive immune responses to Pneumocystis species are dependent on stimulation with the cyst life cycle stage. Conversely, trophic forms suppress β-glucan-induced proinflammatory responses in vitro, suggesting that the trophic forms dampen cyst-induced inflammation in vivo. PMID:27572330

Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility.

PubMed

Green, Judith L; Wall, Richard J; Vahokoski, Juha; Yusuf, Noor A; Ridzuan, Mohd A Mohd; Stanway, Rebecca R; Stock, Jessica; Knuepfer, Ellen; Brady, Declan; Martin, Stephen R; Howell, Steven A; Pires, Isa P; Moon, Robert W; Molloy, Justin E; Kursula, Inari; Tewari, Rita; Holder, Anthony A

2017-10-27

Myosin A (MyoA) is a Class XIV myosin implicated in gliding motility and host cell and tissue invasion by malaria parasites. MyoA is part of a membrane-associated protein complex called the glideosome, which is essential for parasite motility and includes the MyoA light chain myosin tail domain-interacting protein (MTIP) and several glideosome-associated proteins (GAPs). However, most studies of MyoA have focused on single stages of the parasite life cycle. We examined MyoA expression throughout the Plasmodium berghei life cycle in both mammalian and insect hosts. In extracellular ookinetes, sporozoites, and merozoites, MyoA was located at the parasite periphery. In the sexual stages, zygote formation and initial ookinete differentiation precede MyoA synthesis and deposition, which occurred only in the developing protuberance. In developing intracellular asexual blood stages, MyoA was synthesized in mature schizonts and was located at the periphery of segmenting merozoites, where it remained throughout maturation, merozoite egress, and host cell invasion. Besides the known GAPs in the malaria parasite, the complex included GAP40, an additional myosin light chain designated essential light chain (ELC), and several other candidate components. This ELC bound the MyoA neck region adjacent to the MTIP-binding site, and both myosin light chains co-located to the glideosome. Co-expression of MyoA with its two light chains revealed that the presence of both light chains enhances MyoA-dependent actin motility. In conclusion, we have established a system to study the interplay and function of the three glideosome components, enabling the assessment of inhibitors that target this motor complex to block host cell invasion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Cell-cycle regulation of formin-mediated actin cable assembly

PubMed Central

Miao, Yansong; Wong, Catherine C. L.; Mennella, Vito; Michelot, Alphée; Agard, David A.; Holt, Liam J.; Yates, John R.; Drubin, David G.

2013-01-01

Assembly of appropriately oriented actin cables nucleated by formin proteins is necessary for many biological processes in diverse eukaryotes. However, compared with knowledge of how nucleation of dendritic actin filament arrays by the actin-related protein-2/3 complex is regulated, the in vivo regulatory mechanisms for actin cable formation are less clear. To gain insights into mechanisms for regulating actin cable assembly, we reconstituted the assembly process in vitro by introducing microspheres functionalized with the C terminus of the budding yeast formin Bni1 into extracts prepared from yeast cells at different cell-cycle stages. EM studies showed that unbranched actin filament bundles were reconstituted successfully in the yeast extracts. Only extracts enriched in the mitotic cyclin Clb2 were competent for actin cable assembly, and cyclin-dependent kinase 1 activity was indispensible. Cyclin-dependent kinase 1 activity also was found to regulate cable assembly in vivo. Here we present evidence that formin cell-cycle regulation is conserved in vertebrates. The use of the cable-reconstitution system to test roles for the key actin-binding proteins tropomyosin, capping protein, and cofilin provided important insights into assembly regulation. Furthermore, using mass spectrometry, we identified components of the actin cables formed in yeast extracts, providing the basis for comprehensive understanding of cable assembly and regulation. PMID:24133141

SAMHD1 host restriction factor: a link with innate immune sensing of retrovirus infection.

PubMed

Sze, Alexandre; Olagnier, David; Lin, Rongtuan; van Grevenynghe, Julien; Hiscott, John

2013-12-13

SAMHD1 [sterile alpha motif and histidine-aspartic domain (HD) containing protein 1] is the most recent addition to a unique group of host restriction factors that limit retroviral replication at distinct stages of the viral life cycle. SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase that degrades the intracellular pool of deoxynucleoside triphosphates available during early reverse transcription. SAMHD1 activity is blocked by the Vpx accessory function present in human immunodeficiency virus type 2 and SIVsm. Mutations in SAMHD1 are associated with the autoimmune disorder Aicardi-Goutières syndrome, thus emphasizing its role in regulation of the immune response. SAMHD1 antiretroviral activity is modulated by post-translational modifications, cell-cycle-dependent functions and cytokine-mediated changes. Innate receptors that sense retroviral DNA intermediates are the focus of intense study, and recent studies have established a link among SAMHD1 restriction, innate sensing of DNA and protective immune responses. Cell-cycle-dependent regulation of SAMHD1 by phosphorylation and the increasingly broad range of viruses inhibited by SAMHD1 further emphasize the importance of these mechanisms of host restriction. This review highlights current knowledge regarding SAMHD1 regulation and its impact on innate immune signaling and retroviral restriction. © 2013.

A statistical approach to the life cycle analysis of cumulus clouds selected in a virtual reality environment

NASA Astrophysics Data System (ADS)

Heus, Thijs; Jonker, Harm J. J.; van den Akker, Harry E. A.; Griffith, Eric J.; Koutek, Michal; Post, Frits H.

2009-03-01

In this study, a new method is developed to investigate the entire life cycle of shallow cumuli in large eddy simulations. Although trained observers have no problem in distinguishing the different life stages of a cloud, this process proves difficult to automate, because cloud-splitting and cloud-merging events complicate the distinction between a single system divided in several cloudy parts and two independent systems that collided. Because the human perception is well equipped to capture and to make sense of these time-dependent three-dimensional features, a combination of automated constraints and human inspection in a three-dimensional virtual reality environment is used to select clouds that are exemplary in their behavior throughout their entire life span. Three specific cases (ARM, BOMEX, and BOMEX without large-scale forcings) are analyzed in this way, and the considerable number of selected clouds warrants reliable statistics of cloud properties conditioned on the phase in their life cycle. The most dominant feature in this statistical life cycle analysis is the pulsating growth that is present throughout the entire lifetime of the cloud, independent of the case and of the large-scale forcings. The pulses are a self-sustained phenomenon, driven by a balance between buoyancy and horizontal convergence of dry air. The convective inhibition just above the cloud base plays a crucial role as a barrier for the cloud to overcome in its infancy stage, and as a buffer region later on, ensuring a steady supply of buoyancy into the cloud.

Orbital Transfer Vehicle (OTV) engine study. Phase A: Extension

NASA Technical Reports Server (NTRS)

Sobin, A. J.

1980-01-01

The current Phase A-Extension of the OTV engine study program aims to provide additional expander and staged combustion cycle data that will lead to design definition of the OTV engine. The proposed program effort seeks to optimize the expander cycle engine concept (consistent with identified OTV engine requirements), investigate the feasibility of kitting the staged combustion cycle engine to provide extended thrust operation, and conduct in-depth analysis of development risk, crew safety, and reliability for both cycles. Additional tasks address the costing of a 10/K thrust expander cycle engine and support of OTV systems study contractors.

Solar cycle dependence of the heliospheric shape deduced from a global MHD simulation of the interaction process between a nonuniform time-dependent solar wind and the local interstellar medium

NASA Astrophysics Data System (ADS)

Tanaka, T.; Washimi, H.

1999-06-01

The global structure of the solar wind/very local interstellar medium interaction is studied from a fully three-dimensional time-dependent magnetohydrodynamic model, in which the solar wind speed increases from 400 to 800 km/s in going from the ecliptic to pole and the heliolatitude of the low-high-speed boundary changes from 30° to 80° in going from the solar minimum to solar maximum. In addition, the interplanetary magnetic field (IMF) changes its polarity at the solar maximum. As a whole, the shapes of the terminal shock (TS) and heliopause (HP) are elongated along the solar polar axis owing to a high solar wind ram pressure over the poles. In the ecliptic plane, the heliospheric structure changes little throughout a solar cycle. The TS in this plane shows a characteristic bullet-shaped structure. In the polar plane, on the other hand, the shape of the TS exhibits many specific structures according to the stage of the solar cycle. These structures include the polygonal configuration of the polar TS seen around the solar minimum, the mesa- and terrace-shaped TSs in the high- and low-speed solar wind regions seen around the ascending phase, and the chimney-shaped TS in the high-speed solar wind region seen around the solar maximum. These structures are formed from different combinations of right-angle shock, oblique shock, and steep oblique shock so as to transport the heliosheath plasma most efficiently toward the heliotail (HT). In the HT, the hot and weakly-magnetized plasma from the high-heliolatitude TS invades as far as the ecliptic plane. A weakly time-dependent recirculation flow in the HT is a manifestation of invading flow. Distributions of magnetic field in the HT, which are a pile-up of the compressed MF over several solar cycles, are modified by the flow from high-heliolatitude.

The genetic covariance between life cycle stages separated by metamorphosis.

PubMed

Aguirre, J David; Blows, Mark W; Marshall, Dustin J

2014-08-07

Metamorphosis is common in animals, yet the genetic associations between life cycle stages are poorly understood. Given the radical changes that occur at metamorphosis, selection may differ before and after metamorphosis, and the extent that genetic associations between pre- and post-metamorphic traits constrain evolutionary change is a subject of considerable interest. In some instances, metamorphosis may allow the genetic decoupling of life cycle stages, whereas in others, metamorphosis could allow complementary responses to selection across the life cycle. Using a diallel breeding design, we measured viability at four ontogenetic stages (embryo, larval, juvenile and adult viability), in the ascidian Ciona intestinalis and examined the orientation of additive genetic variation with respect to the metamorphic boundary. We found support for one eigenvector of G: (gobsmax ), which contrasted larval viability against embryo viability and juvenile viability. Target matrix rotation confirmed that while gobsmax shows genetic associations can extend beyond metamorphosis, there is still considerable scope for decoupled phenotypic evolution. Therefore, although genetic associations across metamorphosis could limit that range of phenotypes that are attainable, traits on either side of the metamorphic boundary are capable of some independent evolutionary change in response to the divergent conditions encountered during each life cycle stage. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Single-stage-to-orbit versus two-stage-two-orbit: A cost perspective

NASA Astrophysics Data System (ADS)

Hamaker, Joseph W.

1996-03-01

This paper considers the possible life-cycle costs of single-stage-to-orbit (SSTO) and two-stage-to-orbit (TSTO) reusable launch vehicles (RLV's). The analysis parametrically addresses the issue such that the preferred economic choice comes down to the relative complexity of the TSTO compared to the SSTO. The analysis defines the boundary complexity conditions at which the two configurations have equal life-cycle costs, and finally, makes a case for the economic preference of SSTO over TSTO.

A viscoelastic damage rheology and rate- and state-dependent friction

NASA Astrophysics Data System (ADS)

Lyakhovsky, Vladimir; Ben-Zion, Yehuda; Agnon, Amotz

2005-04-01

We analyse the relations between a viscoelastic damage rheology model and rate- and state-dependent (RS) friction. Both frameworks describe brittle deformation, although the former models localization zones in a deforming volume while the latter is associated with sliding on existing surfaces. The viscoelastic damage model accounts for evolving elastic properties and inelastic strain. The evolving elastic properties are related quantitatively to a damage state variable representing the local density of microcracks. Positive and negative changes of the damage variable lead, respectively, to degradation and recovery of the material in response to loading. A model configuration having an existing narrow zone with localized damage produces for appropriate loading and temperature-pressure conditions an overall cyclic stick-slip motion compatible with a frictional response. Each deformation cycle (limit cycle) can be divided into healing and weakening periods associated with decreasing and increasing damage, respectively. The direct effect of the RS friction and the magnitude of the frictional parameter a are related to material strengthening with increasing rate of loading. The strength and residence time of asperities (model elements) in the weakening stage depend on the rates of damage evolution and accumulation of irreversible strain. The evolutionary effect of the RS friction and overall change in the friction parameters (a-b) are controlled by the duration of the healing period and asperity (element) strengthening during this stage. For a model with spatially variable properties, the damage rheology reproduces the logarithmic dependency of the steady-state friction coefficient on the sliding velocity and the normal stress. The transition from a velocity strengthening regime to a velocity weakening one can be obtained by varying the rate of inelastic strain accumulation and keeping the other damage rheology parameters fixed. The developments unify previous damage rheology results on deformation localization leading to formation of new fault zones with detailed experimental results on frictional sliding. The results provide a route for extending the formulation of RS friction into a non-linear continuum mechanics framework.

Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

2015-01-01

This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design.

The optimum intermediate pressure of two-stages vapor compression refrigeration cycle for Air-Conditioning unit

NASA Astrophysics Data System (ADS)

Ambarita, H.; Sihombing, H. V.

2018-03-01

Vapor compression cycle is mainly employed as a refrigeration cycle in the Air-Conditioning (AC) unit. In order to save energy, the Coefficient of Performance (COP) of the need to be improved. One of the potential solutions is to modify the system into multi-stages vapor compression cycle. The suitable intermediate pressure between the high and low pressures is one of the design issues. The present work deals with the investigation of an optimum intermediate pressure of two-stages vapor compression refrigeration cycle. Typical vapor compression cycle that is used in AC unit is taken into consideration. The used refrigerants are R134a. The governing equations have been developed for the systems. An inhouse program has been developed to solve the problem. COP, mass flow rate of the refrigerant and compressor power as a function of intermediate pressure are plotted. It was shown that there exists an optimum intermediate pressure for maximum COP. For refrigerant R134a, the proposed correlations need to be revised.

Ablation of an Ovarian Tumor Family Deubiquitinase Exposes the Underlying Regulation Governing the Plasticity of Cell Cycle Progression in Toxoplasma gondii.

PubMed

Dhara, Animesh; de Paula Baptista, Rodrigo; Kissinger, Jessica C; Snow, E Charles; Sinai, Anthony P

2017-11-21

The Toxoplasma genome encodes the capacity for distinct architectures underlying cell cycle progression in a life cycle stage-dependent manner. Replication in intermediate hosts occurs by endodyogeny, whereas a hybrid of schizogony and endopolygeny occurs in the gut of the definitive feline host. Here, we characterize the consequence of the loss of a cell cycle-regulated o varian tu mor (OTU family) deubiquitinase, OTUD3A of Toxoplasma gondii (TgOTUD3A; TGGT1_258780), in T. gondii tachyzoites. Rather than the mutation being detrimental, mutant parasites exhibited a fitness advantage, outcompeting the wild type. This phenotype was due to roughly one-third of TgOTUD3A-knockout (TgOTUD3A-KO) tachyzoites exhibiting deviations from endodyogeny by employing replication strategies that produced 3, 4, or 5 viable progeny within a gravid mother instead of the usual 2. We established the mechanistic basis underlying these altered replication strategies to be a dysregulation of centrosome duplication, causing a transient loss of stoichiometry between the inner and outer cores that resulted in a failure to terminate S phase at the attainment of 2N ploidy and/or the decoupling of mitosis and cytokinesis. The resulting dysregulation manifested as deviations in the normal transitions from S phase to mitosis (S/M) (endopolygeny-like) or M phase to cytokinesis (M/C) (schizogony-like). Notably, these imbalances are corrected prior to cytokinesis, resulting in the generation of normal progeny. Our findings suggest that decisions regarding the utilization of specific cell cycle architectures are controlled by a ubiquitin-mediated mechanism that is dependent on the absolute threshold levels of an as-yet-unknown target(s). Analysis of the TgOTUD3A-KO mutant provides new insights into mechanisms underlying the plasticity of apicomplexan cell cycle architecture. IMPORTANCE Replication by Toxoplasma gondii can occur by 3 distinct cell cycle architectures. Endodyogeny is used by asexual stages, while a hybrid of schizogony and endopolygeny is used by merozoites in the definitive feline host. Here, we establish that the disruption of an o varian- tu mor (OTU) family deubiquitinase, TgOTUD3A, in tachyzoites results in dysregulation of the mechanism controlling the selection of replication strategy in a subset of parasites. The mechanistic basis for these altered cell cycles lies in the unique biology of the bipartite centrosome that is associated with the transient loss of stoichiometry between the inner and outer centrosome cores in the TgOTUD3A-KO mutant. This highlights the importance of ubiquitin-mediated regulation in the transition from the nuclear to the budding phases of the cell cycle and provides new mechanistic insights into the regulation of the organization of the apicomplexan cell cycle. Copyright © 2017 Dhara et al.

Estrous cycle modulation of extracellular serotonin in mediobasal hypothalamus: role of the serotonin transporter and terminal autoreceptors.

PubMed

Maswood, S; Truitt, W; Hotema, M; Caldarola-Pastuszka, M; Uphouse, L

1999-06-12

In vivo microdialysis was used to examine extracellular serotonin (5-HT) in the mediobasal hypothalamus (MBH) of male and female Fischer (CDF-344) rats. Females from the stages of diestrus, proestrus, and estrus were used. Additionally, ovariectomized rats, primed subcutaneously (s.c.) with estradiol benzoate or estradiol benzoate plus progesterone were examined. Extracellular 5-HT in the MBH varied with stage of the estrous cycle and with the light/dark cycle. Proestrous females had the highest microdialysate concentrations of 5-HT during the light portion of the light/dark cycle and lowest concentrations during the dark portion of the cycle. Diestrous females had the highest levels during the dark portion of the cycle, while males and estrous females showed little change between light and dark portions of the cycle. In ovariectomized rats, there was no effect of 2.5 microg or 25 microg estradiol benzoate (s.c.) on extracellular 5-HT; but the addition of 500 microg progesterone, 48 h after estrogen priming, reduced microdialysate 5-HT near the threshold for detection. In intact females and in males, reverse perfusion with 3 microM fluoxetine, a selective serotonin reuptake inhibitor (SSRI), or 2 microM methiothepin, a 5-HT receptor antagonist, increased microdialysate concentrations of 5-HT. Estrous females and males showed nearly a 4-fold increase in microdialysate 5-HT in response to fluoxetine while smaller responses were seen in diestrous and proestrous rats. In contrast, proestrous rats showed the largest response to methiothepin. Estrous females showed a delayed response to methiothepin, but there was no methiothepin-induced increase in extracellular 5-HT in males. These findings are discussed in reference to the suggestion that extracellular 5-HT in the MBH is regulated in a manner that is gender and estrous cycle dependent. The 5-HT terminal autoreceptor may exert a greater role in proestrous females; the serotonin transporter appears to play a more active role in the regulation of extracellular 5-HT in estrous females and in males. Copyright 1999 Elsevier Science B.V.

Analysing how plants in coastal wetlands respond to varying tidal regimes throughout their life cycles.

PubMed

Xie, Tian; Cui, Baoshan; Li, Shanze

2017-10-15

Important to conserve plant species in coastal wetlands throughout their life cycle. All life stages in these habitats are exposed to varying tidal cycles. It is necessary to investigate all life stages as to how they respond to varying tidal regimes. We examine three wetlands containing populations of an endangered halophyte species, each subjected to different tidal regimes: (1). wetlands completely closed to tidal cycles; (2). wetlands directly exposed to tidal cycles (3). wetlands exposed to a partially closed tidal regime. Our results showed that the most threatened stage varied between wetlands subjected to these varying tidal regimes. We hypothesis that populations of this species have adapted to these different tidal regimes. Such information is useful in developing management options for coastal wetlands and modifying future barriers restricting tidal flushing. Copyright © 2017 Elsevier Ltd. All rights reserved.

The numbers game: quantitative analysis of Neorickettsia sp. propagation through complex life cycle of its digenean host using real-time qPCR.

PubMed

Greiman, Stephen E; Tkach, Vasyl V

2016-07-01

Bacteria of the genus Neorickettsia are obligate intracellular endosymbionts of parasitic flukes (Digenea) and are passed through the entire complex life cycle of the parasite by vertical transmission. Several species of Neorickettsia are known to cause diseases in domestic animals, wildlife, and humans. Quantitative data on the transmission of the bacteria through the digenean life cycle is almost completely lacking. This study quantified for the first time the abundance of Neorickettsia within multiple stages of the life cycle of the digenean Plagiorchis elegans. Snails Lymnaea stagnalis collected from a pond in North Dakota were screened for the presence of digenean cercariae, which were subsequently tested for the presence of Neorickettsia. Three L. stagnalis were found shedding P. elegans cercariae infected with Neorickettsia. These snails were used to initiate three separate laboratory life cycles and obtain all life cycle stages for bacterial quantification. A quantitative real-time PCR assay targeting the GroEL gene was developed to enumerate Neorickettsia sp. within different stages of the digenean life cycle. The number of bacteria significantly increased throughout all stages, from eggs to adults. The two largest increases in number of bacteria occurred during the period from eggs to cercariae and from 6-day metacercariae to 48-h juvenile worms. These two periods seem to be the most important for Neorickettsia propagation through the complex digenean life cycle and maturation in the definitive host.

[CHROMATIN ORGANIZATION IN CELL CYCLE OF AMOEBA PROTEUS ACCORDING TO OPTICAL TOMOGRAPHY DATA].

PubMed

Demin, S Yu; Berdieva, M A; Podlipaeva, Yu I; Yudin, A L; Goodkov, A V

2015-01-01

For the first time the nuclear cycle of large freshwater amoeba Amoeba proteus was studied by the method of optical tomography. The nuclei were fixed in situ in the cells of synchronized culture, stained by DAPI and examined by confocal laser scanning microscope. 3D-images of intranuclear chromatin were studied in details at different stages of nuclear cycle. The obtained data, together with literary ones allow represent the dynamics of structural organization of the nucleus in Amoeba proteus cell cycle in a new fashion. It was concluded that in this species the two-stage interphase takes place, as well as mitosis of peculiar type which does not correspond to any known type of mitosis according to classification existing now. It is presumed that in the course of nuclear cycle the chromosomes and/or their fragments are amplified, this presumption being in a good correspondence with the data about nuclear DNA hyperreplication in the cell cycle of A. proteus. As a result of chromosomes amplification their number may vary at different stages of cell cycle, and it allows to explain the contradictory data concerning the exact number of chromosomes in this species. The elimination of extra-DNA occurs mainly at the stage between prophase and prometaphase. We presume the majority of chromosomes, or may be even all of them to be referred to cholocentric type according to their behaviour during the mitosis.

Singlet oxygen generation as a major cause for parasitic reactions during cycling of aprotic lithium-oxygen batteries

NASA Astrophysics Data System (ADS)

Mahne, Nika; Schafzahl, Bettina; Leypold, Christian; Leypold, Mario; Grumm, Sandra; Leitgeb, Anita; Strohmeier, Gernot A.; Wilkening, Martin; Fontaine, Olivier; Kramer, Denis; Slugovc, Christian; Borisov, Sergey M.; Freunberger, Stefan A.

2017-03-01

Non-aqueous metal-oxygen batteries depend critically on the reversible formation/decomposition of metal oxides on cycling. Irreversible parasitic reactions cause poor rechargeability, efficiency, and cycle life, and have predominantly been ascribed to the reactivity of reduced oxygen species with cell components. These species, however, cannot fully explain the side reactions. Here we show that singlet oxygen forms at the cathode of a lithium-oxygen cell during discharge and from the onset of charge, and accounts for the majority of parasitic reaction products. The amount increases during discharge, early stages of charge, and charging at higher voltages, and is enhanced by the presence of trace water. Superoxide and peroxide appear to be involved in singlet oxygen generation. Singlet oxygen traps and quenchers can reduce parasitic reactions effectively. Awareness of the highly reactive singlet oxygen in non-aqueous metal-oxygen batteries gives a rationale for future research towards achieving highly reversible cell operation.

The number of cycles of neoadjuvant chemotherapy is associated with prognosis of stage IIIc-IV high-grade serous ovarian cancer.

PubMed

Xu, Xia; Deng, Fei; Lv, Mengmeng; Chen, Xiaoxiang

2017-02-01

No consensus exists on the number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced stage epithelial ovarian cancer. The present study aims to explore the optimal number of cycles of neoadjuvant chemotherapy (NAC) and post-operation chemotherapy to treat the International Federation of Gynecology and Obstetrics stage IIIc-IV high-grade serous ovarian cancer (HG-SOC). A total of 129 IIIc-IV stage HG-SOC cases were retrospectively analyzed. Cases were comprised of patients who underwent NAC followed by IDS and who achieved clinical complete response (CCR) at the end of primary therapy. Patients were recruited from the Jiangsu Institute of Cancer Research between 1993 and 2013. Optimal IDS-associated factors were explored with logistic regression. The association between progression-free survival (PFS), overall survival (OS) duration, and covariates was assessed by Cox proportional hazards model and log-rank test. The median number of NAC cycle was 3 (range 1-8). CA-125 decreasing kinetics (p = 0.01) was independently associated with optimal IDS. CA-125 decreasing kinetics, optimal IDS, and NAC cycles was independently associated with OS (p < 0.01, p < 0.01, p = 0.03, respectively) and PFS (p < 0.01, p < 0.01, p = 0.04, respectively). The PFS of patients who underwent ≥5 NAC cycles was shorter than those of patients who underwent <5 NAC cycles (12.3 versus 17.2 months). The PFS and OS of patients who underwent <5 cycles of adjuvant chemotherapy post-IDS were shorter than those of patients who underwent ≥5 cycles (14.2 and 20.3 versus 21.2 and 28.8 months). NAC cycles, CA-125 decreasing kinetics, and optimal debulking are independently associated with the prognosis of patients with advanced stage HG-SOC who underwent NAC/IDS and achieved CCR. The number of administered NAC cycles should not exceed 4.

CDK inhibitors, p21{sup Cip1} and p27{sup Kip1}, participate in cell cycle exit of mammalian cardiomyocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tane, Shoji; Ikenishi, Aiko; Okayama, Hitomi

2014-01-17

Highlights: •Expression of p21 and p27 in the hearts showed a peak during postnatal stages. •p21 and p27 bound to cyclin E, cyclin A and CDK2 in the hearts at postnatal stages. •Cardiomyocytes in both KO mice showed failure in the cell cycle exit at G1-phase. •These data show the first apparent phenotypes in the hearts of Cip/Kip KO mice. -- Abstract: Mammalian cardiomyocytes actively proliferate during embryonic stages, following which cardiomyocytes exit their cell cycle after birth. The irreversible cell cycle exit inhibits cardiac regeneration by the proliferation of pre-existing cardiomyocytes. Exactly how the cell cycle exit occurs remainsmore » largely unknown. Previously, we showed that cyclin E- and cyclin A-CDK activities are inhibited before the CDKs levels decrease in postnatal stages. This result suggests that factors such as CDK inhibitors (CKIs) inhibit CDK activities, and contribute to the cell cycle exit. In the present study, we focused on a Cip/Kip family, which can inhibit cyclin E- and cyclin A-CDK activities. Expression of p21{sup Cip1} and p27{sup Kip1} but not p57{sup Kip2} showed a peak around postnatal day 5, when cyclin E- and cyclin A-CDK activities start to decrease. p21{sup Cip1} and p27{sup Kip1} bound to cyclin E, cyclin A and CDK2 at postnatal stages. Cell cycle distribution patterns of postnatal cardiomyocytes in p21{sup Cip1} and p27{sup Kip1} knockout mice showed failure in the cell cycle exit at G1-phase, and endoreplication. These results indicate that p21{sup Cip1} and p27{sup Kip} play important roles in the cell cycle exit of postnatal cardiomyocytes.« less

Reflectance spectroscopy for evaluating hair follicle cycle

NASA Astrophysics Data System (ADS)

Liu, Caihua; Guan, Yue; Wang, Jianru; Zhu, Dan

2014-02-01

Hair follicle, as a mini-organ with perpetually cycling of telogen, anagen and catagen, provides a valuable experimental model for studying hair and organ regeneration. The transition of hair follicle from telogen to anagen is a significant sign for successful regeneration. So far discrimination of the hair follicle stage is mostly based on canonical histological examination and empirical speculation based on skin color. Hardly a method has been proposed to quantitatively evaluate the hair follicle stage. In this work, a commercial optical fiber spectrometer was applied to monitor diffuse reflectance of mouse skin with hair follicle cycling, and then the change of reflectance was obtained. Histological examination was used to verify the hair follicle stage. In comparison with the histological examination, the skin diffuse reflectance was relatively high for mouse with telogen hair follicles; it decreased once hair follicles transited to anagen stage; then it increased reversely at catagen stage. This study provided a new method to quantitatively evaluate the hair follicle stage, and should be valuable for the basic and therapeutic investigations on hair regeneration.

Multi-stage combustion using nitrogen-enriched air

DOEpatents

Fischer, Larry E.; Anderson, Brian L.

2004-09-14

Multi-stage combustion technology combined with nitrogen-enriched air technology for controlling the combustion temperature and products to extend the maintenance and lifetime cycles of materials in contact with combustion products and to reduce pollutants while maintaining relatively high combustion and thermal cycle efficiencies. The first stage of combustion operates fuel rich where most of the heat of combustion is released by burning it with nitrogen-enriched air. Part of the energy in the combustion gases is used to perform work or to provide heat. The cooled combustion gases are reheated by additional stages of combustion until the last stage is at or near stoichiometric conditions. Additional energy is extracted from each stage to result in relatively high thermal cycle efficiency. The air is enriched with nitrogen using air separation technologies such as diffusion, permeable membrane, absorption, and cryogenics. The combustion method is applicable to many types of combustion equipment, including: boilers, burners, turbines, internal combustion engines, and many types of fuel including hydrogen and carbon-based fuels including methane and coal.

Life cycle and fecundity analysis of Lutzomyia shannoni (Dyar) (Diptera: Psychodidae).

PubMed

Ferro, C; Cárdenas, E; Corredor, D; Morales, A; Munstermann, L E

1998-01-01

The life cycle of Lutzomyia shannoni (Dyar), was described for laboratory conditions with maximum daily temperature of 27-30 degree C, minimum daily temperatures of 22-27 degree C and relative humidity between 87-99%. Life cycle in each stage was as follows: egg 6-12 days (ave, 8.5 days); first stage larva 5-13 days (ave. 9.6 days); second stage larva 4-13 days (ave. 9.2 days); third stage larva 5-19 days (ave. 11.8 days); fourth stage larva 7-37 days (ave. 19.9 days); pupa 7-32 days (ave. 15.2 days). The life expectancy of adults ranged from 4 to 15 days (ave. 8.6 days). The entire egg to adult period ranged from 36 to 74 days (ave. 54.6 days). On average, each female oviposited 22.7 eggs; the average egg retention per female was 24.3 eggs.

ORC1/CDC6 and MCM7 distinct associate with chromatin through Trypanosoma cruzi life cycle.

PubMed

Calderano, Simone; Godoy, Patricia; Soares, Daiane; Sant'Anna, Osvaldo Augusto; Schenkman, Sergio; Elias, M Carolina

2014-02-01

Trypanosoma cruzi alternates between replicative and non-replicative stages. We analyzed the expression of components of the pre-replication machinery TcORC1/CDC6 and TcMCM7 and their interaction with DNA in all T. cruzi stages. TcORC1/CDC6 remains in the nuclear space during all stages of the life cycle and interacts with DNA in the replicative stages; however, it does not bind to DNA in the non-replicative forms. Moreover, TcMCM7 is not present in the non-replicative stages. These data suggest that the lacking of DNA replication during the T. cruzi life cycle may be a consequence of the blocking of TcORC1/CDC6-DNA interaction and of the down regulation of the TcMCM7 expression. Copyright © 2014 Elsevier B.V. All rights reserved.

Sexual dimorphism in immune function changes during the annual cycle in house sparrows

NASA Astrophysics Data System (ADS)

Pap, Péter László; Czirják, Gábor Árpád; Vágási, Csongor István; Barta, Zoltán; Hasselquist, Dennis

2010-10-01

Difference between sexes in parasitism is a common phenomenon among birds, which may be related to differences between males and females in their investment into immune functions or as a consequence of differential exposure to parasites. Because life-history strategies change sex specifically during the annual cycle, immunological responses of the host aiming to reduce the impact of parasites may be sexually dimorphic. Despite the great complexity of the immune system, studies on immunoecology generally characterise the immune status through a few variables, often overlooking potentially important seasonal and gender effects. However, because of the differences in physiological and defence mechanisms among different arms of the immune system, we expect divergent responses of immune components to environmental seasonality. In male and female house sparrows ( Passer domesticus), we measured the major components of the immune system (innate, acquired, cellular and humoral) during four important life-history stages across the year: (1) mating, (2) breeding, (3) moulting and (4) during the winter capture and also following introduction to captivity in aviary. Different individuals were sampled from the same population during the four life cycle stages. We found that three out of eight immune variables showed a significant life cycle stage × sex interaction. The difference in immune response between the sexes was significant in five immune variables during the mating stage, when females had consistently stronger immune function than males, while variables varied generally non-significantly with sex during the remaining three life cycle stages. Our results show that the immune system is highly variable between life cycle stages and sexes, highlighting the potential fine tuning of the immune system to specific physiological states and environmental conditions.

[Activity of the hypophyseal-thyroid gland system in relation to the funcitonal state of the sex glands. Report I].

PubMed

Babichev, V N; Samsonova, V M

1975-01-01

Experiments were conducted on intact female rats; it was revealed that the content of protein-bound iodine (PBI) in the blood depended on the stage of the estral cycle. It was decreased at the metestrus and diestrus stages. Castration produced an even greater reduction in the blood PBI content. The blood PBI content proved to elevate in administration of estradiol dipropionate (EDP) to castrated rats. The TSH content in the hypophysis increased at the metestrus and diestrus stages and decreased at the proestrus and estrus stages. The relationship was reverse in the case with the blood TTH content. Castration was followed by a marked increase in the TSH content in the hypophysis accompanied by a reduction in the blood hormone level. The TSH concentration in the hypophysis decreased and in the blood increased under the effect of EDP in castrated animals. The data obtained indicated that the interrelationship between the thyroid gland and the sex glands was realized at the level of the hypophysis, and possibly, of the hypothalamus.

Variation in the foraging behaviors of two flycatchers: associations with stage of the breeding cycle

Treesearch

H.F. Sakai; B.R. Noon

1990-01-01

The foraging characteristics of Hammond’s and Western flycatchers in northwestern California varied with different stages of the breeding cycle during the breeding seasons (early April-mid August) in 1984 and 1985. The species’ behaviors did not always vary in parallel nor were all foraging behaviors distributed equally during the breeding cycle. For example, the...

Optimal synthesis and design of the number of cycles in the leaching process for surimi production.

PubMed

Reinheimer, M Agustina; Scenna, Nicolás J; Mussati, Sergio F

2016-12-01

Water consumption required during the leaching stage in the surimi manufacturing process strongly depends on the design and the number and size of stages connected in series for the soluble protein extraction target, and it is considered as the main contributor to the operating costs. Therefore, the optimal synthesis and design of the leaching stage is essential to minimize the total annual cost. In this study, a mathematical optimization model for the optimal design of the leaching operation is presented. Precisely, a detailed Mixed Integer Nonlinear Programming (MINLP) model including operating and geometric constraints was developed based on our previous optimization model (NLP model). Aspects about quality, water consumption and main operating parameters were considered. The minimization of total annual costs, which considered a trade-off between investment and operating costs, led to an optimal solution with lesser number of stages (2 instead of 3 stages) and higher volumes of the leaching tanks comparing with previous results. An analysis was performed in order to investigate how the optimal solution was influenced by the variations of the unitary cost of fresh water, waste treatment and capital investment.

The predictive adaptive response: modeling the life-history evolution of the butterfly Bicyclus anynana in seasonal environments.

PubMed

van den Heuvel, Joost; Saastamoinen, Marjo; Brakefield, Paul M; Kirkwood, Thomas B L; Zwaan, Bas J; Shanley, Daryl P

2013-02-01

A predictive adaptive response (PAR) is a type of developmental plasticity where the response to an environmental cue is not immediately advantageous but instead is later in life. The PAR is a way for organisms to maximize fitness in varying environments. Insects living in seasonal environments are valuable model systems for testing the existence and form of PAR. Previous manipulations of the larval and the adult environments of the butterfly Bicyclus anynana have shown that individuals that were food restricted during the larval stage coped better with forced flight during the adult stage compared to those with optimal conditions in the larval stage. Here, we describe a state-dependent energy allocation model, which we use to test whether such a response to food restriction could be adaptive in nature where this butterfly exhibits seasonal cycles. The results from the model confirm the responses obtained in our previous experimental work and show how such an outcome was facilitated by resource allocation patterns to the thorax during the pupal stage. We conclude that for B. anynana, early-stage cues can direct development toward a better adapted phenotype later in life and, therefore, that a PAR has evolved in this species.

Adjuvant therapy in early-stage non-small cell lung cancer.

PubMed

Serke, Monika

2010-01-01

Evidence clearly supports adjuvant chemotherapy following resection in patients with stage II or III non-small cell lung cancer (NSCLC). Based on 3 landmark studies, adjuvant chemotherapy has become standard in completely resected NSCLC stage II and IIIA. Survival benefit from adjuvant chemotherapy is estimated to be between 3% and 15%, depending on stage. Treatment should include 4 cycles of platinum-based combination chemotherapy. There is uncertainty about chemotherapy prescription in those patients with resected stage IB NSCLC, as the risk of recurrence is lower in early NSCLC and the magnitude of benefit of adjuvant therapy is proportional to the risk of relapse according to stage. Postoperative radiotherapy (PORT) should not be used for stage I or II NSCLC, and remains controversial in resected stage IIIA (N2) disease. All positive adjuvant trials have utilized a cisplatin-based regimen, usually in combination with vinorelbine, and this should be considered the standard approach. Prognostic factors to select patients who will benefit from adjuvant therapy in general or from platinum-based chemotherapy are under discussion, but not yet established. In future we hope to optimize treatment convenience for the patients by using other combinations with the hope of better efficacy results. Work is currently under way to identify prognostic factors which in future may help to identify patients who are most likely to benefit from chemotherapy. Copyright 2010 S. Karger AG, Basel.

Physiological age at harvest regulates the variability in postharvest ripening, sensory and nutritional characteristics of mango (Mangifera indica L.) cv. Coghshall due to growing conditions.

PubMed

Joas, Jacques; Vulcain, Emmanuelle; Desvignes, Claire; Morales, Emeline; Léchaudel, Mathieu

2012-04-01

Climacteric fruits are harvested at the green-mature stage and ripen during their marketing cycle. However, growing conditions induce variability into the maturity stage of mangoes at harvest, with an impact on their final quality. Assuming that the physiological age can be correctly evaluated by a criterion based on the variable chlorophyll fluorescence of the skin (F(v)) and that differences in physiological age depend on growing conditions, controlled stress experiments were carried out on mango fruit by manipulating either the leaf/fruit ratio or the light environment. Delays from 9 to 30 days were observed, depending on stress level and harvest stage, to obtain the same F(v) value. For moderate stress, fruit composition after ripening was partially compensated for, with little or no difference in sugar, dry matter, carotenoid and aroma contents. For more pronounced stress, the major metabolites were not particularly affected, but the synthesis capacity of carotenoids and aromas was lower after maturity. The ripening ability of a fruit is acquired on the tree and defines its postharvest changes. Control of the physiological age at harvest can minimise the variability observed under natural conditions and guarantee fruit batches whose postharvest changes will be relatively homogeneous. Copyright © 2011 Society of Chemical Industry.

Plasmodium falciparum Calcium-Dependent Protein Kinase 2 Is Critical for Male Gametocyte Exflagellation but Not Essential for Asexual Proliferation

PubMed Central

Molina-Cruz, Alvaro; Brzostowski, Joseph; Mu, Jianbing

2017-01-01

ABSTRACT Drug development efforts have focused mostly on the asexual blood stages of the malaria parasite Plasmodium falciparum. Except for primaquine, which has its own limitations, there are no available drugs that target the transmission of the parasite to mosquitoes. Therefore, there is a need to validate new parasite proteins that can be targeted for blocking transmission. P. falciparum calcium-dependent protein kinases (PfCDPKs) play critical roles at various stages of the parasite life cycle and, importantly, are absent in the human host. These features mark them as attractive drug targets. In this study, using CRISPR/Cas9 we successfully knocked out PfCDPK2 from blood-stage parasites, which was previously thought to be an indispensable protein. The growth rate of the PfCDPK2 knockout (KO) parasites was similar to that of wild-type parasites, confirming that PfCDPK2 function is not essential for the asexual proliferation of the parasite in vitro. The mature male and female gametocytes of PfCDPK2 KO parasites become round after induction. However, they fail to infect female Anopheles stephensi mosquitoes due to a defect(s) in male gametocyte exflagellation and possibly in female gametes. PMID:29042501

Dose-dependent effect of silver nanoparticles (AgNPs) on fertility and survival of Drosophila: An in-vivo study

PubMed Central

Raj, Akanksha; Shah, Prasanna

2017-01-01

Silver nanoparticles (AgNPs) containing consumer products have been proliferating in the market due to its unique antimicrobial property, however, lack of in-depth knowledge about their potential effect on human health in a longer run is of great concern. Therefore, we investigated dose-dependent in vivo effect of AgNPs using Drosophila as a model system. Drosophila, a genetically tractable organism with distinct developmental stages, short life cycle and significant homology with human serves as an ideal organism to study nanomaterial-mediated toxicity. Our studies suggest that ingestion of AgNPs in Drosophila during adult stage for short and long duration significantly affects egg laying capability along with impaired growth of ovary. Additionally, dietary intake of AgNPs from larval stage has more deleterious effects that result in reduced survival, longevity, ovary size and egg laying capability at a further lower dosage. Interestingly, the trans-generational effect of AgNPs was also observed without feeding progeny with AgNPs, thereby suggesting its impact from previous generation. Our results strongly imply that higher doses of AgNPs and its administration early during development is detrimental to the reproductive health and survival of Drosophila that follows in generations to come without feeding them to AgNPs. PMID:28542630

Dose-dependent effect of silver nanoparticles (AgNPs) on fertility and survival of Drosophila: An in-vivo study.

PubMed

Raj, Akanksha; Shah, Prasanna; Agrawal, Namita

2017-01-01

Silver nanoparticles (AgNPs) containing consumer products have been proliferating in the market due to its unique antimicrobial property, however, lack of in-depth knowledge about their potential effect on human health in a longer run is of great concern. Therefore, we investigated dose-dependent in vivo effect of AgNPs using Drosophila as a model system. Drosophila, a genetically tractable organism with distinct developmental stages, short life cycle and significant homology with human serves as an ideal organism to study nanomaterial-mediated toxicity. Our studies suggest that ingestion of AgNPs in Drosophila during adult stage for short and long duration significantly affects egg laying capability along with impaired growth of ovary. Additionally, dietary intake of AgNPs from larval stage has more deleterious effects that result in reduced survival, longevity, ovary size and egg laying capability at a further lower dosage. Interestingly, the trans-generational effect of AgNPs was also observed without feeding progeny with AgNPs, thereby suggesting its impact from previous generation. Our results strongly imply that higher doses of AgNPs and its administration early during development is detrimental to the reproductive health and survival of Drosophila that follows in generations to come without feeding them to AgNPs.

The negative influence of sperm cryopreservation on the quality and development of the embryo depends on the morphology of the oocyte.

PubMed

Braga, D P A F; Setti, A S; Figueira, R C S; Iaconelli, A; Borges, E

2015-07-01

The present case-control study aimed to identify the effect of sperm cryopreservation on the quality of the embryo and on the probability of blastocyst formation when oocytes free of dimorphisms are injected and when at least one dymorphism is present. The study included 22 186 zygotes, obtained from 2802 patients undergoing intracytoplasmic sperm injection cycles, in a private assisted reproduction center, using either fresh or cryopreserved sperm. The effect of sperm cryopreservation on the embryo quality on cleavage stage and blastocyst formation chance were evaluated when oocytes free of dimorphisms are injected and when at least one dymorphism is present. The quality of the embryo on cleavage stage as well as the chance for blastocyst formation was not influenced by the origin of the spermatozoa when the quality of the oocyte was not considered. When at least one oocyte defect was present, a negative influence of sperm cryopreservation on cleavage stage embryo quality and the chance for blastocyst formation was noted. In oocytes with extra-cytoplasmic dimorphisms, the injection of cryopreserved sperm did not affect the quality of the embryo during the cleavage stage, but did affect the chance for blastocyst formation. Conversely, in oocytes with intracytoplasmic defects, the quality of the embryos on cleavage stage and the chance of blastocyst formation were negatively influenced by the injection of cryopreserved sperm. The results suggest an oocyte quality-dependent negative effect of sperm cryopreservation on embryo quality and on the probability of blastocyst formation. © 2015 American Society of Andrology and European Academy of Andrology.

Evolution of periodicity in periodical cicadas

PubMed Central

Ito, Hiromu; Kakishima, Satoshi; Uehara, Takashi; Morita, Satoru; Koyama, Takuya; Sota, Teiji; Cooley, John R.; Yoshimura, Jin

2015-01-01

Periodical cicadas (Magicicada spp.) in the USA are famous for their unique prime-numbered life cycles of 13 and 17 years and their nearly perfectly synchronized mass emergences. Because almost all known species of cicada are non-periodical, periodicity is assumed to be a derived state. A leading hypothesis for the evolution of periodicity in Magicicada implicates the decline in average temperature during glacial periods. During the evolution of periodicity, the determinant of maturation in ancestral cicadas is hypothesized to have switched from size dependence to time (period) dependence. The selection for the prime-numbered cycles should have taken place only after the fixation of periodicity. Here, we build an individual-based model of cicadas under conditions of climatic cooling to explore the fixation of periodicity. In our model, under cold environments, extremely long juvenile stages lead to extremely low adult densities, limiting mating opportunities and favouring the evolution of synchronized emergence. Our results indicate that these changes, which were triggered by glacial cooling, could have led to the fixation of periodicity in the non-periodical ancestors. PMID:26365061

Does autophagy in the midgut epithelium of centipedes depend on the day/night cycle?

PubMed

Rost-Roszkowska, M M; Chajec, Ł; Vilimova, J; Tajovský, K; Kszuk-Jendrysik, M

2015-01-01

The midgut epithelium of two centipedes, Lithobius forficatus and Scolopendra cingulata, is composed of digestive, secretory and regenerative cells. In L. forficatus, the autophagy occurred only in the cytoplasm of the digestive cells as a sporadic process, while in S. cingulata, it occurred intensively in the digestive, secretory and regenerative cells of the midgut epithelium. In both of the species that were analyzed, this process proceeded in a continuous manner and did not depend on the day/night cycle. Ultrastructural analysis showed that the autophagosomes and autolysosomes were located mainly in the apical and perinuclear cytoplasm of the digestive cells in L. forficatus. However, in S. cingulata, the entire cytoplasm was filled with autophagosomes and autolysosomes. Initially the membranes of phagophores surround organelles during autophagosome formation. Autolysosomes result from the fusion of autophagosomes and lysosomes. Residual bodies which are the last stage of autophagy were released into the midgut lumen due to necrosis. Autophagy in the midgut epithelia that were analyzed was confirmed using acid phosphatase and mono-dansyl-cadaverine stainings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Rocket Based Combined Cycle (RBCC) engine inlet

NASA Technical Reports Server (NTRS)

2004-01-01

Pictured is a component of the Rocket Based Combined Cycle (RBCC) engine. This engine was designed to ultimately serve as the near term basis for Two Stage to Orbit (TSTO) air breathing propulsion systems and ultimately a Single Stage to Orbit (SSTO) air breathing propulsion system.

MicroRNA expression profiling during the life cycle of the silkworm (Bombyx mori)

PubMed Central

Liu, Shiping; Zhang, Liang; Li, Qibin; Zhao, Ping; Duan, Jun; Cheng, Daojun; Xiang, Zhonghuai; Xia, Qingyou

2009-01-01

Background MicroRNAs (miRNAs) are expressed by a wide range of eukaryotic organisms, and function in diverse biological processes. Numerous miRNAs have been identified in Bombyx mori, but the temporal expression profiles of miRNAs corresponding to each stage transition over the entire life cycle of the silkworm remain to be established. To obtain a comprehensive overview of the correlation between miRNA expression and stage transitions, we performed a whole-life test and subsequent stage-by-stage examinations on nearly one hundred miRNAs in the silkworm. Results Our results show that miRNAs display a wide variety of expression profiles over the whole life of the silkworm, including continuous expression from embryo to adult (miR-184), up-regulation over the entire life cycle (let-7 and miR-100), down-regulation over the entire life cycle (miR-124), expression associated with embryogenesis (miR-29 and miR-92), up-regulation from early 3rd instar to pupa (miR-275), and complementary pulses in expression between miR-34b and miR-275. Stage-by-stage examinations revealed further expression patterns, such as emergence at specific time-points during embryogenesis and up-regulation of miRNA groups in late embryos (miR-1 and bantam), expression associated with stage transition between instar and molt larval stages (miR-34b), expression associated with silk gland growth and spinning activity (miR-274), continuous high expression from the spinning larval to pupal and adult stages (miR-252 and miR-31a), a coordinate expression trough in day 3 pupae of both sexes (miR-10b and miR-281), up-regulation in pupal metamorphosis of both sexes (miR-29b), and down-regulation in pupal metamorphosis of both sexes (miR-275). Conclusion We present the full-scale expression profiles of miRNAs throughout the life cycle of Bombyx mori. The whole-life expression profile was further investigated via stage-by-stage analysis. Our data provide an important resource for more detailed functional analysis of miRNAs in this animal. PMID:19785751

MicroRNA expression profiling during the life cycle of the silkworm (Bombyx mori).

PubMed

Liu, Shiping; Zhang, Liang; Li, Qibin; Zhao, Ping; Duan, Jun; Cheng, Daojun; Xiang, Zhonghuai; Xia, Qingyou

2009-09-28

MicroRNAs (miRNAs) are expressed by a wide range of eukaryotic organisms, and function in diverse biological processes. Numerous miRNAs have been identified in Bombyx mori, but the temporal expression profiles of miRNAs corresponding to each stage transition over the entire life cycle of the silkworm remain to be established. To obtain a comprehensive overview of the correlation between miRNA expression and stage transitions, we performed a whole-life test and subsequent stage-by-stage examinations on nearly one hundred miRNAs in the silkworm. Our results show that miRNAs display a wide variety of expression profiles over the whole life of the silkworm, including continuous expression from embryo to adult (miR-184), up-regulation over the entire life cycle (let-7 and miR-100), down-regulation over the entire life cycle (miR-124), expression associated with embryogenesis (miR-29 and miR-92), up-regulation from early 3rd instar to pupa (miR-275), and complementary pulses in expression between miR-34b and miR-275. Stage-by-stage examinations revealed further expression patterns, such as emergence at specific time-points during embryogenesis and up-regulation of miRNA groups in late embryos (miR-1 and bantam), expression associated with stage transition between instar and molt larval stages (miR-34b), expression associated with silk gland growth and spinning activity (miR-274), continuous high expression from the spinning larval to pupal and adult stages (miR-252 and miR-31a), a coordinate expression trough in day 3 pupae of both sexes (miR-10b and miR-281), up-regulation in pupal metamorphosis of both sexes (miR-29b), and down-regulation in pupal metamorphosis of both sexes (miR-275). We present the full-scale expression profiles of miRNAs throughout the life cycle of Bombyx mori. The whole-life expression profile was further investigated via stage-by-stage analysis. Our data provide an important resource for more detailed functional analysis of miRNAs in this animal.

Differential Editosome Protein Function between Life Cycle Stages of Trypanosoma brucei *

PubMed Central

McDermott, Suzanne M.; Guo, Xuemin; Carnes, Jason; Stuart, Kenneth

2015-01-01

Uridine insertion and deletion RNA editing generates functional mitochondrial mRNAs in Trypanosoma brucei. The mRNAs are differentially edited in bloodstream form (BF) and procyclic form (PF) life cycle stages, and this correlates with the differential utilization of glycolysis and oxidative phosphorylation between the stages. The mechanism that controls this differential editing is unknown. Editing is catalyzed by multiprotein ∼20S editosomes that contain endonuclease, 3′-terminal uridylyltransferase, exonuclease, and ligase activities. These editosomes also contain KREPB5 and KREPA3 proteins, which have no functional catalytic motifs, but they are essential for parasite viability, editing, and editosome integrity in BF cells. We show here that repression of KREPB5 or KREPA3 is also lethal in PF, but the effects on editosome structure differ from those in BF. In addition, we found that point mutations in KREPB5 or KREPA3 differentially affect cell growth, editosome integrity, and RNA editing between BF and PF stages. These results indicate that the functions of KREPB5 and KREPA3 editosome proteins are adjusted between the life cycle stages. This implies that these proteins are involved in the processes that control differential editing and that the 20S editosomes differ between the life cycle stages. PMID:26304125

[Spatial mobility on reaching adult age].

PubMed

De Coninck, F

1990-12-01

"Starting with longitudinal data on two cohorts of women living in the Alpes-Maritimes [France] in 1982 (a sample of 1,500 women in total) we try to establish the role of the spatial distribution of opportunities at a number of key stages in the life cycle: marriage, birth of first child, making professional use of qualifications, confrontation of a situation of professional risk and professional mobility during the years immediately following the completion of studies. The underlying hypothesis is that control of social location often depends on the control of spatial location." (SUMMARY IN ENG) excerpt

MBASIC batch processor architectural overview

NASA Technical Reports Server (NTRS)

Reynolds, S. M.

1978-01-01

The MBASIC (TM) batch processor, a language translator designed to operate in the MBASIC (TM) environment is described. Features include: (1) a CONVERT TO BATCH command, usable from the ready mode; and (2) translation of the users program in stages through several levels of intermediate language and optimization. The processor is to be designed and implemented in both machine-independent and machine-dependent sections. The architecture is planned so that optimization processes are transparent to the rest of the system and need not be included in the first design implementation cycle.

Phase II Trial of Adjuvant Pelvic Radiation “Sandwiched” Between Combination Paclitaxel and Carboplatin in Women with Uterine Papillary Serous Carcinoma

PubMed Central

Einstein, Mark H.; Frimer, Marina; Kuo, Dennis Y-S; Reimers, Laura L.; Mehta, Keyur; Mutyala, Subhakar; Huang, Gloria S.; Hou, June Y.; Goldberg, Gary L.

2013-01-01

Objective To evaluate the safety and survival in women treated with adjuvant pelvic radiation “sandwiched” between six cycles of paclitaxel and carboplatin chemotherapy with completely resected UPSC. Methods Surgically staged women with UPSC (FIGO stage 1-4) and no visible residual disease were enrolled. Treatment involved paclitaxel (175 mg/m2) and carboplatin (AUC=6.0-7.5) every 21 days for 3 doses, followed by radiation therapy (RT), followed by an additional 3 cycles of paclitaxel and carboplatin (AUC=5-6). Survival analysis, using Kaplan-Meier methods, was performed on patients who completed at least 3 cycles of chemotherapy and RT. Results A total of 81 patients were enrolled, of which 72 patients completed the first 3 cycles of chemotherapy followed by prescribed RT. Median age was 67 years (range: 43–82 years). 59/72 (82%) had disease confined to the uterus and 13/72 (18%) had completely resected extra-uterine disease (stage 3&4). 65 (83%) completed the protocol. Overall PFS and OS for combined stage 1&2 patients was 65.5±3.6 months and 76.5±4.3 months, respectively. PFS and OS for combined stage 3&4 patients was 25.8±3.0 and 35.9±5.3 months, respectively. Three-year % survival probability for stage 1&2 patients was 84% and for stage 3&4 patients was 50%. Of the 435 chemotherapy cycles administered, there were 11(2.5%) G3/G4 non-hematologic toxicities. 26(6.0%) cycles had dose reductions and 37(8.5%) had dose delays. Conclusions Compared to prior studies of single modality adjuvant therapy, RT “sandwiched” between paclitaxel and carboplatin chemotherapy is well-tolerated and highly efficacious in women with completely resected UPSC. PMID:22035806

Integrative omics analysis. A study based on Plasmodium falciparum mRNA and protein data.

PubMed

Tomescu, Oana A; Mattanovich, Diethard; Thallinger, Gerhard G

2014-01-01

Technological improvements have shifted the focus from data generation to data analysis. The availability of large amounts of data from transcriptomics, protemics and metabolomics experiments raise new questions concerning suitable integrative analysis methods. We compare three integrative analysis techniques (co-inertia analysis, generalized singular value decomposition and integrative biclustering) by applying them to gene and protein abundance data from the six life cycle stages of Plasmodium falciparum. Co-inertia analysis is an analysis method used to visualize and explore gene and protein data. The generalized singular value decomposition has shown its potential in the analysis of two transcriptome data sets. Integrative Biclustering applies biclustering to gene and protein data. Using CIA, we visualize the six life cycle stages of Plasmodium falciparum, as well as GO terms in a 2D plane and interpret the spatial configuration. With GSVD, we decompose the transcriptomic and proteomic data sets into matrices with biologically meaningful interpretations and explore the processes captured by the data sets. IBC identifies groups of genes, proteins, GO Terms and life cycle stages of Plasmodium falciparum. We show method-specific results as well as a network view of the life cycle stages based on the results common to all three methods. Additionally, by combining the results of the three methods, we create a three-fold validated network of life cycle stage specific GO terms: Sporozoites are associated with transcription and transport; merozoites with entry into host cell as well as biosynthetic and metabolic processes; rings with oxidation-reduction processes; trophozoites with glycolysis and energy production; schizonts with antigenic variation and immune response; gametocyctes with DNA packaging and mitochondrial transport. Furthermore, the network connectivity underlines the separation of the intraerythrocytic cycle from the gametocyte and sporozoite stages. Using integrative analysis techniques, we can integrate knowledge from different levels and obtain a wider view of the system under study. The overlap between method-specific and common results is considerable, even if the basic mathematical assumptions are very different. The three-fold validated network of life cycle stage characteristics of Plasmodium falciparum could identify a large amount of the known associations from literature in only one study.

Integrative omics analysis. A study based on Plasmodium falciparum mRNA and protein data

PubMed Central

2014-01-01

Background Technological improvements have shifted the focus from data generation to data analysis. The availability of large amounts of data from transcriptomics, protemics and metabolomics experiments raise new questions concerning suitable integrative analysis methods. We compare three integrative analysis techniques (co-inertia analysis, generalized singular value decomposition and integrative biclustering) by applying them to gene and protein abundance data from the six life cycle stages of Plasmodium falciparum. Co-inertia analysis is an analysis method used to visualize and explore gene and protein data. The generalized singular value decomposition has shown its potential in the analysis of two transcriptome data sets. Integrative Biclustering applies biclustering to gene and protein data. Results Using CIA, we visualize the six life cycle stages of Plasmodium falciparum, as well as GO terms in a 2D plane and interpret the spatial configuration. With GSVD, we decompose the transcriptomic and proteomic data sets into matrices with biologically meaningful interpretations and explore the processes captured by the data sets. IBC identifies groups of genes, proteins, GO Terms and life cycle stages of Plasmodium falciparum. We show method-specific results as well as a network view of the life cycle stages based on the results common to all three methods. Additionally, by combining the results of the three methods, we create a three-fold validated network of life cycle stage specific GO terms: Sporozoites are associated with transcription and transport; merozoites with entry into host cell as well as biosynthetic and metabolic processes; rings with oxidation-reduction processes; trophozoites with glycolysis and energy production; schizonts with antigenic variation and immune response; gametocyctes with DNA packaging and mitochondrial transport. Furthermore, the network connectivity underlines the separation of the intraerythrocytic cycle from the gametocyte and sporozoite stages. Conclusion Using integrative analysis techniques, we can integrate knowledge from different levels and obtain a wider view of the system under study. The overlap between method-specific and common results is considerable, even if the basic mathematical assumptions are very different. The three-fold validated network of life cycle stage characteristics of Plasmodium falciparum could identify a large amount of the known associations from literature in only one study. PMID:25033389

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parvinen, M.; Soeder, O.M.; Mali, P.

Levels of rat testicular interleukin-1-like factor (tIL-1) have been shown to correlate with DNA synthetic activity during the cycle of the rat seminiferous epithelium, suggesting its role as a spermatogonial or meiotic growth factor. To explore this further, a new in vitro model system was developed. Rat seminiferous tubule segments from stages I, V, VIIa, and VIII-IX of the cycle were isolated by transillumination-assisted microdissection, cultured in chemically defined serum-free medium supplemented with human recombinant IL-1 {alpha}, and labeled with (3H)thymidine. During incubation, spontaneous progression of spermatogenesis was noted. Inactive stage VIIa tubule segments differentiated to stage VIII and initiatedmore » DNA synthesis, and concomitantly started to secrete IL-1-like factor. DNA synthesis of stages VIII-IX ceased through differentiation of spermatocytes to leptotene-zygotene (stages XII-XIII of the cycle). IL-1 {alpha} stimulated DNA synthesis significantly in spermatogonia of stage I. Meiotic DNA synthesis at stage VIIa was stimulated (48 h/34 C) and maintained at stages VIII-IX (48 h/34 C). IL-1 {alpha} seems to act as a regulator of spermatogenic DNA synthesis in both mitotic and meiotic phases. It has mainly stimulating and maintaining effects, but it may also be inhibitory under certain conditions.« less

Off-farm employment, land, and life cycle: transmigrant households in South Sumatra, Indonesia.

PubMed

Leinbach, T R; Smith, A

1994-07-01

This paper examines the role that off-farm employment (OFE) plays in the restructuring of peasant economies. In particular, we examine the incidence and pattern of labor allocation as it relates to landownership and family life cycle (FLC) stages in the Indonesian transmigration program.... Using a sample of South Sumatran transmigration schemes, our findings show that both size of landholdings and the life cycle stage of the family influence labor allocation decisions....The results show how landownership and other means of production can influence the trade-off between children's education and the use of child labor at various stages in the FLC."

Stage-Specific Changes in Plasmodium Metabolism Required for Differentiation and Adaptation to Different Host and Vector Environments.

PubMed

Srivastava, Anubhav; Philip, Nisha; Hughes, Katie R; Georgiou, Konstantina; MacRae, James I; Barrett, Michael P; Creek, Darren J; McConville, Malcolm J; Waters, Andrew P

2016-12-01

Malaria parasites (Plasmodium spp.) encounter markedly different (nutritional) environments during their complex life cycles in the mosquito and human hosts. Adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (TCA) metabolism in mosquito stages. Here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage-specific changes in Plasmodium berghei carbon metabolism and determine the functional significance of these changes on parasite survival in the blood and mosquito stages. We show that glutamine serves as the predominant input into TCA metabolism in both asexual and sexual blood stages and is important for complete male gametogenesis. Glutamine catabolism, as well as key reactions in intermediary metabolism and CoA synthesis are also essential for ookinete to oocyst transition in the mosquito. These data extend our knowledge of Plasmodium metabolism and point towards possible targets for transmission-blocking intervention strategies. Furthermore, they highlight significant metabolic differences between Plasmodium species which are not easily anticipated based on genomics or transcriptomics studies and underline the importance of integration of metabolomics data with other platforms in order to better inform drug discovery and design.

Stage-Specific Changes in Plasmodium Metabolism Required for Differentiation and Adaptation to Different Host and Vector Environments

PubMed Central

Srivastava, Anubhav; Philip, Nisha; Hughes, Katie R.; Georgiou, Konstantina; MacRae, James I.; Barrett, Michael P.; McConville, Malcolm J.

2016-01-01

Malaria parasites (Plasmodium spp.) encounter markedly different (nutritional) environments during their complex life cycles in the mosquito and human hosts. Adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (TCA) metabolism in mosquito stages. Here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage-specific changes in Plasmodium berghei carbon metabolism and determine the functional significance of these changes on parasite survival in the blood and mosquito stages. We show that glutamine serves as the predominant input into TCA metabolism in both asexual and sexual blood stages and is important for complete male gametogenesis. Glutamine catabolism, as well as key reactions in intermediary metabolism and CoA synthesis are also essential for ookinete to oocyst transition in the mosquito. These data extend our knowledge of Plasmodium metabolism and point towards possible targets for transmission-blocking intervention strategies. Furthermore, they highlight significant metabolic differences between Plasmodium species which are not easily anticipated based on genomics or transcriptomics studies and underline the importance of integration of metabolomics data with other platforms in order to better inform drug discovery and design. PMID:28027318

The evaluation life cycle: a retrospective assessment of stages and phases of the circles of care initiative.

PubMed

Bess, Gary; Allen, James; Deters, Pamela B

2004-08-12

A life cycle metaphor characterizes the evolving relationship between the evaluator and program staff. This framework suggests that common developmental dynamics occur in roughly the same order across groups and settings. There are stage-specific dynamics that begin with Pre-History, which characterize the relationship between the grantees and evaluator. The stages are: (a) Pre-History, (b) Process, (c) Development, (d) Action, (e) Findings-Compilation, and (f) Transition. The common dynamics, expectations, and activities for each stage are discussed.

Combined chemical and optical methods for monitoring the early decay stages of surrogate human models.

PubMed

Statheropoulos, M; Agapiou, A; Zorba, E; Mikedi, K; Karma, S; Pallis, G C; Eliopoulos, C; Spiliopoulou, C

2011-07-15

As the body decays shortly after death, a variety of gases and volatile organic compounds (VOCs) constantly emanate. Ethical and practical reasons limit the use of human corpses in controlled, time-dependent, intervening experiments for monitoring the chemistry of body decay. Therefore the utilization of pig carcasses serves as a potential surrogate to human models. The aim of this work was to study buried body decay in conditions of entrapment in collapsed buildings. Six domestic pigs were used to study carcass decay. They were enclosed in plastic body bags after being partially buried with rubbles, resembling entrapment in collapsed buildings. Three experimental cycles were performed, employing two pig carcasses in each cycle; VOCs and inorganic gases were measured daily, along with daily visible and thermal images. VOCs were collected in standard sorbent tubes and subsequently analyzed using a Thermal Desorption/Gas Chromatograph/high sensitivity bench-top Time-of-Flight Mass Spectrometer (TD/GC/TOF-MS). A comprehensive, stage by stage, detailed information on the decay process is being presented based on the experimental macroscopic observations, justifying thus the use of pig carcasses as surrogate material. A variety of VOCs were identified including almost all chemical classes: sulfur, nitrogen, oxygen compounds (aldehydes, alcohols, ketones, acids and esters), hydrocarbons, fluorides and chlorides. Carcasses obtained from a pig farm resulted in more sulfur and nitrogen cadaveric volatiles. Carbon dioxide was by far the most abundant inorganic gas identified along with carbon monoxide, hydrogen sulfide and sulfur dioxide. Visual monitoring was based on video captured images allowing for macroscopic observations, while thermal camera monitoring which is mostly temperature dependent, resulted in highlighting the local micro-changes on the carcasses, as a result of the intense microbial activity. The combination of chemical and optical methods proved very useful and informative, uncovering hidden aspects of the early stages of decay and also guiding in the development of combined chemical and imaging methods for the detection of dead bodies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Complete life cycle of a pennellid Peniculus minuticaudae Shiino, 1956 (Copepoda: Siphonostomatoida) infecting cultured threadsail filefish, Stephanolepis cirrhifer

PubMed Central

Ismail, Norshida; Ohtsuka, Susumu; Venmathi Maran, Balu Alagar; Tasumi, Satoshi; Zaleha, Kassim; Yamashita, Hirofumi

2013-01-01

The complete life cycle of a pennellid copepod Peniculus minuticaudae Shiino, 1956 is proposed based on the discovery of all post-embryonic stages together with the post-metamorphic adult females infecting the fins of threadsail filefish Stephanolepis cirrhifer (Monacanthidae) cultured in a fish farm at Ehime Prefecture, Japan. The hatching stage was the infective copepodid. The life cycle of P. minuticaudae consists of six stages separated by moults: the copepodid, four chalimi and adult. In this study, the adult males were observed frequently in precopulatory amplexus with various stages of females however, copulation occurs only between adults. Fertilized pre-metamorphic adult females carrying spermatophores may detach from the host and settle again before undergoing massive differential growth into the post-metamorphic adult female. Comparison of the life cycle of P. minuticaudae has been made with three known pennellids: Lernaeocera branchialis (Linnaeus, 1767), Cardiodectes medusaeus (Wilson, 1908) and Lernaeenicus sprattae (Sowerby, 1806). Among the compared species, P. minuticaudae is the first ectoparasitic pennellid to be discovered to complete its life cycle on a single host without any change in infection site preferences between infective copepodid and fertilized pre-metamorphic female. PMID:24165196

Life cycle-dependent cytoskeletal modifications in Plasmodium falciparum infected erythrocytes.

PubMed

Shi, Hui; Liu, Zhuo; Li, Ang; Yin, Jing; Chong, Alvin G L; Tan, Kevin S W; Zhang, Yong; Lim, Chwee Teck

2013-01-01

Plasmodium falciparum infection of human erythrocytes is known to result in the modification of the host cell cytoskeleton by parasite-coded proteins. However, such modifications and corresponding implications in malaria pathogenesis have not been fully explored. Here, we probed the gradual modification of infected erythrocyte cytoskeleton with advancing stages of infection using atomic force microscopy (AFM). We reported a novel strategy to derive accurate and quantitative information on the knob structures and their connections with the spectrin network by performing AFM-based imaging analysis of the cytoplasmic surface of infected erythrocytes. Significant changes on the red cell cytoskeleton were observed from the expansion of spectrin network mesh size, extension of spectrin tetramers and the decrease of spectrin abundance with advancing stages of infection. The spectrin network appeared to aggregate around knobs but also appeared sparser at non-knob areas as the parasite matured. This dramatic modification of the erythrocyte skeleton during the advancing stage of malaria infection could contribute to the loss of deformability of the infected erythrocyte.

Slow eye movements distribution during nocturnal sleep.

PubMed

Pizza, Fabio; Fabbri, Margherita; Magosso, Elisa; Ursino, Mauro; Provini, Federica; Ferri, Raffaele; Montagna, Pasquale

2011-08-01

To assess the distribution across nocturnal sleep of slow eye movements (SEMs). We evaluated SEMs distribution in the different sleep stages, and across sleep cycles in nocturnal recordings of 10 healthy women. Sleep was scored according to standard criteria, and the percentage of time occupied by the SEMs was automatically detected. SEMs were differently represented during sleep stages with the following order: wakefulness after sleep onset (WASO): 61%, NREM sleep stage 1: 54%, REM sleep: 43%, NREM sleep stage 2: 21%, NREM sleep stage 3: 7%, and NREM sleep stage 4: 3% (p<0.0001). There was no difference between phasic and tonic REM sleep. SEMs progressively decreased across the NREM sleep cycles (38%, 15%, 13% during NREM sleep stage 2 in the first three sleep cycles, p=0.006), whereas no significant difference was found for REM, NREM sleep stage 1, slow-wave sleep and WASO. Our findings confirm that SEMs are a phenomenon typical of the sleep onset period, but are also found in REM sleep. The nocturnal evolution of SEMs during NREM sleep stage 2 parallels the homeostatic process underlying slow-wave sleep. SEMs are a marker of sleepiness and, potentially, of sleep homeostasis. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The pathobiology and mechanisms of infection of HPV.

PubMed

Wood, N H; Khammissa, R A G; Chikte, U M E; Meyerov, R; Lemmer, J; Feller, L

2010-04-01

There are more than 120 types of low-risk and high-risk human papillomaviruses, all of which are epitheliotropic. HPV infection may be latent, or active in a subclinical form or a symptomatic form, the latter manifesting as benign or malignant neoplasms. In basal cells with non-productive HPV infection some early HPV proteins are expressed independently of cell maturation: the productive cycle of HPV replication depends upon specific cellular factors of the maturation of the infected keratinocytes. In HPV-mediated oncogenesis, the combined pathobiological effects of E6 and E7 oncoproteins of high-risk HPV culminate in cellular genomic instability and transformation of persistently infected cells, that progress to the development of a malignant phenotype. In this article we provide insights into the stages of HPV infection, and into the viral genomic organization and replicative cycle.

Noumeavirus replication relies on a transient remote control of the host nucleus

PubMed Central

Fabre, Elisabeth; Jeudy, Sandra; Santini, Sébastien; Legendre, Matthieu; Trauchessec, Mathieu; Couté, Yohann; Claverie, Jean-Michel; Abergel, Chantal

2017-01-01

Acanthamoeba are infected by a remarkable diversity of large dsDNA viruses, the infectious cycles of which have been characterized using genomics, transcriptomics and electron microscopy. Given their gene content and the persistence of the host nucleus throughout their infectious cycle, the Marseilleviridae were initially assumed to fully replicate in the cytoplasm. Unexpectedly, we find that their virions do not incorporate the virus-encoded transcription machinery, making their replication nucleus-dependent. However, instead of delivering their DNA to the nucleus, the Marseilleviridae initiate their replication by transiently recruiting the nuclear transcription machinery to their cytoplasmic viral factory. The nucleus recovers its integrity after becoming leaky at an early stage. This work highlights the importance of virion proteomic analyses to complement genome sequencing in the elucidation of the replication scheme and evolution of large dsDNA viruses. PMID:28429720

Metabolomic analysis of the green microalga Chlamydomonas reinhardtii cultivated under day/night conditions.

PubMed

Willamme, Rémi; Alsafra, Zouheir; Arumugam, Rameshkumar; Eppe, Gauthier; Remacle, Françoise; Levine, R D; Remacle, Claire

2015-12-10

Biomass composition of Chlamydomonas reinhardtii was studied during two consecutive cycles of 12h light/12h dark. As in our experimental conditions the two synchronized divisions were separated by 20h, it was possible to show that accumulation of dry weight, proteins, chlorophyll and fatty acids mainly depends on cell division, whereas starch accumulation depends on a circadian rhythm as reported previously. Our metabolomics analyses also revealed that accumulation of five (Ser, Val, Leu, Ile and Thr) of the nine free amino acids detected displayed rhythmicity, depending on cell division while Glu was 20-50 times more abundant than the other ones probably because this free amino acid serves not only for protein synthesis but also for biosynthesis of nitrogen compounds. In addition, we performed a thermodynamic-motivated theoretical approach known as 'surprisal analysis'. The results from this analysis showed that cells were close to a steady state all along the 48h of the experiment. In addition, calculation of free energy of cellular metabolites showed that the transition point, i.e. the state which immediately precedes cell division, corresponds to the most unstable stage of the cell cycle and that division is identified as the greatest drop in the free energy of metabolites. Copyright © 2015 Elsevier B.V. All rights reserved.

Multi-stage versus single-stage inflation and deflation cycle for alternating low pressure air mattresses to prevent pressure ulcers in hospitalised patients: a randomised-controlled clinical trial.

PubMed

Demarré, L; Beeckman, D; Vanderwee, K; Defloor, T; Grypdonck, M; Verhaeghe, S

2012-04-01

The duration and the amount of pressure and shear must be reduced in order to minimize the risk of pressure ulcer development. Alternating low pressure air mattresses with multi-stage inflation and deflation cycle of the air cells have been developed to relieve pressure by sequentially inflating and deflating the air cells. Evidence about the effectiveness of this type of mattress in clinical practice is lacking. This study aimed to compare the effectiveness of an alternating low pressure air mattress that has a standard single-stage inflation and deflation cycle of the air cells with an alternating low pressure air mattress with multi-stage inflation and deflation cycle of the air cells. A randomised controlled trial was performed in a convenience sample of 25 wards in five hospitals in Belgium. In total, 610 patients were included and randomly assigned to the experimental group (n=298) or the control group (n=312). In the experimental group, patients were allocated to an alternating low pressure air mattress with multi-stage inflation and deflation cycle of the air cells. In the control group, patients were allocated to an alternating low pressure air mattress with a standard single-stage inflation and deflation cycle of the air cells. The outcome was defined as cumulative pressure ulcer incidence (Grade II-IV). An intention-to-treat analysis was performed. There was no significant difference in cumulative pressure ulcer incidence (Grade II-IV) between both groups (Exp.=5.7%, Contr.=5.8%, p=0.97). When patients developed a pressure ulcer, the median time was 5.0 days in the experimental group (IQR=3.0-8.5) and 8.0 days in the control group (IQR=3.0-8.5) (Mann-Whitney U-test=113, p=0.182). The probability to remain pressure ulcer free during the observation period in this trial did not differ significantly between the experimental group and the control group (log-rank χ(2)=0.013, df=1, p=0.911). An alternating low pressure air mattress with multi-stage inflation and deflation of the air cells does not result in a significantly lower pressure ulcer incidence compared to an alternating low pressure air mattress with a standard single-stage inflation and deflation cycle of the air cells. Both alternating mattress types are equally effective to prevent pressure ulcer development. © 2011 Elsevier Ltd. All rights reserved.

Helium process cycle

DOEpatents

Ganni, Venkatarao

2008-08-12

A unique process cycle and apparatus design separates the consumer (cryogenic) load return flow from most of the recycle return flow of a refrigerator and/or liquefier process cycle. The refrigerator and/or liquefier process recycle return flow is recompressed by a multi-stage compressor set and the consumer load return flow is recompressed by an independent consumer load compressor set that maintains a desirable constant suction pressure using a consumer load bypass control valve and the consumer load return pressure control valve that controls the consumer load compressor's suction pressure. The discharge pressure of this consumer load compressor is thereby allowed to float at the intermediate pressure in between the first and second stage recycle compressor sets. Utilizing the unique gas management valve regulation, the unique process cycle and apparatus design in which the consumer load return flow is separate from the recycle return flow, the pressure ratios of each recycle compressor stage and all main pressures associated with the recycle return flow are allowed to vary naturally, thus providing a naturally regulated and balanced floating pressure process cycle that maintains optimal efficiency at design and off-design process cycle capacity and conditions automatically.

Helium process cycle

DOEpatents

Ganni, Venkatarao

2007-10-09

A unique process cycle and apparatus design separates the consumer (cryogenic) load return flow from most of the recycle return flow of a refrigerator and/or liquefier process cycle. The refrigerator and/or liquefier process recycle return flow is recompressed by a multi-stage compressor set and the consumer load return flow is recompressed by an independent consumer load compressor set that maintains a desirable constant suction pressure using a consumer load bypass control valve and the consumer load return pressure control valve that controls the consumer load compressor's suction pressure. The discharge pressure of this consumer load compressor is thereby allowed to float at the intermediate pressure in between the first and second stage recycle compressor sets. Utilizing the unique gas management valve regulation, the unique process cycle and apparatus design in which the consumer load return flow is separate from the recycle return flow, the pressure ratios of each recycle compressor stage and all main pressures associated with the recycle return flow are allowed to vary naturally, thus providing a naturally regulated and balanced floating pressure process cycle that maintains optimal efficiency at design and off-design process cycle capacity and conditions automatically.

Embryonic Cleavage Cycles: How Is a Mouse Like a Fly?

PubMed Central

O’Farrell, Patrick H.; Stumpff, Jason; Su, Tin Tin

2009-01-01

The evolutionary advent of uterine support of embryonic growth in mammals is relatively recent. Nonetheless, striking differences in the earliest steps of embryogenesis make it difficult to draw parallels even with other chordates. We suggest that use of fertilization as a reference point misaligns the earliest stages and masks parallels that are evident when development is aligned at conserved stages surrounding gastrulation. In externally deposited eggs from representatives of all the major phyla, gastrulation is preceded by specialized extremely rapid cleavage cell cycles. Mammals also exhibit remarkably fast cell cycles in close association with gastrulation, but instead of beginning development with these rapid cycles, the mammalian egg first devotes itself to the production of extraembryonic structures. Previous attempts to identify common features of cleavage cycles focused on post-fertilization divisions of the mammalian egg. We propose that comparison to the rapid peri-gastrulation cycles is more appropriate and suggest that these cycles are related by evolutionary descent to the early cleavage stages of embryos such as those of frog and fly. The deferral of events in mammalian embryogenesis might be due to an evolutionary shift in the timing of fertilization. PMID:14711435

Comparison of survival rate of cleavage stage embryos produced from in vitro maturation cycles after slow freezing and after vitrification.

PubMed

Son, Weon-Young; Chung, Jin-Tae; Gidoni, Yariv; Holzer, Hananel; Levin, Dan; Chian, Ri-Cheng; Tan, Seang Lin

2009-09-01

Significantly more embryos survived the vitrification procedure compared to slow freezing (85.5% vs. 61.8%) in cleavage-stage human embryos produced from in vitro maturation cycles, suggesting that vitrification is more efficient than slow freezing for cryopreservation.

The transillumination technique as a method for the assessment of spermatogenesis using medicinal plants: the effect of extracts of black maca (Lepidium meyenii) and camu camu (Myrciaria dubia) on stages of the spermatogenic cycle in male rats.

PubMed

Gonzales, Gustavo F; Vasquez, Vanessa Bertha; Gasco, Manuel

2013-10-01

Transillumination technique for assessment of stages of spermatogenic cycle is a useful tool for toxicological studies. This study was designed to determine the effect of two medicinal plants on spermatogenesis in male rats using the transillumination technique. For this, the effect of the combination of a fruit with highest content of ascorbic acid (Myrciaria dubia, camu camu) and extract of black maca (Lepidium meyenii) on seminiferous tubule stages scored by transillumination on intact tubules in adult male rats was assessed. Animals were treated during seven days with vehicle, black maca, camu camu or a mixture of black maca + camu camu and assessed for daily sperm production (DSP), stages of spermatogenic cycle as well as antioxidant activity and levels of flavonoids and polyphenols. Black maca increased stages of spermiation (VII-VIII) and mitosis of germ cells (IX-XI), whereas camu camu increased stages of mitosis (IX-XI) and meiosis (XII). Mixture of maca + camu camu increased stages of spermiation, mitosis and meiosis. All treatments increased DSP (p<0.05) and epididymal sperm count (p<0.05). Total polyphenols, flavonoids levels and antioxidant activity were higher in camu camu (p<0.001) than in black maca. In conclusion, M. dubia (camu camu) has potential effects improving spermatogenesis and co-administered with maca increase stages of mitosis, meiosis and spermiation of the spermatogenic cycle as assessed by the transillumination technique. This technique is becoming increasingly a useful tool for assessment spermatogenesis.

Lys48 ubiquitination during the intraerythrocytic cycle of the rodent malaria parasite, Plasmodium chabaudi.

PubMed

González-López, Lorena; Carballar-Lejarazú, Rebeca; Arrevillaga Boni, Gerardo; Cortés-Martínez, Leticia; Cázares-Raga, Febe Elena; Trujillo-Ocampo, Abel; Rodríguez, Mario H; James, Anthony A; Hernández-Hernández, Fidel de la Cruz

2017-01-01

Ubiquitination tags proteins for different functions within the cell. One of the most abundant and studied ubiquitin modification is the Lys48 polyubiquitin chain that modifies proteins for their destruction by proteasome. In Plasmodium is proposed that post-translational regulation is fundamental for parasite development during its complex life-cycle; thus, the objective of this work was to analyze the ubiquitination during Plasmodium chabaudi intraerythrocytic stages. Ubiquitinated proteins were detected during intraerythrocytic stages of Plasmodium chabaudi by immunofluorescent microscopy, bidimensional electrophoresis (2-DE) combined with immunoblotting and mass spectrometry. All the studied stages presented protein ubiquitination and Lys48 polyubiquitination with more abundance during the schizont stage. Three ubiquitinated proteins were identified for rings, five for trophozoites and twenty for schizonts. Only proteins detected with a specific anti- Lys48 polyubiquitin antibody were selected for Mass Spectrometry analysis and two of these identified proteins were selected in order to detect the specific amino acid residues where ubiquitin is placed. Ubiquitinated proteins during the ring and trophozoite stages were related with the invasion process and in schizont proteins were related with nucleic acid metabolism, glycolysis and protein biosynthesis. Most of the ubiquitin detection was during the schizont stage and the Lys48 polyubiquitination during this stage was related to proteins that are expected to be abundant during the trophozoite stage. The evidence that these Lys48 polyubiquitinated proteins are tagged for destruction by the proteasome complex suggests that this type of post-translational modification is important in the regulation of protein abundance during the life-cycle and may also contribute to the parasite cell-cycle progression.

Impact of minor actinide recycling on sustainable fuel cycle options

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heidet, F.; Kim, T. K.; Taiwo, T. A.

The recent Evaluation and Screening study chartered by the U.S. Department of Energy, Office of Nuclear Energy, has identified four fuel cycle options as being the most promising. Among these four options, the two single-stage fuel cycles rely on a fast reactor and are differing in the fact that in one case only uranium and plutonium are recycled while in the other case minor actinides are also recycled. The two other fuel cycles are two-stage and rely on both fast and thermal reactors. They also differ in the fact that in one case only uranium and plutonium are recycled whilemore » in the other case minor actinides are also recycled. The current study assesses the impact of recycling minor actinides on the reactor core design, its performance characteristics, and the characteristics of the recycled material and waste material. The recycling of minor actinides is found not to affect the reactor core performance, as long as the same cycle length, core layout and specific power are being used. One notable difference is that the required transuranics (TRU) content is slightly increased when minor actinides are recycled. The mass flows are mostly unchanged given a same specific power and cycle length. Although the material mass flows and reactor performance characteristics are hardly affected by recycling minor actinides, some differences are observed in the waste characteristics between the two fuel cycles considered. The absence of minor actinides in the waste results in a different buildup of decay products, and in somewhat different behaviors depending on the characteristic and time frame considered. Recycling of minor actinides is found to result in a reduction of the waste characteristics ranging from 10% to 90%. These results are consistent with previous studies in this domain and depending on the time frame considered, packaging conditions, repository site, repository strategy, the differences observed in the waste characteristics could be beneficial and help improve the repository performance. On the other hand, recycling minor actinides also results in an increase of the recycled fuel characteristics and therefore of the charged fuel. The radioactivity is slightly increased while the decay heat and radiotoxicities are very significantly increased. Despite these differences, the characteristics of the fuel at time of discharge remain similar whether minor actinides are recycled or not, with the exception of the inhalation radiotoxicity which is significantly larger with minor actinide recycling. After some cooling the characteristics of the discharged fuel become larger when minor actinides are recycled, potentially affecting the reprocessing plant requirements. Recycling minor actinides has a negative impact on the characteristics of the fresh fuel and will make it more challenging to fabricate fuel containing minor actinides.« less

Identification by Random Mutagenesis of Functional Domains in KREPB5 That Differentially Affect RNA Editing between Life Cycle Stages of Trypanosoma brucei.

PubMed

McDermott, Suzanne M; Carnes, Jason; Stuart, Kenneth

2015-12-01

KREPB5 is an essential component of ∼ 20S editosomes in Trypanosoma brucei which contains a degenerate, noncatalytic RNase III domain. To explore the function of this protein, we used a novel approach to make and screen numerous conditional null T. brucei bloodstream form cell lines that express randomly mutagenized KREPB5 alleles. We identified nine single amino acid substitutions that could not complement the conditional loss of wild-type KREPB5. Seven of these were within the RNase III domain, and two were in the C-terminal region that has no homology to known motifs. Exclusive expression of these mutated KREPB5 alleles in the absence of wild-type allele expression resulted in growth inhibition, the loss of ∼ 20S editosomes, and inhibition of RNA editing in BF cells. Eight of these mutations were lethal in bloodstream form parasites but not in procyclic-form parasites, showing that multiple domains function in a life cycle-dependent manner. Amino acid changes at a substantial number of positions, including up to 7 per allele, allowed complementation and thus did not block KREPB5 function. Hence, the degenerate RNase III domain and a newly identified domain are critical for KREPB5 function and have differential effects between the life cycle stages of T. brucei that differentially edit mRNAs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Life-cycle and growth-phase-dependent regulation of the ubiquitin genes of Trypanosoma cruzi.

PubMed

Manning-Cela, Rebeca; Jaishankar, Sobha; Swindle, John

2006-07-01

Trypanosoma cruzi, the causative agent of Chagas disease, exhibits a complex life cycle that is accompanied by the stage-specific gene expression. At the molecular level, very little is known about gene regulation in trypanosomes. Complex gene organizations coupled with polycistronic transcription units make the analysis of regulated gene expression difficult in trypanosomes. The ubiquitin genes of T. cruzi are a good example of this complexity. They are organized as a single cluster containing five ubiquitin fusion (FUS) and five polyubiquitin (PUB) genes that are polycistronically transcribed but expressed differently in response to developmental and environmental changes. Gene replacements were used to study FUS and PUB gene expression at different stages of growth and at different points in the life cycle of T. cruzi. Based on the levels of reporter gene expression, it was determined that FUS1 expression was downregulated as the parasites approached stationary phase, whereas PUB12.5 polyubiquitin gene expression increased. Conversely, FUS1 expression increases when epimastigotes and amastigotes differentiate into trypomastigotes, whereas the expression of PUB12.5 decreases when epimastigotes differentiate into amastigotes and trypomastigotes. Although the level of CAT activity in logarithmic growing epimastigotes is six- to seven-fold higher when the gene was expressed from the FUS1 locus than when expressed from the PUB12.5 locus, the rate of transcription from the two loci was the same implying that post-transcriptional mechanisms play a dominant role in the regulation of gene expression.

A fuel cycle assessment guide for utility and state energy planners

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1994-07-01

This guide, one in a series of documents designed to help assess fuel cycles, is a framework for setting parameters, collecting data, and analyzing fuel cycles for supply-side and demand-side management. It provides an automated tool for entering comparative fuel cycle data that are meaningful to state and utility integrated resource planning, collaborative, and regional energy planning activities. It outlines an extensive range of energy technology characteristics and environmental, social, and economic considerations within each stage of a fuel cycle. The guide permits users to focus on specific stages or effects that are relevant to the technology being evaluated andmore » that meet the user`s planning requirements.« less

Cell cycle-tailored targeting of metastatic melanoma: Challenges and opportunities.

PubMed

Haass, Nikolas K; Gabrielli, Brian

2017-07-01

The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the "bad guy" to the "poster child" in oncology. Current targeted therapies are effective, although here is a clear need to develop combination therapies to delay the onset of resistance. Many antimelanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors. Secondly, if the combination is designed to target different tumor cell subpopulations of a heterogeneous tumor, one drug effective in a particular subpopulation should not negatively impact on the other drug targeting another subpopulation. In addition to the role of cell cycle stage and progression on standard chemotherapeutics and targeted drugs, we discuss the utilization of cell cycle checkpoint control defects to enhance chemotherapeutic responses or as targets themselves. We propose that cell cycle-tailored targeting of metastatic melanoma could further improve therapy outcomes and that our real-time cell cycle imaging 3D melanoma spheroid model could be utilized as a tool to measure and design drug scheduling approaches. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Perspectives on the neuroscience of alcohol from the National Institute on Alcohol Abuse and Alcoholism.

PubMed

Reilly, Matthew T; Noronha, Antonio; Warren, Kenneth

2014-01-01

Mounting evidence over the last 40 years clearly indicates that alcoholism (alcohol dependence) is a disorder of the brain. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has taken significant steps to advance research into the neuroscience of alcohol. The Division of Neuroscience and Behavior (DNB) was formed within NIAAA in 2002 to oversee, fund, and direct all research areas that examine the effects of alcohol on the brain, the genetic underpinnings of alcohol dependence, the neuroadaptations resulting from excessive alcohol consumption, advanced behavioral models of the various stages of the addiction cycle, and preclinical medications development. This research portfolio has produced important discoveries in the etiology, treatment, and prevention of alcohol abuse and dependence. Several of these salient discoveries are highlighted and future areas of neuroscience research on alcohol are presented. © 2014 Elsevier B.V. All rights reserved.

Full cycle trigonometric function on Intel Quartus II Verilog

NASA Astrophysics Data System (ADS)

Mustapha, Muhazam; Zulkarnain, Nur Antasha

2018-02-01

This paper discusses about an improvement of a previous research on hardware based trigonometric calculations. Tangent function will also be implemented to get a complete set. The functions have been simulated using Quartus II where the result will be compared to the previous work. The number of bits has also been extended for each trigonometric function. The design is based on RTL due to its resource efficient nature. At earlier stage, a technology independent test bench simulation was conducted on ModelSim due to its convenience in capturing simulation data so that accuracy information can be obtained. On second stage, Intel/Altera Quartus II will be used to simulate on technology dependent platform, particularly on the one belonging to Intel/Altera itself. Real data on no. logic elements used and propagation delay have also been obtained.

Adaptor protein complexes-1 and 3 are involved at distinct stages of flavivirus life-cycle

PubMed Central

Agrawal, Tanvi; Schu, Peter; Medigeshi, Guruprasad R.

2013-01-01

Intracellular protein trafficking pathways are hijacked by viruses at various stages of viral life-cycle. Heterotetrameric adaptor protein complexes (APs) mediate vesicular trafficking at distinct intracellular sites and are essential for maintaining the organellar homeostasis. In the present study, we studied the effect of AP-1 and AP-3 deficiency on flavivirus infection in cells functionally lacking these proteins. We show that AP-1 and AP-3 participate in flavivirus life-cycle at distinct stages. AP-3-deficient cells showed delay in initiation of Japanese encephalitis virus and dengue virus RNA replication, which resulted in reduction of infectious virus production. AP-3 was found to colocalize with RNA replication compartments in infected wild-type cells. AP-1 deficiency affected later stages of dengue virus infection where increased intracellular accumulation of infectious virus was observed. Therefore, our results propose a novel role for AP-1 and AP-3 at distinct stages of infection of some of the RNA viruses. PMID:23657274

Adaptor protein complexes-1 and 3 are involved at distinct stages of flavivirus life-cycle.

PubMed

Agrawal, Tanvi; Schu, Peter; Medigeshi, Guruprasad R

2013-01-01

Intracellular protein trafficking pathways are hijacked by viruses at various stages of viral life-cycle. Heterotetrameric adaptor protein complexes (APs) mediate vesicular trafficking at distinct intracellular sites and are essential for maintaining the organellar homeostasis. In the present study, we studied the effect of AP-1 and AP-3 deficiency on flavivirus infection in cells functionally lacking these proteins. We show that AP-1 and AP-3 participate in flavivirus life-cycle at distinct stages. AP-3-deficient cells showed delay in initiation of Japanese encephalitis virus and dengue virus RNA replication, which resulted in reduction of infectious virus production. AP-3 was found to colocalize with RNA replication compartments in infected wild-type cells. AP-1 deficiency affected later stages of dengue virus infection where increased intracellular accumulation of infectious virus was observed. Therefore, our results propose a novel role for AP-1 and AP-3 at distinct stages of infection of some of the RNA viruses.

[Family factors associated with co-dependency in nurses at a hospital in Cancun, Quintana Roo, México].

PubMed

Ramírez-Amaro, Margarita; Martínez-Torres, Jorge; Ureña Bogarín, Enrique Leobardo

2014-05-01

Identifying family factors associated with the presence of co-dependency in nurses of a regional hospital in Cancún, Quintana Roo, Mexico. Cross-sectional, comparative study. City of Cancun (México). A random sample of 200nurses who met the inclusion criteria (having a partner for over a year, to be at work on the day of the interview), and who gave informed consent, completed three questionnaires during different shifts. Age, educational level, socioeconomic status, type of family structure, life cycle stage, co-dependency and family functioning. A total of 200nurses, with mean age of 36±8years, took part. The most common socioeconomic status was high (48%), and 47.5% had graduate studies. A co-dependency level of 20.5% (95%CI: 15-26.5) was found. Family factors associated with the presence of co-dependency were; family dysfunction, prevalence ratio (PR)=9.62 (95%CI: 3.47-27.3), stage of independence, PR=3.41 (95%CI: 1.44-7.86), single parent, PR=6.35 (95%CI: 2.41-16.68), and time with partner less than 5 years, PR=3.41 (95%CI: 1.54-7.85). It was found that family dysfunction and being a single parent were significantly associated with co-dependency in hospital nurses, therefore, on being able to identify these factors, family physicians can improve their dynamics and functioning by family study, and improving effective communication with nursing staff and their families. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Psychosocial Implications of Usher Syndrome, Type I, throughout the Life Cycle.

ERIC Educational Resources Information Center

Miner, I. D.

1995-01-01

Usher syndrome, Type I, requires multiple adaptations throughout the life cycle because each stage of life has tasks and losses associated with deafness and progressive retinitis pigmentosa. This article examines the issues raised at each stage, using clinical vignettes from persons who have this condition and their families. (Author/DB)

The Life Cycle of the Child Care Center -- Understanding Center Growth and Development.

ERIC Educational Resources Information Center

Bess, Gary; Ratekin, Cindy

2001-01-01

Identifies the seven stages of the life cycle for child care centers: entrepreneurial; development; formalization; maturity; stagnation; death; and renewal. Suggests that critical transition points exist for organizational development, and that, if they are aware of and understand each stage of development, administrators may intervene at those…

Genomic characterisation of the effector complement of the potato cyst nematode Globodera pallida.

PubMed

Thorpe, Peter; Mantelin, Sophie; Cock, Peter Ja; Blok, Vivian C; Coke, Mirela C; Eves-van den Akker, Sebastian; Guzeeva, Elena; Lilley, Catherine J; Smant, Geert; Reid, Adam J; Wright, Kathryn M; Urwin, Peter E; Jones, John T

2014-10-23

The potato cyst nematode Globodera pallida has biotrophic interactions with its host. The nematode induces a feeding structure - the syncytium - which it keeps alive for the duration of the life cycle and on which it depends for all nutrients required to develop to the adult stage. Interactions of G. pallida with the host are mediated by effectors, which are produced in two sets of gland cells. These effectors suppress host defences, facilitate migration and induce the formation of the syncytium. The recent completion of the G. pallida genome sequence has allowed us to identify the effector complement from this species. We identify 128 orthologues of effectors from other nematodes as well as 117 novel effector candidates. We have used in situ hybridisation to confirm gland cell expression of a subset of these effectors, demonstrating the validity of our effector identification approach. We have examined the expression profiles of all effector candidates using RNAseq; this analysis shows that the majority of effectors fall into one of three clusters of sequences showing conserved expression characteristics (invasive stage nematode only, parasitic stage only or invasive stage and adult male only). We demonstrate that further diversity in the effector pool is generated by alternative splicing. In addition, we show that effectors target a diverse range of structures in plant cells, including the peroxisome. This is the first identification of effectors from any plant pathogen that target this structure. This is the first genome scale search for effectors, combined to a life-cycle expression analysis, for any plant-parasitic nematode. We show that, like other phylogenetically unrelated plant pathogens, plant parasitic nematodes deploy hundreds of effectors in order to parasitise plants, with different effectors required for different phases of the infection process.

Incorporating Erlotinib or Irinotecan Plus Cisplatin into Chemoradiotherapy for Stage III Non-small Cell Lung Cancer According to EGFR Mutation Status.

PubMed

Lee, Youngjoo; Han, Ji-Youn; Moon, Sung Ho; Nam, Byung-Ho; Lim, Kun Young; Lee, Geon Kook; Kim, Heung Tae; Yun, Tak; An, Hye Jin; Lee, Jin Soo

2017-10-01

Concurrent chemoradiotherapy (CCRT) is the standard care for stage III non-small cell lung cancer (NSCLC) patients; however, a more effective regimen is needed to improve the outcome by better controlling occult metastases. We conducted two parallel randomized phase II studies to incorporate erlotinib or irinotecan-cisplatin (IP) into CCRT for stage III NSCLC depending on epidermal growth factor receptor (EGFR) mutation status. Patients with EGFR-mutant tumors were randomized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib (arm A) or CCRT with IP only (arm B). Patients with EGFR unknown or wild-type tumors were randomized to receive either three cycles of IP before (arm C) or after CCRT with IP (arm D). Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were randomized. Overall, there were seven patients in arm A, five in arm B, 22 in arm C, and 25 in arm D. The response rate was 71.4% and 80.0% for arm A and B, and 70.0% and 73.9% for arm C and D. The median overall survival (OS) was 39.3 months versus 31.2 months for arm A and B (p=0.442), and 16.3 months versus 25.3 months for arm C and D (p=0.050). Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients (74.8 months vs. 25.3 months, p=0.034). There were no unexpected toxicities. Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC. EGFR-mutant patients appear to be a distinct subset with longer survival.

A constitutive pan-hexose permease for the Plasmodium life cycle and transgenic models for screening of antimalarial sugar analogs.

PubMed

Blume, Martin; Hliscs, Marion; Rodriguez-Contreras, Dayana; Sanchez, Marco; Landfear, Scott; Lucius, Richard; Matuschewski, Kai; Gupta, Nishith

2011-04-01

Glucose is considered essential for erythrocytic stages of the malaria parasite, Plasmodium falciparum. Importance of sugar and its permease for hepatic and sexual stages of Plasmodium, however, remains elusive. Moreover, increasing global resistance to current antimalarials necessitates the search for novel drugs. Here, we reveal that hexose transporter 1 (HT1) of Plasmodium berghei can transport glucose (K(m)~87 μM), mannose (K(i)~93 μM), fructose (K(i)~0.54 mM), and galactose (K(i)~5 mM) in Leishmania mexicana mutant and Xenopus laevis; and, therefore, is functionally equivalent to HT1 of P. falciparum (Glc, K(m)~175 μM; Man, K(i)~276 μM; Fru, K(i)~1.25 mM; Gal, K(i)~5.86 mM). Notably, a glucose analog, C3361, attenuated hepatic (IC(50)~15 μM) and ookinete development of P. berghei. The PbHT1 could be ablated during intraerythrocytic stages only by concurrent complementation with PbHT1-HA or PfHT1. Together; these results signify that PbHT1 and glucose are required for the entire life cycle of P. berghei. Accordingly, PbHT1 is expressed in the plasma membrane during all parasite stages. To permit a high-throughput screening of PfHT1 inhibitors and their subsequent in vivo assessment, we have generated Saccharomyces cerevisiae mutant expressing codon-optimized PfHT1, and a PfHT1-dependent Δpbht1 parasite strain. This work provides a platform to facilitate the development of drugs against malaria, and it suggests a disease-control aspect by reducing parasite transmission.

Polysomnography (Sleep Study)

MedlinePlus

... it's done Polysomnography monitors your sleep stages and cycles to identify if or when your sleep patterns ... You normally go through four to six sleep cycles a night, cycling between NREM and REM sleep ...

Visual aided pacing in respiratory maneuvers

NASA Astrophysics Data System (ADS)

Rambaudi, L. R.; Rossi, E.; Mántaras, M. C.; Perrone, M. S.; Siri, L. Nicola

2007-11-01

A visual aid to pace self-controlled respiratory cycles in humans is presented. Respiratory manoeuvres need to be accomplished in several clinic and research procedures, among others, the studies on Heart Rate Variability. Free running respiration turns to be difficult to correlate with other physiologic variables. Because of this fact, voluntary self-control is asked from the individuals under study. Currently, an acoustic metronome is used to pace respiratory frequency, its main limitation being the impossibility to induce predetermined timing in the stages within the respiratory cycle. In the present work, visual driven self-control was provided, with separate timing for the four stages of a normal respiratory cycle. This visual metronome (ViMet) was based on a microcontroller which power-ON and -OFF an eight-LED bar, in a four-stage respiratory cycle time series handset by the operator. The precise timing is also exhibited on an alphanumeric display.

Advanced regenerative absorption refrigeration cycles

DOEpatents

Dao, Kim

1990-01-01

Multi-effect regenerative absorption cycles which provide a high coefficient of performance (COP) at relatively high input temperatures. An absorber-coupled double-effect regenerative cycle (ADR cycle) (10) is provided having a single-effect absorption cycle (SEA cycle) (11) as a topping subcycle and a single-effect regenerative absorption cycle (1R cycle) (12) as a bottoming subcycle. The SEA cycle (11) includes a boiler (13), a condenser (21), an expansion device (28), an evaporator (31), and an absorber (40), all operatively connected together. The 1R cycle (12) includes a multistage boiler (48), a multi-stage resorber (51), a multisection regenerator (49) and also uses the condenser (21), expansion device (28) and evaporator (31) of the SEA topping subcycle (11), all operatively connected together. External heat is applied to the SEA boiler (13) for operation up to about 500 degrees F., with most of the high pressure vapor going to the condenser (21) and evaporator (31) being generated by the regenerator (49). The substantially adiabatic and isothermal functioning of the SER subcycle (12) provides a high COP. For higher input temperatures of up to 700 degrees F., another SEA cycle (111) is used as a topping subcycle, with the absorber (140) of the topping subcycle being heat coupled to the boiler (13) of an ADR cycle (10). The 1R cycle (12) itself is an improvement in that all resorber stages (50b-f) have a portion of their output pumped to boiling conduits (71a-f) through the regenerator (49), which conduits are connected to and at the same pressure as the highest pressure stage (48a) of the 1R multistage boiler (48).

Complete life cycle of a pennellid Peniculus minuticaudae Shiino, 1956 (Copepoda: Siphonostomatoida) infecting cultured threadsail filefish, Stephanolepis cirrhifer.

PubMed

Ismail, Norshida; Ohtsuka, Susumu; Maran, Balu Alagar Venmathi; Tasumi, Satoshi; Zaleha, Kassim; Yamashita, Hirofumi

2013-01-01

The complete life cycle of a pennellid copepod Peniculus minuticaudae Shiino, 1956 is proposed based on the discovery of all post-embryonic stages together with the post-metamorphic adult females infecting the fins of threadsail filefish Stephanolepis cirrhifer (Monacanthidae) cultured in a fish farm at Ehime Prefecture, Japan. The hatching stage was the infective copepodid. The life cycle of P. minuticaudae consists of six stages separated by moults: the copepodid, four chalimi and adult. In this study, the adult males were observed frequently in precopulatory amplexus with various stages of females however, copulation occurs only between adults. Fertilized pre-metamorphic adult females carrying spermatophores may detach from the host and settle again before undergoing massive differential growth into the post-metamorphic adult female. Comparison of the life cycle of P. minuticaudae has been made with three known pennellids: Lernaeocera branchialis (Linnaeus, 1767), Cardiodectes medusaeus (Wilson, 1908) and Lernaeenicus sprattae (Sowerby, 1806). Among the compared species, P. minuticaudae is the first ectoparasitic pennellid to be discovered to complete its life cycle on a single host without any change in infection site preferences between infective copepodid and fertilized pre-metamorphic female. © N. Ismail et al., published by EDP Sciences, 2013.

Signatures of natural selection between life cycle stages separated by metamorphosis in European eel.

PubMed

Pujolar, J M; Jacobsen, M W; Bekkevold, D; Lobón-Cervià, J; Jónsson, B; Bernatchez, L; Hansen, M M

2015-08-13

Species showing complex life cycles provide excellent opportunities to study the genetic associations between life cycle stages, as selective pressures may differ before and after metamorphosis. The European eel presents a complex life cycle with two metamorphoses, a first metamorphosis from larvae into glass eels (juvenile stage) and a second metamorphosis into silver eels (adult stage). We tested the hypothesis that different genes and gene pathways will be under selection at different life stages when comparing the genetic associations between glass eels and silver eels. We used two sets of markers to test for selection: first, we genotyped individuals using a panel of 80 coding-gene single nucleotide polymorphisms (SNPs) developed in American eel; second, we investigated selection at the genome level using a total of 153,423 RAD-sequencing generated SNPs widely distributed across the genome. Using the RAD approach, outlier tests identified a total of 2413 (1.57%) potentially selected SNPs. Functional annotation analysis identified signal transduction pathways as the most over-represented group of genes, including MAPK/Erk signalling, calcium signalling and GnRH (gonadotropin-releasing hormone) signalling. Many of the over-represented pathways were related to growth, while others could result from the different conditions that eels inhabit during their life cycle. The observation of different genes and gene pathways under selection when comparing glass eels vs. silver eels supports the adaptive decoupling hypothesis for the benefits of metamorphosis. Partitioning the life cycle into discrete morphological phases may be overall beneficial since it allows the different life stages to respond independently to their unique selection pressures. This might translate into a more effective use of food and niche resources and/or performance of phase-specific tasks (e.g. feeding in the case of glass eels, migrating and reproducing in the case of silver eels).

Filling Knowledge Gaps for Mimivirus Entry, Uncoating, and Morphogenesis

PubMed Central

Andrade, Ana Cláudia dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Oliveira, Graziele Pereira; Andrade, Kétyllen Reis; Bonjardim, Cláudio Antônio; La Scola, Bernard; Kroon, Erna Geessien

2017-01-01

ABSTRACT Since the discovery of mimivirus, its unusual structural and genomic features have raised great interest in the study of its biology; however, many aspects concerning its replication cycle remain uncertain. In this study, extensive analyses of electron microscope images, as well as biological assay results, shed light on unclear points concerning the mimivirus replication cycle. We found that treatment with cytochalasin, a phagocytosis inhibitor, negatively impacted the incorporation of mimivirus particles by Acanthamoeba castellanii, causing a negative effect on viral growth in amoeba monolayers. Treatment of amoebas with bafilomicin significantly impacted mimivirus uncoating and replication. In conjunction with microscopic analyses, these data suggest that mimiviruses indeed depend on phagocytosis for entry into amoebas, and particle uncoating (and stargate opening) appears to be dependent on phagosome acidification. In-depth analyses of particle morphogenesis suggest that the mimivirus capsids are assembled from growing lamellar structures. Despite proposals from previous studies that genome acquisition occurs before the acquisition of fibrils, our results clearly demonstrate that the genome and fibrils can be acquired simultaneously. Our data suggest the existence of a specific area surrounding the core of the viral factory where particles acquire the surface fibrils. Furthermore, we reinforce the concept that defective particles can be formed even in the absence of virophages. Our work provides new information about unexplored steps in the life cycle of mimivirus. IMPORTANCE Investigating the viral life cycle is essential to a better understanding of virus biology. The combination of biological assays and microscopic images allows a clear view of the biological features of viruses. Since the discovery of mimivirus, many studies have been conducted to characterize its replication cycle, but many knowledge gaps remain to be filled. In this study, we conducted a new examination of the replication cycle of mimivirus and provide new evidence concerning some stages of the cycle which were previously unclear, mainly entry, uncoating, and morphogenesis. Furthermore, we demonstrate that atypical virion morphologies can occur even in the absence of virophages. Our results, along with previous data, allow us to present an ultimate model for the mimivirus replication cycle. PMID:28878069

Filling Knowledge Gaps for Mimivirus Entry, Uncoating, and Morphogenesis.

PubMed

Andrade, Ana Cláudia Dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Oliveira, Graziele Pereira; Andrade, Kétyllen Reis; Bonjardim, Cláudio Antônio; La Scola, Bernard; Kroon, Erna Geessien; Abrahão, Jônatas Santos

2017-11-15

Since the discovery of mimivirus, its unusual structural and genomic features have raised great interest in the study of its biology; however, many aspects concerning its replication cycle remain uncertain. In this study, extensive analyses of electron microscope images, as well as biological assay results, shed light on unclear points concerning the mimivirus replication cycle. We found that treatment with cytochalasin, a phagocytosis inhibitor, negatively impacted the incorporation of mimivirus particles by Acanthamoeba castellanii , causing a negative effect on viral growth in amoeba monolayers. Treatment of amoebas with bafilomicin significantly impacted mimivirus uncoating and replication. In conjunction with microscopic analyses, these data suggest that mimiviruses indeed depend on phagocytosis for entry into amoebas, and particle uncoating (and stargate opening) appears to be dependent on phagosome acidification. In-depth analyses of particle morphogenesis suggest that the mimivirus capsids are assembled from growing lamellar structures. Despite proposals from previous studies that genome acquisition occurs before the acquisition of fibrils, our results clearly demonstrate that the genome and fibrils can be acquired simultaneously. Our data suggest the existence of a specific area surrounding the core of the viral factory where particles acquire the surface fibrils. Furthermore, we reinforce the concept that defective particles can be formed even in the absence of virophages. Our work provides new information about unexplored steps in the life cycle of mimivirus. IMPORTANCE Investigating the viral life cycle is essential to a better understanding of virus biology. The combination of biological assays and microscopic images allows a clear view of the biological features of viruses. Since the discovery of mimivirus, many studies have been conducted to characterize its replication cycle, but many knowledge gaps remain to be filled. In this study, we conducted a new examination of the replication cycle of mimivirus and provide new evidence concerning some stages of the cycle which were previously unclear, mainly entry, uncoating, and morphogenesis. Furthermore, we demonstrate that atypical virion morphologies can occur even in the absence of virophages. Our results, along with previous data, allow us to present an ultimate model for the mimivirus replication cycle. Copyright © 2017 American Society for Microbiology.

Stage-dependent and temperature-controlled expression of the gene encoding the precursor protein of diapause hormone and pheromone biosynthesis activating neuropeptide in the silkworm, Bombyx mori.

PubMed

Xu, W H; Sato, Y; Ikeda, M; Yamashita, O

1995-02-24

Embryonic diapause and sex pheromone biosynthesis in the silkworm, Bombyx mori, are, respectively, induced by diapause hormone (DH) and pheromone biosynthesis activating neuropeptide (PBAN), which are produced in the subesophageal ganglion from a common polyprotein precursor (DH-PBAN precursor) encoded by a single gene (DH-PBAN gene). Using DH-PBAN cDNA as a probe, we quantitatively measured DH-PBAN mRNA content throughout embryonic and postembryonic development and observed the effects of incubation temperature, which is a key factor for determination of diapause, on DH-PBAN gene expression. The silkworm, which is programmed to lay diapause eggs by being incubated at 25 degrees C, showed peaks of DH-PBAN mRNA content at five different stages throughout the life cycle: at the late embryonic stage, at the middle of the fourth and the fifth larval instars, and at early and late stages of pupal-adult development. In the non-diapause type silkworms programmed by a 15 degrees C incubation, only the last peak of DH-PBAN mRNA in pupal-adult development was found, and the other peaks were absent. Furthermore, interruption of the incubation period at 25 degrees C by incubation at 15 degrees C decreased both DH-PBAN mRNA content in mature embryos and in subesophageal ganglia of day 3 pupae and the incidence of diapause eggs. Thus, there were two types of regulatory mechanisms for DH-PBAN gene expression. One is a temperature-controlled expression that is responsible for diapause induction, and the other is a temperature-independent, stage-dependent expression related to pheromone production.

The Model Life-cycle: Training Module

EPA Pesticide Factsheets

Model Life-Cycle includes identification of problems & the subsequent development, evaluation, & application of the model. Objectives: define ‘model life-cycle’, explore stages of model life-cycle, & strategies for development, evaluation, & applications.

Sleep-waking cycle in the cerveau isolé cat.

PubMed

Slósarska, M; Zernicki, B

1973-06-01

The experiments were performed on ten chronic low cerveau isolé cats: in eight cats the brain stem transection was prepontine and in two cats, intercollicular. The preparations survived from 24 to 3 days. During 24-36 hr sessions the ECoG activity was continuously recorded, and the ocular and ECoG components of the orienting reflexes to visual and olfactory stimuli were studied. 2. Three periods can be recognized in the recovery process of the low cerveau isolé cat. They are called acute, early chronic and late chronic stages. The acute stage lasts 1 day and the early chronic stage seems to last 3 weeks at least. During the acute stage the ability to desynchronize the EEG, either spontaneously or in response to sensory stimulations, is dramatically impaired and the pupils are fissurated. Thus the cat is comatous. 4. During the early chronic stage, although the ECoG synchronization-desynchronization cycle and the associated fissurated myosis-myosis cycle already exist, the episodes of ECoG desynchronization occupy only a small percentage of time and usually develop slowly. Visual and olfactory stimuli are often ineffective. Thus the cat is semicomatous. In the late chronic stage the sleep-waking cycle is present. The animal can be easily awakened by visual and olfactory stimuli. The intensity of the ECoG arousal to visual stimuli and the distribution of time between alert wakefulness, drowsiness, light synchronized sleep and deep synchronized sleep are similar to those in the chronic pretrigeminal cat. The recovery of the cerveau isolé seems to reach a steady level when the sleep-waking cycle becomes similar to that present in the chronic pretrigeminal cat. During the whole survival period the vertical following reflex is abortive.

Transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition in Trypanosoma cruzi

PubMed Central

Greif, Gonzalo; Rodriguez, Matias; Alvarez-Valin, Fernando

2017-01-01

American trypanosomiasis is a chronic and endemic disease which affects millions of people. Trypanosoma cruzi, its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. This requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation. In this work we conducted an RNAseq analysis of the three major life cycle stages of T. cruzi: amastigotes, epimastigotes and trypomastigotes. This analysis allowed us to delineate specific transcriptomic profiling for each stage, and also to identify those biological processes of major relevance in each state. Stage specific expression profiling evidenced the plasticity of T. cruzi to adapt quickly to different conditions, with particular focus on membrane remodeling and metabolic shifts along the life cycle. Epimastigotes, which replicate in the gut of insect vectors, showed higher expression of genes related to energy metabolism, mainly Krebs cycle, respiratory chain and oxidative phosphorylation related genes, and anabolism related genes associated to nucleotide and steroid biosynthesis; also, a general down-regulation of surface glycoprotein coding genes was seen at this stage. Trypomastigotes, living extracellularly in the bloodstream of mammals, express a plethora of surface proteins and signaling genes involved in invasion and evasion of immune response. Amastigotes mostly express membrane transporters and genes involved in regulation of cell cycle, and also express a specific subset of surface glycoprotein coding genes. In addition, these results allowed us to improve the annotation of the Dm28c genome, identifying new ORFs and set the stage for construction of networks of co-expression, which can give clues about coded proteins of unknown functions. PMID:28286708

Transcriptome profiling of the dynamic life cycle of the scypohozoan jellyfish Aurelia aurita.

PubMed

Brekhman, Vera; Malik, Assaf; Haas, Brian; Sher, Noa; Lotan, Tamar

2015-02-14

The moon jellyfish Aurelia aurita is a widespread scyphozoan species that forms large seasonal blooms. Here we provide the first comprehensive view of the entire complex life of the Aurelia Red Sea strain by employing transcriptomic profiling of each stage from planula to mature medusa. A de novo transcriptome was assembled from Illumina RNA-Seq data generated from six stages throughout the Aurelia life cycle. Transcript expression profiling yielded clusters of annotated transcripts with functions related to each specific life-cycle stage. Free-swimming planulae were found highly enriched for functions related to cilia and microtubules, and the drastic morphogenetic process undergone by the planula while establishing the future body of the polyp may be mediated by specifically expressed Wnt ligands. Specific transcripts related to sensory functions were found in the strobila and the ephyra, whereas extracellular matrix functions were enriched in the medusa due to high expression of transcripts such as collagen, fibrillin and laminin, presumably involved in mesoglea development. The CL390-like gene, suggested to act as a strobilation hormone, was also highly expressed in the advanced strobila of the Red Sea species, and in the medusa stage we identified betaine-homocysteine methyltransferase, an enzyme that may play an important part in maintaining equilibrium of the medusa's bell. Finally, we identified the transcription factors participating in the Aurelia life-cycle and found that 70% of these 487 identified transcription factors were expressed in a developmental-stage-specific manner. This study provides the first scyphozoan transcriptome covering the entire developmental trajectory of the life cycle of Aurelia. It highlights the importance of numerous stage-specific transcription factors in driving morphological and functional changes throughout this complex metamorphosis, and is expected to be a valuable resource to the community.

Impact of CD40 expression by flowcytometry on outcome of patients with non-Hodgkin's lymphoma.

PubMed

Soliman, Mohamed A; Fathy, Amr Ahmed; Alkilani, Amira; Abd El-Bary, Naser; El-Bassal, Fathai

2009-01-01

Lymphoid malignancies represent a wide variety of disease entities characterized by malignant proliferation of lymphoid cells which have distinct clinical features, cellular morphology, immunophenotype, cytogenetic changes and histologic features. CD40 is a member of the tumor necrosis factor receptor super-family. It was first identified and characterized in B cell, signaling through the CD40 receptor was found to play an important role in multiple events in T-cell dependent antibody response including B-cell survival and proliferation, memory B-cell formation and immunoglobulin isotype switching. The aim of this study is to detect the expression of CD40 on B lymphocytes in patients suffering from Non-Hodgkin's Lymphoma and correlate the results with the patients' response to treatment protocols. This study was carried out on 114 patients, of them only 100 patients completed 4 cycles of chemotherapy and were valuable. Their age was ranged from 17 to 63 years old. Fifteen age and gender matched individuals were, also, selected as a control group. CD40 expression was measured on peripheral blood samples by flowcytometry at patient's presentation as well as after 4 cycles of chemotherapy. This study showed that there's significant decrease in the mean values of % of CD40 on B-cell in patients with NHL in all stages when compared with normal control group. Also the study showed that there's statistical significant correlation between percent of CD40 on B-lymphocytes and stage of lymphoma, i.e., the more advanced stage, the lower the % of CD40 on B-cell. After receiving a corresponding treatment, the CD40 expression is increased in significant correlation with the response to treatment. (This is a preliminary result after 4 cycles of CHOP treatment). We concluded that CD40 Lymphocyte development occurs in discrete functional steps that are defined by the onset of expression is highly expressed in healthy subjects and its expression on B-lymphocyte is decreased with advanced stage of NHL. Percent of CD40 on B-lymphocyte can be considered as an evaluation marker for outcome of treatment in NHL patients as its expression is increased in responding patients.

Dysregulated sleep-wake cycles in young people are associated with emerging stages of major mental disorders.

PubMed

Scott, Elizabeth M; Robillard, Rébecca; Hermens, Daniel F; Naismith, Sharon L; Rogers, Naomi L; Ip, Tony K C; White, Django; Guastella, Adam; Whitwell, Bradley; Smith, Kristie Leigh; Hickie, Ian B

2016-02-01

To determine if disturbed sleep-wake cycle patterns in young people with evolving mental disorder are associated with stages of illness. The sleep-wake cycle was monitored using actigraphy across 4 to 22 days. Participants (21 healthy controls and 154 persons seeking help for mental health problems) were aged between 12 and 30 years. Those persons seeking mental health care were categorized as having mild symptoms (stage 1a), an 'attenuated syndrome' (stage 1b) or an 'established mental disorder' (stage 2+). The proportions of individuals with a delayed weekdays sleep schedule increased progressively across illness stages: 9.5% of controls, 11.1% of stage 1a, 25.6% of stage 1b, and 50.0% of stage 2+ (χ(2) (3 d.f.) = 18.4, P < 0.001). A similar pattern was found for weekends (χ(2) (3 d.f.) = 7.6, P = 0.048). Compared with controls, stage 1b participants had later sleep onset on weekends (P = 0.015), and participants at stages 1b and 2+ had later sleep offset on both weekdays and weekends (P < 0.020). Compared with controls, all participants with mental disorders had more wake after sleep onset (P < 0.029) and those at stages 1a and 2+ had lower sleep efficiency (P < 0.040). Older age, medicated status and later weekdays sleep offset were found to be the three strongest correlates of later versus earlier clinical stages. In relation to clinical staging of common mental disorders in young people, the extent of delayed sleep phase is associated with more severe or persistent phases of illness. © 2014 Wiley Publishing Asia Pty Ltd.

Quality improvement on chemistry practicum courses through implementation of 5E learning cycle

NASA Astrophysics Data System (ADS)

Merdekawati, Krisna

2017-03-01

Two of bachelor of chemical education's competences are having practical skills and mastering chemistry material. Practicum courses are organized to support the competency achievement. Based on observation and evaluation, many problems were found in the implementation of practicum courses. Preliminary study indicated that 5E Learning Cycle can be used as an alternative solution in order to improve the quality of chemistry practicum course. The 5E Learning Cycle can provide positive influence on the achievement of the competence, laboratory skills, and students' understanding. The aim of the research was to describe the feasibility of implementation of 5E Learning Cycle on chemistry practicum courses. The research was based on phenomenology method in qualitative approach. The participants of the research were 5 person of chemistry laboratory manager (lecturers at chemistry and chemistry education department). They concluded that the 5E Learning Cycle could be implemented to improve the quality of the chemistry practicum courses. Practicum guides and assistant competences were organized to support the implementation of 5E Learning Cycle. It needed training for assistants to understand and implement in the stages of 5E Learning Cycle. Preparation of practical guidelines referred to the stages of 5E Learning Cycle, started with the introduction of contextual and applicable materials, then followed with work procedures that accommodate the stage of engagement, exploration, explanation, extension, and evaluation

The seminiferous epithelium cycle and its duration in different breeds of dog (Canis familiaris)

PubMed Central

Soares, Jaqueline M; Avelar, Gleide F; França, Luiz R

2009-01-01

Testis structure and function in dogs are relatively poorly investigated. The aim of the present study was to carry out a comparative investigation of the stages of the seminiferous epithelium cycle and its duration in different breeds of dog. Fifty-six sexually mature dogs (mongrel, n = 12; pinscher, n = 12; beagle, n = 5; American pit bull, n = 9; poodle, n = 12; and Labrador retriever, n = 6) were analysed. Intratesticular injections of tritiated thymidine were given to determine the duration of spermatogenesis. Orchiectomy was performed at different time periods following injection (1 h, 2 and 4 weeks). Testis fragments were embedded in plastic and routinely prepared for histological and autoradiographic evaluations. Eight stages were characterized based on the acrosome system. Significant (P < 0.05) differences were found for the frequencies of the different stages characterized (except Stages V, VI and VIII), particularly for the mongrel. Stage IV (when spermiation occurs) was the most frequent in all six breeds (∼25%), whereas Stages II and VIII were the least frequent (< 8%). Each spermatogenic cycle and the total duration of spermatogenesis lasted 13.73 ± 0.03 and 61.9 ± 0.14 days, respectively, for the mongrel, poodle, pinscher, beagle, and Labrador retriever. These values were ∼10% lower (P < 0.03) for the American pit bull (12.55 ± 0.26 and 56.5 ± 1.17 days, respectively). To our knowledge, this is the first comprehensive study to perform a careful investigation of stage frequencies and seminiferous epithelium cycle duration in this very important domestic species. PMID:19627387

Discovery of cashmere goat (Capra hircus) microRNAs in skin and hair follicles by Solexa sequencing.

PubMed

Yuan, Chao; Wang, Xiaolong; Geng, Rongqing; He, Xiaolin; Qu, Lei; Chen, Yulin

2013-07-28

MicroRNAs (miRNAs) are a large family of endogenous, non-coding RNAs, about 22 nucleotides long, which regulate gene expression through sequence-specific base pairing with target mRNAs. Extensive studies have shown that miRNA expression in the skin changes remarkably during distinct stages of the hair cycle in humans, mice, goats and sheep. In this study, the skin tissues were harvested from the three stages of hair follicle cycling (anagen, catagen and telogen) in a fibre-producing goat breed. In total, 63,109,004 raw reads were obtained by Solexa sequencing and 61,125,752 clean reads remained for the small RNA digitalisation analysis. This resulted in the identification of 399 conserved miRNAs; among these, 326 miRNAs were expressed in all three follicular cycling stages, whereas 3, 12 and 11 miRNAs were specifically expressed in anagen, catagen, and telogen, respectively. We also identified 172 potential novel miRNAs by Mireap, 36 miRNAs were expressed in all three cycling stages, whereas 23, 29 and 44 miRNAs were specifically expressed in anagen, catagen, and telogen, respectively. The expression level of five arbitrarily selected miRNAs was analyzed by quantitative PCR, and the results indicated that the expression patterns were consistent with the Solexa sequencing results. Gene Ontology and KEGG pathway analyses indicated that five major biological pathways (Metabolic pathways, Pathways in cancer, MAPK signalling pathway, Endocytosis and Focal adhesion) accounted for 23.08% of target genes among 278 biological functions, indicating that these pathways are likely to play significant roles during hair cycling. During all hair cycle stages of cashmere goats, a large number of conserved and novel miRNAs were identified through a high-throughput sequencing approach. This study enriches the Capra hircus miRNA databases and provides a comprehensive miRNA transcriptome profile in the skin of goats during the hair follicle cycle.

Cell cycle re-entry sensitizes podocytes to injury induced death.

PubMed

Hagen, Manuel; Pfister, Eva; Kosel, Andrea; Shankland, Stuart; Pippin, Jeffrey; Amann, Kerstin; Daniel, Christoph

2016-07-17

Podocytes are terminally differentiated renal cells, lacking the ability to regenerate by proliferation. However, during renal injury, podocytes re-enter into the cell cycle but fail to divide. Earlier studies suggested that re-entry into cell cycle results in loss of podocytes, but a direct evidence for this is lacking. Therefore, we established an in vitro model to test the consequences of re-entry into the cell cycle on podocyte survival. A mouse immortalized podocyte cell line was differentiated to non-permissive podocytes and stimulated with e.g. growth factors. Stimulated cells were analyzed for mRNA-expression or stained for cell cycle analysis using flow cytometry and immunocytofluorescence microscopy. After stimulation to re-entry into cell cycle, podocytes were stressed with puromycin aminonucleoside (PAN) and analyzed for survival. During permissive stage more than 40% of immortalized podocytes were in the S-phase. In contrast, S-phase in non-permissive differentiated podocytes was reduced to 5%. Treatment with b-FGF dose dependently induced re-entry into cell cycle increasing the number of podocytes in the S-phase to 10.7% at an optimal bFGF dosage of 10 ng/ml. Forty eight hours after stimulation with bFGF the number of bi-nucleated podocytes significantly increased. A secondary injury stimulus significantly reduced podocyte survival preferentially in bi-nucleated podocytes In conclusion, stimulation of podocytes using bFGF was able to induce re-entry of podocytes into the cell cycle and to sensitize the cells for cell death by secondary injuries. Therefore, this model is appropriate for testing new podocyte protective substances that can be used for therapy.

Accounting for length-bias and selection effects in estimating the distribution of menstrual cycle length

PubMed Central

Lum, Kirsten J.; Sundaram, Rajeshwari; Louis, Thomas A.

2015-01-01

Prospective pregnancy studies are a valuable source of longitudinal data on menstrual cycle length. However, care is needed when making inferences of such renewal processes. For example, accounting for the sampling plan is necessary for unbiased estimation of the menstrual cycle length distribution for the study population. If couples can enroll when they learn of the study as opposed to waiting for the start of a new menstrual cycle, then due to length-bias, the enrollment cycle will be stochastically larger than the general run of cycles, a typical property of prevalent cohort studies. Furthermore, the probability of enrollment can depend on the length of time since a woman’s last menstrual period (a backward recurrence time), resulting in selection effects. We focus on accounting for length-bias and selection effects in the likelihood for enrollment menstrual cycle length, using a recursive two-stage approach wherein we first estimate the probability of enrollment as a function of the backward recurrence time and then use it in a likelihood with sampling weights that account for length-bias and selection effects. To broaden the applicability of our methods, we augment our model to incorporate a couple-specific random effect and time-independent covariate. A simulation study quantifies performance for two scenarios of enrollment probability when proper account is taken of sampling plan features. In addition, we estimate the probability of enrollment and the distribution of menstrual cycle length for the study population of the Longitudinal Investigation of Fertility and the Environment Study. PMID:25027273

Evaluating Managerial Styles for System Development Life Cycle Stages to Ensure Software Project Success

ERIC Educational Resources Information Center

Kocherla, Showry

2012-01-01

Information technology (IT) projects are considered successful if they are completed on time, within budget, and within scope. Even though, the required tools and methodologies are in place, IT projects continue to fail at a higher rate. Current literature lacks explanation for success within the stages of system development life-cycle (SDLC) such…

The Evaluation Life Cycle: A Retrospective Assessment of Stages and Phases of the Circles of Care Initiative

ERIC Educational Resources Information Center

Bess, Gary; Allen, James; Deters, Pamela B.

2004-01-01

A life cycle metaphor characterizes the evolving relationship between the evaluator and program staff. This framework suggests that common developmental dynamics occur in roughly the same order across groups and settings. There are stage-specific dynamics that begin with Pre-History, which characterize the relationship between the grantees and…

Influence of Life Cycle Stage on Family Social Climate and Attitudes Toward the Residential Environment.

ERIC Educational Resources Information Center

Inman, Marjorie

The existing physical forms of housing are not always compatible with prevalent social patterns. To investigate the relationship between family system characteristics and attitudes about residential space, 64 Indiana families in 4 stages of the family life cycle (early years with no children, crowded years with at least one preschool child, peak…

The Effects of an Intergroup Development OD Intervention as Conditioned by the Life Cycle State of Organizations: A Laboratory Experiment.

ERIC Educational Resources Information Center

Randolph, W. Alan; Posner, Barry Z.

1982-01-01

Explored the effectiveness of an intergroup development organization development (OD) intervention at different stages of an organization's life cycle through four simulated organizations. Results suggest intergroup development interventions can be effective at any life stage, but impacts will be felt in different outcome measures and perceptual…

Organizational Life Cycles and the Development of the National College for School Leadership: An Antipodean View

ERIC Educational Resources Information Center

Mulford, Bill

2004-01-01

This article employs organizational life cycle, organizational learning stages and group development stages literature to examine my experiences at the National College for School Leadership (NCSL) during its establishment phase. Support was found, and other foci suggested, for this literature. As well, future issues to be faced by the NCSL were…

Assessing subunit dependency of the Plasmodium proteasome using small molecule inhibitors and active site probes.

PubMed

Li, Hao; van der Linden, Wouter A; Verdoes, Martijn; Florea, Bogdan I; McAllister, Fiona E; Govindaswamy, Kavitha; Elias, Joshua E; Bhanot, Purnima; Overkleeft, Herman S; Bogyo, Matthew

2014-08-15

The ubiquitin-proteasome system (UPS) is a potential pathway for therapeutic intervention for pathogens such as Plasmodium, the causative agent of malaria. However, due to the essential nature of this proteolytic pathway, proteasome inhibitors must avoid inhibition of the host enzyme complex to prevent toxic side effects. The Plasmodium proteasome is poorly characterized, making rational design of inhibitors that induce selective parasite killing difficult. In this study, we developed a chemical probe that labels all catalytic sites of the Plasmodium proteasome. Using this probe, we identified several subunit selective small molecule inhibitors of the parasite enzyme complex. Treatment with an inhibitor that is specific for the β5 subunit during blood stage schizogony led to a dramatic decrease in parasite replication while short-term inhibition of the β2 subunit did not affect viability. Interestingly, coinhibition of both the β2 and β5 catalytic subunits resulted in enhanced parasite killing at all stages of the blood stage life cycle and reduced parasite levels in vivo to barely detectable levels. Parasite killing was achieved with overall low host toxicity, something that has not been possible with existing proteasome inhibitors. Our results highlight differences in the subunit dependency of the parasite and human proteasome, thus providing a strategy for development of potent antimalarial drugs with overall low host toxicity.

Measurement of formaldehyde concentrations in a subatmospheric steam-formaldehyde autoclave.

PubMed Central

Marcos, D; Wiseman, D

1979-01-01

A method has been developed for measuring formaldehyde concentrations in a subatmospheric steam-formaldehyde autoclave. Data obtained using this method indicate that the concentration of formaldehyde in the chamber atmosphere is not homogeneous and that it decreases rapidly with time. The penetration of formaldehyde vapour into narrow tubes has also been investigated and was shown to be dependent on the length-to-bore ratio of the tubes. The formaldehyde concentration within the tubes could be increased by using a lower vacuum in the air removal stage at the beginning of the cycle. PMID:572833

CHD chromatin remodelers and the transcription cycle

PubMed Central

Murawska, Magdalena

2011-01-01

It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by “opening” or “closing” chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but also are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts. PMID:22223048

Intravenous infusion of PAF affects ovulation, fertilization and preimplantation embryonic development in NZB x NZW F1 hybrid mice.

PubMed

Sakellariou, Maria; Drakakis, Peter; Antonopoulou, Smaragdi; Anagnostou, Elli; Loutradis, Dimitris; Patargias, Theoxaris

2008-03-01

Platelet Activating Factor (PAF) is a bioactive phospholipid, which exhibits a variety of biological activities and plays a significant role in all aspects of reproduction. In this work, a single intravenous injection of various concentrations of PAF shortly after Human Chorionic Gonadotropin (HCG) administration as well as 24 and 48 h before HCG administration was studied in NZB x NZW F1 hybrid mice. Optimum results were observed when PAF was injected just after the administration of HCG. In this protocol, the concentrations of PAF exhibited bell-shaped response to every stage of development. Any concentration of PAF between 5.5 x 10(-11) and 5.5 x 10(-15)g/g b.w., caused an improved ovulation rate, an increased fertilization rate, an increased rate of cell cycle and an enhanced hatching blastocyst rate (P<0.05 for all stages). Injection of lyso-PAF had no effect in any stage. Our data show that the effect of PAF on early stages of embryo development in vitro is dependent on its way of administration, on the concentrations used as well as on the time PAF is injected.

Blastulation rates decline in a linear fashion from euploid to aneuploid embryos with single versus multiple chromosomal errors.

PubMed

Vega, Mario; Breborowicz, Andrzej; Moshier, Erin L; McGovern, Peter G; Keltz, Martin D

2014-08-01

To test the hypothesis that the blastulation rate is higher in euploid embryos than in aneuploid embryos as assessed by cleavage-stage biopsy with array-comprehensive genomic hybridization (aCGH). Retrospective cohort study. University-affiliated institution. Forty-one patients with 48 in vitro fertilization (IVF) cycles and 385 embryos that underwent cleavage-stage preimplantation genetic screening (PGS) with aCGH at the Continuum Reproductive Center between January 2010 and September 2013. None. Probability of blastocyst and/or fully expanded or hatching blastocyst (FEHB) progression depending on number of chromosomal abnormalities. Euploid embryos are twice as likely to progress to blastocyst and three times as likely to progress to FEHB than aneuploid embryos: 76% versus 37% and 56% versus 18%, respectively. For every additional chromosomal abnormality, the likelihood of progressing to the blastocyst stage decreases by 22% and the likelihood of progressing to FEHB decreases by 33%. Euploid embryos are far more likely than aneuploid embryos to progress to the blastocyst and FEHB stages. There is a linear decrease in probability of blastulation with the increasing number of chromosomal abnormalities. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A survival-reproduction trade-off in entomopathogenic nematodes mediated by their bacterial symbionts.

PubMed

Emelianoff, Vanya; Chapuis, Elodie; Le Brun, Nathalie; Chiral, Magali; Moulia, Catherine; Ferdy, Jean-Baptiste

2008-04-01

In this work, we investigate the investment of entomopathogenic Steinernema nematodes (Rhabditidae) in their symbiotic association with Xenorhabdus bacteria (Enterobacteriaceae). Their life cycle comprises two phases: (1) a free stage in the soil, where infective juveniles (IJs) of the nematode carry bacteria in a digestive vesicle and search for insect hosts, and (2) a parasitic stage into the insect where bacterial multiplication, nematode reproduction, and production of new IJs occur. Previous studies clearly showed benefits to the association for the nematode during the parasitic stage, but preliminary data suggest the existence of costs to the association for the nematode in free stage. IJs deprived from their bacteria indeed survive longer than symbiotic ones. Here we show that those bacteria-linked costs and benefits lead to a trade-off between fitness traits of the symbiotic nematodes. Indeed IJs mortality positively correlates with their parasitic success in the insect host for symbiotic IJs and not for aposymbiotic ones. Moreover mortality and parasitic success both positively correlate with the number of bacteria carried per IJ, indicating that the trade-off is induced by symbiosis. Finally, the trade-off intensity depends on parental effects and, more generally, is greater under restrictive environmental conditions.

A Simplified Model for Detonation Based Pressure-Gain Combustors

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

2010-01-01

A time-dependent model is presented which simulates the essential physics of a detonative or otherwise constant volume, pressure-gain combustor for gas turbine applications. The model utilizes simple, global thermodynamic relations to determine an assumed instantaneous and uniform post-combustion state in one of many envisioned tubes comprising the device. A simple, second order, non-upwinding computational fluid dynamic algorithm is then used to compute the (continuous) flowfield properties during the blowdown and refill stages of the periodic cycle which each tube undergoes. The exhausted flow is averaged to provide mixed total pressure and enthalpy which may be used as a cycle performance metric for benefits analysis. The simplicity of the model allows for nearly instantaneous results when implemented on a personal computer. The results compare favorably with higher resolution numerical codes which are more difficult to configure, and more time consuming to operate.

Monoamines and sexual function in rats bred for increased catatonic reactivity.

PubMed

Klochkov, D V; Alekhina, T A; Kuznetsova, E G; Barykina, N N

2009-07-01

Body weight, ovary and uterus weight, the nature of estral cycles, and hypothalamus dopamine and noradrenaline levels and plasma testosterone levels were studied in female GC rats, bred for increased catatonic reactivity, at different stages of the estral cycle (estrus, proestrus). The outbred Wistar strain served as controls. On the background of decreased body weight, GC females showed impairments to the morphological cyclical changes in the ovaries and uterus, with a reduction in ovary weight in diestrus (p < 0.01) and a smaller estrogen-dependent increase in uterus weight in estrus as compared with Wistar females. On the background of decreases in dopamine and noradrenaline contents in the hypothalamus, GC rats showed higher levels of these monoamines in estrus and lower levels in diestrus. Plasma testosterone levels in female GC rats were higher in diestrus than in estrus and in Wistar rats.

The activity of thymidine phosphorylase in the uterine myomas and the myometrium in perimenopausal women.

PubMed

Miszczak-Zaborska, E; Greger, J; Wozniak, K; Kowalska-Koprek, U; Pajszczyk-Kieszkiewicz, T

1997-01-01

The activity of thymidine phosphorylase (dThdPase) in the myometrium and uterine myomas has been investigated in perimenopausal women. Differences in the activity of dThdPase have been found depending on the myoma type, menopause stage and the phase of the menstrual cycle in which the surgery was performed. The enzyme in the cytoplasmatic soluble fraction obtained at 50,000 x g was the most active in cellular leiomyomas of the follicular phase, the least in adenomyomas of the luteal phase of the menstrual cycle, whereas its activity in myometrium was always unchanged. Greater differences can be observed in the activity of dThdPase after a partial purification of the enzyme from myomas. It seems that the increase in dThdPase activity may point to its correlation with transient, premalignant tumor which may later transform into malignant forms.

Repair of DNA Damage Induced by the Cytidine Analog Zebularine Requires ATR and ATM in Arabidopsis[OPEN

PubMed Central

Liu, Chun-Hsin; Finke, Andreas; Díaz, Mariana; Rozhon, Wilfried; Poppenberger, Brigitte; Baubec, Tuncay; Pecinka, Ales

2015-01-01

DNA damage repair is an essential cellular mechanism that maintains genome stability. Here, we show that the nonmethylable cytidine analog zebularine induces a DNA damage response in Arabidopsis thaliana, independent of changes in DNA methylation. In contrast to genotoxic agents that induce damage in a cell cycle stage-independent manner, zebularine induces damage specifically during strand synthesis in DNA replication. The signaling of this damage is mediated by additive activity of ATAXIA TELANGIECTASIA MUTATED AND RAD3-RELATED and ATAXIA TELANGIECTASIA MUTATED kinases, which cause postreplicative cell cycle arrest and increased endoreplication. The repair requires a functional STRUCTURAL MAINTENANCE OF CHROMOSOMES5 (SMC5)-SMC6 complex and is accomplished predominantly by synthesis-dependent strand-annealing homologous recombination. Here, we provide insight into the response mechanism for coping with the genotoxic effects of zebularine and identify several components of the zebularine-induced DNA damage repair pathway. PMID:26023162

The temporal organization of processes of cell reproduction and its connection with rhythms of radiosensitivity of the body

NASA Technical Reports Server (NTRS)

Druzhinin, Y. P.; Romanov, Y. A.; Vatsek, A.

1974-01-01

Radiosensitivity of individual phases of the mitotic cycle was studied in synchronous cell cultures and in several biological objects. It was found that radiosensitivity changed essentially according to phases of the mitotic cycle, depending on the kind of cells, evaluation criteria and the radiation dosage. Tests on partially synchronized HeLa cell populations, according to the criterion of survival, showed them most sensitive during mitosis, as well as in later G sub 1- or early DNA-synthesizing stages. With radiation in doses of 300 rad, the proportion of surviving cells showed a sensitivity directly before DNA synthesis of approximately 4 times higher than the later S-phase and during the major portion of G sub 1- and G sub 2-periods. Sensitivity of cells in mitosis was approximately 3 times higher than in late G sub 1- and early S-phases.

Nucleation and Early Stages of Layer-by-Layer Growth of Metal Organic Frameworks on Surfaces

PubMed Central

2015-01-01

High resolution atomic force microscopy (AFM) is used to resolve the evolution of crystallites of a metal organic framework (HKUST-1) grown on Au(111) using a liquid-phase layer-by-layer methodology. The nucleation and faceting of individual crystallites is followed by repeatedly imaging the same submicron region after each cycle of growth and we find that the growing surface is terminated by {111} facets leading to the formation of pyramidal nanostructures for [100] oriented crystallites, and triangular [111] islands with typical lateral dimensions of tens of nanometres. AFM images reveal that crystallites can grow by 5–10 layers in each cycle. The growth rate depends on crystallographic orientation and the morphology of the gold substrate, and we demonstrate that under these conditions the growth is nanocrystalline with a morphology determined by the minimum energy surface. PMID:26709359

RL-10 Based Combined Cycle For A Small Reusable Single-Stage-To-Orbit Launcher

NASA Technical Reports Server (NTRS)

Balepin, Vladimir; Price, John; Filipenco, Victor

1999-01-01

This paper discusses a new application of the combined propulsion known as the KLIN(TM) cycle, consisting of a thermally integrated deeply cooled turbojet (DCTJ) and liquid rocket engine (LRE). If based on the RL10 rocket engine family, the KLIN (TM) cycle makes a small single-stage-to-orbit (SSTO) reusable launcher feasible and economically very attractive. Considered in this paper are the concept and parameters of a small SSTO reusable launch vehicle (RLV) powered by the KLIN (TM) cycle (sSSTO(TM)) launcher. Also discussed are the benefits of the small launcher, the reusability, and the combined cycle application. This paper shows the significant reduction of the gross take off weight (GTOW) and dry weight of the KLIN(TM) cycle-powered launcher compared to an all-rocket launcher.

Estimation of gonad volume, fecundity, and reproductive stage of shovelnose sturgeon using sonography and endoscopy with application to the endangered pallid sturgeon

USGS Publications Warehouse

Bryan, J.L.; Wildhaber, M.L.; Papoulias, D.M.; DeLonay, A.J.; Tillitt, D.E.; Annis, M.L.

2007-01-01

Most species of sturgeon are declining in the Mississippi River Basin of North America including pallid (Scaphirhynchus albus F. and R.) and shovelnose sturgeons (S. platorynchus R.). Understanding the reproductive cycle of sturgeon in the Mississippi River Basin is important in evaluating the status and viability of sturgeon populations. We used non-invasive, non-lethal methods for examining internal reproductive organs of shovelnose and pallid sturgeon. We used an ultrasound to measure egg diameter, fecundity, and gonad volume; endoscope was used to visually examine the gonad. We found the ultrasound to accurately measure the gonad volume, but it underestimated egg diameter by 52%. After correcting for the measurement error, the ultrasound accurately measured the gonad volume but it was higher than the true gonad volume for stages I and II. The ultrasound underestimated the fecundity of shovelnose sturgeon by 5%. The ultrasound fecundity was lower than the true fecundity for stage III and during August. Using the endoscope, we viewed seven different egg color categories. Using a model selection procedure, the presence of four egg categories correctly predicted the reproductive stage ± one reproductive stage of shovelnose sturgeon 95% of the time. For pallid sturgeon, the ultrasound overestimated the density of eggs by 49% and the endoscope was able to view eggs in 50% of the pallid sturgeon. Individually, the ultrasound and endoscope can be used to assess certain reproductive characteristics in sturgeon. The use of both methods at the same time can be complementary depending on the parameter measured. These methods can be used to track gonad characteristics, including measuring Gonadosomatic Index in individuals and/or populations through time, which can be very useful when associating gonad characteristics with environmental spawning triggers or with repeated examinations of individual fish throughout the reproductive cycle.

Histone deacetylases play a major role in the transcriptional regulation of the Plasmodium falciparum life cycle.

PubMed

Chaal, Balbir K; Gupta, Archna P; Wastuwidyaningtyas, Brigitta D; Luah, Yen-Hoon; Bozdech, Zbynek

2010-01-22

The apparent paucity of molecular factors of transcriptional control in the genomes of Plasmodium parasites raises many questions about the mechanisms of life cycle regulation in these malaria parasites. Epigenetic regulation has been suggested to play a major role in the stage specific gene expression during the Plasmodium life cycle. To address some of these questions, we analyzed global transcriptional responses of Plasmodium falciparum to a potent inhibitor of histone deacetylase activities (HDAC). The inhibitor apicidin induced profound transcriptional changes in multiple stages of the P. falciparum intraerythrocytic developmental cycle (IDC) that were characterized by rapid activation and repression of a large percentage of the genome. A major component of this response was induction of genes that are otherwise suppressed during that particular stage of the IDC or specific for the exo-erythrocytic stages. In the schizont stage, apicidin induced hyperacetylation of histone lysine residues H3K9, H4K8 and the tetra-acetyl H4 (H4Ac4) and demethylation of H3K4me3. Interestingly, we observed overlapping patterns of chromosomal distributions between H4K8Ac and H3K4me3 and between H3K9Ac and H4Ac4. There was a significant but partial association between the apicidin-induced gene expression and histone modifications, which included a number of stage specific transcription factors. Taken together, inhibition of HDAC activities leads to dramatic de-regulation of the IDC transcriptional cascade, which is a result of both disruption of histone modifications and up-regulation of stage specific transcription factors. These findings suggest an important role of histone modification and chromatin remodeling in transcriptional regulation of the Plasmodium life cycle. This also emphasizes the potential of P. falciparum HDACs as drug targets for malaria chemotherapy.

Cell cycle entry triggers a switch between two modes of Cdc42 activation during yeast polarization

PubMed Central

Witte, Kristen; Strickland, Devin; Glotzer, Michael

2017-01-01

Cell polarization underlies many cellular and organismal functions. The GTPase Cdc42 orchestrates polarization in many contexts. In budding yeast, polarization is associated with a focus of Cdc42•GTP which is thought to self sustain by recruiting a complex containing Cla4, a Cdc42-binding effector, Bem1, a scaffold, and Cdc24, a Cdc42 GEF. Using optogenetics, we probe yeast polarization and find that local recruitment of Cdc24 or Bem1 is sufficient to induce polarization by triggering self-sustaining Cdc42 activity. However, the response to these perturbations depends on the recruited molecule, the cell cycle stage, and existing polarization sites. Before cell cycle entry, recruitment of Cdc24, but not Bem1, induces a metastable pool of Cdc42 that is sustained by positive feedback. Upon Cdk1 activation, recruitment of either Cdc24 or Bem1 creates a stable site of polarization that induces budding and inhibits formation of competing sites. Local perturbations have therefore revealed unexpected features of polarity establishment. DOI: http://dx.doi.org/10.7554/eLife.26722.001 PMID:28682236

A translating stage system for µ-PIV measurements surrounding the tip of a migrating semi-infinite bubble.

PubMed

Smith, B J; Yamaguchi, E; Gaver, D P

2010-01-01

We have designed, fabricated and evaluated a novel translating stage system (TSS) that augments a conventional micro particle image velocimetry (µ-PIV) system. The TSS has been used to enhance the ability to measure flow fields surrounding the tip of a migrating semi-infinite bubble in a glass capillary tube under both steady and pulsatile reopening conditions. With conventional µ-PIV systems, observations near the bubble tip are challenging because the forward progress of the bubble rapidly sweeps the air-liquid interface across the microscopic field of view. The translating stage mechanically cancels the mean bubble tip velocity, keeping the interface within the microscope field of view and providing a tenfold increase in data collection efficiency compared to fixed-stage techniques. This dramatic improvement allows nearly continuous observation of the flow field over long propagation distances. A large (136-frame) ensemble-averaged velocity field recorded with the TSS near the tip of a steadily migrating bubble is shown to compare well with fixed-stage results under identical flow conditions. Use of the TSS allows the ensemble-averaged measurement of pulsatile bubble propagation flow fields, which would be practically impossible using conventional fixed-stage techniques. We demonstrate our ability to analyze these time-dependent two-phase flows using the ensemble-averaged flow field at four points in the oscillatory cycle.

Endogenous Life Cycle of Eimeria marmosopos (Apicomplexa: Eimeriidae) from the Opossum, Didelphis marsupialis (Didelphimorphia: Didelphidae) in Costa Rica.

PubMed

Chinchilla, Misael; Valerio, Idalia; Duszynski, Donald

2015-08-01

The endogenous life cycle of Eimeria marmosopos was studied in experimentally infected young opossums, Didelphis marsupialis . All the endogenous stages were located in the epithelial cells of villi in the small intestine. Giemsa-stained mucosal scrapings and histological sections were studied for the diagnosis of all the life cycle stages. Eimeria marmosopos has 3 generations of meronts (M) that differ by size, shape, and number of merozoites (m), which also differ in their size, shape, and location of their nuclei within the cytoplasm of the meronts. The 3 meront types, M(1)-M(3), respectively, had 8-15 (m(1)), 4-9 (m(2)), and 22-30 (m(3)) merozoites. Macrogametocytes and microgametocytes, as well as macrogametes and microgametes, completed the sexual cycle, finishing with the formation of unsporulated oocysts. This parasite's endogenous development produced severe intestinal lesions in experimentally infected opossums. There are 56 Eimeria species known from all marsupials worldwide, but this is the first complete life cycle in which both the asexual and sexual stages have been documented.

Variations in the Life Cycle of Anemone patens L. (Ranunculaceae) in Wild Populations of Canada

PubMed Central

Kricsfalusy, Vladimir

2016-01-01

Based on a study of a perennial herb Anemone patens L. (Ranunculaceae) in a variety of natural habitats in Saskatchewan, Canada, eight life stages (seed, seedling, juvenile, immature, vegetative, generative, subsenile, and senile) are distinguished and characterized in detail. The species ontogenetic growth patterns are investigated. A. patens has a long life cycle that may last for several decades which leads to the formation of compact clumps. The distribution and age of clumps vary substantially in different environments with different levels of disturbance. The plant ontogeny includes the regular cycle with reproduction occurring through seeds. There is an optional subsenile vegetative disintegration at the end of the life span. The following variations in the life cycle of A. patens are identified: with slower development in young age, with an accelerated development, with omission of the generative stage, with retrogression to previous life stages in mature age, and with vegetative dormancy. The range of variations in the life cycle of A. patens may play an important role in maintaining population stability in different environmental conditions and management regimes. PMID:27376340

Oxaliplatin in combination with protracted-infusion fluorouracil and radiation: report of a clinical trial for patients with esophageal cancer.

PubMed

Khushalani, Nikhil I; Leichman, Cynthia Gail; Proulx, Gary; Nava, Hector; Bodnar, Lisa; Klippenstein, Donald; Litwin, Alan; Smith, Judy; Nava, Enriqueta; Pendyala, Lakshmi; Smith, Patrick; Greco, William; Berdzik, Joanne; Douglass, Harold; Leichman, Lawrence

2002-06-15

To identify a dose and schedule of oxaliplatin (OXP) to be safely administered in combination with protracted-infusion (PI) fluorouracil (5-FU) and external-beam radiation therapy (XRT) for patients with primary esophageal carcinoma (EC). Eligibility included therapeutically naïve EC patients with clinical disease stages II, III, or IV. Initial doses and schedules for cycle 1 consisted of OXP 85 mg/m(2) on days 1, 15, and 29; PI 5-FU 180 mg/m(2) for 24 hours for 35 days; and XRT 1.8 Gy in 28 fractions starting on day 8. At completion of cycle 1, eligible patients could undergo an operation or begin cycle 2 without XRT. Postoperative patients were eligible for cycle 2. Stage IV patients were allowed three cycles in the absence of disease progression. OXP and 5-FU increases were based on dose-limiting toxicity (DLT) encountered in cohorts of three consecutive patients. Thirty-eight eligible patients received therapy: 22 noninvasively staged as IV and 16 noninvasively staged as II and III. Thirty-six patients completed cycle 1, 29 patients started cycle 2, and 24 patients completed cycle 2. The combined-modality therapy was well tolerated, but DLT prevented OXP and 5-FU escalation. No grade 4 hematologic toxicity was noted. Eleven grade 3 and two grade 4 clinical toxicities were noted in eight patients. After cycle 1, 29 patients (81%) had no cancer in the esophageal mucosa. Thirteen patients underwent an operation with intent to resect the esophagus; five patients (38%) exhibited pathologic complete responses. OXP 85 mg/m(2) on days 1, 15, and 29 administered with PI 5-FU and XRT is safe, tolerable, and seems effective against primary EC. The role of OXP in multimodality regimens against EC deserves further evaluation.

Phenoloxidase activity among developmental stages and pupal cell types of the ground beetle Carabus (Chaetocarabus) lefebvrei (Coleoptera, Carabidae).

PubMed

Giglio, Anita; Giulianini, Piero Giulio

2013-04-01

In ecological immunology is of great importance the study of the immune defense plasticity as response to a variable environment. In holometabolous insects the fitness of each developmental stage depends on the capacity to mount a response (i.e. physiological, behavioral) under environmental pressure. The immune response is a highly dynamic trait closely related to the ecology of organism and the variation in the expression of an immune system component may affect another fitness relevant trait of organism (i.e. growth, reproduction). The present research quantified immune function (total and differential number of hemocytes, phagocytosis in vivo and activity of phenoloxidase) in the pupal stage of Carabus (Chaetocarabus) lefebvrei. Moreover, the cellular and humoral immune function was compared across the larval, pupal and adult stages to evaluate the changes in immunocompetence across the developmental stages. Four types of circulating hemocytes were characterized via transmission electron microscopy in the pupal stage: prohemocytes, plasmatocytes, granulocytes and oenocytoids. The artificial non-self-challenge treatments performed in vivo have shown that plasmatocytes and granulocytes are responsible for phagocytosis. The level of active phenoloxidase increases with the degree of pigmentation of the cuticle in each stage. In C. lefebvrei, there are different strategies in term of immune response to enhance the fitness of each life stage. The results have shown that the variation in speed and specificity of immune function across the developmental stages is correlated with differences in infection risk, life expectancy and biological function of the life cycle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Host-mediated impairment of parasite maturation during blood-stage Plasmodium infection

PubMed Central

Khoury, David S.; Cromer, Deborah; Akter, Jasmin; Sebina, Ismail; Elliott, Trish; Thomas, Bryce S.; Soon, Megan S. F.; James, Kylie R.; Best, Shannon E.; Haque, Ashraful; Davenport, Miles P.

2017-01-01

Severe malaria and associated high parasite burdens occur more frequently in humans lacking robust adaptive immunity to Plasmodium falciparum. Nevertheless, the host may partly control blood-stage parasite numbers while adaptive immunity is gradually established. Parasite control has typically been attributed to enhanced removal of parasites by the host, although in vivo quantification of this phenomenon remains challenging. We used a unique in vivo approach to determine the fate of a single cohort of semisynchronous, Plasmodium berghei ANKA- or Plasmodium yoelii 17XNL-parasitized red blood cells (pRBCs) after transfusion into naive or acutely infected mice. As previously shown, acutely infected mice, with ongoing splenic and systemic inflammatory responses, controlled parasite population growth more effectively than naive controls. Surprisingly, however, this was not associated with accelerated removal of pRBCs from circulation. Instead, transfused pRBCs remained in circulation longer in acutely infected mice. Flow cytometric assessment and mathematical modeling of intraerythrocytic parasite development revealed an unexpected and substantial slowing of parasite maturation in acutely infected mice, extending the life cycle from 24 h to 40 h. Importantly, impaired parasite maturation was the major contributor to control of parasite growth in acutely infected mice. Moreover, by performing the same experiments in rag1−/− mice, which lack T and B cells and mount weak inflammatory responses, we revealed that impaired parasite maturation is largely dependent upon the host response to infection. Thus, impairment of parasite maturation represents a host-mediated, immune system-dependent mechanism for limiting parasite population growth during the early stages of an acute blood-stage Plasmodium infection. PMID:28673996

Predicting performance of axial pump inducer of LOX booster turbo-pump of staged combustion cycle based rocket engine using CFD

NASA Astrophysics Data System (ADS)

Mishra, Arpit; Ghosh, Parthasarathi

2015-12-01

For low cost, high thrust, space missions with high specific impulse and high reliability, inert weight needs to be minimized and thereby increasing the delivered payload. Turbopump feed system for a liquid propellant rocket engine (LPRE) has the highest power to weight ratio. Turbopumps are primarily equipped with an axial flow inducer to achieve the high angular velocity and low suction pressure in combination with increased system reliability. Performance of the turbopump strongly depends on the performance of the inducer. Thus, for designing a LPRE turbopump, demands optimization of the inducer geometry based on the performance of different off-design operating regimes. In this paper, steady-state CFD analysis of the inducer of a liquid oxygen (LOX) axial pump used as a booster pump for an oxygen rich staged combustion cycle rocket engine has been presented using ANSYS® CFX. Attempts have been made to obtain the performance characteristic curves for the LOX pump inducer. The formalism has been used to predict the performance of the inducer for the throttling range varying from 80% to 113% of nominal thrust and for the different rotational velocities from 4500 to 7500 rpm. The results have been analysed to determine the region of cavitation inception for different inlet pressure.

The Grid Density Dependence of the Unsteady Pressures of the J-2X Turbines

NASA Technical Reports Server (NTRS)

Schmauch, Preston B.

2011-01-01

The J-2X engine was originally designed for the upper stage of the cancelled Crew Launch Vehicle. Although the Crew Launch Vehicle was cancelled the J-2X engine, which is currently undergoing hot-fire testing, may be used on future programs. The J-2X engine is a direct descendent of the J-2 engine which powered the upper stage during the Apollo program. Many changes including a thrust increase from 230K to 294K lbf have been implemented in this engine. As part of the design requirements, the turbine blades must meet minimum high cycle fatigue factors of safety for various vibrational modes that have resonant frequencies in the engine's operating range. The unsteady blade loading is calculated directly from CFD simulations. A grid density study was performed to understand the sensitivity of the spatial loading and the magnitude of the on blade loading due to changes in grid density. Given that the unsteady blade loading has a first order effect on the high cycle fatigue factors of safety, it is important to understand the level of convergence when applying the unsteady loads. The convergence of the unsteady pressures of several grid densities will be presented for various frequencies in the engine's operating range.

Comparative Plasmodium gene overexpression reveals distinct perturbation of sporozoite transmission by profilin

PubMed Central

Sato, Yuko; Hliscs, Marion; Dunst, Josefine; Goosmann, Christian; Brinkmann, Volker; Montagna, Georgina N.; Matuschewski, Kai

2016-01-01

Plasmodium relies on actin-based motility to migrate from the site of infection and invade target cells. Using a substrate-dependent gliding locomotion, sporozoites are able to move at fast speed (1–3 μm/s). This motility relies on a minimal set of actin regulatory proteins and occurs in the absence of detectable filamentous actin (F-actin). Here we report an overexpression strategy to investigate whether perturbations of F-actin steady-state levels affect gliding locomotion and host invasion. We selected two vital Plasmodium berghei G-actin–binding proteins, C-CAP and profilin, in combination with three stage-specific promoters and mapped the phenotypes afforded by overexpression in all three extracellular motile stages. We show that in merozoites and ookinetes, additional expression does not impair life cycle progression. In marked contrast, overexpression of C-CAP and profilin in sporozoites impairs circular gliding motility and salivary gland invasion. The propensity for productive motility correlates with actin accumulation at the parasite tip, as revealed by combinations of an actin-stabilizing drug and transgenic parasites. Strong expression of profilin, but not C-CAP, resulted in complete life cycle arrest. Comparative overexpression is an alternative experimental genetic strategy to study essential genes and reveals effects of regulatory imbalances that are not uncovered from deletion-mutant phenotyping. PMID:27226484

Common Sleep Problems (For Teens)

MedlinePlus

... rapid eye movement) sleep make up a sleep cycle . One complete sleep cycle lasts about 90 to 100 minutes. So during ... a person will experience about four or five cycles of sleep. Stages 1 and 2 are periods ...

Research on conceptual/innovative design for the life cycle

NASA Technical Reports Server (NTRS)

Cagan, Jonathan; Agogino, Alice M.

1990-01-01

The goal of this research is developing and integrating qualitative and quantitative methods for life cycle design. The definition of the problem includes formal computer-based methods limited to final detailing stages of design; CAD data bases do not capture design intent or design history; and life cycle issues were ignored during early stages of design. Viewgraphs outline research in conceptual design; the SYMON (SYmbolic MONotonicity analyzer) algorithm; multistart vector quantization optimization algorithm; intelligent manufacturing: IDES - Influence Diagram Architecture; and 1st PRINCE (FIRST PRINciple Computational Evaluator).

Role of Chemotherapeutic Agents in the Management of Cystic Echinococcosis

PubMed Central

Nazligul, Yasar; Kucukazman, Metin; Akbulut, Sami

2015-01-01

Hydatid disease is caused by infection with the metacestode stage of Echinococcus tapeworms of the family Taeniidae. The primary carriers are dogs and wolves, and humans are accidental hosts that do not contribute to the normal life cycle of this organism. The liver is the most commonly involved organ in the body by cystic echinococcosis (CE) secondary to infection with Echinococcus granulosus. Management options for CE should depend on the World Health Organization (WHO) diagnostic classification. Small (<5 cm) WHO stage CE1 and CE3a cysts may be primarily treated with benzimidazoles; the first-choice drug is albendazole. In some situations the combination of albendazole and praziquantel may be preferred. Chemotherapy with a benzimidazole or albendazole plus praziquantel is also used as adjunctive treatment to surgery and percutaneous treatment. Drug treatments have been the indispensable therapeutic modalities for cystic echinococcosis. PMID:25594649

Monitoring the elasticity changes of HeLa cells during mitosis by atomic force microscopy

NASA Astrophysics Data System (ADS)

Jiang, Ningcheng; Wang, Yuhua; Zeng, Jinshu; Ding, Xuemei; Xie, Shusen; Yang, Hongqin

2016-10-01

Cell mitosis plays a crucial role in cell life activity, which is one of the important phases in cell division cycle. During the mitosis, the cytoskeleton micro-structure of the cell changed and the biomechanical properties of the cell may vary depending upon different mitosis stages. In this study, the elasticity property of HeLa cells during mitosis was monitored by atomic force microscopy. Also, the actin filaments in different mitosis stages of the cells were observed by confocal imaging. Our results show that the cell in anaphase is stiffer than that in metaphase and telophase. Furthermore, lots of actin filaments gathered in cells' center area in anaphase, which contributes to the rigidity of the cell in this phase. Our findings demonstrate that the nano-biomechanics of living cells could provide a new index for characterizing cell physiological states.

Effectively Serving the Needs of Today's Business Student: The Product Life Cycle Approach to Class Organization

ERIC Educational Resources Information Center

Eastman, Jacqueline K.; Aviles, Maria; Hanna, Mark

2012-01-01

We illustrate a class organization process utilizing the concept of the Product Life Cycle to meet the needs of today's millennial student. In the Introduction stage of a business course, professors need to build structure to encourage commitment. In the Growth stage, professors need to promote the structure through multiple, brief activities that…

A Vitex agnus-castus extract inhibits cell growth and induces apoptosis in prostate epithelial cell lines.

PubMed

Weisskopf, M; Schaffner, W; Jundt, G; Sulser, T; Wyler, S; Tullberg-Reinert, H

2005-10-01

Extracts of Vitex agnus-castus fruits (VACF) are described to have beneficial effects on disorders related to hyperprolactinemia (cycle disorders, premenstrual syndrome). A VACF extract has recently been shown to exhibit antitumor activities in different human cancer cell lines. In the present study, we explored the antiproliferative effects of a VACF extract with a particular focus on apoptosis-inducing and potential cytotoxic effects. Three different human prostate epithelial cell lines (BPH-1, LNCaP, PC-3) representing different disease stages and androgen responsiveness were chosen. The action of VACF on cell viability was assessed using the WST-8-tetrazolium assay. Cell proliferation in cells receiving VACF alone or in combination with a pan-caspase inhibitor (Z-VAD-fmk) was quantified using a Crystal Violet assay. Flow cytometric cell cycle analysis and measurement of DNA fragmentation using an ELISA method were used for studying the induction of apoptosis. Lactate dehydrogenase (LDH) activity was determined as a marker of cytotoxicity. The extract inhibited proliferation of all three cell lines in a concentration-dependent manner with IC (50) values below 10 microg/mL after treatment for 48 h. Cell cycle analysis and DNA fragmentation assays suggest that part of the cells were undergoing apoptosis. The VACF-induced decrease in cell number was partially inhibited by Z-VAD-fmk, indicating a caspase-dependent apoptotic cell death. However, the concentration-dependent LDH activity of VACF treated cells indicated cytotoxic effects as well. These data suggest that VACF contains components that inhibit proliferation and induce apoptosis in human prostate epithelial cell lines. The extract may be useful for the prevention and/or treatment not only of benign prostatic hyperplasia but also of human prostate cancer.

Comparison of normal and abnormal fertilization of in vitro-matured human oocyte according to insemination method.

PubMed

Park, Ju Hee; Jee, Byung Chul; Kim, Seok Hyun

2016-04-01

Our purpose was to compare the normal fertilization rate, multi-pronuclei (PN) formation rate, and embryonic development of in vitro-matured oocytes between conventional insemination and intracytoplasmic sperm injection (ICSI). A total of 213 stimulated in vitro fertilization (IVF) cycles were selected, in which at least one immature oocyte was obtained (from 2010 to 2014). Immature oocytes were assigned to germinal vesicle (GV)-stage or metaphase I (MI)-stage oocyte groups. Cycles with obligatory ICSI due to male-factor infertility were excluded. Cycles were divided into two groups according to fertilization method: there were 97 cycles with conventional insemination and 116 cycles with ICSI. After in vitro maturation of 324 GV-stage oocytes and 341 MI-stage oocytes, the fertilization rate, multi-PN formation rate, and embryonic development were compared according to the fertilization method. The normal fertilization rate was similar in the conventional insemination and the ICSI both in GV-derived and MI-derived oocytes. Both fertilization methods resulted in a similar multi-PN formation rate in GV-derived oocytes; however, in MI-derived oocytes, the multi-PN formation rate was zero with ICSI and this was significantly lower than that with conventional insemination (9.6%, P = 0.001). In non-male-factor infertility, ICSI should be considered when MI oocytes are matured. © 2016 Japan Society of Obstetrics and Gynecology.

A systematic analysis of the early transcribed membrane protein family throughout the life cycle of Plasmodium yoelii.

PubMed

MacKellar, Drew C; Vaughan, Ashley M; Aly, Ahmed S I; DeLeon, Sasha; Kappe, Stefan H I

2011-11-01

The early transcribed membrane proteins (ETRAMPs) are a family of small, highly charged transmembrane proteins unique to malaria parasites. Some members of the ETRAMP family have been localized to the parasitophorous vacuole membrane that separates the intracellular parasite from the host cell and thus presumably have a role in host-parasite interactions. Although it was previously shown that two ETRAMPs are critical for rodent malaria parasite liver-stage development, the importance of most ETRAMPs during the parasite life cycle remains unknown. Here, we comprehensively identify nine new etramps in the genome of the rodent malaria parasite Plasmodium yoelii, and elucidate their conservation in other malaria parasites. etramp expression profiles are diverse throughout the parasite life cycle as measured by RT-PCR. Epitope tagging of two ETRAMPs demonstrates protein expression in blood and liver stages, and reveals differences in both their timing of expression and their subcellular localization. Gene targeting studies of each of the nine uncharacterized etramps show that two are refractory to deletion and thus likely essential for blood-stage replication. Seven etramps are not essential for any life cycle stage. Systematic characterization of the members of the ETRAMP family reveals the diversity in importance of each family member at the interface between host and parasite throughout the developmental cycle of the malaria parasite. © 2011 Blackwell Publishing Ltd.

Gallium Arsenide Domino Circuit

NASA Technical Reports Server (NTRS)

Yang, Long; Long, Stephen I.

1990-01-01

Advantages include reduced power and high speed. Experimental gallium arsenide field-effect-transistor (FET) domino circuit replicated in large numbers for use in dynamic-logic systems. Name of circuit denotes mode of operation, which logic signals propagate from each stage to next when successive stages operated at slightly staggered clock cycles, in manner reminiscent of dominoes falling in a row. Building block of domino circuit includes input, inverter, and level-shifting substages. Combinational logic executed in input substage. During low half of clock cycle, result of logic operation transmitted to following stage.

Research on the application of BIM technology in the whole life cycle of construction projects

NASA Astrophysics Data System (ADS)

Chang-liu, CHEN; Wei-wei, KOU; Shuai-hua, YE

2018-05-01

BIM technology can realize information sharing, and good BIM application will reduce the whole life cycle cost of construction projects. The popularization of BIM technology challenges the application of BIM technology at all stages of the whole life cycle of the construction project. It will give full play to the value of BIM, if developing a reasonable BIM project execution plan, defining BIM requirements, specifying Level of Development, determining the BIM quality control plan and clearing BIM application content of each stage, and will provide a unified method for project stakeholders, realize the whole life cycle of construction projects, and achieve the desired information sharing in construction project.

A stochastic spatiotemporal model of a response-regulator network in the Caulobacter crescentus cell cycle

NASA Astrophysics Data System (ADS)

Li, Fei; Subramanian, Kartik; Chen, Minghan; Tyson, John J.; Cao, Yang

2016-06-01

The asymmetric cell division cycle in Caulobacter crescentus is controlled by an elaborate molecular mechanism governing the production, activation and spatial localization of a host of interacting proteins. In previous work, we proposed a deterministic mathematical model for the spatiotemporal dynamics of six major regulatory proteins. In this paper, we study a stochastic version of the model, which takes into account molecular fluctuations of these regulatory proteins in space and time during early stages of the cell cycle of wild-type Caulobacter cells. We test the stochastic model with regard to experimental observations of increased variability of cycle time in cells depleted of the divJ gene product. The deterministic model predicts that overexpression of the divK gene blocks cell cycle progression in the stalked stage; however, stochastic simulations suggest that a small fraction of the mutants cells do complete the cell cycle normally.

Microbial proliferation on gill structures of juvenile European lobster ( Homarus gammarus) during a moult cycle

NASA Astrophysics Data System (ADS)

Middlemiss, Karen L.; Urbina, Mauricio A.; Wilson, Rod W.

2015-12-01

The morphology of gill-cleaning structures is not well described in European lobster ( Homarus gammarus). Furthermore, the magnitude and time scale of microbial proliferation on gill structures is unknown to date. Scanning electron microscopy was used to investigate development of setae in zoea, megalopa and juvenile stages (I-V). Microbes were classified and quantified on gill structures throughout a moult cycle from megalopa (stage IV) to juvenile (stage V). Epipodial serrulate setae, consisting of a naked proximal setal shaft with the distal portion possessing scale-like outgrowths (setules), occur only after zoea stage III. After moulting to megalopa (stage IV), gill structures were completely clean and no microbes were visible on days 1 or 5 postmoult. Microbial proliferation was first evident on day 10 postmoult, with a significant 16-fold increase from day 10 to 15. Rod-shaped bacteria were initially predominant (by day 10); however, by day 15 the microbial community was dominated by cocci-shaped bacteria. This research provides new insights into the morphology of gill-grooming structures, the timing of their development, and the magnitude, timescale and characteristics of gill microbial proliferation during a moult cycle. To some degree, the exponential growth of epibionts on gills found during a moult cycle will likely impair respiratory (gas exchange) and ion regulatory function, yet further research is needed to evaluate the physiological effects of the exponential bacterial proliferation documented here.

Expression of aquaporin-7 and aquaporin-9 in tanycyte cells and choroid plexus during mouse estrus cycle.

PubMed

Yaba, A; Sozen, B; Suzen, B; Demir, N

2017-03-01

Tanycytes are special ependymal cells located in the ventrolateral wall and floor of the third ventricle having processes extending nuclei that regulate reproductive functions and around of vessels in median eminance. The aquaporins (AQPs) are a family of transmembrane proteins that transport water and glycerol. AQP-7 and -9 are permeable to other small molecules as glycerol and therefore called aquaglyceroporins. In this study, we aimed to show localization of AQP-7 and -9 in epithelial cells of choroid plexus and tanycytes during female mouse estrus cycle. AQP-7 and -9 proteins were detected in α2 and β1 tanycytes in prœstrus stage. Interestingly, there is no staining in estrus stage in any type of tanycytes. We observed weak immunoreactivity in α1, α2 and β1 tanycyte cells in metestrus stage for AQP-7 and α1 for AQP-9 protein. AQP-7 and -9 showed intense immunoreactivity in α2, β1 and β2 tanycyte cells during diestrus stage. Consequently, AQP-7 and -9 showed differential staining pattern in different stages of mouse estrus cycle. In the light of our findings and other recent publications, we suggest that AQP-7 and -9-mediated glycerol transport in tanycyte cells might be under hormonal control to use glycerol as a potential energy substrate during mouse estrus cycle. Copyright © 2016. Published by Elsevier Masson SAS.

Biome-scale nitrogen fixation strategies selected by climatic constraints on nitrogen cycle.

PubMed

Sheffer, Efrat; Batterman, Sarah A; Levin, Simon A; Hedin, Lars O

2015-11-23

Dinitrogen fixation by plants (in symbiosis with root bacteria) is a major source of new nitrogen for land ecosystems(1). A long-standing puzzle(2) is that trees capable of nitrogen fixation are abundant in nitrogen-rich tropical forests, but absent or restricted to early successional stages in nitrogen-poor extra-tropical forests. This biome-scale pattern presents an evolutionary paradox(3), given that the physiological cost(4) of nitrogen fixation predicts the opposite pattern: fixers should be out-competed by non-fixers in nitrogen-rich conditions, but competitively superior in nitrogen-poor soils. Here we evaluate whether this paradox can be explained by the existence of different fixation strategies in tropical versus extra-tropical trees: facultative fixers (capable of downregulating fixation(5,6) by sanctioning mutualistic bacteria(7)) are common in the tropics, whereas obligate fixers (less able to downregulate fixation) dominate at higher latitudes. Using a game-theoretic approach, we assess the ecological and evolutionary conditions under which these fixation strategies emerge, and examine their dependence on climate-driven differences in the nitrogen cycle. We show that in the tropics, transient soil nitrogen deficits following disturbance and rapid tree growth favour a facultative strategy and the coexistence of fixers and non-fixers. In contrast, sustained nitrogen deficits following disturbance in extra-tropical forests favour an obligate fixation strategy, and cause fixers to be excluded in late successional stages. We conclude that biome-scale differences in the abundance of nitrogen fixers can be explained by the interaction between individual plant strategies and climatic constraints on the nitrogen cycle over evolutionary time.

Climatic influences on the breeding biology of the agile frog ( Rana dalmatina)

NASA Astrophysics Data System (ADS)

Combes, Magali; Pinaud, David; Barbraud, Christophe; Trotignon, Jacques; Brischoux, François

2018-02-01

Severe population declines of amphibians have been shown to be attributed to climate change. Nevertheless, the various mechanisms through which climate can influence population dynamics of amphibians remain to be assessed, notably to disentangle the relative synergetic or antagonistic influences of temperature and precipitations on specific life history stages. We investigated the impact of rainfall and temperature on the egg-clutch abundance in a population of agile frog ( Rana dalmatina) during 29 years (1987-2016) on 14 breeding sites located in Brenne Natural Park, France. Specifically, we examined the influence of environmental conditions occurring during five temporal windows of the year cycle corresponding to specific life history stages. Overall, our results suggest that the year-to-year fluctuations of egg-clutch abundances in Brenne Natural Park were partly dependent on local climatic conditions (rainfall and temperature). Climate seemed to influence breeding frogs during the autumn-winter period preceding reproduction. Spring and summer conditions did not influence reproduction. Additionally, we failed to detect effects of climatic conditions on newly metamorphosed individuals. Other factors such as density dependence and inter-specific interactions with introduced predators are likely to play a significant role in reproduction dynamics of the studied frog populations.

Climatic influences on the breeding biology of the agile frog (Rana dalmatina).

PubMed

Combes, Magali; Pinaud, David; Barbraud, Christophe; Trotignon, Jacques; Brischoux, François

2017-12-19

Severe population declines of amphibians have been shown to be attributed to climate change. Nevertheless, the various mechanisms through which climate can influence population dynamics of amphibians remain to be assessed, notably to disentangle the relative synergetic or antagonistic influences of temperature and precipitations on specific life history stages. We investigated the impact of rainfall and temperature on the egg-clutch abundance in a population of agile frog (Rana dalmatina) during 29 years (1987-2016) on 14 breeding sites located in Brenne Natural Park, France. Specifically, we examined the influence of environmental conditions occurring during five temporal windows of the year cycle corresponding to specific life history stages. Overall, our results suggest that the year-to-year fluctuations of egg-clutch abundances in Brenne Natural Park were partly dependent on local climatic conditions (rainfall and temperature). Climate seemed to influence breeding frogs during the autumn-winter period preceding reproduction. Spring and summer conditions did not influence reproduction. Additionally, we failed to detect effects of climatic conditions on newly metamorphosed individuals. Other factors such as density dependence and inter-specific interactions with introduced predators are likely to play a significant role in reproduction dynamics of the studied frog populations.

A New Technique for Achieving Impact Velocities Greater Than 10 km/sec

NASA Astrophysics Data System (ADS)

Piekutowski, A. J.

2001-05-01

This Contractor Report describes and presents the results of work that was done in an attempt to develop an augmented acceleration technique that would launch small projectiles of known shape, mass, and state to velocities of 10 km/sec and higher. The higher velocities were to be achieved by adding a third stage to a conventional two-stage, light-gas gun and using a modified firing cycle for the third stage. The technique did not achieve the desired results and was modified for use during the development program. Since the design of the components used for the augmented-acceleration, three-stage launcher could be readily adapted for use as a three-stage launcher that used a single-stage acceleration cycle; the remainder of the contract period was spent performing test firings using the modified three-stage launcher. Work with the modified three-stage launcher, although not complete, did produce test firings in which an 0.11-g cylindrical nylon projectile was launched to a velocity of 8.65 km/sec.

A New Technique for Achieving Impact Velocities Greater Than 10 km/sec

NASA Technical Reports Server (NTRS)

Piekutowski, A. J.; Nolen, Angie (Technical Monitor)

2001-01-01

This Contractor Report describes and presents the results of work that was done in an attempt to develop an augmented acceleration technique that would launch small projectiles of known shape, mass, and state to velocities of 10 km/sec and higher. The higher velocities were to be achieved by adding a third stage to a conventional two-stage, light-gas gun and using a modified firing cycle for the third stage. The technique did not achieve the desired results and was modified for use during the development program. Since the design of the components used for the augmented-acceleration, three-stage launcher could be readily adapted for use as a three-stage launcher that used a single-stage acceleration cycle; the remainder of the contract period was spent performing test firings using the modified three-stage launcher. Work with the modified three-stage launcher, although not complete, did produce test firings in which an 0.11-g cylindrical nylon projectile was launched to a velocity of 8.65 km/sec.

Effects of food conditions on the development of the population of Temora stylifera: A modeling approach

NASA Astrophysics Data System (ADS)

Mazzocchi, M. G.; Buffoni, G.; Carotenuto, Y.; Pasquali, S.; Ribera d'Alcalà, M.

2006-08-01

We integrated field and laboratory data with modeling to determine the extent to which the temporal patterns in population abundance of a copepod species as observed at sea may be explained by differences in production and mortality rates due to diet. A Lagrangian individual-based model utilizing birth and mortality rates whose values and variance were derived from the effects of dietary composition was implemented to simulate the growth of the multi-staged population of Temora stylifera. The four diets considered were represented by unialgal cultures of the dinoflagellate Prorocentrum minimum or the diatom Thalassiosira rotula, a mixture of the two species, and natural particle assemblages < 50 μm. The aim of this work was to set up an exemplary study on a debated issue, i.e., whether the insidious effect of a diatom diet demonstrated in laboratory experiments plays a role in the time course of copepod populations in situ. Our numerical simulations showed that differences in life history parameters, as mainly dependent on diet, caused remarkably different population growth rates. However, our model reproduced the pattern of an average seasonal cycle of T. stylifera in Mediterranean coastal waters only when it utilized time-dependent field data, which evidently integrate all conditions the animals experience at sea. Proper tuning of the mortality term of developmental stages was crucial to reproduce the pattern of the time course of T. stylifera abundance in situ, which confirms that this term plays a major role in shaping the copepod population dynamics. The model also showed that, while dietary composition affects the population growth, it is far from being the only determinant of the cycle of abundance of T. stylifera at sea.

Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitors of matrix metalloproteinase-1 expression.

PubMed

Hussain, Arif; Harish, Geetganga; Prabhu, Sathyen Alwin; Mohsin, Javeria; Khan, Munawwar Ali; Rizvi, Tahir A; Sharma, Chhavi

2012-12-01

One of the most challenging stumbling blocks for the treatment of cancer is the ability of cancer cells to break the natural barriers and spread from its site of origin to non-adjacent regional and distant sites, accounting for high cancer mortality rates. Gamut experimental and epidemiological data advocate the use of pharmacological or nutritional interventions to inhibit or delay various stage(s) of cancer such as invasion and metastasis. Genistein, a promising chemopreventive agent, has gained considerable attention for its powerful anti-carcinogenic, anti-angiogenic and chemosensitizing activities. In this study, the cytotoxic potential of genistein on HeLa cells by cell viability assay and the mode of cell death induced by genistein were determined by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Moreover, to establish its inhibitory effect on migration of HeLa cells, scratch wound assay was performed and these results were correlated with the expression of genes involved in invasion and migration (MMP-9 and TIMP-1) by RT-PCR. The exposure of HeLa cells to genistein resulted in significant dose- and time-dependent growth inhibition, which was found to be mediated by apoptosis and cell cycle arrest at G(2)/M phase. In addition, it induced migration-inhibition in a time-dependent manner by modulating the expression of MMP-9 and TIMP-1. Our results signify that genistein may be an effective anti-neoplastic agent to prevent cancer cell growth and invasion and metastasis. Therefore therapeutic strategies utilizing genistein could be developed to substantially reduce cancer morbidity and mortality. Copyright © 2012 Elsevier Ltd. All rights reserved.

Structural-Phase Transformations of CuZn Alloy Under Thermal-Impact Cycling

NASA Astrophysics Data System (ADS)

Potekaev, A. I.; Chaplygina, A. A.; Kulagina, V. V.; Chaplygin, P. A.; Starostenkov, M. D.; Grinkevich, L. S.

2017-02-01

Using the Monte Carlo method, special features of structural - phase transformations in β-brass are investigated during thermal impact using thermal cycling as an example (a number of successive order - disorder and disorder - order phase transitions in the course of several heating - cooling cycles). It is shown that a unique hysteresis is observed after every heating and cooling cycle, whose presence indicates irreversibility of the processes, which suggests a difference in the structural - phase states both in the heating and cooling stages. A conclusion is drawn that the structural - phase transformations in the heating and cooling stages occur within different temperature intervals, where the thermodynamic stimuli of one or the other structural - phase state are low. This is also demonstrated both in the plots of configurational energy, long- and short-range order parameter, atomic structure variations, and structural - phase state distributions. Simultaneously, there coexist ordered and disordered phases and a certain collection of superstructure domains. This implies the presence of low - stability states in the vicinity of the order - disorder phase transition. The results of investigations demonstrate that the structural - phase transitions within two successive heating and cooling cycles at the same temperature are different in both stages. These changes, though not revolutionary, occur in every cycle and decrease with the increasing cycle number. In fact, the system undergoes training with a tendency towards a certain sequence of structural - phase states.

Absorption Heat Pump Cycles

NASA Astrophysics Data System (ADS)

Kunugi, Yoshifumi; Kashiwagi, Takao

Various advanced absorption cycles are studied, developed and invented. In this paper, their cycles are classified and arranged using the three categories: effect, stage and loop, then an outline of the cycles are explained on the Duehring diagram. Their cycles include high COP cycles for refrigerations and heat pumps, high temperature lift cycles for heat transformer, absorption-compression hybrid cycles and heat pump transformer cycle. The highest COPi is attained by the seven effect cycle. In addition, the cycles for low temperature are invented and explained. Furthermore the power generation • refrigeration cycles are illustrated.

Comparative muscle development of scyphozoan jellyfish with simple and complex life cycles.

PubMed

Helm, Rebecca R; Tiozzo, Stefano; Lilley, Martin K S; Lombard, Fabien; Dunn, Casey W

2015-01-01

Simple life cycles arise from complex life cycles when one or more developmental stages are lost. This raises a fundamental question - how can an intermediate stage, such as a larva, be removed, and development still produce a normal adult? To address this question, we examined the development in several species of pelagiid jellyfish. Most members of Pelagiidae have a complex life cycle with a sessile polyp that gives rise to ephyrae (juvenile medusae); but one species within Pelagiidae, Pelagia noctiluca, spends its whole life in the water column, developing from a larva directly into an ephyra. In many complex life cycles, adult features develop from cell populations that remain quiescent in larvae, and this is known as life cycle compartmentalization and may facilitate the evolution of direct life cycles. A second type of metamorphic processes, known as remodeling, occurs when adult features are formed through modification of already differentiated larval structures. We examined muscle morphology to determine which of these alternatives may be present in Pelagiidae. We first examined the structure and development of polyp and ephyra musculature in Chrysaora quinquecirrha, a close relative of P. noctiluca with a complex life cycle. Using phallotoxin staining and confocal microscopy, we verified that polyps have four to six cord muscles that persist in strobilae and discovered that cord muscles is physically separated from ephyra muscle. When cord muscle is removed from ephyra segments, normal ephyra muscle still develops. This suggests that polyp cord muscle is not necessary for ephyra muscle formation. We also found no evidence of polyp-like muscle in P. noctiluca. In both species, we discovered that ephyra muscle arises de novo in a similar manner, regardless of the life cycle. The separate origins of polyp and ephyra muscle in C. quinquecirrha and the absence of polyp-like muscle in P. noctiluca suggest that polyp muscle is not remodeled to form ephyra muscle in Pelagiidae. Life cycle stages in Scyphozoa may instead be compartmentalized. Because polyp muscle is not directly remodeled, this may have facilitated the loss of the polyp stage in the evolution of P. noctiluca.

Cell Cycle Status of CD34+ Hemopoietic Stem Cells Determines Lentiviral Integration in Actively Transcribed and Development-related Genes

PubMed Central

Papanikolaou, Eleni; Paruzynski, Anna; Kasampalidis, Ioannis; Deichmann, Annette; Stamateris, Evangelos; Schmidt, Manfred; von Kalle, Christof; Anagnou, Nicholas P

2015-01-01

Gene therapy utilizing lentiviral-vectors (LVs) is postulated as a dynamic therapeutic alternative for monogenic diseases. However, retroviral gene transfer may cause insertional mutagenesis. Although, such risks had been originally estimated as extremely low, several reports of leukemias or clonal dominance, have led to a re-evaluation of the mechanisms operating in insertional mutagenesis. Therefore, unraveling the mechanism of retroviral integration is mandatory toward safer gene therapy applications. In the present study, we undertook an experimental approach which enabled direct correlation of the cell cycle stage of the target cell with the integration profile of LVs. CD34+ cells arrested at different stages of cell cycle, were transduced with a GFP-LV. LAM-PCR was employed for integration site detection, followed by microarray analysis to correlate transcribed genes with integration sites. The results indicate that ~10% of integration events occurred in actively transcribed genes and that the cell cycle stage of target cells affects integration pattern. Specifically, use of thymine promoted a safer profile, since it significantly reduced integration within cell cycle-related genes, while we observed increased possibility for integration into genes related to development, and decreased possibility for integration within cell cycle and cancer-related genes, when transduction occurs during mitosis. PMID:25523760

Tough Adults, Frail Babies: An Analysis of Stress Sensitivity across Early Life-History Stages of Widely Introduced Marine Invertebrates

PubMed Central

Pineda, M. Carmen; McQuaid, Christopher D.; Turon, Xavier; López-Legentil, Susanna; Ordóñez, Víctor; Rius, Marc

2012-01-01

All ontogenetic stages of a life cycle are exposed to environmental conditions so that population persistence depends on the performance of both adults and offspring. Most studies analysing the influence of abiotic conditions on species performance have focussed on adults, while studies covering early life-history stages remain rare. We investigated the responses of early stages of two widely introduced ascidians, Styela plicata and Microcosmus squamiger, to different abiotic conditions. Stressors mimicked conditions in the habitats where both species can be found in their distributional ranges and responses were related to the selection potential of their populations by analysing their genetic diversity. Four developmental stages (egg fertilisation, larval development, settlement, metamorphosis) were studied after exposure to high temperature (30°C), low salinities (26 and 22‰) and high copper concentrations (25, 50 and 100 µg/L). Although most stressors effectively led to failure of complete development (fertilisation through metamorphosis), fertilisation and larval development were the most sensitive stages. All the studied stressors affected the development of both species, though responses differed with stage and stressor. S. plicata was overall more resistant to copper, and some stages of M. squamiger to low salinities. No relationship was found between parental genetic composition and responses to stressors. We conclude that successful development can be prevented at several life-history stages, and therefore, it is essential to consider multiple stages when assessing species' abilities to tolerate stress. Moreover, we found that early development of these species cannot be completed under conditions prevailing where adults live. These populations must therefore recruit from elsewhere or reproduce during temporal windows of more benign conditions. Alternatively, novel strategies or behaviours that increase overall reproductive success might be responsible for ensuring population survival. PMID:23077518

Jasmonate Controls Leaf Growth by Repressing Cell Proliferation and the Onset of Endoreduplication while Maintaining a Potential Stand-By Mode1[W][OA

PubMed Central

Noir, Sandra; Bömer, Moritz; Takahashi, Naoki; Ishida, Takashi; Tsui, Tjir-Li; Balbi, Virginia; Shanahan, Hugh; Sugimoto, Keiko; Devoto, Alessandra

2013-01-01

Phytohormones regulate plant growth from cell division to organ development. Jasmonates (JAs) are signaling molecules that have been implicated in stress-induced responses. However, they have also been shown to inhibit plant growth, but the mechanisms are not well understood. The effects of methyl jasmonate (MeJA) on leaf growth regulation were investigated in Arabidopsis (Arabidopsis thaliana) mutants altered in JA synthesis and perception, allene oxide synthase and coi1-16B (for coronatine insensitive1), respectively. We show that MeJA inhibits leaf growth through the JA receptor COI1 by reducing both cell number and size. Further investigations using flow cytometry analyses allowed us to evaluate ploidy levels and to monitor cell cycle progression in leaves and cotyledons of Arabidopsis and/or Nicotiana benthamiana at different stages of development. Additionally, a novel global transcription profiling analysis involving continuous treatment with MeJA was carried out to identify the molecular players whose expression is regulated during leaf development by this hormone and COI1. The results of these studies revealed that MeJA delays the switch from the mitotic cell cycle to the endoreduplication cycle, which accompanies cell expansion, in a COI1-dependent manner and inhibits the mitotic cycle itself, arresting cells in G1 phase prior to the S-phase transition. Significantly, we show that MeJA activates critical regulators of endoreduplication and affects the expression of key determinants of DNA replication. Our discoveries also suggest that MeJA may contribute to the maintenance of a cellular “stand-by mode” by keeping the expression of ribosomal genes at an elevated level. Finally, we propose a novel model for MeJA-regulated COI1-dependent leaf growth inhibition. PMID:23439917

The March Toward Malaria Vaccines.

PubMed

Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

2015-12-01

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

The March Toward Malaria Vaccines

PubMed Central

Hoffman, Stephen L.; Vekemans, Johan; Richie, Thomas L.; Duffy, Patrick E.

2016-01-01

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. PMID:26590432

The march toward malaria vaccines

PubMed Central

Hoffman, Stephen L.; Vekemans, Johan; Richie, Thomas L.; Duffy, Patrick E.

2016-01-01

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. PMID:26324116

The march toward malaria vaccines.

PubMed

Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

2015-11-27

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Ltd.. All rights reserved.

Targeting ticks for control of selected hemoparasitic diseases of cattle.

PubMed

Kocan, K M

1995-03-01

Development in and transmission of hemoparasites by tick vectors are phenomena closely synchronized with the tick feeding cycle. In all known life cycles, initial infection of tick tissues occurs in midgut epithelial cells and transmission is effected as ticks feed after parasites have developed and multiplied in salivary glands. Many factors reviewed affect development and transmission of hemoparasites by ticks including age of ticks, artificial temperature, climate and/or season, tick stage or sex, hemoparasite variation, concurrent infection of ticks with other pathogens, host cell susceptibility, transovarial transmission, effect of hemoparasites on tick biology, and the effect of infecting parasitemia level in cattle on infection rates in ticks. Four hemoparasites of cattle, Anaplasma marginale, Cowdria ruminantium, Theileria parva, and Babesia spp., are all dependent on ticks for biological transmission. Babesia is transmitted transovarially whereas the other three are transmitted transstadially. Mechanical transfer of infective blood via fomites and mouthparts of biting arthropods is also a major means of transmission for Anaplasma marginale but not of the others. Potential control methods for hemoparasites that target parasites as they are developing in their respective tick hosts include tick control, vaccines (against ticks and parasites), and drugs (against ticks and parasites). Successful application of control strategies will be dependent upon thorough understanding of parasite developmental cycles, biology of the tick vectors and the immune response of cattle to ticks and to hemoparasites. The most effective control measures will be those that are targeted against both ticks and the hemoparasites they vector.

Controlled Aerodynamic Loads on an Airfoil in Coupled Pitch/Plunge by Transitory Regulation of Trapped Vorticity

NASA Astrophysics Data System (ADS)

Tan, Yuehan; Crittenden, Thomas; Glezer, Ari

2017-11-01

The aerodynamic loads on an airfoil moving in coupled, time-periodic pitch-plunge beyond the static stall margin are controlled using transitory regulation of trapped vorticity concentrations. Actuation is effected by a spanwise array of integrated miniature chemical (combustion based) impulse actuators that are triggered intermittently during the airfoil's motion and have a characteristic time scale that is an order of magnitude shorter than the airfoil's convective time scale. Each actuation pulse effects momentary interruption and suspension of the vorticity flux with sufficient control authority to alter the airfoil's global aerodynamic characteristics throughout its motion cycle. The effects of the actuation are assessed using time-dependent measurements of the lift and pitching moment coupled with time-resolved particle image velocimetry over the airfoil and in its near wake that is acquired phased-locked to its motion. It is shown that while the presence of the pitch-coupled plunge delays lift and moment stall during upstroke, it also delays flow reattachment during the downstroke and results in significant degradation of the pitch stability. These aerodynamic shortcomings are mitigated using superposition of a limited number of pulses that are staged during the pitch/plunge cycle and lead to enhancement of cycle lift and pitch stability, and reduces the cycle hysteresis and peak pitching moment.

Dynamic protein S-palmitoylation mediates parasite life cycle progression and diverse mechanisms of virulence.

PubMed

Brown, Robert W B; Sharma, Aabha I; Engman, David M

2017-04-01

Eukaryotic parasites possess complex life cycles and utilize an assortment of molecular mechanisms to overcome physical barriers, suppress and/or bypass the host immune response, including invading host cells where they can replicate in a protected intracellular niche. Protein S-palmitoylation is a dynamic post-translational modification in which the fatty acid palmitate is covalently linked to cysteine residues on proteins by the enzyme palmitoyl acyltransferase (PAT) and can be removed by lysosomal palmitoyl-protein thioesterase (PPT) or cytosolic acyl-protein thioesterase (APT). In addition to anchoring proteins to intracellular membranes, functions of dynamic palmitoylation include - targeting proteins to specific intracellular compartments via trafficking pathways, regulating the cycling of proteins between membranes, modulating protein function and regulating protein stability. Recent studies in the eukaryotic parasites - Plasmodium falciparum, Toxoplasma gondii, Trypanosoma brucei, Cryptococcus neoformans and Giardia lamblia - have identified large families of PATs and palmitoylated proteins. Many palmitoylated proteins are important for diverse aspects of pathogenesis, including differentiation into infective life cycle stages, biogenesis and tethering of secretory organelles, assembling the machinery powering motility and targeting virulence factors to the plasma membrane. This review aims to summarize our current knowledge of palmitoylation in eukaryotic parasites, highlighting five exemplary mechanisms of parasite virulence dependent on palmitoylation.

Tumor suppressor Lzap regulates cell cycle progression, doming and zebrafish epiboly

PubMed Central

Liu, Dan; Wang, Wen-Der; Melville, David B.; Cha, Yong I.; Yin, Zhirong; Issaeva, Natalia; Knapik, Ela W.; Yarbrough, Wendell G.

2012-01-01

Initial stages of embryonic development rely on rapid, synchronized cell divisions of the fertilized egg followed by a set of morphogenetic movements collectively called epiboly and gastrulation. Lzap is a putative tumor suppressor whose expression is lost in 30% of head and neck squamous cell carcinomas. Lzap activities include regulation of cell cycle progression and response to therapeutic agents. Here we explore developmental roles of the lzap gene during zebrafish morphogenesis. Lzap is highly conserved among vertebrates and is maternally deposited. Expression is initially ubiquitous during gastrulation, and later becomes more prominent in the pharyngeal arches, digestive tract and brain. Antisense morpholino-mediated depletion of Lzap resulted in delayed cell divisions and apoptosis during blastomere formation, resulting in fewer, larger cells. Cell cycle analysis suggested that Lzap loss in early embryonic cells resulted in a G2/M arrest. Furthermore, the Lzap-deficient embryos failed to initiate epiboly – the earliest morphogenetic movement in animal development – which has been shown to be dependent on cell adhesion and migration of epithelial sheets. Our results strongly implicate Lzap in regulation of cell cycle progression, adhesion and migratory activity of epithelial cell sheets during early development. These functions provide further insight into Lzap activity that may contribute not only to development, but also to tumor formation. PMID:21523853

Rapid Cdc13 turnover and telomere length homeostasis are controlled by Cdk1-mediated phosphorylation of Cdc13.

PubMed

Tseng, Shun-Fu; Shen, Zih-Jie; Tsai, Hung-Ji; Lin, Yi-Hsuan; Teng, Shu-Chun

2009-06-01

Budding yeast telomerase is mainly activated by Tel1/Mec1 (yeast ATM/ATR) on Cdc13 from late S to G2 phase of the cell cycle. Here, we demonstrated that the telomerase-recruitment domain of Cdc13 is also phosphorylated by Cdk1 at the same cell cycle stage as the Tel1/Mec1-dependent regulation. Phosphor-specific gel analysis demonstrated that Cdk1 phosphorylates residues 308 and 336 of Cdc13. The residue T308 of Cdc13 is critical for efficient Mec1-mediated S306 phosphorylation in vitro. Phenotypic analysis in vivo revealed that the mutations in the Cdc13 S/TP motifs phosphorylated by Cdk1 caused cell cycle delay and telomere shortening and these phenotypes could be partially restored by the replacement with a negative charge residue. In the absence of Ku or Tel1, Cdk1-mediated phosphorylation of Cdc13 showed no effect on telomere length maintenance. Moreover, this Cdk1-mediated phosphorylation was required to promote the regular turnover of Cdc13. Together these results demonstrate that Cdk1 phosphorylates the telomerase recruitment domain of Cdc13, thereby preserves optimal function and expression level of Cdc13 for precise telomere replication and cell cycle progression.

The heterotoxicity of Hordeum vulgare L. extracts in four growth stages on germination and seedlings growth of Avena ludoviciana.

PubMed

Kolahi, M; Peivastegan, B; Hadizade, I; Abdali, A

2008-07-15

Phytotoxicity of barley extracts (Hordeum vulgare L.) on wild oat (Avena ludoviciana Durieu) was investigated. Water extracts five varieties of barley were bioassayed on germination and seedling growth of wild-oat to test the heterotoxicity of barley on wild-oat, study the dynamics of allelopathic potential over four growth stages and identify the most allelopathic plant part of barley in each stage. Whole barley plants were extracted at growth stage 4 (stems not developed enough), whilst for the following growth stages roots, stems, panicles and leaves were extracted separately. Seedling growth bioassays demonstrated that the wild-oat responded differently to the allelopathic potential of barley. For wild-oat radical growth and coleoptile growth were more depressed than germination, though. The allelopathic potential of barley plant parts was not stable over its life cycle for wild-oat. Leaves and stems were the most phytotoxic barley plant parts for wild-oat in the all stages. Among the varieties Eizeh appeared as the best one showing toxicity to seed germination of wild oat at its stage 4 and 8. Results suggested that the response by wild-oat varied depending on the source of allelochemicals (plant part) and the growth stage of the barley plant and kind of variety. The results leaded to conclude that Eizeh variety of barley was good to grow as it has good check on seed germination of wild oat plants as well as it also retarded the growth of root and shoot length of oat.

Small subunit ribosomal RNA sequence links the myxospore stage of Henneguya mississippiensis n. sp. from channel catfish Ictalurus punctatus to an actinospore released by the benthic oligochaete Dero digitata

USDA-ARS?s Scientific Manuscript database

There are more than 200 species of Henneguya described from fish. Of these, only three life cycles have been determined, identifying the actinospore and myxospore stages from their respective hosts. Two of these life cycles involve the channel catfish (Ictalurus punctatus) and the freshwater oligo...

A closed cycle cascade Joule Thomson refrigerator for cooling Josephson junction magnetometers

NASA Technical Reports Server (NTRS)

Tward, E.; Sarwinski, R.

1985-01-01

A closed cycle cascade Joule Thomson refrigerator designed to cool Josephson Junction magnetometers to liquid helium temperature is being developed. The refrigerator incorporates 4 stages of cooling using the working fluids CF4 and He. The high pressure gases are provided by a small compressor designed for this purpose. The upper stages have been operated and performance will be described.

Complex life cycles in a pond food web: effects of life stage structure and parasites on network properties, trophic positions and the fit of a probabilistic niche model.

PubMed

Preston, Daniel L; Jacobs, Abigail Z; Orlofske, Sarah A; Johnson, Pieter T J

2014-03-01

Most food webs use taxonomic or trophic species as building blocks, thereby collapsing variability in feeding linkages that occurs during the growth and development of individuals. This issue is particularly relevant to integrating parasites into food webs because parasites often undergo extreme ontogenetic niche shifts. Here, we used three versions of a freshwater pond food web with varying levels of node resolution (from taxonomic species to life stages) to examine how complex life cycles and parasites alter web properties, the perceived trophic position of organisms, and the fit of a probabilistic niche model. Consistent with prior studies, parasites increased most measures of web complexity in the taxonomic species web; however, when nodes were disaggregated into life stages, the effects of parasites on several network properties (e.g., connectance and nestedness) were reversed, due in part to the lower trophic generality of parasite life stages relative to free-living life stages. Disaggregation also reduced the trophic level of organisms with either complex or direct life cycles and was particularly useful when including predation on parasites, which can inflate trophic positions when life stages are collapsed. Contrary to predictions, disaggregation decreased network intervality and did not enhance the fit of a probabilistic niche model to the food webs with parasites. Although the most useful level of biological organization in food webs will vary with the questions of interest, our results suggest that disaggregating species-level nodes may refine our perception of how parasites and other complex life cycle organisms influence ecological networks.

Bilateral pedaling asymmetry during a simulated 40-km cycling time-trial.

PubMed

Carpes, F P; Rossato, M; Faria, I E; Bolli Mota, C

2007-03-01

This study investigated the pedaling asymmetry during a 40-km cycling time-trial (TT). Six sub-elite competitive male cyclists pedaled a SRM Training Systems cycle ergometer throughout a simulated 40-km TT. A SRM scientific crank dynamometer was used to measure the bilateral crank torque (N.m) and pedaling cadence (rpm). All data were analyzed into 4 stages with equal length obtained according to total time. Comparisons between each stage of the 40-km TT were made by an analysis of variance (ANOVA). Dominant (DO) and non-dominant (ND) crank peak torque asymmetry was determined by the equation: asymmetry index (AI%)=[(DO-ND)/DO] 100. Pearson correlation analysis was performed to verify the relationship between exercise intensity, mean and crank peak torque. The crank peak torque was significantly (P<0.05) greater in the 4th stage compared with other stages. During the stages 2 and 3, was observed the AI% of 13.51% and 17.28%, respectively. Exercise intensity (%VO(2max)) was greater for stage 4 (P<0.05) and was highly correlated with mean and crank peak torque (r=0.97 and r=0.92, respectively) for each stage. The DO limb was always responsible for the larger crank peak torque. It was concluded that pedaling asymmetry is present during a simulated 40-km TT and an increase on crank torque output and exercise intensity elicits a reduction in pedaling asymmetry.

Results of an Advanced Fan Stage Operating Over a Wide Range of Speed and Bypass Ratio. Part 1; Fan Stage Design and Experimental Results

NASA Technical Reports Server (NTRS)

Suder, Kenneth L.; Prahst, Patricia S.; Thorp, Scott A.

2011-01-01

NASA s Fundamental Aeronautics Program is investigating turbine-based combined cycle (TBCC) propulsion systems for access to space because it provides the potential for aircraft-like, space-launch operations that may significantly reduce launch costs and improve safety. To this end, National Aeronautics and Space Administration (NASA) and General Electric (GE) teamed to design a Mach 4 variable cycle turbofan/ramjet engine for access to space. To enable the wide operating range of a Mach 4+ variable cycle turbofan ramjet required the development of a unique fan stage design capable of multi-point operation to accommodate variations in bypass ratio (10 ), fan speed (7 ), inlet mass flow (3.5 ), inlet pressure (8 ), and inlet temperature (3 ). In this paper, NASA has set out to characterize a TBCC engine fan stage aerodynamic performance and stability limits over a wide operating range including power-on and hypersonic-unique "windmill" operation. Herein, we will present the fan stage design, and the experimental test results of the fan stage operating from 15 to 100 percent corrected design speed. Whereas, in the companion paper, we will provide an assessment of NASA s APNASA code s ability to predict the fan stage performance and operability over a wide range of speed and bypass ratio.

A Technology Pathway for Airbreathing, Combined-Cycle, Horizontal Space Launch Through SR-71 Based Trajectory Modeling

NASA Technical Reports Server (NTRS)

Kloesel, Kurt J.; Ratnayake, Nalin A.; Clark, Casie M.

2011-01-01

Access to space is in the early stages of commercialization. Private enterprises, mainly under direct or indirect subsidy by the government, have been making headway into the LEO launch systems infrastructure, of small-weight-class payloads of approximately 1000 lbs. These moderate gains have emboldened the launch industry and they are poised to move into the middle-weight class (roughly 5000 lbs). These commercially successful systems are based on relatively straightforward LOX-RP, two-stage, bi-propellant rocket technology developed by the government 40 years ago, accompanied by many technology improvements. In this paper we examine a known generic LOX-RP system with the focus on the booster stage (1st stage). The booster stage is then compared to modeled Rocket-Based and Turbine-Based Combined Cycle booster stages. The air-breathing propulsion stages are based on/or extrapolated from known performance parameters of ground tested RBCC (the Marquardt Ejector Ramjet) and TBCC (the SR-71/J-58 engine) data. Validated engine models using GECAT and SCCREAM are coupled with trajectory optimization and analysis in POST-II to explore viable launch scenarios using hypothetical aerospaceplane platform obeying the aerodynamic model of the SR-71. Finally, and assessment is made of the requisite research technology advances necessary for successful commercial and government adoption of combined-cycle engine systems for space access.

Emiliania huxleyi endures N-limitation with an efficient metabolic budgeting and effective ATP synthesis.

PubMed

Rokitta, Sebastian D; Von Dassow, Peter; Rost, Björn; John, Uwe

2014-12-02

Global change will affect patterns of nutrient upwelling in marine environments, potentially becoming even stricter regulators of phytoplankton primary productivity. To better understand phytoplankton nutrient utilization on the subcellular basis, we assessed the transcriptomic responses of the life-cycle stages of the biogeochemically important microalgae Emiliania huxleyi to nitrogen-limitation. Cells grown in batch cultures were harvested at 'early' and 'full' nitrogen-limitation and were compared with non-limited cells. We applied microarray-based transcriptome profilings, covering ~10.000 known E. huxleyi gene models, and screened for expression patterns that indicate the subcellular responses. The diploid life-cycle stage scavenges nitrogen from external organic sources and -like diatoms- uses the ornithine-urea cycle to rapidly turn over cellular nitrogen. The haploid stage reacts similarly, although nitrogen scavenging is less pronounced and lipid oxidation is more prominent. Generally, polyamines and proline appear to constitute major organic pools that back up cellular nitrogen. Both stages induce a malate:quinone-oxidoreductase that efficiently feeds electrons into the respiratory chain and drives ATP generation with reduced respiratory carbon throughput. The use of the ornithine-urea cycle to budget the cellular nitrogen in situations of limitation resembles the responses observed earlier in diatoms. This suggests that underlying biochemical mechanisms are conserved among distant clades of marine phototrophic protists. The ornithine-urea cycle and proline oxidation appear to constitute a sensory-regulatory system that monitors and controls cellular nitrogen budgets under limitation. The similarity between the responses of the life-cycle stages, despite the usage of different genes, also indicates a strong functional consistency in the responses to nitrogen-limitation that appears to be owed to biochemical requirements. The malate:quinone-oxidoreductase is a genomic feature that appears to be absent from diatom genomes, and it is likely to strongly contribute to the uniquely high endurance of E. huxleyi under nutrient limitation.

Cell cycle re-entry sensitizes podocytes to injury induced death

PubMed Central

Hagen, Manuel; Pfister, Eva; Kosel, Andrea; Shankland, Stuart; Pippin, Jeffrey; Amann, Kerstin; Daniel, Christoph

2016-01-01

ABSTRACT Podocytes are terminally differentiated renal cells, lacking the ability to regenerate by proliferation. However, during renal injury, podocytes re-enter into the cell cycle but fail to divide. Earlier studies suggested that re-entry into cell cycle results in loss of podocytes, but a direct evidence for this is lacking. Therefore, we established an in vitro model to test the consequences of re-entry into the cell cycle on podocyte survival. A mouse immortalized podocyte cell line was differentiated to non-permissive podocytes and stimulated with e.g. growth factors. Stimulated cells were analyzed for mRNA-expression or stained for cell cycle analysis using flow cytometry and immunocytofluorescence microscopy. After stimulation to re-entry into cell cycle, podocytes were stressed with puromycin aminonucleoside (PAN) and analyzed for survival. During permissive stage more than 40% of immortalized podocytes were in the S-phase. In contrast, S-phase in non-permissive differentiated podocytes was reduced to 5%. Treatment with b-FGF dose dependently induced re-entry into cell cycle increasing the number of podocytes in the S-phase to 10.7% at an optimal bFGF dosage of 10 ng/ml. Forty eight hours after stimulation with bFGF the number of bi-nucleated podocytes significantly increased. A secondary injury stimulus significantly reduced podocyte survival preferentially in bi-nucleated podocytes In conclusion, stimulation of podocytes using bFGF was able to induce re-entry of podocytes into the cell cycle and to sensitize the cells for cell death by secondary injuries. Therefore, this model is appropriate for testing new podocyte protective substances that can be used for therapy. PMID:27232327

Accounting for length-bias and selection effects in estimating the distribution of menstrual cycle length.

PubMed

Lum, Kirsten J; Sundaram, Rajeshwari; Louis, Thomas A

2015-01-01

Prospective pregnancy studies are a valuable source of longitudinal data on menstrual cycle length. However, care is needed when making inferences of such renewal processes. For example, accounting for the sampling plan is necessary for unbiased estimation of the menstrual cycle length distribution for the study population. If couples can enroll when they learn of the study as opposed to waiting for the start of a new menstrual cycle, then due to length-bias, the enrollment cycle will be stochastically larger than the general run of cycles, a typical property of prevalent cohort studies. Furthermore, the probability of enrollment can depend on the length of time since a woman's last menstrual period (a backward recurrence time), resulting in selection effects. We focus on accounting for length-bias and selection effects in the likelihood for enrollment menstrual cycle length, using a recursive two-stage approach wherein we first estimate the probability of enrollment as a function of the backward recurrence time and then use it in a likelihood with sampling weights that account for length-bias and selection effects. To broaden the applicability of our methods, we augment our model to incorporate a couple-specific random effect and time-independent covariate. A simulation study quantifies performance for two scenarios of enrollment probability when proper account is taken of sampling plan features. In addition, we estimate the probability of enrollment and the distribution of menstrual cycle length for the study population of the Longitudinal Investigation of Fertility and the Environment Study. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Life cycle strategies of copepods in coastal upwelling zones

NASA Astrophysics Data System (ADS)

Peterson, W.

1998-06-01

Life cycles of copepods of coastal upwelling zones are of the multigenerational type—as many as 10 or more generations may be produced each year, depending upon water temperature, food concentration and length of the upwelling season. Abundant food resources and moderate temperature convey advantages to those copepods living in coastal upwelling zones, however, there is a clear disadvantage in that coastal upwelling zones are highly advective environments. Typically, water circulation patterns are such that surface waters are carried offshore, deeper waters carried onshore and most of the water column over the continental shelf is moving equatorward. The challenge to copepod species that inhabit upwelling systems is life cycle closure—how do eggs, nauplii, juveniles and adults avoid being swept out of these ecosystems in the face of persistent transport out of the system? In this review, I first list the species which dominate coastal upwelling ecosystems then discuss three variations on the multigenerational life cycle scheme that are observed in upwelling systems. The latter part of the review is devoted to discussion of how individuals are retained in the productive continental shelf waters within coastal upwelling ecosystems. The suggestion is made that the only copepod species that successfully achieve life cycle closure in such systems are those that are preadapted to upwelling circulation patterns. Our quantitative understanding of the relative importance of physical factors (such as advection) and biological factors (birth, growth, and mortality) on life cycle strategies and population dynamics is quite rudimentary. It would help our understanding if there were more field studies and more computer modeling studies that focused on seasonal cycles of abundance, development times and vertical distribution of life cycle stages, and measurements of water circulation patterns.

Evidence for photometric activity cycles in 3203 Kepler stars

NASA Astrophysics Data System (ADS)

Reinhold, Timo; Cameron, Robert H.; Gizon, Laurent

2017-07-01

Context. In recent years it has been claimed that the length of stellar activity cycles is determined by the stellar rotation rate. It has been observed that the cycle period increases with rotation period along two distinct sequences, known as the active and inactive sequences. In this picture the Sun occupies a solitary position between the two sequences. Whether the Sun might undergo a transitional evolutionary stage is currently under debate. Aims: Our goal is to measure cyclic variations of the stellar light curve amplitude and the rotation period using four years of Kepler data. Periodic changes in the light curve amplitude or the stellar rotation period are associated with an underlying activity cycle. Methods: Using a recent sample of active stars we compute the rotation period and the variability amplitude for each individual Kepler quarter and search for periodic variations of both time series. To test for periodicity in each stellar time series we consider Lomb-Scargle periodograms and use a selection based on a false alarm probability (FAP). Results: We detect amplitude periodicities in 3203 stars between 0.5 < Pcyc < 6 yr covering rotation periods between 1 < Prot < 40 days. Given our sample size of 23 601 stars and our selection criteria that the FAP is less than 5%, this number is almost three times higher than that expected from pure noise. We do not detect periodicities in the rotation period beyond those expected from noise. Our measurements reveal that the cycle period shows a weak dependence on rotation rate, slightly increasing for longer rotation periods. We further show that the shape of the variability deviates from a pure sine curve, consistent with observations of the solar cycle. The cycle shape does not show a statistically significant dependence on effective temperature. Conclusions: We detect activity cycles in more than 13% of our final sample with a FAP of 5% (calculated by randomly shuffling the measured 90-day variability measurements for each star). Our measurements do not support the existence of distinct sequences in the Prot-Pcyc plane, although there is some evidence for the inactive sequence for rotation periods between 5-25 days. Unfortunately, the total observing time is too short to draw sound conclusions on activity cycles with similar lengths to that of the solar cycle. A table containing all cycle periods and time series is only available in electronic form at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/603/A52

Thermodynamic analysis of performance improvement by reheat on the CO2 transcritical power cycle

NASA Astrophysics Data System (ADS)

Tuo, Hanfei

2012-06-01

The CO2 transcritical rankine power cycle has been widely investigated recently, because of its better temperature glide matching between sensible heat source and working fluid in vapor generator, and its desirable qualities, such as moderate critical point, little environment impact and low cost. A reheat CO2 transcritical power cycle with two stage expansion is presented to improve baseline cycle performance in this paper. Energy and exergy analysis are carried out to investigate effects of important parameters on cycle performance. The main results show that reheat cycle performance is sensitive to the variation of medium pressures and the optimum medium pressures exist for maximizing work output and thermal efficiency, respectively. Reheat cycle is compared to baseline cycle under the same conditions. More significant improvements by reheat are obtained at lower turbine inlet temperatures and larger high cycle pressure. Work output improvement is much higher than thermal efficiency improvement, because extra waste heat is required to reheat CO2. Based on second law analysis, exergy efficiency of reheat cycle is also higher than that of baseline cycle, because more useful work is converted from waste heat. Reheat with two stage expansion has great potential to improve thermal efficiency and especially net work output of a CO2 transcritical power cycle using a low-grade heat source.

Microgravity effects on different stages of higher plant life cycle and completion of the seed-to-seed cycle.

PubMed

De Micco, V; De Pascale, S; Paradiso, R; Aronne, G

2014-01-01

Human inhabitation of Space requires the efficient realisation of crop cultivation in bioregenerative life-support systems (BLSS). It is well known that plants can grow under Space conditions; however, perturbations of many biological phenomena have been highlighted due to the effect of altered gravity and its possible interactions with other factors. The mechanisms priming plant responses to Space factors, as well as the consequences of such alterations on crop productivity, have not been completely elucidated. These perturbations can occur at different stages of plant life and are potentially responsible for failure of the completion of the seed-to-seed cycle. After brief consideration of the main constraints found in the most recent experiments aiming to produce seeds in Space, we focus on two developmental phases in which the plant life cycle can be interrupted more easily than in others also on Earth. The first regards seedling development and establishment; we discuss reasons for slow development at the seedling stage that often occurs under microgravity conditions and can reduce successful establishment. The second stage comprises gametogenesis and pollination; we focus on male gamete formation, also identifying potential constraints to subsequent fertilisation. We finally highlight how similar alterations at cytological level can not only be common to different processes occurring at different life stages, but can be primed by different stress factors; such alterations can be interpreted within the model of 'stress-induced morphogenic response' (SIMR). We conclude by suggesting that a systematic analysis of all growth and reproductive phases during the plant life cycle is needed to optimise resource use in plant-based BLSS. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

Identification of amoebae implicated in the life cycle of Pfiesteria and Pfiesteria-like dinoflagellates

USGS Publications Warehouse

Peglar, M.T.; Nerad, T.A.; Anderson, O.R.; Gillevet, P.M.

2004-01-01

This study was undertaken to assess whether amoebae commonly found in mesohaline environments are in fact stages in the life cycles of Pfiesteria and Pfiesteria-like dinoflagellates. Primary isolations of amoebae and dinoflagellates were made from water and sediment samples from five tributaries of the Chesapeake Bay. Additional amoebae were also cloned from bioassay aquaria where fish mortality was attributed to Pfiesteria. Electron microscopy and small subunit (SSU) rRNA gene sequence analysis of these isolates clearly demonstrated that the commonly depicted amoeboid form of Pfiesteria is very likely a species of Korotnevella and is unrelated to Pfiesteria or Pfiesteria-like dinoflagellates. We have determined that the Pfiesteria and Pfiesteria-like dinoflagellates examined in this study undergo a typical homothallic life cycle without amoeboid stages. Furthermore, we have demonstrated that cloned amoebae sharing morphological characteristics described for stages in the life cycle of Pfiesteria do not transform into dinozoites. The strict clonal isolation and cultivation techniques used in this study substantially support the conclusion that the amoebae and some of the flagellates depicted in the life cycle of Pfiesteria are environmental contaminants of the Pfiesteria culture system and that the Ambush Predator Hypothesis needs to be rigorously reevaluated.

Design for life-cycle profit with simultaneous consideration of initial manufacturing and end-of-life remanufacturing

NASA Astrophysics Data System (ADS)

Kwak, Minjung; Kim, Harrison

2015-01-01

Remanufacturing is emerging as a promising solution for achieving green, profitable businesses. This article considers a manufacturer that produces new products and also remanufactured versions of the new products that become available at the end of their life cycle. For such a manufacturer, design decisions at the initial design stage determine both the current profit from manufacturing and future profit from remanufacturing. To maximize the total profit, design decisions must carefully consider both ends of product life cycle, i.e. manufacturing and end-of-life stages. This article proposes a decision-support model for the life-cycle design using mixed-integer nonlinear programming. With an aim to maximize the total life-cycle profit, the proposed model searches for an (at least locally) optimal product design (i.e. design specifications and the selling price) for the new and remanufactured products. It optimizes both the initial design and design upgrades at the end-of-life stage and also provides corresponding production strategies, including production quantities and take-back rate. The model is extended to a multi-objective model that maximizes both economic profit and environmental-impact saving. To illustrate, the developed model is demonstrated with an example of a desktop computer.

Life Cycle Assessment for Biofuels

EPA Science Inventory

A presentation based on life cycle assessment (LCA) for biofuels is given. The presentation focuses on energy and biofuels, interesting environmental aspects of biofuels, and how to do a life cycle assessment with some examples related to biofuel systems. The stages of a (biofuel...

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

This report compares the energy use, oil use and emissions of electric vehicles (EVs) with those of conventional, gasoline- powered vehicles (CVs) over the total life cycle of the vehicles. The various stages included in the vehicles` life cycles include vehicle manufacture, fuel production, and vehicle operation. Disposal is not included. An inventory of the air emissions associated with each stage of the life cycle is estimated. Water pollutants and solid wastes are reported for individual processes, but no comprehensive inventory is developed. Volume II contains additional details on the vehicle, utility, and materials analyses and discusses several details ofmore » the methodology.« less

Plasma volume losses during simulated weightlessness in women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drew, H.; Fortney, S.; La France, N.

Six healthy women not using oral contraceptives underwent two 11-day intervals of complete bedrest (BR) with the BR periods separated by 4 weeks of ambulatory control. Change in plasma volume (PV) was monitored during BR to test the hypothesis that these women would show a smaller decrease in PV than PV values reported in similarly stressed men due to the water retaining effects of the female hormones. Bedrest periods were timed to coincide with opposing stages of the menstrual cycle in each woman. The menstrual cycle was divided into 4 separate stages; early follicular, ovulatory, early luteal, and late lutealmore » phases. The percent decrease of PV showed a consistent decrease for each who began BR while in stage 1, 3 or 4 of the menstrual cycle. However, the females who began in stage 2 showed a transient attenuation in PV loss. Overall, PV changes seen in women during BR were similar to those reported for men. The water-retaining effects of menstrual hormones were evident only during the high estrogen ovulatory stage. The authors conclude the protective effects of menstrual hormones on PV losses during simulated weightless conditions appear to be only small and transient.« less

The deformation record of olivine in mylonitic peridotites from the Finero Complex, Ivrea Zone: Separate deformation cycles during exhumation

NASA Astrophysics Data System (ADS)

Matysiak, Agnes K.; Trepmann, Claudia A.

2015-12-01

Mylonitic peridotites from the Finero complex are investigated to detect characteristic olivine microfabrics that can resolve separate deformation cycles at different metamorphic conditions. The heterogeneous olivine microstructures are characterized by deformed porphyroclasts surrounded by varying amounts of recrystallized grains. A well-developed but only locally preserved foam structure is present in recrystallized grain aggregates. This indicates an early stage of dynamic recrystallization and subsequent recovery and recrystallization at quasi-static stress conditions, where the strain energy was reduced such that a reduction in surface energy controlled grain boundary migration. Ultramylonites record a renewed stage of localized deformation and recrystallization by a second generation of recrystallized grains that do not show a foam structure. This second generation of recrystallized grains as well as sutured grain and kink band boundaries of porphyroclasts indicate that these microstructures developed during a stage of localized deformation after development of the foam structure. The heterogeneity of the microfabrics is interpreted to represent several (at least two) cycles of localized deformation separated by a marked hiatus with quasi-static recrystallization and recovery and eventually grain growth. The second deformation cycle did not only result in reactivation of preexisting shear zones but instead also locally affected the host rock that was not deformed in the first stage. Such stress cycles can result from sudden increases in differential stress imposed by seismic events, i.e., high stress-loading rates, during exhumation of the Finero complex.

Dose-dependent inhibition of uterine contractility by nitric oxide: A potential mechanism underlying persistent breeding-induced endometritis in the mare.

PubMed

Khan, Firdous A; Chenier, Tracey S; Murrant, Coral L; Foster, Robert A; Hewson, Joanne; Scholtz, Elizabeth L

2017-03-01

Nitric oxide (NO) may have a role in persistent breeding-induced endometritis in mares through an inhibitory effect on uterine contractility. The objectives of this study were to test the effect of NO on spontaneous uterine contractility in-vitro and to evaluate whether this effect varied between the longitudinal and circular muscle layers of the uterus. Reproductive tracts were collected from eight euthanized non-pregnant mares (age 4-19 years; body weight 405-530 kg). Transrectal examination of the reproductive tract was performed before euthanasia to evaluate stage of the estrous cycle and presence of any apparent abnormality. After euthanasia, one uterine tissue sample was collected for histological evaluation and four full-thickness uterine tissue strips (10-12 mm × 2 mm), two parallel to each muscle layer, were excised for in-vitro contractility evaluation. Strips were suspended in tissue chambers containing Krebs-Henseleit solution, with continuous aeration (95% O 2 -5% CO 2 ; pH 7.4) at 37 °C. After equilibration, spontaneous contractility was recorded (pre-treatment) and strips excised in each direction were randomly allocated to each of two groups: 1) SNAP (S-nitroso-N-acetylpenicillamine, an NO donor); or 2) NAP (N-acetyl-d-penicillamine, vehicle and time-matched control). These were treated at 15 min intervals with increasing concentrations (10 -7  M to 10 -3  M) of SNAP and NAP, respectively. Contractility data was recorded throughout the experiment. An interaction effect of group-by-concentration was observed (P < 0.0001). The mean contractility after treatment with 10 -4  M and 10 -3  M SNAP were significantly lower than the pre-treatment contractility and the mean contractility after treatment with lower SNAP concentrations. In contrast, contractility did not change significantly in the NAP treated controls. The effect of treatment on uterine contractility was not influenced by age or weight of the mare, stage of estrous cycle, uterine histology grade, or muscle layer. Secondary findings included significant main effects of stage of estrous cycle (increased contractility in estrus compared to diestrus), uterine histology grade (decreased contractility in grade IIB compared to grade I) and age (decreased contractility in mares aged > 8 years compared to mares aged ≤ 8 years). In conclusion, results of this study indicate that NO has a dose-dependent inhibitory effect on spontaneous uterine contractility irrespective of the muscle layer in the mare. Copyright © 2017 Elsevier Inc. All rights reserved.

Physical and chemical microstructural damage in pressed CL-20 explosives

NASA Astrophysics Data System (ADS)

Demol, Gauthier; Sandusky, Harold W.

2000-04-01

The ultimate utility of CL-20 as an ingredient in explosive and propellant formulations will depend upon the ability to understand the factors that are responsible for batch-to-batch variability with respect to sensitivity, and also to control the sensitivity in formulations within acceptable limits. We used light microscopy of cold-mounted, polished samples to characterize CL-20 at various stages in its life cycle. The evolution of damage from the initial neat crystals of CL-20 to the ready-to-use pressed pellets shows that processing seriously damages the crystals. These crystals are very brittle, and several explanations are proposed.

EEG sleep activities react topographically different to GABAergic sleep modulation by flunitrazepam: relationship to regional distribution of benzodiazepine receptor subtypes?

PubMed

Scheuler, W

Spectral analysis was performed to study the response of various EEG sleep activities to a modification of GABAergic sleep regulation by flunitrazepam. We observed sleep stage- and sleep cycle-dependent differences in the topographic distribution of the reactions. An increase in power density was found in the frontal regions for the alpha 2 and sigma 1 frequency band whereas a decrease in power density was emphasized in the posterior regions for the delta and alpha 1 frequency band. These topographic differences might be related to the regional distribution of benzodiazepine receptor subtypes.

Variation in the excitability of developed D. discoideum cells as a function of agar concentration in the substrate

NASA Astrophysics Data System (ADS)

Oikawa, Noriko; Bae, Albert; Amselem, Gabriel; Bodenschatz, Eberhard

2010-03-01

In the absence of nutrients, Dictyostelium discoideum cells enter a developmental cycle--they signal each other, aggregate, and ultimately form fruiting bodies. During the signaling stage, the cells relay waves of cyclic adenosine 3',5' monophosphate (cAMP). We observed a transition from spiral to circular patterns in the signaling wave, depending on the agar concentration of the substrate. In this talk we will present the changes in the times for the onset of signaling and synchronization versus agar concentration, as measured by spectral entropy. We also will discuss the origin of these effects.

Avian haematozoa 3. Color atlas of leucocytozoon simondi

USGS Publications Warehouse

Herman, C.M.; Desser, S.S.; Bennett, G.F.; Tarshis, I.B.

1977-01-01

The life cycle of Leucocytozoon simondi is Illustrated in a series of color photomicrographs of the various stages of development in the blackfly vector and in the tissues and blood of Anatidae. A brief discussion of the life cycle is presented and taxonomic status of the parasite is reviewed. The bibliography includes references to the stages depicted and other phases of the development, morphology and pathogenesis of .L. simondi.

The new reports on life cycle of Heterosigma akashiwo (Raphidophyceae)

NASA Astrophysics Data System (ADS)

Kim, J. H.

2016-02-01

Heterosigma akashiwo (Hada) Hada (Raphidophyceae) is a noxious bloom-forming algal species that has damaged many fish farms in coastal waters during recent decades. Consequently, many studies focused on the population dynamics of H. akashiwo, while its life cycle was not well studied. In this study, we investigated veiled life cycle of H. akashiwo through culture based method. We cultured eight H. akashiwostrains originated from Korea, Japan, USA under various conditions (water temp., light intensity, salinity, pH). Morphological diversity of cells were observed via light microscopy and scanning electron microscopy. To observe nucleus of living cell, cells were stained with Hoechst and changes of cells in culture were observed through time-lapse. For observation of cysts and their germination process, cysts were isolated from sediment. Different from the previous knowledge, H. akashiwo has only vegetative cell stage and cyst stage, we discovered that H. akashiwo has extra small cell stage and large cell stage. Large cells are much bigger (20-45 µm) than vegetative cells. Large cell formation was resulted from fusion of vegetative cells. Small cells were very small (6.88 ± 0.85 µm), these cell divided from large cell or formed in germination process of cysts rarely. Small cells have lower motility than vegetative cells. These results improved the study of life stages of H. akashiwo and this fundamental investigation provide important new information and improve our understanding of the life cycle of H. akashiwo.

Microstructure Refinement and Mechanical Properties of 304 Stainless Steel by Repetitive Thermomechanical Processing

NASA Astrophysics Data System (ADS)

Al-Fadhalah, Khaled; Aleem, Muhammad

2018-04-01

Repetitive thermomechanical processing (TMP) was applied for evaluating the effect of strain-induced α'-martensite transformation and reversion annealing on microstructure refinement and mechanical properties of 304 austenitic stainless steel. The first TMP scheme consisted of four cycles of tensile deformation to strain of 0.4, while the second TMP scheme applied two cycles of tensile straining to 0.6. For both schemes, tensile tests were conducted at 173 K (- 100 °C) followed by 5-minute annealing at 1073 K (800 °C). The volume fraction of α'-martensite in deformed samples increased with increasing cycles, reaching a maximum of 98 vol pct. Examination of annealed microstructure by electron backscattered diffraction indicated that increasing strain and/or number of cycles resulted in stronger reversion to austenite with finer grain size of 1 μm. Yet, increasing strain reduced the formation of Σ3 boundaries. The annealing textures generally show reversion of α'-martensite texture components to the austenite texture of brass and copper orientations. The increase in strain and/or number of cycles resulted in stronger intensity of copper orientation, accompanied by the formation of recrystallization texture components of Goss, cube, and rotated cube. The reduction in grain size with increasing cycles caused an increase in yield strength. It also resulted in an increase in strain hardening rate during deformation due to the increase in the formation of α'-martensite. The increase in strain hardening rate occurred in two consecutive stages, marked as stages II and III. The strain hardening in stage II is due to the formation of α'-martensite from either austenite or ɛ-martensite, while the stage-III strain hardening is attributed to the necessity to break the α'-martensite-banded structure for forming block-type martensite at high strains.

Transcriptome profiling of the honeybee parasite Varroa destructor provides new biological insights into the mite adult life cycle.

PubMed

Mondet, Fanny; Rau, Andrea; Klopp, Christophe; Rohmer, Marine; Severac, Dany; Le Conte, Yves; Alaux, Cedric

2018-05-04

The parasite Varroa destructor represents a significant threat to honeybee colonies. Indeed, development of Varroa infestation within colonies, if left untreated, often leads to the death of the colony. Although its impact on bees has been extensively studied, less is known about its biology and the functional processes governing its adult life cycle and adaptation to its host. We therefore developed a full life cycle transcriptomic catalogue in adult Varroa females and included pairwise comparisons with males, artificially-reared and non-reproducing females (10 life cycle stages and conditions in total). Extensive remodeling of the Varroa transcriptome was observed, with an upregulation of energetic and chitin metabolic processes during the initial and final phases of the life cycle (e.g. phoretic and post-oviposition stages), whereas during reproductive stages in brood cells genes showing functions related to transcriptional regulation were overexpressed. Several neurotransmitter and neuropeptide receptors involved in behavioural regulation, as well as active compounds of salivary glands, were also expressed at a higher level outside the reproductive stages. No difference was detected between artificially-reared phoretic females and their counterparts in colonies, or between females who failed to reproduce and females who successfully reproduced, indicating that phoretic individuals can be reared outside host colonies without impacting their physiology and that mechanisms underlying reproductive failure occur before oogenesis. We discuss how these new findings reveal the remarkable adaptation of Varroa to its host biology and notably to the switch from living on adults to reproducing in sealed brood cells. By spanning the entire adult life cycle, our work captures the dynamic changes in the parasite gene expression and serves as a unique resource for deciphering Varroa biology and identifying new targets for mite control.

Combined therapy in children and adolescents with classical Hodgkin's lymphoma: A report from the SFCE on MDH-03 national guidelines.

PubMed

Seror, E; Donadieu, J; Pacquement, H; Abbou, S; Lambilliotte, A; Schell, M; Curtillet, C; Gandemer, V; Pasquet, M; Aladjidi, N; Lutz, P; Schmitt, C; Deville, A; Minckes, O; Vanier, J P; Armari-Alla, C; Thomas, C; Gorde-Grosjean, S; Millot, F; Blouin, P; Garnier, N; Coze, C; Devoldere, C; Reguerre, Y; Helfre, S; Claude, L; Clavel, J; Oberlin, O; Landman-Parker, J; Leblanc, T

Hodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1-89.7%) and 97% (94.5-98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.

Identification of chemicals inducing cardiomyocyte proliferation in developmental stage-specific manner with pluripotent stem cells.

PubMed

Uosaki, Hideki; Magadum, Ajit; Seo, Kinya; Fukushima, Hiroyuki; Takeuchi, Ayako; Nakagawa, Yasuaki; Moyes, Kara White; Narazaki, Genta; Kuwahara, Koichiro; Laflamme, Michael; Matsuoka, Satoshi; Nakatsuji, Norio; Nakao, Kazuwa; Kwon, Chulan; Kass, David A; Engel, Felix B; Yamashita, Jun K

2013-12-01

The proliferation of cardiomyocytes is highly restricted after postnatal maturation, limiting heart regeneration. Elucidation of the regulatory machineries for the proliferation and growth arrest of cardiomyocytes is imperative. Chemical biology is efficient to dissect molecular mechanisms of various cellular events and often provides therapeutic potentials. We have been investigating cardiovascular differentiation with pluripotent stem cells. The combination of stem cell and chemical biology can provide novel approaches to investigate the molecular mechanisms and manipulation of cardiomyocyte proliferation. To identify chemicals that regulate cardiomyocyte proliferation, we performed a screening of a defined chemical library based on proliferation of mouse pluripotent stem cell-derived cardiomyocytes and identified 4 chemical compound groups: inhibitors of glycogen synthase kinase-3, p38 mitogen-activated protein kinase, and Ca(2+)/calmodulin-dependent protein kinase II, and activators of extracellular signal-regulated kinase. Several appropriate combinations of chemicals synergistically enhanced proliferation of cardiomyocytes derived from both mouse and human pluripotent stem cells, notably up to a 14-fold increase in mouse cardiomyocytes. We also examined the effects of identified chemicals on cardiomyocytes in various developmental stages and species. Whereas extracellular signal-regulated kinase activators and Ca(2+)/calmodulin-dependent protein kinase II inhibitors showed proliferative effects only on cardiomyocytes in early developmental stages, glycogen synthase kinase-3 and p38 mitogen-activated protein kinase inhibitors substantially and synergistically induced re-entry and progression of cell cycle in neonatal but also as well as adult cardiomyocytes. Our approach successfully uncovered novel molecular targets and mechanisms controlling cardiomyocyte proliferation in distinct developmental stages and offered pluripotent stem cell-derived cardiomyocytes as a potent tool to explore chemical-based cardiac regenerative strategies.

Differential patterns of accumulation and retention of dietary trace elements associated with coal ash during larval development and metamorphosis of an amphibian.

PubMed

Heyes, Andrew; Rowe, Christopher L; Conrad, Phillip

2014-01-01

We performed an experiment in which larval gray tree frogs (Hyla chrysoscelis) were raised through metamorphosis on diets increased with a suite of elements associated with coal combustion residues (silver [Ag], arsenic [As], cadmium [Cd], chromium [Cr], copper [Cu], mercury [Hg], lead [Pb], selenium [Se], vanadium [V], and zinc [Zn]) at "low" and "high" concentrations. We quantified accumulation of metals at three life stages (mid-larval development, initiation of metamorphosis, and completion of metamorphosis) as well as effects on survival, metabolic rate, size at metamorphosis, and duration and loss of weight during metamorphosis. Most elements were accumulated in a dose-dependent pattern by some or all life stages, although this was not the case for Hg. For most elements, larval body burdens exceeded those of later life stages in some or all treatments (control, low, or high). However for Se, As, and Hg, body burdens in control and low concentrations were increased in later compared with earlier life stages. A lack of dose-dependent accumulation of Hg suggests that the presence of high concentrations of other elements (possibly Se) either inhibited accumulation or increased depuration of Hg. The duration of metamorphosis (forelimb emergence through tail resorption) was lengthened in individuals exposed to the highest concentrations of elements, but there were no other statistically significant biological effects. This study shows that patterns of accumulation and possibly depuration of metals and trace elements are complex in animals possessing complex life cycles. Further study is required to determine specific interactions affecting these patterns, in particular which elements may be responsible for affecting accumulation or retention of Hg when organisms are exposed to complex mixtures of elements.

The development of preimplantation mouse parthenogenones in vitro in absence of glucose: influence of the maternally inherited components.

PubMed

Mognetti, B; Leppens, G; Sakkas, D

1996-04-01

Mouse preimplantation embryo development is characterized by a switch from a dependence on the tricarboxylic acid cycle pre-compaction to a metabolism based on glycolysis post-compaction. In-view of this, the role of glucose in embryo culture medium has come under increased analysis and has lead to improved development of outbred mouse embryos in glucose free medium. Another type of embryo that has proven difficult to culture is the parthenogenetic (PN) mouse embryo. With this in mind we have investigated the effect of glucose deprivation on PN embryo development in vitro. Haploid and diploid PN embryos were grown in medium M16 with or without glucose (M16-G) and development, glycolytic rate, and methionine incorporation rates assessed. Haploid PN and normal embryo development to the blastocyst stage did not differ in either M16 or M16-G. In contrast, although diploid PN embryos formed blastocysts in M16 (28.3%), they had difficulty in undergoing the morula/blastocyst transition in M16-G (7.6%). There was no significant difference in mean cell numbers of haploid PN, diploid PN and normal embryos cultured in M16 and M16-G at the morula and blastocyst stage. Transfer of diploid PN embryos from M16-G to M16 at the four- to eight-cell stage dramatically increased blastocyst development. At the morula stage diploid PN embryos grown in M16-G exhibited a higher glucose metabolism and protein synthesis compared to those grown in M16 and to haploid PN embryos. Difficulties of diploid PN embryos in undergoing the morula/blastocyst transition in absence of glucose infer the existence of a link between the maternally inherited components and the preimplantation embryos dependence on glucose.

Circadian Activators Are Expressed Days before They Initiate Clock Function in Late Pacemaker Neurons from Drosophila.

PubMed

Liu, Tianxin; Mahesh, Guruswamy; Houl, Jerry H; Hardin, Paul E

2015-06-03

Circadian pacemaker neurons in the Drosophila brain control daily rhythms in locomotor activity. These pacemaker neurons can be subdivided into early or late groups depending on whether rhythms in period (per) and timeless (tim) expression are initiated at the first instar (L1) larval stage or during metamorphosis, respectively. Because CLOCK-CYCLE (CLK-CYC) heterodimers initiate circadian oscillator function by activating per and tim transcription, a Clk-GFP transgene was used to mark when late pacemaker neurons begin to develop. We were surprised to see that CLK-GFP was already expressed in four of five clusters of late pacemaker neurons during the third instar (L3) larval stage. CLK-GFP is only detected in postmitotic neurons from L3 larvae, suggesting that these four late pacemaker neuron clusters are formed before the L3 larval stage. A GFP-cyc transgene was used to show that CYC, like CLK, is also expressed exclusively in pacemaker neurons from L3 larval brains, demonstrating that CLK-CYC is not sufficient to activate per and tim in late pacemaker neurons at the L3 larval stage. These results suggest that most late pacemaker neurons develop days before novel factors activate circadian oscillator function during metamorphosis. Copyright © 2015 the authors 0270-6474/15/358662-10$15.00/0.

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

PubMed Central

Brown, Kyle S.; Oestmo, Simen; Pereira, Telmo; Ranhorn, Kathryn L.; Schoville, Benjamin J.; Marean, Curtis W.

2017-01-01

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5–6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, ‘place provisioning’, longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6. PMID:28355257

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa.

PubMed

Wilkins, Jayne; Brown, Kyle S; Oestmo, Simen; Pereira, Telmo; Ranhorn, Kathryn L; Schoville, Benjamin J; Marean, Curtis W

2017-01-01

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.

Super's Career Stages and the Decision to Change Careers.

ERIC Educational Resources Information Center

Smart, Roslyn; Peterson, Candida

1997-01-01

Australians (n=226) in one of four stages of a second career (contemplating, choosing a field, implementing, change completed) were compared with 81 nonchangers. Job satisfaction varied as a function of stage. Results supported Super's theory that career changers cycle through the full set of career stages a second time. (SK)

A Multi-Stage Maturity Model for Long-Term IT Outsourcing Relationship Success

ERIC Educational Resources Information Center

Luong, Ming; Stevens, Jeff

2015-01-01

The Multi-Stage Maturity Model for Long-Term IT Outsourcing Relationship Success, a theoretical stages-of-growth model, explains long-term success in IT outsourcing relationships. Research showed the IT outsourcing relationship life cycle consists of four distinct, sequential stages: contract, transition, support, and partnership. The model was…

1977 Nationwide Personal Transportation Study : a life cycle of travel by the American family

DOT National Transportation Integrated Search

1981-07-01

This report provides information about family trips and travel from the point of view of the family life cycle, using data from the 1977 Nationwide Personal Transportation Study. Daily travel characteristics of families in stages of four life cycles ...

Impact of sex steroids and reproductive stage on sleep-dependent memory consolidation in women.

PubMed

Baker, Fiona C; Sattari, Negin; de Zambotti, Massimiliano; Goldstone, Aimee; Alaynick, William A; Mednick, Sara C

2018-03-21

Age and sex are two of the three major risk factors for Alzheimer's disease (ApoE-e4 allele is the third), with women having a twofold greater risk for Alzheimer's disease after the age of 75 years. Sex differences have been shown across a wide range of cognitive skills in young and older adults, and evidence supports a role for sex steroids, especially estradiol, in protecting against the development of cognitive decline in women. Sleep may also be a protective factor against age-related cognitive decline, since specific electrophysiological sleep events (e.g. sleep spindle/slow oscillation coupling) are critical for offline memory consolidation. Furthermore, studies in young women have shown fluctuations in sleep events and sleep-dependent memory consolidation during different phases of the menstrual cycle that are associated with the levels of sex steroids. An under-appreciated possibility is that there may be an important interaction between these two protective factors (sex steroids and sleep) that may play a role in daily fluctuations in cognitive processing, in particular memory, across a woman's lifespan. Here, we summarize the current knowledge of sex steroid-dependent influences on sleep and cognition across the lifespan in women, with special emphasis on sleep-dependent memory processing. We further indicate gaps in knowledge that require further experimental examination in order to fully appreciate the complex and changing landscape of sex steroids and cognition. Lastly, we propose a series of testable predictions for how sex steroids impact sleep events and sleep-dependent cognition across the three major reproductive stages in women (reproductive years, menopause transition, and post-menopause). Copyright © 2018 Elsevier Inc. All rights reserved.

TEN-YEAR FOLLOW UP OF A PHASE II STUDY OF DOSE-INTENSE PACLITAXEL WITH CISPLATIN AND CYCLOPHOSPHAMIDE AS INITIAL THERAPY FOR POOR-PROGNOSIS ADVANCED-STAGE EPITHELIAL OVARIAN CANCER

PubMed Central

Sarosy, Gisele A.; Hussain, Mahrukh M.; Seiden, Michael V.; Fuller, A.F.; Nikrui, N.; Goodman, Annekathryn; Minasian, Lori; Reed, Eddie; Steinberg, Seth M.; Kohn, Elise C.

2009-01-01

SUMMARY Background To assess activity and toxicity in newly diagnosed advanced stage epithelial ovarian cancer (EOC) patients receiving dose-intense paclitaxel, cyclophosphamide, cisplatin, and filgrastim delivered with a flexible dosing schedule. Methods Patients with Stage III/IV EOC received cyclophosphamide 750 mg/m2, followed by 24 hr infusion of paclitaxel 250 mg/m2, and cisplatin 75 mg/m2 on day 2. Filgrastim began on day 3 at 10 μg/kg/d × 9d. Patients received six cycles of all drugs. Those with pathologic complete response or microscopic residual disease at the conclusion of six cycles of therapy received an additional cycles two to four cycles of paclitaxel with cyclophosphamide. Patients with objective response continued cyclophosphamide and paclitaxel. Results 62 patients were enrolled. Thirty-two of these 62 patients had stage IIIC disease, and 26 of 62 had stage IV disease. Using an intent to treat analysis, 55 (89%) experienced clinical complete remission (CCR). With a median potential follow-up of 11.4 years, the median progression free survival is 18.9 months and median survival is 5.4 years. The most serious toxicity was grade 3/4 neutropenic fever (35%). Although all participants developed peripheral neuropathy, improvement in neuropathic symptoms began with decrease or cessation of paclitaxel. Conclusions This regimen yielded a high response rate and encouraging overall survival. These data and those of the Japanese Gynecologic Oncology Group suggest that further study of dose dense or intense paclitaxel regimens in women with newly diagnosed advanced stage EOC is warranted. PMID:20091841

Shifts in microbial community structure and function in stream sediments during experimentally simulated riparian succession.

PubMed

Frossard, Aline; Gerull, Linda; Mutz, Michael; Gessner, Mark O

2013-05-01

Successional changes of terrestrial vegetation can profoundly influence stream ecosystem structure and function. We hypothesized that microbial enzyme production and community structure in stream beds depend on terrestrial litter inputs that reflect different stages of riparian succession. Outdoor experimental channels were supplied with leaf-litter of varying quantities and qualities to mimic litter supply during five successional stages: (1) an initial biofilm stage; (2) an open-land stage with grass litter; (3) a transitional stage with mixed grass and birch litter; (4) an early forest stage with birch litter; and (5) an advanced forest stage with 2.5 × the amount of birch litter. Mean potential activities of nitrogen- and phosphorus-acquiring enzymes in sediments (20.7 and 67.3 μmol g(-1) dry mass) were 12-70 times greater than those of carbon-acquiring enzymes (0.96-1.71 μmol g(-1) dry mass), with the former reduced 1.3-8.3-fold in channels with tree litter. These patterns could suggest gradually diminishing nutrient limitation of microbial activity during riparian succession, potentially linked both to an increasing supply by the added litter and to a lower nutrient demand as algal biomass and labile carbon supply by photosynthetic exudates declined. As the observed shifts in nutrient-acquiring enzymes were reflected in changes of sediment microbial communities, these results indicate that both the type and density of terrestrial vegetation control microbial community structure and function in stream sediments, particularly enzyme production related to nutrient cycling. © 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Vertical distribution of microphysical properties in radiation fogs - A case study

NASA Astrophysics Data System (ADS)

Egli, S.; Maier, F.; Bendix, J.; Thies, B.

2015-01-01

The present study investigates the validity of a theoretical liquid water content (LWC) profile in fog layers currently used for satellite based ground fog detection, with a special focus on the temporal dynamics during fog life cycle. For this purpose, LWC profiles recorded during two different fog events by means of a tethered balloon borne measurement system are presented and discussed. The results indicate a good agreement in trend and gradient between measured and theoretical LWC profiles during the mature stage of the fog life cycle. The profile obtained during the dissipation stage shows less accordance with the theoretical profile. To improve the agreement between theoretical and measured LWC profiles, the evolutionary stages during the fog life cycle should be incorporated. However, the variability within the prenoted measurements points out that more LWC profiles during a great variety of different fog events have to be collected for a well-justified adaptation of the theoretical LWC profile, considering fog life cycle phases in the future. In general, this underlines the existing knowledge gap regarding the vertical distribution of microphysical properties in natural fogs.

Cyclophilin A Is Overexpressed in Hepatocellular Carcinoma and Is Associated with the Cell Cycle.

PubMed

Gong, Zhaohua; Chi, Cheng; Huang, Xiaojuan; Chu, Hongjin; Wang, Jiahui; Du, Fengcai; Jiang, Lixin; Chen, Jian

2017-08-01

To investigate the expression of cyclophilin A (CypA) in human hepatocellular carcinoma (HCC) and explore the effects of CypA on the cell cycle in HCC. CypA expression was assessed by immunohistochemistry in 48 cases of HCC tissues and paired adjacent tissues. CypA plasmid was transfected into HCC cells and the cell cycle was analyzed. Positivity for CypA was higher in HCC tissues than in adjacent tissues (79.1% vs. 12.5%, p<0.05). Positivity for CypA was significantly higher in stage III and IV HCC than in stage I and II (p<0.05). Elevated CypA induced an increase of the percentage of S-phase cells (from 34.79% to 42.14%) and a decrease of G 0 -G 1 phase cells (from 58.10% to 50.64%). CypA is overexpressed in HCC and is associated with TNM stage. CypA also appears to promote the transition of the cell cycle from G 1 to S phase. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Uterine Development and Fertility Are Dependent on Gene Dosage of the Nuclear Receptor Coregulator REA

PubMed Central

Park, Sunghee; Yoon, Sangyeon; Zhao, Yuechao; Park, Seong-Eun; Liao, Lan; Xu, Jianming; Lydon, John P.; DeMayo, Francesco J.; O'Malley, Bert W.; Bagchi, Milan K.

2012-01-01

Although the effectiveness of nuclear hormone-receptor complexes is known to depend on coregulator partner proteins, relatively little is known about the roles of coregulators in uterine development and early stages of pregnancy and implantation. Because conventional genetic deletion of the coregulator, repressor of estrogen receptor activity (REA), was embryonic lethal, we here study REA conditional knockout mice generated by cre-loxP recombination, in which REA function was abrogated only in progesterone receptor-expressing tissues, to define the roles of REA in postembryonic stages and in a tissue-specific manner. We find that REA has gene dose-dependent activity impacting uterine development and fertility. Conditional homozygous mutant (REAd/d) mice developed to adulthood and showed normal ovarian function, but females were infertile with severely compromised uterine development and function characterized by cell cycle arrest, apoptosis, and altered adenogenesis (endometrial gland morphogenesis), resulting in failure of implantation and decidualization. By contrast, mice heterozygous for REA (REAf/d) had a very different phenotype, with estradiol treatment resulting in hyperstimulated, large uteri showing increased proliferation of luminal epithelial cells, and enhanced fluid imbibition associated with altered regulation of aquaporins. These REAf/d female mice showed a subfertility phenotype with reduced numbers and sizes of litters. These findings highlight that uterine development and regulation of estrogen receptor activities show a bimodal dependence on the gene dosage of REA. Optimal uterine development and functional activities require the normal gene dosage of REA, with partial or complete deletion resulting in hyperresponsiveness or underresponsiveness to hormone and subfertility or infertility, respectively. PMID:22585830

MINA controls proliferation and tumorigenesis of glioblastoma by epigenetically regulating cyclins and CDKs via H3K9me3 demethylation.

PubMed

Huang, M-Y; Xuan, F; Liu, W; Cui, H-J

2017-01-19

It is generally known that histone demethylases regulate gene transcription by altering the methylate status on histones, but their roles in cancers and the underlying molecular mechanisms still remain unclear. MYC-induced nuclear antigen (MINA) is reported to be a histone demethylase and highly expressed in many cancers. Here, for the first time, we show that MINA is involved in glioblastoma carcinogenesis and reveal the probable mechanisms of it in cell-cycle control. Kaplan-Meier analysis of progression-free survival showed that high MINA expression was strongly correlated with poor outcome and advancing tumor stage. MINA knockdown significantly repressed the cell proliferation and tumorigenesis abilities of glioblastoma cells in vitro and in vivo that were rescued by overexpressing the full-length MINA afterwards. Microarray analysis after knockdown of MINA revealed that MINA probably regulated glioblastoma carcinogenesis through the predominant cell-cycle pathways. Further investigation showed that MINA deficiency led to a cell-cycle arrest in G1 and G2 phases. And among the downstream genes, we found that cyclins and cyclin-dependent kinases were directly activated by MINA via the demethylation of H3K9me3.

Factors influencing the life cycle burdens of the recovery of energy from residual municipal waste.

PubMed

Burnley, Stephen; Coleman, Terry; Peirce, Adam

2015-05-01

A life cycle assessment was carried out to assess a selection of the factors influencing the environmental impacts and benefits of incinerating the fraction of municipal waste remaining after source-separation for reuse, recycling, composting or anaerobic digestion. The factors investigated were the extent of any metal and aggregate recovery from the bottom ash, the thermal efficiency of the process, and the conventional fuel for electricity generation displaced by the power generated. The results demonstrate that incineration has significant advantages over landfill with lower impacts from climate change, resource depletion, acidification, eutrophication human toxicity and aquatic ecotoxicity. To maximise the benefits of energy recovery, metals, particularly aluminium, should be reclaimed from the residual bottom ash and the energy recovery stage of the process should be as efficient as possible. The overall environmental benefits/burdens of energy from waste also strongly depend on the source of the power displaced by the energy from waste, with coal giving the greatest benefits and combined cycle turbines fuelled by natural gas the lowest of those considered. Regardless of the conventional power displaced incineration presents a lower environmental burden than landfill. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cycle Analysis of a New Air Engine Design

NASA Astrophysics Data System (ADS)

Attar, Wiam Fadi

This thesis investigates a new externally heated engine design being developed by Soony Systems Inc. to serve as the prime mover in a residential-scale combined heat and power system. This is accomplished by developing a thermodynamic model for the engine and sweeping through the design parameter space in order to identify designs that maximize power output, efficiency, and brake mean effective pressure (BMEP). It was discovered that the original engine design was flawed so a new design was proposed and analyzed. The thermodynamic model was developed in four stages. The first model was quasi-static while the other three were time-dependent and used increasingly realistic models of the heat exchangers. For the range of design parameters investigated here, the peak power output is 6.8 kW, the peak efficiency is approximately 60%, and the peak BMEP is 389 kPa. These performance levels are compared to those of other closed-cycle engines. The results suggest that the Soony engine has the potential to be more efficient than Stirlings because it more closely approximates the Carnot cycle, but this comes at the cost of significantly lower BMEP (389 kPa vs. 2,760 kPa for the SOLO Stirling engine).

Regulation of tomato fruit pericarp development by an interplay between CDKB and CDKA1 cell cycle genes

PubMed Central

Czerednik, Anna; Busscher, Marco; Bielen, Bram A.M.; Wolters-Arts, Mieke; de Maagd, Ruud A.; Angenent, Gerco C.

2012-01-01

Growth of tomato fruits is determined by cell division and cell expansion, which are tightly controlled by factors that drive the core cell cycle. The cyclin-dependent kinases (CDKs) and their interacting partners, the cyclins, play a key role in the progression of the cell cycle. In this study the role of CDKA1, CDKB1, and CDKB2 in fruit development was characterized by fruit-specific overexpression and down-regulation. CDKA1 is expressed in the pericarp throughout development, but is strongly up-regulated in the outer pericarp cell layers at the end of the growth period, when CDKB gene expression has ceased. Overexpression of the CDKB genes at later stages of development and the down-regulation of CDKA1 result in a very similar fruit phenotype, showing a reduction in the number of cell layers in the pericarp and alterations in the desiccation of the fruits. Expression studies revealed that CDKA1 is down-regulated by the expression of CDKB1/2 in CDKB1 and CDKB2 overexpression mutants, suggesting opposite roles for these types of CDK proteins in tomato pericarp development. PMID:22282536

SUMOylated MAFB promotes colorectal cancer tumorigenesis

PubMed Central

Xie, Yin-Yin; Sun, Xiao-Jian; Zhao, Ren; Huang, Qiu-Hua

2016-01-01

The transcription factor, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), promotes tumorigenesis in some cancers. In this study, we found that MAFB levels were increased in clinical colorectal cancer (CRC) samples, and higher expression correlated with more advanced TNM stage. We identified MAFB amplifications in a majority of tumor types in an assessment of The Cancer Genome Atlas database. Altered MAFB levels due to gene amplification, deletion, mutation, or transcription upregulation occurred in 9% of CRC cases within the database. shRNA knockdown experiments demonstrated that MAFB deficiency blocked CRC cell proliferation by arresting the cell cycle at G0/G1 phase in vitro. We found that MAFB could be SUMOylated by SUMO1 at lysine 32, and this modification was critical for cell cycle regulation by MAFB in CRC cells. SUMOylated MAFB directly regulated cyclin-dependent kinase 6 transcription by binding to its promoter. MAFB knockdown CRC cell xenograft tumors in mice grew more slowly than controls, and wild-type MAFB-overexpressing tumors grew more quickly than tumors overexpressing MAFB mutated at lysine 32. These data suggest that SUMOylated MAFB promotes CRC tumorigenesis through cell cycle regulation. MAFB and its SUMOylation process may serve as novel therapeutic targets for CRC treatment. PMID:27829226

Natriuretic peptide receptor A inhibition suppresses gastric cancer development through reactive oxygen species-mediated G2/M cell cycle arrest and cell death.

PubMed

Li, Zheng; Wang, Ji-Wei; Wang, Wei-Zhi; Zhi, Xiao-Fei; Zhang, Qun; Li, Bo-Wen; Wang, Lin-Jun; Xie, Kun-Ling; Tao, Jin-Qiu; Tang, Jie; Wei, Song; Zhu, Yi; Xu, Hao; Zhang, Dian-Cai; Yang, Li; Xu, Ze-Kuan

2016-10-01

Natriuretic peptide receptor A (NPRA), the major receptor for atrial natriuretic peptide (ANP), has been implicated in tumorigenesis; however, the role of ANP-NPRA signaling in the development of gastric cancer remains unclear. Immunohistochemical analyses indicated that NPRA expression was positively associated with gastric tumor size and cancer stage. NPRA inhibition by shRNA induced G2/M cell cycle arrest, cell death, and autophagy in gastric cancer cells, due to accumulation of reactive oxygen species (ROS). Either genetic or pharmacologic inhibition of autophagy led to caspase-dependent cell death. Therefore, autophagy induced by NPRA silencing may represent a cytoprotective mechanism. ROS accumulation activated c-Jun N-terminal kinase (JNK) and AMP-activated protein kinase (AMPK). ROS-mediated activation of JNK inhibited cell proliferation by disturbing cell cycle and decreased cell viability. In addition, AMPK activation promoted autophagy in NPRA-downregulated cancer cells. Overall, our results indicate that the inhibition of NPRA suppresses gastric cancer development and targeting NPRA may represent a promising strategy for the treatment of gastric cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Thermogenesis, Flowering and the Association with Variation in Floral Odour Attractants in Magnolia sprengeri (Magnoliaceae)

PubMed Central

Wang, Ruohan; Xu, Sai; Liu, Xiangyu; Zhang, Yiyuan; Wang, Jianzhong; Zhang, Zhixiang

2014-01-01

Magnolia sprengeri Pamp. is an ornamentally and ecologically important tree that blooms at cold temperatures in early spring. In this study, thermogenesis and variation in the chemical compounds of floral odours and insect visitation in relation to flowering cycles were studied to increase our understanding of the role of floral thermogenesis in the pollination biology of M. sprengeri. There were five distinct floral stages across the floral cycle of this species: pre-pistillate, pistillate, pre-staminate, staminate and post-staminate. Floral thermogenesis during anthesis and consisted of two distinct peaks: one at the pistillate stage and the other at the staminate stage. Insects of five families visited M. sprengeri during the floral cycle, and sap beetles (Epuraea sp., Nitidulidae) were determined to be the most effective pollinators, whereas bees (Apis cerana, Apidae) were considered to be occasional pollinators. A strong fragrance was released during thermogenesis, consisting of 18 chemical compounds. Although the relative proportions of these compounds varied at different floral stages across anthesis, linalool, 1-iodo-2-methylundecane and 2,2,6-trimethyl-6-vinyltetrahydro-2H-pyran-3-ol were dominant. Importantly, we found that the floral blends released during the pistillate and staminate stages were very similar, and coincided with flower visitation by sap beetles and the two thermogenic episodes. Based on these results, we propose that odour acts as a signal for a reward (pollen) and that an odour mimicry of staminate-stage flowers occurs during the pistillate stage. PMID:24922537

An 8-Week Low-Intensity Progressive Cycling Training Improves Motor Functions in Patients with Early-Stage Parkinson's Disease.

PubMed

Chang, Hsiu Chen; Lu, Chin Song; Chiou, Wei Da; Chen, Chiung Chu; Weng, Yi Hsin; Chang, Ya Ju

2018-04-01

The effects of high-intensity cycling as an adjuvant therapy for early-stage Parkinson's disease (PD) were highlighted recently. However, patients experience difficulties in maintaining these cycling training programs. The present study investigated the efficacy of cycling at a mild-to-moderate intensity in early-stage PD. Thirteen PD patients were enrolled for 16 serial cycling sessions over a 2-month period. Motor function was assessed using the Unified Parkinson's Disease Rating Scale part III (UPDRS III) and Timed Up and Go (TUG) test as primary outcomes. The Montreal Cognitive Assessment (MoCA), modified Hoehn and Yahr Stage (mHYS), total UPDRS, Falls Efficacy Scale, New Freezing of Gait Questionnaire, Schwab and England Activities of Daily Living, 39-item Parkinson's Disease Questionnaire, Patient Global Impression of Change, and gait performance were assessed as secondary outcomes. The age and the age at onset were 59.67±7.24 and 53.23±10.26 years (mean±SD), respectively. The cycling cadence was 53.27±8.92 revolutions per minute. The UPDRS III score improved significantly after 8 training sessions (p=0.011) and 16 training sessions (T2) (p=0.001) in the off-state, and at T2 (p=0.004) in the on-state compared to pretraining (T0). The TUG duration was significantly shorter at T2 than at T0 (p<0.05). The findings of MoCA, total UPDRS, double limb support time, and mHYS (in both the off- and on-states) also improved significantly at T2. Our pioneer study has demonstrated that a low-intensity progressive cycling exercise can improve motor function in PD, especially akinesia. The beneficial effects were similar to those of high-intensity rehabilitation programs. Copyright © 2018 Korean Neurological Association.

Rocket Based Combined Cycle (RBCC) Engine

NASA Technical Reports Server (NTRS)

2004-01-01

Pictured is an artist's concept of the Rocket Based Combined Cycle (RBCC) launch. The RBCC's overall objective is to provide a technology test bed to investigate critical technologies associated with opperational usage of these engines. The program will focus on near term technologies that can be leveraged to ultimately serve as the near term basis for Two Stage to Orbit (TSTO) air breathing propulsions systems and ultimately a Single Stage To Orbit (SSTO) air breathing propulsion system.

A review of findings of a study of rocket based combined cycle engines applied to extensively axisymmetric single stage to orbit vehicles

NASA Technical Reports Server (NTRS)

Foster, Richard W.

1992-01-01

Extensively axisymmetric and non-axisymmetric Single Stage To Orbit (SSTO) vehicles are considered. The information is presented in viewgraph form and the following topics are presented: payload comparisons; payload as a percent of dry weight - a system hardware cost indicator; life cycle cost estimations; operations and support costs estimation; selected engine type; and rocket engine specific impulse calculation.

A high-resolution transcriptome map of cell cycle reveals novel connections between periodic genes and cancer

PubMed Central

Dominguez, Daniel; Tsai, Yi-Hsuan; Gomez, Nicholas; Jha, Deepak Kumar; Davis, Ian; Wang, Zefeng

2016-01-01

Progression through the cell cycle is largely dependent on waves of periodic gene expression, and the regulatory networks for these transcriptome dynamics have emerged as critical points of vulnerability in various aspects of tumor biology. Through RNA-sequencing of human cells during two continuous cell cycles (>2.3 billion paired reads), we identified over 1 000 mRNAs, non-coding RNAs and pseudogenes with periodic expression. Periodic transcripts are enriched in functions related to DNA metabolism, mitosis, and DNA damage response, indicating these genes likely represent putative cell cycle regulators. Using our set of periodic genes, we developed a new approach termed “mitotic trait” that can classify primary tumors and normal tissues by their transcriptome similarity to different cell cycle stages. By analyzing >4 000 tumor samples in The Cancer Genome Atlas (TCGA) and other expression data sets, we found that mitotic trait significantly correlates with genetic alterations, tumor subtype and, notably, patient survival. We further defined a core set of 67 genes with robust periodic expression in multiple cell types. Proteins encoded by these genes function as major hubs of protein-protein interaction and are mostly required for cell cycle progression. The core genes also have unique chromatin features including increased levels of CTCF/RAD21 binding and H3K36me3. Loss of these features in uterine and kidney cancers is associated with altered expression of the core 67 genes. Our study suggests new chromatin-associated mechanisms for periodic gene regulation and offers a predictor of cancer patient outcomes. PMID:27364684

Cell cycle progression in irradiated endothelial cells cultured from bovine aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubin, D.B.; Drab, E.A.; Ward, W.F.

1988-11-01

Logarithmically growing endothelial cells from bovine aortas were exposed to single doses of 0-10 Gy of 60Co gamma rays, and cell cycle phase distribution and progression were examined by flow cytometry and autoradiography. In some experiments, cells were synchronized in the cell cycle with hydroxyurea (1 mM). Cell number in sham-irradiated control cultures doubled in approximately 24 h. Estimated cycle stage times for control cells were 14.4 h for G1 phase, 7.2 h for S phase, and 2.4 h for G2 + M phase. Irradiated cells demonstrated a reduced distribution at the G1/S phase border at 4 h, and anmore » increased distribution in G2 + M phase at 24 h postirradiation. Autoradiographs of irradiated cells after continuous (3H)thymidine labeling indicated a block in G1 phase or at the G1/S-phase border. The duration of the block was dose dependent (2-3 min/cGy). Progression of the endothelial cells through S phase after removal of the hydroxyurea block also was retarded by irradiation, as demonstrated by increased distribution in early S phase and decreased distribution in late S phase. These results indicate that progression of asynchronous cultured bovine aortic endothelial cells through the DNA synthetic cycle is susceptible to radiation inhibition at specific sites in the cycle, resulting in redistribution and partial synchronization of the population. Thus aortic endothelial cells, diploid cells from a normal tissue, resemble many immortal cell types that have been examined in this regard in vitro.« less

The biogeography of the atlantic salmon (Salmo salar) gut microbiome.

PubMed

Llewellyn, Martin S; McGinnity, Philip; Dionne, Melanie; Letourneau, Justine; Thonier, Florian; Carvalho, Gary R; Creer, Simon; Derome, Nicolas

2016-05-01

Although understood in many vertebrate systems, the natural diversity of host-associated microbiota has been little studied in teleosts. For migratory fishes, successful exploitation of multiple habitats may affect and be affected by the composition of the intestinal microbiome. We collected 96 Salmo salar from across the Atlantic encompassing both freshwater and marine phases. Dramatic differences between environmental and gut bacterial communities were observed. Furthermore, community composition was not significantly impacted by geography. Instead life-cycle stage strongly defined both the diversity and identity of microbial assemblages in the gut, with evidence for community destabilisation in migratory phases. Mycoplasmataceae phylotypes were abundantly recovered in all life-cycle stages. Patterns of Mycoplasmataceae phylotype recruitment to the intestinal microbial community among sites and life-cycle stages support a dual role for deterministic and stochastic processes in defining the composition of the S. salar gut microbiome.

The biogeography of the atlantic salmon (Salmo salar) gut microbiome

PubMed Central

Llewellyn, Martin S; McGinnity, Philip; Dionne, Melanie; Letourneau, Justine; Thonier, Florian; Carvalho, Gary R; Creer, Simon; Derome, Nicolas

2016-01-01

Although understood in many vertebrate systems, the natural diversity of host-associated microbiota has been little studied in teleosts. For migratory fishes, successful exploitation of multiple habitats may affect and be affected by the composition of the intestinal microbiome. We collected 96 Salmo salar from across the Atlantic encompassing both freshwater and marine phases. Dramatic differences between environmental and gut bacterial communities were observed. Furthermore, community composition was not significantly impacted by geography. Instead life-cycle stage strongly defined both the diversity and identity of microbial assemblages in the gut, with evidence for community destabilisation in migratory phases. Mycoplasmataceae phylotypes were abundantly recovered in all life-cycle stages. Patterns of Mycoplasmataceae phylotype recruitment to the intestinal microbial community among sites and life-cycle stages support a dual role for deterministic and stochastic processes in defining the composition of the S. salar gut microbiome. PMID:26517698

Genital mycoplasmas of healthy bitches.

PubMed

Maksimović, Zinka; Maksimović, Alan; Halilbašić, Anis; Rifatbegović, Maid

2018-05-01

Little is known about the presence of mycoplasmas in the genital tracts of domestic and stray bitches or in the vaginas of ovariohysterectomized (OHE) bitches. Moreover, to our knowledge, there has been no research to investigate the presence of canine vaginal mycoplasmas during the different stages of the reproductive cycle. We investigated the occurrence of mycoplasmas in the vaginas of healthy domestic and stray intact bitches, to correlate their presence with specific stages of the reproductive cycle, and to compare them with those in OHE bitches. We also investigated the presence of uterine mycoplasmas. Mycoplasmas were isolated from 41 of 122 vaginal swabs (34%) from domestic (27%) and stray (39%) bitches. Mycoplasma canis was the most commonly identified species ( n = 26; 63%), and was detected in both intact (60%) and OHE (73%) bitches. Mycoplasma isolates from the vaginas of healthy bitches did not vary during the various stages of the estrous cycle. Mycoplasmas were not detected in uterine samples.

Ethanolic extracts of Inula viscosa, Salix alba and Quercus calliprinos, negatively affect the development of the entomopathogenic nematode, Heterorhabditis bacteriophora - A model to compare gastro-intestinal nematodes developmental effect.

PubMed

Santhi, Velayudhan Satheeja; Salame, Liora; Dvash, Levana; Muklada, Hussein; Azaizeh, Hassan; Mreny, Raghda; Awwad, Safaa; Markovics, Alex; Landau, Serge Yan; Glazer, Itamar

2017-05-01

Heterorhabditis bacteriophora can represent a model system for herbal medication against gastro-intestinal strongylid parasites in determining the recovery and development due to their unique parasitic infectious cycle. The fact that plant extracts impair nematode development is known but their differential impact on stages of the life cycle of H. bacteriophora has never been investigated. We examined the developmental stages resumed from eggs, young juveniles (J 1-3 ), infective juveniles (IJs), young and adult hermaphrodites of H. bacteriophora upon exposure to crude ethanolic extracts of Inula viscosa, Salix alba, and Quercus calliprinos at concentrations of 600, 1200, and 2400ppm. Our results showed that plant extracts were highly toxic to the survival of the eggs and young juveniles J 1 to J 3 at all concentrations. The plant extracts inhibited their development and were associated with low reproduction parameters (i.e. fecundity and viability of eggs). The IJs, J 4 , young and developed hermaphrodites displayed concentration-dependent negative effect on development with less egg count, poor vulval muscle development, loss of egg laying capacity and progeny development by matricidal hatching. Plant extract of I. viscosa at low (600ppm) concentration did not impair vulval development. These results suggest that these plant extracts show potential for the control of parasitic rhabditids. Copyright © 2017 Elsevier Inc. All rights reserved.

DECISION-MAKING ALIGNED WITH RAPID-CYCLE EVALUATION IN HEALTH CARE.

PubMed

Schneeweiss, Sebastian; Shrank, William H; Ruhl, Michael; Maclure, Malcolm

2015-01-01

Availability of real-time electronic healthcare data provides new opportunities for rapid-cycle evaluation (RCE) of health technologies, including healthcare delivery and payment programs. We aim to align decision-making processes with stages of RCE to optimize the usefulness and impact of rapid results. Rational decisions about program adoption depend on program effect size in relation to externalities, including implementation cost, sustainability, and likelihood of broad adoption. Drawing on case studies and experience from drug safety monitoring, we examine how decision makers have used scientific evidence on complex interventions in the past. We clarify how RCE alters the nature of policy decisions; develop the RAPID framework for synchronizing decision-maker activities with stages of RCE; and provide guidelines on evidence thresholds for incremental decision-making. In contrast to traditional evaluations, RCE provides early evidence on effectiveness and facilitates a stepped approach to decision making in expectation of future regularly updated evidence. RCE allows for identification of trends in adjusted effect size. It supports adapting a program in midstream in response to interim findings, or adapting the evaluation strategy to identify true improvements earlier. The 5-step RAPID approach that utilizes the cumulating evidence of program effectiveness over time could increase policy-makers' confidence in expediting decisions. RCE enables a step-wise approach to HTA decision-making, based on gradually emerging evidence, reducing delays in decision-making processes after traditional one-time evaluations.

Molecular Biology of Prune Dwarf Virus—A Lesser Known Member of the Bromoviridae but a Vital Component in the Dynamic Virus–Host Cell Interaction Network

PubMed Central

Bujarski, Józef J.

2017-01-01

Prune dwarf virus (PDV) is one of the members of Bromoviridae family, genus Ilarvirus. Host components that participate in the regulation of viral replication or cell-to-cell movement via plasmodesmata are still unknown. In contrast, viral infections caused by some other Bromoviridae members are well characterized. Bromoviridae can be distinguished based on localization of their replication process in infected cells, cell-to-cell movement mechanisms, and plant-specific response reactions. Depending upon the genus, “genome activation” and viral replication are linked to various membranous structures ranging from endoplasmic reticulum, to tonoplast. In the case of PDV, there is still no evidence of natural resistance sources in the host plants susceptible to virus infection. Apparently, PDV has a great ability to overcome the natural defense responses in a wide spectrum of plant hosts. The first manifestations of PDV infection are specific cell membrane alterations, and the formation of replicase complexes that support PDV RNA replication inside the spherules. During each stage of its life cycle, the virus uses cell components to replicate and to spread in whole plants, within the largely suppressed cellular immunity environment. This work presents the above stages of the PDV life cycle in the context of current knowledge about other Bromoviridae members. PMID:29258199

Identification of a Potential Antimalarial Drug Candidate from a Series of 2-Aminopyrazines by Optimization of Aqueous Solubility and Potency across the Parasite Life Cycle.

PubMed

Le Manach, Claire; Nchinda, Aloysius T; Paquet, Tanya; Gonzàlez Cabrera, Diego; Younis, Yassir; Han, Ze; Bashyam, Sridevi; Zabiulla, Mohammed; Taylor, Dale; Lawrence, Nina; White, Karen L; Charman, Susan A; Waterson, David; Witty, Michael J; Wittlin, Sergio; Botha, Mariëtte E; Nondaba, Sindisiswe H; Reader, Janette; Birkholtz, Lyn-Marie; Jiménez-Díaz, María Belén; Martínez, María Santos; Ferrer, Santiago; Angulo-Barturen, Iñigo; Meister, Stephan; Antonova-Koch, Yevgeniya; Winzeler, Elizabeth A; Street, Leslie J; Chibale, Kelly

2016-11-10

Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2Rγ null mice. One of the frontrunners, compound 3, was identified to also have good pharmacokinetics and additionally very potent activity against the liver and gametocyte parasite life-cycle stages.

Applying Movement Ecology to Marine Animals with Complex Life Cycles.

PubMed

Allen, Richard M; Metaxas, Anna; Snelgrove, Paul V R

2018-01-03

Marine animals with complex life cycles may move passively or actively for fertilization, dispersal, predator avoidance, resource acquisition, and migration, and over scales from micrometers to thousands of kilometers. This diversity has catalyzed idiosyncratic and unfocused research, creating unsound paradigms regarding the role of movement in ecology and evolution. The emerging movement ecology paradigm offers a framework to consolidate movement research independent of taxon, life-history stage, scale, or discipline. This review applies the framework to movement among life-history stages in marine animals with complex life cycles to consolidate marine movement research and offer insights for scientists working in aquatic and terrestrial realms. Irrespective of data collection or simulation strategy, breaking each life-history stage down into the fundamental units of movement allows each unit to be studied independently or interactively with other units. Understanding these underlying mechanisms of movement within each life-history stage can then be used to construct lifetime movement paths. These paths can allow further investigation of the relative contributions and interdependencies of steps and phases across a lifetime and how these paths influence larger research topics, such as population-level movements.

Applying Movement Ecology to Marine Animals with Complex Life Cycles

NASA Astrophysics Data System (ADS)

Allen, Richard M.; Metaxas, Anna; Snelgrove, Paul V. R.

2018-01-01

Marine animals with complex life cycles may move passively or actively for fertilization, dispersal, predator avoidance, resource acquisition, and migration, and over scales from micrometers to thousands of kilometers. This diversity has catalyzed idiosyncratic and unfocused research, creating unsound paradigms regarding the role of movement in ecology and evolution. The emerging movement ecology paradigm offers a framework to consolidate movement research independent of taxon, life-history stage, scale, or discipline. This review applies the framework to movement among life-history stages in marine animals with complex life cycles to consolidate marine movement research and offer insights for scientists working in aquatic and terrestrial realms. Irrespective of data collection or simulation strategy, breaking each life-history stage down into the fundamental units of movement allows each unit to be studied independently or interactively with other units. Understanding these underlying mechanisms of movement within each life-history stage can then be used to construct lifetime movement paths. These paths can allow further investigation of the relative contributions and interdependencies of steps and phases across a lifetime and how these paths influence larger research topics, such as population-level movements.

Oscillating in synchrony with a metronome: serial dependence, limit cycle dynamics, and modeling.

PubMed

Torre, Kjerstin; Balasubramaniam, Ramesh; Delignières, Didier

2010-07-01

We analyzed serial dependencies in periods and asynchronies collected during oscillations performed in synchrony with a metronome. Results showed that asynchronies contain 1/f fluctuations, and the series of periods contain antipersistent dependence. The analysis of the phase portrait revealed a specific asymmetry induced by synchronization. We propose a hybrid limit cycle model including a cycle-dependent stiffness parameter provided with fractal properties, and a parametric driving function based on velocity. This model accounts for most experimentally evidenced statistical features, including serial dependence and limit cycle dynamics. We discuss the results and modeling choices within the framework of event-based and emergent timing.

Comparative anatomy and histology of developmental and parasitic stages in the life cycle of the lined sea anemone Edwardsiella lineata.

PubMed

Reitzel, Adam M; Daly, Marymegan; Sullivan, James C; Finnerty, John R

2009-02-01

The evolution of parasitism is often accompanied by profound changes to the developmental program. However, relatively few studies have directly examined the developmental evolution of parasitic species from free-living ancestors. The lined sea anemone Edwardsiella lineata is a relatively recently evolved parasite for which closely related free-living outgroups are known, including the starlet sea anemone Nematostella vectensis. The larva of E. lineata parasitizes the ctenophore Mnemiopsis leidyi, and, once embedded in its host, the anemone assumes a novel vermiform body plan. That we might begin to understand how the developmental program of this species has been transformed during the evolution of parasitism, we characterized the gross anatomy, histology, and cnidom of the parasitic stage, post-parasitic larval stage, and adult stage of the E. lineata life cycle. The distinct parasitic stage of the life cycle differs from the post-parasitic larva with respect to overall shape, external ciliation, cnida frequency, and tissue architecture. The parasitic stage and planula both contain holotrichs, a type of cnida not previously reported in Edwardsiidae. The internal morphology of the post-parasitic planula is extremely similar to the adult morphology, with a complete set of mesenterial tissue and musculature despite this stage having little external differentiation. Finally, we observed 2 previously undocumented aspects of asexual reproduction in E. lineata: (1) the parasitic stage undergoes transverse fission via physal pinching, the first report of asexual reproduction in a pre-adult stage in the Edwardsiidae; and (2) the juvenile polyp undergoes transverse fission via polarity reversal, the first time this form of fission has been reported in E. lineata.

Earth Without Life: A Systems Model of a Global Abiotic Nitrogen Cycle

NASA Astrophysics Data System (ADS)

Laneuville, M.; Kameya, M.; Cleaves, H. J.

2017-07-01

N is the major component of the atmosphere and plays important roles in biochemistry. Presently, the surface N-cycle is dominated by biology. However, before the origin of life, abiotic N-cycling would have set the stage for the origin of life.

Comparison of energy-based indicators used in life cycle assessment tools for buildings

EPA Science Inventory

Traditionally, building rating systems focused on, among others, energy used during operational stage. Recently, there is a strong push by these rating systems to include the life cycle energy use of buildings, particularly using Life Cycle Assessment (LCA), by offering credits t...

Akt-mediated phosphorylation of CDK2 regulates its dual role in cell cycle progression and apoptosis.

PubMed

Maddika, Subbareddy; Ande, Sudharsana Rao; Wiechec, Emilia; Hansen, Lise Lotte; Wesselborg, Sebastian; Los, Marek

2008-04-01

Here, we show that CDK2, an S-phase cyclin-dependent kinase, is a novel target for Akt during cell cycle progression and apoptosis. Akt phosphorylates CDK2 at threonine 39 residue both in vitro and in vivo. Although CDK2 threonine 39 phosphorylation mediated by Akt enhances cyclin-A binding, it is dispensable for its basal binding and the kinase activity. In addition, for the first time, we report a transient nucleo-cytoplasmic shuttling of Akt during specific stages of the cell cycle, in particular during the late S and G2 phases. The Akt that is re-localized to the nucleus phosphorylates CDK2 and causes the temporary cytoplasmic localization of the CDK2-cyclin-A complex. The CDK2 cytoplasmic redistribution is required for cell progression from S to G2-M phase, because the CDK2 T39A mutant, which lacks the phosphorylation site and is defective in cytoplasmic localization, severely affects cell cycle progression at the transition from S to G2-M. Interestingly, we also show that the Akt/CDK2 pathway is constitutively activated by some anticancer drugs, such as methotrexate and docetaxel, and under these conditions it promotes, rather than represses, cell death. Thus, the constitutive activation of the Akt/CDK2 pathway and changed subcellular localization promotes apoptosis. By contrast, the transient, physiological Akt/CDK2 activation is necessary for cell cycle progression.

Cell cycle-related fluctuations in transcellular ionic currents and plasma membrane Ca2+/Mg2+ ATPase activity during early cleavages of Lymnaea stagnalis embryos.

PubMed

Zivkovic, Danica; Créton, Robbert; Dohmen, René

1991-08-01

During the first four mitotic division cycles of Lymnaea stagnalis embryos, we have detected cell cycle-dependent changes in the pattern of transcellular ionic currents and membrane-bound Ca 2+ -stimulated ATPase activity. Ionic currents ranging from 0.05 to 2.50 μA/cm 2 have been measured using the vibrating probe technique. Enzyme activity was detected using Ando's cytochemical method (Ando et al. 1981) which reveals Ca 2+ /Mg 2+ ATPase localization at the ultrastructural level, and under high-stringency conditions with respect to calcium availability, it reveals Ca 2+ -stimulated ATPase. The ionic currents and Ca 2+ -stimulated ATPase localization have in common that important changes occur during the M-phase of the cell cycles. Minimal outward current at the vegetal pole coincides with metaphase/anaphase. Maximal inward current at the animal pole coincides with the onset of cytokinesis at that pole. Ca 2+ -stimulated ATPase is absent from one half of the embryo at metaphase/anaphase of the two- and four-cell stage, whereas it is present in all cells during the remaining part of the cell cycle. Since fluctuations of cytosolic free calcium concentrations appear to correlate with both karyokinesis and cytokinesis, we speculate that part of the cyclic pattern of Ca 2+ -stimulated ATPase localization and of the transcellular ionic currents reflects the elevation of cytosolic free calcium concentration during the M-phase.

Developmental and Cell Cycle Quiescence Is Mediated by the Nuclear Hormone Receptor Coregulator DIN-1S in the Caenorhabditis elegans Dauer Larva.

PubMed

Colella, Eileen; Li, Shaolin; Roy, Richard

2016-08-01

When faced with suboptimal growth conditions, Caenorhabditis elegans larvae can enter a diapause-like stage called "dauer" that is specialized for dispersal and survival. The decision to form a dauer larva is controlled by three parallel signaling pathways, whereby a compromise of TGFβ, cyclic guanosine monophosphate, or insulin/IGF-like signaling (ILS) results in dauer formation. Signals from these pathways converge on DAF-12, a nuclear hormone receptor that triggers the changes required to initiate dauer formation. DAF-12 is related to the vitamin D, liver-X, and androstane receptors, and like these human receptors, it responds to lipophilic hormone ligands. When bound to its ligand, DAF-12 acquires transcriptional activity that directs reproductive development, while unliganded DAF-12 forms a dauer-specifying complex with its interacting protein DIN-1S to regulate the transcription of genes required for dauer development. We report here that din-1S is required in parallel to par-4/LKB1 signaling within the gonad to establish cell cycle quiescence during the onset of the dauer stage. We show that din-1S is important for postdauer reproduction when ILS is impaired and is necessary for long-term dauer survival in response to reduced ILS. Our work uncovers several previously uncharacterized functions of DIN-1S in executing and maintaining many of the cellular and physiological processes required for appropriate dauer arrest, while also shedding light on the coordination of nuclear hormone signaling, the LKB1/AMPK signaling cascade, and ILS/TGFβ in the control of cell cycle quiescence and tissue growth: a key feature that is often misregulated in a number of hormone-dependent cancers. Copyright © 2016 by the Genetics Society of America.

What's in a Number: How we Measure Community Engagement

NASA Astrophysics Data System (ADS)

Budden, A. E.; Aicher, R.; Butland, S.; Varga, M.

2017-12-01

The importance of community management is increasingly recognized and the role of the community manager is becoming professionalized. Yet, activities involved in community management - or community engagement - are widespread, and have typically been taken on by a variety of actors. These activities will look different depending on the type of community an individual is working with, and the maturity of the community. Regardless of the myriad of tools and practices used in community management, most community managers are seeking growth and a transition to a mature and self-sustaining community. Measuring this growth and degree of engagement can be challenging. Harder still is inferring the impact of community growth. In this paper we discuss some of the most commonly used metrics for community engagement, their advantages and limitations, and their context dependency, drawing from case studies of communities at different stages of the community life-cycle.

[Nanotechnology--possibilities and hazards].

PubMed

Snopczyński, Tomasz; Góralczyk, Katarzyna; Czaja, Katarzyna; Struciński, Paweł; Hernik, Agnieszka; Korcz, Wojciech; Ludwicki, Jan K

2009-01-01

Nanoparticles are the objects with at least one demension smaller than 100 nm. Nanoparticles exist in nature or can be produced by human activities, intentionally or unintentionally. Nanotechnology is an emerging science involving manipulation of matter at nanometer scale. Nanoparticles find numerous applications in many fields, starting with electronics, throught medicine, cosmetology, and ending with automotive industry and construction industry. Depending on the use of nanoparticles, the routes of exposure may be inhalation, dermal, oral or parenteral. Nanoparticles have a greater active surface area per unit mass than larger particles. Together with an increase of surface area, toxicity and potential health effects may also increase. Toxicity of nanoparticles depend on many factors, for example: size, shape, chemical composition, solubility, surface area and surface charge. Risk assessment related to human health, should be integrated at all stages of the life cycle of the nanotechnology, starting at the point of conception and including research and development, manufacturing, distribution, use and disposal or recycling.

The artificial and natural isotopes distribution in sedge (Carex L.) biomass from the Yenisei River flood-plain: Adaptation of the sequential elution technique.

PubMed

Kropacheva, Marya; Melgunov, Mikhail; Makarova, Irina

2017-02-01

The study of migration pathways of artificial isotopes in the flood-plain biogeocoenoses, impacted by the nuclear fuel cycle plants, requires determination of isotope speciations in the biomass of higher terrestrial plants. The optimal method for their determination is the sequential elution technique (SET). The technique was originally developed to study atmospheric pollution by metals and has been applied to lichens, terrestrial and aquatic bryophytes. Due to morphological and physiological differences, it was necessary to adapt SET for new objects: coastal macrophytes growing on the banks of the Yenisei flood-plain islands in the near impact zone of Krasnoyarsk Mining and Chemical Combine (KMCC). In the first version of SET, 20 mM Na 2 EDTA was used as a reagent at the first stage; in the second version of SET, it was 1 M CH 3 COONH 4 . Four fractions were extracted. Fraction I included elements from the intercellular space and those connected with the outer side of the cell wall. Fraction II contained intracellular elements; fraction III contained elements firmly bound in the cell wall and associated structures; fraction IV contained insoluble residue. Adaptation of SET has shown that the first stage should be performed immediately after sampling. Separation of fractions III and IV can be neglected, since the output of isotopes into the IV fraction is at the level of error detection. The most adequate version of SET for terrestrial vascular plants is the version using 20 mM Na 2 EDTA at the first stage. Isotope 90 Sr is most sensitive to the technique changes. Its distribution depends strongly on both the extractant used at stage 1 and duration of the first stage. Distribution of artificial radionuclides in the biomass of terrestrial vascular plants can vary from year to year and depends significantly on the age of the plant. Copyright © 2016 Elsevier Ltd. All rights reserved.

Factors Associated with Failed Treatment: an Analysis of 121,744 Women Embarking on Their First IVF Cycles

PubMed Central

Bhattacharya, Siladitya; Maheshwari, Abha; Mollison, Jill

2013-01-01

Background In-vitro fertilization (IVF) is the treatment of choice for unresolved infertility. It comprises a number of key steps, each of which has to be negotiated before the next is attempted, but the factors which are associated with failure at each stage have not been reported. Methods and Findings We analyzed anonymised national data on women undergoing their first fresh autologous IVF and intracytoplasmic sperm injection (ICSI) cycle in the United Kingdom between 2000 and 2007 to predict factors associated with overall lack of livebirth as well as the chance of non-progress at different stages of an IVF cycle. A total of 121,744 women were included in this analysis. Multivariable models underlined the importance of increased female age and duration of infertility, lack of previous pregnancy, and a diagnosis of tubal or male factor infertility in predicting the risk of not having a live birth in an IVF treatment. At each stage, a woman’s chance of proceeding to the next stage of IVF treatment is affected by increased age and duration of infertility. The intention to use intra-cytoplasmic sperm injection (ICSI) is associated with a decreased risk of treatment failure in women starting an IVF cycle (RR 0.93, 99% CI 0.92, 0.94) but this association is reversed at a later stage once fertilisation has been confirmed (RR=1.01, 99%CI 1.00, 1.03). Conclusions Female age is a key predictor of failure to have a livebirth following IVF as well as the risk of poor performance at each stage of treatment. While increased duration of infertility is also associated with worse outcomes at every stage, its impact appears to be less influential. Women embarking on ICSI treatment for male factor infertility have a lower chance of treatment failure but this does not appear to be due to increased chances of implantation of ICSI embryos. PMID:24349236

Cell Cycle Synchronization of HeLa Cells to Assay EGFR Pathway Activation.

PubMed

Wee, Ping; Wang, Zhixiang

2017-01-01

Progression through the cell cycle causes changes in the cell's signaling pathways that can alter EGFR signal transduction. Here, we describe drug-derived protocols to synchronize HeLa cells in various phases of the cell cycle, including G1 phase, S phase, G2 phase, and mitosis, specifically in the mitotic stages of prometaphase, metaphase, and anaphase/telophase. The synchronization procedures are designed to allow synchronized cells to be treated for EGF and collected for the purpose of Western blotting for EGFR signal transduction components.S phase synchronization is performed by thymidine block, G2 phase with roscovitine, prometaphase with nocodazole, metaphase with MG132, and anaphase/telophase with blebbistatin. G1 phase synchronization is performed by culturing synchronized mitotic cells obtained by mitotic shake-off. We also provide methods to validate the synchronization methods. For validation by Western blotting, we provide the temporal expression of various cell cycle markers that are used to check the quality of the synchronization. For validation of mitotic synchronization by microscopy, we provide a guide that describes the physical properties of each mitotic stage, using their cellular morphology and DNA appearance. For validation by flow cytometry, we describe the use of imaging flow cytometry to distinguish between the phases of the cell cycle, including between each stage of mitosis.

The Salmon Louse Lepeophtheirus salmonis (Copepoda: Caligidae) Life Cycle Has Only Two Chalimus Stages

PubMed Central

Dalvin, Sussie T.; Bron, James E.; Nilsen, Frank; Boxshall, Geoff; Skern-Mauritzen, Rasmus

2013-01-01

Each year the salmon louse ( Lepeophtheirus salmonis Krøyer, 1838) causes multi-million dollar commercial losses to the salmon farming industry world-wide, and strict lice control regimes have been put in place to reduce the release of salmon louse larvae from aquaculture facilities into the environment. For half a century, the Lepeophtheirus life cycle has been regarded as the only copepod life cycle including 8 post-nauplius instars as confirmed in four different species, including L . salmonis . Here we prove that the accepted life cycle of the salmon louse is wrong. By observations of chalimus larvae molting in incubators and by morphometric cluster analysis, we show that there are only two chalimus instars: chalimus 1 (comprising the former chalimus I and II stages which are not separated by a molt) and chalimus 2 (the former chalimus III and IV stages which are not separated by a molt). Consequently the salmon louse life cycle has only six post-nauplius instars, as in other genera of caligid sea lice and copepods in general. These findings are of fundamental importance in experimental studies as well as for interpretation of salmon louse biology and for control and management of this economically important parasite. PMID:24069203

Managing the life cycle of electronic clinical documents.

PubMed

Payne, Thomas H; Graham, Gail

2006-01-01

To develop a model of the life cycle of clinical documents from inception to use in a person's medical record, including workflow requirements from clinical practice, local policy, and regulation. We propose a model for the life cycle of clinical documents as a framework for research on documentation within electronic medical record (EMR) systems. Our proposed model includes three axes: the stages of the document, the roles of those involved with the document, and the actions those involved may take on the document at each stage. The model includes the rules to describe who (in what role) can perform what actions on the document, and at what stages they can perform them. Rules are derived from needs of clinicians, and requirements of hospital bylaws and regulators. Our model encompasses current practices for paper medical records and workflow in some EMR systems. Commercial EMR systems include methods for implementing document workflow rules. Workflow rules that are part of this model mirror functionality in the Department of Veterans Affairs (VA) EMR system where the Authorization/ Subscription Utility permits document life cycle rules to be written in English-like fashion. Creating a model of the life cycle of clinical documents serves as a framework for discussion of document workflow, how rules governing workflow can be implemented in EMR systems, and future research of electronic documentation.

Deciphering life history transcriptomes in different environments

PubMed Central

Etges, William J.; Trotter, Meredith V.; de Oliveira, Cássia C.; Rajpurohit, Subhash; Gibbs, Allen G.; Tuljapurkar, Shripad

2014-01-01

We compared whole transcriptome variation in six preadult stages and seven adult female ages in two populations of cactophilic Drosophila mojavensis reared on two host plants in order to understand how differences in gene expression influence standing life history variation. We used Singular Value Decomposition (SVD) to identify dominant trajectories of life cycle gene expression variation, performed pair-wise comparisons of stage and age differences in gene expression across the life cycle, identified when genes exhibited maximum levels of life cycle gene expression, and assessed population and host cactus effects on gene expression. Life cycle SVD analysis returned four significant components of transcriptional variation, revealing functional enrichment of genes responsible for growth, metabolic function, sensory perception, neural function, translation and aging. Host cactus effects on female gene expression revealed population and stage specific differences, including significant host plant effects on larval metabolism and development, as well as adult neurotransmitter binding and courtship behavior gene expression levels. In 3 - 6 day old virgin females, significant up-regulation of genes associated with meiosis and oogenesis was accompanied by down-regulation of genes associated with somatic maintenance, evidence for a life history tradeoff. The transcriptome of D. mojavensis reared in natural environments throughout its life cycle revealed core developmental transitions and genome wide influences on life history variation in natural populations. PMID:25442828

FLASH is essential during early embryogenesis and cooperates with p73 to regulate histone gene transcription.

PubMed

De Cola, A; Bongiorno-Borbone, L; Bianchi, E; Barcaroli, D; Carletti, E; Knight, R A; Di Ilio, C; Melino, G; Sette, C; De Laurenzi, V

2012-02-02

Replication-dependent histone gene expression is a fundamental process occurring in S-phase under the control of the cyclin-E/CDK2 complex. This process is regulated by a number of proteins, including Flice-Associated Huge Protein (FLASH) (CASP8AP2), concentrated in specific nuclear organelles known as HLBs. FLASH regulates both histone gene transcription and mRNA maturation, and its downregulation in vitro results in the depletion of the histone pull and cell-cycle arrest in S-phase. Here we show that the transcription factor p73 binds to FLASH and is part of the complex that regulates histone gene transcription. Moreover, we created a novel gene trap to disrupt FLASH in mice, and we show that homozygous deletion of FLASH results in early embryonic lethality, owing to arrest of FLASH(-/-) embryos at the morula stage. These results indicate that FLASH is an essential, non-redundant regulator of histone transcription and cell cycle during embryogenesis.

Life-cycle energy and GHG emissions of forest biomass harvest and transport for biofuel production in Michigan

DOE PAGES

Zhang, Fengli; Johnson, Dana M.; Wang, Jinjiang

2015-04-01

High dependence on imported oil has increased U.S. strategic vulnerability and prompted more research in the area of renewable energy production. Ethanol production from renewable woody biomass, which could be a substitute for gasoline, has seen increased interest. This study analysed energy use and greenhouse gas emission impacts on the forest biomass supply chain activities within the State of Michigan. A life-cycle assessment of harvesting and transportation stages was completed utilizing peer-reviewed literature. Results for forest-delivered ethanol were compared with those for petroleum gasoline using data specific to the U.S. The analysis from a woody biomass feedstock supply perspective uncoveredmore » that ethanol production is more environmentally friendly (about 62% less greenhouse gas emissions) compared with petroleum based fossil fuel production. Sensitivity analysis was conducted with key inputs associated with harvesting and transportation operations. The results showed that research focused on improving biomass recovery efficiency and truck fuel economy further reduced GHG emissions and energy consumption.« less

Enthalpy-Based Thermal Evolution of Loops: III. Comparison of Zero-Dimensional Models

NASA Technical Reports Server (NTRS)

Cargill, P. J.; Bradshaw, Stephen J.; Klimchuk, James A.

2012-01-01

Zero dimensional (0D) hydrodynamic models, provide a simple and quick way to study the thermal evolution of coronal loops subjected to time-dependent heating. This paper presents a comparison of a number of 0D models that have been published in the past and is intended to provide a guide for those interested in either using the old models or developing new ones. The principal difference between the models is the way the exchange of mass and energy between corona, transition region and chromosphere is treated, as plasma cycles into and out of a loop during a heating-cooling cycle. It is shown that models based on the principles of mass and energy conservation can give satisfactory results at some, or, in the case of the Enthalpy Based Thermal Evolution of Loops (EBTEL) model, all stages of the loop evolution. Empirical models can lead to low coronal densities, spurious delays between the peak density and temperature, and, for short heating pulses, overly short loop lifetimes.

["Light" epithelial cells of swine and bovine oviducts].

PubMed

Suuroia, T; Aunapuu, M; Arend, A; Sépp, E

2002-01-01

The ultrastructure of oviduct epithelium of clinically healthy cows and 15 sows was investigated using scanning and transmission electron microscopy. In all parts of the oviduct, ciliated and non-ciliated epithelial cells are present, but their number varies in both the investigated animals in different regions of the oviduct, depending on the phase of the estrous cycle. In addition to ciliated cells with numerous cilia on their luminal surface, so-called pale ciliary cells were found in all parts of the oviduct of cows and sows. The cytoplasm of these cells is electron-lucent, their luminal surface carries few cilia and short microvilli. The apical cytoplasm contains species specific secretory granules, which means that these cells have features characteristic of both secretory and ciliated cells. It is suggested that the pale ciliated and non-ciliated secretory cells are functional stages of the same tubar epithelium cell, and that the transformation between these two cell types is regulated by functional requirements of the organ in different phases of the estrous cycle.

The influence of implanted yttrium on the cyclic oxidation behaviour of 304 stainless steel

NASA Astrophysics Data System (ADS)

Riffard, F.; Buscail, H.; Caudron, E.; Cueff, R.; Issartel, C.; Perrier, S.

2006-03-01

High-temperature alloys are frequently used in power plants, gasification systems, petrochemical industry, combustion processes and in aerospace applications. Depending on the application, materials are subjected to corrosive atmospheres and thermal cycling. In the present work, thermal cycling was carried out in order to study the influence of implanted yttrium on the oxide scale adherence on 304 steel specimens oxidised in air at 1273 K. In situ X-ray diffraction indicates that the oxides formed at 1273 K are different on blank specimens compared to implanted specimens. Glancing angle XRD allows to analyse the oxide scale composition after cooling to room temperature. Experimental results show that yttrium implantation at a nominal dose of 10 17 ions cm -2 does not improve significantly the cyclic oxidation behaviour of the austenitic AISI 304 steel. However, it appears that yttrium implantation remarkably enhance the oxidation resistance during isothermal oxidation. It reduces the transient oxidation stage and the parabolic oxidation rate constant by one order of magnitude.

Life-cycle energy and GHG emissions of forest biomass harvest and transport for biofuel production in Michigan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Fengli; Johnson, Dana M.; Wang, Jinjiang

High dependence on imported oil has increased U.S. strategic vulnerability and prompted more research in the area of renewable energy production. Ethanol production from renewable woody biomass, which could be a substitute for gasoline, has seen increased interest. This study analysed energy use and greenhouse gas emission impacts on the forest biomass supply chain activities within the State of Michigan. A life-cycle assessment of harvesting and transportation stages was completed utilizing peer-reviewed literature. Results for forest-delivered ethanol were compared with those for petroleum gasoline using data specific to the U.S. The analysis from a woody biomass feedstock supply perspective uncoveredmore » that ethanol production is more environmentally friendly (about 62% less greenhouse gas emissions) compared with petroleum based fossil fuel production. Sensitivity analysis was conducted with key inputs associated with harvesting and transportation operations. The results showed that research focused on improving biomass recovery efficiency and truck fuel economy further reduced GHG emissions and energy consumption.« less

A cell cycle-independent, conditional gene inactivation strategy for differentially tagging wild-type and mutant cells.

PubMed

Nagarkar-Jaiswal, Sonal; Manivannan, Sathiya N; Zuo, Zhongyuan; Bellen, Hugo J

2017-05-31

Here, we describe a novel method based on intronic MiMIC insertions described in Nagarkar-Jaiswal et al. (2015) to perform conditional gene inactivation in Drosophila . Mosaic analysis in Drosophila cannot be easily performed in post-mitotic cells. We therefore, therefore, developed Flip-Flop, a flippase -dependent in vivo cassette-inversion method that marks wild-type cells with the endogenous EGFP-tagged protein, whereas mutant cells are marked with mCherry upon inversion. We document the ease and usefulness of this strategy in differential tagging of wild-type and mutant cells in mosaics. We use this approach to phenotypically characterize the loss of SNF4Aγ , encoding the γ subunit of the AMP Kinase complex. The Flip-Flop method is efficient and reliable, and permits conditional gene inactivation based on both spatial and temporal cues, in a cell cycle-, and developmental stage-independent fashion, creating a platform for systematic screens of gene function in developing and adult flies with unprecedented detail.

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: background to spermatogenesis, spermatogonia, and spermatocytes.

PubMed

Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

2010-04-01

Spermatogenesis, a study of germ cell development, is a long, orderly, and well-defined process occurring in seminiferous tubules of the testis. It is a temporal event whereby undifferentiated spermatogonial germ cells evolve into maturing spermatozoa over a period of several weeks. Spermatogenesis is characterized by three specific functional phases: proliferation, meiosis, and differentiation, and it involves spermatogonia, spermatocytes, and spermatids. Germ cells at steps of development form various cellular associations or stages, with 6, 12, and 14 specific stages being identified in human, mouse, and rat, respectively. The stages evolve over time in a given area of the seminiferous tubule forming a cycle of the seminiferous epithelium that has a well-defined duration for a given species. In this part, we discuss the proliferation and meiotic phase whereby spermatogonia undergo several mitotic divisions to form spermatocytes that undergo two meiotic divisions to form haploid spermatids. In the rat, spermatogonia can be subdivided into several classes: stem cells (A(s)), proliferating cells (A(pr), A(al)), and differentiating cells (A(1)-A(4), In, B). They are dependent on a specific microenvironment (niche) contributed by Sertoli, myoid, and Leydig cells for proper development. Spermatogonia possess several surface markers whereby they can be identified from each other. During meiosis, spermatocytes undergo chromosomal pairing, synapsis, and genetic exchange as well as transforming into haploid cells following meiosis. The meiotic cells form specific structural entities such as the synaptonemal complex and sex body. Many genes involved in spermatogonial renewal and the meiotic process have been identified and shown to be essential for this event. Copyright 2009 Wiley-Liss, Inc.