The effect of taxation and regulation on cigarette smoking: Fresh evidence from Turkey.

PubMed

Cetin, Tamer

2017-12-01

Enacting Law No 5247 in May 2008, Turkey has initiated crucial anti-tobacco policies in the last decade. This paper aims to reveal on the effect of anti-tobacco policies such as excise taxes and regulations on cigarette smoking. To this aim, I empirically investigate the long-term dynamics of demand for cigarettes in Turkey through the OLS estimation strategy under various scenarios and models. Using monthly and quarterly data that cover the pre- and post- anti-smoking policy periods, I estimate demand elasticities and compare the pre- and post- taxation and regulation terms. The results presented in the paper confirm that taxation and regulation have affected the long-term dynamics of demand for cigarettes. The price and income elasticities of demand for cigarettes are significantly higher than the previous literature on Turkey. Demand elasticities have increased on average in the anti-tobacco policies period. Copyright © 2017 Elsevier B.V. All rights reserved.

26 CFR 1.61-11 - Pensions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... employee's contributions may constitute long-term capital gain, rather than ordinary income. (b) Cross... the Code and the regulations thereunder. Amounts received as pensions or annuities under the Social...

26 CFR 1.61-11 - Pensions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... employee's contributions may constitute long-term capital gain, rather than ordinary income. (b) Cross... the Code and the regulations thereunder. Amounts received as pensions or annuities under the Social...

Efficiency of the Regulation of Otolith Mineralisation and Susceptibility to kinetotic Behaviour in Parabolic Aircraft Flights

NASA Astrophysics Data System (ADS)

Knie, M.; Weigele, J.; Hilbig, R.; Anken, R.

Under diminished gravity e g during the respective phase in the course of parabolic aircraft flight PF humans often suffer from motion sickness a kinetsosis due to sensorimotor disorders Using fish as a model system we previously provided ample evidence that an individually differently pronounced asymmetric mineralisation calcification of inner ear stones otoliths leads to the individually different susceptibility to such disorders Depending on the disposition of an individual fish the mineralisation of otoliths is more or less strictly regulated by the central nervous system via a gravity-dependent feedback loop Long-term hypergravity centrifuge e g slows down otolith mineralisation whereas simulated microgravity clinostat yields opposite results Such long-term experiments under altered gravity moreover affect otolith asymmetry According to our working hypothesis the efficiency of the respective regulatory mechanism differs among individual animals This efficiency is postulated to be high in animals who behave normally under microgravity conditions whereas it is assumed to be low in such individuals who reveal a kinetotic behaviour at diminished G-forces In order to test this hypothesis two groups of larval cichlid fish Oreochromis mossambicus were kept under long-term hypergravity centrifuge and simulated microgravity clinostat respectively in order to manipulate the efficiency of the aforementioned regulatory mechanism Subsequently the animals were subjected to diminished gravity in the course of PFs and it was analysed

Regulation of leptin production in humans.

PubMed

Fried, S K; Ricci, M R; Russell, C D; Laferrère, B

2000-12-01

Serum levels of the adipocyte hormone leptin are increased in proportion to body fat stores as a result of increased production in enlarged fat cells from obese subjects. In vitro studies indicate that insulin and glucocorticoids work directly on adipose tissue to upregulate in a synergistic manner leptin mRNA levels and rates of leptin secretion in human adipose tissue over the long term. Thus, the increased leptin expression observed in obesity could result from the chronic hyperinsulinemia and increased cortisol turnover. Superimposed upon the long-term regulation, nutritional status can influence serum leptin over the short term, independent of adiposity. Fasting leads to a gradual decline in serum leptin that is probably attributable to the decline in insulin and the ability of catecholamines to decrease leptin expression, as observed in both in vivo and in vitro studies. In addition, increases in serum leptin occur approximately 4-7 h after meals. Increasing evidence indicates that insulin, in concert with permissive effects of cortisol, can increase serum leptin over this time frame and likely contributes to meal-induced increases in serum leptin. Further research is required to elucidate the cellular and molecular mechanisms underlying short- and long-term nutritional and hormonal regulation of leptin production and secretion.

Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

PubMed Central

Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

2016-01-01

Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals. PMID:27833531

Long-Term Plasticity of Neurotransmitter Release: Emerging Mechanisms and Contributions to Brain Function and Disease.

PubMed

Monday, Hannah R; Younts, Thomas J; Castillo, Pablo E

2018-04-25

Long-lasting changes of brain function in response to experience rely on diverse forms of activity-dependent synaptic plasticity. Chief among them are long-term potentiation and long-term depression of neurotransmitter release, which are widely expressed by excitatory and inhibitory synapses throughout the central nervous system and can dynamically regulate information flow in neural circuits. This review article explores recent advances in presynaptic long-term plasticity mechanisms and contributions to circuit function. Growing evidence indicates that presynaptic plasticity may involve structural changes, presynaptic protein synthesis, and transsynaptic signaling. Presynaptic long-term plasticity can alter the short-term dynamics of neurotransmitter release, thereby contributing to circuit computations such as novelty detection, modifications of the excitatory/inhibitory balance, and sensory adaptation. In addition, presynaptic long-term plasticity underlies forms of learning and its dysregulation participates in several neuropsychiatric conditions, including schizophrenia, autism, intellectual disabilities, neurodegenerative diseases, and drug abuse. Expected final online publication date for the Annual Review of Neuroscience Volume 41 is July 8, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The behavior of renal-regulating hormones during hypogravic stress

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1985-01-01

The regulation of fluid and electrolyte behavior during space flight is believed to be under control, in large part, of a group of hormones which have their major effects on renal excretion. The hormones studied include renin-angitensin, aldosterone, and antidiuretic hormone (ADH). The regulatory systems of these renal-regulating hormones as they act individually and in concert with each other are analyzed. The analysis is based on simulations of the mathematical model of Guyton. A generalized theory is described which accounts for both short-term and long-term behavior of this set of hormones.

iTRAQ-based proteomic analysis reveals the mechanisms of silicon-mediated cadmium tolerance in rice (Oryza sativa) cells.

PubMed

Ma, Jie; Sheng, Huachun; Li, Xiuli; Wang, Lijun

2016-07-01

Silicon (Si) can alleviate cadmium (Cd) stress in rice (Oryza sativa) plants, however, the understanding of the molecular mechanisms at the single-cell level remains limited. To address these questions, we investigated suspension cells of rice cultured in the dark environment in the absence and presence of Si with either short- (12 h) or long-term (5 d) Cd treatments using a combination of isobaric tags for relative and absolute quantitation (iTRAQ), fluorescent staining, and inductively coupled plasma mass spectroscopy (ICP-MS). We identified 100 proteins differentially regulated by Si under the short- or long-term Cd stress. 70% of these proteins were down-regulated, suggesting that Si may improve protein use efficiency by maintaining cells in the normal physiological status. Furthermore, we showed two different mechanisms for Si-mediated Cd tolerance. Under the short-term Cd stress, the Si-modified cell walls inhibited the uptake of Cd ions into cells and consequently reduced the expressions of glycosidase, cell surface non-specific lipid-transfer proteins (nsLTPs), and several stress-related proteins. Under the long-term Cd stress, the amount of Cd in the cytoplasm in Si-accumulating (+Si) cells was decreased by compartmentation of Cd into vacuoles, thus leading to a lower expression of glutathione S-transferases (GST). These results provide protein-level insights into the Si-mediated Cd detoxification in rice single cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

CB1 Cannabinoid Receptors Modulate Kinase and Phosphatase Activity during Extinction of Conditioned Fear in Mice

ERIC Educational Resources Information Center

Kamprath, Kornelia; Hermann, Heike; Lutz, Beat; Marsicano, Giovanni; Cannich, Astrid; Wotjak, Carsten T.

2004-01-01

Cannabinoid receptors type 1 (CB1) play a central role in both short-term and long-term extinction of auditory-cued fear memory. The molecular mechanisms underlying this function remain to be clarified. Several studies indicated extracellular signal-regulated kinases (ERKs), the phosphatidylinositol 3-kinase with its downstream effector AKT, and…

Committing to coal and gas: Long-term contracts, regulation, and fuel switching in power generation

NASA Astrophysics Data System (ADS)

Rice, Michael

Fuel switching in the electricity sector has important economic and environmental consequences. In the United States, the increased supply of gas during the last decade has led to substantial switching in the short term. Fuel switching is constrained, however, by the existing infrastructure. The power generation infrastructure, in turn, represents commitments to specific sources of energy over the long term. This dissertation explores fuel contracts as the link between short-term price response and long-term plant investments. Contracting choices enable power plant investments that are relationship-specific, often regulated, and face uncertainty. Many power plants are subject to both hold-up in investment and cost-of-service regulation. I find that capital bias is robust when considering either irreversibility or hold-up due to the uncertain arrival of an outside option. For sunk capital, the rental rate is inappropriate for determining capital bias. Instead, capital bias depends on the regulated rate of return, discount rate, and depreciation schedule. If policies such as emissions regulations increase fuel-switching flexibility, this can lead to capital bias. Cost-of-service regulation can shorten the duration of a long-term contract. From the firm's perspective, the existing literature provides limited guidance when bargaining and writing contracts for fuel procurement. I develop a stochastic programming framework to optimize long-term contracting decisions under both endogenous and exogenous sources of hold-up risk. These typically include policy changes, price shocks, availability of fuel, and volatility in derived demand. For price risks, the optimal contract duration is the moment when the expected benefits of the contract are just outweighed by the expected opportunity costs of remaining in the contract. I prove that imposing early renegotiation costs decreases contract duration. Finally, I provide an empirical approach to show how coal contracts can limit short-term fuel switching in power production. During the era prior to shale gas and electricity market deregulation, I do not find evidence that gas generation substituted for coal in response to fuel price changes. However, I do find evidence that coal plant operations are constrained by fuel contracts. As the min-take commitment to coal increases, changes to annual coal plant output decrease. My conclusions are robust in spite of bias due to the selective reporting of proprietary coal delivery contracts by utilities.

Long-term load duration induces N-cadherin down-regulation and loss of cell phenotype of nucleus pulposus cells in a disc bioreactor culture.

PubMed

Li, Pei; Zhang, Ruijie; Wang, Liyuan; Gan, Yibo; Xu, Yuan; Song, Lei; Luo, Lei; Zhao, Chen; Zhang, Chengmin; Ouyang, Bin; Tu, Bing; Zhou, Qiang

2017-04-30

Long-term exposure to a mechanical load causes degenerative changes in the disc nucleus pulposus (NP) tissue. A previous study demonstrated that N-cadherin (N-CDH)-mediated signalling can preserve the NP cell phenotype. However, N-CDH expression and the resulting phenotype alteration in NP cells under mechanical compression remain unclear. The present study investigated the effects of the compressive duration on N-CDH expression and on the phenotype of NP cells in an ex vivo disc organ culture. Porcine discs were organ cultured in a self-developed mechanically active bioreactor for 7 days. The discs were subjected to different dynamic compression durations (1 and 8 h at a magnitude of 0.4 MPa and frequency of 1.0 Hz) once per day. Discs that were not compressed were used as controls. The results showed that long-term compression duration (8 h) significantly down-regulated the expression of N-CDH and NP-specific molecule markers (Brachyury, Laminin, Glypican-3 and Keratin 19), attenuated Alcian Blue staining intensity, decreased glycosaminoglycan (GAG) and hydroxyproline (HYP) contents and decreased matrix macromolecule (aggrecan and collagen II) expression compared with the short-term compression duration (1 h). Taken together, these findings demonstrate that long-term load duration can induce N-CDH down-regulation, loss of normal cell phenotype and result in attenuation of NP-related matrix synthesis in NP cells. © 2017 The Author(s).

PKA-CREB-BDNF signaling pathway mediates propofol-induced long-term learning and memory impairment in hippocampus of rats.

PubMed

Zhong, Yu; Chen, Jing; Li, Li; Qin, Yi; Wei, Yi; Pan, Shining; Jiang, Yage; Chen, Jialin; Xie, Yubo

2018-04-20

Studies have found that propofol can induce widespread neuroapoptosis in developing brains, which leads to cause long-term learning and memory abnormalities. However, the specific cellular and molecular mechanisms underlying propofol-induced neuroapoptosis remain elusive. The aim of the present study was to explore the role of PKA-CREB-BDNF signaling pathway in propofol-induced long-term learning and memory impairment during brain development. Seven-day-old rats were randomly assigned to control, intralipid and three treatment groups (n = 5). Rats in control group received no treatment. Intralipid (10%, 10 mL/kg) for vehicle control and different dosage of propofol for three treatment groups (50, 100 and 200 mg/kg) were administered intraperitoneally. FJB staining, immunohistochemistry analysis for neuronal nuclei antigen and transmission electron microscopy were used to detect neuronal apoptosis and structure changes. MWM test examines the long-term spatial learning and memory impairment. The expression of PKA, pCREB and BDNF was quantified using western blots. Propofol induced significant increase of FJB-positive cells and decrease of PKA, pCREB and BDNF protein levels in the immature brain of P7 rats. Using the MWM test, propofol-treated rats demonstrated long-term spatial learning and memory impairment. Moreover, hippocampal NeuN-positive cell loss, long-lasting ultrastructural abnormalities of the neurons and synapses, and long-term down-regulation of PKA, pCREB and BDNF protein expression in adult hippocampus were also found. Our results indicated that neonatal propofol exposure can significantly result in long-term learning and memory impairment in adulthood. The possible mechanism involved in the propofol-induced neuroapoptosis was related to down-regulation of PKA-CREB-BDNF signaling pathway. Copyright © 2018. Published by Elsevier B.V.

Novel energy-saving strategies to multiple stressors in birds: the ultradian regulation of body temperature.

PubMed

Tattersall, Glenn J; Roussel, Damien; Voituron, Yann; Teulier, Loïc

2016-09-28

This study aimed to examine thermoregulatory responses in birds facing two commonly experienced stressors, cold and fasting. Logging devices allowing long-term and precise access to internal body temperature were placed within the gizzards of ducklings acclimated to cold (CA) (5°C) or thermoneutrality (TN) (25°C). The animals were then examined under three equal 4-day periods: ad libitum feeding, fasting and re-feeding. Through the analysis of daily as well as short-term, or ultradian, variations of body temperature, we showed that while ducklings at TN show only a modest decline in daily thermoregulatory parameters when fasted, they exhibit reduced surface temperatures from key sites of vascular heat exchange during fasting. The CA birds, on the other hand, significantly reduced their short-term variations of body temperature while increasing long-term variability when fasting. This phenomenon would allow the CA birds to reduce the energetic cost of body temperature maintenance under fasting. By analysing ultradian regulation of body temperature, we describe a means by which an endotherm appears to lower thermoregulatory costs in response to the combined stressors of cold and fasting. © 2016 The Author(s).

Novel energy-saving strategies to multiple stressors in birds: the ultradian regulation of body temperature

PubMed Central

2016-01-01

This study aimed to examine thermoregulatory responses in birds facing two commonly experienced stressors, cold and fasting. Logging devices allowing long-term and precise access to internal body temperature were placed within the gizzards of ducklings acclimated to cold (CA) (5°C) or thermoneutrality (TN) (25°C). The animals were then examined under three equal 4-day periods: ad libitum feeding, fasting and re-feeding. Through the analysis of daily as well as short-term, or ultradian, variations of body temperature, we showed that while ducklings at TN show only a modest decline in daily thermoregulatory parameters when fasted, they exhibit reduced surface temperatures from key sites of vascular heat exchange during fasting. The CA birds, on the other hand, significantly reduced their short-term variations of body temperature while increasing long-term variability when fasting. This phenomenon would allow the CA birds to reduce the energetic cost of body temperature maintenance under fasting. By analysing ultradian regulation of body temperature, we describe a means by which an endotherm appears to lower thermoregulatory costs in response to the combined stressors of cold and fasting. PMID:27655770

5 CFR 875.104 - What are the steps required to resolve a dispute involving benefit eligibility or payment of a...

Code of Federal Regulations, 2010 CFR

2010-01-01

... Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL LONG TERM.... If you prevail in court, your recovery is limited to the amount of benefits payable under your...

5 CFR 875.104 - What are the steps required to resolve a dispute involving benefit eligibility or payment of a...

Code of Federal Regulations, 2012 CFR

2012-01-01

... Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL LONG TERM.... If you prevail in court, your recovery is limited to the amount of benefits payable under your...

5 CFR 875.104 - What are the steps required to resolve a dispute involving benefit eligibility or payment of a...

Code of Federal Regulations, 2011 CFR

2011-01-01

... Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL LONG TERM.... If you prevail in court, your recovery is limited to the amount of benefits payable under your...

Epigenetic mechanisms: critical contributors to long-term memory formation.

PubMed

Lubin, Farah D; Gupta, Swati; Parrish, R Ryley; Grissom, Nicola M; Davis, Robin L

2011-12-01

Recent advances in chromatin biology have identified a role for epigenetic mechanisms in the regulation of neuronal gene expression changes, a necessary process for proper synaptic plasticity and memory formation. Experimental evidence for dynamic chromatin remodeling influencing gene transcription in postmitotic neurons grew from initial reports describing posttranslational modifications of histones, including phosphorylation and acetylation occurring in various brain regions during memory consolidation. An accumulation of recent studies, however, has also highlighted the importance of other epigenetic modifications, such as DNA methylation and histone methylation, as playing a role in memory formation. This present review examines learning-induced gene transcription by chromatin remodeling underlying long-lasting changes in neurons, with direct implications for the study of epigenetic mechanisms in long-term memory formation and behavior. Furthermore, the study of epigenetic gene regulation, in conjunction with transcription factor activation, can provide complementary lines of evidence to further understanding transcriptional mechanisms subserving memory storage.

26 CFR 1.921-1T - Temporary regulations providing transition rules for DISCs and FSCs.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) for activities which occur before January 1, 1985 in order to use the transfer pricing rules under... before January 1, 1985, in order to use the transfer pricing rules under section 925. (10) Long-term... section 925(c) for activities which occur before January 1, 1985 in order to use the transfer pricing...

Long-term high-soybean oil feeding alters regulation of body temperature in rats.

PubMed

Tsushima, Hiromi; Yamada, Kazuyo; Miyazawa, Daisuke; Mori, Mayumi; Hashimoto, Yoko; Ohkubo, Takeshi; Hibino, Hidehiko; Okuyama, Harumi

2014-01-01

We investigated whether body temperature (BT) regulatory mechanisms are influenced by dietary fatty acids (FA). Male Wistar rats were fed a high-fat diet containing fish oil (HFD), soybean oil (HSD) or lard (HLD). At the 20-week intervention, the BT of the HSD and HLD groups were lower than that of the normal diet (ND) group in the light and dark periods. The intracerebroventricular injections of interleukin-1β and bombesin in the HSD group induced greater hyperthermia and weaker hypothermia, respectively, than in the ND group. The HSD differentially affected BT under both physiological and pharmacological conditions. In the hypothalamus, the ratio of n-6/n-3 FAs was higher in the HSD group compared with the ND group. DNA microarrays revealed increased expression of thyroid-stimulating hormone β-subunit, and decreased expression of several genes in the hypothalamus of the HSD group compared with the ND group. The HSD feeding increased several adipokine concentrations in the plasma. However, there were no adipokines or gene expressions that changed in only the HSD and HLD groups showing significant hypothermia under the physiological condition. These findings suggested that long-term HSD intake produces abnormal BT regulation. It is less likely that adipokines or proteins/peptides are involved in abnormal BT regulation under the physiological conditions after HSD feeding.

Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression

NASA Astrophysics Data System (ADS)

Matsuda, Shinji; Kakegawa, Wataru; Budisantoso, Timotheus; Nomura, Toshihiro; Kohda, Kazuhisa; Yuzaki, Michisuke

2013-11-01

Long-term depression (LTD) underlies learning and memory in various brain regions. Although postsynaptic AMPA receptor trafficking mediates LTD, its underlying molecular mechanisms remain largely unclear. Here we show that stargazin, a transmembrane AMPA receptor regulatory protein, forms a ternary complex with adaptor proteins AP-2 and AP-3A in hippocampal neurons, depending on its phosphorylation state. Inhibiting the stargazin-AP-2 interaction disrupts NMDA-induced AMPA receptor endocytosis, and inhibiting that of stargazin-AP-3A abrogates the late endosomal/lysosomal trafficking of AMPA receptors, thereby upregulating receptor recycling to the cell surface. Similarly, stargazin’s interaction with AP-2 or AP-3A is necessary for low-frequency stimulus-evoked LTD in CA1 hippocampal neurons. Thus, stargazin has a crucial role in NMDA-dependent LTD by regulating two trafficking pathways of AMPA receptors—transport from the cell surface to early endosomes and from early endosomes to late endosomes/lysosomes—through its sequential binding to AP-2 and AP-3A.

Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release.

PubMed

Younts, Thomas J; Monday, Hannah R; Dudok, Barna; Klein, Matthew E; Jordan, Bryen A; Katona, István; Castillo, Pablo E

2016-10-19

Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remain unclear. Here, using paired whole-cell recordings in rodent hippocampal slices, we report that presynaptic protein synthesis is required for long-term, but not short-term, plasticity of GABA release from type 1 cannabinoid receptor (CB 1 )-expressing axons. This long-term depression of inhibitory transmission (iLTD) involves cap-dependent protein synthesis in presynaptic interneuron axons, but not somata. Translation is required during the induction, but not maintenance, of iLTD. Mechanistically, CB 1 activation enhances protein synthesis via the mTOR pathway. Furthermore, using super-resolution STORM microscopy, we revealed eukaryotic ribosomes in CB 1 -expressing axon terminals. These findings suggest that presynaptic local protein synthesis controls neurotransmitter release during long-term plasticity in the mature mammalian brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Upregulation of CREB-mediated transcription enhances both short- and long-term memory.

PubMed

Suzuki, Akinobu; Fukushima, Hotaka; Mukawa, Takuya; Toyoda, Hiroki; Wu, Long-Jun; Zhao, Ming-Gao; Xu, Hui; Shang, Yuze; Endoh, Kengo; Iwamoto, Taku; Mamiya, Nori; Okano, Emiko; Hasegawa, Shunsuke; Mercaldo, Valentina; Zhang, Yue; Maeda, Ryouta; Ohta, Miho; Josselyn, Sheena A; Zhuo, Min; Kida, Satoshi

2011-06-15

Unraveling the mechanisms by which the molecular manipulation of genes of interest enhances cognitive function is important to establish genetic therapies for cognitive disorders. Although CREB is thought to positively regulate formation of long-term memory (LTM), gain-of-function effects of CREB remain poorly understood, especially at the behavioral level. To address this, we generated four lines of transgenic mice expressing dominant active CREB mutants (CREB-Y134F or CREB-DIEDML) in the forebrain that exhibited moderate upregulation of CREB activity. These transgenic lines improved not only LTM but also long-lasting long-term potentiation in the CA1 area in the hippocampus. However, we also observed enhanced short-term memory (STM) in contextual fear-conditioning and social recognition tasks. Enhanced LTM and STM could be dissociated behaviorally in these four lines of transgenic mice, suggesting that the underlying mechanism for enhanced STM and LTM are distinct. LTM enhancement seems to be attributable to the improvement of memory consolidation by the upregulation of CREB transcriptional activity, whereas higher basal levels of BDNF, a CREB target gene, predicted enhanced shorter-term memory. The importance of BDNF in STM was verified by microinfusing BDNF or BDNF inhibitors into the hippocampus of wild-type or transgenic mice. Additionally, increasing BDNF further enhanced LTM in one of the lines of transgenic mice that displayed a normal BDNF level but enhanced LTM, suggesting that upregulation of BDNF and CREB activity cooperatively enhances LTM formation. Our findings suggest that CREB positively regulates memory consolidation and affects memory performance by regulating BDNF expression.

Variation of DNA Methylome of Zebrafish Cells under Cold Pressure

PubMed Central

Xu, Qiongqiong; Luo, Juntao; Shi, Yingdi; Li, Xiaoxia; Yan, Xiaonan; Zhang, Junfang

2016-01-01

DNA methylation is an essential epigenetic mechanism involved in multiple biological processes. However, the relationship between DNA methylation and cold acclimation remains poorly understood. In this study, Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq) was performed to reveal a genome-wide methylation profile of zebrafish (Danio rerio) embryonic fibroblast cells (ZF4) and its variation under cold pressure. MeDIP-seq assay was conducted with ZF4 cells cultured at appropriate temperature of 28°C and at low temperature of 18°C for 5 (short-term) and 30 (long-term) days, respectively. Our data showed that DNA methylation level of whole genome increased after a short-term cold exposure and decreased after a long-term cold exposure. It is interesting that metabolism of folate pathway is significantly hypomethylated after short-term cold exposure, which is consistent with the increased DNA methylation level. 21% of methylation peaks were significantly altered after cold treatment. About 8% of altered DNA methylation peaks are located in promoter regions, while the majority of them are located in non-coding regions. Methylation of genes involved in multiple cold responsive biological processes were significantly affected, such as anti-oxidant system, apoptosis, development, chromatin modifying and immune system suggesting that those processes are responsive to cold stress through regulation of DNA methylation. Our data indicate the involvement of DNA methylation in cellular response to cold pressure, and put a new insight into the genome-wide epigenetic regulation under cold pressure. PMID:27494266

Long-Term Homeostatic Properties Complementary to Hebbian Rules in CuPc-Based Multifunctional Memristor

NASA Astrophysics Data System (ADS)

Wang, Laiyuan; Wang, Zhiyong; Lin, Jinyi; Yang, Jie; Xie, Linghai; Yi, Mingdong; Li, Wen; Ling, Haifeng; Ou, Changjin; Huang, Wei

2016-10-01

Most simulations of neuroplasticity in memristors, which are potentially used to develop artificial synapses, are confined to the basic biological Hebbian rules. However, the simplex rules potentially can induce excessive excitation/inhibition, even collapse of neural activities, because they neglect the properties of long-term homeostasis involved in the frameworks of realistic neural networks. Here, we develop organic CuPc-based memristors of which excitatory and inhibitory conductivities can implement both Hebbian rules and homeostatic plasticity, complementary to Hebbian patterns and conductive to the long-term homeostasis. In another adaptive situation for homeostasis, in thicker samples, the overall excitement under periodic moderate stimuli tends to decrease and be recovered under intense inputs. Interestingly, the prototypes can be equipped with bio-inspired habituation and sensitization functions outperforming the conventional simplified algorithms. They mutually regulate each other to obtain the homeostasis. Therefore, we develop a novel versatile memristor with advanced synaptic homeostasis for comprehensive neural functions.

Antimicrobial peptides keep insect endosymbionts under control.

PubMed

Login, Frédéric H; Balmand, Séverine; Vallier, Agnès; Vincent-Monégat, Carole; Vigneron, Aurélien; Weiss-Gayet, Michèle; Rochat, Didier; Heddi, Abdelaziz

2011-10-21

Vertically transmitted endosymbionts persist for millions of years in invertebrates and play an important role in animal evolution. However, the functional basis underlying the maintenance of these long-term resident bacteria is unknown. We report that the weevil coleoptericin-A (ColA) antimicrobial peptide selectively targets endosymbionts within the bacteriocytes and regulates their growth through the inhibition of cell division. Silencing the colA gene with RNA interference resulted in a decrease in size of the giant filamentous endosymbionts, which escaped from the bacteriocytes and spread into insect tissues. Although this family of peptides is commonly linked with microbe clearance, this work shows that endosymbiosis benefits from ColA, suggesting that long-term host-symbiont coevolution might have shaped immune effectors for symbiont maintenance.

Regulated provider perceptions of feedback reports.

PubMed

O'Rourke, Hannah M; Fraser, Kimberly D; Boström, Anne-Marie; Baylon, Melba Andrea B; Sales, Anne E

2013-11-01

This paper reports on regulated (or licensed) care providers' understanding and perceptions of feedback reports in a sample of Canadian long-term care settings using a cross-sectional survey design. Audit with feedback quality improvement studies have seldom targeted front-line providers in long-term care to receive feedback information. Feedback reports were delivered to front-line regulated care providers in four long-term care facilities for 13 months in 2009-10. Providers completed a postfeedback survey. Most (78%) regulated care providers (n = 126) understood the reports and felt they provided useful information for making changes to resident care (64%). Perceptions of the report differed, depending on the role of the regulated care provider. In multivariable logistic regression, the regulated nurses' understanding of more than half the report was negatively associated with 'usefulness of information for changing resident care', and perceiving the report as generally useful had a positive association. Front-line regulated providers are an appropriate target for feedback reports in long-term care. Long-term care administrators should share unit-level information on care quality with unit-level managers and other professional front-line direct care providers. © 2013 John Wiley & Sons Ltd.

42 CFR 483.405 - Relationship to other HHS regulations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SERVICES (CONTINUED) STANDARDS AND CERTIFICATION REQUIREMENTS FOR STATES AND LONG TERM CARE FACILITIES Conditions of Participation for Intermediate Care Facilities for the Mentally Retarded § 483.405 Relationship... participation under this Part, their violation may result in the termination or suspension of, or the refusal to...

Dormancy behaviors and underlying regulatory mechanisms: from perspective of pathways to epigenetic regulation

USDA-ARS?s Scientific Manuscript database

Temperate perennials exploit dormancy as one strategy to survive long term environmental stresses. As the current trend in global warming continues, many regions are experiencing warmer winters that fail to provide sufficient chilling temperature for dormancy release, impacting fruit tree productiv...

Metabotropic Glutamate Receptors in the Trafficking of Ionotropic Glutamate and GABAA Receptors at Central Synapses

PubMed Central

Xiao, Min-Yi; Gustafsson, Bengt; Niu, Yin-Ping

2006-01-01

The trafficking of ionotropic glutamate (AMPA, NMDA and kainate) and GABAA receptors in and out of, or laterally along, the postsynaptic membrane has recently emerged as an important mechanism in the regulation of synaptic function, both under physiological and pathological conditions, such as information processing, learning and memory formation, neuronal development, and neurodegenerative diseases. Non-ionotropic glutamate receptors, primarily group I metabotropic glutamate receptors (mGluRs), co-exist with the postsynaptic ionotropic glutamate and GABAA receptors. The ability of mGluRs to regulate postsynaptic phosphorylation and Ca2+ concentration, as well as their interactions with postsynaptic scaffolding/signaling proteins, makes them well suited to influence the trafficking of ionotropic glutamate and GABAA receptors. Recent studies have provided insights into how mGluRs may impose such an influence at central synapses, and thus how they may affect synaptic signaling and the maintenance of long-term synaptic plasticity. In this review we will discuss some of the recent progress in this area: i) long-term synaptic plasticity and the involvement of mGluRs; ii) ionotropic glutamate receptor trafficking and long-term synaptic plasticity; iii) the involvement of postsynaptic group I mGluRs in regulating ionotropic glutamate receptor trafficking; iv) involvement of postsynaptic group I mGluRs in regulating GABAA receptor trafficking; v) and the trafficking of postsynaptic group I mGluRs themselves. PMID:18615134

Metabotropic glutamate receptors in the trafficking of ionotropic glutamate and GABA(A) receptors at central synapses.

PubMed

Xiao, Min-Yi; Gustafsson, Bengt; Niu, Yin-Ping

2006-01-01

The trafficking of ionotropic glutamate (AMPA, NMDA and kainate) and GABA(A) receptors in and out of, or laterally along, the postsynaptic membrane has recently emerged as an important mechanism in the regulation of synaptic function, both under physiological and pathological conditions, such as information processing, learning and memory formation, neuronal development, and neurodegenerative diseases. Non-ionotropic glutamate receptors, primarily group I metabotropic glutamate receptors (mGluRs), co-exist with the postsynaptic ionotropic glutamate and GABA(A) receptors. The ability of mGluRs to regulate postsynaptic phosphorylation and Ca(2+) concentration, as well as their interactions with postsynaptic scaffolding/signaling proteins, makes them well suited to influence the trafficking of ionotropic glutamate and GABA(A) receptors. Recent studies have provided insights into how mGluRs may impose such an influence at central synapses, and thus how they may affect synaptic signaling and the maintenance of long-term synaptic plasticity. In this review we will discuss some of the recent progress in this area: i) long-term synaptic plasticity and the involvement of mGluRs; ii) ionotropic glutamate receptor trafficking and long-term synaptic plasticity; iii) the involvement of postsynaptic group I mGluRs in regulating ionotropic glutamate receptor trafficking; iv) involvement of postsynaptic group I mGluRs in regulating GABA(A) receptor trafficking; v) and the trafficking of postsynaptic group I mGluRs themselves.

Long term load forecasting accuracy in electric utility integrated resource planning

DOE PAGES

Carvallo, Juan Pablo; Larsen, Peter H.; Sanstad, Alan H.; ...

2018-05-23

Forecasts of electricity consumption and peak demand over time horizons of one or two decades are a key element in electric utilities’ meeting their core objective and obligation to ensure reliable and affordable electricity supplies for their customers while complying with a range of energy and environmental regulations and policies. These forecasts are an important input to integrated resource planning (IRP) processes involving utilities, regulators, and other stake-holders. Despite their importance, however, there has been little analysis of long term utility load forecasting accuracy. We conduct a retrospective analysis of long term load forecasts on twelve Western U. S. electricmore » utilities in the mid-2000s to find that most overestimated both energy consumption and peak demand growth. A key reason for this was the use of assumptions that led to an overestimation of economic growth. We find that the complexity of forecast methods and the accuracy of these forecasts are mildly correlated. In addition, sensitivity and risk analysis of load growth and its implications for capacity expansion were not well integrated with subsequent implementation. As a result, we review changes in the utilities load forecasting methods over the subsequent decade, and discuss the policy implications of long term load forecast inaccuracy and its underlying causes.« less

Long term load forecasting accuracy in electric utility integrated resource planning

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

Carvallo, Juan Pablo; Larsen, Peter H.; Sanstad, Alan H.

Forecasts of electricity consumption and peak demand over time horizons of one or two decades are a key element in electric utilities’ meeting their core objective and obligation to ensure reliable and affordable electricity supplies for their customers while complying with a range of energy and environmental regulations and policies. These forecasts are an important input to integrated resource planning (IRP) processes involving utilities, regulators, and other stake-holders. Despite their importance, however, there has been little analysis of long term utility load forecasting accuracy. We conduct a retrospective analysis of long term load forecasts on twelve Western U. S. electricmore » utilities in the mid-2000s to find that most overestimated both energy consumption and peak demand growth. A key reason for this was the use of assumptions that led to an overestimation of economic growth. We find that the complexity of forecast methods and the accuracy of these forecasts are mildly correlated. In addition, sensitivity and risk analysis of load growth and its implications for capacity expansion were not well integrated with subsequent implementation. As a result, we review changes in the utilities load forecasting methods over the subsequent decade, and discuss the policy implications of long term load forecast inaccuracy and its underlying causes.« less

Transcript Profile of the Response of Two Soybean Genotypes to Potassium Deficiency

PubMed Central

Hao, QingNan; Sha, AiHua; Shan, ZhiHui; Chen, LiMiao; Zhou, Rong; Zhi, HaiJian; Zhou, XinAn

2012-01-01

The macronutrient potassium (K) is essential to plant growth and development. Crop yield potential is often affected by lack of soluble K. The molecular regulation mechanism of physiological and biochemical responses to K starvation in soybean roots and shoots is not fully understood. In the present study, two soybean varieties were subjected to low-K stress conditions: a low-K-tolerant variety (You06-71) and a low-K-sensitive variety (HengChun04-11). Eight libraries were generated for analysis: 2 genotypes ×2 tissues (roots and shoots) ×2 time periods [short term (0.5 to 12 h) and long term (3 to 12 d)]. RNA derived from the roots and shoots of these two varieties across two periods (short term and long term) were sequenced and the transcriptomes were compared using high-throughput tag-sequencing. To this end, a large number of clean tags (tags used for analysis after removal of dirty tags) corresponding to distinct tags (all types of clean tags) were identified in eight libraries (L1, You06-71-root short term; L2, HengChun04-11-root short term; L3, You06-71-shoot short term; L4, HengChun04-11-shoot short term; L5, You06-71-root long term; L6, HengChun04-11-root long term; L7, You06-71-shoot long term; L8, HengChun04-11-shoot long term). All clean tags were mapped to the available soybean (Glycine max) transcript database (http://www.soybase.org). Many genes showed substantial differences in expression across the libraries. In total, 5,440 transcripts involved in 118 KEGG pathways were either up- or down-regulated. Fifteen genes were randomly selected and their expression levels were confirmed using quantitative RT-PCR. Our results provide preliminary information on the molecular mechanism of potassium absorption and transport under low-K stress conditions in different soybean tissues. PMID:22792192

Effect of circadian phase on memory acquisition and recall: operant conditioning vs. classical conditioning.

PubMed

Garren, Madeleine V; Sexauer, Stephen B; Page, Terry L

2013-01-01

There have been several studies on the role of circadian clocks in the regulation of associative learning and memory processes in both vertebrate and invertebrate species. The results have been quite variable and at present it is unclear to what extent the variability observed reflects species differences or differences in methodology. Previous results have shown that following differential classical conditioning in the cockroach, Rhyparobia maderae, in an olfactory discrimination task, formation of the short-term and long-term memory is under strict circadian control. In contrast, there appeared to be no circadian regulation of the ability to recall established memories. In the present study, we show that following operant conditioning of the same species in a very similar olfactory discrimination task, there is no impact of the circadian system on either short-term or long-term memory formation. On the other hand, ability to recall established memories is strongly tied to the circadian phase of training. On the basis of these data and those previously reported for phylogenetically diverse species, it is suggested that there may be fundamental differences in the way the circadian system regulates learning and memory in classical and operant conditioning.

Effect of Circadian Phase on Memory Acquisition and Recall: Operant Conditioning vs. Classical Conditioning

PubMed Central

Garren, Madeleine V.; Sexauer, Stephen B.; Page, Terry L.

2013-01-01

There have been several studies on the role of circadian clocks in the regulation of associative learning and memory processes in both vertebrate and invertebrate species. The results have been quite variable and at present it is unclear to what extent the variability observed reflects species differences or differences in methodology. Previous results have shown that following differential classical conditioning in the cockroach, Rhyparobia maderae, in an olfactory discrimination task, formation of the short-term and long-term memory is under strict circadian control. In contrast, there appeared to be no circadian regulation of the ability to recall established memories. In the present study, we show that following operant conditioning of the same species in a very similar olfactory discrimination task, there is no impact of the circadian system on either short-term or long-term memory formation. On the other hand, ability to recall established memories is strongly tied to the circadian phase of training. On the basis of these data and those previously reported for phylogenetically diverse species, it is suggested that there may be fundamental differences in the way the circadian system regulates learning and memory in classical and operant conditioning. PMID:23533587

Global gene expression analysis of the response of physic nut (Jatropha curcas L.) to medium- and long-term nitrogen deficiency

PubMed Central

Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu

2017-01-01

Jatropha curcas L. is an important biofuel plant with excellent tolerance of barren environments. However, studies on the regulatory mechanisms that operate in this plant in response to nitrogen (N) shortage are scarce. In this study, genome-wide transcriptional profiles of the roots and leaves of 8-week old physic nut seedlings were analyzed after 2 and 16 days of N starvation. Enrichment results showed that genes associated with N metabolism, processing and regulation of RNA, and transport predominated among those showing alterations in expression. Genes encoding transporter families underwent major changes in expression in both roots and leaves; in particular, those with roles in ammonia, amino acid and peptide transport were generally up-regulated after long-term starvation, while AQUAPORIN genes, whose products function in osmoregulation, were down-regulated. We also found that ASPARA−GINASE B1 and SARCOSINE OXIDASE genes were up-regulated in roots and leaves after 2 and 16 d N starvation. Genes associated with ubiquitination-mediated protein degradation were significantly up-regulated. In addition, genes in the JA biosynthesis pathway were strongly activated while expression of those in GA signaling was inhibited in leaves. We showed that four major classes of genes, those with roles in N uptake, N reutilization, C/N ratio balance, and cell structure and synthesis, were particularly influenced by long-term N limitation. Our discoveries may offer clues to the molecular mechanisms that regulate N reallocation and reutilization so as to maintain or increase plant performance even under adverse environmental conditions. PMID:28817702

Global gene expression analysis of the response of physic nut (Jatropha curcas L.) to medium- and long-term nitrogen deficiency.

PubMed

Kuang, Qi; Zhang, Sheng; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

2017-01-01

Jatropha curcas L. is an important biofuel plant with excellent tolerance of barren environments. However, studies on the regulatory mechanisms that operate in this plant in response to nitrogen (N) shortage are scarce. In this study, genome-wide transcriptional profiles of the roots and leaves of 8-week old physic nut seedlings were analyzed after 2 and 16 days of N starvation. Enrichment results showed that genes associated with N metabolism, processing and regulation of RNA, and transport predominated among those showing alterations in expression. Genes encoding transporter families underwent major changes in expression in both roots and leaves; in particular, those with roles in ammonia, amino acid and peptide transport were generally up-regulated after long-term starvation, while AQUAPORIN genes, whose products function in osmoregulation, were down-regulated. We also found that ASPARA-GINASE B1 and SARCOSINE OXIDASE genes were up-regulated in roots and leaves after 2 and 16 d N starvation. Genes associated with ubiquitination-mediated protein degradation were significantly up-regulated. In addition, genes in the JA biosynthesis pathway were strongly activated while expression of those in GA signaling was inhibited in leaves. We showed that four major classes of genes, those with roles in N uptake, N reutilization, C/N ratio balance, and cell structure and synthesis, were particularly influenced by long-term N limitation. Our discoveries may offer clues to the molecular mechanisms that regulate N reallocation and reutilization so as to maintain or increase plant performance even under adverse environmental conditions.

HDAC3 and the Molecular Brake Pad Hypothesis

PubMed Central

McQuown, Susan C.; Wood, Marcelo A.

2011-01-01

Successful transcription of specific genes required for long-term memory processes involves the orchestrated effort of not only transcription factors, but also very specific enzymatic protein complexes that modify chromatin structure. Chromatin modification has been identified as a pivotal molecular mechanism underlying certain forms of synaptic plasticity and memory. The best-studied form of chromatin modification in the learning and memory field is histone acetylation, which is regulated by histone acetyltransferases and histone deacetylases (HDACs). HDAC inhibitors have been shown to strongly enhance long-term memory processes, and recent work has aimed to identify contributions of individual HDACs. In this review, we focus on HDAC3 and discuss its recently defined role as a negative regulator of long-term memory formation. HDAC3 is part of a corepressor complex and has direct interactions with class II HDACs that may be important for its molecular and behavioral consequences. And last, we propose the “molecular brake pad” hypothesis of HDAC function. The HDACs and associated corepressor complexes may function in neurons, in part, as “molecular brake pads.” HDACs are localized to promoters of active genes and act as a persistent clamp that requires strong activity-dependent signaling to temporarily release these complexes (or brake pads) to activate gene expression required for long-term memory formation. Thus, HDAC inhibition removes the “molecular brake pads” constraining the processes necessary for long-term memory and results in strong, persistent memory formation. PMID:21521655

7 CFR 625.10 - Cost-share payments.

Code of Federal Regulations, 2011 CFR

2011-01-01

... recovery of listed species under the ESA, candidate, or other species covered by this regulation. These protections operate with lands enrolled in the HFRP and are valid for as long as the landowner is in compliance with the terms and conditions of such assurances, any associated permit, the easement, contract...

7 CFR 625.10 - Cost-share payments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... recovery of listed species under the ESA, candidate, or other species covered by this regulation. These protections operate with lands enrolled in the HFRP and are valid for as long as the landowner is in compliance with the terms and conditions of such assurances, any associated permit, the easement, contract...

7 CFR 625.10 - Cost-share payments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... recovery of listed species under the ESA, candidate, or other species covered by this regulation. These protections operate with lands enrolled in the HFRP and are valid for as long as the landowner is in compliance with the terms and conditions of such assurances, any associated permit, the easement, contract...

7 CFR 625.10 - Cost-share payments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... recovery of listed species under the ESA, candidate, or other species covered by this regulation. These protections operate with lands enrolled in the HFRP and are valid for as long as the landowner is in compliance with the terms and conditions of such assurances, any associated permit, the easement, contract...

75 FR 21749 - Spring 2010 Semiannual Agenda of Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

...In compliance with Executive Order 12866, entitled ``Regulatory Planning and Review,'' and the Regulatory Flexibility Act, as amended, the Department of Commerce (Department), in the spring and fall of each year, publishes in the Federal Register an agenda of regulations under development of review over the next 12 months. Rulemaking actions are grouped according to prerulemaking, proposed rules, final rules, long-term actions, and rulemaking actions completed since the fall 2009 agenda. The purpose of the agenda is to provide information to the public on regulations currently under review, being proposed, or issued by the Department. The agenda is intended to facilitate comments and views by interested members of the public.

The Multi-Frequency Correlation Between Eua and sCER Futures Prices: Evidence from the Emd Approach

NASA Astrophysics Data System (ADS)

Zhang, Yue-Jun; Huang, Yi-Song

2015-05-01

Currently European Union Allowances (EUA) and secondary Certified Emission Reduction (sCER) have become two dominant carbon trading assets for investors and their linkage attracts much attention from academia and practitioners in recent years. Under this circumstance, we use the empirical mode decomposition (EMD) approach to decompose the two carbon futures contract prices and discuss their correlation from the multi-frequency perspective. The empirical results indicate that, first, the EUA and sCER futures price movements can be divided into those triggered by the long-term, medium-term and short-term market impacts. Second, the price movements in the EUA and sCER futures markets are primarily caused by the long-term impact, while the short-term impact can only explain a small fraction. Finally, the long-term (short-term) effect on EUA prices is statistically uncorrelated with the short-term (long-term) effect of sCER prices, and there is a medium or strong lead-and-lag correlation between the EUA and sCER price components with the same time scales. These results may provide some important insights of price forecast and arbitraging activities for carbon futures market investors, analysts and regulators.

Cortical neuroinflammation contributes to long-term cognitive dysfunctions following adolescent delta-9-tetrahydrocannabinol treatment in female rats.

PubMed

Zamberletti, Erica; Gabaglio, Marina; Prini, Pamela; Rubino, Tiziana; Parolaro, Daniela

2015-12-01

Over 180 million people consume cannabis globally. Cannabis use peaks during adolescence with a trend for continued consumption by adults. Notably, several studies have shown that long-term and heavy cannabis use during adolescence can impair brain maturation and predispose to neurodevelopmental disorders, although the neurobiological mechanisms underlying this association remain largely unknown. In this study, we evaluated whether, in female rats, chronic administration of increasing doses of the psychotropic plant-derived cannabis constituent, delta-9-tetrahydrocannabinol (THC), during adolescence (PND 35-45) could affect microglia function in the long-term. Furthermore, we explored a possible contribution of microglia to the development of THC-induced alterations in mood and cognition in adult female rats. Present data indicate that adolescent THC administration induces a persistent neuroinflammatory state specifically localized within the adult prefrontal cortex (PFC), characterized by increased expression of the pro-inflammatory markers, TNF-α, iNOS and COX-2, and reduction of the anti-inflammatory cytokine, IL-10. This neuroinflammatory phenotype is associated with down-regulation of CB1 receptor on neuronal cells and up-regulation of CB2 on microglia cells, conversely. Interestingly, blocking microglia activation with ibudilast during THC treatment significantly attenuates short-term memory impairments in adulthood, simultaneously preventing the increases in TNF-α, iNOS, COX-2 levels as well as the up-regulation of CB2 receptors on microglia cells. In contrast, THC-induced depressive-like behaviors were unaffected by ibudilast treatment. Our findings demonstrate that adolescent THC administration is associated with persistent neuroinflammation within the PFC and provide evidence for a causal association between microglial activation and the development long-term cognitive deficits induced by adolescent THC treatment. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Factors affecting the entry of for-profit providers into a price regulated market for formal long-term care services: a case study from Japan.

PubMed

Tokunaga, Mutsumi; Hashimoto, Hideki

2013-01-01

While the distinct behaviors of for-profit and non-profit providers in the healthcare market have been compared in the economic literature, their choices regarding market entry and exit have only recently been debated. Since 2000, when public Long-Term Care Insurance was introduced in Japan, for-profit providers have been able to provide formal long-term homecare services. The aim of this study is to determine which factors have affected market entry of for-profit providers under price regulation and in competition with existing non-profit providers. We used nation-wide panel data from 2002 to 2010, aggregated at the level of local public insurers (n = 1557), a basic area unit of service provision. The number of for-profit providers per elderly population in the area unit was regressed against factors related to local demand and service costs using first-difference linear regression, a fixed effects model, and Tobit regression for robustness checking. Results showed that demand (the number of eligible care recipients) and cost factors (population density and minimum wage) significantly influenced for-profit providers' choice of market entry. These findings indicate that for-profit providers will strategically choose a local market for maximizing profit. We believe that price regulation should be redesigned to incorporate quality of care and market conditions, regardless of the profit status of the providers, to ensure equal access to efficient delivery of long-term care across all regions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Regulation of appetite to treat obesity

PubMed Central

Kim, Gilbert W; Lin, Jieru E; Valentino, Michael A; Colon-Gonzalez, Francheska; Waldman, Scott A

2011-01-01

Obesity has escalated into a pandemic over the past few decades. In turn, research efforts have sought to elucidate the molecular mechanisms underlying the regulation of energy balance. A host of endogenous mediators regulate appetite and metabolism, and thereby control both short- and long-term energy balance. These mediators, which include gut, pancreatic and adipose neuropeptides, have been targeted in the development of anti-obesity pharmacotherapy, with the goal of amplifying anorexigenic and lipolytic signaling or blocking orexigenic and lipogenic signaling. This article presents the efficacy and safety of these anti-obesity drugs. PMID:21666781

Obesity treatment: novel peripheral targets

PubMed Central

Field, Benjamin C T; Chaudhri, Owais B; Bloom, Stephen R

2009-01-01

Our knowledge of the complex mechanisms underlying energy homeostasis has expanded enormously in recent years. Food intake and body weight are tightly regulated by the hypothalamus, brainstem and reward circuits, on the basis both of cognitive inputs and of diverse humoral and neuronal signals of nutritional status. Several gut hormones, including cholecystokinin, glucagon-like peptide-1, peptide YY, oxyntomodulin, amylin, pancreatic polypeptide and ghrelin, have been shown to play an important role in regulating short-term food intake. These hormones therefore represent potential targets in the development of novel anti-obesity drugs. This review focuses on the role of gut hormones in short- and long-term regulation of food intake, and on the current state of development of gut hormone-based obesity therapies. PMID:20002077

7 CFR 634.1 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM General § 634.1 Purpose and scope. (a) The purpose.... Environmental Protection Agency (EPA), to set forth regulations to carry out a Rural Clean Water Program (RCWP) under section 35, Pub. L. 95-217; 91 Stat. 1579; 33 U.S.C. 1288. (b) The Rural Clean Water Program...

7 CFR 634.1 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM General § 634.1 Purpose and scope. (a) The purpose.... Environmental Protection Agency (EPA), to set forth regulations to carry out a Rural Clean Water Program (RCWP) under section 35, Pub. L. 95-217; 91 Stat. 1579; 33 U.S.C. 1288. (b) The Rural Clean Water Program...

7 CFR 634.1 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE LONG TERM CONTRACTING RURAL CLEAN WATER PROGRAM General § 634.1 Purpose and scope. (a) The purpose.... Environmental Protection Agency (EPA), to set forth regulations to carry out a Rural Clean Water Program (RCWP) under section 35, Pub. L. 95-217; 91 Stat. 1579; 33 U.S.C. 1288. (b) The Rural Clean Water Program...

26 CFR 1.460-0 - Outline of regulations under section 460.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Examples. § 1.460-2Long-term manufacturing contracts. (a) In general. (b) Unique. (1) In general. (2) Safe... complete. (1) In general. (2) Production by related parties. (d) Qualified ship contracts. (e) Examples... improvements. (iv) Mixed use costs. (3) $10,000,000 gross receipts test. (i) In general. (ii) Single employer...

26 CFR 1.460-0 - Outline of regulations under section 460.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Examples. § 1.460-2Long-term manufacturing contracts. (a) In general. (b) Unique. (1) In general. (2) Safe... complete. (1) In general. (2) Production by related parties. (d) Qualified ship contracts. (e) Examples... improvements. (iv) Mixed use costs. (3) $10,000,000 gross receipts test. (i) In general. (ii) Single employer...

26 CFR 1.460-0 - Outline of regulations under section 460.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Examples. § 1.460-2Long-term manufacturing contracts. (a) In general. (b) Unique. (1) In general. (2) Safe... complete. (1) In general. (2) Production by related parties. (d) Qualified ship contracts. (e) Examples... improvements. (iv) Mixed use costs. (3) $10,000,000 gross receipts test. (i) In general. (ii) Single employer...

26 CFR 1.460-0 - Outline of regulations under section 460.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Examples. § 1.460-2Long-term manufacturing contracts. (a) In general. (b) Unique. (1) In general. (2) Safe... complete. (1) In general. (2) Production by related parties. (d) Qualified ship contracts. (e) Examples... improvements. (iv) Mixed use costs. (3) $10,000,000 gross receipts test. (i) In general. (ii) Single employer...

Effects of Simulated Microgravity on Functions of Neutrophil-like HL-60 Cells

NASA Astrophysics Data System (ADS)

Wang, Chengzhi; Li, Ning; Zhang, Chen; Sun, Shujin; Gao, Yuxin; Long, Mian

2015-11-01

Altered gravity, especially microgravity affects cellular functions of immune cells and can result in immune dysfunction for long-term, manned spaceflight and space exploration. The underlying mechanism, however, of sensing and responding to the gravity alteration is poorly understood. Here, a rotary cell culture system (RCCS) bioreactor was used to elucidate the effects of simulated microgravity on polymorphonuclear neutrophils (PMN)-like HL-60 cells. Alteration of cell morphology, up-regulation of (nitric oxide) NO production, enhancement of interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein 1 (MCP-1) secretion, and diversity of cellular adhesion molecule expression were observed for the cells cultured in RCCS, leading to the up-regulated inflammatory immune responses and host defense. It was also indicated that such alterations in biological responses of PMNs mediated the reduced rolling velocity and decreased adhesion of PMN-like HL-60 cells on endothelial cells under shear flow. This work furthers the understandings in the effects and mechanism of microgravity on PMN functions, which are potentially helpful for optimizing the countermeasures to immune suppression in the future long-term, manned spaceflight.

Beyond regulation: A social compact' for gas and electricity

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

Stram, B.; Thorn, T.

The public utility covenant, granting franchise protection to firms in return for just and reasonable rate regulation, has come under increasing scrutiny as socially inefficient for several reasons. First, cost-based regulation fails to adequately incite cost-minimization and new product development. Second, public utility regulation has turned into a micro-management exercise where prospective strategies are laboriously scrutinized and past performance is penalized from 20-20 hind-sight. Third, traditional regulation has provided a forum for nontraditional special interest regulation that may not be in the ratepayer's interest. An alternative to the regulatory covenant is the social compact where long-term contracts among the affectedmore » parties set price and service terms. The advantages of such contracting would be to reduce the administrative costs of regulation, better incite the market's entrepreneurial discovery process, deregulate upstream production and transportation, and eliminate extraneous regulation of electric and gas distribution. The winners would be gas consumers and the most efficient industry suppliers.« less

Medium-chain triglycerides impair lipid metabolism and induce hepatic steatosis in very long-chain acyl-CoA dehydrogenase (VLCAD)-deficient mice.

PubMed

Tucci, Sara; Primassin, Sonja; Ter Veld, Frank; Spiekerkoetter, Ute

2010-09-01

A medium-chain-triglyceride (MCT)-based diet is mainstay of treatment in very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), a long-chain fatty acid beta-oxidation defect. Beneficial effects have been reported with an MCT-bolus prior to exercise. Little is known about the impact of a long-term MCT diet on hepatic lipid metabolism. Here we investigate the effects of MCT-supplementation on liver and blood lipids in the murine model of VLCADD. Wild-type (WT) and VLCAD-knock-out (KO) mice were fed (1) a long-chain triglyceride (LCT)-diet over 5weeks, (2) an MCT diet over 5 weeks and (3) an LCT diet plus MCT-bolus. Blood and liver lipid content were determined. Expression of genes regulating lipogenesis was analyzed by RT-PCR. Under the LCT diet, VLCAD-KO mice accumulated significantly higher blood cholesterol concentrations compared to WT mice. The MCT-diet induced severe hepatic steatosis, significantly higher serum free fatty acids and impaired hepatic lipid mobilization in VLCAD-KO mice. Expression at mRNA level of hepatic lipogenic genes was up-regulated. The long-term MCT diet stimulates lipogenesis and impairs hepatic lipid metabolism in VLCAD-KO mice. These results suggest a critical reconsideration of a long-term MCT-modified diet in human VLCADD. In contrast, MCT in situations of increased energy demand appears to be a safer treatment alternative.

Bursts of seizures in long-term recordings of human focal epilepsy

PubMed Central

Karoly, Philippa J.; Nurse, Ewan S.; Freestone, Dean R.; Ung, Hoameng; Cook, Mark J.; Boston, Ray

2017-01-01

Summary Objective We report on temporally clustered seizures detected from continuous long-term ambulatory human electroencephalographic data. The objective was to investigate short-term seizure clustering, which we have termed bursting, and consider implications for patient care, seizure prediction, and evaluating therapies. Methods Chronic ambulatory intracranial EEG data collected for the purpose of seizure prediction were annotated to identify seizure events. A detection algorithm was used to identify bursts of events. Burst events were compared to non-burst events to evaluate event dispersion, duration and dynamics. Results Bursts of seizures were present in six of fifteen patients, and detections were consistent over long term monitoring (> 2 years). Seizures within bursts are highly overdispersed compared to non-burst seizures. There was a complicated relationship between bursts and clinical seizures, although bursts were associated with multi-modal distributions of seizure duration, and poorer predictive outcomes. For three subjects, bursts demonstrated distinctive pre-ictal dynamics compared to clinical seizures. Significance We have previously hypothesized that there are distinct physiological pathways underlying short and long duration seizures. Here we show that burst seizures fall almost exclusively within the short population of seizure durations; however, a short duration was not sufficient to induce or imply bursting. We can therefore conclude that in addition to distinct mechanisms underlying seizure duration, there are separate factors regulating bursts of seizures. We show that bursts were a robust phenomenon in our patient cohort, which were consistent with overdispersed seizure rates, suggesting long-memory dynamics. PMID:28084639

Passion and Pacing in Endurance Performance

PubMed Central

Schiphof-Godart, Lieke; Hettinga, Florentina J.

2017-01-01

Endurance sports are booming, with sports passionates of varying skills and expertise battering city streets and back roads on their weekly or daily exercise rounds. The investments required for performing in endurance exercise are nevertheless considerable, and passion for their sport might explain the efforts endurance athletes are willing to make. Passion may be defined as a strong motivational force and as such might be related to the neurophysiological basis underlying the drive to exercise. A complex relationship between the brain and other systems is responsible for athletes' exercise behavior and thus performance in sports. We anticipate important consequences of athletes' short term choices, for example concerning risk taking actions, on long term outcomes, such as injuries, overtraining and burnout. We propose to consider athletes' type of passion, in combination with neurophysiological parameters, as an explanatory factor inunderstanding the apparent disparity in the regulation of exercise intensity during endurance sports. Previous research has demonstrated that athletes can be passionate toward their sport in either a harmonious or an obsessive way. Although both lead to considerable investments and therefore often to successful performances, obsessive passion may affect athlete well-being and performance on the long run, due to the corresponding inflexible exercise behavior. In this perspective we will thus examine the influence of passion in sport on athletes' short term and long term decision-making and exercise behavior, in particular related to the regulation of exercise intensity, and discuss the expected long term effects of both types of passion for sport. PMID:28265245

Passion and Pacing in Endurance Performance.

PubMed

Schiphof-Godart, Lieke; Hettinga, Florentina J

2017-01-01

Endurance sports are booming, with sports passionates of varying skills and expertise battering city streets and back roads on their weekly or daily exercise rounds. The investments required for performing in endurance exercise are nevertheless considerable, and passion for their sport might explain the efforts endurance athletes are willing to make. Passion may be defined as a strong motivational force and as such might be related to the neurophysiological basis underlying the drive to exercise. A complex relationship between the brain and other systems is responsible for athletes' exercise behavior and thus performance in sports. We anticipate important consequences of athletes' short term choices, for example concerning risk taking actions, on long term outcomes, such as injuries, overtraining and burnout. We propose to consider athletes' type of passion, in combination with neurophysiological parameters, as an explanatory factor inunderstanding the apparent disparity in the regulation of exercise intensity during endurance sports. Previous research has demonstrated that athletes can be passionate toward their sport in either a harmonious or an obsessive way. Although both lead to considerable investments and therefore often to successful performances, obsessive passion may affect athlete well-being and performance on the long run, due to the corresponding inflexible exercise behavior. In this perspective we will thus examine the influence of passion in sport on athletes' short term and long term decision-making and exercise behavior, in particular related to the regulation of exercise intensity, and discuss the expected long term effects of both types of passion for sport.

Signalling from the periphery to the brain that regulates energy homeostasis.

PubMed

Kim, Ki-Suk; Seeley, Randy J; Sandoval, Darleen A

2018-04-01

The CNS regulates body weight; however, we still lack a clear understanding of what drives decisions about when, how much and what to eat. A vast array of peripheral signals provides information to the CNS regarding fluctuations in energy status. The CNS then integrates this information to influence acute feeding behaviour and long-term energy homeostasis. Previous paradigms have delegated the control of long-term energy homeostasis to the hypothalamus and short-term changes in feeding behaviour to the hindbrain. However, recent studies have identified target hindbrain neurocircuitry that integrates the orchestration of individual bouts of ingestion with the long-term regulation of energy balance.

Antimicrobial Treatment Improves Mycobacterial Survival in Nonpermissive Growth Conditions

PubMed Central

Turapov, Obolbek; Waddell, Simon J.; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A.; Tudo, Griselda; Labesse, Gilles; Young, Danielle I.; Young, Michael; Andrew, Peter W.; Butcher, Philip D.; Cohen-Gonsaud, Martin

2014-01-01

Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis. PMID:24590482

How long can fisheries management delay action in response to ecosystem and climate change?

PubMed

Brown, Christopher J; Fulton, Elizabeth A; Possingham, Hugh P; Richardson, Anthony J

2012-01-01

Sustainable management of fisheries is often compromised by management delaying implementation of regulations that reduce harvest, in order to maintain higher catches in the short-term. Decreases or increases in fish population growth rate driven by environmental change, including ecosystem and climate change, affect the harvest that can be taken sustainably. If not acted on rapidly, environmental change could result in unsustainable fishing or missed opportunity for higher catches. Using simulation models of harvested fish populations influenced by environmental change, we explore how long fisheries managers can afford to wait before changing harvest regulations in response to changes in population growth. If environmental change causes population declines, delays greater than five years increase the probability of population collapse. Species with fast and highly variable population growth rates are more susceptible to collapse under delays and should be a priority for revised management where delays occur. Generally, the long-term cost of delay, in terms of lost fishing opportunity, exceeds the short-term benefits of overfishing. Lowering harvest limits and monitoring for environmental change can alleviate the impact of delays; however, these measures may be more costly than reducing delays. We recommend that management systems that allow rapid responses to population growth changes be enacted for fisheries management to adapt to ecosystem and climate change.

The Adolescent Self-Regulatory Inventory: The Development and Validation of a Questionnaire of Short-Term and Long-Term Self-Regulation

ERIC Educational Resources Information Center

Moilanen, Kristin L.

2007-01-01

This manuscript presents a study in which the factor structure and validity of the Adolescent Self-Regulatory Inventory (ASRI) were examined. The ASRI is a theoretically-based questionnaire that taps two temporal aspects of self-regulation (regulation in the short- and long-term). 169 students in the 6th, 8th, and 10th grades of a small,…

Proportional Feedback Control of Energy Intake During Obesity Pharmacotherapy.

PubMed

Hall, Kevin D; Sanghvi, Arjun; Göbel, Britta

2017-12-01

Obesity pharmacotherapies result in an exponential time course for energy intake whereby large early decreases dissipate over time. This pattern of declining drug efficacy to decrease energy intake results in a weight loss plateau within approximately 1 year. This study aimed to elucidate the physiology underlying the exponential decay of drug effects on energy intake. Placebo-subtracted energy intake time courses were examined during long-term obesity pharmacotherapy trials for 14 different drugs or drug combinations within the theoretical framework of a proportional feedback control system regulating human body weight. Assuming each obesity drug had a relatively constant effect on average energy intake and did not affect other model parameters, our model correctly predicted that long-term placebo-subtracted energy intake was linearly related to early reductions in energy intake according to a prespecified equation with no free parameters. The simple model explained about 70% of the variance between drug studies with respect to the long-term effects on energy intake, although a significant proportional bias was evident. The exponential decay over time of obesity pharmacotherapies to suppress energy intake can be interpreted as a relatively constant effect of each drug superimposed on a physiological feedback control system regulating body weight. © 2017 The Obesity Society.

What Legislators Need to Know about Long-Term Care Insurance.

ERIC Educational Resources Information Center

Landes, David

This booklet discusses the potential importance to states of long-term care insurance, describes general policy characteristics, and summarizes state actions to both regulate and promote long-term care insurance. It is intended as a resource for legislators and others involved in long-term care financing and public policy formulation. Long-term…

Long-term manure amendments reduced soil aggregate stability via redistribution of the glomalin-related soil protein in macroaggregates

PubMed Central

Xie, Hongtu; Li, Jianwei; Zhang, Bin; Wang, Lianfeng; Wang, Jingkuan; He, Hongbo; Zhang, Xudong

2015-01-01

Glomalin-related soil protein (GRSP) contributes to the formation and maintenance of soil aggregates, it is however remains unclear whether long-term intensive manure amendments alter soil aggregates stability and whether GRSP regulates these changes. Based on a three-decade long fertilization experiment in northeast China, this study examined the impact of long-term manure input on soil organic carbon (SOC), total and easily extractable GRSP (GRSPt and GRSPe) and their respective allocations in four soil aggregates (>2000 μm; 2000–250 μm; 250–53 μm; and <53 μm). The treatments include no fertilization (CK), low and high manure amendment (M1, M2), chemical nitrogen, phosphorus and potassium fertilizers (NPK), and combined manure and chemical fertilizers (NPKM1, NPKM2). Though SOC, GRSPe and GRSPt in soil and SOC in each aggregate generally increased with increasing manure input, GRSPt and GRSPe in each aggregate showed varying changes with manure input. Both GRSP in macroaggregates (2000–250 μm) were significantly higher under low manure input, a pattern consistent with changes in soil aggregate stability. Constituting 38~49% of soil mass, macroaggregates likely contributed to the nonlinear changes of aggregate stability under manure amendments. The regulatory process of GRSP allocations in soil aggregates has important implications for manure management under intensive agriculture. PMID:26423355

42 CFR 412.541 - Method of payment under the long-term care hospital prospective payment system.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as long-term care hospital... 42 Public Health 2 2011-10-01 2011-10-01 false Method of payment under the long-term care hospital... SERVICES Prospective Payment System for Long-Term Care Hospitals § 412.541 Method of payment under the long...

42 CFR 412.541 - Method of payment under the long-term care hospital prospective payment system.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as long-term care hospital... 42 Public Health 2 2014-10-01 2014-10-01 false Method of payment under the long-term care hospital... SERVICES Prospective Payment System for Long-Term Care Hospitals § 412.541 Method of payment under the long...

42 CFR 412.541 - Method of payment under the long-term care hospital prospective payment system.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as long-term care hospital... 42 Public Health 2 2013-10-01 2013-10-01 false Method of payment under the long-term care hospital... SERVICES Prospective Payment System for Long-Term Care Hospitals § 412.541 Method of payment under the long...

42 CFR 412.541 - Method of payment under the long-term care hospital prospective payment system.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as long-term care hospital... 42 Public Health 2 2010-10-01 2010-10-01 false Method of payment under the long-term care hospital... SERVICES Prospective Payment System for Long-Term Care Hospitals § 412.541 Method of payment under the long...

42 CFR 412.541 - Method of payment under the long-term care hospital prospective payment system.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Recovery of payment. Recovery of the accelerated payment is made by recoupment as long-term care hospital... 42 Public Health 2 2012-10-01 2012-10-01 false Method of payment under the long-term care hospital... SERVICES Prospective Payment System for Long-Term Care Hospitals § 412.541 Method of payment under the long...

12 CFR Supplement I to Part 213 - Official Staff Commentary to Regulation M

Code of Federal Regulations, 2010 CFR

2010-01-01

... primary use. 2. Period of time. To be a consumer lease, the initial term of the lease must be more than... lease (unless terminable without penalty at any time by the consumer) under which the consumer: i... the lease contract, so long as all disclosures are given at the same time. Alternatively, all...

12 CFR Supplement I to Part 213 - Official Staff Commentary to Regulation M

Code of Federal Regulations, 2011 CFR

2011-01-01

... primary use. 2. Period of time. To be a consumer lease, the initial term of the lease must be more than... lease (unless terminable without penalty at any time by the consumer) under which the consumer: i... the lease contract, so long as all disclosures are given at the same time. Alternatively, all...

Regulation of Oil Biosynthesis in Algae

DTIC Science & Technology

2014-10-06

renewed interest in microalgae as potential feed stock for renewable fuels including high energy density aviation fuels. Microalgae accumulate large...mechanisms of TAG accumulation relevant to other microalgae and perhaps dedicated biofuel crop plants. Knowledge and understanding of algal model systems...energy density liquid fuels. Long Term Objectives. Under permissive conditions, i.e. nutrient deprivation, many microalgae accumulate oils (TAGs

When mothering goes awry: Challenges and opportunities for utilizing evidence across rodent, nonhuman primate and human studies to better define the biological consequences of negative early caregiving☆

PubMed Central

Sánchez, Mar M.; Gonzalez, Andrea

2016-01-01

Across mammalian species, mothers shape socio-emotional development and serve as essential external regulators of infant physiology, brain development, behavior patterns, and emotional regulation. Caregiving quality, consistency and predictability shape the infant's underlying neurobiological processes. Although the requirements for “optimal” caregiving differ across species, the negative long-term consequences of the absence of needed caregiving (e.g. neglect) or the presence of harmful/aversive caregiving (e.g. physical abuse), are translatable across species. Recognizing the significant potential of cross species comparisons in terms of defining underlying mechanisms, effective translation requires consideration of the evolutionary, ecological, and fundamental biological and developmental differences between and among species. This review provides both an overview of several success stories of cross-species translations in relation to negative caregiving and a template for future studies seeking to most effectively define the underlying biological processes and advance research dedicated to mitigating the lasting negative health consequences of child maltreatment. PMID:26506032

Cultured bovine granulosa cells rapidly lose important features of their identity and functionality but partially recover under long-term culture conditions.

PubMed

Yenuganti, Vengala Rao; Vanselow, Jens

2017-05-01

Cell culture models are essential for the detailed study of molecular processes. We analyze the dynamics of changes in a culture model of bovine granulosa cells. The cells were cultured for up to 8 days and analyzed for steroid production and gene expression. According to the expression of the marker genes CDH1, CDH2 and VIM, the cells maintained their mesenchymal character throughout the time of culture. In contrast, the levels of functionally important transcripts and of estradiol and progesterone production were rapidly down-regulated but showed a substantial up-regulation from day 4. FOXL2, a marker for granulosa cell identity, was also rapidly down-regulated after plating but completely recovered towards the end of culture. In contrast, expression of the Sertoli cell marker SOX9 and the lesion/inflammation marker PTGS2 increased during the first 2 days after plating but gradually decreased later on. We conclude that only long-term culture conditions (>4 days) allow the cells to recover from plating stress and to re-acquire characteristic granulosa cell features.

Narp regulates long-term aversive effects of morphine withdrawal

PubMed Central

Reti, Irving M.; Crombag, Hans S.; Takamiya, Kogo; Sutton, Jeffrey M.; Guo, Ning; Dinenna, Megan L.; Huganir, Richard L.; Holland, Peter C.; Baraban, Jay M.

2008-01-01

Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. As Narp is an immediate early gene product that is secreted at synaptic sites and binds to AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, we found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, we evaluated whether long-term aversive effects of morphine withdrawal are altered in Narp KO mice. We found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than WT controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. PMID:18729628

Long Term Hydrological (Radiological) Site Monitoring Data

EPA Pesticide Factsheets

Quality Data Asset includes all current and historical data on the quality of water with regard to the presence of water pollutants of all kinds regulated by the Clean Water Act. Under the new Interagency Agreement with the Department of Energy (DOE), the Radiation & Indoor Environments National Laboratory (R&IE), Office of Radiation and Indoor Air (ORIA), EPA, located in Las Vegas, NV, conducts a Long-Term Hydrological Monitoring Program (LTHMP) providing laboratory sampling/analysis and Quality Assurance and Control to measure radioactivity concentrations in the water sources near the sites of former underground nuclear explosions. The results of the LTHMP provide assurance that radioactive material from the tests have not migrated into water supplies.

Formative Evaluation of MyFit: A Curriculum to Promote Self-Regulation of Physical Activity among Middle School Students

ERIC Educational Resources Information Center

Grim, Melissa; Petosa, Rick; Hortz, Brian; Hunt, Laura

2013-01-01

Background: Previous interventions to increase physical activity among middle school students have not produced long-term results. Often, students lack the self-regulation skills needed to support long-term adherence to physical activity. Purpose: The purpose of this study was to conduct a formative evaluation of a self-regulation based physical…

Transcriptional and Physiological Characterizations of Escherichia coli MG1655 that have been grown under Low Shear Stress Environment for 1000 Generations

NASA Astrophysics Data System (ADS)

Karouia, Fathi; Tirumalai, Madhan R.; Nelman-Gonzalez, Mayra A.; Sams, Clarence F.; Ott, Mark C.; Pierson, Duane L.; Fofanov, Yuriy; Willson, Richard C.; Fox, George E.

Human space travelers experience a unique environment that affects homeostasis and physio-logic adaptation. One of the important regulatory biology interactions affected by space flight is the alteration of the immune response. As such, the impairment of the immune system may lead to higher risk of bacterial and/or viral infection during human space flight missions. Mi-crobiological contaminants have been a source of concern over the years for NASA and there is evidence to suggest that microbes in space do not behave like they do on Earth. Previ-ous studies have examined the physiological response of bacteria when exposed to short-term microgravity either during spaceflight or in a Low Shear Modeled Microgravity (LSMMG) en-vironment. Exposure to these environments has been found to induce increased resistance to stresses and antibiotics, and in one case increase of virulence. As NASA increases the duration of space flight missions and is starting to envision human presence on the lunar surface and Mars, it becomes legitimate to question the long-term effects of microgravity on bacteria. The effect of long-term exposure to LSMMG on microbial gene expression and physiology in Escherichia coli (E. coli) is being examined using functional genomics, and molecular tech-niques. In previous E. coli short term studies, reproducible changes in transcription were seen but no direct responses to changes in the gravity vector were identified. Instead, absence of shear and a randomized gravity vector appeared to cause local extra-cellular environmental changes, which elicited cellular responses. In order to evaluate the long-term effects of micro-gravity on bacteria, E. coli was grown under simulated microgravity for 1000 generations and gene expression patterns and cellular physiology were analyzed in comparison with short-term exposure. The analysis revealed that the long-term response differed significantly from the short-term exposure and 357 genes were expressed significantly differently. Fimbriae encoding genes were significantly up-regulated whereas genes encoding the flagellar motor complex were down-regulated. Additionally, 81 significantly expressed genes have been implicated in and/or associated with biofilm formation. The remaining up-regulated genes seemed to be involved in a response that triggered expression of genes associated with the type II secretion complex. This complex has been involved in virulence factors and members of the multidrug efflux system which confer resistance to a multitude of antimicrobial agents and antibiotics. Biofilm formation and the aggregation of cells were evaluated by scanning electron microscopy (SEM). The analysis revealed that extracellular matrix and complex cellular networking were present among cells that were exposed to the long-term LSMMG environment. In addition the response to a variety of stresses and antibiotics were examined. Significant differences were seen between long-term exposure to LSMMG and the short-term control. Changes in expression may predispose the cells to more efficiently attach to surfaces and/or other cells and thereby confer resistance to antibiotics. Future studies will seek to determine the extent to which the long-term adaptation is influenced by genomic changes. These studies will contribute to the knowledge base needed to develop countermeasures that will decrease the risks associated with astronaut health and mission integrity that are presented by microorganisms.

Remote Memory and Cortical Synaptic Plasticity Require Neuronal CCCTC-Binding Factor (CTCF).

PubMed

Kim, Somi; Yu, Nam-Kyung; Shim, Kyu-Won; Kim, Ji-Il; Kim, Hyopil; Han, Dae Hee; Choi, Ja Eun; Lee, Seung-Woo; Choi, Dong Il; Kim, Myung Won; Lee, Dong-Sung; Lee, Kyungmin; Galjart, Niels; Lee, Yong-Seok; Lee, Jae-Hyung; Kaang, Bong-Kiun

2018-05-30

The molecular mechanism of long-term memory has been extensively studied in the context of the hippocampus-dependent recent memory examined within several days. However, months-old remote memory maintained in the cortex for long-term has not been investigated much at the molecular level yet. Various epigenetic mechanisms are known to be important for long-term memory, but how the 3D chromatin architecture and its regulator molecules contribute to neuronal plasticity and systems consolidation is still largely unknown. CCCTC-binding factor (CTCF) is an 11-zinc finger protein well known for its role as a genome architecture molecule. Male conditional knock-out mice in which CTCF is lost in excitatory neurons during adulthood showed normal recent memory in the contextual fear conditioning and spatial water maze tasks. However, they showed remarkable impairments in remote memory in both tasks. Underlying the remote memory-specific phenotypes, we observed that female CTCF conditional knock-out mice exhibit disrupted cortical LTP, but not hippocampal LTP. Similarly, we observed that CTCF deletion in inhibitory neurons caused partial impairment of remote memory. Through RNA sequencing, we observed that CTCF knockdown in cortical neuron culture caused altered expression of genes that are highly involved in cell adhesion, synaptic plasticity, and memory. These results suggest that remote memory storage in the cortex requires CTCF-mediated gene regulation in neurons, whereas recent memory formation in the hippocampus does not. SIGNIFICANCE STATEMENT CCCTC-binding factor (CTCF) is a well-known 3D genome architectural protein that regulates gene expression. Here, we use two different CTCF conditional knock-out mouse lines and reveal, for the first time, that CTCF is critically involved in the regulation of remote memory. We also show that CTCF is necessary for appropriate expression of genes, many of which we found to be involved in the learning- and memory-related processes. Our study provides behavioral and physiological evidence for the involvement of CTCF-mediated gene regulation in the remote long-term memory and elucidates our understanding of systems consolidation mechanisms. Copyright © 2018 the authors 0270-6474/18/385042-11$15.00/0.

Long-term impacts of selective logging on two Amazonian tree species with contrasting ecological and reproductive characteristics: inferences from Eco-gene model simulations.

PubMed

Vinson, C C; Kanashiro, M; Sebbenn, A M; Williams, T C R; Harris, S A; Boshier, D H

2015-08-01

The impact of logging and subsequent recovery after logging is predicted to vary depending on specific life history traits of the logged species. The Eco-gene simulation model was used to evaluate the long-term impacts of selective logging over 300 years on two contrasting Brazilian Amazon tree species, Dipteryx odorata and Jacaranda copaia. D. odorata (Leguminosae), a slow growing climax tree, occurs at very low densities, whereas J. copaia (Bignoniaceae) is a fast growing pioneer tree that occurs at high densities. Microsatellite multilocus genotypes of the pre-logging populations were used as data inputs for the Eco-gene model and post-logging genetic data was used to verify the output from the simulations. Overall, under current Brazilian forest management regulations, there were neither short nor long-term impacts on J. copaia. By contrast, D. odorata cannot be sustainably logged under current regulations, a sustainable scenario was achieved by increasing the minimum cutting diameter at breast height from 50 to 100 cm over 30-year logging cycles. Genetic parameters were only slightly affected by selective logging, with reductions in the numbers of alleles and single genotypes. In the short term, the loss of alleles seen in J. copaia simulations was the same as in real data, whereas fewer alleles were lost in D. odorata simulations than in the field. The different impacts and periods of recovery for each species support the idea that ecological and genetic information are essential at species, ecological guild or reproductive group levels to help derive sustainable management scenarios for tropical forests.

Long-term impacts of selective logging on two Amazonian tree species with contrasting ecological and reproductive characteristics: inferences from Eco-gene model simulations

PubMed Central

Vinson, C C; Kanashiro, M; Sebbenn, A M; Williams, T CR; Harris, S A; Boshier, D H

2015-01-01

The impact of logging and subsequent recovery after logging is predicted to vary depending on specific life history traits of the logged species. The Eco-gene simulation model was used to evaluate the long-term impacts of selective logging over 300 years on two contrasting Brazilian Amazon tree species, Dipteryx odorata and Jacaranda copaia. D. odorata (Leguminosae), a slow growing climax tree, occurs at very low densities, whereas J. copaia (Bignoniaceae) is a fast growing pioneer tree that occurs at high densities. Microsatellite multilocus genotypes of the pre-logging populations were used as data inputs for the Eco-gene model and post-logging genetic data was used to verify the output from the simulations. Overall, under current Brazilian forest management regulations, there were neither short nor long-term impacts on J. copaia. By contrast, D. odorata cannot be sustainably logged under current regulations, a sustainable scenario was achieved by increasing the minimum cutting diameter at breast height from 50 to 100 cm over 30-year logging cycles. Genetic parameters were only slightly affected by selective logging, with reductions in the numbers of alleles and single genotypes. In the short term, the loss of alleles seen in J. copaia simulations was the same as in real data, whereas fewer alleles were lost in D. odorata simulations than in the field. The different impacts and periods of recovery for each species support the idea that ecological and genetic information are essential at species, ecological guild or reproductive group levels to help derive sustainable management scenarios for tropical forests. PMID:24424164

miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression

NASA Astrophysics Data System (ADS)

Hu, Zhonghua; Yu, Danni; Gu, Qin-Hua; Yang, Yanqin; Tu, Kang; Zhu, Jun; Li, Zheng

2014-02-01

Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.

THE EFFECT OF LONG TERM WASTEWATER CROSS-CONNECTION'S EFFECT ON THE BIOFILM OF A SIMULATED WATER DISTRIBUTION SYSTEM

EPA Science Inventory

Under the current regulations (CFR 503), Class B biosolids may be land applied with certain site restrictions. One method for achieving Class B status is to raise the pH of the sludge to >12 for a minimum of 2 hours with an alkaline material (normally lime). Alternately, a Clas...

Cerebellar learning mechanisms

PubMed Central

Freeman, John H.

2014-01-01

The mechanisms underlying cerebellar learning are reviewed with an emphasis on old arguments and new perspectives on eyeblink conditioning. Eyeblink conditioning has been used for decades a model system for elucidating cerebellar learning mechanisms. The standard model of the mechanisms underlying eyeblink conditioning is that there two synaptic plasticity processes within the cerebellum that are necessary for acquisition of the conditioned response: 1) long-term depression (LTD) at parallel fiber-Purkinje cell synapses and 2) long-term potentiation (LTP) at mossy fiber-interpositus nucleus synapses. Additional Purkinje cell plasticity mechanisms may also contribute to eyeblink conditioning including LTP, excitability, and entrainment of deep nucleus activity. Recent analyses of the sensory input pathways necessary for eyeblink conditioning indicate that the cerebellum regulates its inputs to facilitate learning and maintain plasticity. Cerebellar learning during eyeblink conditioning is therefore a dynamic interactive process which maximizes responding to significant stimuli and suppresses responding to irrelevant or redundant stimuli. PMID:25289586

Ethylene-dependent regulation of an α-L-arabinofuranosidase is associated to firmness loss in 'Gala' apples under long term cold storage.

PubMed

Storch, Tatiane Timm; Finatto, Taciane; Pegoraro, Camila; Dal Cero, Joceani; Laurens, François; Rombaldi, Cesar Valmor; Quecini, Vera; Girardi, César Luís

2015-09-01

Fruit texture changes impair the quality of apples submitted to long term storage, especially under cold. The changes are due to cell wall modifications during ripening and senescence and are associated to ethylene. We have investigated the activity of α-l-arabinofuranosidase, a glycosyl hydrolase acting on the side chains of pectin in the cell wall and middle lamella. The transcription of arabinofuranosidase coding sequences 1 and 3 was investigated in plant organs and in response to ethylene, employing hormone application and 1-methylcyclopropene. The transcription of arabinofuranosidase genes is not restricted to fruits, although upregulated by ripening and ethylene. Transcripts of the genes were detected under cold storage up to 180 days. Similarly, arabinofuranosidase activity increased with rising levels of ethylene and under cold storage. Levels of arabinofuranosidase3 transcripts were higher than those of arabinofuranosidase1, suggesting that the first is an important contributor to enzyme activity and texture changes during cold storage. Copyright © 2015 Elsevier Ltd. All rights reserved.

HOP family plays a major role in long-term acquired thermotolerance in Arabidopsis.

PubMed

Fernández-Bautista, Nuria; Fernández-Calvino, Lourdes; Muñoz, Alfonso; Toribio, René; Mock, Hans P; Castellano, M Mar

2018-05-08

HSP70-HSP90 organizing protein (HOP) is a family of cytosolic cochaperones whose molecular role in thermotolerance is quite unknown in eukaryotes and unexplored in plants. In this article, we describe that the three members of the AtHOP family display a different induction pattern under heat, being HOP3 highly regulated during the challenge and the attenuation period. Despite HOP3 is the most heat-regulated member, the analysis of the hop1 hop2 hop3 triple mutant demonstrates that the three HOP proteins act redundantly to promote long-term acquired thermotolerance in Arabidopsis. HOPs interact strongly with HSP90 and part of the bulk of HOPs shuttles from the cytoplasm to the nuclei and to cytoplasmic foci during the challenge. RNAseq analyses demonstrate that, although the expression of the Hsf targets is not generally affected, the transcriptional response to heat is drastically altered during the acclimation period in the hop1 hop2 hop3 triple mutant. This mutant also displays an unusual high accumulation of insoluble and ubiquitinated proteins under heat, which highlights the additional role of HOP in protein quality control. These data reveal that HOP family is involved in different aspects of the response to heat, affecting the plant capacity to acclimate to high temperatures for long periods. © 2018 John Wiley & Sons Ltd.

Mood dysregulation and stabilization: perspectives from emotional cognitive neuroscience.

PubMed

Yamawaki, Shigeto; Okada, Go; Okamoto, Yasumasa; Liberzon, Israel

2012-06-01

Mood is conceptualized as a long-lasting emotional state, which can have profound implications for mental and physical health. The development of neuroimaging methods has enabled significant advances towards elucidating the mechanisms underlying regulation of mood and emotion; however, our understanding of mood and emotion dysregulation in stress-related psychiatric disorders is still largely lacking. From the cognitive-affective neuroscience perspective, achieving deeper, more mechanistic understanding of mood disorders necessitates detailed understanding of specific components of neural systems involved in mood dysregulation and stabilization. In this review, we provide an overview of neural systems implicated in the development of a long-term negative mood state, as well as those related to emotion and emotion regulation, and discuss their proposed involvement in mood and anxiety disorders.

76 FR 16856 - Proposed Collection; Comment Request for Regulation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

... Reduction Act of 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the IRS is soliciting comments concerning existing final regulations, REG-208156-91 (TD 8929), Accounting for Long-Term Contracts... the Internet at [email protected] . SUPPLEMENTARY INFORMATION: Title: Accounting for Long-Term...

Sustainability and Long Term-Tenure: Lion Trophy Hunting in Tanzania

PubMed Central

Brink, Henry; Skinner, Kirsten; Leader-Williams, Nigel

2016-01-01

It is argued that trophy hunting of large, charismatic mammal species can have considerable conservation benefits but only if undertaken sustainably. Social-ecological theory suggests such sustainability only results from developing governance systems that balance financial and biological requirements. Here we use lion (Panthera leo) trophy hunting data from Tanzania to investigate how resource ownership patterns influence hunting revenue and offtake levels. Tanzania contains up to half of the global population of free-ranging lions and is also the main location for lion trophy hunting in Africa. However, there are concerns that current hunting levels are unsustainable. The lion hunting industry in Tanzania is run by the private sector, although the government leases each hunting block to companies, enforces hunting regulation, and allocates them a species-specific annual quota per block. The length of these leases varies and theories surrounding property rights and tenure suggest hunting levels would be less sustainable in blocks experiencing a high turnover of short-term leases. We explored this issue using lion data collected from 1996 to 2008 in the Selous Game Reserve (SGR), the most important trophy hunting destination in Tanzania. We found that blocks in SGR with the highest lion hunting offtake were also those that experienced the steepest declines in trophy offtake. In addition, we found this high hunting offtake and the resultant offtake decline tended to be in blocks under short-term tenure. In contrast, lion hunting levels in blocks under long-term tenure matched more closely the recommended sustainable offtake of 0.92 lions per 1000 km2. However, annual financial returns were higher from blocks under short-term tenure, providing $133 per km2 of government revenue as compared to $62 per km2 from long-term tenure blocks. Our results provide evidence for the importance of property rights in conservation, and support calls for an overhaul of the system in Tanzania by developing competitive market-based approaches for block allocation based on long-term tenure of ten years. PMID:27648566

Sustainability and Long Term-Tenure: Lion Trophy Hunting in Tanzania.

PubMed

Brink, Henry; Smith, Robert J; Skinner, Kirsten; Leader-Williams, Nigel

2016-01-01

It is argued that trophy hunting of large, charismatic mammal species can have considerable conservation benefits but only if undertaken sustainably. Social-ecological theory suggests such sustainability only results from developing governance systems that balance financial and biological requirements. Here we use lion (Panthera leo) trophy hunting data from Tanzania to investigate how resource ownership patterns influence hunting revenue and offtake levels. Tanzania contains up to half of the global population of free-ranging lions and is also the main location for lion trophy hunting in Africa. However, there are concerns that current hunting levels are unsustainable. The lion hunting industry in Tanzania is run by the private sector, although the government leases each hunting block to companies, enforces hunting regulation, and allocates them a species-specific annual quota per block. The length of these leases varies and theories surrounding property rights and tenure suggest hunting levels would be less sustainable in blocks experiencing a high turnover of short-term leases. We explored this issue using lion data collected from 1996 to 2008 in the Selous Game Reserve (SGR), the most important trophy hunting destination in Tanzania. We found that blocks in SGR with the highest lion hunting offtake were also those that experienced the steepest declines in trophy offtake. In addition, we found this high hunting offtake and the resultant offtake decline tended to be in blocks under short-term tenure. In contrast, lion hunting levels in blocks under long-term tenure matched more closely the recommended sustainable offtake of 0.92 lions per 1000 km2. However, annual financial returns were higher from blocks under short-term tenure, providing $133 per km2 of government revenue as compared to $62 per km2 from long-term tenure blocks. Our results provide evidence for the importance of property rights in conservation, and support calls for an overhaul of the system in Tanzania by developing competitive market-based approaches for block allocation based on long-term tenure of ten years.

Sexual dimorphism of lipid metabolism in very long-chain acyl-CoA dehydrogenase deficient (VLCAD-/-) mice in response to medium-chain triglycerides (MCT).

PubMed

Tucci, Sara; Flögel, Ulrich; Spiekerkoetter, Ute

2015-07-01

Medium-chain triglycerides (MCT) are widely applied in the treatment of long-chain fatty acid oxidation disorders. Previously it was shown that long-term MCT supplementation strongly affects lipid metabolism in mice. We here investigate sex-specific effects in mice with very-long-chain-acyl-CoA dehydrogenase (VLCAD) deficiency in response to a long-term MCT modified diet. We quantified blood lipids, acylcarnitines, glucose, insulin and free fatty acids, as well as tissue triglycerides in the liver and skeletal muscle under a control and an MCT diet over 1 year. In addition, visceral and hepatic fat content and muscular intramyocellular lipids (IMCL) were assessed by in vivo(1)H magnetic resonance spectroscopy (MRS) techniques. The long-term application of an MCT diet induced a marked alteration of glucose homeostasis. However, only VLCAD-/- female mice developed a severe metabolic syndrome characterized by marked insulin resistance, dyslipidemia, severe hepatic and visceral steatosis, whereas VLCAD-/- males seemed to be protected and only presented with milder insulin resistance. Moreover, the highly saturated MCT diet is associated with a decreased hepatic stearoyl-CoA desaturase 1 (SCD1) activity in females aggravating the harmful effects of a saturated MCT diet. Long-term MCT supplementation deeply affects lipid metabolism in a sexual dimorphic manner resulting in a severe metabolic syndrome only in female mice. These findings are striking since the first signs of insulin resistance already occur in female VLCAD-/- mice during their reproductive period. How these metabolic adaptations are finally regulated needs to be determined. More important, the relevance of these findings for humans under these dietary modifications needs to be investigated. Copyright © 2015 Elsevier B.V. All rights reserved.

Expression Patterns of Three Genes Under Short and Long Term Cold Exposure in Thitarodes pui (Lepidoptera: Hepialidae), A Host of Ophiocordyceps sinensis.

PubMed

Min, Q; Cheng, S Y; Xi, J F; Ma, J; Xin, T R; Xia, B; Zou, Z W

　　BACKGROUND: Thitarodes larvae are the host of the caterpillar fungus Ophiocordyceps sinensis. Low temperature is the main environmental limitation for larvae growth. To better understand the cold adaption process in T. pui larvae, the expression patterns of trehalose-6-phosphate synthase (TpTPS), heat shock protein 70 (TpHSP70), and heat shock protein 90 (TpHSP90) were investigated upon short and long-term exposure to 0°C. The 6th instar T. pui larvae were collected in July 2013. TpTPS was firstly sequenced and expression patterns of TpTPS, TpHSP70 and TpHSP90 were investigated using quantitative PCR. Full-length cDNA of TpTPS was 3,012 bp, with an open reading frame of 2,472 bp and an encoding protein of 823 amino acids. TpTPS up-regulation was induced by cold exposure. TpHSP70 expression is altered by cold exposure, but remained low. TpHSP90 expression was obviously up regulated in long-term cold stimulation. All three genes (TpTPS, TpHSP70 and TpHSP90) have likely contributed to cold tolerance in T. pui larvae, TpTPS and TpHSP90 potentially being more important.

EVIDENCE FOR REGULATION OF TYROSINE HYDROXLASE mRNA TRANSLATION BY STRESS IN RAT ADRENAL MEDULLA

PubMed Central

Xu, Lu; Chen, Xiqun; Sun, Baoyong; Sterling, Carol; Tank, A. William

2009-01-01

Long-term stress leads to induction of tyrosine hydroxylase (TH) protein and enzymatic activity in the adrenal medulla. This adaptive response is necessary to maintain the catecholamine biosynthetic capacity of adrenal chromaffin cells during periods of sustained catecholamine secretion. In this report we demonstrate that when rats are subjected to short-term stress, TH mRNA is induced for at least 24 hr, but TH protein and TH activity (assayed under Vmax conditions) are not increased. In contrast, adrenal TH mRNA, TH protein and TH activity are induced in rats subjected to long-term stress. Using sucrose gradient fractionation, we show that the lack of induction of TH protein after one type of short-term stressor, a single 2 hr immobilization stress is associated with a decrease in the percentage of TH mRNA molecules associated with polysomes. In contrast, after repeated immobilizations the polysome profile of TH mRNA is identical to that observed in control animals, even though TH mRNA is induced 2–3 fold. These results are consistent with the hypothesis that even though TH mRNA is induced by short-term stressors, mechanisms that control TH mRNA translation must also be appropriately regulated for TH protein to be induced. PMID:17543899

Differential transcriptome profiling of chilling stress response between shoots and rhizomes of Oryza longistaminata using RNA sequencing

PubMed Central

Wang, Yinxiao; Wang, Wensheng; Zhao, Xiuqin; Zhang, Shilai; Zhang, Jing; Hu, Fengyi; Li, Zhikang

2017-01-01

Rice (Oryza sativa) is very sensitive to chilling stress at seedling and reproductive stages, whereas wild rice, O. longistaminata, tolerates non-freezing cold temperatures and has overwintering ability. Elucidating the molecular mechanisms of chilling tolerance (CT) in O. longistaminata should thus provide a basis for rice CT improvement through molecular breeding. In this study, high-throughput RNA sequencing was performed to profile global transcriptome alterations and crucial genes involved in response to long-term low temperature in O. longistaminata shoots and rhizomes subjected to 7 days of chilling stress. A total of 605 and 403 genes were respectively identified as up- and down-regulated in O. longistaminata under 7 days of chilling stress, with 354 and 371 differentially expressed genes (DEGs) found exclusively in shoots and rhizomes, respectively. GO enrichment and KEGG pathway analyses revealed that multiple transcriptional regulatory pathways were enriched in commonly induced genes in both tissues; in contrast, only the photosynthesis pathway was prevalent in genes uniquely induced in shoots, whereas several key metabolic pathways and the programmed cell death process were enriched in genes induced only in rhizomes. Further analysis of these tissue-specific DEGs showed that the CBF/DREB1 regulon and other transcription factors (TFs), including AP2/EREBPs, MYBs, and WRKYs, were synergistically involved in transcriptional regulation of chilling stress response in shoots. Different sets of TFs, such as OsERF922, OsNAC9, OsWRKY25, and WRKY74, and eight genes encoding antioxidant enzymes were exclusively activated in rhizomes under long-term low-temperature treatment. Furthermore, several cis-regulatory elements, including the ICE1-binding site, the GATA element for phytochrome regulation, and the W-box for WRKY binding, were highly abundant in both tissues, confirming the involvement of multiple regulatory genes and complex networks in the transcriptional regulation of CT in O. longistaminata. Finally, most chilling-induced genes with alternative splicing exclusive to shoots were associated with photosynthesis and regulation of gene expression, while those enriched in rhizomes were primarily related to stress signal transduction; this indicates that tissue-specific transcriptional and post-transcriptional regulation mechanisms synergistically contribute to O. longistaminata long-term CT. Our findings provide an overview of the complex regulatory networks of CT in O. longistaminata. PMID:29190752

Differential transcriptome profiling of chilling stress response between shoots and rhizomes of Oryza longistaminata using RNA sequencing.

PubMed

Zhang, Ting; Huang, Liyu; Wang, Yinxiao; Wang, Wensheng; Zhao, Xiuqin; Zhang, Shilai; Zhang, Jing; Hu, Fengyi; Fu, Binying; Li, Zhikang

2017-01-01

Rice (Oryza sativa) is very sensitive to chilling stress at seedling and reproductive stages, whereas wild rice, O. longistaminata, tolerates non-freezing cold temperatures and has overwintering ability. Elucidating the molecular mechanisms of chilling tolerance (CT) in O. longistaminata should thus provide a basis for rice CT improvement through molecular breeding. In this study, high-throughput RNA sequencing was performed to profile global transcriptome alterations and crucial genes involved in response to long-term low temperature in O. longistaminata shoots and rhizomes subjected to 7 days of chilling stress. A total of 605 and 403 genes were respectively identified as up- and down-regulated in O. longistaminata under 7 days of chilling stress, with 354 and 371 differentially expressed genes (DEGs) found exclusively in shoots and rhizomes, respectively. GO enrichment and KEGG pathway analyses revealed that multiple transcriptional regulatory pathways were enriched in commonly induced genes in both tissues; in contrast, only the photosynthesis pathway was prevalent in genes uniquely induced in shoots, whereas several key metabolic pathways and the programmed cell death process were enriched in genes induced only in rhizomes. Further analysis of these tissue-specific DEGs showed that the CBF/DREB1 regulon and other transcription factors (TFs), including AP2/EREBPs, MYBs, and WRKYs, were synergistically involved in transcriptional regulation of chilling stress response in shoots. Different sets of TFs, such as OsERF922, OsNAC9, OsWRKY25, and WRKY74, and eight genes encoding antioxidant enzymes were exclusively activated in rhizomes under long-term low-temperature treatment. Furthermore, several cis-regulatory elements, including the ICE1-binding site, the GATA element for phytochrome regulation, and the W-box for WRKY binding, were highly abundant in both tissues, confirming the involvement of multiple regulatory genes and complex networks in the transcriptional regulation of CT in O. longistaminata. Finally, most chilling-induced genes with alternative splicing exclusive to shoots were associated with photosynthesis and regulation of gene expression, while those enriched in rhizomes were primarily related to stress signal transduction; this indicates that tissue-specific transcriptional and post-transcriptional regulation mechanisms synergistically contribute to O. longistaminata long-term CT. Our findings provide an overview of the complex regulatory networks of CT in O. longistaminata.

Does stress remove the HDAC brakes for the formation and persistence of long-term memory?

PubMed

White, André O; Wood, Marcelo A

2014-07-01

It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

Does stress remove the HDAC brakes for the formation and persistence of long-term memory?

PubMed Central

White, André O.; Wood, Marcelo A.

2013-01-01

It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms. PMID:24149059

European Long-Term Care Programs: Lessons for Community Living Assistance Services and Supports?

PubMed Central

Nadash, Pamela; Doty, Pamela; Mahoney, Kevin J; von Schwanenflugel, Matthias

2012-01-01

Objective To uncover lessons from abroad for Community Living Assistance Services and Supports (CLASS), a federally run voluntary public long-term care (LTC) insurance program created under the Accountable Care Act of 2010. Data Sources Program administrators and policy researchers from Austria, England, France, Germany, and the Netherlands. Study Design Qualitative methods focused on key parameters of cash for care: how programs set benefit levels; project expenditures; control administrative costs; regulate the use of benefits; and protect workers. Data Collection/Extraction Methods Structured discussions were conducted during an international conference of LTC experts, followed by personal meetings and individual correspondence. Principal Findings Germany's self-financing mandate and tight targeting of benefits have resulted in a solvent program with low premiums. Black markets for care are likely in the absence of regulation; France addresses this via a unique system ensuing legal payment of workers. Conclusions Programs in the five countries studied have lessons, both positive and negative, relevant to CLASS design. PMID:22091672

Maintaining the pluripotency of mouse embryonic stem cells on gold nanoparticle layers with nanoscale but not microscale surface roughness

NASA Astrophysics Data System (ADS)

Lyu, Zhonglin; Wang, Hongwei; Wang, Yanyun; Ding, Kaiguo; Liu, Huan; Yuan, Lin; Shi, Xiujuan; Wang, Mengmeng; Wang, Yanwei; Chen, Hong

2014-05-01

Efficient control of the self-renewal and pluripotency maintenance of embryonic stem cell (ESC) is a prerequisite for translating stem cell technologies to clinical applications. Surface topography is one of the most important factors that regulates cell behaviors. In the present study, micro/nano topographical structures composed of a gold nanoparticle layer (GNPL) with nano-, sub-micro-, and microscale surface roughnesses were used to study the roles of these structures in regulating the behaviors of mouse ESCs (mESCs) under feeder-free conditions. The distinctive results from Oct-4 immunofluorescence staining and quantitative real-time polymerase chain reaction (qPCR) demonstrate that nanoscale and low sub-microscale surface roughnesses (Rq less than 392 nm) are conducive to the long-term maintenance of mESC pluripotency, while high sub-microscale and microscale surface roughnesses (Rq greater than 573 nm) result in a significant loss of mESC pluripotency and a faster undirectional differentiation, particularly in long-term culture. Moreover, the likely signalling cascades engaged in the topological sensing of mESCs were investigated and their role in affecting the maintenance of the long-term cell pluripotency was discussed by analyzing the expression of proteins related to E-cadherin mediated cell-cell adhesions and integrin-mediated focal adhesions (FAs). Additionally, the conclusions from MTT, cell morphology staining and alkaline phosphatase (ALP) activity assays show that the surface roughness can provide a potent regulatory signal for various mESC behaviors, including cell attachment, proliferation and osteoinduction.Efficient control of the self-renewal and pluripotency maintenance of embryonic stem cell (ESC) is a prerequisite for translating stem cell technologies to clinical applications. Surface topography is one of the most important factors that regulates cell behaviors. In the present study, micro/nano topographical structures composed of a gold nanoparticle layer (GNPL) with nano-, sub-micro-, and microscale surface roughnesses were used to study the roles of these structures in regulating the behaviors of mouse ESCs (mESCs) under feeder-free conditions. The distinctive results from Oct-4 immunofluorescence staining and quantitative real-time polymerase chain reaction (qPCR) demonstrate that nanoscale and low sub-microscale surface roughnesses (Rq less than 392 nm) are conducive to the long-term maintenance of mESC pluripotency, while high sub-microscale and microscale surface roughnesses (Rq greater than 573 nm) result in a significant loss of mESC pluripotency and a faster undirectional differentiation, particularly in long-term culture. Moreover, the likely signalling cascades engaged in the topological sensing of mESCs were investigated and their role in affecting the maintenance of the long-term cell pluripotency was discussed by analyzing the expression of proteins related to E-cadherin mediated cell-cell adhesions and integrin-mediated focal adhesions (FAs). Additionally, the conclusions from MTT, cell morphology staining and alkaline phosphatase (ALP) activity assays show that the surface roughness can provide a potent regulatory signal for various mESC behaviors, including cell attachment, proliferation and osteoinduction. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01540a

Comparison of Models of Stress Relaxation in Failure Analysis for Connectors under Long-term Storage

NASA Astrophysics Data System (ADS)

Zhou, Yilin; Wan, Mengru

2018-03-01

Reliability requirements of the system equipment under long-term storage are put forward especially for the military products, so that the connectors in the equipment also need long-term storage life correspondingly. In this paper, the effects of stress relaxation of the elastic components on electrical contact of the connectors in long-term storage process were studied from the failure mechanism and degradation models. A wire spring connector was taken as an example to discuss the life prediction method for electrical contacts of the connectors based on stress relaxation degradation under long -term storage.

Serotonin- and Training-Induced Dynamic Regulation of CREB2 in "Aplysia"

ERIC Educational Resources Information Center

Liu, Rong-Yu; Shah, Shreyansh; Cleary, Leonard J.; Byrne, John H.

2011-01-01

Long-term memory and plasticity, including long-term synaptic facilitation (LTF) of the "Aplysia" sensorimotor synapse, depend on the activation of transcription factors that regulate genes necessary for synaptic plasticity. In the present study we found that treatment with 5-HT and behavioral training produce biphasic changes in the expression of…

Decrease in calcitonin and parathyroid hormone mRNA levels and hormone secretion under long-term hypervitaminosis D3 in rats.

PubMed

Fernández-Santos, J M; Utrilla, J C; Conde, E; Hevia, A; Loda, M; Martín-Lacave, I

2001-04-01

In calcium homeostasis, vitamin D3 is a potent serum calcium-raising agent which in vivo regulates both calcitonin (CT) and parathyroid hormone (PTH) gene expression. Serum calcium is the major secretagogue for CT, a hormone product whose biosynthesis is the main biological activity of thyroid C-cells. Taking advantage of this regulatory mechanism, long-term vitamin D3-induced hypercalcemia has been extensively used as a model to produce hyperactivation, hyperplasia and even proliferative lesions of C-cells, supposedly to reduce the sustained high calcium serum concentrations. We have recently demonstrated that CT serum levels did not rise after long-term hypervitaminosis D3. Moreover, C-cells did not have a proliferative response, rather a decrease in CT-producing C-cell number was observed. In order to confirm the inhibitory effect of vitamin D3 on C-cells, Wistar rats were administered vitamin D3 chronically (25,000 IU/d) with or without calcium chloride (CaCl2). Under these long-term vitamin D3-hypercalcemic conditions, calcium, active metabolites of vitamin D3, CT and PTH serum concentrations were determined by RIA; CT and PTH mRNA levels were analysed by Northern blot and in situ hybridization; and, finally, the ultrastructure of calciotrophic hormone-producing cells was analysed by electron microscopy. Our results show, that, in rats, long term administration of vitamin D3 results in a decrease in hormone biosynthetic activities of both PTH and CT-producing cells, albeit at different magnitudes. Based upon these results, we conclude that hypervitaminosis D3-based methods do not stimulate C-cell activity and can not be used to induce proliferative lesions of calcitonin-producing cells.

Improved short-term drought response of transgenic rice over-expressing maize C4 phosphoenolpyruvate carboxylase via calcium signal cascade.

PubMed

Liu, Xiaolong; Li, Xia; Dai, Chuanchao; Zhou, Jiayu; Yan, Ting; Zhang, Jinfei

2017-11-01

To understand the link between long-term drought tolerance and short-term drought responses in plants, transgenic rice (Oryza sativa L.) plants over-expressing the maize C 4- pepc gene encoding phosphoenolpyruvate carboxylase (PC) and wild-type (WT) rice plants were subjected to PEG 6000 treatments to simulate drought stress. Compared with WT, PC had the higher survival rate and net photosynthetic rate after 16days of drought treatment, and had higher relative water content in leaves after 2h of drought treatment as well, conferring drought tolerance. WT accumulated higher amounts of malondialdehyde, superoxide radicals, and H 2 O 2 than PC under the 2-h PEG 6000 treatment, indicating greater damages in WT. Results from pretreatments with a Ca 2+ chelator and/or antagonist showed that the regulation of the early drought response in PC was Ca 2+ -dependent. The NO and H 2 O 2 levels in PC lines were also up-regulated via Ca 2+ signals, indicating that Ca 2+ in PC lines also reacted upstream of NO and H 2 O 2 . 2-h drought treatment increased the transcripts of CPK9 and CPK4 in PC via positive up-regulation of Ca 2+ . The transcripts of NAC6 [NACs (NAM, ATAF1, ATAF2, and CUC2)] and bZIP60 (basic leucine zipper, bZIP) were up-regulated, but those of DREB2B (dehydration-responsive element-binding protein, DREB) were down-regulated, both via Ca 2+ signals in PC. PEPC activity, expressions of C 4 -pepc, and the antioxidant enzyme activities in PC lines were up-regulated via Ca 2+ . These results indicated that Ca 2+ signals in PC lines can up-regulate the NAC6 and bZIP60 and the downstream targets for early drought responses, conferring drought tolerance for the long term. Copyright © 2017 Elsevier GmbH. All rights reserved.

Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase in hippocampal circuitry is required for consolidation and reconsolidation of recognition memory.

PubMed

Kelly, Aine; Laroche, Serge; Davis, Sabrina

2003-06-15

Consolidation and reconsolidation of long-term memory have been shown to be dependent on the synthesis of new proteins, but the specific molecular mechanisms underlying these events remain to be elucidated. The mitogen-activated protein kinase (MAPK) pathway can trigger genomic responses in neurons, leading to changes in protein synthesis, and several studies have identified its pivotal role in synaptic plasticity and long-term memory formation. In this study, we analyze the involvement of this pathway in the consolidation and reconsolidation of long-term recognition memory, using an object recognition task. We show that inhibition of the MAPK pathway by intracerebroventricular injection of the MEK [MAPK/extracellular signal-regulated kinase (ERK)] inhibitor UO126 blocks consolidation of object recognition memory but does not affect short-term memory. Brain regions of the entorhinal cortex-hippocampal circuitry were analyzed for ERK activation, and it was shown that consolidation of recognition memory was associated with increased phosphorylation of ERK in the dentate gyrus and entorhinal cortex, although total expression of ERK was unchanged. We also report that inhibition of the MAPK pathway blocks reconsolidation of recognition memory, and this was shown to be dependent on reactivation of the memory trace by brief reexposure to the objects. In addition, reconsolidation of memory was associated with an increase in the phosphorylation of ERK in entorhinal cortex and CA1. In summary, our data show that the MAPK kinase pathway is required for both consolidation and reconsolidation of long-term recognition memory, and that this is associated with hyperphosphorylation of ERK in different subregions of the entorhinal cortex-hippocampal circuitry.

The Histone Deacetylase HDAC4 Regulates Long-Term Memory in Drosophila

PubMed Central

Fitzsimons, Helen L.; Schwartz, Silvia; Given, Fiona M.; Scott, Maxwell J.

2013-01-01

A growing body of research indicates that pharmacological inhibition of histone deacetylases (HDACs) correlates with enhancement of long-term memory and current research is concentrated on determining the roles that individual HDACs play in cognitive function. Here, we investigate the role of HDAC4 in long-term memory formation in Drosophila. We show that overexpression of HDAC4 in the adult mushroom body, an important structure for memory formation, resulted in a specific impairment in long-term courtship memory, but had no affect on short-term memory. Overexpression of an HDAC4 catalytic mutant also abolished LTM, suggesting a mode of action independent of catalytic activity. We found that overexpression of HDAC4 resulted in a redistribution of the transcription factor MEF2 from a relatively uniform distribution through the nucleus into punctate nuclear bodies, where it colocalized with HDAC4. As MEF2 has also been implicated in regulation of long-term memory, these data suggest that the repressive effects of HDAC4 on long-term memory may be through interaction with MEF2. In the same genetic background, we also found that RNAi-mediated knockdown of HDAC4 impairs long-term memory, therefore we demonstrate that HDAC4 is not only a repressor of long-term memory, but also modulates normal memory formation. PMID:24349558

Stochasticity and bifurcations in a reduced model with interlinked positive and negative feedback loops of CREB1 and CREB2 stimulated by 5-HT.

PubMed

Hao, Lijie; Yang, Zhuoqin; Bi, Yuanhong

2016-04-01

The cyclic AMP (cAMP)-response element-binding protein (CREB) family of transcription factors is crucial in regulating gene expression required for long-term memory (LTM) formation. Upon exposure of sensory neurons to the neurotransmitter serotonin (5-HT), CREB1 is activated via activation of the protein kinase A (PKA) intracellular signaling pathways, and CREB2 as a transcriptional repressor is relieved possibly via phosphorylation of CREB2 by mitogen-activated protein kinase (MAPK). Song et al. [18] proposed a minimal model with only interlinked positive and negative feedback loops of transcriptional regulation by the activator CREB1 and the repressor CREB2. Without considering feedbacks between the CREB proteins, Pettigrew et al. [8] developed a computational model characterizing complex dynamics of biochemical pathways downstream of 5-HT receptors. In this work, to describe more simply the biochemical pathways and gene regulation underlying 5-HT-induced LTM, we add the important extracellular sensitizing stimulus 5-HT as well as the product Ap-uch into the Song's minimal model. We also strive to examine dynamical properties of the gene regulatory network under the changing concentration of the stimulus, [5-HT], cooperating with the varying positive feedback strength in inducing a high state of CREB1 for the establishment of long-term memory. Different dynamics including monostability, bistability and multistability due to coexistence of stable steady states and oscillations is investigated by means of codimension-2 bifurcation analysis. At the different positive feedback strengths, comparative analysis of deterministic and stochastic dynamics reveals that codimension-1 bifurcation with respect to [5-HT] as the parameter can predict diverse stochastic behaviors resulted from the finite number of molecules, and the number of CREB1 molecules more and more preferentially resides near the high steady state with increasing [5-HT], which contributes to long-term memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.

Flowering in space

NASA Astrophysics Data System (ADS)

Zheng, Hui Qiong

2018-05-01

The reproductive success of plants is often dependent on their flowering time being adapted to the terrestrial environment, in which gravity remain constant. Whether plants can follow the same rule to determine their flowering time under microgravity in space is unknown. Although numerous attempts have been made to grow a plant through a complete life cycle in space, apparently no published information exists concerning the flowering control of plants under microgravity in space. Here, we focused on two aspects. Firstly the environmental and intrinsic factors under microgravity related to flowering control. Secondly, the plant-derived regulators are involved in flowering control under microgravity condition. The potential environmental and intrinsic factors affect plant flowering under microgravity may include light, biological circadian clock as well as long-distance signaling, while the plant-derived flowering regulators in response to microgravity could include gibberellic acid, ethylene, microRNA and sugar. The results we have obtained from the space experiments on board the Chinese recoverable satellites (the SJ-8 and the SJ-10) and the experiment on the Chinese space lab TG-2 are also introduced. We conclude by suggesting that long-term space experiments from successive generations and a systematic analysis of regulatory networks at the molecular level is needed to understand the mechanism of plant flowering control under microgravity conditions in space.

Regulation of metabolism and body fat mass by leptin.

PubMed

Baile, C A; Della-Fera, M A; Martin, R J

2000-01-01

The relative stability of body weight over the long term and under a variety of environmental conditions that alter short-term energy intake and expenditure provides strong evidence for the regulation of body energy content. The lipostatic theory of energy balance regulation proposed 40 years ago that circulating factors, generated in proportion to body fat stores, acted as signals to the brain, eliciting changes in energy intake and expenditure. The discovery of leptin and its receptors has now provided a molecular basis for this theory. Leptin functions as much more than an adipocyte-derived signal of lipid stores, however. Although suppression of food intake is an important centrally mediated effect of leptin, considerable evidence indicates that leptin also functions both directly and indirectly, via the brain, to orchestrate complex metabolic changes in a number of organs and tissues, altering nutrient flux to favor energy expenditure over energy storage.

Neonatal immune challenge does not affect body weight regulation in rats.

PubMed

Spencer, Sarah J; Mouihate, Abdeslam; Galic, Michael A; Ellis, Shaun L; Pittman, Quentin J

2007-08-01

The perinatal environment plays a crucial role in programming many aspects of adult physiology. Myriad stressors during pregnancy, from maternal immune challenge to nutritional deficiency, can alter long-term body weight set points of the offspring. In light of the increasing concern over body weight issues, such as obesity and anorexia, in modern societies and accumulating evidence that developmental stressors have long-lasting effects on other aspects of physiology (e.g., fever, pain), we explored the role of immune system activation during neonatal development and its impact on body weight regulation in adulthood. Here we present a thorough evaluation of the effects of immune system activation (LPS, 100 microg/kg ip) at postnatal days 3, 7, or 14 on long-term body weight, adiposity, and body weight regulation after a further LPS injection (50 microg/kg ip) or fasting and basal and LPS-induced circulating levels of the appetite-regulating proinflammatory cytokine leptin. We show that neonatal exposure to LPS at various times during the neonatal period has no long-term effects on growth, body weight, or adiposity. We also observed no effects on body weight regulation in response to a short fasting period or a further exposure to LPS. Despite reductions in circulating leptin levels in response to LPS during the neonatal period, no long-term effects on leptin were seen. These results convincingly demonstrate that adult body weight and weight regulation are, unlike many other aspects of adult physiology, resistant to programming by a febrile-dose neonatal immune challenge.

Effect of aromatherapy massage on elderly patients under long-term hospitalization in Japan.

PubMed

Satou, Tadaaki; Chikama, Mizuki; Chikama, Yoshiko; Hachigo, Masato; Urayama, Haruna; Murakami, Shio; Hayashi, Shinichiro; Koikem, Kazuo

2013-03-01

To verify the effectiveness of aromatherapy massage on elderly patients under long-term hospitalization. Aromatherapy massage was performed twice a week for a total of eight times. Nursing home. Elderly women under long-term hospitalization. Questionnaire and measurement of stress marker levels (salivary amylase activity) before and after the first, fifth, and eighth aromatherapy massages. Questionnaire (Face scale, General Health Questionnaire-12 [GHQ-12]), measurement of salivary amylase activity. A decrease in stress after aromatherapy massage compared to before each massage was confirmed at all measurement times and with the stress marker. No marked reduction was observed in Face scale or saliva amylase activity as a whole over the long term, although decreasing tendencies were seen. Marked reductions in GHQ-12 were observed over the long term. Aroma massage appears likely to prove effective in reducing psychological stress among elderly patients under long-term hospitalization.

When mothering goes awry: Challenges and opportunities for utilizing evidence across rodent, nonhuman primate and human studies to better define the biological consequences of negative early caregiving.

PubMed

Drury, Stacy S; Sánchez, Mar M; Gonzalez, Andrea

2016-01-01

This article is part of a Special Issue "Parental Care".Across mammalian species, mothers shape socio-emotional development and serve as essential external regulators of infant physiology, brain development, behavior patterns, and emotional regulation. Caregiving quality, consistency and predictability shape the infant's underlying neurobiological processes. Although the requirements for "optimal" caregiving differ across species, the negative long-term consequences of the absence of needed caregiving (e.g. neglect) or the presence of harmful/aversive caregiving (e.g. physical abuse), are translatable across species. Recognizing the significant potential of cross species comparisons in terms of defining underlying mechanisms, effective translation requires consideration of the evolutionary, ecological, and fundamental biological and developmental differences between and among species. This review provides both an overview of several success stories of cross-species translations in relation to negative caregiving and a template for future studies seeking to most effectively define the underlying biological processes and advance research dedicated to mitigating the lasting negative health consequences of child maltreatment. Copyright © 2015 Elsevier Inc. All rights reserved.

The integrated role of ACh, ERK and mTOR in the mechanisms of hippocampal inhibitory avoidance memory.

PubMed

Giovannini, Maria Grazia; Lana, Daniele; Pepeu, Giancarlo

2015-03-01

The purpose of this review is to summarize the present knowledge on the interplay among the cholinergic system, Extracellular signal-Regulated Kinase (ERK) and Mammalian Target of Rapamycin (mTOR) pathways in the development of short and long term memories during the acquisition and recall of the step-down inhibitory avoidance in the hippocampus. The step-down inhibitory avoidance is a form of associative learning that is acquired in a relatively simple one-trial test through several sensorial inputs. Inhibitory avoidance depends on the integrated activity of hippocampal CA1 and other brain areas. Recall can be performed at different times after acquisition, thus allowing for the study of both short and long term memory. Among the many neurotransmitter systems involved, the cholinergic neurons that originate in the basal forebrain and project to the hippocampus are of crucial importance in inhibitory avoidance processes. Acetylcholine released from cholinergic fibers during acquisition and/or recall of behavioural tasks activates muscarinic and nicotinic acetylcholine receptors and brings about a long-lasting potentiation of the postsynaptic membrane followed by downstream activation of intracellular pathway (ERK, among others) that create conditions favourable for neuronal plasticity. ERK appears to be salient not only in long term memory, but also in the molecular mechanisms underlying short term memory formation in the hippocampus. Since ERK can function as a biochemical coincidence detector in response to extracellular signals in neurons, the activation of ERK-dependent downstream effectors is determined, in part, by the duration of ERK phosphorylation itself. Long term memories require protein synthesis, that in the synapto-dendritic compartment represents a direct mechanism that can produce rapid changes in protein content in response to synaptic activity. mTOR in the brain regulates protein translation in response to neuronal activity, thereby modulating synaptic plasticity and long term memory formation. Some studies demonstrate a complex interplay among the cholinergic system, ERK and mTOR. It has been shown that co-activation of muscarinic acetylcholine receptors and β-adrenergic receptors facilitates the conversion of short term to long term synaptic plasticity through an ERK- and mTOR-dependent mechanism which requires translation initiation. It seems therefore that the complex interplay among the cholinergic system, ERK and mTOR is crucial in the development of new inhibitory avoidance memories in the hippocampus. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-Term Self-Regulation of Biology Learning Using Standard Junior High School Science Curriculum

ERIC Educational Resources Information Center

Eilam, Billie; Reiter, Shoshi

2014-01-01

In today's world of information explosion, independent lifelong self-regulated learning (SRL) is becoming a necessity. However, opportunities in schools to experience such learning modes are relatively rare. This long-term explorative field study examined students' SRL of science. Changes in students' self-reported and enacted SRL…

Narp regulates long-term aversive effects of morphine withdrawal.

PubMed

Reti, Irving M; Crombag, Hans S; Takamiya, Kogo; Sutton, Jeffrey M; Guo, Ning; Dinenna, Megan L; Huganir, Richard L; Holland, Peter C; Baraban, Jay M

2008-08-01

Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. Because Narp is an immediate early gene product that is secreted at synaptic sites and binds to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, the authors found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, the authors evaluate whether long-term aversive effects of morphine withdrawal are altered in Narp knockout (KO) mice. The authors found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than do wild type (WT) controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction.

Short and long-lasting behavioral consequences of agonistic encounters between male Drosophila melanogaster.

PubMed

Trannoy, Séverine; Penn, Jill; Lucey, Kenia; Popovic, David; Kravitz, Edward A

2016-04-26

In many animal species, learning and memory have been found to play important roles in regulating intra- and interspecific behavioral interactions in varying environments. In such contexts, aggression is commonly used to obtain desired resources. Previous defeats or victories during aggressive interactions have been shown to influence the outcome of later contests, revealing loser and winner effects. In this study, we asked whether short- and/or long-term behavioral consequences accompany victories and defeats in dyadic pairings between male Drosophila melanogaster and how long those effects remain. The results demonstrated that single fights induced important behavioral changes in both combatants and resulted in the formation of short-term loser and winner effects. These decayed over several hours, with the duration depending on the level of familiarity of the opponents. Repeated defeats induced a long-lasting loser effect that was dependent on de novo protein synthesis, whereas repeated victories had no long-term behavioral consequences. This suggests that separate mechanisms govern the formation of loser and winner effects. These studies aim to lay a foundation for future investigations exploring the molecular mechanisms and circuitry underlying the nervous system changes induced by winning and losing bouts during agonistic encounters.

Long-term continuous corticosterone treatment decreases VEGF receptor-2 expression in frontal cortex.

PubMed

Howell, Kristy R; Kutiyanawalla, Ammar; Pillai, Anilkumar

2011-01-01

Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under long-term continuous glucocorticoid exposure has not been elucidated. We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects. We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects. The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecular mechanism of the neurobiological effects of chronic stress.

Erection capability is potentiated by long-term sildenafil treatment: role of blood flow-induced endothelial nitric-oxide synthase phosphorylation.

PubMed

Musicki, Biljana; Champion, Hunter C; Becker, Robyn E; Liu, Tongyun; Kramer, Melissa F; Burnett, Arthur L

2005-07-01

Despite demonstrated clinical efficacy of sildenafil for the temporary treatment of erectile dysfunction, the possibility that sildenafil used long-term durably augments erectile ability remains unclear. We investigated whether continuous long-term administration of sildenafil at clinically relevant levels to aged rats "primes" the penis for improved erectile ability and involves nitric oxide (NO) or RhoA/Rho-kinase signaling pathways. In aged, but not young rats, sildenafil prolonged erection and increased the protein expressions of phosphorylated endothelial NO synthase (eNOS) at serine-1177 and phosphorylated Akt at serine-473 in penes. Only in the young rat penis, protein expressions of phosphodiesterase-5 and phosphomyosin phosphatase target subunit 1, a marker of Rho-kinase activity, were increased by sildenafil. Sildenafil inhibited phosphodiesterase-5 activity in penes of young and aged rats coincident with assayed free plasma levels of the drug equivalent to clinically therapeutic measurements. We conclude that erectile ability can be enhanced under preconditions of erectile impairment by long-term inhibition of phosphodiesterase-5 and that the effect is mediated by Akt-dependent eNOS phosphorylation. The lack of erectile ability enhancement in young rats by long-term phosphodiesterase-5 inhibition may relate to restrained NO signaling by phosphodiesterase-5 up-regulation, lack of incremental Akt and eNOS phosphorylation, and heightened Rho-kinase signaling in the penis.

An Evaluation of Economists’ Influence on Electric Utility Rate Reforms,

DTIC Science & Technology

1982-01-01

PURPA ) of 1978 required all 50 state utility commissions and more than 150 other jurisdictions regulating electric utility rates to con- sider the...complex rate structure). The "cost effectiveness" language of PURPA suggests such an evaluation criterion based on long term considerations without...detailing the components of benefit; see Joskow. Individual hearings under PURPA have generally employed three standards: fuel or energy savings (if a TOU

The M-current inhibitor XE991 decreases the stimulation threshold for long-term synaptic plasticity in healthy mice and in models of cognitive disease.

PubMed

Fontán-Lozano, Angela; Suárez-Pereira, Irene; Delgado-García, José María; Carrión, Angel Manuel

2011-01-01

Aging, mental retardation, number of psychiatric and neurological disorders are all associated with learning and memory impairments. As the underlying causes of such conditions are very heterogeneous, manipulations that can enhance learning and memory in mice under different circumstances might be able to overcome the cognitive deficits in patients. The M-current regulates neuronal excitability and action potential firing, suggesting that its inhibition may increase cognitive capacities. We demonstrate that XE991, a specific M-current blocker, enhances learning and memory in healthy mice. This effect may be achieved by altering basal hippocampal synaptic activity and by diminishing the stimulation threshold for long-term changes in synaptic efficacy and learning-related gene expression. We also show that training sessions regulate the M-current by transiently decreasing the levels of KCNQ/Kv7.3 protein, a pivotal subunit for the M-current. Furthermore, we found that XE991 can revert the cognitive impairment associated with acetylcholine depletion and the neurodegeneration induced by kainic acid. Together, these results show that inhibition of the M-current as a general strategy may be useful to enhance cognitive capacities in healthy and aging individuals, as well as in those with neurodegenerative diseases. Copyright © 2010 Wiley-Liss, Inc.

Long-term nitrogen regulation of forest carbon sequestration

NASA Astrophysics Data System (ADS)

Yang, Y.; Luo, Y.

2009-12-01

It is well established that nitrogen (N) limits plant production but unclear how N regulates long-term terrestrial carbon (C) sequestration in response to rising atmospheric C dioxide (CO2)(Luo et al., 2004). Most experimental evidence on C-N interactions is primarily derived from short-term CO2 manipulative studies (e.g. Oren et al., 2001; Reich et al., 2006a), which abruptly increase C inputs into ecosystems and N demand from soil while atmospheric CO2 concentration in the real world is gradually increasing over time (Luo & Reynolds, 1999). It is essential to examine long-term N regulations of C sequestration in natural ecosystems. Here we present results of a synthesis of more than 100 studies on long-term C-N interactions during secondary succession. C significantly accumulates in plant, litter and forest floor in most studies, and in mineral soil in one-third studies during stand development. Substantial increases in C stock are tightly coupled with N accretion. The C: N ratio in plant increases with stand age in most cases, but remains relatively constant in litter, forest floor and mineral soil. Our results suggest that natural ecosystems could have the intrinsic capacity to maintain long-term C sequestration through external N accrual, high N use efficiency, and efficient internal N cycling.

Gap Junctions in the Ventral Hippocampal-Medial Prefrontal Pathway Are Involved in Anxiety Regulation

PubMed Central

Schoenfeld, Timothy J.; Kloth, Alexander D.; Hsueh, Brian; Runkle, Matthew B.; Kane, Gary A.; Wang, Samuel S.-H.

2014-01-01

Anxiety disorders are highly prevalent but little is known about their underlying mechanisms. Gap junctions exist in brain regions important for anxiety regulation, such as the ventral hippocampus (vHIP) and mPFC, but their functions in these areas have not been investigated. Using pharmacological blockade of neuronal gap junctions combined with electrophysiological recordings, we found that gap junctions play a role in theta rhythm in the vHIP and mPFC of adult mice. Bilateral infusion of neuronal gap junction blockers into the vHIP decreased anxiety-like behavior on the elevated plus maze and open field. Similar anxiolytic effects were observed with unilateral infusion of these drugs into the vHIP combined with contralateral infusion into the mPFC. No change in anxious behavior was observed with gap junction blockade in the unilateral vHIP alone or in the bilateral dorsal HIP. Since physical exercise is known to reduce anxiety, we examined the effects of long-term running on the expression of the neuronal gap junction protein connexin-36 among inhibitory interneurons and found a reduction in the vHIP. Despite this change, we observed no alteration in theta frequency or power in long-term runners. Collectively, these findings suggest that neuronal gap junctions in the vHIP–mPFC pathway are important for theta rhythm and anxiety regulation under sedentary conditions but that additional mechanisms are likely involved in running-induced reduction in anxiety. PMID:25411496

Long-term soluble Abeta1-40 activates CaM kinase II in organotypic hippocampal cultures.

PubMed

Tardito, Daniela; Gennarelli, Massimo; Musazzi, Laura; Gesuete, Raffaella; Chiarini, Stefania; Barbiero, Valentina Sara; Rydel, Russell E; Racagni, Giorgio; Popoli, Maurizio

2007-09-01

Recent findings suggested a role for soluble amyloid-beta (Abeta) peptides in Alzheimer's disease associated cognitive decline. We investigated the action of soluble, monomeric Abeta(1-40) on CaM kinase II, a kinase involved in neuroplasticity and cognition. We treated organotypic hippocampal cultures short-term (up to 4h) and long-term (5 days) with Abeta(1-40) (1nM-5microM). Abeta did not induce cell damage, apoptosis or synaptic loss. Short-term treatment down-regulated enzymatic activity of the kinase, by reducing its Thr(286) phosphorylation. In contrast, long-term treatment (1nM-microM) markedly and significantly up-regulated enzymatic activity, with peak stimulation at 10nM (three-fold). Up-regulation of activity was associated with increased expression of the alpha-isoform of CaM kinase II, increased phosphorylation at Thr(286) (activator residue) and decreased phosphorylation at Thr(305-306) (inhibitory residues). We investigated the effect of glutamate on CaM kinase II following exposure to 1 or 10nM Abeta(1-40). As previously reported, glutamate increased CaM kinase II activity. However, the glutamate effect was not altered by pretreatment of slices with Abeta. Short- and long-term Abeta treatment showed opposite effects on CaM kinase II, suggesting that long-term changes are an adaptation to the kinase early down-regulation. The marked effect of Abeta(1-40) on the kinase suggests that semi-physiological and slowly raising peptide concentrations may have a significant impact on synaptic plasticity in the absence of synaptic loss or neuronal cell death.

HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner

PubMed Central

Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

2011-01-01

Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory. PMID:21224411

Population Dynamics of Genetic Regulatory Networks

NASA Astrophysics Data System (ADS)

Braun, Erez

2005-03-01

Unlike common objects in physics, a biological cell processes information. The cell interprets its genome and transforms the genomic information content, through the action of genetic regulatory networks, into proteins which in turn dictate its metabolism, functionality and morphology. Understanding the dynamics of a population of biological cells presents a unique challenge. It requires to link the intracellular dynamics of gene regulation, through the mechanism of cell division, to the level of the population. We present experiments studying adaptive dynamics of populations of genetically homogeneous microorganisms (yeast), grown for long durations under steady conditions. We focus on population dynamics that do not involve random genetic mutations. Our experiments follow the long-term dynamics of the population distributions and allow to quantify the correlations among generations. We focus on three interconnected issues: adaptation of genetically homogeneous populations following environmental changes, selection processes on the population and population variability and expression distributions. We show that while the population exhibits specific short-term responses to environmental inputs, it eventually adapts to a robust steady-state, largely independent of external conditions. Cycles of medium-switch show that the adapted state is imprinted in the population and that this memory is maintained for many generations. To further study population adaptation, we utilize the process of gene recruitment whereby a gene naturally regulated by a specific promoter is placed under a different regulatory system. This naturally occurring process has been recognized as a major driving force in evolution. We have recruited an essential gene to a foreign regulatory network and followed the population long-term dynamics. Rewiring of the regulatory network allows us to expose their complex dynamics and phase space structure.

2013 Annual Site Inspection and Monitoring Report for Uranium Mill Tailings Radiation Control Act Title I Disposal Sites

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

None, None

This report, in fulfillment of a license requirement, presents the results of long-term surveillance and maintenance activities conducted by the U.S. Department of Energy (DOE) Office of Legacy Management (LM) in 2013 at 19 uranium mill tailings disposal sites established under Title I of the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 1978.1 These activities verified that the UMTRCA Title I disposal sites remain in compliance with license requirements. DOE operates 18 UMTRCA Title I sites under a general license granted by the U.S. Nuclear Regulatory Commission (NRC) in accordance with Title 10 Code of Federal Regulations Part 40.27more » (10 CFR 40.27). As required under the general license, a long-term surveillance plan (LTSP) for each site was prepared by DOE and accepted by NRC. The Grand Junction, Colorado, Disposal Site, one of the 19 Title I sites, will not be included under the general license until the open, operating portion of the cell is closed. The open portion will be closed either when it is filled or in 2023. This site is inspected in accordance with an interim LTSP. Long-term surveillance and maintenance services for these disposal sites include inspecting and maintaining the sites; monitoring environmental media and institutional controls; conducting any necessary corrective actions; and performing administrative, records, stakeholder relations, and other regulatory stewardship functions. Annual site inspections and monitoring are conducted in accordance with site-specific LTSPs and procedures established by DOE to comply with license requirements. Each site inspection is performed to verify the integrity of visible features at the site; to identify changes or new conditions that may affect the long-term performance of the site; and to determine the need, if any, for maintenance, follow-up or contingency inspections, or corrective action in accordance with the LTSP. LTSPs and site compliance reports are available on the Internet at http://www.lm.doe.gov/.« less

Anesthesiology Devices; Reclassification of Membrane Lung for Long-Term Pulmonary Support; Redesignation as Extracorporeal Circuit and Accessories for Long-Term Respiratory/Cardiopulmonary Failure. Final order.

PubMed

2016-02-12

The Food and Drug Administration (FDA) is issuing a final order to redesignate membrane lung devices for long-term pulmonary support, a preamendments class III device, as extracorporeal circuit and accessories for long-term respiratory/cardiopulmonary failure, and to reclassify the device to class II (special controls) in patients with acute respiratory failure or acute cardiopulmonary failure where other available treatment options have failed, and continued clinical deterioration is expected or the risk of death is imminent. A membrane lung device for long-term pulmonary support (>6 hours) refers to the oxygenator in an extracorporeal circuit used during long-term procedures, commonly referred to as extracorporeal membrane oxygenation (ECMO). Because a number of other devices and accessories are used with the oxygenator in the circuit, the title and identification of the regulation are revised to include extracorporeal circuit and accessories for long-term respiratory/cardiopulmonary failure. Although an individual device or accessory used in an ECMO circuit may already have its own classification regulation when the device or accessory is intended for short-term use (<=6 hours), such device or accessory will be subject to the same regulatory controls applied to the oxygenator (i.e., class II, special controls) when evaluated as part of the ECMO circuit for long-term use (>6 hours). On its own initiative, based on new information, FDA is revising the classification of the membrane lung device for long-term pulmonary support.

Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.

PubMed

Zhu, G; Wang, Y; Li, J; Wang, J

2015-04-30

Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Fan-Shaped Body Neurons Are Involved in "Period"-Dependent Regulation of Long-Term Courtship Memory in "Drosophila"

ERIC Educational Resources Information Center

Sakai, Takaomi; Inami, Show; Sato, Shoma; Kitamoto, Toshihiro

2012-01-01

In addition to its established function in the regulation of circadian rhythms, the "Drosophila" gene "period" ("per") also plays an important role in processing long-term memory (LTM). Here, we used courtship conditioning as a learning paradigm and revealed that (1) overexpression and knocking down of "per" in subsets of brain neurons enhance and…

Dancing the Two-Step in Ontario's Long-term Care Sector: More Deterrence-oriented Regulation = Ownership and Management Consolidation.

PubMed

Daly, Tamara

2015-03-01

This paper explores shifts in public and private delivery over time through an analysis of Ontario's approach to LTC funding and regulation in relation to other jurisdictions in Canada and abroad. The case of Ontario's long-term care (LTC) policy evolution - from the 1940s until early 2013 -- shows how moving from compliance to deterrence oriented regulation can support consolidation of commercial providers' ownership and increase the likelihood of non-profit and public providers outsourcing their management.

A critical review of sex differences in decision-making tasks: focus on the Iowa Gambling Task.

PubMed

van den Bos, Ruud; Homberg, Judith; de Visser, Leonie

2013-02-01

It has been observed that men and women show performance differences in the Iowa Gambling Task (IGT), a task of decision-making in which subjects through exploration learn to differentiate long-term advantageous from long-term disadvantageous decks of cards: men choose more cards from the long-term advantageous decks than women within the standard number of 100 trials. Here, we aim at discussing psychological mechanisms and neurobiological substrates underlying sex differences in IGT-like decision-making. Our review suggests that women focus on both win-loss frequencies and long-term pay-off of decks, while men focus on long-term pay-off. Furthermore, women may be more sensitive to occasional losses in the long-term advantageous decks than men. As a consequence hereof, women need 40-60 trials in addition before they reach the same level of performance as men. These performance differences are related to differences in activity in the orbitofrontal cortex and dorsolateral prefrontal cortex as well as in serotonergic activity and left-right hemispheric activity. Sex differences in orbitofrontal cortex activity may be due to organisational effects of gonadal hormones early in life. The behavioural and neurobiological differences in the IGT between men and women are an expression of more general sex differences in the regulation of emotions. We discuss these findings in the context of sex differences in information processing related to evolutionary processes. Furthermore we discuss the relationship between these findings and real world decision-making. Copyright © 2012 Elsevier B.V. All rights reserved.

GLIMPSE: a rapid decision framework for energy and environmental policy.

PubMed

Akhtar, Farhan H; Pinder, Robert W; Loughlin, Daniel H; Henze, Daven K

2013-01-01

Over the coming decades, new energy production technologies and the policies that oversee them will affect human health, the vitality of our ecosystems, and the stability of the global climate. The GLIMPSE decision model framework provides insights about the implications of technology and policy decisions on these outcomes. Using GLIMPSE, decision makers can identify alternative techno-policy futures, examining their air quality, health, and short- and long-term climate impacts. Ultimately, GLIMPSE will support the identification of cost-effective strategies for simultaneously achieving performance goals for these metrics. Here, we demonstrate the utility of GLIMPSE by analyzing several future energy scenarios under existing air quality regulations and potential CO2 emission reduction policies. We find opportunities for substantial cobenefits in setting both climate change mitigation and health-benefit based air quality improvement targets. Though current policies which prioritize public health protection increase near-term warming, establishing policies that also reduce greenhouse gas emissions may offset warming in the near-term and lead to significant reductions in long-term warming.

43 CFR 3904.40 - Long-term water treatment trust funds.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Long-term water treatment trust funds. 3904.40 Section 3904.40 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RANGE MANAGEMENT (4000) OIL SHALE MANAGEMENT-GENERAL Bonds and Trust Funds § 3904.40 Long-term water...

2013 Annual Site Inspection and Monitoring Report for Uranium Mill Tailings Radiation Control Act Title II Disposal Sites

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

None

This report, in fulfillment of a license requirement, presents the results of long-term surveillance and maintenance activities conducted by the U.S. Department of Energy (DOE) Office of Legacy Management in 2013 at six uranium mill tailings disposal sites reclaimed under Title II of the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 1978. These activities verified that the UMTRCA Title II disposal sites remain in compliance with license requirements. DOE manages six UMTRCA Title II disposal sites under a general license granted by the U.S. Nuclear Regulatory Commission (NRC) established at Title 10 Code of Federal Regulations Part 40.28. Reclamationmore » and site transition activities continue at other sites, and DOE ultimately expects to manage approximately 27 Title II disposal sites. Long-term surveillance and maintenance activities and services for these disposal sites include inspecting and maintaining the sites; monitoring environmental media and institutional controls; conducting any necessary corrective action; and performing administrative, records, stakeholder services, and other regulatory functions. Annual site inspections and monitoring are conducted in accordance with site-specific long-term surveillance plans (LTSPs) and procedures established by DOE to comply with license requirements. Each site inspection is performed to verify the integrity of visible features at the site; to identify changes or new conditions that may affect the long-term performance of the site; and to determine the need, if any, for maintenance, follow-up inspections, or corrective action. LTSPs and site compliance reports are available online at http://www.lm.doe.gov« less

Alteration of synaptic activity-regulating genes underlying functional improvement by long-term exposure to an enriched environment in the adult brain.

PubMed

Lee, Min-Young; Yu, Ji Hea; Kim, Ji Yeon; Seo, Jung Hwa; Park, Eun Sook; Kim, Chul Hoon; Kim, Hyongbum; Cho, Sung-Rae

2013-01-01

Housing animals in an enriched environment (EE) enhances behavioral function. However, the mechanism underlying this EE-mediated functional improvement and the resultant changes in gene expression have yet to be elucidated. We attempted to investigate the underlying mechanisms associated with long-term exposure to an EE by evaluating gene expression patterns. We housed 6-week-old CD-1 (ICR) mice in standard cages or an EE comprising a running wheel, novel objects, and social interaction for 2 months. Motor and cognitive performances were evaluated using the rotarod test and passive avoidance test, and gene expression profile was investigated in the cerebral hemispheres using microarray and gene set enrichment analysis (GSEA). In behavioral assessment, an EE significantly enhanced rotarod performance and short-term working memory. Microarray analysis revealed that genes associated with neuronal activity were significantly altered by an EE. GSEA showed that genes involved in synaptic transmission and postsynaptic signal transduction were globally upregulated, whereas those associated with reuptake by presynaptic neurotransmitter transporters were downregulated. In particular, both microarray and GSEA demonstrated that EE exposure increased opioid signaling, acetylcholine release cycle, and postsynaptic neurotransmitter receptors but decreased Na+ / Cl- -dependent neurotransmitter transporters, including dopamine transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner. An EE enhanced motor and cognitive function through the alteration of synaptic activity-regulating genes, improving the efficient use of neurotransmitters and synaptic plasticity by the upregulation of genes associated with postsynaptic receptor activity and downregulation of presynaptic reuptake by neurotransmitter transporters.

Experts' consensus on use of electronic cigarettes: a Delphi survey from Switzerland.

PubMed

Blaser, Jeremie; Cornuz, Jacques

2015-04-15

In some countries, nicotine-containing electronic cigarettes (e-cigarettes) are considered a consumer product without specific regulations. In others (eg, Switzerland), the sale of e-cigarettes containing nicotine is forbidden, despite the eagerness of many smokers to obtain them. As scientific data about efficacy and long-term safety of these products are scarce, tobacco control experts are divided on how to regulate them. In order to gain consensus among experts to provide recommendations to health authorities, we performed a national consensus study. We used a Delphi method with electronic questionnaires to bring together the opinion of Swiss experts on e-cigarettes. 40 Swiss experts from across the country. We measured the degree of consensus between experts on recommendations regarding regulation, sale, use of and general opinion about e-cigarettes containing nicotine. New recommendations and statements were added following the experts' answers and comments. There was consensus that e-cigarettes containing nicotine should be made available, but only under specific conditions. Sale should be restricted to adults, using quality standards, a maximum level of nicotine and with an accompanying list of authorised ingredients. Advertisement should be restricted and use in public places should be forbidden. These recommendations encompass three principles: (1) the reality principle, as the product is already on the market; (2) the prevention principle, as e-cigarettes provide an alternative to tobacco for actual smokers, and (3) the precautionary principle, to protect minors and non-smokers, since long-term effects are not yet known. Swiss authorities should design specific regulations to sell nicotine-containing e-cigarettes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

16 CFR 300.1 - Terms defined.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Terms defined. 300.1 Section 300.1 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER THE WOOL PRODUCTS LABELING ACT OF 1939 Definitions § 300.1 Terms defined. (a) The term Act...

42 CFR 423.154 - Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 3 2014-10-01 2014-10-01 false Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD plans. 423.154 Section 423.154 Public Health CENTERS FOR... § 423.154 Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD...

42 CFR 423.154 - Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 3 2011-10-01 2011-10-01 false Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD plans. 423.154 Section 423.154 Public Health CENTERS FOR... Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD plans. (a) In...

42 CFR 423.154 - Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 3 2013-10-01 2013-10-01 false Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD plans. 423.154 Section 423.154 Public Health CENTERS FOR... § 423.154 Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD...

42 CFR 423.154 - Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 3 2012-10-01 2012-10-01 false Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD plans. 423.154 Section 423.154 Public Health CENTERS FOR... § 423.154 Appropriate dispensing of prescription drugs in long-term care facilities under PDPs and MA-PD...

Role of "Aplysia" Cell Adhesion Molecules during 5-HT-Induced Long-Term Functional and Structural Changes

ERIC Educational Resources Information Center

Han, Jin-Hee; Lim, Chae-Seok; Lee, Yong-Seok; Kandel, Eric R.; Kaang, Bong-Kiun

2004-01-01

We previously reported that five repeated pulses of 5-HT lead to down-regulation of the TM-apCAM isoform at the surface of "Aplysia" sensory neurons (SNs). We here examined whether apCAM down-regulation is required for 5-HT-induced long-term facilitation. We also analyzed the role of the cytoplasmic and extracellular domains by overexpressing…

Energy Density, Energy Intake, and Body Weight Regulation in Adults12345

PubMed Central

Karl, J. Philip; Roberts, Susan B.

2014-01-01

The role of dietary energy density (ED) in the regulation of energy intake (EI) is controversial. Methodologically, there is also debate about whether beverages should be included in dietary ED calculations. To address these issues, studies examining the effects of ED on EI or body weight in nonelderly adults were reviewed. Different approaches to calculating dietary ED do not appear to alter the direction of reported relations between ED and body weight. Evidence that lowering dietary ED reduces EI in short-term studies is convincing, but there are currently insufficient data to determine long-term effectiveness for weight loss. The review also identified key barriers to progress in understanding the role of ED in energy regulation, in particular the absence of a standard definition of ED, and the lack of data from multiple long-term clinical trials examining the effectiveness of low-ED diet recommendations for preventing both primary weight gain and weight regain in nonobese individuals. Long-term clinical trials designed to examine the impact of dietary ED on energy regulation, and including multiple ED calculation methods within the same study, are still needed to determine the importance of ED in the regulation of EI and body weight. PMID:25398750

Stratum Electricity Markets: Toward Multi-temporal Distributed Risk Management for Sustainable Electricity Provision

NASA Astrophysics Data System (ADS)

Wu, Zhiyong (Richard)

Motivated by the overall challenge of ensuring long-term sustainable electricity service, we view this challenge as a long-term decision making problem under uncertainties. We start by recognizing that, independent of the industry organization, the uncertainties are enormous and often exogenous to the energy service providers. They are multi-dimensional and are result of fundamental drivers, ranging from the supply side, through the demand side, to the regulatory and policy sides. The basic contribution of this thesis comes from the recognition that long-term investments for ensuring reliable and stable electricity service critically depend on how these uncertainties are perceived, valued and managed by the different stakeholders within the complex industry organization such as the electric power industry. We explain several reasons why price signals obtained from current short-term electricity markets alone are not sufficient enough for long-term sustainable provision. Some enhancements are presented in the thesis to improve the short-term electricity market price signals to reflect the true cost of operation. New market mechanisms and instruments are needed to facilitate the stakeholders to better deal with long-term risks. The problems of ensuring long-term stable reliable service in the sense of the traditional resource adequacy requirements are revisited in both the restructuring industry and regulated industry. We introduce a so-called Stratum Electricity Market (SEM) design as the basic market mechanism for solving the problem of long-term reliable electricity service through a series of interactive multi-lateral market exchange platforms for risks communication, management and evaluations over various time horizons and by the different groups of stakeholders. In other words, our proposed SEM is a basic IT-enabled framework for the decision making processes by various parties over different time. Because of the uniqueness of electricity as a commodity, the values for the same amount of energy during different time and at different location can vary dramatically. Moreover, for the same hour, the values for the same amount of power at base load level or at peak load level are different due to the different generation technologies and other non-convex constraints like unit commitment. The multiple market products at zonal/nodal levels with different time horizon and time of use categories are designed to reflect more realistic demand and supply conditions at various temporal and spatial granularities. Detailed market rules, rights and regulations (3Rs) concerning the sub-markets interactions, product hierarchy and financial settlements are also examined.

[Adaptive adjustment of rhizome and root system on morphology, biomass and nutrient in Phyllostachys rivalis under long-term waterlogged condition].

PubMed

Liu, Yu-fang; Chen, Shuang-lin; Li Ying-chun; Guo, Zi-wu; Li, Ying-chun; Yang, Qing-ping

2015-12-01

The research was to approach the growth strategy of rhizome and roots based on the morphology, biomass and nutrient in Phyllostachys rivalis under long-term waterlogged conditions, and provided a theoretical basis for its application for vegetation restoration in wetland and water-level fluctuation belts. The morphological characteristics, physiological and biochemical indexes of annual bamboo rhizome and roots were investigated with an experiment using individually potted P. rivalis which was treated by artificial water-logging for 3, 6, and 12 months. Accordingly the morphological characteristics, biomass allocation, nutrient absorption and balance in rhizome and roots of P. rivalis were analyzed. The results showed that there was no obvious impact of long-term water-logging on the length and diameter of rhizomes, diameter of roots in P. rivalis. The morphological characteristics of rhizome had been less affected generally under water-logging for 3 months. And less rhizomes were submerged, while the growth of roots was inhibited to some extent. Furthermore, with waterlogging time extended, submerged roots and rhizomes grew abundantly, and the roots and rhizomes in soil were promoted. Moreover for ratios of rhizome biomass in soil and water, there were no obvious variations, the same for the root biomass in soil to total biomass. The ratio of root biomass in water to total biomass and the ratio of root biomass in water to root biomass in soil both increased significantly. The results indicated that P. rivalis could adapt to waterlogged conditions gradually through growth regulation and reasonable biomass distribution. However, the activity of rhizome roots in soil decreased and the nutrient absorption was inhibited by long-term water-logging, although it had no effect on stoichiometric ratios of root nutrient in soil. The activity of rhizome root in water increased and the stoichiometric ratios adjusted adaptively to waterlogged conditions, the ratio of N/P increased, while N/K and P/K decreased, which implied that roots in water absorbed oxygen and nutrients could help P. rivalis adapt to long-term waterlogged environment effectively.

Superior Long-Term Synaptic Memory Induced by Combining Dual Pharmacological Activation of PKA and ERK with an Enhanced Training Protocol

ERIC Educational Resources Information Center

Liu, Rong-Yu; Neveu, Curtis; Smolen, Paul; Cleary, Leonard J.; Byrne, John H.

2017-01-01

Developing treatment strategies to enhance memory is an important goal of neuroscience research. Activation of multiple biochemical signaling cascades, such as the protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways, is necessary to induce long-term synaptic facilitation (LTF), a correlate of long-term memory (LTM).…

Design for pressure regulating components

NASA Technical Reports Server (NTRS)

Wichmann, H.

1973-01-01

The design development for Pressure Regulating Components included a regulator component trade-off study with analog computer performance verification to arrive at a final optimized regulator configuration for the Space Storable Propulsion Module, under development for a Jupiter Orbiter mission. This application requires the pressure regulator to be capable of long-term fluorine exposure. In addition, individual but basically identical (for purposes of commonality) units are required for separate oxidizer and fuel pressurization. The need for dual units requires improvement in the regulation accuracy over present designs. An advanced regulator concept was prepared featuring redundant bellows, all metallic/ceramic construction, friction-free guidance of moving parts, gas damping, and the elimination of coil springs normally used for reference forces. The activities included testing of actual size seat/poppet components to determine actual discharge coefficients and flow forces. The resulting data was inserted into the computer model of the regulator. Computer simulation of the propulsion module performance over two mission profiles indicated satisfactory minimization of propellant residual requirements imposed by regulator performance uncertainties.

Process for Transition of Uranium Mill Tailings Radiation Control Act Title II Disposal Sites to the U.S. Department of Energy Office of Legacy Management for Long-Term Surveillance and Maintenance

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

None

This document presents guidance for implementing the process that the U.S. Department of Energy (DOE) Office of Legacy Management (LM) will use for assuming perpetual responsibility for a closed uranium mill tailings site. The transition process specifically addresses sites regulated under Title II of the Uranium Mill Tailings Radiation Control Act (UMTRCA) but is applicable in principle to the transition of sites under other regulatory structures, such as the Formerly Utilized Sites Remedial Action Program.

Long-Term Monitoring of Pavement Maintenance Materials Test Sites

DOT National Transportation Integrated Search

1998-06-01

The Strategic Highway Research Program's {SHRP) H-106 pothole repair experiment was part of the most extensive pavement maintenance experiment ever conducted. Started under SHRP and continued under the Long-Term Pavement Performance program's Long-Te...

Dancing the Two-Step in Ontario’s Long-term Care Sector: More Deterrence-oriented Regulation = Ownership and Management Consolidation

PubMed Central

Daly, Tamara

2016-01-01

This paper explores shifts in public and private delivery over time through an analysis of Ontario’s approach to LTC funding and regulation in relation to other jurisdictions in Canada and abroad. The case of Ontario’s long-term care (LTC) policy evolution – from the 1940s until early 2013 -- shows how moving from compliance to deterrence oriented regulation can support consolidation of commercial providers’ ownership and increase the likelihood of non-profit and public providers outsourcing their management. PMID:27777495

Hormonal regulation of fluid and electrolyte metabolism in zero-g and bedrest

NASA Technical Reports Server (NTRS)

Vernikos, Joan

1991-01-01

The study of man in spaceflight has consistently indicated changes in fluid and electrolyte balance. Sodium (Na), Potassium (K), and Calcium (Ca) excretion are increased, accompanied by changes in the levels and responsiveness of adrenal hormones and the sympathetic nervous system (SNS). These hormones and neurohumors are critical to the regulation of blood pressure, blood flow, and blood volume. The primary objectives of the research conducted under this task have been to use -6 deg head down bedrest (BR) as the analog to spaceflight, to determine the long term changes in these systems, their relationship to orthostatic tolerance, and to develop and test suitable countermeasures.

Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging.

PubMed

Pocock, Ginger M; Zimdars, Laraine L; Yuan, Ming; Eliceiri, Kevin W; Ahlquist, Paul; Sherer, Nathan M

2017-02-01

Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other posttranscriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus), and an intron-retaining transcript encoded by the cellular NXF1 gene. Striking behaviors include "burst" RNA nuclear export dynamics regulated by HIV-1's Rev response element and the viral Rev protein; transient aggregations of RNAs into discrete foci at or near the nuclear membrane triggered by multiple elements; and a novel, pulsiform RNA export activity regulated by the hepadnaviral posttranscriptional regulatory element. We incorporate single-cell tracking and a data-mining algorithm into our approach to obtain RNA element-specific, high-resolution gene expression signatures. Together these imaging assays constitute a tractable, systems-based platform for studying otherwise difficult to access spatiotemporal features of viral and cellular gene regulation. © 2017 Pocock et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Test Results of Selected Commercial DC/DC Converters under Cryogenic Temperatures - A Digest

NASA Technical Reports Server (NTRS)

Patterson, Richard; Hammoud, Ahmad

2010-01-01

DC/DC converters are widely used in space power systems in the areas of power management and distribution, signal conditioning, and motor control. Design of DC/DC converters to survive cryogenic temperatures will improve the power system performance, simplify design, and reduce development and launch costs. In this work, the performance of nine COTS modular, low-tomedium power DC/DC converters was investigated under cryogenic temperatures. The converters were evaluated in terms of their output regulation, efficiency, and input and output currents. At a given temperature, these properties were obtained at various input voltages and at different load levels. A summary on the performance of the tested converters was given. More comprehensive testing and in-depth analysis of performance under long-term exposure to extreme temperatures are deemed necessary to establish the suitability of these and other devices for use in the harsh environment of space exploration missions.

Neuromodulation, development and synaptic plasticity.

PubMed

Foehring, R C; Lorenzon, N M

1999-03-01

We discuss parallels in the mechanisms underlying use-dependent synaptic plasticity during development and long-term potentiation (LTP) and long-term depression (LTD) in neocortical synapses. Neuromodulators, such as norepinephrine, serotonin, and acetylcholine have also been implicated in regulating both developmental plasticity and LTP/LTD. There are many potential levels of interaction between neuromodulators and plasticity. Ion channels are substrates for modulation in many cell types. We discuss examples of modulation of voltage-gated Ca2+ channels and Ca(2+)-dependent K+ channels and the consequences for neocortical pyramidal cell firing behaviour. At the time when developmental plasticity is most evident in rat cortex, the substrate for modulation is changing as the densities and relative proportions of various ion channels types are altered during ontogeny. We discuss examples of changes in K+ and Ca2+ channels and the consequence for modulation of neuronal activity.

Timing and Targeting of Treatment in Left Ventricular Hypertrophy.

PubMed

Nam, Deokhwa; Reineke, Erin L

2017-01-01

In most clinical cases, left ventricular hypertrophy (LVH) occurs over time from persistent cardiac stress. At the molecular level, this results in both transient and long-term changes to metabolic, sarcomeric, ion handling, and stress signaling pathways. Although this is initially an adaptive change, the mechanisms underlying LVH eventually lead to maladaptive changes including fibrosis, decreased cardiac function, and failure. Understanding the regulators of long-term changes, which are largely driven by transcriptional remodeling, is a crucial step in identifying novel therapeutic targets for preventing the downstream negative effects of LVH and treatments that could reverse or prevent it. The development of effective therapeutics, however, will require a critical understanding of what to target, how to modify important pathways, and how to identify the stage of pathology in which a specific treatment should be used.

Implications of long-term culture for mesenchymal stem cells: genetic defects or epigenetic regulation?

PubMed Central

2012-01-01

Mesenchymal stem cells change dramatically during culture expansion. Long-term culture has been suspected to evoke oncogenic transformation: overall, the genome appears to be relatively stable throughout culture but transient clonal aneuploidies have been observed. Oncogenic transformation does not necessarily entail growth advantage in vitro and, therefore, the available methods - such as karyotypic analysis or genomic profiling - cannot exclude this risk. On the other hand, long-term culture is associated with specific senescence-associated DNA methylation (SA-DNAm) changes, particularly in developmental genes. SA-DNAm changes are highly reproducible and can be used to monitor the state of senescence for quality control. Notably, neither telomere attrition nor SA-DNAm changes occur in pluripotent stem cells, which can evade the 'Hayflick limit'. Long-term culture of mesenchymal stem cells seems to involve a tightly regulated epigenetic program. These epigenetic modifications may counteract dominant clones, which are more prone to transformation. PMID:23257053

Implications of long-term culture for mesenchymal stem cells: genetic defects or epigenetic regulation?

PubMed

Wagner, Wolfgang

2012-12-20

Mesenchymal stem cells change dramatically during culture expansion. Long-term culture has been suspected to evoke oncogenic transformation: overall, the genome appears to be relatively stable throughout culture but transient clonal aneuploidies have been observed. Oncogenic transformation does not necessarily entail growth advantage in vitro and, therefore, the available methods - such as karyotypic analysis or genomic profiling - cannot exclude this risk. On the other hand, long-term culture is associated with specific senescence-associated DNA methylation (SA-DNAm) changes, particularly in developmental genes. SA-DNAm changes are highly reproducible and can be used to monitor the state of senescence for quality control. Notably, neither telomere attrition nor SA-DNAm changes occur in pluripotent stem cells, which can evade the 'Hayflick limit'. Long-term culture of mesenchymal stem cells seems to involve a tightly regulated epigenetic program. These epigenetic modifications may counteract dominant clones, which are more prone to transformation.

16 CFR 304.1 - Terms defined.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Terms defined. 304.1 Section 304.1 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER THE HOBBY PROTECTION ACT § 304.1 Terms defined. (a) Act means the Hobby Protection Act...

Heavy metal pollution decreases microbial abundance, diversity and activity within particle-size fractions of a paddy soil.

PubMed

Chen, Junhui; He, Feng; Zhang, Xuhui; Sun, Xuan; Zheng, Jufeng; Zheng, Jinwei

2014-01-01

Chemical and microbial characterisations of particle-size fractions (PSFs) from a rice paddy soil subjected to long-term heavy metal pollution (P) and nonpolluted (NP) soil were performed to investigate whether the distribution of heavy metals (Cd, Cu, Pb and Zn) regulates microbial community activity, abundance and diversity at the microenvironment scale. The soils were physically fractionated into coarse sand, fine sand, silt and clay fractions. Long-term heavy metal pollution notably decreased soil basal respiration (a measurement of the total activity of the soil microbial community) and microbial biomass carbon (MBC) across the fractions by 3-45% and 21-53%, respectively. The coarse sand fraction was more affected by pollution than the clay fraction and displayed a significantly lower MBC content and respiration and dehydrogenase activity compared with the nonpolluted soils. The abundances and diversities of bacteria were less affected within the PSFs under pollution. However, significant decreases in the abundances and diversities of fungi were noted, which may have strongly contributed to the decrease in MBC. Sequencing of denaturing gradient gel electrophoresis bands revealed that the groups Acidobacteria, Ascomycota and Chytridiomycota were clearly inhibited under pollution. Our findings suggest that long-term heavy metal pollution decreased the microbial biomass, activity and diversity in PSFs, particularly in the large-size fractions. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Patterns and Drivers of Soil Respiration under Long-Term Citrus reticulate in Southern China

PubMed Central

Zhang, Yan-Jie; Zhang, Su-Yan; Yang, Jie; Yan, Yue; Fu, Xiang-ping; Lu, Shun-Bao

2015-01-01

Soil respiration (Rs) is a major source of carbon emission in terrestrial ecosystems. Despite the fact that the influence of land use practice on Rs has been widely studied, the patterns and drivers on Rs of Citrus reticulata cultivation, a worldwide land use practice are unclear. In this current study, we investigated the influence of long-term cultivation of Citrus reticulata (CO) and of CO intercropped with soybean (CB) on soil nutrients, water availability, and Rs in southern China. Results indicated that after 21 years of cultivation, CO and CB significantly increased total soil carbon (TC), total soil nitrogen (TN), and soil organic matter (OM) at 0–20 cm and 20–40 cm, both at upslope and downslope compared with bare soil (CK). However, soil moisture (SM), dissolved organic carbon (DOC), and microbial biomass carbon (MBC) decreased under CB. In addition, no significant variation was found in soil pH between CK, CO, and CB. Across incubation time (56 days), Rs decreased exponentially with incubation time and CB showed the highest Rs rate irrespective of soil depth or topography. Linear regression further showed TC and TN as the two major factors influencing Rs upslope, while DOC was the dominant factor in regulating Rs downslope. These findings demonstrated that long-term cultivation of citrus significantly changed soil nutrients, water availability, and Rs rate. PMID:26368561

Investigation of the Behavior of Hardening Masonry Exposed to Variable Stresses

PubMed Central

Šlivinskas, Tomas; Jonaitis, Bronius; Marčiukaitis, Jonas Gediminas

2018-01-01

This paper analyzes the behavior of masonry under variable loads during execution (construction stage). It specifies the creep coefficient for calcium silicate brick masonry, presenting the research data of masonry deformation under variable and constant long-term loads. The interaction of separate layers of composite material in masonry is introduced and the formulae for determining long-term deformations are offered. The research results of masonry’s compressive strength and deformation properties under variable and constant long-term loads are presented. These are then compared to calculated ones. According to the presented comparison, the calculated long-term deformations coincide quite well with those determined experimentally. PMID:29710802

Investigation of the Behavior of Hardening Masonry Exposed to Variable Stresses.

PubMed

Šlivinskas, Tomas; Jonaitis, Bronius; Marčiukaitis, Jonas Gediminas; Zavalis, Robertas

2018-04-28

This paper analyzes the behavior of masonry under variable loads during execution (construction stage). It specifies the creep coefficient for calcium silicate brick masonry, presenting the research data of masonry deformation under variable and constant long-term loads. The interaction of separate layers of composite material in masonry is introduced and the formulae for determining long-term deformations are offered. The research results of masonry’s compressive strength and deformation properties under variable and constant long-term loads are presented. These are then compared to calculated ones. According to the presented comparison, the calculated long-term deformations coincide quite well with those determined experimentally.

Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus.

PubMed

Rocchetti, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; Tronche, François; Levesque, Daniel; Moquin, Luc; Gratton, Alain; Wong, Tak Pan; Rubinstein, Marcelo; Giros, Bruno

2015-03-15

Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

26 CFR 54.4980B-2 - Plans that must comply.

Code of Federal Regulations, 2011 CFR

2011-04-01

... exception for qualified long-term care services is set forth in paragraph (e) of this Q&A-1, and for medical... all of the coverage provided under the plan is for qualified long-term care services (as defined in... whether substantially all of the coverage provided under the plan is for qualified long-term care services...

Long-term changes in soil organic carbon and nitrogen under semiarid tillage and cropping practices

USDA-ARS?s Scientific Manuscript database

Understanding long-term changes in soil organic carbon (SOC) and total soil nitrogen (TSN) is important for evaluating C fluxes and optimizing N management. We evaluated long-term SOC and TSN changes under dryland rotations for historical stubble-mulch (HSM) and graded terrace (GT) plots on a clay l...

Maintaining the pluripotency of mouse embryonic stem cells on gold nanoparticle layers with nanoscale but not microscale surface roughness.

PubMed

Lyu, Zhonglin; Wang, Hongwei; Wang, Yanyun; Ding, Kaiguo; Liu, Huan; Yuan, Lin; Shi, Xiujuan; Wang, Mengmeng; Wang, Yanwei; Chen, Hong

2014-06-21

Efficient control of the self-renewal and pluripotency maintenance of embryonic stem cell (ESC) is a prerequisite for translating stem cell technologies to clinical applications. Surface topography is one of the most important factors that regulates cell behaviors. In the present study, micro/nano topographical structures composed of a gold nanoparticle layer (GNPL) with nano-, sub-micro-, and microscale surface roughnesses were used to study the roles of these structures in regulating the behaviors of mouse ESCs (mESCs) under feeder-free conditions. The distinctive results from Oct-4 immunofluorescence staining and quantitative real-time polymerase chain reaction (qPCR) demonstrate that nanoscale and low sub-microscale surface roughnesses (Rq less than 392 nm) are conducive to the long-term maintenance of mESC pluripotency, while high sub-microscale and microscale surface roughnesses (Rq greater than 573 nm) result in a significant loss of mESC pluripotency and a faster undirectional differentiation, particularly in long-term culture. Moreover, the likely signalling cascades engaged in the topological sensing of mESCs were investigated and their role in affecting the maintenance of the long-term cell pluripotency was discussed by analyzing the expression of proteins related to E-cadherin mediated cell-cell adhesions and integrin-mediated focal adhesions (FAs). Additionally, the conclusions from MTT, cell morphology staining and alkaline phosphatase (ALP) activity assays show that the surface roughness can provide a potent regulatory signal for various mESC behaviors, including cell attachment, proliferation and osteoinduction.

26 CFR 1.613A-7 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... regulations thereunder— (a) Domestic. The term domestic, as applied to oil and gas wells (or to production..., as defined in section 638 and the regulations thereunder. (b) Natural gas. The term natural gas means... mineral or minerals produced. (d) Natural gas sold under a fixed contract. The term natural gas sold under...

FHF2 isoforms differentially regulate Nav1.6 mediated resurgent sodium currents in dorsal root ganglion neurons

PubMed Central

Barbosa, Cindy; Xiao, Yucheng; Johnson, Andrew J.; Xie, Wenrui; Strong, Judith A.; Zhang, Jun-Ming; Cummins, Theodore R.

2017-01-01

Nav1.6 and Nav1.6 mediated resurgent currents have been implicated in several pain pathologies. However, our knowledge of how fast resurgent currents are modulated in neurons is limited. Our study explored the potential regulation of Nav1.6 mediated resurgent currents by isoforms of Fibroblast growth Factor Homologous factor 2 (FHF2) in an effort to address the gap in our knowledge. FHF2 isoforms colocalize with Nav1.6 in peripheral sensory neurons. Cell line studies suggest that these proteins differentially regulate inactivation. In particular, FHF2A mediates long-term inactivation, a mechanism proposed to compete with the open-channel blocker mechanism that mediates resurgent currents. On the other hand, FHF2B lacks the ability to mediate long-term inactivation and may delay inactivation favoring open-channel block. Based on these observations, we hypothesized that FHF2A limits resurgent currents, whereas, FHF2B enhances resurgent currents. Overall our results suggest that FHF2A negatively regulates fast resurgent current by enhancing long-term inactivation and delaying recovery. In contrast FHF2B positively regulated resurgent current and did not alter long-term inactivation. Chimeric constructs of FHF2A and Navβ4 (likely the endogenous open channel blocker in sensory neurons) exhibited differential effects on resurgent currents suggesting that specific regions within FHF2A and Navβ4 have important regulatory functions. Our data also indicate FHFAs and FHF2B isoform expression are differentially regulated in a radicular pain model and that associated neuronal hyperexcitability is substantially attenuated by a FHFA peptide. As such, these findings suggest that FHF2A and FHF2B regulate resurgent current in sensory neurons and may contribute to hyperexcitability associated with some pain pathologies. PMID:27999940

Population regulation in a changing environment: Long-term changes in growth, condition and survival of sprat, Sprattus sprattus L. in the Bristol Channel, UK

NASA Astrophysics Data System (ADS)

Henderson, Peter A.; Henderson, Rowena C.

2017-02-01

Sprat, Sprattus sprattus, is the dominant pelagic species in British inshore and estuarine waters. Within the Bristol Channel the population is almost totally composed of fish < 3 years old with the adults overwintering in Bridgwater Bay. Sprat follow regular seasonal migrations and occasionally form huge aggregations which together generate considerable between sample variability. Using a 36-year monthly time series collected in the Bristol Channel since 1980, together with two periods of intensive daily and weekly sampling, sprat growth is shown to have declined almost linearly over the last 36 years coincident with increasing late summer-autumn seawater temperatures. Longevity has also declined, with age 3 + sprat > 140 mm standard length lost to the population by 1999. Further, adult condition, measured as the average weight of a 103 mm standard length adult, declined rapidly from 13.7 g in 2007 to 9 g in 2011. Despite these changes, which would have reduced age-specific fecundity, a sign-rank test showed abundance of adult sprat has shown no long-term trend and Bulmer's test indicates density-dependent regulation is operating. While sprat recruitment is shown to be responding to the sunspot cycle, the North Atlantic Oscillation and sea water temperature, the impact of these variables on adult population density is damped because of density-dependent regulation. The result is that sprat respond to environmental change with large changes in their growth and condition, but the adult abundance is constrained and shows no long-term trend. Recruitment was modelled by combining a Ricker curve with terms for the response of sprat to solar activity, the North Atlantic Oscillation and spring temperature. It is shown that the stock-recruitment relationship does not form a simple curve, but is bounded within a region in which the upper and lower constraints are defined by environmental conditions. Within this bounded region the population trajectory under differing environmental regimes can be predicted.

Long term effects of neonatal hypoglycaemia on pancreatic function.

PubMed

Anju, T R; Paulose, C S

2015-02-01

Low blood glucose in neonates predisposes to long term pancreatic damage. We focused on evaluating long term consequences of neonatal hypoglycaemia in pancreatic functions. Pancreatic function was analysed by measuring DNA/protein synthesis, glucose/ATP uptake in vitro. Gene expression of Pdx1, NeuroD1, Pax4, Bax, caspase 3, Beclin1 were done. Muscarinic receptors were analysed by radio receptor assay. Overall pancreatic efficiency was reduced in one-month-old rats exposed to neonatal hypoglycaemia as indicated by decreased DNA/protein synthesis and glucose/ATP uptake in vitro. Both Pdx1 and Neuro D1 expression were significantly down-regulated whereas Pax4 was up-regulated. Up-regulated Bax, caspase 3 and beclin1 along with reduced muscarinic receptors accounts for activation of cell death pathways. The study revealed a drastic reduction in pancreatic functions along with activation of apoptotic factors in one month old rats exposed to neonatal hypoglycaemia.

Nitrogen enrichment regulates calcium sources in forests

USGS Publications Warehouse

Hynicka, Justin D.; Pett-Ridge, Julie C.; Perakis, Steven

2016-01-01

Nitrogen (N) is a key nutrient that shapes cycles of other essential elements in forests, including calcium (Ca). When N availability exceeds ecosystem demands, excess N can stimulate Ca leaching and deplete Ca from soils. Over the long term, these processes may alter the proportion of available Ca that is derived from atmospheric deposition vs. bedrock weathering, which has fundamental consequences for ecosystem properties and nutrient supply. We evaluated how landscape variation in soil N, reflecting long-term legacies of biological N fixation, influenced plant and soil Ca availability and ecosystem Ca sources across 22 temperate forests in Oregon. We also examined interactions between soil N and bedrock Ca using soil N gradients on contrasting basaltic vs. sedimentary bedrock that differed 17-fold in underlying Ca content. We found that low-N forests on Ca-rich basaltic bedrock relied strongly on Ca from weathering, but that soil N enrichment depleted readily weatherable mineral Ca and shifted forest reliance toward atmospheric Ca. Forests on Ca-poor sedimentary bedrock relied more consistently on atmospheric Ca across all levels of soil N enrichment. The broad importance of atmospheric Ca was unexpected given active regional uplift and erosion that are thought to rejuvenate weathering supply of soil minerals. Despite different Ca sources to forests on basaltic vs. sedimentary bedrock, we observed consistent declines in plant and soil Ca availability with increasing N, regardless of the Ca content of underlying bedrock. Thus, traditional measures of Ca availability in foliage and soil exchangeable pools may poorly reflect long-term Ca sources that sustain soil fertility. We conclude that long-term soil N enrichment can deplete available Ca and cause forests to rely increasingly on Ca from atmospheric deposition, which may limit ecosystem Ca supply in an increasingly N-rich world.

Regulatory Requirements and Technical Analysis for Department of Energy Regulated Performance Assessments of Shallow-Trench Disposal of Low-Level Radioactive Waste at the Nevada Test Site

NASA Astrophysics Data System (ADS)

Crowe, B.; Black, P.; Tauxe, J.; Yucel, V.; Rawlinson, S.; Colarusso, A.; DiSanza, F.

2001-12-01

The National Nuclear Security Administration, Nevada Operations Office (NNSA/NV) operates and maintains two active facilities on the Nevada Test Site (NTS) that dispose Department of Energy (DOE) defense-generated low-level radioactive (LLW), mixed radioactive, and classified waste in shallow trenches, pits and large-diameter boreholes. The operation and maintenance of the LLW disposal sites are self-regulated under DOE Order 435.1, which requires review of a Performance Assessment for four performance objectives: 1) all pathways 25 mrem/yr limit; 2) atmospheric pathways 10 mrem/yr limit; 3) radon flux density of 20 pCi/m2/s; and 4) groundwater resource protection (Safe Drinking Water Act; 4 mrem/yr limit). The inadvertent human intruder is protected under a dual 500- and 100-mrem limit (acute and chronic exposure). In response to the Defense Nuclear Facilities Safety Board Recommendation 92 2, a composite analysis is required that must examine all interacting sources for compliance against both 30 and 100 mrem/yr limits. A small component of classified transuranic waste is buried at intermediate depths in 3-meter diameter boreholes at the Area 5 LLW disposal facility and is assessed through DOE-agreement against the requirements of the Environmental Protection Agency (EPA)'s 40 CFR 191. The hazardous components of mixed LLW are assessed against RCRA requirements. The NTS LLW sites fall directly under three sets of federal regulations and the regulatory differences result not only in organizational challenges, but also in different decision objectives and technical paths to completion. The DOE regulations require deterministic analysis for a 1,000-year compliance assessment supplemented by probabilistic analysis under a long-term maintenance program. The EPA regulations for TRU waste are probabilistically based for a compliance interval of 10,000 years. Multiple steps in the assessments are strongly dependent on assumptions for long-term land use policies. Integrating the different requirements into coherent and consistent sets of conceptual models of the disposal setting, alternative scenarios, and system models of fate, transport and dose-based assessments is technically challenging. Environmental assessments for these sites must be broad-based and flexible to accommodate the multiple objectives.

Short- and long-term antidepressant effects of ketamine in a rat chronic unpredictable stress model.

PubMed

Jiang, Yinghong; Wang, Yiqiang; Sun, Xiaoran; Lian, Bo; Sun, Hongwei; Wang, Gang; Du, Zhongde; Li, Qi; Sun, Lin

2017-08-01

This research was aimed to evaluate the behaviors of short- or long-term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS). Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory. After 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43-75). The influence of ketamine on behavioral reactivity was assessed 24 hr (short-term) or 7 weeks after ketamine treatment (long-term). Behavioral tests used to assess the effects of these treatments included the sucrose preference (SP), open field (OF), elevated plus maze (EPM), forced swimming (FS), and water maze (WM) to detect anxiety-like behavior (OF and EPM), forced swimming (FS), and water maze (WM). Results: Short-term ketamine administration resulted in increases of body weight gain, higher sensitivity to sucrose, augmented locomotor activity in the OF, more entries into the open arms of the EPM, along increased activity in the FS test; all responses indicative of reductions in depression/despair in anxiety-eliciting situations. No significant differences in these behaviors were obtained under conditions of long-term ketamine administration ( p  > .05). The CUS + Ketamine group showed significantly increased activity as compared with the CUS + Vehicle group for analysis of the long-term effects of ketamine (* p  < .05). Nor were significant differences obtained in learning and memory performance in rats receiving ketamine ( p  > .05). Taken together these findings demonstrate that a short-term administration of ketamine induced rapid antidepressant-like effects in adult male rats exposed to CUS conditions, effects that were not observed in response to the long-term treatment regime.

Altered Gene Regulation and Synaptic Morphology in "Drosophila" Learning and Memory Mutants

ERIC Educational Resources Information Center

Guan, Zhuo; Buhl, Lauren K.; Quinn, William G.; Littleton, J. Troy

2011-01-01

Genetic studies in "Drosophila" have revealed two separable long-term memory pathways defined as anesthesia-resistant memory (ARM) and long-lasting long-term memory (LLTM). ARM is disrupted in "radish" ("rsh") mutants, whereas LLTM requires CREB-dependent protein synthesis. Although the downstream effectors of ARM and LLTM are distinct, pathways…

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains.

PubMed

Sudhakaran, Indulekha P; Ramaswami, Mani

2017-05-04

Long-term and short-term memories differ primarily in the duration of their retention. At a molecular level, long-term memory (LTM) is distinguished from short-term memory (STM) by its requirement for new gene expression. In addition to transcription (nuclear gene expression) the translation of stored mRNAs is necessary for LTM formation. The mechanisms and functions for temporal and spatial regulation of mRNAs required for LTM is a major contemporary problem, of interest from molecular, cell biological, neurobiological and clinical perspectives. This review discusses primary evidence in support for translational regulatory events involved in LTM and a model in which different phases of translation underlie distinct phases of consolidation of memories. However, it focuses largely on mechanisms of memory persistence and the role of prion-like domains in this defining aspect of long-term memory. We consider primary evidence for the concept that Cytoplasmic Polyadenylation Element Binding (CPEB) protein enables the persistence of formed memories by transforming in prion-like manner from a soluble monomeric state to a self-perpetuating and persistent polymeric translationally active state required for maintaining persistent synaptic plasticity. We further discuss prion-like domains prevalent on several other RNA-binding proteins involved in neuronal translational control underlying LTM. Growing evidence indicates that such RNA regulatory proteins are components of mRNP (RiboNucleoProtein) granules. In these proteins, prion-like domains, being intrinsically disordered, could mediate weak transient interactions that allow the assembly of RNP granules, a source of silenced mRNAs whose translation is necessary for LTM. We consider the structural bases for RNA granules formation as well as functions of disordered domains and discuss how these complicate the interpretation of existing experimental data relevant to general mechanisms by which prion-domain containing RBPs function in synapse specific plasticity underlying LTM.

Down-regulation of let-7 microRNA increased K-ras expression in lung damage induced by radon.

PubMed

Chen, Zhihai; Wang, Dapeng; Gu, Chao; Liu, Xing; Pei, Weiwei; Li, Jianxiang; Cao, Yi; Jiao, Yang; Tong, Jian; Nie, Jihua

2015-09-01

Radon has long been recognized as a human carcinogen leading to lung cancer, but the underlying mechanisms remain obscure. Recent studies have shown that the let-7 microRNA and K-ras play an important role in the development of various cancers. However, the exact role between let-7 and K-ras in radon induced lung damage has not been explored so far. In the present study, wistar rats and human bronchial epithelial (HBE) cells were long-term exposed to radon, and then alterations in histological pathology of rat lung tissue, ROS, antioxidant enzymes activities and clonogenic formation in HBE cells, as well as changes in let-7 and K-ras expression were determined to observe the adverse effects induced by radon. The results showed that long-term exposure to radon produced severe lung damage in rats, significantly increased ROS production and clonogenic formation ratios and decreased SOD activities in HBE cells. In addition, an obvious down-regulation of let-7 and up-regulation of K-ras were also revealed both in mRNA and in protein level in lung tissue of rats and HBE cells exposed to radon. Furthermore, a significant down-regulation of K-ras was then confirmed in both let-7b-3p and let-7a-2-3p transfected HBE cells. Taken together, the present results propose an involvement of let-7 microRNA and K-ras in radon induced lung damage both in vivo and in vitro, which may thus be of potential value in early diagnosis and therapy of radon-induced lung tumorgenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

Arp2/3 and VASP Are Essential for Fear Memory Formation in Lateral Amygdala.

PubMed

Basu, Sreetama; Kustanovich, Irina; Lamprecht, Raphael

2016-01-01

The actin cytoskeleton is involved in key neuronal functions such as synaptic transmission and morphogenesis. However, the roles and regulation of actin cytoskeleton in memory formation remain to be clarified. In this study, we unveil the mechanism whereby actin cytoskeleton is regulated to form memory by exploring the roles of the major actin-regulatory proteins Arp2/3, VASP, and formins in long-term memory formation. Inhibition of Arp2/3, involved in actin filament branching and neuronal morphogenesis, in lateral amygdala (LA) with the specific inhibitor CK-666 during fear conditioning impaired long-term, but not short-term, fear memory. The inactive isomer CK-689 had no effect on memory formation. We observed that Arp2/3 is colocalized with the actin-regulatory protein profilin in LA neurons of fear-conditioned rats. VASP binding to profilin is needed for profilin-mediated stabilization of actin cytoskeleton and dendritic spine morphology. Microinjection of poly-proline peptide [G(GP 5 ) 3 ] into LA, to interfere with VASP binding to profilin, impaired long-term but not short-term fear memory formation. Control peptide [G(GA 5 ) 3 ] had no effect. Inhibiting formins, which regulate linear actin elongation, in LA during fear conditioning by microinjecting the formin-specific inhibitor SMIFH2 into LA had no effect on long-term fear memory formation. We conclude that Arp2/3 and VASP, through the profilin binding site, are essential for the formation of long-term fear memory in LA and propose a model whereby these proteins subserve cellular events, leading to memory consolidation.

Simulation of Halocarbon Production and Emissions and Effects on Ozone Depletion

PubMed

Holmes; Ellis

1997-09-01

/ This paper describes an integrated model that simulates future halocarbon production/emissions and potential ozone depletion. Applications and historical production levels for various halocarbons are discussed first. A framework is then presented for modeling future halocarbon impacts incorporating differences in underlying demands, applications, regulatory mandates, and environmental characteristics. The model is used to simulate the potential impacts of several prominent issues relating to halocarbon production, regulation, and environmental interactions, notably: changes in agricultural methyl bromide use, increases in effectiveness of bromine for ozone depletion, modifications to the elimination schedule for HCFCs, short-term expansion of CFC demand in low use compliance countries, and delays in Russian Federation compliance. Individually, each issue does not unequivocally represent a significant likely increase in long-term atmospheric halogen loading and stratospheric ozone depletion. In combination, however, these impacts could increase peak halogen concentrations and long-term integral halogen loading, resulting in higher levels of stratospheric ozone depletion and longer exposure to increased levels of UV radiation.KEY WORDS: Halocarbons; Ozone depletion; Montreal Protocol; Integrated assessment

Five Conditions Commonly Used to Down-regulate Tor Complex 1 Generate Different Physiological Situations Exhibiting Distinct Requirements and Outcomes*

PubMed Central

Tate, Jennifer J.; Cooper, Terrance G.

2013-01-01

Five different physiological conditions have been used interchangeably to establish the sequence of molecular events needed to achieve nitrogen-responsive down-regulation of TorC1 and its subsequent regulation of downstream reporters: nitrogen starvation, methionine sulfoximine (Msx) addition, nitrogen limitation, rapamycin addition, and leucine starvation. Therefore, we tested a specific underlying assumption upon which the interpretation of data generated by these five experimental perturbations is premised. It is that they generate physiologically equivalent outcomes with respect to TorC1, i.e. its down-regulation as reflected by TorC1 reporter responses. We tested this assumption by performing head-to-head comparisons of the requirements for each condition to achieve a common outcome for a downstream proxy of TorC1 inactivation, nuclear Gln3 localization. We demonstrate that the five conditions for down-regulating TorC1 do not elicit physiologically equivalent outcomes. Four of the methods exhibit hierarchical Sit4 and PP2A phosphatase requirements to elicit nuclear Gln3-Myc13 localization. Rapamycin treatment required Sit4 and PP2A. Nitrogen limitation and short-term nitrogen starvation required only Sit4. G1 arrest-correlated, long-term nitrogen starvation and Msx treatment required neither PP2A nor Sit4. Starving cells of leucine or treating them with leucyl-tRNA synthetase inhibitors did not elicit nuclear Gln3-Myc13 localization. These data indicate that the five commonly used nitrogen-related conditions of down-regulating TorC1 are not physiologically equivalent and minimally involve partially differing regulatory mechanisms. Further, identical requirements for Msx treatment and long-term nitrogen starvation raise the possibility that their effects are achieved through a common regulatory pathway with glutamine, a glutamate or glutamine metabolite level as the sensed metabolic signal. PMID:23935103

26 CFR 1.7702B-2 - Special rules for pre-1997 long-term care insurance contracts.

Code of Federal Regulations, 2011 CFR

2011-04-01

... treated as a qualified long-term care insurance contract. Example 2. (i) The facts are the same as in Example 1, except that the insurance coverage under the contract does not become effective until March 1.... Example 3. (i) B, an individual, is the policyholder under a long-term care insurance contract purchased...

The Long-Term Budget Outlook

DTIC Science & Technology

2005-12-01

Revenues Under CBO’s Long-Term Budget Scenarios 56A-8. Real Gross Domestic Product Under CBO’s Long-Term Budget Scenarios 57A-9. Total Surplus or...scenarios suggest that total federal spending for Medicare and Medicaid in 2050 could range anywhere from 7 percent of gross domestic product (GDP)—a...see the Congressional Budget Office’s glossary of budgetary and economic terms, available at www.cbo.gov. 2. The future path of productivity growth

The Epidemiology of Longevity and Exceptional Survival

PubMed Central

Newman, Anne B.; Murabito, Joanne M.

2013-01-01

The field of the “epidemiology of longevity” has been expanding rapidly in recent years. Several long-term cohort studies have followed older adults long enough to identify the most long-lived and to define many factors that lead to a long life span. Very long-lived people such as centenarians have been examined using case-control study designs. Both cohort and case-control studies have been the subject of genome-wide association studies that have identified genetic variants associated with longevity. With growing recognition of the importance of rare variations, family studies of longevity will be useful. Most recently, exome and whole-genome sequencing, gene expression, and epigenetic studies have been undertaken to better define functional variation and regulation of the genome. In this review, we consider how these studies are leading to a deeper understanding of the underlying biologic pathways to longevity. PMID:23372024

Transcription Factors in Long-Term Memory and Synaptic Plasticity

PubMed Central

Alberini, Cristina M.

2013-01-01

Transcription is a molecular requisite for long-term synaptic plasticity and long-term memory formation. Thus, in the last several years, one main interest of molecular neuroscience has been the identification of families of transcription factors that are involved in both of these processes. Transcription is a highly regulated process that involves the combined interaction and function of chromatin and many other proteins, some of which are essential for the basal process of transcription, while others control the selective activation or repression of specific genes. These regulated interactions ultimately allow a sophisticated response to multiple environmental conditions, as well as control of spatial and temporal differences in gene expression. Evidence based on correlative changes in expression, genetic mutations, and targeted molecular inhibition of gene expression have shed light on the function of transcription in both synaptic plasticity and memory formation. This review provides a brief overview of experimental work showing that several families of transcription factors, including CREB, C/EBP, Egr, AP-1, and Rel have essential functions in both processes. The results of this work suggest that patterns of transcription regulation represent the molecular signatures of long-term synaptic changes and memory formation. PMID:19126756

Central role for ferritin in the day/night regulation of iron homeostasis in marine phytoplankton

PubMed Central

Botebol, Hugo; Lesuisse, Emmanuel; Šuták, Robert; Six, Christophe; Lozano, Jean-Claude; Schatt, Philippe; Vergé, Valérie; Kirilovsky, Amos; Morrissey, Joe; Léger, Thibaut; Camadro, Jean-Michel; Gueneugues, Audrey; Bowler, Chris; Blain, Stéphane; Bouget, François-Yves

2015-01-01

In large regions of the open ocean, iron is a limiting resource for phytoplankton. The reduction of iron quota and the recycling of internal iron pools are among the diverse strategies that phytoplankton have evolved to allow them to grow under chronically low ambient iron levels. Phytoplankton species also have evolved strategies to cope with sporadic iron supply such as long-term storage of iron in ferritin. In the picophytoplanktonic species Ostreococcus we report evidence from observations both in the field and in laboratory cultures that ferritin and the main iron-binding proteins involved in photosynthesis and nitrate assimilation pathways show opposite diurnal expression patterns, with ferritin being maximally expressed during the night. Biochemical and physiological experiments using a ferritin knock-out line subsequently revealed that this protein plays a central role in the diel regulation of iron uptake and recycling and that this regulation of iron homeostasis is essential for cell survival under iron limitation. PMID:26553998

Central role for ferritin in the day/night regulation of iron homeostasis in marine phytoplankton.

PubMed

Botebol, Hugo; Lesuisse, Emmanuel; Šuták, Robert; Six, Christophe; Lozano, Jean-Claude; Schatt, Philippe; Vergé, Valérie; Kirilovsky, Amos; Morrissey, Joe; Léger, Thibaut; Camadro, Jean-Michel; Gueneugues, Audrey; Bowler, Chris; Blain, Stéphane; Bouget, François-Yves

2015-11-24

In large regions of the open ocean, iron is a limiting resource for phytoplankton. The reduction of iron quota and the recycling of internal iron pools are among the diverse strategies that phytoplankton have evolved to allow them to grow under chronically low ambient iron levels. Phytoplankton species also have evolved strategies to cope with sporadic iron supply such as long-term storage of iron in ferritin. In the picophytoplanktonic species Ostreococcus we report evidence from observations both in the field and in laboratory cultures that ferritin and the main iron-binding proteins involved in photosynthesis and nitrate assimilation pathways show opposite diurnal expression patterns, with ferritin being maximally expressed during the night. Biochemical and physiological experiments using a ferritin knock-out line subsequently revealed that this protein plays a central role in the diel regulation of iron uptake and recycling and that this regulation of iron homeostasis is essential for cell survival under iron limitation.

Erythropoietin regulations in humans under different environmental and experimental conditions.

PubMed

Gunga, H-C; Kirsch, K A; Roecker, L; Kohlberg, E; Tiedemann, J; Steinach, M; Schobersberger, W

2007-09-30

In the adult human, the kidney is the main organ for the production and release of erythropoietin (EPO). EPO is stimulating erythropoiesis by increasing the proliferation, differentiation and maturation of the erythroid precursors. In the last decades, enormous efforts were made in the purification, molecular encoding and description of the EPO gene. This led to an incredible increase in the understanding of the EPO-feedback-regulation loop at a molecular level, especially the oxygen-dependent EPO gene expression, a key function in the regulation loop. However, studies in humans at a systemic level are still very scanty. Therefore, it is the purpose of the present review to report on the main recent investigations on EPO production and release in humans under different environmental and experimental conditions, including: (i) studies on EPO circadian, monthly and even annual variations, (ii) studies in connection with short-, medium- and long-term exercise at sea-level which will be followed (iii) by studies performed at moderate and high altitude.

LncRNA pathway involved in premature preterm rupture of membrane (PPROM): an epigenomic approach to study the pathogenesis of reproductive disorders.

PubMed

Luo, Xiucui; Shi, Qingxi; Gu, Yang; Pan, Jing; Hua, Maofang; Liu, Meilin; Dong, Ziqing; Zhang, Meijiao; Wang, Leilei; Gu, Ying; Zhong, Julia; Zhao, Xinliang; Jenkins, Edmund C; Brown, W Ted; Zhong, Nanbert

2013-01-01

Preterm birth (PTB) is a live birth delivered before 37 weeks of gestation (GW). About one-third of PTBs result from the preterm premature rupture of membranes (PPROM). Up to the present, the pathogenic mechanisms underlying PPROM are not clearly understood. Here, we investigated the differential expression of long chain non-coding RNAs (lncRNAs) in placentas of PTBs with PPROM, and their possible involvement in the pathogenic pathways leading to PPROM. A total number of 1954, 776, and 1050 lncRNAs were identified with a microarray from placentas of PPROM (group A), which were compared to full-term birth (FTB) (group B), PTB (group C), and premature rupture of membrane (PROM) (group D) at full-term, respectively. Instead of investigating the individual pathogenic role of each lncRNA involved in the molecular mechanism underlying PPROM, we have focused on investigating the metabolic pathways and their functions to explore what is the likely association and how they are possibly involved in the development of PPROM. Six groups, including up-regulation and down-regulation in the comparisons of A vs. B, A vs. C, and A vs. D, of pathways were analyzed. Our results showed that 22 pathways were characterized as up-regulated 7 down-regulated in A vs. C, 18 up-regulated and 15 down-regulated in A vs. D, and 33 up-regulated and 7 down-regulated in A vs. B. Functional analysis showed pathways of infection and inflammatory response, ECM-receptor interactions, apoptosis, actin cytoskeleton, and smooth muscle contraction are the major pathogenic mechanisms involved in the development of PPROM. Characterization of these pathways through identification of lncRNAs opened new avenues for further investigating the epigenomic mechanisms of lncRNAs in PPROM as well as PTB.

Long-Term Live Cell Imaging of Cell Migration: Effects of Pathogenic Fungi on Human Epithelial Cell Migration.

PubMed

Wöllert, Torsten; Langford, George M

2016-01-01

Long-term live cell imaging was used in this study to determine the responses of human epithelial cells to pathogenic biofilms formed by Candida albicans. Epithelial cells of the skin represent the front line of defense against invasive pathogens such as C. albicans but under certain circumstances, especially when the host's immune system is compromised, the skin barrier is breached. The mechanisms by which the fungal pathogen penetrates the skin and invade the deeper layers are not fully understood. In this study we used keratinocytes grown in culture as an in vitro model system to determine changes in host cell migration and the actin cytoskeleton in response to virulence factors produced by biofilms of pathogenic C. albicans. It is clear that changes in epithelial cell migration are part of the response to virulence factors secreted by biofilms of C. albicans and the actin cytoskeleton is the downstream effector that mediates cell migration. Our goal is to understand the mechanism by which virulence factors hijack the signaling pathways of the actin cytoskeleton to alter cell migration and thereby invade host tissues. To understand the dynamic changes of the actin cytoskeleton during infection, we used long-term live cell imaging to obtain spatial and temporal information of actin filament dynamics and to identify signal transduction pathways that regulate the actin cytoskeleton and its associated proteins. Long-term live cell imaging was achieved using a high resolution, multi-mode epifluorescence microscope equipped with specialized light sources, high-speed cameras with high sensitivity detectors, and specific biocompatible fluorescent markers. In addition to the multi-mode epifluorescence microscope, a spinning disk confocal long-term live cell imaging system (Olympus CV1000) equipped with a stage incubator to create a stable in vitro environment for long-term real-time and time-lapse microscopy was used. Detailed descriptions of these two long-term live cell imaging systems are provided.

Deregulating electricity in the American states

NASA Astrophysics Data System (ADS)

Terbush, Thomas Lee

This dissertation develops nine stylized facts that summarize the major consequences of deregulation and tests these against recent experience in the electric utility industry. The experience of the electric utility industry matches the predictions of the stylized facts, except in one instance: although real electricity prices fell between 1982 and 1999, real prices fell less in states that deregulated. This dissertation presents three possible explanations for this discrepancy. First, through dynamic efficiency, consumers may benefit in the long run through lower rates and better service in the electricity market, or deregulation may be a public good that benefits electricity consumers through economy-wide improvements in efficiency. Second, higher prices may be a long-run outcome as predicted by the theory of the second best. Or third, both regulators and utilities may use deregulation to generate new rents. Because the original rents from regulation had dissipated, new rents could be generated under deregulation by making consumers pay off the utilities and then creating more new rents through re-regulation of the industry. Close examination tends to support the first and third explanations, although the second-best explanation cannot yet be ruled out completely. Higher prices appear to be a transitional phenomenon, resulting from a short-term payoff from consumers to incumbent utilities that was required to move deregulation forward. This payoff occurs as residential and commercial consumers bear relatively higher rates over three to five years to compensate utilities for stranded costs, investments thought to be unrecoverable under full competition. All states are benefiting from deregulation, but states that are deregulating are benefiting less while stranded costs are being recovered. This dissertation also examines California electricity deregulation and finds that the experience in California conforms with to the stylized facts, and that certain structural, demand and supply factors caused the electricity crisis in 2000 and 2001. The most important factor was the disallowance of long-term contracts and other instruments for shedding price risk, which discouraged the construction of new generating plants.

[Regulation, innovation, and improvement of health care. The pharmaceutical sector].

PubMed

López-Casasnovas, Guillem

2008-01-01

The paper comments on present and future scenarios for the pharmaceutical sector in Spain, framed a highly regulated system. So far the drug industry has evolved under the short term public financial constraints for additional health care spending and the long term efforts to innovate. This has not proved to offer a stable setting for the relationship between the industry and Health Authorities. The author offers from the economic analysis and a subjective appraisal from his experience some recommendations for regulatory changes in order to better align the incentives of the parts for improving the health system as a whole. The basic point is that 'consumption levels' (quantities) and not (unit costs) are the main challenge to tackle today in our Public Health Care system, and for this the decentralisation of financial responsibility is not in itself 'the' problem but it may well be a part of the solution.

Temporal profiling of gene networks associated with the late phase of long-term potentiation in vivo.

PubMed

Ryan, Margaret M; Ryan, Brigid; Kyrke-Smith, Madeleine; Logan, Barbara; Tate, Warren P; Abraham, Wickliffe C; Williams, Joanna M

2012-01-01

Long-term potentiation (LTP) is widely accepted as a cellular mechanism underlying memory processes. It is well established that LTP persistence is strongly dependent on activation of constitutive and inducible transcription factors, but there is limited information regarding the downstream gene networks and controlling elements that coalesce to stabilise LTP. To identify these gene networks, we used Affymetrix RAT230.2 microarrays to detect genes regulated 5 h and 24 h (n = 5) after LTP induction at perforant path synapses in the dentate gyrus of awake adult rats. The functional relationships of the differentially expressed genes were examined using DAVID and Ingenuity Pathway Analysis, and compared with our previous data derived 20 min post-LTP induction in vivo. This analysis showed that LTP-related genes are predominantly upregulated at 5 h but that there is pronounced downregulation of gene expression at 24 h after LTP induction. Analysis of the structure of the networks and canonical pathways predicted a regulation of calcium dynamics via G-protein coupled receptors, dendritogenesis and neurogenesis at the 5 h time-point. By 24 h neurotrophin-NFKB driven pathways of neuronal growth were identified. The temporal shift in gene expression appears to be mediated by regulation of protein synthesis, ubiquitination and time-dependent regulation of specific microRNA and histone deacetylase expression. Together this programme of genomic responses, marked by both homeostatic and growth pathways, is likely to be critical for the consolidation of LTP in vivo.

KCNQ Channels Regulate Age-Related Memory Impairment

PubMed Central

Cavaliere, Sonia; Malik, Bilal R.; Hodge, James J. L.

2013-01-01

In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ) when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment. PMID:23638087

Early and delayed long-term transcriptional changes and short-term transient responses during cold acclimation in olive leaves

PubMed Central

Leyva-Pérez, María de la O; Valverde-Corredor, Antonio; Valderrama, Raquel; Jiménez-Ruiz, Jaime; Muñoz-Merida, Antonio; Trelles, Oswaldo; Barroso, Juan Bautista; Mercado-Blanco, Jesús; Luque, Francisco

2015-01-01

Low temperature severely affects plant growth and development. To overcome this constraint, several plant species from regions having a cool season have evolved an adaptive response, called cold acclimation. We have studied this response in olive tree (Olea europaea L.) cv. Picual. Biochemical stress markers and cold-stress symptoms were detected after the first 24 h as sagging leaves. After 5 days, the plants were found to have completely recovered. Control and cold-stressed plants were sequenced by Illumina HiSeq 1000 paired-end technique. We also assembled a new olive transcriptome comprising 157,799 unigenes and found 6,309 unigenes differentially expressed in response to cold. Three types of response that led to cold acclimation were found: short-term transient response, early long-term response, and late long-term response. These subsets of unigenes were related to different biological processes. Early responses involved many cold-stress-responsive genes coding for, among many other things, C-repeat binding factor transcription factors, fatty acid desaturases, wax synthesis, and oligosaccharide metabolism. After long-term exposure to cold, a large proportion of gene down-regulation was found, including photosynthesis and plant growth genes. Up-regulated genes after long-term cold exposure were related to organelle fusion, nucleus organization, and DNA integration, including retrotransposons. PMID:25324298

Social isolation mediated anxiety like behavior is associated with enhanced expression and regulation of BDNF in the female mouse brain.

PubMed

Kumari, Anita; Singh, Padmanabh; Baghel, Meghraj Singh; Thakur, M K

2016-05-01

Adverse early life experience is prominent risk factors for numerous psychiatric illnesses, including mood and anxiety disorders. It imposes serious long-term costs on the individual as well as health and social systems. Hence, developing therapies that prevent the long-term consequences of early life stress is of utmost importance, and necessitates a better understanding of the mechanisms by which early life stress triggers long-lasting alterations in gene expression and behavior. Post-weaning isolation rearing of rodents models the behavioral consequences of adverse early life experiences in humans and it is reported to cause anxiety like behavior which is more common in case of females. Therefore, in the present study, we have studied the impact of social isolation of young female mice for 8weeks on the anxiety like behavior and the underlying molecular mechanism. Elevated plus maze and open field test revealed that social isolation caused anxiety like behavior. BDNF, a well-known molecule implicated in the anxiety like behavior, was up-regulated both at the message and protein level in cerebral cortex by social isolation. CREB-1 and CBP, which play a crucial role in BDNF transcription, were up-regulated at mRNA level in cerebral cortex by social isolation. HDAC-2, which negatively regulates BDNF expression, was down-regulated at mRNA and protein level in cerebral cortex by social isolation. Furthermore, BDNF acts in concert with Limk-1, miRNA-132 and miRNA-134 for the regulation of structural and morphological plasticity. Social isolation resulted in up-regulation of Limk-1 mRNA and miRNA-132 expression in the cerebral cortex. MiRNA-134, which inhibits the translation of Limk-1, was decreased in cerebral cortex by social isolation. Taken together, our study suggests that social isolation mediated anxiety like behavior is associated with up-regulation of BDNF expression and concomitant increase in the expression of CBP, CREB-1, Limk-1 and miRNA-132, and decrease in the expression of HDAC-2 and miRNA-134 in the cerebral cortex. Copyright © 2016. Published by Elsevier Inc.

Too proud to regulate: The differential effect of pride versus joy on children's ability to delay gratification.

PubMed

Shimoni, Einav; Asbe, Marwa; Eyal, Tal; Berger, Andrea

2016-01-01

We examined the effect of the distinct positive emotions pride and joy on children's self-regulation, focusing on their ability to delay gratification (i.e., resist a temptation in favor of a long-term goal). We hypothesized that because pride corresponds to the attainment of long-term goals and joy corresponds to the attainment of immediate desires, the experience of pride may signal sufficient progress toward a long-term goal, resulting in less delay of gratification than the experience of joy. To test this hypothesis, we induced an experience of pride or joy in 8-year-old children. At this age, the ability to self-regulate--and to experience pride and joy distinctively--is relatively mature. We then measured performance in a delay discounting task. We found that, compared with the joy condition and a control condition, children who experienced pride performed worse on the delay discounting task (p=.045), indicating poorer self-regulation. This result suggests that emotions may function as cues for sufficient goal pursuit, thereby influencing self-regulation from a very young age. Copyright © 2015 Elsevier Inc. All rights reserved.

Coordinated approaches to quantify long-term ecosystem dynamics in response to global change

Treesearch

Yiqi Luo; Jerry Melillo; Shuli Niu; Claus Beier; James S. Clark; Aime E.T. Classen; Eric Dividson; Jeffrey S. Dukes; R. Dave Evans; Christopher B. Field; Claudia I. Czimczik; Michael Keller; Bruce A. Kimball; Lara M. Kueppers; Richard J. Norby; Shannon L. Pelini; Elise Pendall; Edward Rastetter; Johan Six; Melinda Smith; Mark G. Tjoelker; Margaret S. Torn

2011-01-01

Many serious ecosystem consequences of climate change will take decades or even centuries to emerge. Long-term ecological responses to global change are strongly regulated by slow processes, such as changes in species composition, carbon dynamics in soil and by long-lived plants, and accumulation of nutrient capitals. Understanding and predicting these processes...

Postsynaptic activity reverses the sign of the acetylcholine-induced long-term plasticity of GABAA inhibition

PubMed Central

Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

2014-01-01

Acetylcholine (ACh) regulates forms of plasticity that control cognitive functions but the underlying mechanisms remain largely unknown. ACh controls the intrinsic excitability, as well as the synaptic excitation and inhibition of CA1 hippocampal pyramidal cells (PCs), cells known to participate in circuits involved in cognition and spatial navigation. However, how ACh regulates inhibition in function of postsynaptic activity has not been well studied. Here we show that in rat PCs, a brief pulse of ACh or a brief stimulation of cholinergic septal fibers combined with repeated depolarization induces strong long-term enhancement of GABAA inhibition (GABAA-LTP). Indeed, this enhanced inhibition is due to the increased activation of α5βγ2 subunit-containing GABAA receptors by the GABA released. GABAA-LTP requires the activation of M1-muscarinic receptors and an increase in cytosolic Ca2+. In the absence of PC depolarization ACh triggered a presynaptic depolarization-induced suppression of inhibition (DSI), revealing that postsynaptic activity gates the effects of ACh from presynaptic DSI to postsynaptic LTP. These results provide key insights into mechanisms potentially linked with cognitive functions, spatial navigation, and the homeostatic control of abnormal hyperexcitable states. PMID:24938789

Short- and long-term behavioural, physiological and stoichiometric responses to predation risk indicate chronic stress and compensatory mechanisms.

PubMed

Van Dievel, Marie; Janssens, Lizanne; Stoks, Robby

2016-06-01

Prey organisms are expected to use different short- and long-term responses to predation risk to avoid excessive costs. Contrasting both types of responses is important to identify chronic stress responses and possible compensatory mechanisms in order to better understand the full impact of predators on prey life history and population dynamics. Using larvae of the damselfly Enallagma cyathigerum, we contrasted the effects of short- and long-term predation risk, with special focus on consequences for body stoichiometry. Under short-term predation risk, larvae reduced growth rate, which was associated with a reduced food intake, increased metabolic rate and reduced glucose content. Under long-term predation risk, larvae showed chronic predator stress as indicated by persistent increases in metabolic rate and reduced food intake. Despite this, larvae were able to compensate for the short-term growth reduction under long-term predation risk by relying on physiological compensatory mechanisms, including reduced energy storage. Only under long-term predation risk did we observe an increase in body C:N ratio, as predicted under the general stress paradigm (GSP). Although this was caused by a predator-induced decrease in N content, there was no associated increase in C content. These stoichiometric changes could not be explained by GSP responses because, under chronic predation risk, there was no decrease in N-rich proteins or increase in C-rich fat and sugars; instead glycogen decreased. Our results highlight the importance of compensatory mechanisms and the value of explicitly integrating physiological mechanisms to obtain insights into the temporal dynamics of non-consumptive effects, including effects on body stoichiometry.

Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

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

Yu, Cheng-Chia; School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan

Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulatemore » ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si-Snail blocked xenograft tumorigenesis of long-term nicotine-treated OSCC cells.« less

26 CFR 1.467-3 - Disqualified leasebacks and long-term agreements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 6 2011-04-01 2011-04-01 false Disqualified leasebacks and long-term agreements... Disqualified leasebacks and long-term agreements. (a) General rule. Under § 1.467-1(d)(2)(i), constant rental... long-term agreement within the meaning of paragraph (b) of this section. Constant rental accrual may...

26 CFR 1.467-3 - Disqualified leasebacks and long-term agreements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 6 2012-04-01 2012-04-01 false Disqualified leasebacks and long-term agreements... Disqualified leasebacks and long-term agreements. (a) General rule. Under § 1.467-1(d)(2)(i), constant rental... long-term agreement within the meaning of paragraph (b) of this section. Constant rental accrual may...

26 CFR 1.467-3 - Disqualified leasebacks and long-term agreements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 6 2013-04-01 2013-04-01 false Disqualified leasebacks and long-term agreements... Disqualified leasebacks and long-term agreements. (a) General rule. Under § 1.467-1(d)(2)(i), constant rental... long-term agreement within the meaning of paragraph (b) of this section. Constant rental accrual may...

26 CFR 1.467-3 - Disqualified leasebacks and long-term agreements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Disqualified leasebacks and long-term agreements... Disqualified leasebacks and long-term agreements. (a) General rule. Under § 1.467-1(d)(2)(i), constant rental... long-term agreement within the meaning of paragraph (b) of this section. Constant rental accrual may...

26 CFR 1.467-3 - Disqualified leasebacks and long-term agreements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 6 2014-04-01 2014-04-01 false Disqualified leasebacks and long-term agreements... Disqualified leasebacks and long-term agreements. (a) General rule. Under § 1.467-1(d)(2)(i), constant rental... long-term agreement within the meaning of paragraph (b) of this section. Constant rental accrual may...

Adaptive Flow Management in Regulated Rivers: Successes and Challenges (Invited)

NASA Astrophysics Data System (ADS)

Robinson, C. T.; Melis, T. S.; Kennedy, T.; Korman, J.; Ortlepp, J.

2013-12-01

Experimental high flows are becoming common management actions in rivers affected by large dams. When implemented under clear objectives and goals, experimental flows provide opportunities for long-term ecological successes but also impose various ecological challenges as systems shift under environmental change or from human-related actions. We present case studies from long-term adaptive flow management programs on the River Spöl, Switzerland and the Colorado River, USA, both of which are regulated by high dams and flow through National Parks. The management goals in each system differ thus reflecting the different high flow practices implemented over time. Regulated flows in the Spöl reflect a compromise between hydropower needs and ecology (native brown trout fishery), whereas Glen Canyon Dam flows have mainly been directed towards maintenance of river beaches in Grand Canyon National Park with co-management of both nonnative rainbow trout in the tailwater immediately below the dam and downstream endangered native fish of Grand Canyon also an objective. Some 24 experimental floods have occurred on the Spöl over the last 13 years, resulting in a positive effect on the trout fishery and a zoobenthic assemblage having a more typical alpine stream composition. The system has experienced various shifts in assemblage composition over time with the last shift occurring 7 years after the initial floods. A major challenge occurred in spring 2013 with an accidental release of fine sediments from the reservoir behind Punt dal Gall Dam, causing high fish mortality and smothering of the river bottom. Results showed that the effect was pronounced near the dam and gradually lessened downriver to the lower reservoir. Zoobenthic assemblages displayed relatively high resistance to the event and some fish found refugia in the lower reservoir and larger side tributaries, thus projecting a faster recovery than initially thought. Below Glen Canyon dam, benefits to sandbars have been marginal since experimental constrained hydropower releases began in 1991 and controlled floods began in 1996 (7 have been released through 2012), while native fish populations have increased, although apparently not in response to flows. However, nonnative rainbow trout have been shown to increase in abundance repeatedly below Glen Canyon Dam in response to both controlled floods and more stable flows, both of which were originally proposed to benefit Grand Canyon beaches. Survival of trout fry following the 2008 spring flood was apparently tied to increased abundance of benthic invertebrates in the tailwater. Expansion of nonnative trout in response to high flows pose a potential threat to native fish downstream through competition for limited food and habitat, and through predation of juvenile native fish. Challenges are presented for each system in terms of flow implementation under hydropower needs (Spöl) and environmental change (Colorado). We close with perspectives on improving adaptive flow management actions in regulated rivers as learning-based, long-term ecological experiments.

40 CFR 1.47 - Office of Solid Waste and Emergency Response.

Code of Federal Regulations, 2012 CFR

2012-07-01

... waste sites and spills (including oil spills); long-term strategic planning and special studies; economic and long-term environmental analyses; economic impact assessment of RCRA and CERCLA regulations... responsibility for implementing the Resource Conservation and Recovery Act (RCRA) and the Comprehensive...

40 CFR 1.47 - Office of Solid Waste and Emergency Response.

Code of Federal Regulations, 2013 CFR

2013-07-01

... waste sites and spills (including oil spills); long-term strategic planning and special studies; economic and long-term environmental analyses; economic impact assessment of RCRA and CERCLA regulations... responsibility for implementing the Resource Conservation and Recovery Act (RCRA) and the Comprehensive...

45 CFR 144.204 - Applicability of regulations.

Code of Federal Regulations, 2012 CFR

2012-10-01

....204 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance Partnerships... this subpart for reporting data apply only to those insurers that have issued qualified long-term care...

45 CFR 144.204 - Applicability of regulations.

Code of Federal Regulations, 2013 CFR

2013-10-01

....204 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance Partnerships... this subpart for reporting data apply only to those insurers that have issued qualified long-term care...

45 CFR 144.204 - Applicability of regulations.

Code of Federal Regulations, 2014 CFR

2014-10-01

....204 Public Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance Partnerships... this subpart for reporting data apply only to those insurers that have issued qualified long-term care...

1 CFR 18.20 - Identification of subjects in agency regulations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Indexing Terms. Agencies may include additional terms not contained in the Thesaurus as long as the appropriate Thesaurus terms are also used. Copies of the Federal Register Thesaurus of Indexing Terms are...

1 CFR 18.20 - Identification of subjects in agency regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Indexing Terms. Agencies may include additional terms not contained in the Thesaurus as long as the appropriate Thesaurus terms are also used. Copies of the Federal Register Thesaurus of Indexing Terms are...

1 CFR 18.20 - Identification of subjects in agency regulations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Indexing Terms. Agencies may include additional terms not contained in the Thesaurus as long as the appropriate Thesaurus terms are also used. Copies of the Federal Register Thesaurus of Indexing Terms are...

Regulation of tumor progression via the Snail-RKIP signaling pathway by nicotine exposure in head and neck squamous cell carcinoma.

PubMed

Nieh, Shin; Jao, Shu-Wen; Yang, Chin-Yuh; Lin, Yaoh-Shiang; Tseng, Yi-Han; Liu, Chia-Lin; Lee, Tsai-Yu; Liu, Tsung-Yun; Chu, Yueng-Hsiang; Chen, Su-Feng

2015-12-01

Recent studies suggest that long-term exposure of the carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK) found in tobacco smoke is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The underlying nicotine-mediated mechanism remains unclear. An analysis of SCC-25 and Fadu cells with or without NNK exposure focusing on the evaluation of migration and invasion abilities, the expression of epithelial-mesenchymal transition, drug-resistance-related genes, properties of cancer stem cells (CSCs), and anti-apoptosis was performed. Long-term NNK exposure enhances migration and invasion with morphological alterations in a dose-dependently manner. Furthermore, NNK exposure also upregulates Snail, promotes sphere-forming ability, and overexpresses aldehyde dehydrogenase 1 (ALDH1), Nanog, OCT4, ABCG2, and MDR1. The current study confirmed that long-term NNK exposure plays a role in HNSCC by increasing anti-apoptosis and therapeutic resistance via the Snail-RKIP signaling pathway. Our data also suggest that α7 nicotinic acetylcholine receptor (α7-nAChR) inhibition or targeting Snail may provide a feasible rationale for preventing the progression of HNSCC. © 2015 Wiley Periodicals, Inc.

Thick-tissue bioreactor as a platform for long-term organotypic culture and drug delivery.

PubMed

Markov, Dmitry A; Lu, Jenny Q; Samson, Philip C; Wikswo, John P; McCawley, Lisa J

2012-11-07

We have developed a novel, portable, gravity-fed, microfluidics-based platform suitable for optical interrogation of long-term organotypic cell culture. This system is designed to provide convenient control of cell maintenance, nutrients, and experimental reagent delivery to tissue-like cell densities housed in a transparent, low-volume microenvironment. To demonstrate the ability of our Thick-Tissue Bioreactor (TTB) to provide stable, long-term maintenance of high-density cellular arrays, we observed the morphogenic growth of human mammary epithelial cell lines, MCF-10A and their invasive variants, cultured under three-dimensional (3D) conditions inside our system. Over the course of 21 days, these cells typically develop into hollow "mammospheres" if cultured in standard 3D Matrigel. This complex morphogenic process requires alterations in a variety of cellular functions, including degradation of extracellular matrix that is regulated by cell-produced matrix proteinases. For our "drug" delivery testing and validation experiments we have introduced proteinase inhibitors into the fluid supply system, and we observed both reduced proteinase activity and inhibited cellular morphogenesis. The size inhibition results correlated well with the overall proteinase activities of the tested cells.

Molecular regulation of effector and memory T cell differentiation

PubMed Central

Chang, John T; Wherry, E John; Goldrath, Ananda W

2015-01-01

Immunological memory is a cardinal feature of adaptive immunity and an important goal of vaccination strategies. Here we highlight advances in the understanding of the diverse T lymphocyte subsets that provide acute and long-term protection from infection. These include new insights into the transcription factors, and the upstream ‘pioneering’ factors that regulate their accessibility to key sites of gene regulation, as well as metabolic regulators that contribute to the differentiation of effector and memory subsets; ontogeny and defining characteristics of tissue-resident memory lymphocytes; and origins of the remarkable heterogeneity exhibited by activated T cells. Collectively, these findings underscore progress in delineating the underlying pathways that control diversification in T cell responses but also reveal gaps in the knowledge, as well as the challenges that arise in the application of this knowledge to rationally elicit desired T cell responses through vaccination and immunotherapy. PMID:25396352

Enhanced decomposition of stable soil organic carbon and microbial catabolic potentials by long-term field warming

DOE PAGES

Feng, Wenting; Liang, Junyi; Hale, Lauren E.; ...

2017-06-09

Quantifying soil organic carbon (SOC) decomposition under warming is critical to predict carbon–climate feedbacks. According to the substrate regulating principle, SOC decomposition would decrease as labile SOC declines under field warming, but observations of SOC decomposition under warming do not always support this prediction. This discrepancy could result from varying changes in SOC components and soil microbial communities under warming. This study aimed to determine the decomposition of SOC components with different turnover times after subjected to long-term field warming and/or root exclusion to limit C input, and to test whether SOC decomposition is driven by substrate lability under warming.more » Taking advantage of a 12-year field warming experiment in a prairie, we assessed the decomposition of SOC components by incubating soils from control and warmed plots, with and without root exclusion for 3 years. We assayed SOC decomposition from these incubations by combining inverse modeling and microbial functional genes during decomposition with a metagenomic technique (GeoChip). The decomposition of SOC components with turnover times of years and decades, which contributed to 95% of total cumulative CO 2 respiration, was greater in soils from warmed plots. But the decomposition of labile SOC was similar in warmed plots compared to the control. The diversity of C-degradation microbial genes generally declined with time during the incubation in all treatments, suggesting shifts of microbial functional groups as substrate composition was changing. Compared to the control, soils from warmed plots showed significant increase in the signal intensities of microbial genes involved in degrading complex organic compounds, implying enhanced potential abilities of microbial catabolism. These are likely responsible for accelerated decomposition of SOC components with slow turnover rates. Overall, the shifted microbial community induced by long-term warming accelerates the decomposition of SOC components with slow turnover rates and thus amplify the positive feedback to climate change.« less

Enhanced decomposition of stable soil organic carbon and microbial catabolic potentials by long-term field warming

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

Feng, Wenting; Liang, Junyi; Hale, Lauren E.

Quantifying soil organic carbon (SOC) decomposition under warming is critical to predict carbon–climate feedbacks. According to the substrate regulating principle, SOC decomposition would decrease as labile SOC declines under field warming, but observations of SOC decomposition under warming do not always support this prediction. This discrepancy could result from varying changes in SOC components and soil microbial communities under warming. This study aimed to determine the decomposition of SOC components with different turnover times after subjected to long-term field warming and/or root exclusion to limit C input, and to test whether SOC decomposition is driven by substrate lability under warming.more » Taking advantage of a 12-year field warming experiment in a prairie, we assessed the decomposition of SOC components by incubating soils from control and warmed plots, with and without root exclusion for 3 years. We assayed SOC decomposition from these incubations by combining inverse modeling and microbial functional genes during decomposition with a metagenomic technique (GeoChip). The decomposition of SOC components with turnover times of years and decades, which contributed to 95% of total cumulative CO 2 respiration, was greater in soils from warmed plots. But the decomposition of labile SOC was similar in warmed plots compared to the control. The diversity of C-degradation microbial genes generally declined with time during the incubation in all treatments, suggesting shifts of microbial functional groups as substrate composition was changing. Compared to the control, soils from warmed plots showed significant increase in the signal intensities of microbial genes involved in degrading complex organic compounds, implying enhanced potential abilities of microbial catabolism. These are likely responsible for accelerated decomposition of SOC components with slow turnover rates. Overall, the shifted microbial community induced by long-term warming accelerates the decomposition of SOC components with slow turnover rates and thus amplify the positive feedback to climate change.« less

Enhanced decomposition of stable soil organic carbon and microbial catabolic potentials by long-term field warming.

PubMed

Feng, Wenting; Liang, Junyi; Hale, Lauren E; Jung, Chang Gyo; Chen, Ji; Zhou, Jizhong; Xu, Minggang; Yuan, Mengting; Wu, Liyou; Bracho, Rosvel; Pegoraro, Elaine; Schuur, Edward A G; Luo, Yiqi

2017-11-01

Quantifying soil organic carbon (SOC) decomposition under warming is critical to predict carbon-climate feedbacks. According to the substrate regulating principle, SOC decomposition would decrease as labile SOC declines under field warming, but observations of SOC decomposition under warming do not always support this prediction. This discrepancy could result from varying changes in SOC components and soil microbial communities under warming. This study aimed to determine the decomposition of SOC components with different turnover times after subjected to long-term field warming and/or root exclusion to limit C input, and to test whether SOC decomposition is driven by substrate lability under warming. Taking advantage of a 12-year field warming experiment in a prairie, we assessed the decomposition of SOC components by incubating soils from control and warmed plots, with and without root exclusion for 3 years. We assayed SOC decomposition from these incubations by combining inverse modeling and microbial functional genes during decomposition with a metagenomic technique (GeoChip). The decomposition of SOC components with turnover times of years and decades, which contributed to 95% of total cumulative CO 2 respiration, was greater in soils from warmed plots. But the decomposition of labile SOC was similar in warmed plots compared to the control. The diversity of C-degradation microbial genes generally declined with time during the incubation in all treatments, suggesting shifts of microbial functional groups as substrate composition was changing. Compared to the control, soils from warmed plots showed significant increase in the signal intensities of microbial genes involved in degrading complex organic compounds, implying enhanced potential abilities of microbial catabolism. These are likely responsible for accelerated decomposition of SOC components with slow turnover rates. Overall, the shifted microbial community induced by long-term warming accelerates the decomposition of SOC components with slow turnover rates and thus amplify the positive feedback to climate change. © 2017 John Wiley & Sons Ltd.

Critical Role of Endoplasmic Reticulum Stress in Chronic Intermittent Hypoxia-Induced Deficits in Synaptic Plasticity and Long-Term Memory

PubMed Central

Xu, Lin-Hao; Xie, Hui; Shi, Zhi-Hui; Du, Li-Da; Wing, Yun-Kwok; Li, Albert M.

2015-01-01

Abstract Aims: This study examined the role of endoplasmic reticulum (ER) stress in mediating chronic intermittent hypoxia (IH)-induced neurocognitive deficits. We designed experiments to demonstrate that ER stress is initiated in the hippocampus under chronic IH and determined its role in apoptotic cell death, impaired synaptic structure and plasticity, and memory deficits. Results: Two weeks of IH disrupted ER fine structure and upregulated ER stress markers, glucose-regulated protein 78, caspase-12, and C/EBP homologous protein, in the hippocampus, which could be suppressed by ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid. Meanwhile, ER stress induced apoptosis via decreased Bcl-2, promoted reactive oxygen species production, and increased malondialdehyde formation and protein carbonyl, as well as suppressed mitochondrial function. These effects were largely prevented by ER stress inhibitors. On the other hand, suppression of oxidative stress could reduce ER stress. In addition, the length of the synaptic active zone and number of mature spines were reduced by IH. Long-term recognition memory and spatial memory were also impaired, which was accompanied by reduced long-term potentiation in the Schaffer collateral pathway. These effects were prevented by coadministration of the TUDCA. Innovation and Conclusion: These results show that ER stress plays a critical role in underlying memory deficits in obstructive sleep apnea (OSA)-associated IH. Attenuators of ER stress may serve as novel adjunct therapeutic agents for ameliorating OSA-induced neurocognitive impairment. Antioxid. Redox Signal. 23, 695–710. PMID:25843188

Network, cellular, and molecular mechanisms underlying long-term memory formation.

PubMed

Carasatorre, Mariana; Ramírez-Amaya, Víctor

2013-01-01

The neural network stores information through activity-dependent synaptic plasticity that occurs in populations of neurons. Persistent forms of synaptic plasticity may account for long-term memory storage, and the most salient forms are the changes in the structure of synapses. The theory proposes that encoding should use a sparse code and evidence suggests that this can be achieved through offline reactivation or by sparse initial recruitment of the network units. This idea implies that in some cases the neurons that underwent structural synaptic plasticity might be a subpopulation of those originally recruited; However, it is not yet clear whether all the neurons recruited during acquisition are the ones that underwent persistent forms of synaptic plasticity and responsible for memory retrieval. To determine which neural units underlie long-term memory storage, we need to characterize which are the persistent forms of synaptic plasticity occurring in these neural ensembles and the best hints so far are the molecular signals underlying structural modifications of the synapses. Structural synaptic plasticity can be achieved by the activity of various signal transduction pathways, including the NMDA-CaMKII and ACh-MAPK. These pathways converge with the Rho family of GTPases and the consequent ERK 1/2 activation, which regulates multiple cellular functions such as protein translation, protein trafficking, and gene transcription. The most detailed explanation may come from models that allow us to determine the contribution of each piece of this fascinating puzzle that is the neuron and the neural network.

40 CFR 439.52 - Effluent limitations attainable by the application of the best practicable control technology...

Code of Federal Regulations, 2011 CFR

2011-07-01

... day, must reflect not less than 74 percent reduction in the long-term average daily COD load of the... required to attain a limitation for COD that is less than the equivalent of 220 mg/L. (d) The long-term... of NPDES permit limitations regulating discharges subject to this subpart, calculation of the long...

40 CFR 439.52 - Effluent limitations attainable by the application of the best practicable control technology...

Code of Federal Regulations, 2010 CFR

2010-07-01

... day, must reflect not less than 74 percent reduction in the long-term average daily COD load of the... required to attain a limitation for COD that is less than the equivalent of 220 mg/L. (d) The long-term... of NPDES permit limitations regulating discharges subject to this subpart, calculation of the long...

45 CFR 144.208 - Deadlines for submission of reports.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 144.208 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance... regulations. (b) All reports on the registry of qualified long-term care insurance policies issued to...

45 CFR 144.208 - Deadlines for submission of reports.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Section 144.208 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance... regulations. (b) All reports on the registry of qualified long-term care insurance policies issued to...

45 CFR 144.208 - Deadlines for submission of reports.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Section 144.208 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance... regulations. (b) All reports on the registry of qualified long-term care insurance policies issued to...

45 CFR 144.208 - Deadlines for submission of reports.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Section 144.208 Public Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance... regulations. (b) All reports on the registry of qualified long-term care insurance policies issued to...

Long-term trends in fire behavior and changes in population at risk

EPA Science Inventory

Long-term trends in fire behavior and changes in population at risk Rappold AG, Peterson GC, US EPA Matt Jolly, USFS Air pollution regulations and technological advances have successfully reduced emissions of air pollutants from many anthropogenic sources in recent decades. Duri...

Homeostatic regulation of adult hippocampal neurogenesis in aging rats: long-term effects of early exercise

PubMed Central

Merkley, Christina M.; Jian, Charles; Mosa, Adam; Tan, Yao-Fang; Wojtowicz, J. Martin

2014-01-01

Adult neurogenesis is highly responsive to environmental and physiological factors. The majority of studies to date have examined short-term consequences of enhancing or blocking neurogenesis but long-term changes remain less well understood. Current evidence for age-related declines in neurogenesis warrant further investigation into these long-term changes. In this report we address the hypothesis that early life experience, such as a period of voluntary running in juvenile rats, can alter properties of adult neurogenesis for the remainder of the animal's life. The results indicate that the number of proliferating and differentiating neuronal precursors is not altered in runners beyond the initial weeks post-running, suggesting homeostatic regulation of these processes. However, the rate of neuronal maturation and survival during a 4 week period after cell division was enhanced up to 11 months of age (the end of the study period). This study is the first to show that a transient period of physical activity at a young age promotes changes in neurogenesis that persist over the long-term, which is important for our understanding of the modulation of neurogenesis by exercise with age. Functional integration of adult-born neurons within the hippocampus that resist homeostatic regulation with aging, rather than the absolute number of adult-born neurons, may be an essential feature of adult neurogenesis that promotes the maintenance of neural plasticity in old age. PMID:25071426

The changing flow of management information systems in long-term care facilities.

PubMed

Stokes, D F

1997-08-01

Over the past three decades, the long-term care community has seen continual increases in the complexity and sophistication of management information systems. These changes have been brought about by the ever-increasing demands on owners and managers to provide accurate and timely data to both regulators and financial investors. The evolution of these systems has increased rapidly in recent years as the nation attempts to reinvent the funding mechanisms for long-term care.

Study of Histopathological and Molecular Changes of Rat Kidney under Simulated Weightlessness and Resistance Training Protective Effect

PubMed Central

Li, Zhili; Tian, Jijing; Abdelalim, Saed; Du, Fang; She, Ruiping; Wang, Desheng; Tan, Cheng; Wang, Huijuan; Chen, Wenjuan; Lv, Dongqiang; Chang, Lingling

2011-01-01

To explore the effects of long-term weightlessness on the renal tissue, we used the two months tail suspension model to simulate microgravity and investigated the simulated microgravity on the renal morphological damages and related molecular mechanisms. The microscopic examination of tissue structure and ultrastructure was carried out for histopathological changes of renal tissue morphology. The immunohistochemistry, real-time PCR and Western blot were performed to explore the molecular mechanisms associated the observations. Hematoxylin and eosin (HE) staining showed severe pathological kidney lesions including glomerular atrophy, degeneration and necrosis of renal tubular epithelial cells in two months tail-suspended rats. Ultrastructural studies of the renal tubular epithelial cells demonstrated that basal laminas of renal tubules were rough and incrassate with mitochondria swelling and vacuolation. Cell apoptosis in kidney monitored by the expression of Bax/Bcl-2 and caspase-3 accompanied these pathological damages caused by long-term microgravity. Analysis of the HSP70 protein expression illustrated that overexpression of HSP70 might play a crucial role in inducing those pathological damages. Glucose regulated protein 78 (GRP78), one of the endoplasmic reticulum (ER) chaperones, was up-regulated significantly in the kidney of tail suspension rat, which implied that ER-stress was associated with apoptosis. Furthermore, CHOP and caspase-12 pathways were activated in ER-stress induced apoptosis. Resistance training not only reduced kidney cell apoptosis and expression of HSP70 protein, it also can attenuate the kidney impairment imposed by weightlessness. The appropriate optimization might be needed for the long term application for space exploration. PMID:21625440

The organization of plasticity in the cerebellar cortex: from synapses to control.

PubMed

D'Angelo, Egidio

2014-01-01

The cerebellum is thought to play a critical role in procedural learning, but the relationship between this function and the underlying cellular and synaptic mechanisms remains largely speculative. At present, at least nine forms of long-term synaptic and nonsynaptic plasticity (some of which are bidirectional) have been reported in the cerebellar cortex and deep cerebellar nuclei. These include long-term potentiation (LTP) and long-term depression at the mossy fiber-granule cell synapse, at the synapses formed by parallel fibers, climbing fibers, and molecular layer interneurons on Purkinje cells, and at the synapses formed by mossy fibers and Purkinje cells on deep cerebellar nuclear cells, as well as LTP of intrinsic excitability in granule cells, Purkinje cells, and deep cerebellar nuclear cells. It is suggested that the complex properties of cerebellar learning would emerge from the distribution of plasticity in the network and from its dynamic remodeling during the different phases of learning. Intrinsic and extrinsic factors may hold the key to explain how the different forms of plasticity cooperate to select specific transmission channels and to regulate the signal-to-noise ratio through the cerebellar cortex. These factors include regulation of neuronal excitation by local inhibitory networks, engagement of specific molecular mechanisms by spike bursts and theta-frequency oscillations, and gating by external neuromodulators. Therefore, a new and more complex view of cerebellar plasticity is emerging with respect to that predicted by the original "Motor Learning Theory," opening issues that will require experimental and computational testing. © 2014 Elsevier B.V. All rights reserved.

16 CFR 300.20 - Use of the terms “virgin” or “new.”

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Use of the terms âvirginâ or ânew.â 300.20 Section 300.20 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER THE WOOL PRODUCTS LABELING ACT OF 1939 Labeling § 300.20 Use of the terms...

16 CFR 300.17 - Use of the term “all” or “100%.”

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Use of the term âallâ or â100%.â 300.17 Section 300.17 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER THE WOOL PRODUCTS LABELING ACT OF 1939 Labeling § 300.17 Use of the term...

Sexual conflict explains the extraordinary diversity of mechanisms regulating mitochondrial inheritance.

PubMed

Radzvilavicius, Arunas L; Lane, Nick; Pomiankowski, Andrew

2017-10-26

Mitochondria are predominantly inherited from the maternal gamete, even in unicellular organisms. Yet an extraordinary array of mechanisms enforce uniparental inheritance, which implies shifting selection pressures and multiple origins. We consider how this high turnover in mechanisms controlling uniparental inheritance arises using a novel evolutionary model in which control of mitochondrial transmission occurs either during spermatogenesis (by paternal nuclear genes) or at/after fertilization (by maternal nuclear genes). The model treats paternal leakage as an evolvable trait. Our evolutionary analysis shows that maternal control consistently favours strict uniparental inheritance with complete exclusion of sperm mitochondria, whereas some degree of paternal leakage of mitochondria is an expected outcome under paternal control. This difference arises because mito-nuclear linkage builds up with maternal control, allowing the greater variance created by asymmetric inheritance to boost the efficiency of purifying selection and bring benefits in the long term. In contrast, under paternal control, mito-nuclear linkage tends to be much weaker, giving greater advantage to the mixing of cytotypes, which improves mean fitness in the short term, even though it imposes a fitness cost to both mating types in the long term. Sexual conflict is an inevitable outcome when there is competition between maternal and paternal control of mitochondrial inheritance. If evolution has led to complete uniparental inheritance through maternal control, it creates selective pressure on the paternal nucleus in favour of subversion through paternal leakage, and vice versa. This selective divergence provides a reason for the repeated evolution of novel mechanisms that regulate the transmission of paternal mitochondria, both in the fertilized egg and spermatogenesis. Our analysis suggests that the widespread occurrence of paternal leakage and prevalence of heteroplasmy are natural outcomes of this sexual conflict.

Assessing stress responses to atmospheric cold plasma exposure using Escherichia coli knock-out mutants.

PubMed

Han, L; Boehm, D; Patil, S; Cullen, P J; Bourke, P

2016-08-01

This study investigated the effect of atmospheric cold plasma (ACP) exposure-induced stress on microbial inactivation patterns and the regulation of genes involved in the microbial stress response in conjunction with key processing parameters of exposure time and post-treatment storage time. Cell suspensions of Escherichia coli BW 25113 and its isogenic knock-out mutants in rpoS, soxR, soxS, oxyR and dnaK genes were treated with high-voltage ACP in a sealed package for 1, 3 and 5 min followed by 0-, 1- and 24-h post-treatment storage. Reactive oxygen species (ROS) densities and colony formation were determined. ΔrpoS strain showed higher microbial reduction and greater cell permeability than other mutants, while ΔoxyR only showed this effect after 5 min of treatment. With increased post-treatment storage time, ΔsoxS and ΔsoxR had increased sensitivity and resistance respectively. ΔdnaK cell suspensions had much higher ROS than other strains and showed increased sensitivity with 24 h post-treatment storage. RpoS and oxyR genes have both short-term and long-term regulatory effects under plasma stress. However, knocking out dnaK gene had an immediate response on ROS scavenging and long-term repairing mechanisms. ΔsoxR and ΔsoxS had different responses to ACP treatment with the increase in post-treatment time in relation to clearance of reactive species implying the different characteristics and functions as subunits. By comparing the response of mutants under ACP exposure to key processing parameters, the mechanism of microbial inactivation was partly revealed with respect to cellular regulation and repairing genes. © 2016 The Society for Applied Microbiology.

Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells

PubMed Central

Luckey, Chance John; Bhattacharya, Deepta; Goldrath, Ananda W.; Weissman, Irving L.; Benoist, Christophe; Mathis, Diane

2006-01-01

The only cells of the hematopoietic system that undergo self-renewal for the lifetime of the organism are long-term hematopoietic stem cells and memory T and B cells. To determine whether there is a shared transcriptional program among these self-renewing populations, we first compared the gene-expression profiles of naïve, effector and memory CD8+ T cells with those of long-term hematopoietic stem cells, short-term hematopoietic stem cells, and lineage-committed progenitors. Transcripts augmented in memory CD8+ T cells relative to naïve and effector T cells were selectively enriched in long-term hematopoietic stem cells and were progressively lost in their short-term and lineage-committed counterparts. Furthermore, transcripts selectively decreased in memory CD8+ T cells were selectively down-regulated in long-term hematopoietic stem cells and progressively increased with differentiation. To confirm that this pattern was a general property of immunologic memory, we turned to independently generated gene expression profiles of memory, naïve, germinal center, and plasma B cells. Once again, memory-enriched and -depleted transcripts were also appropriately augmented and diminished in long-term hematopoietic stem cells, and their expression correlated with progressive loss of self-renewal function. Thus, there appears to be a common signature of both up- and down-regulated transcripts shared between memory T cells, memory B cells, and long-term hematopoietic stem cells. This signature was not consistently enriched in neural or embryonic stem cell populations and, therefore, appears to be restricted to the hematopoeitic system. These observations provide evidence that the shared phenotype of self-renewal in the hematopoietic system is linked at the molecular level. PMID:16492737

The roles of Eph receptors in contextual fear conditioning memory formation.

PubMed

Dines, Monica; Grinberg, Svetlana; Vassiliev, Maria; Ram, Alon; Tamir, Tal; Lamprecht, Raphael

2015-10-01

Eph receptors regulate glutamate receptors functions, neuronal morphology and synaptic plasticity, cellular events believed to be involved in memory formation. In this study we aim to explore the roles of Eph receptors in learning and memory. Toward that end, we examined the roles of EphB2 and EphA4 receptors, key regulators of synaptic functions, in fear conditioning memory formation. We show that mice lacking EphB2 (EphB2(-/-)) are impaired in short- and long-term contextual fear conditioning memory. Mice that express a carboxy-terminally truncated form of EphB2 that lacks forward signaling, instead of the full EphB2, are impaired in long-term, but not short-term, contextual fear conditioning memory. Long-term contextual fear conditioning memory is attenuated in CaMKII-cre;EphA4(lx/-) mice where EphA4 is removed from all pyramidal neurons of the forebrain. Mutant mice with targeted kinase-dead EphA4 (EphA4(KD)) exhibit intact long-term contextual fear conditioning memory showing that EphA4 kinase-mediated forward signaling is not needed for contextual fear memory formation. The ability to form long-term conditioned taste aversion (CTA) memory is not impaired in the EphB2(-/-) and CaMKII-cre;EphA4(lx/-) mice. We conclude that EphB2 forward signaling is required for long-term contextual fear conditioning memory formation. In contrast, EphB2 mediates short-term contextual fear conditioning memory formation in a forward signaling-independent manner. EphA4 mediates long-term contextual fear conditioning memory formation in a kinase-independent manner. Copyright © 2015 Elsevier Inc. All rights reserved.

Wildfires, Ecosystem Services, and Biodiversity in Tropical Dry Forest in India.

PubMed

Schmerbeck, Joachim; Fiener, Peter

2015-08-01

This review is intended to contribute to the understanding of the interlinkage between wildfire in India's tropical dry forest (TDF) and selected ecosystem services (ES), namely forest provisioning and water regulating services, as well as biodiversity. TDF covers approximately 146,000 km(2) (4.4%) of India, whereas according to the MODIS fire product about 2200 km(2) (1.4%) burns per year. As studies on wildfire effects upon ESs and biodiversity in Indian TDFs are rare we partly transferred findings from other (dry) forest areas to the environmental situation in India. In India (intentionally lit) wildfires have a very important connection to local livelihoods and the availability of non-wood forest products. Very important adverse long-term effects are the deterioration of forest ecosystems and soil degradation. The potential for TDF to regulate hydrological cycles is expected to be greater in the absence of fire than with it. A general judgment on the effect of fire on biodiversity is difficult as it depends on the community and species involved but a loss of biodiversity under regular burnings is apparent. Consequently, forest managers need sound knowledge regarding the interplay of wildfires and ecosystem behavior in general and more specific knowledge regarding the effects on taxa being considered for conservation efforts. Generally, much more research is needed to understand the trade-offs between the short-term benefits gained from forest provisioning services and long-term adverse effects.

Wildfires, Ecosystem Services, and Biodiversity in Tropical Dry Forest in India

NASA Astrophysics Data System (ADS)

Schmerbeck, Joachim; Fiener, Peter

2015-08-01

This review is intended to contribute to the understanding of the interlinkage between wildfire in India's tropical dry forest (TDF) and selected ecosystem services (ES), namely forest provisioning and water regulating services, as well as biodiversity. TDF covers approximately 146,000 km2 (4.4 %) of India, whereas according to the MODIS fire product about 2200 km2 (1.4 %) burns per year. As studies on wildfire effects upon ESs and biodiversity in Indian TDFs are rare we partly transferred findings from other (dry) forest areas to the environmental situation in India. In India (intentionally lit) wildfires have a very important connection to local livelihoods and the availability of non-wood forest products. Very important adverse long-term effects are the deterioration of forest ecosystems and soil degradation. The potential for TDF to regulate hydrological cycles is expected to be greater in the absence of fire than with it. A general judgment on the effect of fire on biodiversity is difficult as it depends on the community and species involved but a loss of biodiversity under regular burnings is apparent. Consequently, forest managers need sound knowledge regarding the interplay of wildfires and ecosystem behavior in general and more specific knowledge regarding the effects on taxa being considered for conservation efforts. Generally, much more research is needed to understand the trade-offs between the short-term benefits gained from forest provisioning services and long-term adverse effects.

Concentration-Dependent Effects of Rhodiola Rosea on Long-Term Survival and Stress Resistance of Yeast Saccharomyces Cerevisiae: The Involvement of YAP 1 and MSN2/4 Regulatory Proteins

PubMed Central

Bayliak, Maria M.; Burdyliuk, Nadia I.; Izers’ka, Lilia I.; Lushchak, Volodymyr I.

2014-01-01

Concentration-dependent effects of aqueous extract from R. rosea root on long-term survival and stress resistance of budding yeast Saccharomyces cerevisiae were studied. At low concentrations, R. rosea aqueous extract extended yeast chronological lifespan, enhanced oxidative stress resistance of stationary-phase cells and resistance to number stressors in exponentially growing cultures. At high concentrations, R. rosea extract sensitized yeast cells to stresses and shortened yeast lifespan. These biphasic concentration-responses describe a common hormetic phenomenon characterized by a low-dose stimulation and a high-dose inhibition. Yeast pretreatment with low doses of R. rosea extract enhanced yeast survival and prevented protein oxidation under H2O2-induced oxidative stress. Positive effect of R. rosea extract on yeast survival under heat shock exposure was not accompanied with changes in antioxidant enzyme activities and levels of oxidized proteins. The deficiency in transcriptional regulators, Msn2/Msn4 and Yap1, abolished the positive effect of low doses of R. rosea extract on yeast viability under stress challenges. Potential involvement of Msn2/Msn4 and Yap1 regulatory proteins in realization of R. rosea beneficial effects is discussed. PMID:24659935

Response of mitochondrial thioredoxin PsTrxo1, antioxidant enzymes, and respiration to salinity in pea (Pisum sativum L.) leaves.

PubMed

Martí, María C; Florez-Sarasa, Igor; Camejo, Daymi; Ribas-Carbó, Miquel; Lázaro, Juan J; Sevilla, Francisca; Jiménez, Ana

2011-07-01

Mitochondria play an essential role in reactive oxygen species (ROS) signal transduction in plants. Redox regulation is an essential feature of mitochondrial function, with thioredoxin (Trx), involved in disulphide/dithiol interchange, playing a prominent role. To explore the participation of mitochondrial PsTrxo1, Mn-superoxide dismutase (Mn-SOD), peroxiredoxin (PsPrxII F), and alternative oxidase (AOX) under salt stress, their transcriptional and protein levels were analysed in pea plants growing under 150 mM NaCl for a short and a long period. The activities of mitochondrial Mn-SOD and Trx together with the in vivo activities of the alternative pathway (AP) and the cytochrome pathway (CP) were also determined, combined with the characterization of the plant physiological status as well as the mitochondrial oxidative indicators. The analysis of protein and mRNA levels and activities revealed the importance of the post-transcriptional and post-translational regulation of these proteins in the response to salt stress. Increases in AOX protein amount correlated with increases in AP capacity, whereas in vivo AP activity was maintained under salt stress. Similarly, Mn-SOD activity was also maintained. Under all the stress treatments, photosynthesis, stomatal conductance, and CP activity were decreased although the oxidative stress in leaves was only moderate. However, an increase in lipid peroxidation and protein oxidation was found in mitochondria isolated from leaves under the short-term salinity conditions. In addition, an increase in mitochondrial Trx activity was produced in response to the long-term NaCl treatment. The results support a role for PsTrxo1 as a component of the defence system induced by NaCl in pea mitochondria, providing the cell with a mechanism by which it can respond to changing environment protecting mitochondria from oxidative stress together with Mn-SOD, AOX, and PrxII F.

Early and delayed long-term transcriptional changes and short-term transient responses during cold acclimation in olive leaves.

PubMed

Leyva-Pérez, María de la O; Valverde-Corredor, Antonio; Valderrama, Raquel; Jiménez-Ruiz, Jaime; Muñoz-Merida, Antonio; Trelles, Oswaldo; Barroso, Juan Bautista; Mercado-Blanco, Jesús; Luque, Francisco

2015-02-01

Low temperature severely affects plant growth and development. To overcome this constraint, several plant species from regions having a cool season have evolved an adaptive response, called cold acclimation. We have studied this response in olive tree (Olea europaea L.) cv. Picual. Biochemical stress markers and cold-stress symptoms were detected after the first 24 h as sagging leaves. After 5 days, the plants were found to have completely recovered. Control and cold-stressed plants were sequenced by Illumina HiSeq 1000 paired-end technique. We also assembled a new olive transcriptome comprising 157,799 unigenes and found 6,309 unigenes differentially expressed in response to cold. Three types of response that led to cold acclimation were found: short-term transient response, early long-term response, and late long-term response. These subsets of unigenes were related to different biological processes. Early responses involved many cold-stress-responsive genes coding for, among many other things, C-repeat binding factor transcription factors, fatty acid desaturases, wax synthesis, and oligosaccharide metabolism. After long-term exposure to cold, a large proportion of gene down-regulation was found, including photosynthesis and plant growth genes. Up-regulated genes after long-term cold exposure were related to organelle fusion, nucleus organization, and DNA integration, including retrotransposons. © The Author 2014. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

A Model of Bidirectional Synaptic Plasticity: From Signaling Network to Channel Conductance

ERIC Educational Resources Information Center

Castellani, Gastone C.; Quinlan, Elizabeth M.; Bersani, Ferdinando; Cooper, Leon N.; Shouval, Harel Z.

2005-01-01

In many regions of the brain, including the mammalian cortex, the strength of synaptic transmission can be bidirectionally regulated by cortical activity (synaptic plasticity). One line of evidence indicates that long-term synaptic potentiation (LTP) and long-term synaptic depression (LTD), correlate with the phosphorylation/dephosphorylation of…

34 CFR 386.1 - What is the Rehabilitation Long-Term Training program?

Code of Federal Regulations, 2010 CFR

2010-07-01

...; (12) Physical education; (13) Therapeutic recreation; (14) Community rehabilitation program personnel... 34 Education 2 2010-07-01 2010-07-01 false What is the Rehabilitation Long-Term Training program? 386.1 Section 386.1 Education Regulations of the Offices of the Department of Education (Continued...

Progesterone Regulation of Synaptic Transmission and Plasticity in Rodent Hippocampus

ERIC Educational Resources Information Center

Foy, Michael R.; Akopian, Garnik; Thompson, Richard F.

2008-01-01

Ovarian hormones influence memory formation by eliciting changes in neural activity. The effects of various concentrations of progesterone (P4) on synaptic transmission and plasticity associated with long-term potentiation (LTP) and long-term depression (LTD) were studied using in vitro hippocampal slices. Extracellular studies show that the…

Long-term effect of set potential on biocathodes in microbial fuel cells: electrochemical and phylogenetic characterization.

PubMed

Xia, Xue; Sun, Yanmei; Liang, Peng; Huang, Xia

2012-09-01

The long-term effect of set potential on oxygen reducing biocathodes was investigated in terms of electrochemical and biological characteristics. Three biocathodes were poised at 200, 60 and -100 mV vs. saturated calomel electrode (SCE) for 110 days, including the first 17 days for startup. Electrochemical analyses showed that 60 mV was the optimum potential during long-term operation. The performance of all the biocathodes kept increasing after startup, suggesting a period longer than startup time needed to make potential regulation more effective. The inherent characteristics without oxygen transfer limitation were studied. Different from short-term regulation, the amounts of biomass were similar while the specific electrochemical activity was significantly influenced by potential. Moreover, potential showed a strong selection for cathode bacteria. Clones 98% similar with an uncultured Bacteroidetes bacterium clone CG84 accounted for 75% to 80% of the sequences on the biocathodes that showed higher electrochemical activity (60 and -100 mV). Copyright © 2012 Elsevier Ltd. All rights reserved.

Workshop to address gaps in regulation of minimally manipulated autologous cell therapies for homologous use in Canada.

PubMed

Chisholm, Jolene; von Tigerstrom, Barbara; Bedford, Patrick; Fradette, Julie; Viswanathan, Sowmya

2017-12-01

In Canada, minimally manipulated autologous cell therapies for homologous use (MMAC-H) are either regulated under the practice of medicine, or as drugs or devices under the Food and Drugs Act, Food and Drug Regulations (F&DR) or Medical Device Regulations (MDR). Cells, Tissues and Organs (CTO) Regulations in Canada are restricted to minimally manipulated allogeneic products for homologous use. This leaves an important gap in the interpretation of existing regulations. The purposes of this workshop co-organized by the Stem Cell Network and the Centre for Commercialization of Regenerative Medicine (CCRM) were to discuss the current state of regulation of MMAC-H therapies in Canada and compare it with other regulatory jurisdictions, with the intent of providing specific policy recommendations to Health Canada. Participants came to a consensus on the need for well-defined common terminology between regulators and stakeholders, a common source of confusion and misinformation. A need for a harmonized national approach to oversight of facilities providing MMAC-H therapies based on existing standards, such as Canadian Standards Association (CSA), was also voiced. Facilities providing MMAC-H therapies should also participate in collection of long-term data to ensure patient safety and efficacy of therapies. Harmonization across provinces of the procedures and practices involving administration of MMAC-H would be preferred. Participants felt that devices used to process MMAC-H are adequately regulated under existing MDR. Overly prescriptive regulation will stifle innovation, whereas insufficient regulation might allow unsafe or ineffective therapies to be offered. Until a clear, balanced and explicit approach is articulated, regulatory uncertainty remains a barrier. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Calcium sensor regulation of the CaV2.1 Ca2+ channel contributes to long-term potentiation and spatial learning.

PubMed

Nanou, Evanthia; Scheuer, Todd; Catterall, William A

2016-11-15

Many forms of short-term synaptic plasticity rely on regulation of presynaptic voltage-gated Ca 2+ type 2.1 (Ca V 2.1) channels. However, the contribution of regulation of Ca V 2.1 channels to other forms of neuroplasticity and to learning and memory are not known. Here we have studied mice with a mutation (IM-AA) that disrupts regulation of Ca V 2.1 channels by calmodulin and related calcium sensor proteins. Surprisingly, we find that long-term potentiation (LTP) of synaptic transmission at the Schaffer collateral-CA1 synapse in the hippocampus is substantially weakened, even though this form of synaptic plasticity is thought to be primarily generated postsynaptically. LTP in response to θ-burst stimulation and to 100-Hz tetanic stimulation is much reduced. However, a normal level of LTP can be generated by repetitive 100-Hz stimulation or by depolarization of the postsynaptic cell to prevent block of NMDA-specific glutamate receptors by Mg 2+ The ratio of postsynaptic responses of NMDA-specific glutamate receptors to those of AMPA-specific glutamate receptors is decreased, but the postsynaptic current from activation of NMDA-specific glutamate receptors is progressively increased during trains of stimuli and exceeds WT by the end of 1-s trains. Strikingly, these impairments in long-term synaptic plasticity and the previously documented impairments in short-term synaptic plasticity in IM-AA mice are associated with pronounced deficits in spatial learning and memory in context-dependent fear conditioning and in the Barnes circular maze. Thus, regulation of Ca V 2.1 channels by calcium sensor proteins is required for normal short-term synaptic plasticity, LTP, and spatial learning and memory in mice.

45 CFR 144.202 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance Partnerships: Reporting... to a qualified long-term care insurance policy issued under a qualified State long-term care...

45 CFR 144.202 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance Partnerships: Reporting... to a qualified long-term care insurance policy issued under a qualified State long-term care...

45 CFR 144.202 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance Partnerships: Reporting... to a qualified long-term care insurance policy issued under a qualified State long-term care...

45 CFR 144.202 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance Partnerships: Reporting... to a qualified long-term care insurance policy issued under a qualified State long-term care...

The Longevity of Hippocampus-Dependent Memory Is Orchestrated by the Locus Coeruleus-Noradrenergic System

PubMed Central

2017-01-01

The locus coeruleus is connected to the dorsal hippocampus via strong fiber projections. It becomes activated after arousal and novelty, whereupon noradrenaline is released in the hippocampus. Noradrenaline from the locus coeruleus is involved in modulating the encoding, consolidation, retrieval, and reversal of hippocampus-based memory. Memory storage can be modified by the activation of the locus coeruleus and subsequent facilitation of hippocampal long-term plasticity in the forms of long-term depression and long-term potentiation. Recent evidence indicates that noradrenaline and dopamine are coreleased in the hippocampus from locus coeruleus terminals, thus fostering neuromodulation of long-term synaptic plasticity and memory. Noradrenaline is an inductor of epigenetic modifications regulating transcriptional control of synaptic long-term plasticity to gate the endurance of memory storage. In conclusion, locus coeruleus activation primes the persistence of hippocampus-based long-term memory. PMID:28695015

Biochemical Changes in Erythrocytes as a Molecular Marker of Cell Damage during Long-Term Simvastatin Treatment.

PubMed

Mikashinovich, Z I; Belousova, E S

2016-08-01

Long-term administration of simvastatin to rats, irrespective of the baseline cholesterol levels, induced biochemical changes in erythrocytes attesting to hypoxic damage (accumulation of lactate and 2,3-diphosphoglycerate), disturbances in ATP-dependent mechanisms of ion homeostasis regulation (decrease in total ATPase and Ca(2+)-ATPase activities), and antioxidant enzymes system imbalance. These changes can be considered as a sensitive indicator and molecular basis of cell damage during long-term administration of statins.

16 CFR 303.40 - Use of terms in written advertisements that imply presence of a fiber.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Use of terms in written advertisements that imply presence of a fiber. 303.40 Section 303.40 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER THE TEXTILE FIBER PRODUCTS IDENTIFICATION ACT § 303.40 Use of terms in written...

Expression of urea transporters and their regulation.

PubMed

Klein, Janet D

2014-01-01

UT-A and UT-B families of urea transporters consist of multiple isoforms that are subject to regulation of both acutely and by long-term measures. This chapter provides a brief overview of the expression of the urea transporter forms and their locations in the kidney. Rapid regulation of UT-A1 results from the combination of phosphorylation and membrane accumulation. Phosphorylation of UT-A1 has been linked to vasopressin and hyperosmolality, although through different kinases. Other acute influences on urea transporter activity are ubiquitination and glycosylation, both of which influence the membrane association of the urea transporter, again through different mechanisms. Long-term regulation of urea transport is most closely associated with the environment that the kidney experiences. Low-protein diets may influence the amount of urea transporter available. Conditions of osmotic diuresis, where urea concentrations are low, will prompt an increase in urea transporter abundance. Although adrenal steroids affect urea transporter abundance, conflicting reports make conclusions tenuous. Urea transporters are upregulated when P2Y2 purinergic receptors are decreased, suggesting a role for these receptors in UT regulation. Hypercalcemia and hypokalemia both cause urine concentration deficiencies. Urea transporter abundances are reduced in aging animals and animals with angiotensin-converting enzyme deficiencies. This chapter will provide information about both rapid and long-term regulation of urea transporters and provide an introduction into the literature.

Regulating food service in North Carolina's long-term care facilities.

PubMed

DePorter, Cindy H

2005-01-01

Other commentaries in this issue of the North Carolina Medical Journal describe innovative food and dining practices in some of our state's long-term care facilities. Federal and state regulations do not prohibit these innovations, and DFS supports the concept of "enhancements" of the dining experience in these facilities. The Division of Facilities Services, therefore, encourages facilities to assess and operationalize various dining methods, allowing residents to select their foods, dining times, dining partners, and other preferences. The regulations allow facilities to utilize innovative dining approaches, such as buffet lines, or family-style serving options, which allow residents to order at the table as they would in a restaurant. The regulations do not dictate whether facilities should serve food to residents on trays, in buffet lines, or in a family style. While there are many regulations, they leave room for innovative new ideas as long as these ideas do not compromise resident health or safety.. Food consumption and the dining experience are an integral part of the resident's life in a nursing facility. It is important that resident preferences are being honored, and the dining experience is as pleasant and home-like as possible. The facility's responsibility is to provide adequate nutrition and hydration that assures the resident is at his/her highest level of functioning emotionally, functionally, and physically. Meeting the unique needs of each resident in a facility can be a daunting task, but one of immense importance to the quality long-term care.

Guidance for implementing the long-term surveillance program for UMTRA Project Title I Disposal Sites

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

NONE

1996-02-01

This guidance document has two purposes: it provides guidance for writing site-specific long-term surveillance plans (LTSP) and it describes site surveillance, monitoring, and long-term care techniques for Title I disposal sites of the Uranium Mill Tailings Radiation Control Act (UMTRCA) (42 USC Section 7901 et seq.). Long-term care includes monitoring, maintenance, and emergency measures needed to protect public health and safety and the environment after remedial action is completed. This document applies to the UMTRCA-designated Title I disposal sites. The requirements for long-term care of the Title I sites and the contents of the LTSPs are provided in U.S. Nuclearmore » Regulatory Commission (NRC) regulations (10 CFR Section 40.27) provided in Attachment 1.« less

Effects of six priority controlled phthalate esters with long-term low-dose integrated exposure on male reproductive toxicity in rats.

PubMed

Gao, Hai-Tao; Xu, Run; Cao, Wei-Xin; Qian, Liang-Liang; Wang, Min; Lu, Lingeng; Xu, Qian; Yu, Shu-Qin

2017-03-01

Human beings are inevitably exposed to ubiquitous phthalate esters (PEs) surroundings. The purposes of this study were to investigate the effects of long-term low-dose exposure to the mixture of six priority controlled phthalate esters (MIXPs): dimethyl phthalate (DMP), diethyl phthalate (DEP), di(n-butyl) phthalate (DBP), butyl benzyl phthalate (BBP), di(2-ethyhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP), on male rat reproductive system and further to explore the underlying mechanisms of the reproductive toxicity. The male rats were orally exposed to either sodium carboxymethyl cellulose as controls or MIXPs at three different low-doses by gavage for 15 weeks. Testosterone and luteinizing hormone (LH) in serum were analyzed, and pathological examinations were performed for toxicity evaluation. Steroidogenic proteins (StAR, P450scc, CYP17A1 and 17β-HSD), cell cycle and apoptosis-related proteins (p53, Chk1, Cdc2, CDK6, Bcl-2 and Bax) were measured for mechanisms exploration. MIXPs with long-term low-dose exposure could cause male reproductive toxicity to the rats, including the decrease of both serum and testicular testosterone, and the constructional damage of testis. These effects were related to down-regulated steroidogenic proteins, arresting cell cycle progression and promoting apoptosis in rat testicular cells. The results indicate that MIXPs with long-term low-dose exposure may pose male reproductive toxicity in human. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanism underlying the effect of long-term exposure to low dose of pesticides on DNA integrity.

PubMed

Alleva, Renata; Manzella, Nicola; Gaetani, Simona; Bacchetti, Tiziana; Bracci, Massimo; Ciarapica, Veronica; Monaco, Federica; Borghi, Battista; Amati, Monica; Ferretti, Gianna; Tomasetti, Marco

2018-04-01

Pesticides, including herbicides, insecticides and fungicides, are widely used in intensive agriculture. Recently, the long-term effects of pesticide exposure were found to be associated with many diseases. In this study, we evaluated the long-term effect of low-level exposure to a mixture of pesticides on DNA damage response (DDR) in relation to individual detoxifying variability. A residential population chronically exposed to pesticides was enrolled, biological/environmental pesticide levels; paroxonase 1 (PON-1) activity and 192 Q/R polymorphism and DDR were evaluated at three different periods of pesticide exposure. OGG1-dependent DNA repair activity was decreased in relation to pesticide exposure. The increase of DNA lesions and pesticide levels in the intensive pesticide-spraying period was independent on PON-1 activity. Next, human bronchial epithelial and neuronal cells were used as a model for in vitro evaluation of the mechanistic effect of pesticides. Pesticides induced mitochondrial dysfunction leading to ROS formation. ROS from mitochondria induced DNA damage, which in turn induced OGG1-dependent DNA repair activity through 8-oxoguanine DNA glycosylase 1 (OGG1) expression and activation. Even though OGG1 was overexpressed, an inhibition of its activity, associated with DNA lesion accumulation, was found at prolonged pesticide-exposure. A post-translational regulation of OGG1 by pesticide may be postulated. Taken together, long-term exposure to low-levels of pesticides affects DDR resulting in accumulation of DNA lesions that eventually may lead to cancer or neurological disorders. © 2018 Wiley Periodicals, Inc.

Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

PubMed Central

Kroeze, Y; Peeters, D; Boulle, F; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

2015-01-01

The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders. PMID:26393488

Outcomes related to effective nurse supervision in long-term care homes: an integrative review.

PubMed

McGilton, Katherine S; Chu, Charlene H; Shaw, Alexander C; Wong, Rosalind; Ploeg, Jenny

2016-11-01

The aim of this integrative review was to describe the organisational, unregulated nurse, and resident outcomes associated with effective supervisory performance of regulated nurses (registered nurses or registered practical nurses) in long-term care homes. While there are data on the influence of regulated nurse staffing levels on resident outcomes, the influence of effective supervisory performance of regulated nurses on resident and organisational outcomes, nursing assistant outcomes have yet to be comprehensively explored. A search of six databases was made for articles dating from 2000 to 2015. Twenty-four articles were selected and an integrative review was performed. Effective nurse supervision had statistically significant positive associations (P < 0.05, P < 0.000) with six different organisational, unregulated nurse and resident outcomes: nurse assistant job satisfaction, turnover/intention to leave, effectiveness, decision making, job stress and consumer satisfaction. Qualitative analyses corroborate these findings. There appear to be some associations between effective supervisory performance of regulated nurses with positive organisational, unregulated nursing and resident outcomes. Nursing managers and leaders in long-term care may promote improvements in effective nurse supervision performance as a way of reducing turnover and improving resident outcomes. © 2016 John Wiley & Sons Ltd.

45 CFR 144.206 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS RELATING TO HEALTH INSURANCE COVERAGE Qualified State Long-Term Care Insurance Partnerships... that sells a qualified long-term care insurance policy under a qualified State long-term care insurance...

12 CFR 563c.102 - Financial statement presentation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... deposits in depository institutions held as compensating balances against long- or short-term borrowing... and the conditions under which commitments may be withdrawn) of unused commitments for long-term... long-term borrowings. Include interest on bonds, capital notes, debentures, mortgages on association...

Modulation of Specific and Allergy-Related Immune Responses by Helminths

PubMed Central

Daniłowicz-Luebert, Emilia; O'Regan, Noëlle L.; Steinfelder, Svenja; Hartmann, Susanne

2011-01-01

Helminths are master regulators of host immune responses utilising complex mechanisms to dampen host protective Th2-type responses and favour long-term persistence. Such evasion mechanisms ensure mutual survival of both the parasite and the host. In this paper, we present recent findings on the cells that are targeted by helminths and the molecules and mechanisms that are induced during infection. We discuss the impact of these factors on the host response as well as their effect in preventing the development of aberrant allergic inflammation. We also examine recent findings on helminth-derived molecules that can be used as tools to pinpoint the underlying mechanisms of immune regulation or to determine new anti-inflammatory therapeutics. PMID:22219659

Body Fluid Regulation and Hemopoiesis in Space Flight

NASA Technical Reports Server (NTRS)

1997-01-01

In this session, Session JA2, the discussion focuses on the following topics: Bodymass and Fluid Distribution During Longterm Spaceflight with and without Countermeasures; Plasma Volume, Extracellular Fluid Volume, and Regulatory Hormones During Long-Term Space Flight; Effect of Microgravity and its Ground-Based Models on Fluid Volumes and Hemocirculatory Volumes; Seventeen Weeks of Horizontal Bed Rest, Lower Body Negative Pressure Testing, and the Associated Plasma Volume Response; Evaporative Waterloss in Space Theoretical and Experimental Studies; Erythropoietin Under Real and Simulated Micro-G Conditions in Humans; and Vertebral Bone Marrow Changes Following Space Flight.

Short Meditation Trainings Enhance Non-REM Sleep Low-Frequency Oscillations.

PubMed

Dentico, Daniela; Ferrarelli, Fabio; Riedner, Brady A; Smith, Richard; Zennig, Corinna; Lutz, Antoine; Tononi, Giulio; Davidson, Richard J

2016-01-01

We have recently shown higher parietal-occipital EEG gamma activity during sleep in long-term meditators compared to meditation-naive individuals. This gamma increase was specific for NREM sleep, was present throughout the entire night and correlated with meditation expertise, thus suggesting underlying long-lasting neuroplastic changes induced through prolonged training. The aim of this study was to explore the neuroplastic changes acutely induced by 2 intensive days of different meditation practices in the same group of practitioners. We also repeated baseline recordings in a meditation-naive cohort to account for time effects on sleep EEG activity. High-density EEG recordings of human brain activity were acquired over the course of whole sleep nights following intervention. Sound-attenuated sleep research room. Twenty-four long-term meditators and twenty-four meditation-naïve controls. Two 8-h sessions of either a mindfulness-based meditation or a form of meditation designed to cultivate compassion and loving kindness, hereafter referred to as compassion meditation. We found an increase in EEG low-frequency oscillatory activities (1-12 Hz, centered around 7-8 Hz) over prefrontal and left parietal electrodes across whole night NREM cycles. This power increase peaked early in the night and extended during the third cycle to high-frequencies up to the gamma range (25-40 Hz). There was no difference in sleep EEG activity between meditation styles in long-term meditators nor in the meditation naïve group across different time points. Furthermore, the prefrontal-parietal changes were dependent on meditation life experience. This low-frequency prefrontal-parietal activation likely reflects acute, meditation-related plastic changes occurring during wakefulness, and may underlie a top-down regulation from frontal and anterior parietal areas to the posterior parietal and occipital regions showing chronic, long-lasting plastic changes in long-term meditators.

The Womanly World of Long Term Care: The Plight of the Long Term Care Worker. Gray Paper.

ERIC Educational Resources Information Center

Older Women's League, Washington, DC.

Long-term care workers (those who are paid to provide custodial care for long-term patients in nursing homes or at home) must care for a growing number of increasingly disabled or dependent persons. They are working for agencies and institutions under growing pressure to increase productivity. They face new training and competency requirements,…

Coordinated Approaches to Quantify Long-Term Ecosystem dynamics in Response to Global Change

USDA-ARS?s Scientific Manuscript database

Climate change and its impact on ecosystems are usually assessed at decadal and century time scales. Ecological responses to climate change at those scales are strongly regulated by long-term processes, such as changes in species composition, carbon dynamics in soil and by big trees, and nutrient r...

5 CFR 875.414 - Will benefits be coordinated with other coverage?

Code of Federal Regulations, 2010 CFR

2010-01-01

... SERVICE REGULATIONS (CONTINUED) FEDERAL LONG TERM CARE INSURANCE PROGRAM Coverage § 875.414 Will benefits... coordination of benefits (COB) guidelines set by the National Association of Insurance Commissioners. The total benefits from all plans that pay a long term care benefit to you should not exceed the actual costs you...

Transgenic Mice Expressing an Inhibitory Truncated Form of p300 Exhibit Long-Term Memory Deficits

ERIC Educational Resources Information Center

Oliveira, Ana M. M.; Wood, Marcelo A.; McDonough, Conor B.; Abel, Ted

2007-01-01

The formation of many forms of long-term memory requires several molecular mechanisms including regulation of gene expression. The mechanisms directing transcription require not only activation of individual transcription factors but also recruitment of transcriptional coactivators. CBP and p300 are transcriptional coactivators that interact with…

Satb2 determines miRNA expression and long-term memory in the adult central nervous system.

PubMed

Jaitner, Clemens; Reddy, Chethan; Abentung, Andreas; Whittle, Nigel; Rieder, Dietmar; Delekate, Andrea; Korte, Martin; Jain, Gaurav; Fischer, Andre; Sananbenesi, Farahnaz; Cera, Isabella; Singewald, Nicolas; Dechant, Georg; Apostolova, Galina

2016-11-29

SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.

77 FR 76740 - Endangered and Threatened Species; Threatened Status for the Beringia and Okhotsk Distinct...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

...We, NMFS, issue a final determination to list the Beringia and Okhotsk distinct populations segments (DPSs) of the Erignathus barbatus nauticus subspecies of the bearded seal (Erignathus barbatus) as threatened under the Endangered Species Act (ESA). We will propose to designate critical habitat for the Beringia DPS in a future rulemaking. To assist us with this effort, we solicit information that may be relevant to the designation of critical habitat for the Beringia DPS. In light of public comments and upon further review, we are withdrawing the proposed ESA section 4(d) protective regulations for the Beringia and Okhotsk DPSs because we have determined that such regulations are not necessary or advisable for the conservation of the Beringia and Okhotsk DPSs at this time. Given their current population sizes, the long-term nature of the primary threat to these DPSs (habitat alteration stemming from climate change), and the existing protections under the Marine Mammal Protection Act, it is unlikely that the proposed protective regulations would provide appreciable conservation benefits.

Insulin signaling is acutely required for long-term memory in Drosophila.

PubMed

Chambers, Daniel B; Androschuk, Alaura; Rosenfelt, Cory; Langer, Steven; Harding, Mark; Bolduc, Francois V

2015-01-01

Memory formation has been shown recently to be dependent on energy status in Drosophila. A well-established energy sensor is the insulin signaling (InS) pathway. Previous studies in various animal models including human have revealed the role of insulin levels in short-term memory but its role in long-term memory remains less clear. We therefore investigated genetically the spatial and temporal role of InS using the olfactory learning and long-term memory model in Drosophila. We found that InS is involved in both learning and memory. InS in the mushroom body is required for learning and long-term memory whereas long-term memory specifically is impaired after InS signaling disruption in the ellipsoid body, where it regulates the level of p70s6k, a downstream target of InS and a marker of protein synthesis. Finally, we show also that InS is acutely required for long-term memory formation in adult flies.

The norepinephrine transporter and its regulation.

PubMed

Mandela, Prashant; Ordway, Gregory A

2006-04-01

For many years, the norepinephrine transporter (NET) was considered a 'static' protein that contributed to the termination of the action of norepinephrine in the synapse of noradrenergic neurons. The concept that the NET is dynamically regulated, adjusting noradrenergic transmission by changing its function and/or expression, was considered initially in the mid 1980s. Since that time, a plethora of studies demonstrate that the NET is regulated by several intracellular and extracellular signaling molecules, and that phosphorylation of the NET is a major pathway regulating its cell surface expression and thereby its function. The NET is a target of action of a number of drugs that are used long-term therapeutically or abused chronically. This has driven numerous investigations of how the NET and its function are regulated by long-term exposure to drugs. While repeated exposure to many drugs has been shown to affect NET function and expression, the intracellular mechanisms for these effects remains elusive.

The cytoskeleton of Drosophila-derived Schneider line-1 and Kc23 cells undergoes significant changes during long-term culture

NASA Technical Reports Server (NTRS)

Schatten, H.; Hedrick, J.; Chakrabarti, A.

1998-01-01

Insect cell cultures derived from Drosophila melanogaster are increasingly being used as an alternative system to mammalian cell cultures, as they are amenable to genetic manipulation. Although Drosophila cells are an excellent tool for the study of genes and expression of proteins, culture conditions have to be considered in the interpretation of biochemical results. Our studies indicate that significant differences occur in cytoskeletal structure during the long-term culture of the Drosophila-derived cell lines Schneider Line-1 (S1) and Kc23. Scanning, transmission-electron, and immunofluorescence microscopy studies reveal that microfilaments, microtubules, and centrosomes become increasingly different during the culture of these cells from 24 h to 7-14 days. Significant cytoskeletal changes are observed at the cell surface where actin polymerizes into microfilaments, during the elongation of long microvilli. Additionally, long protrusions develop from the cell surface; these protrusions are microtubule-based and establish contact with neighboring cells. In contrast, the microtubule network in the interior of the cells becomes disrupted after four days of culture, resulting in altered transport of mitochondria. Microtubules and centrosomes are also affected in a small percent of cells during cell division, indicating an instability of centrosomes. Thus, the cytoskeletal network of microfilaments, microtubules, and centrosomes is affected in Drosophila cells during long-term culture. This implies that gene regulation and post-translational modifications are probably different under different culture conditions.

Using Simulation to Compare 4 Categories of Intervention for Reducing Cardiovascular Disease Risks

PubMed Central

Homer, Jack; Trogdon, Justin; Wile, Kristina; Orenstein, Diane

2014-01-01

The Prevention Impacts Simulation Model (PRISM) projects the multiyear impacts of 22 different interventions aimed at reducing risk of cardiovascular disease. We grouped these into 4 categories: clinical, behavioral support, health promotion and access, and taxes and regulation. We simulated impacts for the United States overall and also for a less-advantaged county with a higher death rate. Of the 4 categories of intervention, taxes and regulation reduce costs the most in the short term (through 2020) and long term (through 2040) and reduce deaths the most in the long term; they are second to clinical interventions in reducing deaths in the short term. All 4 categories combined were required to bring costs and deaths in the less-advantaged county down to the national level. PMID:24832142

[Urine metabonomic study on long-term use of total ginsenosides in rats].

PubMed

Xie, Xie; Chen, Shao-Qiu; Lv, Ying-Fang; Wang, Xiao-Yan; Jia, Wei

2014-12-01

Due to its effect of systems regulation and promotion on body, Ginseng is always referred to be long-term used as a dietary supplement. But it was still unclear about its target of the tonic effects and also the side-effects long-term use may bring. Urine metabolomic method is suitable for long-term studies of pharmaco-dynamics, pharmacology and toxicology of traditional Chinese medicine because of its characteristics of non-invasive and monitoring the whole-body metabolism. This study was designed to detect the dynamic variation of rat urine metabolome along with a long-term administration of total ginsenosides using GC-TOF based metabolomic technology. Our result showed that either short-term or chronic administration of ginsenosides did not impact the rat urine metabolome significantly (as the PCA subgroup was not successful). By comparison, the short-term (1-3 w) dose of ginsenosides had the biggest metabolic influence including TCA cycle, catecholamines and neurotransmitter amino acids. Medium-term (6-10 w) dose had a gradually lower effect and long-term (27 w) dose almost had no effect. Our study indicates that both short and long-term administration of ginsenosides showed almost no obvious side-effect on the experimental animals.

Neural Protein Synthesis during Aging: Effects on Plasticity and Memory

PubMed Central

Schimanski, Lesley A.; Barnes, Carol A.

2010-01-01

During aging, many experience a decline in cognitive function that includes memory loss. The encoding of long-term memories depends on new protein synthesis, and this is also reduced during aging. Thus, it is possible that changes in the regulation of protein synthesis contribute to the memory impairments observed in older animals. Several lines of evidence support this hypothesis. For instance, protein synthesis is required for a longer period following learning to establish long-term memory in aged rodents. Also, under some conditions, synaptic activity or pharmacological activation can induce de novo protein synthesis and lasting changes in synaptic transmission in aged, but not young, rodents; the opposite results can be observed in other conditions. These changes in plasticity likely play a role in manifesting the altered place field properties observed in awake and behaving aged rats. The collective evidence suggests a link between memory loss and the regulation of protein synthesis in senescence. In fact, pharmaceuticals that target the signaling pathways required for induction of protein synthesis have improved memory, synaptic plasticity, and place cell properties in aged animals. We suggest that a better understanding of the mechanisms that lead to different protein expression patterns in the neural circuits that change as a function of age will enable the development of more effective therapeutic treatments for memory loss. PMID:20802800

Effects of Long-Term Dharma-Chan Meditation on Cardiorespiratory Synchronization and Heart Rate Variability Behavior

PubMed Central

Chang, Chih-Hao

2013-01-01

Abstract Remarkable changes in cardiorespiratory interactions are frequently experienced by Chan meditation practitioners following years of practice. This study compares the results of our study on cardiorespiratory interactions for novice (control group) and experienced (experimental group) Chan meditation practitioners. The effectual co-action between the cardiac and respiratory systems was evaluated by the degree of cardiorespiratory phase synchronization (CRPS). In addition, an adaptive-frequency-range (AFR) scheme to reliably quantify heart rate variability (HRV) was developed for assessing the regulation of sympathetic–parasympathetic activity and the efficiency of pulmonary gas exchange. The enhanced HRV method, named HRVAFR, can resolve the issue of overestimating HRV under the condition of slow respiration rates, which is frequently encountered in studies on Chan meditation practitioners. In the comparison of the three data sets collected from the two groups, our findings resulted in innovative hypotheses to interpret the extraordinary process of the rejuvenation of cardiorespiratory functions through long-term Dharma-Chan meditation practice. Particularly, advanced practitioners exhibit a continuously high degree of cardiorespiratory phase synchronization, even during rapid breathing. Based on our post-experimental interview with advanced practitioners, the activation of inner Chakra energy, during the course of Chan-detachment practice, frequently induces perceptible physiological-mental reformation, including an efficient mechanism for regulating cardiorespiratory interactions. PMID:23323597

Effects of long-term dharma-chan meditation on cardiorespiratory synchronization and heart rate variability behavior.

PubMed

Chang, Chih-Hao; Lo, Pei-Chen

2013-04-01

Remarkable changes in cardiorespiratory interactions are frequently experienced by Chan meditation practitioners following years of practice. This study compares the results of our study on cardiorespiratory interactions for novice (control group) and experienced (experimental group) Chan meditation practitioners. The effectual co-action between the cardiac and respiratory systems was evaluated by the degree of cardiorespiratory phase synchronization (CRPS). In addition, an adaptive-frequency-range (AFR) scheme to reliably quantify heart rate variability (HRV) was developed for assessing the regulation of sympathetic-parasympathetic activity and the efficiency of pulmonary gas exchange. The enhanced HRV method, named HRVAFR, can resolve the issue of overestimating HRV under the condition of slow respiration rates, which is frequently encountered in studies on Chan meditation practitioners. In the comparison of the three data sets collected from the two groups, our findings resulted in innovative hypotheses to interpret the extraordinary process of the rejuvenation of cardiorespiratory functions through long-term Dharma-Chan meditation practice. Particularly, advanced practitioners exhibit a continuously high degree of cardiorespiratory phase synchronization, even during rapid breathing. Based on our post-experimental interview with advanced practitioners, the activation of inner Chakra energy, during the course of Chan-detachment practice, frequently induces perceptible physiological-mental reformation, including an efficient mechanism for regulating cardiorespiratory interactions.

Pannexin 1 regulates bidirectional hippocampal synaptic plasticity in adult mice.

PubMed

Ardiles, Alvaro O; Flores-Muñoz, Carolina; Toro-Ayala, Gabriela; Cárdenas, Ana M; Palacios, Adrian G; Muñoz, Pablo; Fuenzalida, Marco; Sáez, Juan C; Martínez, Agustín D

2014-01-01

The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca(2+) concentration and NMDA receptor (NMDAR) composition of GluN2 subunits. Pannexin 1 (Panx1), a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP), it remains unknown whether these channels also modulate long-term depression (LTD) or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory.

Pannexin 1 regulates bidirectional hippocampal synaptic plasticity in adult mice

PubMed Central

Ardiles, Alvaro O.; Flores-Muñoz, Carolina; Toro-Ayala, Gabriela; Cárdenas, Ana M.; Palacios, Adrian G.; Muñoz, Pablo; Fuenzalida, Marco; Sáez, Juan C.; Martínez, Agustín D.

2014-01-01

The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca2+ concentration and NMDA receptor (NMDAR) composition of GluN2 subunits. Pannexin 1 (Panx1), a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP), it remains unknown whether these channels also modulate long-term depression (LTD) or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory. PMID:25360084

Proteome-wide analysis and diel proteomic profiling of the cyanobacterium Arthrospira platensis PCC 8005.

PubMed

Matallana-Surget, Sabine; Derock, Jérémy; Leroy, Baptiste; Badri, Hanène; Deschoenmaeker, Frédéric; Wattiez, Ruddy

2014-01-01

The filamentous cyanobacterium Arthrospira platensis has a long history of use as a food supply and it has been used by the European Space Agency in the MELiSSA project, an artificial microecosystem which supports life during long-term manned space missions. This study assesses progress in the field of cyanobacterial shotgun proteomics and light/dark diurnal cycles by focusing on Arthrospira platensis. Several fractionation workflows including gel-free and gel-based protein/peptide fractionation procedures were used and combined with LC-MS/MS analysis, enabling the overall identification of 1306 proteins, which represents 21% coverage of the theoretical proteome. A total of 30 proteins were found to be significantly differentially regulated under light/dark growth transition. Interestingly, most of the proteins showing differential abundance were related to photosynthesis, the Calvin cycle and translation processes. A novel aspect and major achievement of this work is the successful improvement of the cyanobacterial proteome coverage using a 3D LC-MS/MS approach, based on an immobilized metal affinity chromatography, a suitable tool that enabled us to eliminate the most abundant protein, the allophycocyanin. We also demonstrated that cell growth follows a light/dark cycle in A. platensis. This preliminary proteomic study has highlighted new characteristics of the Arthrospira platensis proteome in terms of diurnal regulation.

Proteome-Wide Analysis and Diel Proteomic Profiling of the Cyanobacterium Arthrospira platensis PCC 8005

PubMed Central

Matallana-Surget, Sabine; Derock, Jérémy; Leroy, Baptiste; Badri, Hanène; Deschoenmaeker, Frédéric; Wattiez, Ruddy

2014-01-01

The filamentous cyanobacterium Arthrospira platensis has a long history of use as a food supply and it has been used by the European Space Agency in the MELiSSA project, an artificial microecosystem which supports life during long-term manned space missions. This study assesses progress in the field of cyanobacterial shotgun proteomics and light/dark diurnal cycles by focusing on Arthrospira platensis. Several fractionation workflows including gel-free and gel-based protein/peptide fractionation procedures were used and combined with LC-MS/MS analysis, enabling the overall identification of 1306 proteins, which represents 21% coverage of the theoretical proteome. A total of 30 proteins were found to be significantly differentially regulated under light/dark growth transition. Interestingly, most of the proteins showing differential abundance were related to photosynthesis, the Calvin cycle and translation processes. A novel aspect and major achievement of this work is the successful improvement of the cyanobacterial proteome coverage using a 3D LC-MS/MS approach, based on an immobilized metal affinity chromatography, a suitable tool that enabled us to eliminate the most abundant protein, the allophycocyanin. We also demonstrated that cell growth follows a light/dark cycle in A. platensis. This preliminary proteomic study has highlighted new characteristics of the Arthrospira platensis proteome in terms of diurnal regulation. PMID:24914774

On the nature and consequences of early loss.

PubMed

Hofer, M A

1996-01-01

To describe how an animal model system can be used to explore basic questions about the nature of loss and the effects of early loss on later vulnerability to disease. The physiological and behavioral responses of infant rats to separation from their mothers are first described and then analyzed experimentally into component mechanisms. These studies have revealed an extensive layer of processes underlying the psychological constructs generally used to understand the response to loss. Hidden within the observable interactions of parent and offspring, we found a number of discrete sensorimotor, thermal, and nutrient-based events that have unexpected long-term regulatory effects on specific components of infant physiology and behavior. Release from all of these inhibitory and excitatory regulators together during maternal separation constitutes a novel mechanism by which the experience of loss can be translated into a complex patterned response. Evidence for early regulatory processes has also been found in monkey and human mother-infant interactions. Here they may well constitute the building blocks from which attachment and object representations develop. We and others have found long-term effects of loss, and of selective replacement of regulators, on behavioral development and on later vulnerability to disease. The results give us a new understanding of early attachment as a developmental force and of human grief as a risk to health.

Increased core body temperature in astronauts during long-duration space missions.

PubMed

Stahn, Alexander C; Werner, Andreas; Opatz, Oliver; Maggioni, Martina A; Steinach, Mathias; von Ahlefeld, Victoria Weller; Moore, Alan; Crucian, Brian E; Smith, Scott M; Zwart, Sara R; Schlabs, Thomas; Mendt, Stefan; Trippel, Tobias; Koralewski, Eberhard; Koch, Jochim; Choukèr, Alexander; Reitz, Günther; Shang, Peng; Röcker, Lothar; Kirsch, Karl A; Gunga, Hanns-Christian

2017-11-23

Humans' core body temperature (CBT) is strictly controlled within a narrow range. Various studies dealt with the impact of physical activity, clothing, and environmental factors on CBT regulation under terrestrial conditions. However, the effects of weightlessness on human thermoregulation are not well understood. Specifically, studies, investigating the effects of long-duration spaceflight on CBT at rest and during exercise are clearly lacking. We here show that during exercise CBT rises higher and faster in space than on Earth. Moreover, we observed for the first time a sustained increased astronauts' CBT also under resting conditions. This increase of about 1 °C developed gradually over 2.5 months and was associated with augmented concentrations of interleukin-1 receptor antagonist, a key anti-inflammatory protein. Since even minor increases in CBT can impair physical and cognitive performance, both findings have a considerable impact on astronauts' health and well-being during future long-term spaceflights. Moreover, our findings also pinpoint crucial physiological challenges for spacefaring civilizations, and raise questions about the assumption of a thermoregulatory set point in humans, and our evolutionary ability to adapt to climate changes on Earth.

Global and regional alterations of hippocampal anatomy in long-term meditation practitioners.

PubMed

Luders, Eileen; Thompson, Paul M; Kurth, Florian; Hong, Jui-Yang; Phillips, Owen R; Wang, Yalin; Gutman, Boris A; Chou, Yi-Yu; Narr, Katherine L; Toga, Arthur W

2013-12-01

Studies linking meditation and brain structure are still relatively sparse, but the hippocampus is consistently implicated as one of the structures altered in meditation practitioners. To explore hippocampal features in the framework of meditation, we analyzed high-resolution structural magnetic resonance imaging data from 30 long-term meditators and 30 controls, closely matched for sex, age, and handedness. Hippocampal formations were manually traced following established protocols. In addition to calculating left and right hippocampal volumes (global measures), regional variations in surface morphology were determined by measuring radial distances from the hippocampal core to spatially matched surface points (local measures). Left and right hippocampal volumes were larger in meditators than in controls, significantly so for the left hippocampus. The presence and direction of this global effect was confirmed locally by mapping the exact spatial locations of the group differences. Altogether, radial distances were larger in meditators compared to controls, with up to 15% difference. These local effects were observed in several hippocampal regions in the left and right hemisphere though achieved significance primarily in the left hippocampal head. Larger hippocampal dimensions in long-term meditators may constitute part of the underlying neurological substrate for cognitive skills, mental capacities, and/or personal traits associated with the practice of meditation. Alternatively, given that meditation positively affects autonomic regulation and immune activity, altered hippocampal dimensions may be one result of meditation-induced stress reduction. However, given the cross-sectional design, the lack of individual stress measures, and the limited resolution of brain data, the exact underlying neuronal mechanisms remain to be established. Copyright © 2012 Wiley Periodicals, Inc.

Global and Regional Alterations of Hippocampal Anatomy in Long-Term Meditation Practitioners

PubMed Central

Luders, Eileen; Thompson, Paul M.; Kurth, Florian; Hong, Jui-Yang; Phillips, Owen R.; Wang, Yalin; Gutman, Boris A.; Chou, Yi-Yu; Narr, Katherine L.; Toga, Arthur W.

2014-01-01

Studies linking meditation and brain structure are still relatively sparse, but the hippocampus is consistently implicated as one of the structures altered in meditation practitioners. To explore hippocampal features in the framework of meditation, we analyzed high-resolution structural magnetic resonance imaging data from 30 long-term meditators and 30 controls, closely matched for sex, age, and handedness. Hippocampal formations were manually traced following established protocols. In addition to calculating left and right hippocampal volumes (global measures), regional variations in surface morphology were determined by measuring radial distances from the hippocampal core to spatially matched surface points (local measures). Left and right hippocampal volumes were larger in meditators than in controls, significantly so for the left hippocampus. The presence and direction of this global effect was confirmed locally by mapping the exact spatial locations of the group differences. Altogether, radial distances were larger in meditators compared to controls, with up to 15% difference. These local effects were observed in several hippocampal regions in the left and right hemisphere though achieved significance primarily in the left hippocampal head. Larger hippocampal dimensions in long-term meditators may constitute part of the underlying neurological substrate for cognitive skills, mental capacities, and/or personal traits associated with the practice of meditation. Alternatively, given that meditation positively affects autonomic regulation and immune activity, altered hippocampal dimensions may be one result of meditation-induced stress reduction. However, given the cross-sectional design, the lack of individual stress measures, and the limited resolution of brain data, the exact underlying neuronal mechanisms remain to be established. PMID:22815233

Short and long-term energy intake patterns and their implications for human body weight regulation.

PubMed

Chow, Carson C; Hall, Kevin D

2014-07-01

Adults consume millions of kilocalories over the course of a few years, but the typical weight gain amounts to only a few thousand kilocalories of stored energy. Furthermore, food intake is highly variable from day to day and yet body weight is remarkably stable. These facts have been used as evidence to support the hypothesis that human body weight is regulated by active control of food intake operating on both short and long time scales. Here, we demonstrate that active control of human food intake on short time scales is not required for body weight stability and that the current evidence for long term control of food intake is equivocal. To provide more data on this issue, we emphasize the urgent need for developing new methods for accurately measuring energy intake changes over long time scales. We propose that repeated body weight measurements can be used along with mathematical modeling to calculate long-term changes in energy intake and thereby quantify adherence to a diet intervention and provide dynamic feedback to individuals that seek to control their body weight. Published by Elsevier Inc.

Short and long-term energy intake patterns and their implications for human body weight regulation

PubMed Central

Chow, Carson C.; Hall, Kevin D.

2014-01-01

Adults consume millions of kilocalories over the course of a few years, but the typical weight gain amounts to only a few thousand kilocalories of stored energy. Furthermore, food intake is highly variable from day to day and yet body weight is remarkably stable. These facts have been used as evidence to support the hypothesis that human body weight is regulated by active control of food intake operating on both short and long time scales. Here, we demonstrate that active control of human food intake on short time scales is not required for body weight stability and that the current evidence for long term control of food intake is equivocal. To provide more data on this issue, we emphasize the urgent need for developing new methods for accurately measuring energy intake changes over long time scales. We propose that repeated body weight measurements can be used along with mathematical modeling to calculate long-term changes in energy intake and thereby quantify adherence to a diet intervention and provide dynamic feedback to individuals that seek to control their body weight. PMID:24582679

Long-Term Evolution Studies of E. Coli under Combined Effects of Simulated Microgravity and Antibiotic.

NASA Astrophysics Data System (ADS)

Karouia, Fathi; Tirumalai, Madhan R.; Ott, Mark C.; Pierson, Duane L.; Fox, George E.; Tran, Quyen

2016-07-01

Multiple spaceflight and simulated microgravity experiments have shown changes in phenotypic microbial characteristics such as microbial growth, morphology, metabolism, genetic transfer, antibiotic and stress susceptibility, and an increase in virulence factors. However, while these studies have contributed to expand our understanding of the short-term effects of spaceflight or simulated microgravity on biological systems, it remains unclear the type of responses subsequent to long-term exposure to space environment and microgravity in particular. As such, organisms exposed to the space environment for extended periods of time may evolve in unanticipated ways thereby negatively impacting long duration space missions. We report here for the first time, an experimental study of microbial evolution in which the effect of long-term exposure to Low Shear Modeled MicroGravity (LSMMG) on microbial gene expression and physiology in Escherichia coli (E. coli) MG1655 was examined using functional genomics, and molecular techniques with and without simultaneous exposure to broad spectrum antibiotic chloramphenicol. E. coli cells were grown under simulated microgravity for 1000 generations in High Aspect Ratio Vessels (HARVs) that were either heat-sterilized (115 deg C, 15 min) or by using/rinsing the HARVs with a saturated solution of the broad-spectrum antibiotic chloramphenicol. In the case of the cells evolved using the antibiotic sterilized HARVs, the expression levels of 357 genes were significantly changed. In particular, fimbriae encoding genes were significantly up-regulated whereas genes encoding the flagellar motor complex were down-regulated. Re-sequencing of the genome revealed that a number of the flagellar genes were actually deleted. The antibiotic resistance levels of the evolved strains were analyzed using VITEK analyzer. The evolved strain was consistently resistant to the antibiotics used (viz., Ampicillin, Cefalotin, Cefurox-ime, Cefuroxime Axetil, Cefoxitin and Tetracycline), even after 11 cycles of 'erasure' of the 'adaptation memory' - this 'erasure' was accomplished by re-growing the evolved cells under shaker flask conditions and 1 cycle equals 10 generations. In the case of the cells evolved using heat sterilized HARVs, no resistance was observed to any of the an-tibiotics used (Ampicillin, Amoxicillin/Clavulanic Acid, Piperacillin/Tazobactam, Cefalotin, Cefazolin, Cefuroxime, Cefuroxime Axetil, Cefoxitin, Cefpodox-ime, Ceftazidime, Ceftriaxone, Cefepime, Gentamicin, Tobramycin, Ciprofloxacin, Levofloxacin, Norfloxacin, Tetracycline, Nitrofurantoin, and Trimethoprim/Sulfamethoxazole), even after 1000 generations of growth under LSMMG. Competition experiments using an isogenic pair revealed that the adaptive advantage of the 1000G strain (in both cases) over an unexposed strain was rapidly eliminated. While this obviously implies that the adaptation was primarily environmental rather than genomic, the levels of antibiotic resistance observed to be consistently maintained, raises the concern of persistent resistance conferred to bacterial communities through exposure to antibiotics on space missions. Supported by grants from the Center for Bionanotechnology and Environmental Research at Texas Southern University (NASA Cooperative Agreement NNX08B4A47A).

Significance of microbial asynchronous anabolism to soil carbon dynamics driven by litter inputs

PubMed Central

Fan, Zhaosheng; Liang, Chao

2015-01-01

Soil organic carbon (SOC) plays an important role in the global carbon cycle. However, it remains largely unknown how plant litter inputs impact magnitude, composition and source configuration of the SOC stocks over long term through microbial catabolism and anabolism, mostly due to uncoupled research on litter decomposition and SOC formation. This limits our ability to predict soil system responses to changes in land-use and climate. Here, we examine how microbes act as a valve controlling carbon sequestrated from plant litters versus released to the atmosphere in natural ecosystems amended with plant litters varying in quantity and quality. We find that litter quality – not quantity – regulates long-term SOC dynamics under different plausible scenarios. Long-term changes in bulk SOC stock occur only when the quality of carbon inputs causes asynchronous change in a microbial physiological trait, defined as “microbial biosynthesis acceleration” (MBA). This is the first theoretical demonstration that the response of the SOC stocks to litter inputs is critically determined by the microbial physiology. Our work suggests that total SOC at an equilibrium state may be an intrinsic property of a given ecosystem, which ultimately is controlled by the asynchronous MBA between microbial functional groups. PMID:25849864

Significance of microbial asynchronous anabolism to soil carbon dynamics driven by litter inputs

DOE PAGES

Fan, Zhaosheng; Liang, Chao

2015-04-02

Soil organic carbon (SOC) plays an important role in the global carbon cycle. However, it remains largely unknown how plant litter inputs impact magnitude, composition and source configuration of the SOC stocks over long term through microbial catabolism and anabolism, mostly due to uncoupled research on litter decomposition and SOC formation. This limits our ability to predict soil system responses to changes in land-use and climate. Here, we examine how microbes act as a valve controlling carbon sequestrated from plant litters versus released to the atmosphere in natural ecosystems amended with plant litters varying in quantity and quality. We findmore » that litter quality – not quantity – regulates long-term SOC dynamics under different plausible scenarios. Long-term changes in bulk SOC stock occur only when the quality of carbon inputs causes asynchronous change in a microbial physiological trait, defined as ‘‘microbial biosynthesis acceleration’’ (MBA). This is the first theoretical demonstration that the response of the SOC stocks to litter inputs is critically determined by the microbial physiology. Our work suggests that total SOC at an equilibrium state may be an intrinsic property of a given ecosystem, which ultimately is controlled by the asynchronous MBA between microbial functional groups.« less

Contributions of Bcl-xL to acute and long term changes in bioenergetics during neuronal plasticity.

PubMed

Jonas, Elizabeth A

2014-08-01

Mitochondria manufacture and release metabolites and manage calcium during neuronal activity and synaptic transmission, but whether long term alterations in mitochondrial function contribute to the neuronal plasticity underlying changes in organism behavior patterns is still poorly understood. Although normal neuronal plasticity may determine learning, in contrast a persistent decline in synaptic strength or neuronal excitability may portend neurite retraction and eventual somatic death. Anti-death proteins such as Bcl-xL not only provide neuroprotection at the neuronal soma during cell death stimuli, but also appear to enhance neurotransmitter release and synaptic growth and development. It is proposed that Bcl-xL performs these functions through its ability to regulate mitochondrial release of bioenergetic metabolites and calcium, and through its ability to rapidly alter mitochondrial positioning and morphology. Bcl-xL also interacts with proteins that directly alter synaptic vesicle recycling. Bcl-xL translocates acutely to sub-cellular membranes during neuronal activity to achieve changes in synaptic efficacy. After stressful stimuli, pro-apoptotic cleaved delta N Bcl-xL (ΔN Bcl-xL) induces mitochondrial ion channel activity leading to synaptic depression and this is regulated by caspase activation. During physiological states of decreased synaptic stimulation, loss of mitochondrial Bcl-xL and low level caspase activation occur prior to the onset of long term decline in synaptic efficacy. The degree to which Bcl-xL changes mitochondrial membrane permeability may control the direction of change in synaptic strength. The small molecule Bcl-xL inhibitor ABT-737 has been useful in defining the role of Bcl-xL in synaptic processes. Bcl-xL is crucial to the normal health of neurons and synapses and its malfunction may contribute to neurodegenerative disease. Copyright © 2013. Published by Elsevier B.V.

Extracellular signal-regulated protein kinases 1 and 2 activation by addictive drugs: a signal toward pathological adaptation.

PubMed

Pascoli, Vincent; Cahill, Emma; Bellivier, Frank; Caboche, Jocelyne; Vanhoutte, Peter

2014-12-15

Addiction is a chronic and relapsing psychiatric disorder that is thought to occur in vulnerable individuals. Synaptic plasticity evoked by drugs of abuse in the so-called neuronal circuits of reward has been proposed to underlie behavioral adaptations that characterize addiction. By increasing dopamine in the striatum, addictive drugs alter the balance of dopamine and glutamate signals converging onto striatal medium-sized spiny neurons (MSNs) and activate intracellular events involved in long-term behavioral alterations. Our laboratory contributed to the identification of salient molecular changes induced by administration of addictive drugs to rodents. We pioneered the observation that a common feature of addictive drugs is to activate, by a double tyrosine/threonine phosphorylation, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the striatum, which control a plethora of substrates, some of them being critically involved in cocaine-mediated molecular and behavioral adaptations. Herein, we review how the interplay between dopamine and glutamate signaling controls cocaine-induced ERK1/2 activation in MSNs. We emphasize the key role of N-methyl-D-aspartate receptor potentiation by D1 receptor to trigger ERK1/2 activation and its subsequent nuclear translocation where it modulates both epigenetic and genetic processes engaged by cocaine. We discuss how cocaine-induced long-term synaptic and structural plasticity of MSNs, as well as behavioral adaptations, are influenced by ERK1/2-controlled targets. We conclude that a better knowledge of molecular mechanisms underlying ERK1/2 activation by drugs of abuse and/or its role in long-term neuronal plasticity in the striatum may provide a new route for therapeutic treatment in addiction. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Long-Term Overgrazing-Induced Memory Decreases Photosynthesis of Clonal Offspring in a Perennial Grassland Plant.

PubMed

Ren, Weibo; Hu, Ningning; Hou, Xiangyang; Zhang, Jize; Guo, Huiqin; Liu, Zhiying; Kong, Lingqi; Wu, Zinian; Wang, Hui; Li, Xiliang

2017-01-01

Previous studies of transgenerational plasticity have demonstrated that long-term overgrazing experienced by Leymus chinensis , an ecologically dominant, rhizomatous grass species in eastern Eurasian temperate grassland, significantly affects its clonal growth in subsequent generations. However, there is a dearth of information on the reasons underlying this overgrazing-induced memory effect in plant morphological plasticity. We characterized the relationship between a dwarf phenotype and photosynthesis function decline of L. chinensis from the perspective of leaf photosynthesis by using both field measurement and rhizome buds culture cultivated in a greenhouse. Leaf photosynthetic functions (net photosynthetic rate, stomatal conductance, intercellular carbon dioxide concentration, and transpiration rate) were significantly decreased in smaller L. chinensis individuals that were induced to have a dwarf phenotype by being heavily grazed in the field. This decreased photosynthetic function was maintained a generation after greenhouse tests in which grazing was excluded. Both the response of L. chinensis morphological traits and photosynthetic functions in greenhouse were deceased relative to those in the field experiment. Further, there were significant decreases in leaf chlorophyll content and Rubisco enzyme activities of leaves between bud-cultured dwarf and non-dwarf L. chinensis in the greenhouse. Moreover, gene expression patterns showed that the bud-cultured dwarf L. chinensis significantly down-regulated (by 1.86- to 5.33-fold) a series of key genes that regulate photosynthetic efficiency, stomata opening, and chloroplast development compared with the non-dwarf L. chinensis . This is among the first studies revealing a linkage between long-term overgrazing affecting the transgenerational morphological plasticity of clonal plants and physiologically adaptive photosynthesis function. Overall, clonal transgenerational effects in L. chinensis phenotypic traits heavily involve photosynthetic plasticity.

Long-Term Overgrazing-Induced Memory Decreases Photosynthesis of Clonal Offspring in a Perennial Grassland Plant

PubMed Central

Ren, Weibo; Hu, Ningning; Hou, Xiangyang; Zhang, Jize; Guo, Huiqin; Liu, Zhiying; Kong, Lingqi; Wu, Zinian; Wang, Hui; Li, Xiliang

2017-01-01

Previous studies of transgenerational plasticity have demonstrated that long-term overgrazing experienced by Leymus chinensis, an ecologically dominant, rhizomatous grass species in eastern Eurasian temperate grassland, significantly affects its clonal growth in subsequent generations. However, there is a dearth of information on the reasons underlying this overgrazing-induced memory effect in plant morphological plasticity. We characterized the relationship between a dwarf phenotype and photosynthesis function decline of L. chinensis from the perspective of leaf photosynthesis by using both field measurement and rhizome buds culture cultivated in a greenhouse. Leaf photosynthetic functions (net photosynthetic rate, stomatal conductance, intercellular carbon dioxide concentration, and transpiration rate) were significantly decreased in smaller L. chinensis individuals that were induced to have a dwarf phenotype by being heavily grazed in the field. This decreased photosynthetic function was maintained a generation after greenhouse tests in which grazing was excluded. Both the response of L. chinensis morphological traits and photosynthetic functions in greenhouse were deceased relative to those in the field experiment. Further, there were significant decreases in leaf chlorophyll content and Rubisco enzyme activities of leaves between bud-cultured dwarf and non-dwarf L. chinensis in the greenhouse. Moreover, gene expression patterns showed that the bud-cultured dwarf L. chinensis significantly down-regulated (by 1.86- to 5.33-fold) a series of key genes that regulate photosynthetic efficiency, stomata opening, and chloroplast development compared with the non-dwarf L. chinensis. This is among the first studies revealing a linkage between long-term overgrazing affecting the transgenerational morphological plasticity of clonal plants and physiologically adaptive photosynthesis function. Overall, clonal transgenerational effects in L. chinensis phenotypic traits heavily involve photosynthetic plasticity. PMID:28484469

Long-term neurocognitive dysfunction in offspring via NGF/ ERK/CREB signaling pathway caused by ketamine exposure during the second trimester of pregnancy in rats.

PubMed

Li, Yanan; Li, Xinran; Guo, Cen; Li, Lina; Wang, Yuxin; Zhang, Yiming; Chen, Yu; Liu, Wenhan; Gao, Li

2017-05-09

Early life exposure to ketamine caused neurohistopathologic changes and persistent cognitive dysfunction. For this study, a pregnant rat model was developed to investigate neurocognitive effects in the offspring, following ketamine exposure during the second trimester. Pregnant rats on gestational day 14 (equal to midtrimester pregnancy in humans), intravenously received 200 mg/kg ketamine for 3 h. Their behavior was tested (Morris water maze, odor recognition test, and fear conditioning) at postnatal days (P25-30). Furthermore, hippocampal morphology of the offspring (P30) was examined via Nissl staining and hippocampal dendritic spine density was determined via Golgi staining. The hippocampal protein levels of nerve growth factor (NGF), extracellular signal-regulated kinase (ERK), phosphorylated-ERK (p-ERK), cyclic adenosine monophosphate response element-binding (CREB), p-CREB, synaptophysin (SYP), synapsin (SYN), and postsynaptic density-95 (PSD95) were measured via western blot. Additionally, SCH772984 (an ERK inhibitor) was used to evaluate both role and underlying mechanism of the ERK pathway in PC12 cells. We found that ketamine caused long-term neurocognitive dysfunction, reduced the density of the dendritic spin, caused neuronal loss, and down-regulated the expression of NGF, ERK, p-ERK, mitogen, and stress-activated protein kinase (MSK), CREB, p-CREB, SYP, SYN, and PSD95 in the hippocampus. These results suggest that ketamine induced maternal anesthesia during period of the fetal brain development can cause long-term neurocognitive dysfunction in the offspring, which likely happens via inhibition of the NGF-ERK-CREB pathway in the hippocampus. Our results highlight the central role of ERK in neurocognition.

New parity, same old attitude towards psychotherapy?

PubMed

Clemens, Norman A

2010-03-01

Full parity of health insurance benefits for treatment of mental illness, including substance use disorders, is a major achievement. However, the newly-published regulations implementing the legislation strongly endorse aggressive managed care as a way of containing costs for the new equality of coverage. Reductions in "very long episodes of out-patient care," hospitalization, and provider fees, along with increased utilization, are singled out as achievements of managed care. Medical appropriateness as defined by expert medical panels is to be the basis of authorizing care, though clinicians are familiar with a history of insurance companies' application of "medical necessity" to their own advantage. The regulations do not single out psychotherapy for attention, but long-term psychotherapy geared to the needs of each patient appears to be at risk. The author recommends that the mental health professions strongly advocate for the growing evidence base for psychotherapy including long-term therapy for complex mental disorders; respect for the structure and process of psychotherapy individualized to patients' needs; awareness of the costs of aggressive managed care in terms of money, time, administrative burden, and interference with the therapy; and recognition of the extensive training and experience required to provide psychotherapy as well as the stresses and demands of the work. Parity in out-of-network benefits could lead to aggressive management of care given by non-network practitioners. Since a large percentage of psychiatrists and other mental health professionals stay out of networks, implementation of parity for out-of-network providers will have to be done in a way that respects the conditions under which they would be willing and able to provide services, especially psychotherapy, to insured patients. The shortage of psychiatrists makes this an important access issue for the insured population in need of care.

76 FR 15004 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-18

... company (``fund'') distributions of long-term capital gains made more frequently than once every twelve months. Rule 19b-1 under the Act \\1\\ prohibits funds from distributing long-term capital gains more than... fixed-income securities to distribute long-term capital gains more than once every twelve months, if: (i...

Long-term tillage frequency effects on dryland soil physical and hydraulic properties

USDA-ARS?s Scientific Manuscript database

Long-term tillage influences physical, chemical, and biological properties of the soil environment and thereby crop production and quality. We evaluated the effect of long-term (> 22 years) tillage frequency [no-till (NT), spring till (ST), and fall and spring till (FST)] under continuous spring whe...

Focus on the short- and long-term effects of ghrelin on energy homeostasis.

PubMed

De Vriese, Carine; Perret, Jason; Delporte, Christine

2010-06-01

The endogenous ligand for the growth hormone secretagogue receptor, ghrelin, is a 28-amino-acid peptide acylated with an octanoyl group at the serine in position 3. Most of the circulating ghrelin results from its synthesis and secretion by the X/A-like endocrine cells from the stomach and proximal small intestine. Besides its potent growth hormone secretory action, ghrelin is a highly pleiotropic hormone, contributing significantly to the regulation of appetite and food intake control, gastrointestinal motility, gastric acid secretion, endocrine and exocrine pancreatic secretions, cell proliferation, glucose and lipid metabolism, and cardiovascular and immunologic processes. The purpose of this review is to consider the orexigenic effects of ghrelin on short-term regulation of food intake and long-term regulation of body weight, the implications of genetic ghrelin and growth hormone secretagogue receptor polymorphism, and the use of antagonists and agonists of ghrelin in pathophysiological conditions. Copyright 2010 Elsevier Inc. All rights reserved.

Alcohol and cannabis: Comparing their adverse health effects and regulatory regimes.

PubMed

Hall, Wayne

2017-04-01

The claim that the adverse health effects of cannabis are much less serious than those of alcohol has been central to the case for cannabis legalisation. Regulators in US states that have legalised cannabis have adopted regulatory models based on alcohol. This paper critically examines the claim about adverse health effects and the wisdom of regulating cannabis like alcohol. First, it compares what we know about the adverse health effects of alcohol and cannabis. Second, it discusses the uncertainties about the long term health effects of sustained daily cannabis use. Third, it speculates about how the adverse health effects of cannabis may change after legalisation. Fourth, it questions the assumption that alcohol provides the best regulatory model for a legal cannabis market. Fifth, it outlines the major challenges in regulating cannabis under the liberal alcohol-like regulatory regimes now being introduced. Copyright © 2016 Elsevier B.V. All rights reserved.

Long term betaine supplementation regulates genes involved in lipid and cholesterol metabolism of two muscles from an obese pig breed.

PubMed

Albuquerque, A; Neves, José A; Redondeiro, M; Laranjo, M; Félix, M R; Freitas, Amadeu; Tirapicos, José L; Martins, José M

2017-02-01

This study evaluates the effects of betaine supplementation (1gkg -1 for 20weeks) on the regulation of genes involved in lipid and cholesterol metabolism of Longissimus lumborum and Biceps femoris from obese Alentejano pigs. Betaine supplementation led to an increase in total cholesterol in both muscles, complementing results previously published indicating a significant increase on the intramuscular lipid content. The expression of twelve genes involved in lipogenesis, lipolysis/FA oxidation, FA transport, and cholesterol metabolism, as well as two transcription factors were also evaluated. Genes related to lipid and cholesterol synthesis plus FA transport were consistently up-regulated in both muscles of betaine fed pigs. On the other hand, genes related to lipolysis/FA oxidation were not affected or down-regulated by betaine supplementation. Our data suggest that the underlying mechanism regulating IMF and cholesterol accumulation in Alentejano pigs supplemented with betaine is associated with the up-regulation of genes involved in lipid synthesis, FA transport, and cholesterol synthesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

LncRNA Pathway Involved in Premature Preterm Rupture of Membrane (PPROM): An Epigenomic Approach to Study the Pathogenesis of Reproductive Disorders

PubMed Central

Gu, Yang; Pan, Jing; Hua, Maofang; Liu, Meilin; Dong, Ziqing; Zhang, Meijiao; Wang, Leilei; Gu, Ying; Zhong, Julia; Zhao, Xinliang; Jenkins, Edmund C.; Brown, W. Ted; Zhong, Nanbert

2013-01-01

Preterm birth (PTB) is a live birth delivered before 37 weeks of gestation (GW). About one-third of PTBs result from the preterm premature rupture of membranes (PPROM). Up to the present, the pathogenic mechanisms underlying PPROM are not clearly understood. Here, we investigated the differential expression of long chain non-coding RNAs (lncRNAs) in placentas of PTBs with PPROM, and their possible involvement in the pathogenic pathways leading to PPROM. A total number of 1954, 776, and 1050 lncRNAs were identified with a microarray from placentas of PPROM (group A), which were compared to full-term birth (FTB) (group B), PTB (group C), and premature rupture of membrane (PROM) (group D) at full-term, respectively. Instead of investigating the individual pathogenic role of each lncRNA involved in the molecular mechanism underlying PPROM, we have focused on investigating the metabolic pathways and their functions to explore what is the likely association and how they are possibly involved in the development of PPROM. Six groups, including up-regulation and down-regulation in the comparisons of A vs. B, A vs. C, and A vs. D, of pathways were analyzed. Our results showed that 22 pathways were characterized as up-regulated 7 down-regulated in A vs. C, 18 up-regulated and 15 down-regulated in A vs. D, and 33 up-regulated and 7 down-regulated in A vs. B. Functional analysis showed pathways of infection and inflammatory response, ECM-receptor interactions, apoptosis, actin cytoskeleton, and smooth muscle contraction are the major pathogenic mechanisms involved in the development of PPROM. Characterization of these pathways through identification of lncRNAs opened new avenues for further investigating the epigenomic mechanisms of lncRNAs in PPROM as well as PTB. PMID:24312190

Long-Term Soil Chemistry Changes in Aggrading Forest Ecosystems

Treesearch

Jennifer D. Knoepp; Wayne T. Swank

1994-01-01

Assessing potential long-term forest productivity requires identification of the processes regulating chemical changes in forest soils. We resampled the litter layer and upper two mineral soil horizons, A and AB/BA, in two aggrading southern Appalachian watersheds 20 yr after an earlier sampling. Soils from a mixed-hardwood watershed exhibited a small but significant...

Use of a geriatric formulary in long-term care.

PubMed

Babington, M A

1997-01-01

The use of drug formularies in nursing facilities (NFs) is a fairly new idea. A large long-term care pharmacy provider prepared a formulary specific to a geriatric population. This open formulary is contained within a handbook of clinical monographs, complete with dosing information, cost comparisons, and references to NF regulations affecting the use of particular drugs.

Transcriptional Correlates of Memory Maintenance Following Long-Term Sensitization of "Aplysia Californica"

ERIC Educational Resources Information Center

Conte, Catherine; Herdegen, Samantha; Kamal, Saman; Patel, Jency; Patel, Ushma; Perez, Leticia; Rivota, Marissa; Calin-Jageman, Robert J.; Calin-Jageman, Irina E.

2017-01-01

We characterized the transcriptional response accompanying maintenance of long-term sensitization (LTS) memory in the pleural ganglia of "Aplysia californica" using microarray (N = 8) and qPCR (N = 11 additional samples). We found that 24 h after memory induction there is strong regulation of 1198 transcripts (748 up and 450 down) in a…

Proteasome Inhibition Enhances the Induction and Impairs the Maintenance of Late-Phase Long-Term Potentiation

ERIC Educational Resources Information Center

Dong, Chenghai; Upadhya, Sudarshan C.; Ding, Lan; Smith, Thuy K.; Hegde, Ashok N.

2008-01-01

Protein degradation by the ubiquitin-proteasome pathway plays important roles in synaptic plasticity, but the molecular mechanisms by which proteolysis regulates synaptic strength are not well understood. We investigated the role of the proteasome in hippocampal late-phase long-term potentiation (L-LTP), a model for enduring synaptic plasticity.…

Transforming Growth Factor ß Recruits Persistent MAPK Signaling to Regulate Long-Term Memory Consolidation in "Aplysia Californica"

ERIC Educational Resources Information Center

Shobe, Justin; Philips, Gary T.; Carew, Thomas J.

2016-01-01

In this study, we explore the mechanistic relationship between growth factor signaling and kinase activity that supports the protein synthesis-dependent phase of long-term memory (LTM) consolidation for sensitization of "Aplysia." Specifically, we examine LTM for tail shock-induced sensitization of the tail-elicited siphon withdrawal…

Roles of p75NTR, long-term depression and cholinergic transmission in anxiety and acute stress coping

PubMed Central

Martinowich, Keri; Schloesser, Robert J.; Lu, Yuan; Jimenez, Dennisse V.; Paredes, Daniel; Greene, Joshua S.; Greig, Nigel H.; Manji, Husseini K.; Lu, Bai

2011-01-01

Background Stress is causally associated with anxiety. While the underlying cellular mechanisms are not well understood, the basal forebrain cholinergic neurons (BFCNs) have been implicated in stress response. p75NTR is a pan-neurotrophin receptor expressed almost exclusively in BFCNs in adult brain. The present study investigates whether and how p75NTR, via regulation of the cholinergic system and hippocampal synaptic plasticity, influences stress-related behaviors. Methods We used a combination of slice electrophysiology, behavioral analyses, pharmacology, in vivo microdialysis and neuronal activity mapping to assess the role of p75NTR in mood and stress-related behaviors and its underlying cellular and molecular mechanisms. Results We show that acute stress enables hippocampal long-term depression (LTD) in adult wild-type mice, but not in mice lacking p75NTR. The p75NTR mutant mice also exhibit two distinct behavioral impairments: baseline anxiety-like behavior and a deficit in coping with and recovering from stressful situations. Blockade of stress-enabled LTD with a GluA2-derived peptide impaired stress recovery without affecting baseline anxiety. Pharmacological manipulations of cholinergic transmission mimicked the p75NTR perturbation in both baseline anxiety and responses to acute stress. Finally, we show evidence of misregulated cholinergic signaling in animals with p75NTR deletion. Conclusions Our results suggest that loss of p75NTR leads to changes in hippocampal cholinergic signaling, which may be involved in regulation of stress-enabled hippocampal LTD and in modulating behaviors related to stress and anxiety. PMID:21978521

Food-Experience Induced Taste Desensitization Modulated by the Drosophila TRPL Channel

PubMed Central

Zhang, Yali V.; Raghuwanshi, Rakesh P.; Shen, Wei L.; Montell, Craig

2013-01-01

Animals tend to reject bitter foods. However, long-term exposure to some unpalatable tastants increases acceptance of the foods. Here, we showed that dietary exposure to the unappealing food but safe additive, camphor, caused the fruit fly, Drosophila melanogaster, to decrease camphor rejection. The TRPL cation channel was a direct target for camphor in gustatory receptor neurons (GRNs), and long-term feeding on a camphor diet led to reversible down-regulation of TRPL protein levels. The turnover of TRPL was controlled by an E3 ubiquitin ligase, Ube3a. The decline in TRPL levels and increased acceptance of camphor reversed after returning the flies long-term to a camphor-free diet. We propose that dynamic regulation of taste receptor levels by ubiquitin-mediated protein degradation comprises an important molecular mechanism that allows an animal to alter taste behavior in response to a changing food environment. PMID:24013593

The defence of body weight: a physiological basis for weight regain after weight loss.

PubMed

Sumithran, Priya; Proietto, Joseph

2013-02-01

Although weight loss can usually be achieved by restricting food intake, the majority of dieters regain weight over the long-term. In the hypothalamus, hormonal signals from the gastrointestinal tract, adipose tissue and other peripheral sites are integrated to influence appetite and energy expenditure. Diet-induced weight loss is accompanied by several physiological changes which encourage weight regain, including alterations in energy expenditure, substrate metabolism and hormone pathways involved in appetite regulation, many of which persist beyond the initial weight loss period. Safe effective long-term strategies to overcome these physiological changes are needed to help facilitate maintenance of weight loss. The present review, which focuses on data from human studies, begins with an outline of body weight regulation to provide the context for the subsequent discussion of short- and long-term physiological changes which accompany diet-induced weight loss.

Long-term remission of a Her2/neu positive primary breast cancer under double monoclonal antibody therapy with trastuzumab and bevacizumab

PubMed Central

Königsberg, Robert; Maierhofer, Julia; Steininger, Tanja; Kienzer, Gabriele; Dittrich, Christian

2014-01-01

Background The attempt to act on several signalling pathways involved in tumour development simultaneously appears to be more attractive than attacking a single target structure alone. Vascular endothelial growth factor (VEGF) over-expression is frequently observed in human epidermal growth factor receptor 2 (Her2/neu) positive patients with breast cancer and over-expression of the proto-oncogene Her2/neu is associated with an up-regulation of VEGF. Case report The case of a Her2/neu positive patient with breast cancer who refused cytotoxic chemotherapy with its potential side effects as well as mastectomy is presented. Our patient has been receiving the combined double administration of bevacizumab and trastuzumab for more than 4 years. Conclusions This case report shows that (a) the combined double administration of bevacizumab and trastuzumab was be clinically effective. (b) The combination of bevacizumab and trastuzumab is safe and non-toxic. (c) Bevacizumab and trastuzumab can be used as a long-term application. PMID:24991208

Anti-Urokinase Receptor Antisense Oligonucleotide (uPAR-aODN) to Prevent and Cure Long-Term Space Exploration-Related Retinal Pathological Angiogenesis

NASA Astrophysics Data System (ADS)

Lazzarano, Stefano; Lulli, Matteo; Fibbi, Gabriella; Margheri, Francesca; Papucci, Laura; Serrati, Simona; Witort, Ewa; Chilla, Anastasia; Lapucci, Andrea; Donnini, Martino; Quaglierini, Paolo; Romiti, Alice; Specogna, Rebecca; Del Rosso, Mario; Capaccioli, Sergio

2008-06-01

Angiogenesis underlies a variety of physiological processes and its possible deregulation during long term space exploration needs to be investigated. Angiogenesis is a multistep process of new blood capillary formation, where degradation of the extracellular matrix (ECM) by proteolytic enzymes, including uPA (urokinase plasminogen activator) and opening the way to migration of endothelial cells (EC), is critical. Plasminogen activation system regulates angiogenesis by both uPA-driven ECM degradation and uPA receptor (uPAR). Microgravity and low dose irradiations promote tissue neoangiogeenesis and neovascularization is often common occurence in ophthalmologic pathologies. We have designed and patented the uPAR antisense oligonucleotide (aODN) and evaluated its antiangiogenetic activity by EC cellular migration and capillary morphogenesis assays. The uPAR aODN treatment caused a 75% inhibition of human microvascular EC migration and a complete inhibition of capillary morphogenesis, suggesting its therapeutic application to prevent neoangiogenesis-related ophthalmologic pathologies during space exploration.

Beta-catenin is required for memory consolidation.

PubMed

Maguschak, Kimberly A; Ressler, Kerry J

2008-11-01

beta-catenin has been implicated in neuronal synapse regulation and remodeling. Here we have examined beta-catenin expression in the adult mouse brain and its role in amygdala-dependent learning and memory. We found alterations in beta-catenin mRNA and protein phosphorylation during fear-memory consolidation. Such alterations correlated with a change in the association of beta-catenin with cadherin. Pharmacologically, this consolidation was enhanced by lithium-mediated facilitation of beta-catenin. Genetically, the role of beta-catenin was confirmed with site-specific deletions of loxP-flanked Ctnnb1 (encoding beta-catenin) in the amygdala. Baseline locomotion, anxiety-related behaviors and acquisition or expression of conditioned fear were normal. However, amygdala-specific deletion of Ctnnb1 prevented the normal transfer of newly formed fear learning into long-term memory. Thus, beta-catenin may be required in the amygdala for the normal consolidation, but not acquisition, of fear memory. This suggests a general role for beta-catenin in the synaptic remodeling and stabilization underlying long-term memory in adults.

48 CFR 46.706 - Warranty terms and conditions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Supplies of a Complex Nature; and 52.246-19, Warranty of Systems and Equipment under Performance... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Warranty terms and conditions. 46.706 Section 46.706 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION...

48 CFR 46.706 - Warranty terms and conditions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Supplies of a Complex Nature; and 52.246-19, Warranty of Systems and Equipment under Performance... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Warranty terms and conditions. 46.706 Section 46.706 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION...

Metabolic shifts in the Antarctic fish Notothenia rossii in response to rising temperature and PCO2

PubMed Central

2012-01-01

Introduction Ongoing ocean warming and acidification increasingly affect marine ecosystems, in particular around the Antarctic Peninsula. Yet little is known about the capability of Antarctic notothenioid fish to cope with rising temperature in acidifying seawater. While the whole animal level is expected to be more sensitive towards hypercapnia and temperature, the basis of thermal tolerance is set at the cellular level, with a putative key role for mitochondria. This study therefore investigates the physiological responses of the Antarctic Notothenia rossii after long-term acclimation to increased temperatures (7°C) and elevated PCO2 (0.2 kPa CO2) at different levels of physiological organisation. Results For an integrated picture, we analysed the acclimation capacities of N. rossii by measuring routine metabolic rate (RMR), mitochondrial capacities (state III respiration) as well as intra- and extracellular acid–base status during acute thermal challenges and after long-term acclimation to changing temperature and hypercapnia. RMR was partially compensated during warm- acclimation (decreased below the rate observed after acute warming), while elevated PCO2 had no effect on cold or warm acclimated RMR. Mitochondrial state III respiration was unaffected by temperature acclimation but depressed in cold and warm hypercapnia-acclimated fish. In both cold- and warm-exposed N. rossii, hypercapnia acclimation resulted in a shift of extracellular pH (pHe) towards more alkaline values. A similar overcompensation was visible in muscle intracellular pH (pHi). pHi in liver displayed a slight acidosis after warm normo- or hypercapnia acclimation, nevertheless, long-term exposure to higher PCO2 was compensated for by intracellular bicarbonate accumulation. Conclusion The partial warm compensation in whole animal metabolic rate indicates beginning limitations in tissue oxygen supply after warm-acclimation of N. rossii. Compensatory mechanisms of the reduced mitochondrial capacities under chronic hypercapnia may include a new metabolic equilibrium to meet the elevated energy demand for acid–base regulation. New set points of acid–base regulation under hypercapnia, visible at the systemic and intracellular level, indicate that N. rossii can at least in part acclimate to ocean warming and acidification. It remains open whether the reduced capacities of mitochondrial energy metabolism are adaptive or would impair population fitness over longer timescales under chronically elevated temperature and PCO2. PMID:23075125

Regulation of early human growth: impact on long-term health.

PubMed

Koletzko, Berthold; Chourdakis, Michael; Grote, Veit; Hellmuth, Christian; Prell, Christine; Rzehak, Peter; Uhl, Olaf; Weber, Martina

2014-01-01

Growth and development are central characteristics of childhood. Deviations from normal growth can indicate serious health challenges. The adverse impact of early growth faltering and malnutrition on later health has long been known. In contrast, the impact of rapid early weight and body fat gain on programming of later disease risk have only recently received increased attention. Numerous observational studies related diet in early childhood and rapid early growth to the risk of later obesity and associated disorders. Causality was confirmed in a large, double-blind randomised trial testing the 'Early Protein Hypothesis'. In this trial we found that attenuation of protein supply in infancy normalized early growth and markedly reduced obesity prevalence in early school age. These results indicate the need to describe and analyse growth patterns and their regulation through diet in more detail and to characterize the underlying metabolic and epigenetic mechanisms, given the potential major relevance for public health and policy. Better understanding of growth patterns and their regulation could have major benefits for the promotion of public health, consumer-orientated nutrition recommendations, and the development of improved food products for specific target populations. © 2014 S. Karger AG, Basel.

26 CFR 1.737-3 - Basis adjustments; Recovery rules.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Properties A1, A2, and A3 is long-term, U.S.-source capital gain or loss. The character of gain on Property A4 is long-term, foreign-source capital gain. B contributes Property B, nondepreciable real property...-term, foreign-source capital gain ($3,000 total gain under section 737 × $2,000 net long-term, foreign...

26 CFR 1.737-3 - Basis adjustments; Recovery rules.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Properties A1, A2, and A3 is long-term, U.S.-source capital gain or loss. The character of gain on Property A4 is long-term, foreign-source capital gain. B contributes Property B, nondepreciable real property...-term, foreign-source capital gain ($3,000 total gain under section 737 × $2,000 net long-term, foreign...

26 CFR 1.737-3 - Basis adjustments; Recovery rules.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Properties A1, A2, and A3 is long-term, U.S.-source capital gain or loss. The character of gain on Property A4 is long-term, foreign-source capital gain. B contributes Property B, nondepreciable real property...-term, foreign-source capital gain ($3,000 total gain under section 737 × $2,000 net long-term, foreign...

26 CFR 1.737-3 - Basis adjustments; Recovery rules.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Properties A1, A2, and A3 is long-term, U.S.-source capital gain or loss. The character of gain on Property A4 is long-term, foreign-source capital gain. B contributes Property B, nondepreciable real property...-term, foreign-source capital gain ($3,000 total gain under section 737 × $2,000 net long-term, foreign...

26 CFR 1.737-3 - Basis adjustments; Recovery rules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Properties A1, A2, and A3 is long-term, U.S.-source capital gain or loss. The character of gain on Property A4 is long-term, foreign-source capital gain. B contributes Property B, nondepreciable real property...-term, foreign-source capital gain ($3,000 total gain under section 737 × $2,000 net long-term, foreign...

Turnover of regulated nurses in long-term care facilities.

PubMed

Chu, Charlene H; Wodchis, Walter P; McGilton, Katherine S

2014-07-01

To describe the relationship between nursing staff turnover in long-term care (LTC) homes and organisational factors consisting of leadership practices and behaviours, supervisory support, burnout, job satisfaction and work environment satisfaction. The turnover of regulated nursing staff [Registered Nurses (RNs) and Registered Practical Nurses (RPNs)] in LTC facilities is a pervasive problem, but there is a scarcity of research examining this issue in Canada. The study was conceptualized using a Stress Process model. Distinct surveys were distributed to administrators to measure organisational factors and to regulated nurses to measure personal and job-related sources of stress and workplace support. In total, 324 surveys were used in the linear regression analysis to examine factors associated with high turnover rates. Higher leadership practice scores were associated with lower nursing turnover; a one score increase in leadership correlated with a 49% decrease in nursing turnover. A significant inverse relationship between leadership turnover and nurse turnover was found: the higher the administrator turnover the lower the nurse turnover rate. Leadership practices and administrator turnover are significant in influencing regulated nurse turnover in LTC. Long-term care facilities may want to focus on building good leadership and communication as an upstream method to minimize nurse turnover. © 2013 John Wiley & Sons Ltd.

The effect of the social regulation of emotion on emotional long-term memory.

PubMed

Flores, Luis E; Berenbaum, Howard

2017-04-01

Memories for emotional events tend to be stronger than for neutral events, and weakening negative memories can be helpful to promote well-being. The present study examined whether the social regulation of emotion (in the form of handholding) altered the strength of emotional long-term memory. A sample of 219 undergraduate students viewed sets of negative, neutral, and positive images. Each participant held a stress ball while viewing half of the images and held someone's hand while viewing the other half. Participants returned 1 week later to complete a recognition task. Performance on the recognition task demonstrated that participants had lower memory accuracy for negative but not for positive pictures that were shown while they were holding someone's hand compared with when they were holding a stress ball. Although handholding altered the strength of negative emotional long-term memory, it did not down-regulate negative affective response as measured by self-report or facial expressivity. The present findings provide evidence that the social regulation of emotion can help weaken memory for negative information. Given the role of strong negative memories in different forms of psychopathology (e.g., depression, posttraumatic stress disorder), these findings may help better understand how close relationships protect against psychopathology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Reciprocal interactions between fluvial processes and riparian plants at multiple scales: ecogeomorphic feedbacks drive coevolution of floodplain morphology and vegetation communities

NASA Astrophysics Data System (ADS)

Stella, J. C.; Kui, L.; Diehl, R. M.; Bywater-Reyes, S.; Wilcox, A. C.; Shafroth, P. B.; Lightbody, A.

2017-12-01

Fluvial forces interact with woody riparian plants in complex ways to influence the coevolution of river morphology and floodplain plant communities. Here, we report on an integrated suite of multi-disciplinary studies that contrast the responses of plants with different morphologies, tamarisk (Tamarix spp.) and cottonwood (Populus fremontii) in terms of (1) differences in vulnerability to scour and burial during floods; (2) interactions and feedbacks between plants and river morphodynamics; and (3) long-term coevolution of river floodplains and riparian communities following flow regulation from dams. The focus of these studies is sand-bed rivers in arid-land regions where invasion by tamarisk has strongly influenced riverine plant communities and geomorphic processes. We complemented a suite of field-scale flume experiments using live seedlings to quantify the initial stages of plant-river interactions with an analysis of long-term vegetation and geomorphic changes along the dammed Bill Williams River (AZ, USA) using time-series air photographs. Vegetation-fluvial interactions varied with plant characteristics, river hydraulics and sediment conditions, across the wide range of scales we investigated. In the flume studies, tamarisk's denser crowns and stiffer stems induced greater sedimentation compared to cottonwood. This resulted in tamarisk's greater mortality from burial as small seedlings under sediment equilibrium conditions but higher relative survival in larger floods under sediment deficit scenarios, in which more cottonwoods were lost to root scour. Sediment deficit conditions, as occurs downstream of dams, induced both greater scour and greater plant loss. With larger size and at higher densities, plants' vulnerability diminished due to greater root anchoring and canopy effects on hydraulics. At the corridor scale, we observed a pattern of plant encroachment during five decades of flow regulation, in which channel narrowing and simplification was more associated with tamarisk-dominated reaches compared with native woodlands. Together, these multi-scale plant-river dynamics help explain the persistence of tamarisk along regulated rivers where catastrophic floods have been reduced and also highlight limitations of using flow releases for invasive species management.

Underlying Mechanisms of Cooperativity, Input Specificity, and Associativity of Long-Term Potentiation Through a Positive Feedback of Local Protein Synthesis.

PubMed

Hao, Lijie; Yang, Zhuoqin; Lei, Jinzhi

2018-01-01

Long-term potentiation (LTP) is a specific form of activity-dependent synaptic plasticity that is a leading mechanism of learning and memory in mammals. The properties of cooperativity, input specificity, and associativity are essential for LTP; however, the underlying mechanisms are unclear. Here, based on experimentally observed phenomena, we introduce a computational model of synaptic plasticity in a pyramidal cell to explore the mechanisms responsible for the cooperativity, input specificity, and associativity of LTP. The model is based on molecular processes involved in synaptic plasticity and integrates gene expression involved in the regulation of neuronal activity. In the model, we introduce a local positive feedback loop of protein synthesis at each synapse, which is essential for bimodal response and synapse specificity. Bifurcation analysis of the local positive feedback loop of brain-derived neurotrophic factor (BDNF) signaling illustrates the existence of bistability, which is the basis of LTP induction. The local bifurcation diagram provides guidance for the realization of LTP, and the projection of whole system trajectories onto the two-parameter bifurcation diagram confirms the predictions obtained from bifurcation analysis. Moreover, model analysis shows that pre- and postsynaptic components are required to achieve the three properties of LTP. This study provides insights into the mechanisms underlying the cooperativity, input specificity, and associativity of LTP, and the further construction of neural networks for learning and memory.

A Place at the Table: LTD as a Mediator of Memory Genesis.

PubMed

Connor, Steven A; Wang, Yu Tian

2016-08-01

Resolving how our brains encode information requires an understanding of the cellular processes taking place during memory formation. Since the 1970s, considerable effort has focused on determining the properties and mechanisms underlying long-term potentiation (LTP) at glutamatergic synapses and how these processes influence initiation of new memories. However, accumulating evidence suggests that long-term depression (LTD) of synaptic strength, particularly at glutamatergic synapses, is a bona fide learning and memory mechanism in the mammalian brain. The known range of mechanisms capable of inducing LTD has been extended to those including NMDAR-independent forms, neuromodulator-dependent LTD, synaptic depression following stress, and non-synaptically induced forms. The examples of LTD observed at the hippocampal CA1 synapse to date demonstrate features consistent with LTP, including homo- and heterosynaptic expression, extended duration beyond induction (several hours to weeks), and association with encoding of distinct types of memories. Canonical mechanisms through which synapses undergo LTD include activation of phosphatases, initiation of protein synthesis, and dynamic regulation of presynaptic glutamate release and/or postsynaptic glutamate receptor endocytosis. Here, we will discuss the pre- and postsynaptic changes underlying LTD, recent advances in the identification and characterization of novel mechanisms underlying LTD, and how engagement of these processes constitutes a cellular analog for the genesis of specific types of memories. © The Author(s) 2015.

42 CFR 412.540 - Method of payment for preadmission services under the long-term care hospital prospective payment...

Code of Federal Regulations, 2010 CFR

2010-10-01

... the long-term care hospital prospective payment system. 412.540 Section 412.540 Public Health CENTERS... PAYMENT SYSTEMS FOR INPATIENT HOSPITAL SERVICES Prospective Payment System for Long-Term Care Hospitals... payment system. The prospective payment system includes payment for inpatient operating costs of...

Long-term Tillage influences on soil carbon, nitrogen, physical, chemical, and biological properties

USDA-ARS?s Scientific Manuscript database

Long-term tillage influences physical, chemical, and biological properties of the soil environment and thereby crop production and quality. We evaluated the effect of long-term (>20 yrs) tillage no-till, spring till, and fall plus spring till under continuous spring wheat (Triticum aestivum L.) on s...

Key Federal Regulations Affecting the Handicapped 1975-1976.

ERIC Educational Resources Information Center

National Association of Coordinators of State Programs for the Mentally Retarded, Arlington, VA.

Summarized are major federal regulations affecting the handicapped issued during 1976. Regulations are organized according to the following categories: health (such as long term care and home health services, health planning, and facilities construction); education (such as handicapped education grants to the states, early childhood education, and…

Lithium in the Kidney: Friend and Foe?

PubMed Central

Alsady, Mohammad; Baumgarten, Ruben; Deen, Peter M.T.

2016-01-01

Trace amounts of lithium are essential for our physical and mental health, and administration of lithium has improved the quality of life of millions of patients with bipolar disorder for >60 years. However, in a substantial number of patients with bipolar disorder, long–term lithium therapy comes at the cost of severe renal side effects, including nephrogenic diabetes insipidus and rarely, ESRD. Although the mechanisms underlying the lithium–induced renal pathologies are becoming clearer, several recent animal studies revealed that short-term administration of lower amounts of lithium prevents different forms of experimental AKI. In this review, we discuss the knowledge of the pathologic and therapeutic effects of lithium in the kidney. Furthermore, we discuss the underlying mechanisms of these seemingly paradoxical effects of lithium, in which fine-tuned regulation of glycogen synthase kinase type 3, a prime target for lithium, seems to be key. The new discoveries regarding the protective effect of lithium against AKI in rodents call for follow-up studies in humans and suggest that long-term therapy with low lithium concentrations could be beneficial in CKD. PMID:26577775

Short-term and long-term effects of protein kinase C on the trafficking and stability of human organic anion transporter 3

PubMed Central

Zhang, Qiang; Suh, Wonmo; Pan, Zui; You, Guofeng

2012-01-01

Human organic anion transporter 3 (hOAT3) belongs to a family of organic anion transporters that play critical roles in the body disposition of numerous clinically important drugs. Therefore, understanding the regulation of this transporter has profound clinical significance. In the current study, we investigated the short-term and long-term regulation of hOAT3 by protein kinase C (PKC). We showed that short-term activation of PKC by phobol 12-Myristate 13-Acetate (PMA) inhibited hOAT3 activity through accelerating its internalization from cell surface to intracellular recycling endosomes. The colocalization of hOAT3 with EEA1-positive recycling endosomes was demonstrated by immunolocalization with confocal microscopy. Furthermore, we showed that long-term activation of PKC resulted in the enhanced degradation of cell surface hOAT3. The pathways for hOAT3 degradation were further examined using proteasomal and lysosomal inhibitors. Our results showed that both proteasomal inhibitors and the lysosomal inhibitors significantly blocked hOAT3 degradation. These results demonstrate that PKC plays critical roles in the trafficking and the stability of hOAT3. PMID:22773962

Photoacclimation in a tropical population of Cladophora glomerata (L.) Kützing 1843 (Chlorophyta) from southeastern Brazil.

PubMed

Bautista, A I N; Necchi-Júnior, O

2008-02-01

Photoacclimation of photosynthesis was investigated in a tropical population of C. glomerata (São Paulo State, southeastern Brazil, 20 degrees 48' 24" S and 49 degrees 22' 24" W) by chlorophyll fluorescence parameters and chlorophyll a content. Plants were acclimated to two levels of irradiance: low (65 +/- 5 micromol.m(-2).s(-1)) and high (300 +/- 10 micromol.m(-2).s(-1)) and exposed short-term (4 days) and long-term (28 days) under a light-dark cycle of 12:12 hours. Photosynthesis-irradiance (PI) curves revealed distinct strategies of photoacclimation. In long-term exposure, plants acclimated by altering the photosynthetic units (PSU) number and keeping fixed the PSU size, revealed by increased rates of maximum photosynthesis (Pmax), lower photosynthetic efficiency (alpha) and higher values of the saturation parameter (Ik) under high irradiance. The short-term acclimation strategy consisted of changing the PSU size, with a fixed number of PSUs, as revealed by similar Pmax but higher alpha and lower Ik under low irradiance. Chlorophyll a contents followed the general pattern reported in green algae of higher concentrations under lower irradiance. Dark/light induction curves revealed consistently higher values of potential quantum yield under low irradiance. Initial and final values showed a higher recovery capacity in the short (84.4-90.6%) term exposure than in the long-term case (81.4-81.5%). ETR (electron transport rate) and NPQ (non-photochemical quenching) values were consistently higher under low irradiance. ETR showed a continuous and steady increase along the light exposure period in the short and long-term experiments, whereas NPQ values revealed a rapid increase after 15 seconds of light exposure, kept a slightly increasing trend and stabilized in most treatments. Lower photosynthetic performance (ETR) and recovery capacity of potential quantum yield were observed, particularly in long-term exposure, suggesting that this population is constrained by the typical high light environment of tropical regions.

HIST-EU - a dataset of European relevance, a database to enable long-term climate variability studies on regional scale

NASA Astrophysics Data System (ADS)

Auer, I.; Böhm, R.; Ganekind, M.; Schöner, W.; Nemec, J.; Chimani, B.

2010-09-01

Instrumental time series of different climate elements are an important requisite for climate and climate impact studies. Long-term time series can improve our understanding of climate change during the instrumental period. During recent decades a number of national and international initiatives in European countries have significantly increased the number of existing long-term instrumental series; however a publically available data base covering Europe has not been created so far. For the "Greater Alpine Region" (4-19 deg E, 43-49 deg N, 0-3500m asl) the HISTALP data base has been established consisting of monthly homogenised temperature, pressure, precipitation, sunshine and cloudiness records. The data set may be described as follows: Long-term (fully exploiting the potential of systematically measured data). dense (network density adequate in respect to the spatial coherence of the given climate element) quality improved (outliers removed, gaps filled) homogenised (earlier sections adjusted to the recent state of the measuring site) multiple (covering more than one climate element) user friendly (well described and kept in different modes for different applications) HIST-EU is inteded to be a data set of European relevance allowing studying climate variability on regional scale. It focuses on data collection, data recovery and rescue, and homogenizing. HIST-EU will use the infrastructure of HISTALP (www.zamg.ac.at/histalp) and will allow free or restricted data access due to the regulations of data providers. HIST-EU will be carried out under the umbrella of ECSN/EUMETNET.

Dynamic self-regulating prosthesis (protesi autoregolantesi dinamica): the long-term results in the treatment of primary inguinal hernias.

PubMed

Valenti, Gabriele; Baldassarre, Emanuele; Testa, Alessandro; Arturi, Alessandro; Torino, Giovanni; Campisi, Costantino; Capuano, Giorgio

2006-03-01

The dynamic self-regulating prosthesis (protesi autoregolantesi dinamica, PAD) is a double-layered prosthesi, in use since 1992 in inguinal hernia repair. In 1999, we published the short-term results on 500 patients and herein we report the long-term follow-up. Five hundred eighty-five PAD procedures were performed on 500 adult male, unselected patients. Hernias were unilateral in 415 patients, were bilateral in 85 patients, were direct in 197 patients (33.7%), were indirect in 269 patients (46.0%), and were combined in 119 patients (20.3%). Four hundred sixty-four patients were alive at the follow-up period of minimum 5 years, whereas 36 died (7.2%) of causes unrelated to the hernia. No information was available on 73 patients (14.6%). Therefore, the follow-up was consisted of 391 patients (78.2%) with 469 hernias. The recurrence and testicular atrophy rates were nil. Three patients (0.77%) presented chronic pain and 18 (4.6%) suffered persistent discomfort or paresthesia. A hydrocoele was observed in one patient (0.2%). The long-term data confirm the efficacy of the dynamic self-regulating posthesis hernioplasty. We propose it as a standard of care in all cases of primary inguinal hernia in adult males, retaining it as a definitive and comfortable solution.

Upweighting rare favourable alleles increases long-term genetic gain in genomic selection programs.

PubMed

Liu, Huiming; Meuwissen, Theo H E; Sørensen, Anders C; Berg, Peer

2015-03-21

The short-term impact of using different genomic prediction (GP) models in genomic selection has been intensively studied, but their long-term impact is poorly understood. Furthermore, long-term genetic gain of genomic selection is expected to improve by using Jannink's weighting (JW) method, in which rare favourable marker alleles are upweighted in the selection criterion. In this paper, we extend the JW method by including an additional parameter to decrease the emphasis on rare favourable alleles over the time horizon, with the purpose of further improving the long-term genetic gain. We call this new method dynamic weighting (DW). The paper explores the long-term impact of different GP models with or without weighting methods. Different selection criteria were tested by simulating a population of 500 animals with truncation selection of five males and 50 females. Selection criteria included unweighted and weighted genomic estimated breeding values using the JW or DW methods, for which ridge regression (RR) and Bayesian lasso (BL) were used to estimate marker effects. The impacts of these selection criteria were compared under three genetic architectures, i.e. varying numbers of QTL for the trait and for two time horizons of 15 (TH15) or 40 (TH40) generations. For unweighted GP, BL resulted in up to 21.4% higher long-term genetic gain and 23.5% lower rate of inbreeding under TH40 than RR. For weighted GP, DW resulted in 1.3 to 5.5% higher long-term gain compared to unweighted GP. JW, however, showed a 6.8% lower long-term genetic gain relative to unweighted GP when BL was used to estimate the marker effects. Under TH40, both DW and JW obtained significantly higher genetic gain than unweighted GP. With DW, the long-term genetic gain was increased by up to 30.8% relative to unweighted GP, and also increased by 8% relative to JW, although at the expense of a lower short-term gain. Irrespective of the number of QTL simulated, BL is superior to RR in maintaining genetic variance and therefore results in higher long-term genetic gain. Moreover, DW is a promising method with which high long-term genetic gain can be expected within a fixed time frame.

New Long-Term Care Policies in Latin America: The National System of Care in Uruguay.

PubMed

Matus-Lopez, Mauricio; Pedraza, Camilo Cid

2016-07-01

Uruguay is the Latin American country with the largest share of elderly population and it has the greatest pressure for formal long-term care services in the region. For this reason, last year the government approved a law creating a National System of Care. This article describes and analyzes the long-term care policy in the recently created National System of Care of Uruguay. The Director of the National System of Care was asked to complete a questionnaire with a description and management of long-term care programs. This information was completed with official information and peer-reviewed articles of long-term care in Uruguay. The National System of Care includes long-term care services. The main services are carried out through a cash-for-care system for home-based services, but in the future the benefits will expand to day centers and residential and nursing homes. The system follows international trends in terms of universality, services, and regulations dealing with care. However, the current and future financing is low, and this condition could undermine its development capacity. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

7 CFR 27.38 - Terms defined for purposes of classification.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Terms defined for purposes of classification. 27.38... CONTAINER REGULATIONS COTTON CLASSIFICATION UNDER COTTON FUTURES LEGISLATION Regulations Classification and Micronaire Determinations § 27.38 Terms defined for purposes of classification. For the purposes of...

7 CFR 27.38 - Terms defined for purposes of classification.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Terms defined for purposes of classification. 27.38... CONTAINER REGULATIONS COTTON CLASSIFICATION UNDER COTTON FUTURES LEGISLATION Regulations Classification and Micronaire Determinations § 27.38 Terms defined for purposes of classification. For the purposes of...

75 FR 27557 - Agency Information Collection Activities: Final Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

... many FTEs were supported or created for this deal; and d. Changed the amount of financeable local costs... transaction requests submitted to the Export Import Bank under its long term guarantee and direct loan... transaction requests submitted to the Export Import Bank under its long term guarantee and direct loan...

The E3 Ligase APC/C-Cdh1 Is Required for Associative Fear Memory and Long-Term Potentiation in the Amygdala of Adult Mice

ERIC Educational Resources Information Center

Pick, Joseph E.; Malumbres, Marcos; Klann, Eric

2013-01-01

The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C-Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role of Cdh1 in synaptic plasticity and memory by generating…

c-Rel, an NF-[kappa]B Family Transcription Factor, Is Required for Hippocampal Long-Term Synaptic Plasticity and Memory Formation

ERIC Educational Resources Information Center

Ahn, Hyung Jin; Hernandez, Caterina M.; Levenson, Jonathan M.; Lubin, Farah D.; Liou, Hsiou-Chi; Sweatt, J. David

2008-01-01

Transcription is a critical component for consolidation of long-term memory. However, relatively few transcriptional mechanisms have been identified for the regulation of gene expression in memory formation. In the current study, we investigated the activity of one specific member of the NF-[kappa]B transcription factor family, c-Rel, during…

Developing Long-Term Computing Skills among Low-Achieving Students via Web-Enabled Problem-Based Learning and Self-Regulated Learning

ERIC Educational Resources Information Center

Tsai, Chia-Wen; Lee, Tsang-Hsiung; Shen, Pei-Di

2013-01-01

Many private vocational schools in Taiwan have taken to enrolling students with lower levels of academic achievement. The authors re-designed a course and conducted a series of quasi-experiments to develop students' long-term computing skills, and examined the longitudinal effects of web-enabled, problem-based learning (PBL) and self-regulated…

An Account of Performance in Accessing Information Stored in Long-Term Memory. A Fixed-Links Model Approach

ERIC Educational Resources Information Center

Altmeyer, Michael; Schweizer, Karl; Reiss, Siegbert; Ren, Xuezhu; Schreiner, Michael

2013-01-01

Performance in working memory and short-term memory tasks was employed for predicting performance in a long-term memory task in order to find out about the underlying processes. The types of memory were represented by versions of the Posner Task, the Backward Counting Task and the Sternberg Task serving as measures of long-term memory, working…

Abscisic Acid Flux Alterations Result in Differential Abscisic Acid Signaling Responses and Impact Assimilation Efficiency in Barley under Terminal Drought Stress1[C][W][OPEN

PubMed Central

Seiler, Christiane; Harshavardhan, Vokkaliga T.; Reddy, Palakolanu S.; Hensel, Götz; Kumlehn, Jochen; Eschen-Lippold, Lennart; Rajesh, Kalladan; Korzun, Viktor; Wobus, Ulrich; Lee, Justin; Selvaraj, Gopalan; Sreenivasulu, Nese

2014-01-01

Abscisic acid (ABA) is a central player in plant responses to drought stress. How variable levels of ABA under short-term versus long-term drought stress impact assimilation and growth in crops is unclear. We addressed this through comparative analysis, using two elite breeding lines of barley (Hordeum vulgare) that show senescence or stay-green phenotype under terminal drought stress and by making use of transgenic barley lines that express Arabidopsis (Arabidopsis thaliana) 9-cis-epoxycarotenoid dioxygenase (AtNCED6) coding sequence or an RNA interference (RNAi) sequence of ABA 8′-hydroxylase under the control of a drought-inducible barley promoter. The high levels of ABA and its catabolites in the senescing breeding line under long-term stress were detrimental for assimilate productivity, whereas these levels were not perturbed in the stay-green type that performed better. In transgenic barley, drought-inducible AtNCED expression afforded temporal control in ABA levels such that the ABA levels rose sooner than in wild-type plants but also subsided, unlike as in the wild type , to near-basal levels upon prolonged stress treatment due to down-regulation of endogenous HvNCED genes. Suppressing of ABA catabolism with the RNA interference approach of ABA 8′-hydroxylase caused ABA flux during the entire period of stress. These transgenic plants performed better than the wild type under stress to maintain a favorable instantaneous water use efficiency and better assimilation. Gene expression analysis, protein structural modeling, and protein-protein interaction analyses of the members of the PYRABACTIN RESISTANCE1/PYRABACTIN RESISTANCE1-LIKE/REGULATORY COMPONENT OF ABA RECEPTORS, TYPE 2C PROTEIN PHOSPHATASE Sucrose non-fermenting1-related protein kinase2, and ABA-INSENSITIVE5/ABA-responsive element binding factor family identified specific members that could potentially impact ABA metabolism and stress adaptation in barley. PMID:24610749

Responses of Nannochloropsis oceanica IMET1 to Long-Term Nitrogen Starvation and Recovery1[C][W][OA

PubMed Central

Dong, Hong-Po; Williams, Ernest; Wang, Da-zhi; Xie, Zhang-Xian; Hsia, Ru-ching; Jenck, Alizée; Halden, Rolf; Li, Jing; Chen, Feng; Place, Allen R.

2013-01-01

The Nannochloropsis genus contains oleaginous microalgae that have served as model systems for developing renewable biodiesel. Recent genomic and transcriptomic studies on Nannochloropsis species have provided insights into the regulation of lipid production in response to nitrogen stress. Previous studies have focused on the responses of Nannochloropsis species to short-term nitrogen stress, but the effect of long-term nitrogen deprivation remains largely unknown. In this study, physiological and proteomic approaches were combined to understand the mechanisms by which Nannochloropsis oceanica IMET1 is able to endure long-term nitrate deprivation and its ability to recover homeostasis when nitrogen is amended. Changes of the proteome during chronic nitrogen starvation espoused the physiological changes observed, and there was a general trend toward recycling nitrogen and storage of lipids. This was evidenced by a global down-regulation of protein expression, a retained expression of proteins involved in glycolysis and the synthesis of fatty acids, as well as an up-regulation of enzymes used in nitrogen scavenging and protein turnover. Also, lipid accumulation and autophagy of plastids may play a key role in maintaining cell vitality. Following the addition of nitrogen, there were proteomic changes and metabolic changes observed within 24 h, which resulted in a return of the culture to steady state within 4 d. These results demonstrate the ability of N. oceanica IMET1 to recover from long periods of nitrate deprivation without apparent detriment to the culture and provide proteomic markers for genetic modification. PMID:23637339

ERK/MAPK Regulates Hippocampal Histone Phosphorylation Following Contextual Fear Conditioning

ERIC Educational Resources Information Center

Levenson, Jonathan M.; Sweatt, J. David; Chwang, Wilson B.; O'Riordan, Kenneth J.

2006-01-01

Long-term memory formation is regulated by many distinct molecular mechanisms that control gene expression. An emerging model for effecting a stable, coordinated pattern of gene transcription involves epigenetic tagging through modifications of histones or DNA. In this study, we investigated the regulation of histone phosphorylation in the…

[Variation characteristics of maize yield and fertilizer utilization rate on an upland yellow soil under long term fertilization].

PubMed

Luo, Long-Zao; Li, Yu; Zhang, Wen-An; Xiao, Hou-Jun; Jiang, Tai-Ming

2013-10-01

An analysis was made on the 16-year experimental data from the long term fertilization, experiment of maize on a yellow soil in Guizhou of Southwest China. Four treatments, i. e. , no fertilization (CK), chemical fertilization (165 kg N x hm(-2), 82.5 kg P2O5 x hm(-2), and 82.5 kg K2O x hm(-2), NPK), organic manure (30555 kg x hm(-2), M), and combined applicatioin of chemical fertilizers and organic manure (NPKM), were selected to analyze the variation trends of maize yield and fertilizer use efficiency on yellow soil under effects of different long term fertilization modes, aimed to provide references for evaluating and establishing long term fertilization mode and promote the sustainable development of crop production. Overall, the maize yield under long term fertilization had an increasing trend, with a large annual variation. Treatment NPKM had the best yield-increasing effect, with the maize yield increased by 4075.71 kg x hm(-2) and the increment being up to 139.2%. Long term fertilization increased the fertilizer utilization efficiency of maize. In treatment M, the nitrogen and phosphorus utilization rates were increased significantly by 35.4% and 18.8%, respectively. Treatment NPK had obvious effect in improving potassium utilization rate, with an increment of 20% and being far higher than that in treatments M (8.7%) and NPKM (9.2%). The results showed that long term fertilization, especially the combined application of chemical fertilizers and organic manure, was of great importance in increasing crop yield and fertilizer use efficiency.

Limitations on scientific prediction and how they could affect repository licensing

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

Van Konynenburg, R.A.

The best possibility for gaining an understanding of the likely future behavior of a high level nuclear waste disposal system is to use the scientific method. However, the scientific approach has inherent limitations when it comes to making long-term predictions with confidence. This paper examines some of these limiting factors as well as the criteria for admissibility of scientific evidence in the legal arena, and concludes that the prospects are doubtful for successful licensing of a potential repository under the regulations that are now being reconsidered. Suggestions am made for remedying this situation.

Better Redd than Dead: Optimizing Reservoir Operations for Wild Fish Survival During Drought

NASA Astrophysics Data System (ADS)

Adams, L. E.; Lund, J. R.; Quiñones, R.

2014-12-01

Extreme droughts are difficult to predict and may incur large economic and ecological costs. Dam operations in drought usually consider minimizing economic costs. However, dam operations also offer an opportunity to increase wild fish survival under difficult conditions. Here, we develop a probabilistic optimization approach to developing reservoir release schedules to maximize fish survival in regulated rivers. A case study applies the approach to wild Fall-run Chinook Salmon below Folsom Dam on California's American River. Our results indicate that releasing more water early in the drought will, on average, save more wild fish over the long term.

The benefits of cholinergic enhancement during perceptual learning are long-lasting

PubMed Central

Rokem, Ariel; Silver, Michael A.

2013-01-01

The neurotransmitter acetylcholine (ACh) regulates many aspects of cognition, including attention and memory. Previous research in animal models has shown that plasticity in sensory systems often depends on the behavioral relevance of a stimulus and/or task. However, experimentally increasing ACh release in the cortex can result in experience-dependent plasticity, even in the absence of behavioral relevance. In humans, the pharmacological enhancement of ACh transmission by administration of the cholinesterase inhibitor donepezil during performance of a perceptual task increases the magnitude of perceptual learning (PL) and its specificity to physical parameters of the stimuli used for training. Behavioral effects of PL have previously been shown to persist for many months. In the present study, we tested whether enhancement of PL by donepezil is also long-lasting. Healthy human subjects were trained on a motion direction discrimination task during cholinergic enhancement, and follow-up testing was performed 5–15 months after the end of training and without additional drug administration. Increases in performance associated with training under donepezil were evident in follow-up retesting, indicating that cholinergic enhancement has beneficial long-term effects on PL. These findings suggest that cholinergic enhancement of training procedures used to treat clinical disorders should improve long-term outcomes of these procedures. PMID:23755006

Retrieval under stress decreases the long-term expression of a human declarative memory via reconsolidation.

PubMed

Larrosa, Pablo Nicolás Fernández; Ojea, Alejandro; Ojea, Ignacio; Molina, Victor Alejandro; Zorrilla-Zubilete, María Aurelia; Delorenzi, Alejandro

2017-07-01

Acute stress impairs memory retrieval of several types of memories. An increase in glucocorticoids, several minutes after stressful events, is described as essential to the impairing retrieval-effects of stressors. Moreover, memory retrieval under stress can have long-term consequences. Through what process does the reactivated memory under stress, despite the disrupting retrieval effects, modify long-term memories? The reconsolidation hypothesis proposes that a previously consolidated memory reactivated by a reminder enters a vulnerability phase (labilization) during which it is transiently sensitive to modulation, followed by a re-stabilization phase. However, previous studies show that the expression of memories during reminder sessions is not a condition to trigger the reconsolidation process since unexpressed memories can be reactivated and labilized. Here we evaluate whether it is possible to reactivate-labilize a memory under the impairing-effects of a mild stressor. We used a paradigm of human declarative memory whose reminder structure allows us to differentiate between a reactivated-labile memory state and a reactivated but non-labile state. Subjects memorized a list of five cue-syllables associated with their respective response-syllables. Seventy-two hours later, results showed that the retrieval of the paired-associate memory was impaired when tested 20min after a mild stressor (cold pressor stress (CPS)) administration, coincident with cortisol levels increase. Then, we investigated the long-term effects of CPS administration prior to the reminder session. Under conditions where the reminder initiates the reconsolidation process, CPS impaired the long-term memory expression tested 24h later. In contrast, CPS did not show effects when administered before a reminder session that does not trigger reconsolidation. Results showed that memory reactivation-labilization occurs even when retrieval was impaired. Memory reactivation under stress could hinder -via reconsolidation- the probability of the traces to be expressed in the long term. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Deeb, Rula A.; Hawley, Elisabeth L.

The goal of United States (U.S.) Department of Energy's (DOE)'s environmental remediation programs is to restore groundwater to beneficial use, similar to many other Federal and state environmental cleanup programs. Based on past experience, groundwater remediation to pre-contamination conditions (i.e., drinking water standards or non-detectable concentrations) can be successfully achieved at many sites. At a subset of the most complex sites, however, complete restoration is not likely achievable within the next 50 to 100 years using today's technology. This presentation describes several approaches used at complex sites in the face of these technical challenges. Many complex sites adopted a long-termmore » management approach, whereby contamination was contained within a specified area using active or passive remediation techniques. Consistent with the requirements of their respective environmental cleanup programs, several complex sites selected land use restrictions and used risk management approaches to accordingly adopt alternative cleanup goals (alternative endpoints). Several sites used long-term management designations and approaches in conjunction with the alternative endpoints. Examples include various state designations for groundwater management zones, technical impracticability (TI) waivers or greater risk waivers at Superfund sites, and the use of Monitored Natural Attenuation (MNA) or other passive long-term management approaches over long time frames. This presentation will focus on findings, statistics, and case studies from a recently-completed report for the Department of Defense's Environmental Security Technology Certification Program (ESTCP) (Project ER-0832) on alternative endpoints and approaches for groundwater remediation at complex sites under a variety of Federal and state cleanup programs. The primary objective of the project was to provide environmental managers and regulators with tools, metrics, and information needed to evaluate alternative endpoints for groundwater remediation at complex sites. A statistical analysis of Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) sites receiving TI waivers will be presented as well as case studies of other types of alternative endpoints and alternative remedial strategies that illustrate the variety of approaches used at complex sites and the technical analyses used to predict and document cost, time frame, and potential remedial effectiveness. This presentation is intended to inform DOE program managers, state regulators, practitioners and other stakeholders who are evaluating technical cleanup challenges within their own programs, and establishing programmatic approaches to evaluating and implementing long-term management approaches. Case studies provide examples of long-term management designations and strategies to manage and remediate groundwater at complex sites. At least 13 states consider some designation for groundwater containment in their corrective action policies, such as groundwater management zones, containment zones, and groundwater classification exemption areas. Long-term management designations are not a way to 'do nothing' or walk away from a site. Instead, soil and groundwater within the zone is managed to be protective of human health and the environment. Understanding when and how to adopt a long-term management approach can lead to cost savings and the more efficient use of resources across DOE and at numerous other industrial and military sites across the U.S. This presentation provides context for assessing the use and appropriate role of alternative endpoints and supporting long-term management designations in final remedies. (authors)« less

HSP70 reduces chronic hypoxia-induced neural suppression via regulating expression of syntaxin.

PubMed

Fei, Guanghe; Guo, Conghui; Sun, Hong-Shuo; Feng, Zhong-Ping

2008-01-01

Long-term exposure to modest hypoxia conditions may result in neural dysfunction; however, the involvement of presynaptic proteins has not been tested directly. Here, we reported that adult snails, Lymnaea stagnalis, developed a slow righting movement after placement in low O2 (approximately 5%) for 4 days. Semi-quantitative Western blot analysis showed that hypoxia induced heat shock protein 70 (HSP70) up-regulation and a reduction of syntaxin I. The inducible HSP70 occurs within 6 hours preceding the down-regulation of syntaxin I, suggesting that HSP70 may be involved in regulation of syntaxin expression. Injecting directly double-stranded RNAs (dsRNA) into the center ganglia region, we found that dsRNA HSP70, not the scrambled RNA, prevented the hypoxia-induced HSP70 expression, enhanced the hypoxia-dependent down-regulation of syntaxin I, and aggravated motor suppression. We thus provided the first evidence that early induction of HSP70 by chronic hypoxia is critical for maintaining expression levels of presynaptic proteins and neural function. These findings implicate a new molecular mechanism underlying chronic hypoxia-induced neurobehavioral adaptation and impairment.

7 CFR 28.40 - Terms defined; cotton classification.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Terms defined; cotton classification. 28.40 Section 28... REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Regulations Under the United States Cotton Standards Act Classification § 28.40 Terms defined; cotton classification. For the purposes of classification of any cotton or...

7 CFR 28.40 - Terms defined; cotton classification.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Terms defined; cotton classification. 28.40 Section 28... REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Regulations Under the United States Cotton Standards Act Classification § 28.40 Terms defined; cotton classification. For the purposes of classification of any cotton or...

7 CFR 28.40 - Terms defined; cotton classification.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Terms defined; cotton classification. 28.40 Section 28... REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Regulations Under the United States Cotton Standards Act Classification § 28.40 Terms defined; cotton classification. For the purposes of classification of any cotton or...

7 CFR 28.40 - Terms defined; cotton classification.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Terms defined; cotton classification. 28.40 Section 28... REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Regulations Under the United States Cotton Standards Act Classification § 28.40 Terms defined; cotton classification. For the purposes of classification of any cotton or...

7 CFR 28.40 - Terms defined; cotton classification.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Terms defined; cotton classification. 28.40 Section 28... REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Regulations Under the United States Cotton Standards Act Classification § 28.40 Terms defined; cotton classification. For the purposes of classification of any cotton or...

42 CFR 412.505 - Conditions for payment under the prospective payment system for long-term care hospitals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... payment system for long-term care hospitals. 412.505 Section 412.505 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM PROSPECTIVE PAYMENT SYSTEMS FOR INPATIENT HOSPITAL SERVICES Prospective Payment System for Long-Term Care Hospitals § 412.505 Conditions for...

Mechanisms of soil organic carbon accumulation from long-term fertilization strategies in two soils: Evidence from nuclear magnetic resonance spectroscopy analysis

USDA-ARS?s Scientific Manuscript database

Long-term fertilization strategies have been proven to significantly influence soil organic carbon (SOC) accumulation, while the underlying mechanism remains unclear. Using two long-term (>20 y) field experiments of a double-cropped maize-wheat rotation on a Calcaric Fluvisol and paddy rice on a Hyd...

A Retentive Memory of Tetrachloroethene Respiration in Sulfurospirillum halorespirans - involved Proteins and a possible link to Acetylation of a Two-Component Regulatory System.

PubMed

Türkowsky, Dominique; Esken, Jens; Goris, Tobias; Schubert, Torsten; Diekert, Gabriele; Jehmlich, Nico; von Bergen, Martin

2018-06-15

Organohalide respiration (OHR), comprising the reductive dehalogenation of halogenated organic compounds, is subject to a unique memory effect and long-term transcriptional downregulation of the involved genes in Sulfurospirillum multivorans. Gene expression ceases slowly over approximately 100 generations in the absence of tetrachloroethene (PCE). However, the molecular mechanisms of this regulation process are not understood. We show here that Sulfurospirillum halorespirans undergoes the same type of regulation when cultivated without chlorinated ethenes for a long period of time. In addition, we compared the proteomes of S. halorespirans cells cultivated in the presence of PCE with those of cells long- and short-term cultivated with nitrate as the sole electron acceptor. Important OHR-related proteins previously unidentified in S. multivorans include a histidine kinase, a putative quinol dehydrogenase membrane protein, and a PCE-induced porin. Since for some regulatory proteins a posttranslational regulation of activity by lysine acetylations is known, we also analyzed the acetylome of S. halorespirans, revealing that 32% of the proteome was acetylated in at least one condition. The data indicate that the response regulator and the histidine kinase of a two-component system most probably involved in induction of PCE respiration are highly acetylated during short-term cultivation with nitrate in the absence of PCE. The so far unique long-term downregulation of organohalide respiration is now identified in a second species suggesting a broader distribution of this regulatory phenomenon. An improved protein extraction method allowed the identification of proteins most probably involved in transcriptional regulation of OHR in Sulfurospirillum spp. Our data indicate that acetylations of regulatory proteins are involved in this extreme, sustained standby-mode of metabolic enzymes in the absence of a substrate. This first published acetylome of Epsilonproteobacteria might help to study other ecologically or medically important species of this clade. Copyright © 2018 Elsevier B.V. All rights reserved.

Long-term hypoxia modulates expression of key genes regulating adipose function in the late-gestation ovine fetus.

PubMed

Myers, Dean A; Hanson, Krista; Mlynarczyk, Malgorzata; Kaushal, Kanchan M; Ducsay, Charles A

2008-04-01

A major function of abdominal adipose in the newborn is nonshivering thermogenesis. Uncoupling protein (UCP) UCP1 and UCP2 play major roles in thermogenesis. The present study tested the hypothesis that long-term hypoxia (LTH) modulates expression of UCP1 and UCP2, and key genes regulating expression of these genes in the late-gestation ovine fetus. Ewes were maintained at high altitude (3,820 m) from 30 to 138 days gestation (dG); perirenal adipose tissue was collected from LTH and age-matched, normoxic control fetuses at 139-141 dG. Quantitative real-time PCR was used to analyze mRNA for UCP1, UCP2, 11beta hydroxysteroid dehydrogenase type 1 (HSD11B1) and 2 (HSD11B2), glucocorticoid receptor (GR), beta3 adrenergic receptor (beta3AR), deiodinase type 1 (DIO1) and DIO2, peroxisome proliferator activated receptor (PPAR) alpha and gamma and PPARgamma coactivator 1 (PGC1alpha). Concentrations of mRNA for UCP1, HSD11B1, PPARgamma, PGC1, DIO1, and DIO2 were significantly higher in perirenal adipose of LTH compared with control fetuses, while mRNA for HSD11B2, GR, or PPARalpha in perirenal adipose did not differ between control and LTH fetuses. The increased expression of UCP1 is likely an adaptive response to LTH, assuring adequate thermogenesis in the event of birth under oxygen-limiting conditions. Because both glucocorticoids and thyroid hormone regulate UCP1 expression, the increase in HSD11B1, DIO1, and DIO2 implicate increased adipose capacity for local synthesis of these hormones. PPARgamma and its coactivator may provide an underlying mechanism via which LTH alters development of the fetal adipocyte. These findings have important implications regarding fetal/neonatal adipose tissue function in response to LTH.

Long-term Kinetics of Uranyl Desorption from Sediments Under Advective Conditions

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

Shang, Jianying; Liu, Chongxuan; Wang, Zheming

2014-02-15

Long-term (> 4 months) column experiments were performed to investigate the kinetics of uranyl (U(VI)) desorption in sediments collected from the Integrated Field Research Challenge (IFRC) site at the US Department of Energy (DOE) Hanford 300 Area. The experimental results were used to evaluate alternative multi-rate surface complexation reaction (SCR) approaches to describe the short- and long-term kinetics of U(VI) desorption under flow conditions. The SCR stoichiometry, equilibrium constants, and multi-rate parameters were independently characterized in batch and stirred flow-cell reactors. Multi-rate SCR models that were either additively constructed using the SCRs for individual size fractions (e.g., Shang et al.,more » 2011), or composite in nature could effectively describe short-term U(VI) desorption under flow conditions. The long-term desorption results, however, revealed that using a labile U concentration measured by carbonate extraction under-estimated desorbable U(VI) and the long-term rate of U(VI) desorption. An alternative modeling approach using total U as the desorbable U(VI) concentration was proposed to overcome this difficulty. This study also found that the gravel size fraction (2-8 mm), which is typically treated as non-reactive in modeling U(VI) reactive transport because of low external surface area, can have an important effect on the U(VI) desorption in the sediment. This study demonstrates an approach to effectively extrapolate U(VI) desorption kinetics for field-scale application, and identifies important parameters and uncertainties affecting model predictions.« less

Direct evidence that density-dependent regulation underpins the temporal stability of abundant species in a diverse animal community

PubMed Central

Henderson, Peter A.; Magurran, Anne E.

2014-01-01

To understand how ecosystems are structured and stabilized, and to identify when communities are at risk of damage or collapse, we need to know how the abundances of the taxa in the entire assemblage vary over ecologically meaningful timescales. Here, we present an analysis of species temporal variability within a single large vertebrate community. Using an exceptionally complete 33-year monthly time series following the dynamics of 81 species of fishes, we show that the most abundant species are least variable in terms of temporal biomass, because they are under density-dependent (negative feedback) regulation. At the other extreme, a relatively large number of low abundance transient species exhibit the greatest population variability. The high stability of the consistently common high abundance species—a result of density-dependence—is reflected in the observation that they consistently represent over 98% of total fish biomass. This leads to steady ecosystem nutrient and energy flux irrespective of the changes in species number and abundance among the large number of low abundance transient species. While the density-dependence of the core species ensures stability under the existing environmental regime, the pool of transient species may support long-term stability by replacing core species should environmental conditions change. PMID:25100702

Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice

PubMed Central

Smith, Mark A.; Katsouri, Loukia; Irvine, Elaine E.; Hankir, Mohammed K.; Pedroni, Silvia M.A.; Voshol, Peter J.; Gordon, Matthew W.; Choudhury, Agharul I.; Woods, Angela; Vidal-Puig, Antonio; Carling, David; Withers, Dominic J.

2015-01-01

Summary Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons. PMID:25865886

Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice.

PubMed

Smith, Mark A; Katsouri, Loukia; Irvine, Elaine E; Hankir, Mohammed K; Pedroni, Silvia M A; Voshol, Peter J; Gordon, Matthew W; Choudhury, Agharul I; Woods, Angela; Vidal-Puig, Antonio; Carling, David; Withers, Dominic J

2015-04-21

Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

European experience of regulating distance selling of medicines for Ukraine.

PubMed

Pashkov, Vitalii; Hrekov, Yevhen; Hrekova, Maryna

Some countries have already tried and tested mechanisms of regulating distance sales as form of distribution of medicines that have been used more or less effectively for a fairly long time. Herewith, so far, the approach of the competent authorities of some countries including Ukraine can be called prevailing in quantitative terms under which the official prohibition on distance sales of medicines is set. The aim of this study is a detailed examination of the nature of the prohibition of the medicines distance selling in Ukraine, namely the an analysis of advantages and disadvantages of this form of distribution of medicines and identification of appropriate ways for gradual repeal of the prohibition in terms of regulatory reform in Ukraine in the sphere of circulation of medicines due to the process of adaptation of statutory regulation in this area to the EU legislation. This study is based on Ukrainian regulation acts, Council Directives 97/7/EC, 2000/31/EC, 2001/83/EC, scientific works and opinions of progressiveminded people in this sphere. Such methods as dialectical, comparative, analytic, synthetic and comprehensive have been used in the article. Reception of the described experience of regulation in EU will allow a further review of the principles of regulation in Ukraine in the sphere of medicines with a shift in the main emphasis in the direction of ensuring adequate consumer rights in this area and preventing the risks of patients' and public health.

A self-determination theory approach to adults' healthy body weight motivation: A longitudinal study focussing on food choices and recreational physical activity.

PubMed

Hartmann, Christina; Dohle, Simone; Siegrist, Michael

2015-01-01

This study focuses on body weight motivation based on self-determination theory. The impact of body weight motivation on longitudinal changes in food choices, recreational physical activity and body mass index was explored. A sample of adults (N = 2917, 47% men), randomly selected from the telephone book, completed a questionnaire in two consecutive years (2012, 2013), self-reporting food choices, recreational physical activity and body weight motivation. Types of body weight motivation at T1 (autonomous regulation, introjected regulation, and external regulation) were tested with regard to their predictive potential for changes in food choices, recreational physical activity and body mass index (BMI). Autonomous motivation predicted improvements in food choices and long-term adherence to vigorous recreational physical activity in both genders. Introjected motivation predicted long-term adherence to vigorous recreational physical activity only in women. External motivation predicted negative changes in food choices; however, the type of body weight motivation had no impact on BMI in overweight adults in the long term. Autonomous goal-setting regarding body weight seems to be substantial for healthy food choices and adherence to recreational physical activity.

Mind bomb-1 is an essential modulator of long-term memory and synaptic plasticity via the Notch signaling pathway

PubMed Central

2012-01-01

Background Notch signaling is well recognized as a key regulator of the neuronal fate during embryonic development, but its function in the adult brain is still largely unknown. Mind bomb-1 (Mib1) is an essential positive regulator in the Notch pathway, acting non-autonomously in the signal-sending cells. Therefore, genetic ablation of Mib1 in mature neuron would give valuable insight to understand the cell-to-cell interaction between neurons via Notch signaling for their proper function. Results Here we show that the inactivation of Mib1 in mature neurons in forebrain results in impaired hippocampal dependent spatial memory and contextual fear memory. Consistently, hippocampal slices from Mib1-deficient mice show impaired late-phase, but not early-phase, long-term potentiation and long-term depression without change in basal synaptic transmission at SC-CA1 synapses. Conclusions These data suggest that Mib1-mediated Notch signaling is essential for long-lasting synaptic plasticity and memory formation in the rodent hippocampus. PMID:23111145

Poly-victimization and trajectories of binge drinking from adolescence to young adulthood among serious juvenile offenders.

PubMed

Davis, Jordan P; Dumas, Tara M; Berey, Benjamin; Merrin, Gabriel J; Tan, Kevin; Madden, Danielle R

2018-05-01

Justice involved youth exposed to multiple forms of victimization (i.e., poly-victimization) may be at risk for long term substance use problems and difficulty in self-regulation, placing them at higher risk of long-term problematic behaviors. This study empirically identifies victimization classifications in a sample of justice involved youth and how long-term binge drinking is related to victimization experiences. We further sought to understand how self-regulatory abilities such as impulse control and emotion regulation effect emergent profiles and binge drinking trajectories. Based on a sample of 1354 justice involved youth from 15 to 25 years old, classes of victimization were extracted. Emergent classes were examined in relationship to their binge drinking trajectories using latent growth models. Finally, self-regulation was examined as a predictor of binge drinking trajectories across emergent classes. The analyses indicated three classes of victimization: poly-victimized, indirectly victimized, and lowly victimized. Latent growth models revealed that the poly-victimized class had significantly steeper growth in binge drinking as compared to the indirect and low victimized patterns. Impulse and emotional regulation both significantly decelerated binge drinking only for the indirect victimization group. Findings highlight the need to focus on poly-victimization in understanding binge drinking trajectories as well as the role impulse control and emotional regulation play among justice involved youth. Findings are discussed through the lens of adolescent development, coping strategies, and early traumatic experiences. Copyright © 2018 Elsevier B.V. All rights reserved.

Environmental, health, and safety issues of sodium-sulfur batteries for electric and hybrid vehicles. Volume 2, Battery recycling and disposal

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

Corbus, D

1992-09-01

Recycling and disposal of spent sodium-sulfur (Na/S) batteries are important issues that must be addressed as part of the commercialization process of Na/S battery-powered electric vehicles. The use of Na/S batteries in electric vehicles will result in significant environmental benefits, and the disposal of spent batteries should not detract from those benefits. In the United States, waste disposal is regulated under the Resource Conservation and Recovery Act (RCRA). Understanding these regulations will help in selecting recycling and disposal processes for Na/S batteries that are environmentally acceptable and cost effective. Treatment processes for spent Na/S battery wastes are in the beginningmore » stages of development, so a final evaluation of the impact of RCRA regulations on these treatment processes is not possible. The objectives of tills report on battery recycling and disposal are as follows: Provide an overview of RCRA regulations and requirements as they apply to Na/S battery recycling and disposal so that battery developers can understand what is required of them to comply with these regulations; Analyze existing RCRA regulations for recycling and disposal and anticipated trends in these regulations and perform a preliminary regulatory analysis for potential battery disposal and recycling processes. This report assumes that long-term Na/S battery disposal processes will be capable of handling large quantities of spent batteries. The term disposal includes treatment processes that may incorporate recycling of battery constituents. The environmental regulations analyzed in this report are limited to US regulations. This report gives an overview of RCRA and discusses RCRA regulations governing Na/S battery disposal and a preliminary regulatory analysis for Na/S battery disposal.« less

Lime and phosphogypsum impacts on soil organic matter pools in a tropical Oxisol under long-term no-till conditions

USDA-ARS?s Scientific Manuscript database

Improving soil organic matter (SOM) quality in tropical acid soils is important for increasing the sustainability of agricultural ecosystems. This research evaluated the effect of the surface application of lime and phosphogypsum on the quality and amount of SOM in a long-term crop rotation under no...

Structural composite panel performance under long-term load

Treesearch

Theodore L. Laufenberg

1988-01-01

Information on the performance of wood-based structural composite panels under long-term load is currently needed to permit their use in engineered assemblies and systems. A broad assessment of the time-dependent properties of panels is critical for creating databases and models of the creep-rupture phenomenon that lead to reliability-based design procedures. This...

78 FR 1698 - Semiannual Regulatory Flexibility Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-08

... Transition Provisions. (Docket No. R- 1442). 524 Regulation LL--Savings and 7100-AD80 Loan Holding Companies and Regulation MM--Mutual Holding Companies (Docket No. R-1429). Federal Reserve System--Long-Term... Holding Companies (Docket No. R-1430). [[Page 1699

Towards a better monitoring of seed ageing under ex situ seed conservation

PubMed Central

Fu, Yong-Bi; Ahmed, Zaheer; Diederichsen, Axel

2015-01-01

Long-term conservation of 7.4 million ex situ seed accessions held in agricultural genebanks and botanic gardens worldwide is a challenging mission for human food security and ecosystem services. Recent advances in seed biology and genomics may have opened new opportunities for effective management of seed germplasm under long-term storage. Here, we review the current development of tools for assessing seed ageing and research advances in seed biology and genomics, with a focus on exploring their potential as better tools for monitoring of seed ageing. Seed ageing is found to be associated with the changes reflected in reactive oxygen species and mitochondria-triggered programmed cell deaths, expression of antioxidative genes and DNA and protein repair genes, chromosome telomere lengths, epigenetic regulation of related genes (microRNA and methylation) and altered organelle and nuclear genomes. Among these changes, the signals from mitochondrial and nuclear genomes may show the most promise for use in the development of tools to predict seed ageing. Non-destructive and non-invasive analyses of stored seeds through calorimetry or imaging techniques are also promising. It is clear that research into developing advanced tools for monitoring seed ageing to supplement traditional germination tests will be fruitful for effective conservation of ex situ seed germplasm. PMID:27293711

Homeostatic maintenance via degradation and repair of elastic fibers under tension

NASA Astrophysics Data System (ADS)

Alves, Calebe; Araújo, Ascanio D.; Oliveira, Cláudio L. N.; Imsirovic, Jasmin; Bartolák-Suki, Erzsébet; Andrade, José S.; Suki, Béla

2016-06-01

Cellular maintenance of the extracellular matrix requires an effective regulation that balances enzymatic degradation with the repair of collagen fibrils and fibers. Here, we investigate the long-term maintenance of elastic fibers under tension combined with diffusion of general degradative and regenerative particles associated with digestion and repair processes. Computational results show that homeostatic fiber stiffness can be achieved by assuming that cells periodically probe fiber stiffness to adjust the production and release of degradative and regenerative particles. However, this mechanism is unable to maintain a homogeneous fiber. To account for axial homogeneity, we introduce a robust control mechanism that is locally governed by how the binding affinity of particles is modulated by mechanical forces applied to the ends of the fiber. This model predicts diameter variations along the fiber that are in agreement with the axial distribution of collagen fibril diameters obtained from scanning electron microscopic images of normal rat thoracic aorta. The model predictions match the experiments only when the applied force on the fiber is in the range where the variance of local stiffness along the fiber takes a minimum value. Our model thus predicts that the biophysical properties of the fibers play an important role in the long-term regulatory maintenance of these fibers.

Beyond post-marketing research and MedWatch: Long-term studies of drug risks.

PubMed

Resnik, David B

2007-10-01

Critics of the drug safety system have discussed many different potential reforms, ranging from mandatory registration of clinical trials to increasing the power of regulatory agencies, but few have discussed one of the most important ways of enhancing safety: increasing the number of long-term studies of medications. Long-term studies of the risks and benefits of drugs can provide useful information for regulators, healthcare professionals, and patients. Government funding agencies should lead the effort to conduct long-term studies of drugs, but private companies should also be required to lend financial support. Because cost-effectiveness is likely to be an important consideration in conducting this research, funding agencies should focus, at first, on drugs that are used to treat common, chronic conditions.

Beyond post-marketing research and MedWatch: Long-term studies of drug risks

PubMed Central

Resnik, David B

2007-01-01

Critics of the drug safety system have discussed many different potential reforms, ranging from mandatory registration of clinical trials to increasing the power of regulatory agencies, but few have discussed one of the most important ways of enhancing safety: increasing the number of long-term studies of medications. Long-term studies of the risks and benefits of drugs can provide useful information for regulators, healthcare professionals, and patients. Government funding agencies should lead the effort to conduct long-term studies of drugs, but private companies should also be required to lend financial support. Because cost-effectiveness is likely to be an important consideration in conducting this research, funding agencies should focus, at first, on drugs that are used to treat common, chronic conditions. PMID:19727333

Ecosystem processes and human influences regulate streamflow response to climate change at long-term ecological research sites

Treesearch

Julia A. Jones; Irena F. Creed; Kendra L. Hatcher; Robert J. Warren; Mary Beth Adams; Melinda H. Benson; Emery Boose; Warren A. Brown; John L. Campbell; Alan Covich; David W. Clow; Clifford N. Dahm; Kelly Elder; Chelcy R. Ford; Nancy B. Grimm; Donald L Henshaw; Kelli L. Larson; Evan S. Miles; Kathleen M. Miles; Stephen D. Sebestyen; Adam T. Spargo; Asa B. Stone; James M. Vose; Mark W. Williams

2012-01-01

Analyses of long-term records at 35 headwater basins in the United States and Canada indicate that climate change effects on streamflow are not as clear as might be expected, perhaps because of ecosystem processes and human influences. Evapotranspiration was higher than was predicted by temperature in water-surplus ecosystems and lower than was predicted in water-...

Staufen 2 Regulates mGluR Long-Term Depression and Map1b mRNA Distribution in Hippocampal Neurons

ERIC Educational Resources Information Center

Lebeau, Genevieve; Miller, Linda C.; Tartas, Maylis; McAdam, Robyn; Laplante, Isabel; Badeaux, Frederique; DesGroseillers, Luc; Sossin, Wayne S.; Lacaille, Jean-Claude

2011-01-01

The two members of the Staufen family of RNA-binding proteins, Stau1 and Stau2, are present in distinct ribonucleoprotein complexes and associate with different mRNAs. Stau1 is required for protein synthesis-dependent long-term potentiation (L-LTP) in hippocampal pyramidal cells. However, the role of Stau2 in synaptic plasticity remains…

Intrahippocampal Glutamine Administration Inhibits mTORC1 Signaling and Impairs Long-Term Memory

ERIC Educational Resources Information Center

Rozas, Natalia S.; Redell, John B.; Pita-Almenar, Juan D.; McKenna, James, III.; Moore, Anthony N.; Gambello, Michael J.; Dash, Pramod K.

2015-01-01

The mechanistic Target of Rapamycin Complex 1 (mTORC1), a key regulator of protein synthesis and cellular growth, is also required for long-term memory formation. Stimulation of mTORC1 signaling is known to be dependent on the availability of energy and growth factors, as well as the presence of amino acids. In vitro studies using serum- and amino…

Long-term dietary effects on substrate selection and muscle fiber type in very-long-chain acyl-CoA dehydrogenase deficient (VLCAD(-/-)) mice.

PubMed

Tucci, Sara; Pearson, Sonja; Herebian, Diran; Spiekerkoetter, Ute

2013-04-01

Dietary fat restriction and increased carbohydrate intake are part of treatment in very-long-chain acyl-CoA dehydrogenase (VLCAD)-deficiency, the most common defect of long-chain fatty acid oxidation. The long-term impact of these interventions is unknown. We characterized here the effects of a fat-reduced, carbohydrate-enriched diet and an increased fat intake on energy metabolism in a mouse model of VLCAD-deficiency. Wild-type and VLCAD(-/-) mice were fed one year either with a normal (5.1%), a high fat (10.6%) or a low-fat, carbohydrate-enriched (2.6%) diet. Dietary effects on genes involved in lipogenesis, energy homeostasis and substrate selection were quantified by real-time-PCR. Acylcarnitines as sign of impaired energy production were determined in dried blood spots and tissues. White skeletal muscle was analyzed for muscle fiber type as well as for glycogen and triglyceride content. Both dietary modifications induced enhanced triacylglyceride accumulation in skeletal muscle and inhibition of glucose oxidation. This was accompanied by an up-regulation of genes coding for oxidative muscle fiber type I and a marked accumulation of acylcarnitines, especially prominent in the heart (164±2.8 in VLCAD(-/-) vs. 82.3±2.1 in WT μmol/mg) under a low-fat, carbohydrate-enriched diet. We demonstrate here that both dietary interventions with respect to the fat content of the diet reverse endogenous compensatory mechanisms in muscle that have evolved in VLCAD(-/-) mice resulting in pronounced energy deficiency. In particular, the low-fat carbohydrate-enriched diet was not effective in the long term. Further experiments are necessary to define the optimal energy provision for fatty acid oxidation defects. Copyright © 2013 Elsevier B.V. All rights reserved.

Adipose tissue-derived mesenchymal stem cells in long-term dialysis patients display downregulation of PCAF expression and poor angiogenesis activation.

PubMed

Yamanaka, Shuichiro; Yokote, Shinya; Yamada, Akifumi; Katsuoka, Yuichi; Izuhara, Luna; Shimada, Yohta; Omura, Nobuo; Okano, Hirotaka James; Ohki, Takao; Yokoo, Takashi

2014-01-01

We previously demonstrated that mesenchymal stem cells (MSCs) differentiate into functional kidney cells capable of urine and erythropoietin production, indicating that they may be used for kidney regeneration. However, the viability of MSCs from dialysis patients may be affected under uremic conditions. In this study, we isolated MSCs from the adipose tissues of end-stage kidney disease (ESKD) patients undergoing long-term dialysis (KD-MSCs; mean: 72.3 months) and from healthy controls (HC-MSCs) to compare their viability. KD-MSCs and HC-MSCs were assessed for their proliferation potential, senescence, and differentiation capacities into adipocytes, osteoblasts, and chondrocytes. Gene expression of stem cell-specific transcription factors was analyzed by PCR array and confirmed by western blot analysis at the protein level. No significant differences of proliferation potential, senescence, or differentiation capacity were observed between KD-MSCs and HC-MSCs. However, gene and protein expression of p300/CBP-associated factor (PCAF) was significantly suppressed in KD-MSCs. Because PCAF is a histone acetyltransferase that mediates regulation of hypoxia-inducible factor-1α (HIF-1α), we examined the hypoxic response in MSCs. HC-MSCs but not KD-MSCs showed upregulation of PCAF protein expression under hypoxia. Similarly, HIF-1α and vascular endothelial growth factor (VEGF) expression did not increase under hypoxia in KD-MSCs but did so in HC-MSCs. Additionally, a directed in vivo angiogenesis assay revealed a decrease in angiogenesis activation of KD-MSCs. In conclusion, long-term uremia leads to persistent and systematic downregulation of PCAF gene and protein expression and poor angiogenesis activation of MSCs from patients with ESKD. Furthermore, PCAF, HIF-1α, and VEGF expression were not upregulated by hypoxic stimulation of KD-MSCs. These results suggest that the hypoxic response may be blunted in MSCs from ESKD patients.

Adipose Tissue-Derived Mesenchymal Stem Cells in Long-Term Dialysis Patients Display Downregulation of PCAF Expression and Poor Angiogenesis Activation

PubMed Central

Yamanaka, Shuichiro; Yokote, Shinya; Yamada, Akifumi; Katsuoka, Yuichi; Izuhara, Luna; Shimada, Yohta; Omura, Nobuo; Okano, Hirotaka James; Ohki, Takao; Yokoo, Takashi

2014-01-01

We previously demonstrated that mesenchymal stem cells (MSCs) differentiate into functional kidney cells capable of urine and erythropoietin production, indicating that they may be used for kidney regeneration. However, the viability of MSCs from dialysis patients may be affected under uremic conditions. In this study, we isolated MSCs from the adipose tissues of end-stage kidney disease (ESKD) patients undergoing long-term dialysis (KD-MSCs; mean: 72.3 months) and from healthy controls (HC-MSCs) to compare their viability. KD-MSCs and HC-MSCs were assessed for their proliferation potential, senescence, and differentiation capacities into adipocytes, osteoblasts, and chondrocytes. Gene expression of stem cell-specific transcription factors was analyzed by PCR array and confirmed by western blot analysis at the protein level. No significant differences of proliferation potential, senescence, or differentiation capacity were observed between KD-MSCs and HC-MSCs. However, gene and protein expression of p300/CBP-associated factor (PCAF) was significantly suppressed in KD-MSCs. Because PCAF is a histone acetyltransferase that mediates regulation of hypoxia-inducible factor-1α (HIF-1α), we examined the hypoxic response in MSCs. HC-MSCs but not KD-MSCs showed upregulation of PCAF protein expression under hypoxia. Similarly, HIF-1α and vascular endothelial growth factor (VEGF) expression did not increase under hypoxia in KD-MSCs but did so in HC-MSCs. Additionally, a directed in vivo angiogenesis assay revealed a decrease in angiogenesis activation of KD-MSCs. In conclusion, long-term uremia leads to persistent and systematic downregulation of PCAF gene and protein expression and poor angiogenesis activation of MSCs from patients with ESKD. Furthermore, PCAF, HIF-1α, and VEGF expression were not upregulated by hypoxic stimulation of KD-MSCs. These results suggest that the hypoxic response may be blunted in MSCs from ESKD patients. PMID:25025381

Density-Dependent Recycling Promotes the Long-Term Survival of Bacterial Populations during Periods of Starvation.

PubMed

Takano, Sotaro; Pawlowska, Bogna J; Gudelj, Ivana; Yomo, Tetsuya; Tsuru, Saburo

2017-02-07

The amount of natural resources in the Earth's environment is in flux, which can trigger catastrophic collapses of ecosystems. How populations survive under nutrient-poor conditions is a central question in ecology. Curiously, some bacteria persist for a long time in nutrient-poor environments. Although this survival may be accomplished through cell death and the recycling of dead cells, the importance of these processes and the mechanisms underlying the survival of the populations have not been quantitated. Here, we use microbial laboratory experiments and mathematical models to demonstrate that death and recycling are essential activities for the maintenance of cell survival. We also show that the behavior of the survivors is governed by population density feedback, wherein growth is limited not only by the available resources but also by the population density. The numerical simulations suggest that population density-dependent recycling could be an advantageous behavior under starvation conditions. How organisms survive after exhaustion of resources is a central question in ecology. Starving Escherichia coli constitute a model system to understand survival mechanisms during long-term starvation. Although death and the recycling of dead cells might play a key role in the maintenance of long-term survival, their mechanisms and importance have not been quantitated. Here, we verified the significance of social recycling of dead cells for long-term survival. We also show that the survivors restrained their recycling and did not use all available nutrients released from dead cells, which may be advantageous under starvation conditions. These results indicate that not only the utilization of dead cells but also restrained recycling coordinate the effective utilization of limited resources for long-term survival under starvation. Copyright © 2017 Takano et al.

Long-term exposure to microwave radiation provokes cancer growth: evidences from radars and mobile communication systems.

PubMed

Yakymenko, I; Sidorik, E; Kyrylenko, S; Chekhun, V

2011-06-01

In this review we discuss alarming epidemiological and experimental data on possible carcinogenic effects of long term exposure to low intensity microwave (MW) radiation. Recently, a number of reports revealed that under certain conditions the irradiation by low intensity MW can substantially induce cancer progression in humans and in animal models. The carcinogenic effect of MW irradiation is typically manifested after long term (up to 10 years and more) exposure. Nevertheless, even a year of operation of a powerful base transmitting station for mobile communication reportedly resulted in a dramatic increase of cancer incidence among population living nearby. In addition, model studies in rodents unveiled a significant increase in carcinogenesis after 17-24 months of MW exposure both in tumor-prone and intact animals. To that, such metabolic changes, as overproduction of reactive oxygen species, 8-hydroxi-2-deoxyguanosine formation, or ornithine decarboxylase activation under exposure to low intensity MW confirm a stress impact of this factor on living cells. We also address the issue of standards for assessment of biological effects of irradiation. It is now becoming increasingly evident that assessment of biological effects of non-ionizing radiation based on physical (thermal) approach used in recommendations of current regulatory bodies, including the International Commission on Non-Ionizing Radiation Protection (ICNIRP) Guidelines, requires urgent reevaluation. We conclude that recent data strongly point to the need for re-elaboration of the current safety limits for non-ionizing radiation using recently obtained knowledge. We also emphasize that the everyday exposure of both occupational and general public to MW radiation should be regulated based on a precautionary principles which imply maximum restriction of excessive exposure.

Effects of Long-Term 50Hz Power-Line Frequency Electromagnetic Field on Cell Behavior in Balb/c 3T3 Cells

PubMed Central

An, Guang-Zhou; Xu, Hui; Zhou, Yan; Du, Le; Miao, Xia; Jiang, Da-Peng; Li, Kang-Chu; Guo, Guo-Zhen; Zhang, Chen; Ding, Gui-Rong

2015-01-01

Power-line frequency electromagnetic field (PF-EMF) was reported as a human carcinogen by some epidemiological research, but the conclusion is lack of robust experiment evidence. To identify the effects of long-term PF-EMF exposure on cell behavior, Balb/c 3T3 cells in exponential growth phase were exposed or sham-exposed to 50 Hertz (Hz) PF-EMF at 2.3 mT for 2 hours (h) one day, 5 days every week. After 11 weeks exposure, cells were collected instantly. Cell morphology was observed under invert microscope and Giemsa staining, cell viability was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle and apoptosis was examined by flow cytometry, the protein level of Proliferating Cell Nuclear Antigen (PCNA) and CyclinD1 was detected by western blot, cell transformation was examined by soft agar clone assay and plate clone forming test, and cell migration ability was observed by scratch adhesion test. It was found that after PF-EMF exposure, cell morphology, apoptosis, cell migration ability and cell transformation didn’t change. However, compared with sham group, cell viability obviously decreased and cell cycle distribution also changed after 11 weeks PF-EMF exposure. Meanwhile, the protein level of PCNA and CyclinD1 significantly decreased after PF-EMF exposure. These data suggested that although long-term 50Hz PF-EMF exposure under this experimental condition had no effects on apoptosis, cell migration ability and cell transformation, it could affect cell proliferation and cell cycle by down-regulation the expression of PCNA and CyclinD1 protein. PMID:25695503

Effects of long-term 50Hz power-line frequency electromagnetic field on cell behavior in Balb/c 3T3 cells.

PubMed

An, Guang-Zhou; Xu, Hui; Zhou, Yan; Du, Le; Miao, Xia; Jiang, Da-Peng; Li, Kang-Chu; Guo, Guo-Zhen; Zhang, Chen; Ding, Gui-Rong

2015-01-01

Power-line frequency electromagnetic field (PF-EMF) was reported as a human carcinogen by some epidemiological research, but the conclusion is lack of robust experiment evidence. To identify the effects of long-term PF-EMF exposure on cell behavior, Balb/c 3T3 cells in exponential growth phase were exposed or sham-exposed to 50 Hertz (Hz) PF-EMF at 2.3 mT for 2 hours (h) one day, 5 days every week. After 11 weeks exposure, cells were collected instantly. Cell morphology was observed under invert microscope and Giemsa staining, cell viability was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle and apoptosis was examined by flow cytometry, the protein level of Proliferating Cell Nuclear Antigen (PCNA) and CyclinD1 was detected by western blot, cell transformation was examined by soft agar clone assay and plate clone forming test, and cell migration ability was observed by scratch adhesion test. It was found that after PF-EMF exposure, cell morphology, apoptosis, cell migration ability and cell transformation didn't change. However, compared with sham group, cell viability obviously decreased and cell cycle distribution also changed after 11 weeks PF-EMF exposure. Meanwhile, the protein level of PCNA and CyclinD1 significantly decreased after PF-EMF exposure. These data suggested that although long-term 50Hz PF-EMF exposure under this experimental condition had no effects on apoptosis, cell migration ability and cell transformation, it could affect cell proliferation and cell cycle by down-regulation the expression of PCNA and CyclinD1 protein.

Effects of Substrate Addition on Soil Respiratory Carbon Release Under Long-Term Warming and Clipping in a Tallgrass Prairie

PubMed Central

Jia, Xiaohong; Zhou, Xuhui; Luo, Yiqi; Xue, Kai; Xue, Xian; Xu, Xia; Yang, Yuanhe; Wu, Liyou; Zhou, Jizhong

2014-01-01

Regulatory mechanisms of soil respiratory carbon (C) release induced by substrates (i.e., plant derived substrates) are critical for predicting ecosystem responses to climate change, but the mechanisms are not well understood. In this study, we sampled soils from a long-term field manipulative experiment and conducted a laboratory incubation to explore the role of substrate supply in regulating the differences in soil C release among the experimental treatments, including control, warming, clipping, and warming plus clipping. Three types of substrates (glucose, C3 and C4 plant materials) were added with an amount equal to 1% of soil dry weight under the four treatments. We found that the addition of all three substrates significantly stimulated soil respiratory C release in all four warming and clipping treatments. In soils without substrate addition, warming significantly stimulated soil C release but clipping decreased it. However, additions of glucose and C3 plant materials (C3 addition) offset the warming effects, whereas C4 addition still showed the warming-induced stimulation of soil C release. Our results suggest that long-term warming may inhibit microbial capacity for decomposition of C3 litter but may enhance it for decomposition of C4 litter. Such warming-induced adaptation of microbial communities may weaken the positive C-cycle feedback to warming due to increased proportion of C4 species in plant community and decreased litter quality. In contrast, clipping may weaken microbial capacity for warming-induced decomposition of C4 litter but may enhance it for C3 litter. Warming- and clipping-induced shifts in microbial metabolic capacity may be strongly associated with changes in plant species composition and could substantially influence soil C dynamics in response to global change. PMID:25490701

Effects of substrate addition on soil respiratory carbon release under long-term warming and clipping in a tallgrass prairie.

PubMed

Jia, Xiaohong; Zhou, Xuhui; Luo, Yiqi; Xue, Kai; Xue, Xian; Xu, Xia; Yang, Yuanhe; Wu, Liyou; Zhou, Jizhong

2014-01-01

Regulatory mechanisms of soil respiratory carbon (C) release induced by substrates (i.e., plant derived substrates) are critical for predicting ecosystem responses to climate change, but the mechanisms are not well understood. In this study, we sampled soils from a long-term field manipulative experiment and conducted a laboratory incubation to explore the role of substrate supply in regulating the differences in soil C release among the experimental treatments, including control, warming, clipping, and warming plus clipping. Three types of substrates (glucose, C3 and C4 plant materials) were added with an amount equal to 1% of soil dry weight under the four treatments. We found that the addition of all three substrates significantly stimulated soil respiratory C release in all four warming and clipping treatments. In soils without substrate addition, warming significantly stimulated soil C release but clipping decreased it. However, additions of glucose and C3 plant materials (C3 addition) offset the warming effects, whereas C4 addition still showed the warming-induced stimulation of soil C release. Our results suggest that long-term warming may inhibit microbial capacity for decomposition of C3 litter but may enhance it for decomposition of C4 litter. Such warming-induced adaptation of microbial communities may weaken the positive C-cycle feedback to warming due to increased proportion of C4 species in plant community and decreased litter quality. In contrast, clipping may weaken microbial capacity for warming-induced decomposition of C4 litter but may enhance it for C3 litter. Warming- and clipping-induced shifts in microbial metabolic capacity may be strongly associated with changes in plant species composition and could substantially influence soil C dynamics in response to global change.

77 FR 76706 - Endangered and Threatened Species; Threatened Status for the Arctic, Okhotsk, and Baltic...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

...We, NMFS, issue a final determination to list the Arctic (Phoca hispida hispida), Okhotsk (Phoca hispida ochotensis), and Baltic (Phoca hispida botnica) subspecies of the ringed seal (Phoca hispida) as threatened and the Ladoga (Phoca hispida ladogensis) subspecies of the ringed seal as endangered under the Endangered Species Act (ESA). We will propose to designate critical habitat for the Arctic ringed seal in a future rulemaking. To assist us in this effort, we solicit information that may be relevant to the designation of critical habitat for Arctic ringed seals. In light of public comments and upon further review, we are withdrawing the proposed ESA section 4(d) protective regulations for threatened subspecies of the ringed seal because we have determined that such regulations are not necessary or advisable for the conservation of the Arctic, Okhotsk, or Baltic subspecies of the ringed seal at this time. Given their current population sizes, the long-term nature of the primary threat to these subspecies (habitat alteration stemming from climate change), and the existing protections under the Marine Mammal Protection Act, it is unlikely that the proposed protective regulations would provide appreciable conservation benefits.

Neonatal isolation delays the developmental decline of long-term depression in the CA1 region of rat hippocampus.

PubMed

Ku, Hsiao-Yun; Huang, Yu-Fei; Chao, Pei-Hsuan; Huang, Chiung-Chun; Hsu, Kuei-Sen

2008-11-01

Activity-dependent alterations of synaptic efficacy or connectivity are essential for the development, signal processing, and learning and memory functions of the nervous system. It was observed that, in particular in the CA1 region of the hippocampus, low-frequency stimulation (LFS) became progressively less effective at inducing long-term depression (LTD) with advancing developmental age. The physiological factors regulating this developmental plasticity change, however, have not yet been elucidated. Here we examined the hypothesis that neonatal isolation (once per day for 1 h from postnatal days 1-7) is able to alter processes underlying the developmental decline of LTD. We confirm that the magnitude of LTD induced by LFS (900 stimuli at 1 Hz) protocol correlates negatively with developmental age and illustrates that neonatal isolation delays this developmental decline via the activation of corticotrophin-releasing factor (CRF) system. Furthermore, this modulation appears to be mediated by an increased transcription of N-methyl-D-aspartate receptor NR2B subunits. We also demonstrate that intracerebroventricular injection of CRF postnatally mimicked the effect of neonatal isolation to increase the expression of NR2B subunits and delayed the developmental decline of LTD, which was specifically blocked by CRF receptor 1 antagonist NBI27914 pretreatment. These results suggest a novel role for CRF in regulating developmental events in the hippocampus and indicate that although maternal deprivation is stressful for neonate, appropriate neonatal isolation can serve to promote an endocrine state that may regulate the gradual developmental change in the induction rules for synaptic plasticity in the hippocampal CA1 region.

Short- and long-term salinity challenge, Osmoregulatory ability, and (Na+, K+)-ATPase KINETICS AND α-SUBUNIT mRNA expression in the gills of the thinstripe hermit CRAB Clibanarius symmetricus.

PubMed

Faleiros, Rogério O; Garçon, Daniela P; Lucena, Malson N; McNamara, John C; Leone, Francisco A

2018-06-19

The evolutionary history of the Crustacea reveals ample adaptive radiation and the subsequent occupation of many osmotic niches resulting from physiological plasticity in their osmoregulatory mechanisms. We evaluate osmoregulatory ability in the intertidal, thinstripe hermit crab Clibanarius symmetricus after short-term exposure (6 h) or long-term acclimation (10 days) to a wide salinity range, also analyzing kinetic behavior and α-subunit mRNA expression of the gill (Na + , K + )-ATPase. The crab strongly hyper-regulates its hemolymph at 5 and 15‰S (Salinity, g L -1 ) but weakly hyper-regulates up to ≈27‰S. After 6 h exposure to 35‰S and 45‰S, C. symmetricus slightly hypo-regulates its hemolymph, becoming isosmotic after 10 days acclimation to these salinities. (Na + , K + )-ATPase specific activity decreases with increasing salinity for both exposure periods, reflecting physiological adjustment to isosmoticity. At low salinities, the gill enzyme exhibits a single, low affinity ATP binding site. However, at elevated salinities, a second, high affinity, ATP binding site appears, independently of exposure time. (Na + , K + )-ATPase α-subunit mRNA expression increases only after 10 days acclimation to 5‰S. Our findings suggest that hemolymph hyper-regulation is effected by alterations in enzyme activity during short-term exposure, but is sustained by increased mRNA expression during long-term acclimation. The decrease in gill (Na + , K + )-ATPase activity seen as a consequence of increasing salinity appears to underlie biochemical adjustments to hemolymph isosmoticity as hypo-regulatory ability diminishes. Copyright © 2018. Published by Elsevier Inc.

Long-Term Fine Particulate Matter Exposure and Major Depressive Disorder in a Community-Based Urban Cohort

PubMed Central

Kim, Kyoung-Nam; Lim, Youn-Hee; Bae, Hyun Joo; Kim, Myounghee; Jung, Kweon; Hong, Yun-Chul

2016-01-01

Background: Previous studies have associated short-term air pollution exposure with depression. Although an animal study showed an association between long-term exposure to particulate matter ≤ 2.5 μm (PM2.5) and depression, epidemiological studies assessing the long-term association are scarce. Objective: We aimed to determine the association between long-term PM2.5 exposure and major depressive disorder (MDD). Methods: A total of 27,270 participants 15–79 years of age who maintained an address within the same districts in Seoul, Republic of Korea, throughout the entire study period (between 2002 and 2010) and without a previous MDD diagnosis were analyzed. We used three district-specific exposure indices as measures of long-term PM2.5 exposure. Cox proportional hazards models adjusted for potential confounding factors and measured at district and individual levels were constructed. We further conducted stratified analyses according to underlying chronic diseases such as diabetes mellitus, cardiovascular disease, and chronic obstructive pulmonary disease. Results: The risk of MDD during the follow-up period (2008–2010) increased with an increase of 10 μg/m3 in PM2.5 in 2007 [hazard ratio (HR) = 1.44; 95% CI: 1.17, 1.78], PM2.5 between 2007 and 2010 (HR = 1.59; 95% CI: 1.02, 2.49), and 12-month moving average of PM2.5 until an event or censor (HR = 1.47; 95% CI: 1.14, 1.90). The association between long-term PM2.5 exposure and MDD was greater in participants with underlying chronic diseases than in participants without these diseases. Conclusion: Long-term PM2.5 exposure increased the risk of MDD among the general population. Individuals with underlying chronic diseases are more vulnerable to long-term PM2.5 exposure. Citation: Kim KN, Lim YH, Bae HJ, Kim M, Jung K, Hong YC. 2016. Long-term fine particulate matter exposure and major depressive disorder in a community-based urban cohort. Environ Health Perspect 124:1547–1553; http://dx.doi.org/10.1289/EHP192 PMID:27129131

Does drug price-regulation affect healthcare expenditures?

PubMed

Ben-Aharon, Omer; Shavit, Oren; Magnezi, Racheli

2017-09-01

Increasing health costs in developed countries are a major concern for decision makers. A variety of cost containment tools are used to control this trend, including maximum price regulation and reimbursement methods for health technologies. Information regarding expenditure-related outcomes of these tools is not available. To evaluate the association between different cost-regulating mechanisms and national health expenditures in selected countries. Price-regulating and reimbursement mechanisms for prescription drugs among OECD countries were reviewed. National health expenditure indices for 2008-2012 were extracted from OECD statistical sources. Possible associations between characteristics of different systems for regulation of drug prices and reimbursement and health expenditures were examined. In most countries, reimbursement mechanisms are part of publicly financed plans. Maximum price regulation is composed of reference-pricing, either of the same drug in other countries, or of therapeutic alternatives within the country, as well as value-based pricing (VBP). No association was found between price regulation or reimbursement mechanisms and healthcare costs. However, VBP may present a more effective mechanism, leading to reduced costs in the long term. Maximum price and reimbursement mechanism regulations were not found to be associated with cost containment of national health expenditures. VBP may have the potential to do so over the long term.

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation*

PubMed Central

Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert

2016-01-01

Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein trafficking, enhancement of metabolic activity, and Wnt signaling pathway during the steep phase of memory formation; and (3) cytoskeleton organization proteins. Taken together, this study clearly demonstrates dynamic assembly and disassembly of protein-protein interaction networks depending on the stage of memory formation engrams. PMID:26598641

The Chemokine MIP-1α/CCL3 impairs mouse hippocampal synaptic transmission, plasticity and memory.

PubMed

Marciniak, Elodie; Faivre, Emilie; Dutar, Patrick; Alves Pires, Claire; Demeyer, Dominique; Caillierez, Raphaëlle; Laloux, Charlotte; Buée, Luc; Blum, David; Humez, Sandrine

2015-10-29

Chemokines are signaling molecules playing an important role in immune regulations. They are also thought to regulate brain development, neurogenesis and neuroendocrine functions. While chemokine upsurge has been associated with conditions characterized with cognitive impairments, their ability to modulate synaptic plasticity remains ill-defined. In the present study, we specifically evaluated the effects of MIP1-α/CCL3 towards hippocampal synaptic transmission, plasticity and spatial memory. We found that CCL3 (50 ng/ml) significantly reduced basal synaptic transmission at the Schaffer collateral-CA1 synapse without affecting NMDAR-mediated field potentials. This effect was ascribed to post-synaptic regulations, as CCL3 did not impact paired-pulse facilitation. While CCL3 did not modulate long-term depression (LTD), it significantly impaired long-term potentiation (LTP), an effect abolished by Maraviroc, a CCR5 specific antagonist. In addition, sub-chronic intracerebroventricular (icv) injections of CCL3 also impair LTP. In accordance with these electrophysiological findings, we demonstrated that the icv injection of CCL3 in mouse significantly impaired spatial memory abilities and long-term memory measured using the two-step Y-maze and passive avoidance tasks. These effects of CCL3 on memory were inhibited by Maraviroc. Altogether, these data suggest that the chemokine CCL3 is an hippocampal neuromodulator able to regulate synaptic plasticity mechanisms involved in learning and memory functions.

Biotic Nitrogen Enrichment Regulates Calcium Sources to Forests

NASA Astrophysics Data System (ADS)

Pett-Ridge, J. C.; Perakis, S. S.; Hynicka, J. D.

2015-12-01

Calcium is an essential nutrient in forest ecosystems that is susceptible to leaching loss and depletion. Calcium depletion can affect plant and animal productivity, soil acid buffering capacity, and fluxes of carbon and water. Excess nitrogen supply and associated soil acidification are often implicated in short-term calcium loss from soils, but the long-term role of nitrogen enrichment on calcium sources and resupply is unknown. Here we use strontium isotopes (87Sr/86Sr) as a proxy for calcium to investigate how soil nitrogen enrichment from biological nitrogen fixation interacts with bedrock calcium to regulate both short-term available supplies and the long-term sources of calcium in montane conifer forests. Our study examines 22 sites in western Oregon, spanning a 20-fold range of bedrock calcium on sedimentary and basaltic lithologies. In contrast to previous studies emphasizing abiotic control of weathering as a determinant of long-term ecosystem calcium dynamics and sources (via bedrock fertility, climate, or topographic/tectonic controls) we find instead that that biotic nitrogen enrichment of soil can strongly regulate calcium sources and supplies in forest ecosystems. For forests on calcium-rich basaltic bedrock, increasing nitrogen enrichment causes calcium sources to shift from rock-weathering to atmospheric dominance, with minimal influence from other major soil forming factors, despite regionally high rates of tectonic uplift and erosion that can rejuvenate weathering supply of soil minerals. For forests on calcium-poor sedimentary bedrock, we find that atmospheric inputs dominate regardless of degree of nitrogen enrichment. Short-term measures of soil and ecosystem calcium fertility are decoupled from calcium source sustainability, with fundamental implications for understanding nitrogen impacts, both in natural ecosystems and in the context of global change. Our finding that long-term nitrogen enrichment increases forest reliance on atmospheric calcium helps explain reports of greater ecological calcium limitation in an increasingly nitrogen-rich world.

Long-term regulation of carotid body function: acclimatization and adaptation--invited article.

PubMed

Prabhakar, N R; Peng, Y-J; Kumar, G K; Nanduri, J; Di Giulio, C; Lahiri, Sukhamay

2009-01-01

Physiological responses to hypoxia either continuous (CH) or intermittent (IH) depend on the O(2)-sensing ability of the peripheral arterial chemoreceptors, especially the carotid bodies, and the ensuing reflexes play important roles in maintaining homeostasis. The purpose of this article is to summarize the effects of CH and IH on carotid body function and the underlying mechanisms. CH increases baseline carotid body activity and sensitizes the response to acute hypoxia. These effects are associated with hyperplasia of glomus cells and neovascularization. Enhanced hypoxic sensitivity is due to alterations in ion current densities as well as changes in neurotransmitter dynamics and recruitment of additional neuromodulators (endothelin-1, ET-1) in glomus cells. Morphological alterations are in part due to up-regulation of growth factors (e.g. VEGF). Hypoxia-inducible factor-1 (HIF-1), a transcriptional activator might underlie the remodeling of carotid body structure and function by CH. Chronic IH, on the other hand, is associated with recurrent apneas in adults and premature infants. Two major effects of chronic IH on the adult carotid body are sensitization of the hypoxic sensory response and long-lasting increase in baseline activity i.e., sensory long-term facilitation (LTF) which involve reactive oxygen species (ROS) and HIF-1. In neonates, chronic IH leads to sensitization of the hypoxic response but does not induce sensory LTF. Chronic IH-induced sensitization of the carotid body response to hypoxia increases the likelihood of unstable breathing perpetuating in more number of apneas, whereas sensory LTF may contribute to increased sympathetic tone and systemic hypertension associated with recurrent apneas.

Networking Omic Data to Envisage Systems Biological Regulation.

PubMed

Kalapanulak, Saowalak; Saithong, Treenut; Thammarongtham, Chinae

To understand how biological processes work, it is necessary to explore the systematic regulation governing the behaviour of the processes. Not only driving the normal behavior of organisms, the systematic regulation evidently underlies the temporal responses to surrounding environments (dynamics) and long-term phenotypic adaptation (evolution). The systematic regulation is, in effect, formulated from the regulatory components which collaboratively work together as a network. In the drive to decipher such a code of lives, a spectrum of technologies has continuously been developed in the post-genomic era. With current advances, high-throughput sequencing technologies are tremendously powerful for facilitating genomics and systems biology studies in the attempt to understand system regulation inside the cells. The ability to explore relevant regulatory components which infer transcriptional and signaling regulation, driving core cellular processes, is thus enhanced. This chapter reviews high-throughput sequencing technologies, including second and third generation sequencing technologies, which support the investigation of genomics and transcriptomics data. Utilization of this high-throughput data to form the virtual network of systems regulation is explained, particularly transcriptional regulatory networks. Analysis of the resulting regulatory networks could lead to an understanding of cellular systems regulation at the mechanistic and dynamics levels. The great contribution of the biological networking approach to envisage systems regulation is finally demonstrated by a broad range of examples.

Intrahippocampal glutamine administration inhibits mTORC1 signaling and impairs long-term memory

PubMed Central

Rozas, Natalia S.; Redell, John B.; Pita-Almenar, Juan D.; Mckenna, James; Moore, Anthony N.; Gambello, Michael J.

2015-01-01

The mechanistic Target of Rapamycin Complex 1 (mTORC1), a key regulator of protein synthesis and cellular growth, is also required for long-term memory formation. Stimulation of mTORC1 signaling is known to be dependent on the availability of energy and growth factors, as well as the presence of amino acids. In vitro studies using serum- and amino acid-starved cells have reported that glutamine addition can either stimulate or repress mTORC1 activity, depending on the particular experimental system that was used. However, these experiments do not directly address the effect of glutamine on mTORC1 activity under physiological conditions in nondeprived cells in vivo. We present experimental results indicating that intrahippocampal administration of glutamine to rats reduces mTORC1 activity. Moreover, post-training administration of glutamine impairs long-term spatial memory formation, while coadministration of glutamine with leucine had no influence on memory. Intracellular recordings in hippocampal slices showed that glutamine did not alter either excitatory or inhibitory synaptic activity, suggesting that the observed memory impairments may not result from conversion of glutamine to either glutamate or GABA. Taken together, these findings indicate that glutamine can decrease mTORC1 activity in the brain and may have implications for treatments of neurological diseases associated with high mTORC1 signaling. PMID:25878136

Laminar distribution of cholinergic- and serotonergic-dependent plasticity within kitten visual cortex.

PubMed

Kojic, L; Gu, Q; Douglas, R M; Cynader, M S

2001-02-28

Both cholinergic and serotonergic modulatory projections to mammalian striate cortex have been demonstrated to be involved in the regulation of postnatal plasticity, and a striking alteration in the number and intracortical distribution of cholinergic and serotonergic receptors takes place during the critical period for cortical plasticity. As well, agonists of cholinergic and serotonergic receptors have been demonstrated to facilitate induction of long-term synaptic plasticity in visual cortical slices supporting their involvement in the control of activity-dependent plasticity. We recorded field potentials from layers 4 and 2/3 in visual cortex slices of 60--80 day old kittens after white matter stimulation, before and after a period of high frequency stimulation (HFS), in the absence or presence of either cholinergic or serotonergic agonists. At these ages, the HFS protocol alone almost never induced long-term changes of synaptic plasticity in either layers 2/3 or 4. In layer 2/3, agonist stimulation of m1 receptors facilitated induction of long-term potentiation (LTP) with HFS stimulation, while the activation of serotonergic receptors had only a modest effect. By contrast, a strong serotonin-dependent LTP facilitation and insignificant muscarinic effects were observed after HFS within layer 4. The results show that receptor-dependent laminar stratification of synaptic modifiability occurs in the cortex at these ages. This plasticity may underly a control system gating the experience-dependent changes of synaptic organization within developing visual cortex.

Automated analysis of long-term grooming behavior in Drosophila using a k-nearest neighbors classifier

PubMed Central

Allen, Victoria W; Shirasu-Hiza, Mimi

2018-01-01

Despite being pervasive, the control of programmed grooming is poorly understood. We addressed this gap by developing a high-throughput platform that allows long-term detection of grooming in Drosophila melanogaster. In our method, a k-nearest neighbors algorithm automatically classifies fly behavior and finds grooming events with over 90% accuracy in diverse genotypes. Our data show that flies spend ~13% of their waking time grooming, driven largely by two major internal programs. One of these programs regulates the timing of grooming and involves the core circadian clock components cycle, clock, and period. The second program regulates the duration of grooming and, while dependent on cycle and clock, appears to be independent of period. This emerging dual control model in which one program controls timing and another controls duration, resembles the two-process regulatory model of sleep. Together, our quantitative approach presents the opportunity for further dissection of mechanisms controlling long-term grooming in Drosophila. PMID:29485401

Floodplain inundation response to climate, valley form, and flow regulation on a gravel-bed river in a Mediterranean-climate region

NASA Astrophysics Data System (ADS)

Cienciala, P.; Pasternack, G. B.

2017-04-01

Floodplain inundation regime defines hydrological connectivity between river channel and floodplain and thus strongly controls structure and function of these highly diverse and productive ecosystems. We combined an extensive LiDAR data set on topography and vegetation, long-term hydrological records, as well as the outputs of hydrological and two-dimensional hydraulic models to examine how floodplain inundation regimes in a dynamic, regulated, gravel-cobble river in a Mediterranean-climate region are controlled by reach-scale valley morphology, hydroclimatic conditions, and flow regulation. Estimated relative differences in the extent, duration, and cumulative duration of inundation events were often as large as an order of magnitude and generally greatest for large and long duration events. The relative impact of flow regulation was greatest under dry hydroclimatic conditions. Although the effects of hydroclimate and flow impairment are larger than that of valley floor topography, the latter controls sensitivity of floodplain hydroperiod to flow regime changes and should not be ignored. These quantitative estimates of the relative importance of factors that control floodplain processes in Mediterranean, semiarid rivers contributes to better understanding of hydrology and geomorphology of this important class of channels. We also discuss implications of our findings for processes that shape floodplain habitat for riparian vegetation and salmonid fish, especially in the context of ecological restoration.

[Study on mechanism of SOM stabilization of paddy soils under long-term fertilizations].

PubMed

Luo, Lu; Zhou, Ping; Tong, Cheng-Li; Shi, Hui; Wu, Jin-Shui; Huang, Tie-Ping

2013-02-01

Fourier transform infrared spectroscopy (FTIR) was applied to study the structure of soil organic matter (SOM) of paddy soils under long-term different fertilization treatments. The aim was to clarify the different distribution of SOM between different fertilization methods and between topsoil and subsoil, and to explore the stability mechanism of SOM under different fertilization treatments. The results showed that the content of topsoil organic carbon (SOC) was the highest under organic-inorganic fertilizations, with the increment of SOC by 18.5%, 12.9% and 18.4% under high organic manure (HOM), low organic manure (LOM) and straw returning (STW) respectively compared with no fertilization treatment (CK). The long-term fertilizations also changed the chemical structure of SOM. As compared with CK, different fertilization treatments increased the functional group absorbing intensity of chemical resistance compounds (aliphatic, aromaticity), carbohydrate and organo-silicon compounds, which was the most distinctive under treatments of HOM, LOM and STW. For example, the absorbing intensity of alkyl was 0.30, 0.25 and 0.29 under HOM, LOM and STW, respectively. These values were increased by 87% , 56% and 81% as compared with that under CK treatment. The functional group absorbing intensity of SOM in the topsoil was stronger than that in the subsoil, with the most distinctive difference under HOM, LOM and STW treatments. The present research indicated that the enhanced chemical resistance of functional group of SOM may contribute to the high contents of SOC in the paddy soils under long-term organic-inorganic fertilizations, which also suggested a chemical stabilization mechanism of SOM in the paddy soils.

Evaluation of the CENTURY Model Using Long-Term Fertilization Trials under Corn-Wheat Cropping Systems in the Typical Croplands of China

PubMed Central

Cong, Rihuan; Wang, Xiujun; Xu, Minggang; Ogle, Stephen M.; Parton, William J.

2014-01-01

Soil organic matter models are widely used to study soil organic carbon (SOC) dynamics. Here, we used the CENTURY model to simulate SOC in wheat-corn cropping systems at three long-term fertilization trials. Our study indicates that CENTURY can simulate fertilization effects on SOC dynamics under different climate and soil conditions. The normalized root mean square error is less than 15% for all the treatments. Soil carbon presents various changes under different fertilization management. Treatment with straw return would enhance SOC to a relatively stable level whereas chemical fertilization affects SOC differently across the three sites. After running CENTURY over the period of 1990–2050, the SOC levels are predicted to increase from 31.8 to 52.1 Mg ha−1 across the three sites. We estimate that the carbon sequestration potential between 1990 and 2050 would be 9.4–35.7 Mg ha−1 under the current high manure application at the three sites. Analysis of SOC in each carbon pool indicates that long-term fertilization enhances the slow pool proportion but decreases the passive pool proportion. Model results suggest that change in the slow carbon pool is the major driver of the overall trends in SOC stocks under long-term fertilization. PMID:24751981

Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation

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

Calin-Jageman, Robert J

Work funded on this grant has explored the mechanisms of long-term habituation, a ubiquitous form of learning that plays a key role in basic cognitive functioning. Specifically, behavioral, physiological, and molecular mechanisms of habituation have been explored using a simple model system, the tail-elicited siphon-withdrawal reflex (T-SWR) in the marine mollusk Aplysia californica. Substantial progress has been made on the first and third aims, providing some fundamental insights into the mechanisms by which memories are stored. We have characterized the physiological correlates of short- and long-term habituation. We found that short-term habituation is accompanied by a robust sensory adaptation, whereasmore » long-term habituation is accompanied by alterations in sensory and interneuron synaptic efficacy. Thus, our data indicates memories can be shifted between different sites in a neural network as they are consolidated from short to long term. At the molecular level, we have accomplished microarray analysis comparing gene expression in both habituated and control ganglia. We have identified a network of putatively regulated transcripts that seems particularly targeted towards synaptic changes (e.g. SNAP25, calmodulin) . We are now beginning additional work to confirm regulation of these transcripts and build a more detailed understanding of the cascade of molecular events leading to the permanent storage of long-term memories. On the third aim, we have fostered a nascent neuroscience program via a variety of successful initiatives. We have funded over 11 undergraduate neuroscience scholars, several of whom have been recognized at national and regional levels for their research. We have also conducted a pioneering summer research program for community college students which is helping enhance access of underrepresented groups to life science careers. Despite minimal progress on the second aim, this project has provided a) novel insight into the network mechanisms by which short-term memories are permanently stored, and b) a strong foundation for continued growth of an excellent undergraduate neuroscience program.« less

Sulfur poisoning of Ni/Gadolinium-doped ceria anodes: A long-term study outlining stable solid oxide fuel cell operation

NASA Astrophysics Data System (ADS)

Riegraf, Matthias; Zekri, Atef; Knipper, Martin; Costa, Rémi; Schiller, Günter; Friedrich, K. Andreas

2018-03-01

This work presents an analysis of the long-term behavior of nickel/gadolinium-doped ceria (CGO) anode-based solid oxide fuel cells (SOFC) under sulfur poisoning conditions. A parameter study of sulfur-induced irreversible long-term degradation of commercial, high-performance single cells was carried out at 900 °C for different H2/N2/H2S fuel gas atmospheres, current densities and Ni/CGO anodes. The poisoning periods of the cells varied from 200 to 1500 h. The possibility of stable long-term Ni/CGO anode operation under sulfur exposure is established and the critical operating regime is outlined. Depending on the operating conditions, two degradation phenomena can be observed. Small degradation of the ohmic resistance was witnessed for sulfur exposure times of approximately 1000 h. Moreover, degradation of the anode charge transfer resistance was observed to be triggered by the combination of a small anodic potential step and high sulfur coverage on Ni. The microstructural evolution of altered Ni/CGO anodes was examined post-mortem by means of SEM and FIB/SEM, and is correlated to the anode performance degradation under critical operating conditions, establishing Ni depletion, porosity increase and a tripe phase boundary density decrease in the anode functional layer. It is shown that short-term sulfur poisoning behavior can be used to assess long-term stability.

Short Meditation Trainings Enhance Non-REM Sleep Low-Frequency Oscillations

PubMed Central

Dentico, Daniela; Ferrarelli, Fabio; Riedner, Brady A.; Smith, Richard; Zennig, Corinna; Lutz, Antoine; Tononi, Giulio; Davidson, Richard J.

2016-01-01

Study Objectives We have recently shown higher parietal-occipital EEG gamma activity during sleep in long-term meditators compared to meditation-naive individuals. This gamma increase was specific for NREM sleep, was present throughout the entire night and correlated with meditation expertise, thus suggesting underlying long-lasting neuroplastic changes induced through prolonged training. The aim of this study was to explore the neuroplastic changes acutely induced by 2 intensive days of different meditation practices in the same group of practitioners. We also repeated baseline recordings in a meditation-naive cohort to account for time effects on sleep EEG activity. Design High-density EEG recordings of human brain activity were acquired over the course of whole sleep nights following intervention. Setting Sound-attenuated sleep research room. Patients or Participants Twenty-four long-term meditators and twenty-four meditation-naïve controls. Interventions Two 8-h sessions of either a mindfulness-based meditation or a form of meditation designed to cultivate compassion and loving kindness, hereafter referred to as compassion meditation. Measurements and Results We found an increase in EEG low-frequency oscillatory activities (1–12 Hz, centered around 7–8 Hz) over prefrontal and left parietal electrodes across whole night NREM cycles. This power increase peaked early in the night and extended during the third cycle to high-frequencies up to the gamma range (25–40 Hz). There was no difference in sleep EEG activity between meditation styles in long-term meditators nor in the meditation naïve group across different time points. Furthermore, the prefrontal-parietal changes were dependent on meditation life experience. Conclusions This low-frequency prefrontal-parietal activation likely reflects acute, meditation-related plastic changes occurring during wakefulness, and may underlie a top-down regulation from frontal and anterior parietal areas to the posterior parietal and occipital regions showing chronic, long-lasting plastic changes in long-term meditators. PMID:26900914

Effects of harvesting forest biomass on water and climate regulation services: A synthesis of long-term ecosystem experiments in eastern North America

USGS Publications Warehouse

Caputo, Jesse; Beier, Colin D; Groffman, Peter M; Burns, Douglas A.; Beall, Frederick D; Hazlett, Paul W.; Yorks, Thad E

2016-01-01

Demand for woody biomass fuels is increasing amidst concerns about global energy security and climate change, but there may be negative implications of increased harvesting for forest ecosystem functions and their benefits to society (ecosystem services). Using new methods for assessing ecosystem services based on long-term experimental research, post-harvest changes in ten potential benefits were assessed for ten first-order northern hardwood forest watersheds at three long-term experimental research sites in northeastern North America. As expected, we observed near-term tradeoffs between biomass provision and greenhouse gas regulation, as well as tradeoffs between intensive harvest and the capacity of the forest to remediate nutrient pollution. In both cases, service provision began to recover along with the regeneration of forest vegetation; in the case of pollution remediation, the service recovered to pre-harvest levels within 10 years. By contrast to these two services, biomass harvesting had relatively nominal and transient impacts on other ecosystem services. Our results are sensitive to empirical definitions of societal demand, including methods for scaling societal demand to ecosystem units, which are often poorly resolved. Reducing uncertainty around these parameters can improve confidence in our results and increase their relevance for decision-making. Our synthesis of long-term experimental studies provides insights on the social-ecological resilience of managed forest ecosystems to multiple drivers of change.

Effect of stresses on the structural changes in high-chromium steel upon creep

NASA Astrophysics Data System (ADS)

Fedoseeva, A. E.; Dudova, N. R.; Kaibyshev, R. O.

2017-06-01

The effect of stresses on the microstructure and dispersed particles in a heating-performance Fe‒0.12C-0.06Si-0.04Ni-0.2Mn-9.5Cr-3.2Co-0.45Mo-3.1W-0.2V-0.06Nb-0.005B-0.05N (wt %) steel has been studied under long-term strength tests at T = 650°C under initial applied stresses ranging from 220 to 100 MPa with a step of 20 MPa. Under an applied stress of 160 MPa, which corresponds to a time to fracture of 1703 h, a transfer from short- to long-term creep takes place. It has been shown that alloying with 3% Co and an increase in W content to 3% significantly increase the short-term creep resistance and slightly increase the long-term strength upon tests by more than 104 h. The transfer from short- to the long-term creep is accompanied by substantial changes in the microstructure of the steel. Under long-term creep, the solid solution became depleted of tungsten and of molybdenum down to the thermodynamically equilibrium content of these elements in the solid solution, which leads to the precipitation of a large amount of fine particles of the Laves phase at the boundaries of laths and prior austenitic grains. At a time to fracture of more than 4 × 103 h, the coalescence of the M23C6 carbides and Laves-phase particles occurs, which causes the transformation of the structure of fine tempered martensite lath structure into a subgrained structure.

Long-Term Stability of Oxide Nanowire Sensors via Heavily Doped Oxide Contact.

PubMed

Zeng, Hao; Takahashi, Tsunaki; Kanai, Masaki; Zhang, Guozhu; He, Yong; Nagashima, Kazuki; Yanagida, Takeshi

2017-12-22

Long-term stability of a chemical sensor is an essential quality for long-term collection of data related to exhaled breath, environmental air, and other sources in the Internet of things (IoT) era. Although an oxide nanowire sensor has shown great potential as a chemical sensor, the long-term stability of sensitivity has not been realized yet due to electrical degradation under harsh sensing conditions. Here, we report a rational concept to accomplish long-term electrical stability of metal oxide nanowire sensors via introduction of a heavily doped metal oxide contact layer. Antimony-doped SnO 2 (ATO) contacts on SnO 2 nanowires show much more stable and lower electrical contact resistance than conventional Ti contacts for high temperature (200 °C) conditions, which are required to operate chemical sensors. The stable and low contact resistance of ATO was confirmed for at least 1960 h under 200 °C in open air. This heavily doped oxide contact enables us to realize the long-term stability of SnO 2 nanowire sensors while maintaining the sensitivity for both NO 2 gas and light (photo) detections. The applicability of our method is confirmed for sensors on a flexible polyethylene naphthalate (PEN) substrate. Since the proposed fundamental concept can be applied to various oxide nanostructures, it will give a foundation for designing long-term stable oxide nanomaterial-based IoT sensors.

Zeitgeists and development trends in long-term care facility design.

PubMed

Wang, Chia-Hui; Kuo, Nai-Wen

2006-06-01

Through literature analysis, in-depth interviews, and the application of the Delphi survey, this study explored long-term care resident priorities with regard to long-term care facility design in terms of both physical and psychological needs. This study further clarified changing trends in long-term care concepts; illustrated the impact that such changes are having on long-term care facility design; and summarized zeitgeists related to the architectural design of long-term care facilities. Results of our Delphi survey indicated the following top five priorities in long-term care facility design: (1) creating a home-like feeling; (2) adhering to Universal Design concepts; (3) providing well-defined private sleeping areas; (4) providing adequate social space; and (5) decentralizing residents' rooms into clusters. The three major zeitgeists related to long-term care facility design include: (1) modern long-term care facilities should abandon their traditional "hospital" image and gradually reposition facilities into homelike settings; (2) institution-based care for the elderly should be de-institutionalized under the concept of aging-in-place; and (3) living clusters, rather than traditional hospital-like wards, should be designed into long-term care facilities.

Acute and long-term in vitro effects of zinc oxide nanoparticles.

PubMed

Annangi, Balasubramanyam; Rubio, Laura; Alaraby, Mohamed; Bach, Jordi; Marcos, Ricard; Hernández, Alba

2016-09-01

Since most of the toxic studies of zinc oxide nanoparticles (ZnO NPs) focused on acute and high-dose exposure conditions, the aim of the present study was to fill the existing knowledge gap of long-term effects of ZnO NPs at sub-toxic doses. To overcome this point, we have evaluated the toxic, genotoxic, and carcinogenic effects of ZnO NPs under long-term treatments (12 weeks), using a sub-toxic dose (1 µg/mL) according to acute 48-h exposure. Preliminarily, oxidative stress and genotoxic/oxidative DNA damage were determined under acute exposure and high-dose conditions. To determine the role of oxidative DNA damage, a wild-type mouse embryonic fibroblast (MEF Ogg1 (+/+)) and its isogenic 8-oxo-guanine DNA glycosylase 1 (Ogg1) knockout partner (MEF Ogg1 (-/-)) cell lines were used. Although short-term exposure (24-h) experiments demonstrated that ZnO NPs were able to induce ROS, genotoxicity, and oxidative DNA damage in both cell lines, no effects were obtained under long-term exposure scenario. Thus, 1 µg/mL exposure over 12 weeks was unable to induce genotoxicity as well as cellular transformation in both cell types, as indicated by the lack of observed morphological cell changes, variations in the secretion of matrix metalloproteinases, and anchorage-independent cell growth ability, regarded as cancer-like phenotypic hallmarks. Our results indicate that short-term effects of ZnO NP exposure are not replicated under long-term and sub-toxic dose conditions. All together, the lack of genotoxic/carcinogenic effects after chronic treatments seem to indicate a reduced risk associated with ZnO NP exposure.

Downregulation of MicroRNA eca-mir-128 in Seminal Exosomes and Enhanced Expression of CXCL16 in the Stallion Reproductive Tract Are Associated with Long-Term Persistence of Equine Arteritis Virus.

PubMed

Carossino, Mariano; Dini, Pouya; Kalbfleisch, Theodore S; Loynachan, Alan T; Canisso, Igor F; Shuck, Kathleen M; Timoney, Peter J; Cook, R Frank; Balasuriya, Udeni B R

2018-05-01

Equine arteritis virus (EAV) can establish long-term persistent infection in the reproductive tract of stallions and is shed in the semen. Previous studies showed that long-term persistence is associated with a specific allele of the CXCL16 gene ( CXCL16S ) and that persistent infection is maintained despite the presence of a local inflammatory and humoral and mucosal antibody responses. In this study, we demonstrated that equine seminal exosomes (SEs) are enriched in a small subset of microRNAs (miRNAs). Most importantly, we demonstrated that long-term EAV persistence is associated with the downregulation of an SE-associated miRNA (eca-mir-128) and with an enhanced expression of CXCL16 in the reproductive tract, a putative target of eca-mir-128. The findings presented here suggest that SE eca-mir-128 is implicated in the regulation of the CXCL16/CXCR6 axis in the reproductive tract of persistently infected stallions, a chemokine axis strongly implicated in EAV persistence. This is a novel finding and warrants further investigation to identify its specific mechanism in modulating the CXCL16/CXCR6 axis in the reproductive tract of the EAV long-term carrier stallion. IMPORTANCE Equine arteritis virus (EAV) has the ability to establish long-term persistent infection in the stallion reproductive tract and to be shed in semen, which jeopardizes its worldwide control. Currently, the molecular mechanisms of viral persistence are being unraveled, and these are essential for the development of effective therapeutics to eliminate persistent infection. Recently, it has been determined that long-term persistence is associated with a specific allele of the CXCL16 gene ( CXCL16S ) and is maintained despite induction of local inflammatory, humoral, and mucosal antibody responses. This study demonstrated that long-term persistence is associated with the downregulation of seminal exosome miRNA eca-mir-128 and enhanced expression of its putative target, CXCL16, in the reproductive tract. For the first time, this study suggests complex interactions between eca-mir-128 and cellular elements at the site of EAV persistence and implicates this miRNA in the regulation of the CXCL16/CXCR6 axis in the reproductive tract during long-term persistence. Copyright © 2018 American Society for Microbiology.

Positioning Vascularized Composite Allotransplantation in the Spectrum of Transplantation

DTIC Science & Technology

2016-10-01

did not reject the third-party cardiac allografts , but instead rejected the original VCA tissues (Fig. 2, left panel). To test whether RPM impaired...long-term VCA survival, but the rejection of VCA tissues as a result of third party cardiac allografting suggests the incomplete regulation of host...mechanisms contributing to rejection of vascularized composite allografts (VCA) in murine models, and how these may be overcome to promote long-term

10 CFR 40.28 - General license for custody and long-term care of uranium or thorium byproduct materials disposal...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false General license for custody and long-term care of uranium... long-term care of uranium or thorium byproduct materials disposal sites. (a) A general license is... in this part for uranium or thorium mill tailings sites closed under title II of the Uranium Mill...

10 CFR 40.28 - General license for custody and long-term care of uranium or thorium byproduct materials disposal...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false General license for custody and long-term care of uranium... long-term care of uranium or thorium byproduct materials disposal sites. (a) A general license is... in this part for uranium or thorium mill tailings sites closed under title II of the Uranium Mill...

10 CFR 40.28 - General license for custody and long-term care of uranium or thorium byproduct materials disposal...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false General license for custody and long-term care of uranium... long-term care of uranium or thorium byproduct materials disposal sites. (a) A general license is... in this part for uranium or thorium mill tailings sites closed under title II of the Uranium Mill...

10 CFR 40.28 - General license for custody and long-term care of uranium or thorium byproduct materials disposal...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false General license for custody and long-term care of uranium... long-term care of uranium or thorium byproduct materials disposal sites. (a) A general license is... in this part for uranium or thorium mill tailings sites closed under title II of the Uranium Mill...

LIMK1 regulates long-term memory and synaptic plasticity via the transcriptional factor CREB.

PubMed

Todorovski, Zarko; Asrar, Suhail; Liu, Jackie; Saw, Ner Mu Nar; Joshi, Krutika; Cortez, Miguel A; Snead, O Carter; Xie, Wei; Jia, Zhengping

2015-04-01

Deletion of the LIMK1 gene is associated with Williams syndrome, a unique neurodevelopmental disorder characterized by severe defects in visuospatial cognition and long-term memory (LTM). However, whether LIMK1 contributes to these deficits remains elusive. Here, we show that LIMK1-knockout (LIMK1(-/-)) mice are drastically impaired in LTM but not short-term memory (STM). In addition, LIMK1(-/-) mice are selectively defective in late-phase long-term potentiation (L-LTP), a form of long-lasting synaptic plasticity specifically required for the formation of LTM. Furthermore, we show that LIMK1 interacts and regulates the activity of cyclic AMP response element-binding protein (CREB), an extensively studied transcriptional factor critical for LTM. Importantly, both L-LTP and LTM deficits in LIMK1(-/-) mice are rescued by increasing the activity of CREB. These results provide strong evidence that LIMK1 deletion is sufficient to lead to an LTM deficit and that this deficit is attributable to CREB hypofunction. Our study has identified a direct gene-phenotype link in mice and provides a potential strategy to restore LTM in patients with Williams syndrome through the enhancement of CREB activity in the adult brain. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Long-Term Use and Perceived Benefits of Goal-Oriented Attentional Self-Regulation Training in Chronic Brain Injury.

PubMed

Loya, Fred; Novakovic-Agopian, Tatjana; Binder, Deborah; Rossi, Annemarie; Rome, Scott; Murphy, Michelle; Chen, Anthony J-W

2017-01-01

Primary Objective. To investigate the long-term use and perceived benefit(s) of strategies included in Goal-Oriented Attentional Self-Regulation (GOALS) training (Novakovic-Agopian et al., 2011) by individuals with acquired brain injury (ABI) and chronic executive dysfunction. Research Design. Longitudinal follow-up of training. Methods and Procedures. Sixteen participants with chronic ABI participated in structured telephone interviews 20 months (range 11 to 31 months) following completion of GOALS training. Participants responded to questions regarding the range of strategies they continued to utilize, perceived benefit(s) of strategy use, situations in which strategy use was found helpful, and functional changes attributed to training. Results. Nearly all participants (94%) reported continued use of at least one trained strategy in their daily lives, with 75% of participants also reporting improved functioning resulting from training. However, there was considerable variability with respect to the specific strategies individuals found helpful as well as the perceived impact of training on overall functioning. Conclusions. GOALS training shows promising long-term benefits for individuals in the chronic phase of brain injury. Identifying individual- and injury-level factors that account for variability in continued strategy use and the perceived long-term benefits of training will help with ongoing intervention development.

Long-Term Use and Perceived Benefits of Goal-Oriented Attentional Self-Regulation Training in Chronic Brain Injury

PubMed Central

Novakovic-Agopian, Tatjana; Binder, Deborah; Rossi, Annemarie; Rome, Scott; Murphy, Michelle; Chen, Anthony J.-W.

2017-01-01

Primary Objective. To investigate the long-term use and perceived benefit(s) of strategies included in Goal-Oriented Attentional Self-Regulation (GOALS) training (Novakovic-Agopian et al., 2011) by individuals with acquired brain injury (ABI) and chronic executive dysfunction. Research Design. Longitudinal follow-up of training. Methods and Procedures. Sixteen participants with chronic ABI participated in structured telephone interviews 20 months (range 11 to 31 months) following completion of GOALS training. Participants responded to questions regarding the range of strategies they continued to utilize, perceived benefit(s) of strategy use, situations in which strategy use was found helpful, and functional changes attributed to training. Results. Nearly all participants (94%) reported continued use of at least one trained strategy in their daily lives, with 75% of participants also reporting improved functioning resulting from training. However, there was considerable variability with respect to the specific strategies individuals found helpful as well as the perceived impact of training on overall functioning. Conclusions. GOALS training shows promising long-term benefits for individuals in the chronic phase of brain injury. Identifying individual- and injury-level factors that account for variability in continued strategy use and the perceived long-term benefits of training will help with ongoing intervention development. PMID:28265472

Antidepressants Rescue Stress-Induced Disruption of Synaptic Plasticity via Serotonin Transporter-Independent Inhibition of L-Type Calcium Channels.

PubMed

Normann, Claus; Frase, Sibylle; Haug, Verena; von Wolff, Gregor; Clark, Kristin; Münzer, Patrick; Dorner, Alexandra; Scholliers, Jonas; Horn, Max; Vo Van, Tanja; Seifert, Gabriel; Serchov, Tsvetan; Biber, Knut; Nissen, Christoph; Klugbauer, Norbert; Bischofberger, Josef

2017-10-19

Long-term synaptic plasticity is a basic ability of the brain to dynamically adapt to external stimuli and regulate synaptic strength and ultimately network function. It is dysregulated by behavioral stress in animal models of depression and in humans with major depressive disorder. Antidepressants have been shown to restore disrupted synaptic plasticity in both animal models and humans; however, the underlying mechanism is unclear. We examined modulation of synaptic plasticity by selective serotonin reuptake inhibitors (SSRIs) in hippocampal brain slices from wild-type rats and serotonin transporter (SERT) knockout mice. Recombinant voltage-gated calcium (Ca 2+ ) channels in heterologous expression systems were used to determine the modulation of Ca 2+ channels by SSRIs. We tested the behavioral effects of SSRIs in the chronic behavioral despair model of depression both in the presence and in the absence of SERT. SSRIs selectively inhibited hippocampal long-term depression. The inhibition of long-term depression by SSRIs was mediated by a direct block of voltage-activated L-type Ca 2+ channels and was independent of SERT. Furthermore, SSRIs protected both wild-type and SERT knockout mice from behavioral despair induced by chronic stress. Finally, long-term depression was facilitated in animals subjected to the behavioral despair model, which was prevented by SSRI treatment. These results showed that antidepressants protected synaptic plasticity and neuronal circuitry from the effects of stress via a modulation of Ca 2+ channels and synaptic plasticity independent of SERT. Thus, L-type Ca 2+ channels might constitute an important signaling hub for stress response and for pathophysiology and treatment of depression. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Short-Term and Long-Term Effects of an Exercise-Based Patient Education Programme in People with Multiple Sclerosis: A Pilot Study

PubMed Central

Haas, Christian T.

2017-01-01

Background. Although people with Multiple Sclerosis (pwMS) benefit from physical exercise, they still show reduced physical activity and exercise behaviour. This study aimed to investigate short- and long-term effects of an exercise-based patient education programme (ePEP) that focuses on empowering pwMS to a sustainable and self-regulated exercise training management. Methods. Fourteen pwMS were randomly assigned to immediate experimental group (EG-I: n = 8) and waitlist-control group (EG-W: n = 6) and attended biweekly in a six-week ePEP. All participants were measured for walking ability, quality of life, fatigue, and self-efficacy towards physical exercise before and after the ePEP, after 12 weeks, and one year after baseline. Short-term effects were analysed in a randomised control trial and long-term effects of all ePEP participants (EG-I + EG-W = EG-all) in a quasi-experimental design. Results. Only functional gait significantly improved in EG-I compared to EG-W (p = 0.008, r = −0.67). Moderate to large effects were found in EG-all for walking ability. Not significant, however, relevant changes were detected for quality of life and fatigue. Self-efficacy showed no changes. Conclusion. The ePEP seems to be a feasible option to empower pwMS to a self-regulated and sustainable exercise training management shown in long-term walking improvements. PMID:28900546

Reduced generation of lung tissue–resident memory T cells during infancy

PubMed Central

Zens, Kyra D.; Chen, Jun Kui; Wu, Felix L.; Cvetkovski, Filip

2017-01-01

Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared with adults, although the underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRMs) mediate optimal protection to respiratory pathogens, and we hypothesized that reduced protection in infancy could be due to impaired establishment of lung TRM. Using an infant mouse model, we demonstrate generation of lung-homing, virus-specific T effectors after influenza infection or live-attenuated vaccination, similar to adults. However, infection during infancy generated markedly fewer lung TRMs, and heterosubtypic protection was reduced compared with adults. Impaired TRM establishment was infant–T cell intrinsic, and infant effectors displayed distinct transcriptional profiles enriched for T-bet–regulated genes. Notably, mouse and human infant T cells exhibited increased T-bet expression after activation, and reduction of T-bet levels in infant mice enhanced lung TRM establishment. Our findings reveal that infant T cells are intrinsically programmed for short-term responses, and targeting key regulators could promote long-term, tissue-targeted protection at this critical life stage. PMID:28855242

Intermediate-term emotional bookkeeping is necessary for long-term reciprocal grooming partner preferences in an agent-based model of macaque groups

PubMed Central

Evers, Ellen; de Vries, Han; Spruijt, Berry M.

2016-01-01

Whether and how primates are able to maintain long-term affiliative relationships is still under debate. Emotional bookkeeping (EB), the partner-specific accumulation of emotional responses to earlier interactions, is a candidate mechanism that does not require high cognitive abilities. EB is difficult to study in real animals, due to the complexity of primate social life. Therefore, we developed an agent-based model based on macaque behavior, the EMO-model, that implements arousal and two emotional dimensions, anxiety-FEAR and satisfaction-LIKE, which regulate social behavior. To implement EB, model individuals assign dynamic LIKE attitudes towards their group members, integrating partner-specific emotional responses to earlier received grooming episodes. Two key parameters in the model were varied to explore their effects on long-term affiliative relationships: (1) the timeframe over which earlier affiliation is accumulated into the LIKE attitudes; and (2) the degree of partner selectivity. EB over short and long timeframes gave rise to low variation in LIKE attitudes, and grooming partner preferences were only maintained over one to two months. Only EB over intermediate-term timeframes resulted in enough variation in LIKE attitudes, which, in combination with high partner selectivity, enables individuals to differentiate between regular and incidental grooming partners. These specific settings resulted in a strong feedback between differentiated LIKE attitudes and the distribution of grooming, giving rise to strongly reciprocated partner preferences that could be maintained for longer periods, occasionally up to one or two years. Moreover, at these settings the individual’s internal, socio-emotional memory of earlier affiliative episodes (LIKE attitudes) corresponded best to observable behavior (grooming partner preferences). In sum, our model suggests that intermediate-term LIKE dynamics and high partner selectivity seem most plausible for primates relying on emotional bookkeeping to maintain their social bonds. PMID:26839737

Intermediate-term emotional bookkeeping is necessary for long-term reciprocal grooming partner preferences in an agent-based model of macaque groups.

PubMed

Evers, Ellen; de Vries, Han; Spruijt, Berry M; Sterck, Elisabeth H M

2016-01-01

Whether and how primates are able to maintain long-term affiliative relationships is still under debate. Emotional bookkeeping (EB), the partner-specific accumulation of emotional responses to earlier interactions, is a candidate mechanism that does not require high cognitive abilities. EB is difficult to study in real animals, due to the complexity of primate social life. Therefore, we developed an agent-based model based on macaque behavior, the EMO-model, that implements arousal and two emotional dimensions, anxiety-FEAR and satisfaction-LIKE, which regulate social behavior. To implement EB, model individuals assign dynamic LIKE attitudes towards their group members, integrating partner-specific emotional responses to earlier received grooming episodes. Two key parameters in the model were varied to explore their effects on long-term affiliative relationships: (1) the timeframe over which earlier affiliation is accumulated into the LIKE attitudes; and (2) the degree of partner selectivity. EB over short and long timeframes gave rise to low variation in LIKE attitudes, and grooming partner preferences were only maintained over one to two months. Only EB over intermediate-term timeframes resulted in enough variation in LIKE attitudes, which, in combination with high partner selectivity, enables individuals to differentiate between regular and incidental grooming partners. These specific settings resulted in a strong feedback between differentiated LIKE attitudes and the distribution of grooming, giving rise to strongly reciprocated partner preferences that could be maintained for longer periods, occasionally up to one or two years. Moreover, at these settings the individual's internal, socio-emotional memory of earlier affiliative episodes (LIKE attitudes) corresponded best to observable behavior (grooming partner preferences). In sum, our model suggests that intermediate-term LIKE dynamics and high partner selectivity seem most plausible for primates relying on emotional bookkeeping to maintain their social bonds.

Short-term pain for long-term gain: seagrass communities increase short-term extremes and long-term offset of CO2 under future ocean acidification

EPA Science Inventory

The impacts of ocean acidification in nearshore estuarine environments remain poorly characterized, despite these areas being some of the most ecologically, economically, and culturally important habitats in the global ocean. Here, we quantify how rising atmospheric CO2 from 1765...

20 CFR 220.28 - How long the impairment must last.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true How long the impairment must last. 220.28 Section 220.28 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT DETERMINING DISABILITY Disability Under the Railroad Retirement Act for Any Regular Employment § 220.28 How...

AMPK Signaling in the Dorsal Hippocampus Negatively Regulates Contextual Fear Memory Formation

PubMed Central

Han, Ying; Luo, Yixiao; Sun, Jia; Ding, Zengbo; Liu, Jianfeng; Yan, Wei; Jian, Min; Xue, Yanxue; Shi, Jie; Wang, Ji-Shi; Lu, Lin

2016-01-01

Both the formation of long-term memory (LTM) and dendritic spine growth that serves as a physical basis for the long-term storage of information require de novo protein synthesis. Memory formation also critically depends on transcription. Adenosine monophosphate-activated protein kinase (AMPK) is a transcriptional regulator that has emerged as a major energy sensor that maintains cellular energy homeostasis. However, still unknown is its role in memory formation. In the present study, we found that AMPK is primarily expressed in neurons in the hippocampus, and then we demonstrated a time-dependent decrease in AMPK activity and increase in mammalian target of rapamycin complex 1 (mTORC1) activity after contextual fear conditioning in the CA1 but not CA3 area of the dorsal hippocampus. Using pharmacological methods and adenovirus gene transfer to bidirectionally regulate AMPK activity, we found that increasing AMPK activity in the CA1 impaired the formation of long-term fear memory, and decreasing AMPK activity enhanced fear memory formation. These findings were associated with changes in the phosphorylation of AMPK and p70s6 kinase (p70s6k) and expression of BDNF and membrane GluR1 and GluR2 in the CA1. Furthermore, the prior administration of an mTORC1 inhibitor blocked the enhancing effect of AMPK inhibition on fear memory formation, suggesting that this negative regulation of contextual fear memory by AMPK in the CA1 depends on the mTORC1 signaling pathway. Finally, we found that AMPK activity regulated hippocampal spine growth associated with memory formation. In summary, our results indicate that AMPK is a key negative regulator of plasticity and fear memory formation. PMID:26647974

Native ungulates of diverse body sizes collectively regulate long-term woody plant demography and structure of a semi-arid savanna

USDA-ARS?s Scientific Manuscript database

Large mammalian herbivores and fire are both well recognized to play important roles in regulating tree cover and biomass in savannas. However, the extent to which browsing ungulates are capable of regulating tree populations in the absence of other synergistic disturbances such as fire is unclear. ...

Nitric Oxide Is an Activity-Dependent Regulator of Target Neuron Intrinsic Excitability

PubMed Central

Steinert, Joern R.; Robinson, Susan W.; Tong, Huaxia; Haustein, Martin D.; Kopp-Scheinpflug, Cornelia; Forsythe, Ian D.

2011-01-01

Summary Activity-dependent changes in synaptic strength are well established as mediating long-term plasticity underlying learning and memory, but modulation of target neuron excitability could complement changes in synaptic strength and regulate network activity. It is thought that homeostatic mechanisms match intrinsic excitability to the incoming synaptic drive, but evidence for involvement of voltage-gated conductances is sparse. Here, we show that glutamatergic synaptic activity modulates target neuron excitability and switches the basis of action potential repolarization from Kv3 to Kv2 potassium channel dominance, thereby adjusting neuronal signaling between low and high activity states, respectively. This nitric oxide-mediated signaling dramatically increases Kv2 currents in both the auditory brain stem and hippocampus (>3-fold) transforming synaptic integration and information transmission but with only modest changes in action potential waveform. We conclude that nitric oxide is a homeostatic regulator, tuning neuronal excitability to the recent history of excitatory synaptic inputs over intervals of minutes to hours. PMID:21791288

Myostatin induces interstitial fibrosis in the heart via TAK1 and p38.

PubMed

Biesemann, Nadine; Mendler, Luca; Kostin, Sawa; Wietelmann, Astrid; Borchardt, Thilo; Braun, Thomas

2015-09-01

Myostatin, a member of the TGF-β superfamily of secreted growth factors, is a negative regulator of skeletal muscle growth. In the heart, it is expressed at lower levels compared to skeletal muscle but up-regulated under disease conditions. Cre recombinase-mediated inactivation of myostatin in adult cardiomyocytes leads to heart failure and increased mortality but cardiac function of surviving mice is restored after several weeks probably due to compensatory expression in non-cardiomyocytes. To study long-term effects of increased myostatin expression in the heart and to analyze the putative crosstalk between cardiomyocytes and fibroblasts, we overexpressed myostatin in cardiomyocytes. Increased expression of myostatin in heart muscle cells caused interstitial fibrosis via activation of the TAK-1-MKK3/6-p38 signaling pathway, compromising cardiac function in older mice. Our results uncover a novel role of myostatin in the heart and highlight the necessity for tight regulation of myostatin to maintain normal heart function.

Taotie neurons regulate appetite in Drosophila

PubMed Central

Zhan, Yin Peng; Liu, Li; Zhu, Yan

2016-01-01

The brain has an essential role in maintaining a balance between energy intake and expenditure of the body. Deciphering the processes underlying the decision-making for timely feeding of appropriate amounts may improve our understanding of physiological and psychological disorders related to feeding control. Here, we identify a group of appetite-enhancing neurons in a behavioural screen for flies with increased appetite. Manipulating the activity of these neurons, which we name Taotie neurons, induces bidirectional changes in feeding motivation. Long-term stimulation of Taotie neurons results in flies with highly obese phenotypes. Furthermore, we show that the in vivo activity of Taotie neurons in the neuroendocrine region reflects the hunger/satiety states of un-manipulated animals, and that appetitive-enhancing Taotie neurons control the secretion of insulin, a known regulator of feeding behaviour. Thus, our study reveals a new set of neurons regulating feeding behaviour in the high brain regions that represents physiological hunger states and control feeding behaviour in Drosophila. PMID:27924813

A long-term high-fat, high-sucrose diet in Bama minipigs promotes lipid deposition and amyotrophy by up-regulating the myostatin pathway.

PubMed

Ruan, Jinxue; Zhang, Yuanyuan; Yuan, Jing; Xin, Leilei; Xia, Jihan; Liu, Nan; Mu, Yulian; Chen, Yaoxing; Yang, Shulin; Li, Kui

2016-04-15

Skeletal muscle is as an important regulator of blood glucose and glycolipid metabolism and is closely related to motor ability. The underlying mechanisms by which dietary ectopic lipids in skeletal muscle prevents muscle growth remain elusive. We utilized miniature Bama swine as a model to mimic human obesity using prolonged dietary induction. After 23 months on a high-fat, high-sucrose diet, metabolic disorders were induced in the animals, which exhibited increased body weight, extensive lipid deposition in the skeletal muscle and amyotrophy. Microarray profiles demonstrated the up-regulation of genes related to fat deposition and muscle growth inhibition. We outline a clear potential pathway that in combination with increased 11β-hydroxysteroid dehydrogenase type 1, promotes expression of a major inhibitor, myostatin, by converting corticosterone to cortisol, which leads to the growth inhibition of skeletal muscle. This research provides new insights into the treatment of muscle diseases induced by obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The ubiquitin-proteasome system is necessary for long-term synaptic depression in Aplysia.

PubMed

Fioravante, Diasinou; Liu, Rong-Yu; Byrne, John H

2008-10-08

The neuropeptide Phe-Met-Arg-Phe-NH(2) (FMRFa) can induce transcription-dependent long-term synaptic depression (LTD) in Aplysia sensorimotor synapses. We investigated the role of the ubiquitin-proteasome system and the regulation of one of its components, ubiquitin C-terminal hydrolase (ap-uch), in LTD. LTD was sensitive to presynaptic inhibition of the proteasome and was associated with upregulation of ap-uch mRNA and protein. This upregulation appeared to be mediated by CREB2, which is generally regarded as a transcription repressor. Binding of CREB2 to the promoter region of ap-uch was accompanied by histone hyperacetylation, suggesting that CREB2 cannot only inhibit but also promote gene expression. CREB2 was phosphorylated after FMRFa, and blocking phospho-CREB2 blocked LTD. In addition to changes in the expression of ap-uch, the synaptic vesicle-associated protein synapsin was downregulated in LTD in a proteasome-dependent manner. These results suggest that proteasome-mediated protein degradation is engaged in LTD and that CREB2 may act as a transcription activator under certain conditions.

Strategic decision making under climate change: a case study on Lake Maggiore water system

NASA Astrophysics Data System (ADS)

Micotti, M.; Soncini Sessa, R.; Weber, E.

2014-09-01

Water resources planning processes involve different kinds of decisions that are generally evaluated under a stationary climate scenario assumption. In general, the possible combinations of interventions are mutually compared as single alternatives. However, the ongoing climate change requires us to reconsider this approach. Indeed, what have to be compared are not individual alternatives, but families of alternatives, characterized by the same structural decisions, i.e. by actions that have long-term effects and entail irrevocable changes in the system. The rationale is that the structural actions, once they have been implemented, cannot be easily modified, while the management decisions can be adapted to the evolving conditions. This paper considers this methodological problem in a real case study, in which a strategic decision has to be taken: a new barrage was proposed to regulate Lake Maggiore outflow, but, alternatively, either the present barrage can be maintained with its present regulation norms or with a new one. The problem was dealt with by multi-criteria decision analysis involving many stakeholders and two decision-makers. An exhaustive set of indicators was defined in the participatory process, conducted under the integrated water resource management paradigm, and many efficient (in Pareto sense) regulation policies were identified. The paper explores different formulations of a global index to evaluate and compare the effectiveness of the classes of alternatives under both stationary and changing hydrological scenarios in order to assess their adaptability to the ongoing climate change.

SWTR Fact Sheet - EPA Region 8, May 2018

EPA Pesticide Factsheets

Contains information for public water systems under the Surface Water Treatment Rule (SWTR), Filter Backwash Recycling Rule, Interim Enhanced SWTR (IESWTR), Long Term 1 Enhanced SWTR (LT1ESWTR) and Long Term 2 Enhanced SWTR (LT2).

SWTR Fact Sheet - EPA Region 8, July 2016

EPA Pesticide Factsheets

Contains information for public water systems under the Surface Water Treatment Rule (SWTR), Filter Backwash Recycling Rule, Interim Enhanced SWTR (IESWTR), Long Term 1 Enhanced SWTR (LT1ESWTR) and Long Term 2 Enhanced SWTR (LT2).

Metal accumulation and differentially expressed proteins in gill of oyster (Crassostrea hongkongensis) exposed to long-term heavy metal-contaminated estuary.

PubMed

Luo, Lianzhong; Ke, Caihuan; Guo, Xiaoyu; Shi, Bo; Huang, Miaoqin

2014-06-01

Bio-accumulation and bio-transmission of toxic metals and the toxicological responses of organisms exposed to toxic metals have been focused, due to heavy metal contaminations have critically threatened the ecosystem and food security. However, still few investigations focused on the responses of certain organisms exposed to the long term and severe heavy metal contamination in specific environments. In present investigation, the Hong Kong oyster, Crassostrea hongkongensis were obtained from 3 sites which were contaminated by different concentrations of heavy metals (such as zinc, copper, manganese and lead etc.), respectively. Heavy metal concentrations in the sea water samples collected from the 3 sites and the dissected tissues of the oysters with blue visceral mass were determinated to estimate the metal contamination levels in environments and the bio-accumulation ratios of the heavy metals in the different tissues of oysters. Moreover, Proteomic methods were employed to analyze the differentially expressed proteins in the gills of oysters exposed to long-term heavy metal contaminations. Results indicated that the Jiulong River estuary has been severely contaminated by Cu, Zn and slightly with Cr, Ni, Mn, etc, moreover, Zn and Cu were the major metals accumulated by oysters to phenomenally high concentrations (more than 3.0% of Zn and about 2.0% of Cu against what the dry weight of tissues were accumulated), and Cr, Ni, Mn, etc were also significantly accumulated. The differentially expressed proteins in the gills of oysters exposed to heavy metals participate in several cell processes, such as metal binding, transporting and saving, oxidative-reduction balance maintaining, stress response, signal transduction, etc. Significantly up-regulated expression (about 10 folds) of an important metal binding protein, metallothionein (MT) and granular cells was observed in the gills of oysters exposed to long-term and severely heavy-metal-contaminated estuary, it suggested that binding toxic metals with metallothionein-like proteins (MTLP) and storing toxic metals in metal-rich granules (MRG) with insoluble forms were the important strategies of oyster to detoxify the toxic metals and adapt to the high level of metal-contaminated environment. Most of the stress and immunity responsive proteins, such as heat shock proteins (HSP), extracellular superoxide dismutase (ECSOD) and cavortin, and the cellular redox reaction relative proteins such as 20G-Fe (II) oxygenase family oxidoreductase, aldehyde dehydrogenase and retinal dehydrogenase 2, were detected significantly down-regulated in the gills of oysters exposed to long term heavy metal contaminated environments, it indicated that long term exposure different from emergent exposure to heavy metal contamination may significantly suppress the stress and immunity response system of oysters. Moreover, Formin homology 2 domain containing protein (FH2). The only protein domain to directly nucleate actin monomers into unbranched filament polymers, by which will subsequently control gene expression and chromatin remodelling complexes, was also detected greatly up-regulated in the gills of oysters exposed to long-term heavy metal contaminations. It indicated that nuclear activity regulation may also be important for oyster to adapt to the long-term heavy-metal-contaminated environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Priming of Short-Term Potentiation and Synaptic Tagging/Capture Mechanisms by Ryanodine Receptor Activation in Rat Hippocampal CA1

ERIC Educational Resources Information Center

Sajikumar, Sreedharan; Li, Qin; Abraham, Wickliffe C.; Xiao, Zhi Cheng

2009-01-01

Activity-dependent changes in synaptic strength such as long-term potentiation (LTP) and long-term depression (LTD) are considered to be cellular mechanisms underlying learning and memory. Strengthening of a synapse for a few seconds or minutes is termed short-term potentiation (STP) and is normally unable to take part in the processes of synaptic…

Effects of long-term hypergravity treatment on the development of inflorescence stems of arabidopsis

NASA Astrophysics Data System (ADS)

Karahara, Ichirou; Tamaoki, Daisuke; Kamisaka, Seiichiro; Yamaguchi, Takashi; Shinohara, Hironori; Kume, Atsushi; Inoue, Hiroshi

Hypergravity experiments with plants have been mostly performed using a commercial centrifuge in the dark. In order to see longer-term effect of hypergravity on the development of plant shoots, however, it is necessary to carry out the experiments in the light. In the present study, we have set up a centrifuge equipped with lighting system, which supports long-term plant growth under hypergravity condition, in order to see long-term effects of hypergravity on the development of vascular tissues of inflorescence stems. Arabidopsis plants (Arabidopsis thaliana (L.) Heynh., Col-0), which were grown under 1 G conditions for 20-23 days and having the first visible flower bud, i.e., at Arabidopsis growth stage number 5 (according to Boys et al., 2001), were selected as the plant material. These plants were exposed to hypergravity stimulus at 10 G in a direction from the shoot to root for 10 days in the continuous light. Effects of hypergravity on growth of inflorescence stems, lignin content, and morphometrical parameters of the stem tissues were examined. As a result, the length of the inflorescence stem was decreased. Cross sectional area as well as cell number, and lignin content in the stem were increased under hypergravity. The length of basal internodes of the stem was decreased under hypergravity. In conclusion, the inflorescence stem was suggested to be strengthened through changes in its morphological characteristics as well as lignin deposition under long-term hypergravity conditions.

Organ size control is dominant over Rb family inactivation to restrict proliferation in vivo.

PubMed

Ehmer, Ursula; Zmoos, Anne-Flore; Auerbach, Raymond K; Vaka, Dedeepya; Butte, Atul J; Kay, Mark A; Sage, Julien

2014-07-24

In mammals, a cell's decision to divide is thought to be under the control of the Rb/E2F pathway. We previously found that inactivation of the Rb family of cell cycle inhibitors (Rb, p107, and p130) in quiescent liver progenitors leads to uncontrolled division and cancer initiation. Here, we show that, in contrast, deletion of the entire Rb gene family in mature hepatocytes is not sufficient for their long-term proliferation. The cell cycle block in Rb family mutant hepatocytes is independent of the Arf/p53/p21 checkpoint but can be abrogated upon decreasing liver size. At the molecular level, we identify YAP, a transcriptional regulator involved in organ size control, as a factor required for the sustained expression of cell cycle genes in hepatocytes. These experiments identify a higher level of regulation of the cell cycle in vivo in which signals regulating organ size are dominant regulators of the core cell cycle machinery. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Long-lived rodents reveal signatures of positive selection in genes associated with lifespan

PubMed Central

Görlach, Matthias; Müller, Christine; Schwab, Matthias; Kraus, Johann; Cellerino, Alessandro; Hildebrandt, Thomas

2018-01-01

The genetics of lifespan determination is poorly understood. Most research has been done on short-lived animals and it is unclear if these insights can be transferred to long-lived mammals like humans. Some African mole-rats (Bathyergidae) have life expectancies that are multiple times higher than similar sized and phylogenetically closely related rodents. To gain new insights into genetic mechanisms determining mammalian lifespans, we obtained genomic and transcriptomic data from 17 rodent species and scanned eleven evolutionary branches associated with the evolution of enhanced longevity for positively selected genes (PSGs). Indicating relevance for aging, the set of 250 identified PSGs showed in liver of long-lived naked mole-rats and short-lived rats an expression pattern that fits the antagonistic pleiotropy theory of aging. Moreover, we found the PSGs to be enriched for genes known to be related to aging. Among these enrichments were “cellular respiration” and “metal ion homeostasis”, as well as functional terms associated with processes regulated by the mTOR pathway: translation, autophagy and inflammation. Remarkably, among PSGs are RHEB, a regulator of mTOR, and IGF1, both central components of aging-relevant pathways, as well as genes yet unknown to be aging-associated but representing convincing functional candidates, e.g. RHEBL1, AMHR2, PSMG1 and AGER. Exemplary protein homology modeling suggests functional consequences for amino acid changes under positive selection. Therefore, we conclude that our results provide a meaningful resource for follow-up studies to mechanistically link identified genes and amino acids under positive selection to aging and lifespan determination. PMID:29570707

Long-lived rodents reveal signatures of positive selection in genes associated with lifespan.

PubMed

Sahm, Arne; Bens, Martin; Szafranski, Karol; Holtze, Susanne; Groth, Marco; Görlach, Matthias; Calkhoven, Cornelis; Müller, Christine; Schwab, Matthias; Kraus, Johann; Kestler, Hans A; Cellerino, Alessandro; Burda, Hynek; Hildebrandt, Thomas; Dammann, Philip; Platzer, Matthias

2018-03-01

The genetics of lifespan determination is poorly understood. Most research has been done on short-lived animals and it is unclear if these insights can be transferred to long-lived mammals like humans. Some African mole-rats (Bathyergidae) have life expectancies that are multiple times higher than similar sized and phylogenetically closely related rodents. To gain new insights into genetic mechanisms determining mammalian lifespans, we obtained genomic and transcriptomic data from 17 rodent species and scanned eleven evolutionary branches associated with the evolution of enhanced longevity for positively selected genes (PSGs). Indicating relevance for aging, the set of 250 identified PSGs showed in liver of long-lived naked mole-rats and short-lived rats an expression pattern that fits the antagonistic pleiotropy theory of aging. Moreover, we found the PSGs to be enriched for genes known to be related to aging. Among these enrichments were "cellular respiration" and "metal ion homeostasis", as well as functional terms associated with processes regulated by the mTOR pathway: translation, autophagy and inflammation. Remarkably, among PSGs are RHEB, a regulator of mTOR, and IGF1, both central components of aging-relevant pathways, as well as genes yet unknown to be aging-associated but representing convincing functional candidates, e.g. RHEBL1, AMHR2, PSMG1 and AGER. Exemplary protein homology modeling suggests functional consequences for amino acid changes under positive selection. Therefore, we conclude that our results provide a meaningful resource for follow-up studies to mechanistically link identified genes and amino acids under positive selection to aging and lifespan determination.

Idaho National Laboratory Test Area North: Application of Endpoints to Guide Adaptive Remediation at a Complex Site: INL Test Area North: Application of Endpoints

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

Lee, M. Hope; Truex, Mike; Freshley, Mark

Complex sites are defined as those with difficult subsurface access, deep and/or thick zones of contamination, large areal extent, subsurface heterogeneities that limit the effectiveness of remediation, or where long-term remedies are needed to address contamination (e.g., because of long-term sources or large extent). The Test Area North at the Idaho National Laboratory, developed for nuclear fuel operations and heavy metal manufacturing, is used as a case study. Liquid wastes and sludge from experimental facilities were disposed in an injection well, which contaminated the subsurface aquifer located deep within fractured basalt. The wastes included organic, inorganic, and low-level radioactive constituents,more » with the focus of this case study on trichloroethylene. The site is used as an example of a systems-based framework that provides a structured approach to regulatory processes established for remediation under existing regulations. The framework is intended to facilitate remedy decisions and implementation at complex sites where restoration may be uncertain, require long timeframes, or involve use of adaptive management approaches. The framework facilitates site, regulator, and stakeholder interactions during the remedial planning and implementation process by using a conceptual model description as a technical foundation for decisions, identifying endpoints, which are interim remediation targets or intermediate decision points on the path to an ultimate end, and maintaining protectiveness during the remediation process. At the Test Area North, using a structured approach to implementing concepts in the endpoint framework, a three-component remedy is largely functioning as intended and is projected to meet remedial action objectives by 2095 as required. The remedy approach is being adjusted as new data become available. The framework provides a structured process for evaluating and adjusting the remediation approach, allowing site owners, regulators, and stakeholders to manage contamination at complex sites where adaptive remedies are needed.« less

18 CFR 34.1 - Applicability; definitions; exemptions in case of certain State regulation, certain short-term...

Code of Federal Regulations, 2013 CFR

2013-04-01

... Commission's regulations; and (2) Public utilities pursuant to section 204 of the Federal Power Act (49 Stat... Power Act; (2) The term securities includes any note, stock, treasury stock, bond, or debenture or other... regulations under this part, with respect to such securities. (2) This part does not apply to the issue or...

18 CFR 34.1 - Applicability; definitions; exemptions in case of certain State regulation, certain short-term...

Code of Federal Regulations, 2011 CFR

2011-04-01

... Commission's regulations; and (2) Public utilities pursuant to section 204 of the Federal Power Act (49 Stat... Power Act; (2) The term securities includes any note, stock, treasury stock, bond, or debenture or other... regulations under this part, with respect to such securities. (2) This part does not apply to the issue or...

18 CFR 34.1 - Applicability; definitions; exemptions in case of certain State regulation, certain short-term...

Code of Federal Regulations, 2012 CFR

2012-04-01

... Commission's regulations; and (2) Public utilities pursuant to section 204 of the Federal Power Act (49 Stat... Power Act; (2) The term securities includes any note, stock, treasury stock, bond, or debenture or other... regulations under this part, with respect to such securities. (2) This part does not apply to the issue or...

18 CFR 34.1 - Applicability; definitions; exemptions in case of certain State regulation, certain short-term...

Code of Federal Regulations, 2010 CFR

2010-04-01

... Commission's regulations; and (2) Public utilities pursuant to section 204 of the Federal Power Act (49 Stat... Power Act; (2) The term securities includes any note, stock, treasury stock, bond, or debenture or other... regulations under this part, with respect to such securities. (2) This part does not apply to the issue or...

18 CFR 34.1 - Applicability; definitions; exemptions in case of certain State regulation, certain short-term...

Code of Federal Regulations, 2014 CFR

2014-04-01

... Commission's regulations; and (2) Public utilities pursuant to section 204 of the Federal Power Act (49 Stat... Power Act; (2) The term securities includes any note, stock, treasury stock, bond, or debenture or other... regulations under this part, with respect to such securities. (2) This part does not apply to the issue or...

75 FR 47465 - Pymetrozine; Regulation Denying NRDC's Objections on Remand

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

... adverse effects are caused by either short-term (e.g., acute) or longer-term (e.g., chronic) pesticide... correspondingly levels of concern, for both short and long exposure periods as well as for the different routes of..., short-term, chronic, and cancer risks and EPA quantitatively assessed these risks in making its safety...

Multiple division cycles and long-term survival of hepatocytes are distinctly regulated by extracellular signal-regulated kinases ERK1 and ERK2.

PubMed

Frémin, Christophe; Bessard, Anne; Ezan, Frédéric; Gailhouste, Luc; Régeard, Morgane; Le Seyec, Jacques; Gilot, David; Pagès, Gilles; Pouysségur, Jacques; Langouët, Sophie; Baffet, Georges

2009-03-01

We investigated the specific role of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1 (ERK1)/ERK2 pathway in the regulation of multiple cell cycles and long-term survival of normal hepatocytes. An early and sustained epidermal growth factor (EGF)-dependent MAPK activation greatly improved the potential of cell proliferation. In this condition, almost 100% of the hepatocytes proliferated, and targeting ERK1 or ERK2 via RNA interference revealed the specific involvement of ERK2 in this regulation. However, once their first cell cycle was performed, hepatocytes failed to undergo a second round of replication and stayed blocked in G1 phase. We demonstrated that sustained EGF-dependent activation of the MAPK/ERK kinase (MEK)/ERK pathway was involved in this blockage as specific transient inhibition of the cascade repotentiated hepatocytes to perform a new wave of replication and multiple cell cycles. We identified this mechanism by showing that this blockage was in part supported by ERK2-dependent p21 expression. Moreover, continuous MEK inhibition was associated with a lower apoptotic engagement, leading to an improvement of survival up to 3 weeks. Using RNA interference and ERK1 knockout mice, we extended these results by showing that this improved survival was due to the specific inhibition of ERK1 expression/phosphorylation and did not involve ERK2. Our results emphasize that transient MAPK inhibition allows multiple cell cycles in primary cultures of hepatocytes and that ERK2 has a key role in the regulation of S phase entry. Moreover, we revealed a major and distinct role of ERK1 in the regulation of hepatocyte survival. Taken together, our results represent an important advance in understanding long-term survival and cell cycle regulation of hepatocytes.

The role of mesocorticolimbic dopamine in regulating interactions between drugs of abuse and social behavior.

PubMed

Young, Kimberly A; Gobrogge, Kyle L; Wang, Zuoxin

2011-01-01

The use of addictive drugs can have profound short- and long-term consequences on social behaviors. Similarly, social experiences and the presence or absence of social attachments during early development and throughout life can greatly influence drug intake and the susceptibility to drug abuse. The following review details this reciprocal interaction, focusing on common drugs of abuse (e.g., psychostimulants, opiates, alcohol and nicotine) and social behaviors (e.g., maternal, sexual, play, aggressive and bonding behaviors). The neural mechanisms underlying this interaction are discussed, with a particular emphasis on the involvement of the mesocorticolimbic dopamine system. Copyright © 2010 Elsevier Ltd. All rights reserved.

THE ROLE OF MESOCORTICOLIMBIC DOPAMINE IN REGULATING INTERACTIONS BETWEEN DRUGS OF ABUSE AND SOCIAL BEHAVIOR

PubMed Central

Young, Kimberly A.; Gobrogge, Kyle L.; Wang, Zuoxin

2010-01-01

The use of addictive drugs can have profound short- and long-term consequences on social behaviors. Similarly, social experiences and the presence or absence of social attachments during early development and throughout life can greatly influence drug intake and the susceptibility to drug abuse. The following review details this reciprocal interaction, focusing on common drugs of abuse (e.g., psychostimulants, opiates, alcohol and nicotine) and social behaviors (e.g., maternal, sexual, play, aggressive and bonding behaviors). The neural mechanisms underlying this interaction are discussed, with a particular emphasis on the involvement of the mesocorticolimbic dopamine system. PMID:20600286

European network using fish as osteoporosis research models (ENFORM)

NASA Astrophysics Data System (ADS)

Goerlich, R.; Renn, J.; Alestrom, P.; Nouizadeh-Lillabadi, R.; Schartl, M.; Winkler, C.; Muller, M.; Midtyng, P. J.; Eberius, M.; Slenzka, K.

2005-08-01

Osteoporosis, characterised by loss of bone density, is one of the most important bone diseases of humans worldwide. It causes problems in post-menopausal women, in astronauts during long-term spaceflights and in industrial animal production. Bone alterations leading to osteoporosis are well-documented at the cellular level, but the underlying molecular events are still poorly understood and most of our knowledge is derived from in vitro studies using cell culture systems. Recent findings indicate a remarkable conservation of the key regulators of bone development and homeostasis between mammals and fish. Medaka (Oryzias latipes) and zebrafish (Danio rerio) offer experimental advantages that can be exploited for bone research.

White Matter Microstructural Correlates of Superior Long-term Skill Gained Implicitly under Randomized Practice

PubMed Central

Song, Sunbin; Sharma, Nikhil; Buch, Ethan R.

2012-01-01

We value skills we have learned intentionally, but equally important are skills acquired incidentally without ability to describe how or what is learned, referred to as implicit. Randomized practice schedules are superior to grouped schedules for long-term skill gained intentionally, but its relevance for implicit learning is not known. In a parallel design, we studied healthy subjects who learned a motor sequence implicitly under randomized or grouped practice schedule and obtained diffusion-weighted images to identify white matter microstructural correlates of long-term skill. Randomized practice led to superior long-term skill compared with grouped practice. Whole-brain analyses relating interindividual variability in fractional anisotropy (FA) to long-term skill demonstrated that 1) skill in randomized learners correlated with FA within the corticostriatal tract connecting left sensorimotor cortex to posterior putamen, while 2) skill in grouped learners correlated with FA within the right forceps minor connecting homologous regions of the prefrontal cortex (PFC) and the corticostriatal tract connecting lateral PFC to anterior putamen. These results demonstrate first that randomized practice schedules improve long-term implicit skill more than grouped practice schedules and, second, that the superior skill acquired through randomized practice can be related to white matter microstructure in the sensorimotor corticostriatal network. PMID:21914632

3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

DOE PAGES

Maiti, A.; Small, W.; Lewicki, J.; ...

2016-04-27

3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curvesmore » predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. As a result, this indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.« less

3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

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

Maiti, A.; Small, W.; Lewicki, J.

3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curvesmore » predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. As a result, this indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.« less

3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

NASA Astrophysics Data System (ADS)

Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

2016-04-01

3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.

3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

PubMed Central

Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

2016-01-01

3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance. PMID:27117858

Long-term nitrogen fertilization decreases bacterial diversity and favors the growth of Actinobacteria and Proteobacteria in agro-ecosystems across the globe.

PubMed

Dai, Zhongmin; Su, Weiqin; Chen, Huaihai; Barberán, Albert; Zhao, Haochun; Yu, Mengjie; Yu, Lu; Brookes, Philip C; Schadt, Christopher W; Chang, Scott X; Xu, Jianming

2018-04-12

Long-term elevated nitrogen (N) input from anthropogenic sources may cause soil acidification and decrease crop yield, yet the response of the belowground microbial community to long-term N input alone or in combination with phosphorus (P) and potassium (K) is poorly understood. We explored the effect of long-term N and NPK fertilization on soil bacterial diversity and community composition using meta-analysis of a global dataset. Nitrogen fertilization decreased soil pH, and increased soil organic carbon (C) and available N contents. Bacterial taxonomic diversity was decreased by N fertilization alone, but was increased by NPK fertilization. The effect of N fertilization on bacterial diversity varied with soil texture and water management, but was independent of crop type or N application rate. Changes in bacterial diversity were positively related to both soil pH and organic C content under N fertilization alone, but only to soil organic C under NPK fertilization. Microbial biomass C decreased with decreasing bacterial diversity under long-term N fertilization. Nitrogen fertilization increased the relative abundance of Proteobacteria and Actinobacteria, but reduced the abundance of Acidobacteria, consistent with the general life history strategy theory for bacteria. The positive correlation between N application rate and the relative abundance of Actinobacteria indicates that increased N availability favored the growth of Actinobacteria. This first global analysis of long-term N and NPK fertilization that differentially affects bacterial diversity and community composition provides a reference for nutrient management strategies for maintaining belowground microbial diversity in agro-ecosystems worldwide. © 2018 John Wiley & Sons Ltd.

Long-term dynamics of adaptive evolution in a globally important phytoplankton species to ocean acidification

PubMed Central

Schlüter, Lothar; Lohbeck, Kai T.; Gröger, Joachim P.; Riebesell, Ulf; Reusch, Thorsten B. H.

2016-01-01

Marine phytoplankton may adapt to ocean change, such as acidification or warming, because of their large population sizes and short generation times. Long-term adaptation to novel environments is a dynamic process, and phenotypic change can take place thousands of generations after exposure to novel conditions. We conducted a long-term evolution experiment (4 years = 2100 generations), starting with a single clone of the abundant and widespread coccolithophore Emiliania huxleyi exposed to three different CO2 levels simulating ocean acidification (OA). Growth rates as a proxy for Darwinian fitness increased only moderately under both levels of OA [+3.4% and +4.8%, respectively, at 1100 and 2200 μatm partial pressure of CO2 (Pco2)] relative to control treatments (ambient CO2, 400 μatm). Long-term adaptation to OA was complex, and initial phenotypic responses of ecologically important traits were later reverted. The biogeochemically important trait of calcification, in particular, that had initially been restored within the first year of evolution was later reduced to levels lower than the performance of nonadapted populations under OA. Calcification was not constitutively lost but returned to control treatment levels when high CO2–adapted isolates were transferred back to present-day control CO2 conditions. Selection under elevated CO2 exacerbated a general decrease of cell sizes under long-term laboratory evolution. Our results show that phytoplankton may evolve complex phenotypic plasticity that can affect biogeochemically important traits, such as calcification. Adaptive evolution may play out over longer time scales (>1 year) in an unforeseen way under future ocean conditions that cannot be predicted from initial adaptation responses. PMID:27419227

This Is Your Brain: A Decision-Making Machine

DTIC Science & Technology

2015-11-01

brain has vast comput-ing power that performs a plethora of vital tasks. It regu-lates your bodily functions, movements and emotions . It processes and...system beneath the cerebrum and associated with long-term memory and emotions . In our “The brain is a wonderful organ. It starts working when you get...presence of perceived danger. Long-term memories and experiences also are stored here, often along with their emotional connections to pain or

Assessment of genetic and epigenetic variation during long-term Taxus cell culture.

PubMed

Fu, Chunhua; Li, Liqin; Wu, Wenjuan; Li, Maoteng; Yu, Xiaoqing; Yu, Longjiang

2012-07-01

Gradual loss of secondary metabolite production is a common obstacle in the development of a large-scale plant cell production system. In this study, cell morphology, paclitaxel (Taxol®) biosynthetic ability, and genetic and epigenetic variations in the long-term culture of Taxus media cv Hicksii cells were assessed over a 5-year period to evaluate the mechanisms of the loss of secondary metabolites biosynthesis capacity in Taxus cell. The results revealed that morphological variations, gradual loss of paclitaxel yield and decreased transcriptional level of paclitaxel biosynthesis key genes occurred during long-term subculture. Genetic and epigenetic variations in these cultures were also studied at different times during culture using amplified fragment-length polymorphism (AFLP), methylation-sensitive amplified polymorphism (MSAP), and high-performance liquid chromatography (HPLC) analyses. A total of 32 primer combinations were used in AFLP amplification, and none of the AFLP loci were found to be polymorphic, thus no major genetic rearrangements were detected in any of the tested samples. However, results from both MSAP and HPLC indicated that there was a higher level of DNA methylation in the low-paclitaxel yielding cell line after long-term culture. Based on these results, we proposed that accumulation of paclitaxel in Taxus cell cultures might be regulated by DNA methylation. To our knowledge, this is the first report of increased methylation with the prolongation of culture time in Taxus cell culture. It provides substantial clues for exploring the gradual loss of the taxol biosynthesis capacity of Taxus cell lines during long-term subculture. DNA methylation maybe involved in the regulation of paclitaxel biosynthesis in Taxus cell culture.

Investigation of long-term prestress losses in pretensioned high performance concrete girders.

DOT National Transportation Integrated Search

2005-01-01

Effective determination of long-term prestress losses is important in the design of prestressed concrete bridges. Over-predicting prestress losses results in an overly conservative design for service load stresses, and under-predicting prestress loss...

The interaction of short-term and long-term memory in phonetic category formation

NASA Astrophysics Data System (ADS)

Harnsberger, James D.

2002-05-01

This study examined the role that short-term memory capacity plays in the relationship between novel stimuli (e.g., non-native speech sounds, native nonsense words) and phonetic categories in long-term memory. Thirty native speakers of American English were administered five tests: categorial AXB discrimination using nasal consonants from Malayalam; categorial identification, also using Malayalam nasals, which measured the influence of phonetic categories in long-term memory; digit span; nonword span, a short-term memory measure mediated by phonetic categories in long-term memory; and paired-associate word learning (word-word and word-nonword pairs). The results showed that almost all measures were significantly correlated with one another. The strongest predictor for the discrimination and word-nonword learning results was nonword (r=+0.62) and digit span (r=+0.51), respectively. When the identification test results were partialed out, only nonword span significantly correlated with discrimination. The results show a strong influence of short-term memory capacity on the encoding of phonetic detail within phonetic categories and suggest that long-term memory representations regulate the capacity of short-term memory to preserve information for subsequent encoding. The results of this study will also be discussed with regards to resolving the tension between episodic and abstract models of phonetic category structure.

Intragraft Molecular Pathways Associated with Tolerance Induction in Renal Transplantation.

PubMed

Gallon, Lorenzo; Mathew, James M; Bontha, Sai Vineela; Dumur, Catherine I; Dalal, Pranav; Nadimpalli, Lakshmi; Maluf, Daniel G; Shetty, Aneesha A; Ildstad, Suzanne T; Leventhal, Joseph R; Mas, Valeria R

2018-02-01

The modern immunosuppression regimen has greatly improved short-term allograft outcomes but not long-term allograft survival. Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival. Inducing and understanding pathways underlying clinical tolerance after transplantation are, therefore, necessary. We previously showed full donor chimerism and immunosuppression withdrawal in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Here, we evaluated the gene expression and microRNA expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection. Unlike allograft samples showing acute rejection, samples from FCRx recipients did not show upregulation of T cell- and B cell-mediated rejection pathways. Gene expression pathways differed slightly between FCRx samples and the paired preimplantation donor organ samples, but most of the functional gene networks overlapped. Notably, compared with SIS samples, FCRx samples showed upregulation of genes involved in pathways, like B cell receptor signaling. Additionally, prediction analysis showed inhibition of proinflammatory regulators and activation of anti-inflammatory pathways in FCRx samples. Furthermore, integrative analyses (microRNA and gene expression profiling from the same biopsy sample) identified the induction of regulators with demonstrated roles in the downregulation of inflammatory pathways and maintenance of tissue homeostasis in tolerance-induced FCRx samples compared with SIS samples. This pilot study highlights the utility of molecular intragraft evaluation of pathways related to FCRx-induced tolerance and the use of integrative analyses for identifying upstream regulators of the affected downstream molecular pathways. Copyright © 2018 by the American Society of Nephrology.