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  1. Methamphetamine compromises gap junctional communication in astrocytes and neurons.

    PubMed

    Castellano, Paul; Nwagbo, Chisom; Martinez, Luis R; Eugenin, Eliseo A

    2016-05-01

    Methamphetamine (meth) is a central nervous system (CNS) stimulant that results in psychological and physical dependency. The long-term effects of meth within the CNS include neuronal plasticity changes, blood-brain barrier compromise, inflammation, electrical dysfunction, neuronal/glial toxicity, and an increased risk to infectious diseases including HIV. Most of the reported meth effects in the CNS are related to dysregulation of chemical synapses by altering the release and uptake of neurotransmitters, especially dopamine, norepinephrine, and epinephrine. However, little is known about the effects of meth on connexin (Cx) containing channels, such as gap junctions (GJ) and hemichannels (HC). We examined the effects of meth on Cx expression, function, and its role in NeuroAIDS. We found that meth altered Cx expression and localization, decreased GJ communication between neurons and astrocytes, and induced the opening of Cx43/Cx36 HC. Furthermore, we found that these changes in GJ and HC induced by meth treatment were mediated by activation of dopamine receptors, suggesting that dysregulation of dopamine signaling induced by meth is essential for GJ and HC compromise. Meth-induced changes in GJ and HC contributed to amplified CNS toxicity by dysregulating glutamate metabolism and increasing the susceptibility of neurons and astrocytes to bystander apoptosis induced by HIV. Together, our results indicate that connexin containing channels, GJ and HC, are essential in the pathogenesis of meth and increase the sensitivity of the CNS to HIV CNS disease. Methamphetamine (meth) is an extremely addictive central nervous system stimulant. Meth reduced gap junctional (GJ) communication by inducing internalization of connexin-43 (Cx43) in astrocytes and reducing expression of Cx36 in neurons by a mechanism involving activation of dopamine receptors (see cartoon). Meth-induced changes in Cx containing channels increased extracellular levels of glutamate and resulted in higher

  2. 3-bromopyruvate inhibits glycolysis, depletes cellular glutathione, and compromises the viability of cultured primary rat astrocytes.

    PubMed

    Ehrke, Eric; Arend, Christian; Dringen, Ralf

    2015-07-01

    The pyruvate analogue 3-bromopyruvate (3-BP) is an electrophilic alkylator that is considered a promising anticancer drug because it has been shown to kill cancer cells efficiently while having little toxic effect on nontumor cells. To test for potential adverse effects of 3-BP on brain cells, we exposed cultured primary rat astrocytes to 3-BP and investigated the effects of this compound on cell viability, glucose metabolism, and glutathione (GSH) content. The presence of 3-BP severely compromised cell viability and slowed cellular glucose consumption and lactate production in a time- and concentration-dependent manner, with half-maximal effects observed at about 100 µM 3-BP after 4 hr of incubation. The cellular hexokinase activity was not affected in 3-BP-treated astrocytes, whereas within 30 min after application of 3-BP the activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was inhibited, and cellular GSH content was depleted in a concentration-dependent manner, with half-maximal effects observed at about 30 µM 3-BP. The depletion of cellular GSH after exposure to 100 µM 3-BP was not prevented by the presence of 10 mM of the monocarboxylates lactate or pyruvate, suggesting that 3-BP is not taken up into astrocytes predominantly by monocarboxylate transporters. The data suggest that inhibition of glycolysis by inactivation of GAPDH and GSH depletion contributes to the toxicity that was observed for 3-BP-treated cultured astrocytes. PMID:25196479

  3. Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro

    PubMed Central

    Perez-Alcazar, Marta; Culley, Georgia; Lyckenvik, Tim; Mobarrez, Kristoffer; Bjorefeldt, Andreas; Wasling, Pontus; Seth, Henrik; Asztely, Frederik; Harrer, Andrea; Iglseder, Bernhard; Aigner, Ludwig; Hanse, Eric; Illes, Sebastian

    2016-01-01

    For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse into the brain parenchyma and influence the function of neurons. However, the functional consequences of CSF on neuronal circuits are largely unexplored and unknown. A major reason for this is the absence of appropriate neuronal in vitro model systems, and it is uncertain if neurons cultured in pure CSF survive and preserve electrophysiological functionality in vitro. In this article, we present an approach to address how human CSF (hCSF) influences neuronal circuits in vitro. We validate our approach by comparing the morphology, viability, and electrophysiological function of single neurons and at the network level in rat organotypic slice and primary neuronal cultures cultivated either in hCSF or in defined standard culture media. Our results demonstrate that rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and preserve synaptic transmission. Importantly, we show that hCSF increases neuronal viability and the number of electrophysiologically active neurons in comparison to the culture media. In summary, our data indicate that hCSF represents a physiological environment for neurons in vitro and a superior culture condition compared to the defined standard media. Moreover, this experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling. PMID:26973467

  4. Sustained NMDA receptor activation by spreading depolarizations can initiate excitotoxic injury in metabolically compromised neurons

    PubMed Central

    Aiba, Isamu; Shuttleworth, C William

    2012-01-01

    Spreading depolarizations (SDs) are slowly propagating waves of near-complete neuronal and glial depolarization. SDs have been recorded in patients with brain injury, and the incidence of SD significantly correlates with outcome severity. Although it is well accepted that the ionic dyshomeostasis of SD presents a severe metabolic burden, there is currently limited understanding of SD-induced injury processes at a cellular level. In the current study we characterized events accompanying SD in the hippocampal CA1 region of murine brain slices, using whole-cell recordings and single-cell Ca2+ imaging. We identified an excitatory phase that persisted for approximately 2 min following SD onset, and accompanied with delayed dendritic ionic dyshomeostasis. The excitatory phase coincided with a significant increase in presynaptic glutamate release, evidenced by a transient increase in spontaneous EPSC frequency and paired-pulse depression of evoked EPSCs. Activation of NMDA receptors (NMDARs) during this late excitatory phase contributed to the duration of individual neuronal depolarizations and delayed recovery of extracellular slow potential changes. Selectively targeting the NMDAR activation following SD onset (by delayed pressure application of a competitive NMDAR antagonist) significantly decreased the duration of cellular depolarizations. Recovery of dendritic Ca2+ elevations following SD were also sensitive to delayed NMDA antagonist application. Partial inhibition of neuronal energy metabolism converted SD into an irrecoverable event with persistent Ca2+ overload and membrane compromise. Delayed NMDAR block was sufficient to prevent these acute injurious events in metabolically compromised neurons. These results identify a significant contribution of a late component of SD that could underlie neuronal injury in pathological circumstances. PMID:22907056

  5. Dipeptide Piracetam Analogue Noopept Improves Viability of Hippocampal HT-22 Neurons in the Glutamate Toxicity Model.

    PubMed

    Antipova, T A; Nikolaev, S V; Ostrovskaya, P U; Gudasheva, T A; Seredenin, S B

    2016-05-01

    Effect of noopept (N-phenylacetyl-prolylglycine ethyl ester) on viability of neurons exposed to neurotoxic action of glutamic acid (5 mM) was studied in vitro in immortalized mouse hippocampal HT-22 neurons. Noopept added to the medium before or after glutamic acid improved neuronal survival in a concentration range of 10-11-10-5 M. Comparison of the effective noopept concentrations determined in previous studies on cultured cortical and cerebellar neurons showed that hippocampal neurons are more sensitive to the protective effect of noopept. PMID:27265136

  6. VPS10P-domain receptors - regulators of neuronal viability and function.

    PubMed

    Willnow, Thomas E; Petersen, Claus M; Nykjaer, Anders

    2008-12-01

    VPS10P-domain receptors, such as SORLA and sortilin, constitute a recently identified class of type-1 receptors that are expressed in neurons. Family members are multifunctional proteins that target a range of ligands, including trophic factors and neuropeptides but also other transmembrane proteins. New findings have revealed unexpected roles for VPS10P-domain receptors as regulators of neuronal viability and function through the regulation of both protein transport and signal transduction. Loss of these activities might contribute to the pathophysiology of devastating disorders of the nervous system, including Alzheimer's disease, affective disorders and post-traumatic neuronal cell death. PMID:19002190

  7. Identification of neurotoxic cytokines by profiling Alzheimer’s disease tissues and neuron culture viability screening

    PubMed Central

    Wood, Levi B.; Winslow, Ashley R.; Proctor, Elizabeth A.; McGuone, Declan; Mordes, Daniel A.; Frosch, Matthew P.; Hyman, Bradley T.; Lauffenburger, Douglas A.; Haigis, Kevin M.

    2015-01-01

    Alzheimer’s disease (AD) therapeutics based on the amyloid hypothesis have shown minimal efficacy in patients, suggesting that the activity of amyloid beta (Aβ) represents only one aspect of AD pathogenesis. Since neuroinflammation is thought to play an important role in AD, we hypothesized that cytokines may play a direct role in promoting neuronal death. Here, we profiled cytokine expression in a small cohort of human AD and control brain tissues. We identified AD-associated cytokines using partial least squares regression to correlate cytokine expression with quantified pathologic disease state and then used neuron cultures to test whether cytokines up-regulated in AD tissues could affect neuronal viability. This analysis identified cytokines that were associated with the pathological severity. Of the top correlates, only TNF-α reduced viability in neuron culture when applied alone. VEGF also reduced viability when applied together with Aβ, which was surprising because VEGF has been viewed as a neuro-protective protein. We found that this synthetic pro-death effect of VEGF in the context of Aβ was commensurate with VEGFR-dependent changes in multiple signaling pathways that govern cell fate. Our findings suggest that profiling of tissues combined with a culture-based screening approach can successfully identify new mechanisms driving neuronal death. PMID:26564777

  8. Cellular viability effects of fatty acid amide hydrolase inhibition on cerebellar neurons

    PubMed Central

    2011-01-01

    The endocannabinoid anandamide (ANA) participates in the control of cell death inducing the formation of apoptotic bodies and DNA fragmentation. The aim of this study was to evaluate whether the ANA degrading enzyme, the fatty acid amide hydrolase (FAAH), would induce cellular death. Experiments were performed in cerebellar granule neurons cultured with the FAAH inhibitor, URB597 (25, 50 or 100 nM) as well as endogenous lipids such as oleoylethanolamide (OEA) or palmitoylethanolamide (PEA) and cellular viability was determined by MTT test. Neurons cultured with URB597 (25, 50 or 100 nM) displayed a decrease in cellular viability. In addition, if cultured with OEA (25 nM) or PEA (100 nM), cellular death was found. These results further suggest that URB597, OEA or PEA promote cellular death. PMID:21854612

  9. Effects of Cryopreservation on the Cell Viability, Proliferative Capacity and Neuronal Differentiation Potential of Canine Bone Marrow Stromal Cells

    PubMed Central

    EDAMURA, Kazuya; NAKANO, Rei; FUJIMOTO, Kyohei; TESHIMA, Kenji; ASANO, Kazushi; TANAKA, Shigeo

    2013-01-01

    ABSTRACT We investigated the cell viability, proliferative capacity and neuronal differentiation potential of canine bone marrow stromal cells (BMSCs) after cryopreservation. BMSCs were cryopreserved using cryoprotectant solutions with 10% DMSO and 10% FBS (DF group) or without DMSO and FBS (DF-free group); fresh BMSCs were used as a control. The cell viability and proliferative capacity of BMSCs were similar in the DF-free and control groups, while those in the DF group were lower. In all groups, BMSCs differentiated into neuron-like cells that stained positive against neuron markers, and the mRNA expression levels of neuron markers increased after neuronal induction. In conclusion, cryopreservation with DF-free cryoprotectant solution did not diminish the cell viability, proliferative capacity or neuronal differentiation potential of canine BMSCs. PMID:24334862

  10. Effects of borate-based bioactive glass on neuron viability and neurite extension.

    PubMed

    Marquardt, Laura M; Day, Delbert; Sakiyama-Elbert, Shelly E; Harkins, Amy B

    2014-08-01

    Bioactive glasses have recently been shown to promote regeneration of soft tissues by positively influencing tissue remodeling during wound healing. We were interested to determine whether bioactive glasses have the potential for use in the treatment of peripheral nerve injury. In these experiments, degradable bioactive borate glass was fabricated into rods and microfibers. To study the compatibility with neurons, embryonic chick dorsal root ganglia (DRG) were cultured with different forms of bioactive borate glass. Cell viability was measured with no media exchange (static condition) or routine media exchange (transient condition). Neurite extension was measured within fibrin scaffolds with embedded glass microfibers or aligned rod sheets. Mixed cultures of neurons, glia, and fibroblasts growing in static conditions with glass rods and microfibers resulted in decreased cell viability. However, the percentage of neurons compared with all cell types increased by the end of the culture protocol compared with culture without glass. Furthermore, bioactive glass and fibrin composite scaffolds promoted neurite extension similar to that of control fibrin scaffolds, suggesting that glass does not have a significant detrimental effect on neuronal health. Aligned glass scaffolds guided neurite extension in an oriented manner. Together these findings suggest that bioactive glass can provide alignment to support directed axon growth. PMID:24027222

  11. Morphological remodeling of C. elegans neurons during aging is modified by compromised protein homeostasis

    PubMed Central

    Vayndorf, Elena M; Scerbak, Courtney; Hunter, Skyler; Neuswanger, Jason R; Toth, Marton; Parker, J Alex; Neri, Christian; Driscoll, Monica; Taylor, Barbara E

    2016-01-01

    Understanding cellular outcomes, such as neuronal remodeling, that are common to both healthy and diseased aging brains is essential to the development of successful brain aging strategies. Here, we used Caenorhabdits elegans to investigate how the expression of proteotoxic triggers, such as polyglutamine (polyQ)-expanded huntingtin and silencing of proteostasis regulators, such as the ubiquitin–proteasome system (UPS) and protein clearance components, may impact the morphological remodeling of individual neurons as animals age. We examined the effects of disrupted proteostasis on the integrity of neuronal cytoarchitecture by imaging a transgenic C. elegans strain in which touch receptor neurons express the first 57 amino acids of the human huntingtin (Htt) gene with expanded polyQs (128Q) and by using neuron-targeted RNA interference in adult wild-type neurons to knockdown genes encoding proteins involved in proteostasis. We found that proteostatic challenges conferred by polyQ-expanded Htt and knockdown of specific genes involved in protein homeostasis can lead to morphological changes that are restricted to specific domains of specific neurons. The age-associated branching of PLM neurons is suppressed by N-ter polyQ-expanded Htt expression, whereas ALM neurons with polyQ-expanded Htt accumulate extended outgrowths and other soma abnormalities. Furthermore, knockdown of genes important for ubiquitin-mediated degradation, lysosomal function, and autophagy modulated these age-related morphological changes in otherwise normal neurons. Our results show that the expression of misfolded proteins in neurodegenerative disease such as Huntington’s disease modifies the morphological remodeling that is normally associated with neuronal aging. Our results also show that morphological remodeling of healthy neurons during aging can be regulated by the UPS and other proteostasis pathways. Collectively, our data highlight a model in which morphological remodeling during

  12. Knocking down of the KCC2 in rat hippocampal neurons increases intracellular chloride concentration and compromises neuronal survival

    PubMed Central

    Pellegrino, Christophe; Gubkina, Olena; Schaefer, Michael; Becq, Hélène; Ludwig, Anastasia; Mukhtarov, Marat; Chudotvorova, Ilona; Corby, Severine; Salyha, Yuriy; Salozhin, Sergey; Bregestovski, Piotr; Medina, Igor

    2011-01-01

    Abstract KCC2 is a neuron-specific potassium–chloride co-transporter controlling intracellular chloride homeostasis in mature and developing neurons. It is implicated in the regulation of neuronal migration, dendrites outgrowth and formation of the excitatory and inhibitory synaptic connections. The function of KCC2 is suppressed under several pathological conditions including neuronal trauma, different types of epilepsies, axotomy of motoneurons, neuronal inflammations and ischaemic insults. However, it remains unclear how down-regulation of the KCC2 contributes to neuronal survival during and after toxic stress. Here we show that in primary hippocampal neuronal cultures the suppression of the KCC2 function using two different shRNAs, dominant-negative KCC2 mutant C568A or DIOA inhibitor, increased the intracellular chloride concentration [Cl−]i and enhanced the toxicity induced by lipofectamine-dependent oxidative stress or activation of the NMDA receptors. The rescuing of the KCC2 activity using over-expression of the active form of the KCC2, but not its non-active mutant Y1087D, effectively restored [Cl−]i and enhanced neuronal resistance to excitotoxicity. The reparative effects of KCC2 were mimicked by over-expression of the KCC3, a homologue transporter. These data suggest an important role of KCC2-dependent potassium/chloride homeostasis under neurototoxic conditions and reveal a novel role of endogenous KCC2 as a neuroprotective molecule. PMID:21486764

  13. Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice.

    PubMed

    Jeong, Suh Young; Crooks, Daniel R; Wilson-Ollivierre, Hayden; Ghosh, Manik C; Sougrat, Rachid; Lee, Jaekwon; Cooperman, Sharon; Mitchell, James B; Beaumont, Carole; Rouault, Tracey A

    2011-01-01

    Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice. PMID:22003390

  14. Postnatal loss of brainstem serotonin neurones compromises the ability of neonatal rats to survive episodic severe hypoxia.

    PubMed

    Cummings, Kevin J; Hewitt, Julie C; Li, Aihua; Daubenspeck, John A; Nattie, Eugene E

    2011-11-01

    Pet-1(-/-) mice with a prenatal, genetically induced loss of 5-hydroxytryptamine (5-HT, serotonin) neurones are compromised in their ability to withstand episodic environmental anoxia via autoresuscitation. Given the prenatal role of 5-HT neurones in the development of neural networks, here we ask if a postnatal loss of 5-HT neurones also compromises autoresuscitation. We treated neonatal rat pups at postnatal day (P)2-3 with an intra-cisternal injection of 5,7-dihydroxytryptamine (5,7-DHT; ~40 μg; n = 8) to pharmacologically lesion the 5-HT system, or vehicle (control; n = 14). At P7-10 we exposed unanaesthetized treated and control pups to 15 episodes of environmental anoxia (97% N(2), 3% CO(2)). Medullary 5-HT content was reduced 80% by 5,7-DHT treatment (P < 0.001). Baseline ventilation (V(E)), metabolic rate (V(O(2))), ventilatory equivalent (V(E)/V(O(2))), heart rate (HR), heart rate variability (HRV) and arterial haemoglobin saturation (S(aO(2))) were no different in 5-HT-deficient pups compared to controls. However, only 25% of 5-HT-deficient pups survived all 15 episodes of environmental anoxia, compared to 79% of control littermates (P = 0.007). High mortality of 5,7-DHT-treated pups was associated with delayed onset of gasping (P < 0.001), delayed recovery of HR from hypoxic-induced bradycardia (P < 0.001), and delayed recovery of eupnoea from hypoxic-induced apnoea (P < 0.001). Treatment with 5,7-DHT affected neither the gasping pattern once initiated, nor HR, V(E)/V(O(2)) or S(aO(2)) during the intervening episodes of room air. A significant increase in HRV occurred in all animals with repeated exposure, and in 5-HT-deficient pups this increase occurred immediately prior to death. We conclude that a postnatal loss of brainstem 5-HT content compromises autoresuscitation in response to environmental anoxia. This report provides new evidence in rat pups that 5-HT neurones serve a physiological role in autoresuscitation. Our data may be relevant to

  15. Femtosecond near-infrared laser pulses as a versatile non-invasive tool for intra-tissue nanoprocessing in plants without compromising viability.

    PubMed

    Tirlapur, Uday K; König, Karsten

    2002-08-01

    In this report, we describe a highly reproducible femtosecond near-infrared (NIR) laser-based nanoprocessing technique that can be used both for non-invasive intra-tissue nanodissection of plant cell walls as well as selective destruction of a single plastid or part thereof without compromising the viability of the cells. The ultra-precise intra-tissue nanoprocessing is achieved by the generation of high light intensity (10(12)W cm(-2)) by diffraction-limited focusing of the radiation of an NIR (lambda = 740 and 800 nm) femtosecond titanium-sapphire laser to a sub-femtolitre volume and subsequent highly localized instantaneous plasma formation. Following nanosurgery, electron microscopical analysis of the corresponding cellular target areas revealed clean non-staggering lesions across the cell wall with a cut width measuring less than 400 nm. To our knowledge, this is the smallest cut made non-invasively within a plant tissue. Further evidence, including two-photon imaging of chlorophyll fluorescence, revealed that a single target chloroplast or part thereof can be completely knocked out using intense ultra-fast NIR pulses without any visible deleterious effect on the adjacent plastids. The vitality of the cells after nanoprocessing has been ascertained by exclusion of propidium iodide from the cells as well as by the presence of cytoplasmic streaming. The potential applications of this technical advance include developmental biology applications, particularly studies addressing spatio-temporal control of ontogenetic events and cell-cell interactions, and gravitational biology applications. PMID:12164815

  16. Role of miR-211 in Neuronal Differentiation and Viability: Implications to Pathogenesis of Alzheimer’s Disease

    PubMed Central

    Fan, Chunying; Wu, Qi; Ye, Xiaoyang; Luo, Hongxue; Yan, Dongdong; Xiong, Yi; Zhu, Haili; Diao, Yarui; Zhang, Wei; Wan, Jun

    2016-01-01

    Alzheimer’s disease (AD) is an age-related irreversible neurodegenerative disorder characterized by extracellular β Amyloid(Aβ) deposition, intracellular neurofibrillary tangles and neuronal loss. The dysfunction of neurogenesis and increased degeneration of neurons contribute to the pathogenesis of AD. We now report that miR-211-5p, a small non-coding RNA, can impair neurite differentiation by directly targeting NUAK1, decrease neuronal viability and accelerate the progression of Aβ-induced pathologies. In this study, we observed that during embryonic development, the expression levels of miR-211-5p were down-regulated in the normal cerebral cortexes of mice. However, in APPswe/PS1ΔE9 double transgenic adult mice, it was up-regulated from 9 months of age compared to that of the age-matched wild type mice. Studies in primary cortical neuron cultures demonstrated that miR-211-5p can inhibit neurite growth and branching via NUAK1 repression and decrease mature neuron viability. The impairments were more obvious under the action of Aβ. Our data showed that miR-211-5p could inhibit cortical neuron differentiation and survival, which may contribute to the synaptic failure, neuronal loss and cognitive dysfunction in AD. PMID:27458373

  17. Cognitive dysfunction might be improved in association with recovered neuronal viability after intracranial meningioma resection.

    PubMed

    Koizumi, Hiroyasu; Ideguchi, Makoto; Iwanaga, Hideyuki; Shirao, Satoshi; Sadahiro, Hirokazu; Oka, Fumiaki; Suehiro, Eiichi; Yoneda, Hiroshi; Ishihara, Hideyuki; Nomura, Sadahiro; Suzuki, Michiyasu

    2014-07-29

    Intracranial meningiomas are the most common types of neoplasms that cause mental disorders. Although higher brain function can be restored and even improved in some patients after tumor resection, the mechanisms remain unclear. We investigated changes in the brains of patients after resection of an intracranial meningioma using (123)I-Iomazenil (IMZ)-single photon emission computed tomography (SPECT). Ten patients underwent IMZ-SPECT within 4 weeks before and 3 months after intracranial meningioma resection. Changes in IMZ accumulation in brain parenchyma were assessed as ratios of counts in the lesion-to-contralateral hemisphere (L/C ratios). Mean Mini-Mental State Examination scores before and after resection of 19.9±11.4 vs. 26.5±3.8, respectively (p=0.03) indicated that the cognitive function of these patients was significantly improved after tumor resection. The average L/C ratios calculated from image counts of IMZ were 0.92±0.05 and 0.98±0.02 before and after surgery, respectively. The L/C ratio of IMZ accumulation was significantly decreased after tumor resection (p=0.0003). In contrast, regional cerebral blood flow calculated from (123)I-Iodoamphetamine-SPECT images did not significantly differ after tumor resection. The recovered binding potential of IMZ in brain parenchyma surrounding the tumor bulk after resection indicates that the viability of central benzodiazepine receptors was reversibly depressed and recoverable after release from compression by the tumor. The recovered neuronal viability revealed by IMZ-SPECT might be responsible for the improved cognitive function after intracranial meningioma resection. PMID:24928615

  18. Astrocytic CCAAT/Enhancer Binding Protein δ Regulates Neuronal Viability and Spatial Learning Ability via miR-135a.

    PubMed

    Chu, Yu-Yi; Ko, Chiung-Yuan; Wang, Wei-Jan; Wang, Shao-Ming; Gean, Po-Wu; Kuo, Yu-Min; Wang, Ju-Ming

    2016-08-01

    The progression of Alzheimer's disease (AD) has been associated with astrocytes-induced neuroinflammation. However, the detailed mechanism of astrocytes associated with learning impairments and neuronal loss in AD is poorly defined. Here, we provide novel evidences that astrocytic miR-135a is critical for neuronal viability and spatial learning ability in vivo. The AppTg/Cebpd (-/-) mice showed a spatial learning improvement compared with the APPswe/PS1/E9 bigenic (AppTg) mice. miR-135a was found to be a CCAAT/enhancer binding protein δ (CEBPD) responsive miRNA and can repress the transcription of thrombospondin 1 (THBS1) / Thbs1 (mouse) via its 3'-untranslated region (3'UTR). We used different experimental approaches to attenuate the expression of CEBPD/Cebpd (mouse) or miR-135a in astrocytes and found the following results: increase in THBS1/Thbs1 expression, decrease in neuronal apoptosis, and increase in growth of neurites. Importantly, injection of miR-135a antagonist (AM135a) into the brain of AppTg mice was found to prevent neuronal apoptosis and improved the spatial learning ability. Together, our findings demonstrate a critical function for the astrocytic CEBPD, and point to miR-135a antagonist as an attractive therapeutic target for the treatment of Alzheimer's disease. PMID:26208701

  19. [In vitro viability and glutathione levels in mesencephalic neurons after seven days hibernation].

    PubMed

    De La Cuétara-Bernal, K; Castillo-Díaz, L; Cruz-Aguado, R; González-Mena, Y; García-Varona, A Y

    In embryonic mesencephalic transplant in patients with Parkinson s disease dopaminergic survival is low (5 10%), and for this reason the use of multiple donors has been considered. The difficulty of obtaining more tissue determines the need for a procedure that enables human nigral tissue to be stored for a time without affecting its physiological state in any significant way. This study was designed to determine whether hibernation of tissue fragments has any influence on viability, how the viability of the mesencephalic cells behaves after 7 days hibernation and the glutathione levels in the hibernated tissue (HT). The viability of the HT in pieces (82.37 2.12) was found to be higher than the value for the whole mesencephalon (70.29 3.43). Viability of the HT, seven days at 4 C, at different post dissociation times, did not differ significantly. Despite the significant differences found between hibernated and fresh tissue at t= 0, this procedure does not seem to affect the mesencephalic tissue in any significant way, as it conserved a 94% viability after hibernation. No evidence was found of increased glutathione content as an antioxidizing response to the damage that might be caused by hibernation. These results suggest that since hibernation does not have any significant effect on the state of the cells it could be considered a useful procedure for conserving tissue to be used in clinical transplants. Moreover, further research is needed on survival and functionality of hibernated cells after being transplanted into animal models in order to evaluate their potential for use in cell therapy. PMID:12134300

  20. Insights into the regulation of neuronal viability by nucleophosmin/B23

    PubMed Central

    Pfister, Jason A; D’Mello, Santosh R

    2015-01-01

    The vastness of the neuronal network that constitutes the human brain proves challenging when trying to understand its complexity. Furthermore, due to the senescent state they enter into upon maturation, neurons lack the ability to regenerate in the face of insult, injury or death. Consequently, their excessive death can be detrimental to the proper functioning of the brain. Therefore, elucidating the mechanisms regulating neuronal survival is, while challenging, of great importance as the incidence of neurological disease is becoming more prevalent in today’s society. Nucleophosmin/B23 (NPM) is an abundant and ubiquitously expressed protein that regulates vital cellular processes such as ribosome biogenesis, cell proliferation and genomic stability. As a result, it is necessary for proper embryonic development, but has also been implicated in many cancers. While highly studied in the context of proliferative cells, there is a lack of understanding NPM’s role in post-mitotic neurons. By exploring its role in healthy neurons as well as its function in the regulation of cell death and neurodegeneration, there can be a better understanding of how these diseases initiate and progress. Owing to what is thus far known about its function in the cell, NPM could be an attractive therapeutic target in the treatment of neurodegenerative diseases. PMID:25908633

  1. Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

    PubMed Central

    Sanchez, Ana B.; Varano, Giuseppe P.; de Rozieres, Cyrus M.; Maung, Ricky; Catalan, Irene C.; Dowling, Cari C.; Sejbuk, Natalia E.; Hoefer, Melanie M.

    2015-01-01

    HIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART). Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine. PMID:26482305

  2. Novel role of KCNQ2/3 channels in regulating neuronal cell viability.

    PubMed

    Zhou, X; Wei, J; Song, M; Francis, K; Yu, S P

    2011-03-01

    Overactivation of certain K(+) channels can mediate excessive K(+) efflux and intracellular K(+) depletion, which are early ionic events in apoptotic cascade. The present investigation examined a possible role of the KCNQ2/3 channel or M-channel (also named Kv7.2/7.3 channels) in the pro-apoptotic process. Whole-cell recordings detected much larger M-currents (212 ± 31 pA or 10.5 ± 1.5 pA/pF) in cultured hippocampal neurons than that in cultured cortical neurons (47 ± 21 pA or 2.4 ± 0.8 pA/pF). KCNQ2/3 channel openers N-ethylmaleimide (NEM) and flupirtine caused dose-dependent K(+) efflux, intracellular K(+) depletion, and cell death in hippocampal cultures, whereas little cell death was induced by NEM in cortical cultures. The NEM-induced cell death was antagonized by co-applied KCNQ channel inhibitor XE991 (10 μM), or by elevated extracellular K(+) concentration. Supporting a mediating role of KCNQ2/3 channels in apoptosis, expression of KCNQ2 or KCNQ2/3 channels in Chinese hamster ovary (CHO) cells initiated caspase-3 activation. Consistently, application of NEM (20 μM, 8 h) in hippocampal cultures similarly caused caspase-3 activation assessed by immunocytochemical staining and western blotting. NEM increased the expression of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), induced mitochondria membrane depolarization, cytochrome c release, formation of apoptosome complex, and apoptosis-inducing factor (AIF) translocation into nuclear. All these events were attenuated by blocking KCNQ2/3 channels. These findings provide novel evidence that KCNQ2/3 channels could be an important regulator in neuronal apoptosis. PMID:20885443

  3. Elevated metals compromise repair of oxidative DNA damage via the base excision repair pathway: implications of pathologic iron overload in the brain on integrity of neuronal DNA.

    PubMed

    Li, Hui; Swiercz, Rafal; Englander, Ella W

    2009-09-01

    Tissue-specific iron content is tightly regulated to simultaneously satisfy specialized metabolic needs and avoid cytotoxicity. In the brain, disruption of iron homeostasis may occur in acute as well as progressive injuries associated with neuronal dysfunction and death. We hypothesized that adverse effects of disrupted metal homeostasis on brain function may involve impairment of DNA repair processes. Because in the brain, the base excision repair (BER) pathway is central for handling oxidatively damaged DNA, we investigated effects of elevated iron and zinc on key BER enzymes. In vitro DNA repair assays revealed inhibitory effects of metals on BER activities, including the incision of abasic sites, 5'-flap cleavage, gap filling DNA synthesis and ligation. Using the comet assay, we showed that while metals at concentrations which inhibit BER activities in in vitro assays, did not induce direct genomic damage in cultured primary neurons, they significantly delayed repair of genomic DNA damage induced by sublethal exposure to H(2)O(2). Thus, in the brain even a mild transient metal overload, may adversely affect the DNA repair capacity and thereby compromise genomic integrity and initiate long-term deleterious sequelae including neuronal dysfunction and death. PMID:19619136

  4. Beclin 1 Is Required for Neuron Viability and Regulates Endosome Pathways via the UVRAG-VPS34 Complex

    PubMed Central

    Wold, Mitchell S.; Gong, Shiaoching; Phillips, Greg R.; Dou, Zhixun; Zhao, Yanxiang; Heintz, Nathaniel; Zong, Wei-Xing; Yue, Zhenyu

    2014-01-01

    Deficiency of autophagy protein beclin 1 is implicated in tumorigenesis and neurodegenerative diseases, but the molecular mechanism remains elusive. Previous studies showed that Beclin 1 coordinates the assembly of multiple VPS34 complexes whose distinct phosphatidylinositol 3-kinase III (PI3K-III) lipid kinase activities regulate autophagy at different steps. Recent evidence suggests a function of beclin 1 in regulating multiple VPS34-mediated trafficking pathways beyond autophagy; however, the precise role of beclin 1 in autophagy-independent cellular functions remains poorly understood. Herein we report that beclin 1 regulates endocytosis, in addition to autophagy, and is required for neuron viability in vivo. We find that neuronal beclin 1 associates with endosomes and regulates EEA1/early endosome localization and late endosome formation. Beclin 1 maintains proper cellular phosphatidylinositol 3-phosphate (PI(3)P) distribution and total levels, and loss of beclin 1 causes a disruption of active Rab5 GTPase-associated endosome formation and impairment of endosome maturation, likely due to a failure of Rab5 to recruit VPS34. Furthermore, we find that Beclin 1 deficiency causes complete loss of the UVRAG-VPS34 complex and associated lipid kinase activity. Interestingly, beclin 1 deficiency impairs p40phox-linked endosome formation, which is rescued by overexpressed UVRAG or beclin 1, but not by a coiled-coil domain-truncated beclin 1 (a UVRAG-binding mutant), Atg14L or RUBICON. Thus, our study reveals the essential role for beclin 1 in neuron survival involving multiple membrane trafficking pathways including endocytosis and autophagy, and suggests that the UVRAG-beclin 1 interaction underlies beclin 1's function in endocytosis. PMID:25275521

  5. Biased Type 1 Cannabinoid Receptor Signaling Influences Neuronal Viability in a Cell Culture Model of Huntington Disease.

    PubMed

    Laprairie, Robert B; Bagher, Amina M; Kelly, Melanie E M; Denovan-Wright, Eileen M

    2016-03-01

    Huntington disease (HD) is an inherited, autosomal dominant, neurodegenerative disorder with limited treatment options. Prior to motor symptom onset or neuronal cell loss in HD, levels of the type 1 cannabinoid receptor (CB1) decrease in the basal ganglia. Decreasing CB1 levels are strongly correlated with chorea and cognitive deficit. CB1 agonists are functionally selective (biased) for divergent signaling pathways. In this study, six cannabinoids were tested for signaling bias in in vitro models of medium spiny projection neurons expressing wild-type (STHdh(Q7/Q7)) or mutant huntingtin protein (STHdh(Q111/Q111)). Signaling bias was assessed using the Black and Leff operational model. Relative activity [ΔlogR (τ/KA)] and system bias (ΔΔlogR) were calculated relative to the reference compound WIN55,212-2 for Gαi/o, Gαs, Gαq, Gβγ, and β-arrestin1 signaling following treatment with 2-arachidonoylglycerol (2-AG), anandamide (AEA), CP55,940, Δ(9)-tetrahydrocannabinol (THC), cannabidiol (CBD), and THC+CBD (1:1), and compared between wild-type and HD cells. The Emax of Gαi/o-dependent extracellular signal-regulated kinase (ERK) signaling was 50% lower in HD cells compared with wild-type cells. 2-AG and AEA displayed Gαi/o/Gβγ bias and normalized CB1 protein levels and improved cell viability, whereas CP55,940 and THC displayed β-arrestin1 bias and reduced CB1 protein levels and cell viability in HD cells. CBD was not a CB1 agonist but inhibited THC-dependent signaling (THC+CBD). Therefore, enhancing Gαi/o-biased endocannabinoid signaling may be therapeutically beneficial in HD. In contrast, cannabinoids that are β-arrestin-biased--such as THC found at high levels in modern varieties of marijuana--may be detrimental to CB1 signaling, particularly in HD where CB1 levels are already reduced. PMID:26700564

  6. Neuron-Specific Enolase Is Correlated to Compromised Cerebral Metabolism in Patients Suffering from Acute Bacterial Meningitis; An Observational Cohort Study

    PubMed Central

    Bartek, Jiri; Thelin, Eric Peter; Ghatan, Per Hamid; Glimaker, Martin; Bellander, Bo-Michael

    2016-01-01

    Introduction Patients suffering from acute bacterial meningitis (ABM) with a decreased level of consciousness have been shown to have an improved clinical outcome if treated with an intracranial pressure (ICP) guided therapy. By using intracranial microdialysis (MD) to monitor cerebral metabolism in combination with serum samples of biomarkers indicating brain tissue injury, S100B and Neuron Specific Enolase (NSE), additional information might be provided. The aim of this study was to evaluate biomarkers in serum and MD parameters in patients with ABM. Methods From a prior study on patients (n = 52) with a confirmed ABM and impaired consciousness (GCS ≤ 9, or GCS = 10 combined with lumbar spinal opening pressure > 400 mmH2O), a subgroup of patients (n = 21) monitored with intracerebral MD and biomarkers was included in the present study. All patients were treated in the NICU with intracranial pressure (ICP) guided therapy. Serum biomarkers were obtained at admission and every 12 hours. The MD parameters glucose, lactate, pyruvate and glycerol were analyzed. Outcome was assessed at 12–55 months after discharge from hospital. Mann-Whitney U-Test and Wilcoxon matched-pairs signed rank test were applied. Results The included patients had a mean GCS of 8 (range, 3–10) on admission and increased ICP (>20 mmHg) was observed in 62% (n = 13/21) of the patients. Patients with a lactate:pyruvate ratio (LPR) >40 (n = 9/21, 43%) had significantly higher peak levels of serum NSE (p = 0.03), with similar, although non-significant observations made in patients with high levels of glycerol (>500 μmol/L, p = 0.11) and those with a metabolic crisis (Glucose <0.8 mmol/L, LPR >25, p = 0.09). No associations between serum S100B and MD parameters were found. Furthermore, median MD glucose levels decreased significantly between day 1 (0–24h) and day 3 (48–72h) after admission to the NICU (p = 0.0001). No correlation between MD parameters or biomarkers and outcome was found

  7. Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen-glucose deprivation.

    PubMed

    Voytenko, L P; Lushnikova, I V; Savotchenko, A V; Isaeva, E V; Skok, M V; Lykhmus, O Yu; Patseva, M A; Skibo, G G

    2015-08-01

    The hippocampal interneurons are very diverse by chemical profiles and rather inconsistent by sensitivity to CI. Some hippocampal GABAergic interneurons survive certain time after ischemia while ischemia-sensitive interneurons and pyramidal neurons are damaged. GABAergic signaling, nicotinic receptors expressing α7-subunit (α7nAChRs(+)) and connexin-36 (Cx36(+), electrotonic gapjunctions protein) contradictory modulate post-ischemic environment. We hypothesized that hippocampal ischemia-resistant GABAergic interneurons coexpressing glutamate decarboxylase-67 isoform (GAD67(+)), α7nAChRs(+), Cx36(+) are able to enhance neuronal viability. To check this hypothesis the histochemical and electrophysiological investigations have been performed using rat hippocampal organotypic culture in the condition of 30-min oxygen-glucose deprivation (OGD). Post-OGD reoxygenation (4h) revealed in CA1 pyramidal layer numerous damaged cells, decreased population spike amplitude and increased pair-pulse depression. In these conditions GAD67(+) interneurons displayed the OGD-resistance and significant increase of GABA synthesis/metabolism (GAD67-immunofluorescence, mitochondrial activity). The α7nAChRs(+) and Cx36(+) co-localizations were revealed in resistant GAD67(+) interneurons. Under OGD: GABAA-receptors (GABAARs) blockade increased cell damage and exacerbated the pair-pulse depression in CA1 pyramidal layer; α7nAChRs and Cx36-channels separate blockades sufficiently decreased cell damage while interneuronal GAD67-immunofluorescence and mitochondrial activity were similar to the control. Thus, hippocampal GABAergic interneurons co-expressing α7nAChRs and Cx36 remained resistant certain time after OGD and were able to modulate CA1 neuron survival through GABAARs, α7nAChRs and Cx36-channels activity. The enhancements of the neuronal viability together with GABA synthesis/metabolism normalization suggest cooperative neuroprotective mechanism that could be used for increase in

  8. Rabies Virus CVS-N2c(ΔG) Strain Enhances Retrograde Synaptic Transfer and Neuronal Viability.

    PubMed

    Reardon, Thomas R; Murray, Andrew J; Turi, Gergely F; Wirblich, Christoph; Croce, Katherine R; Schnell, Matthias J; Jessell, Thomas M; Losonczy, Attila

    2016-02-17

    Virally based transsynaptic tracing technologies are powerful experimental tools for neuronal circuit mapping. The glycoprotein-deletion variant of the SAD-B19 vaccine strain rabies virus (RABV) has been the reagent of choice in monosynaptic tracing, since it permits the mapping of synaptic inputs to genetically marked neurons. Since its introduction, new helper viruses and reagents that facilitate complementation have enhanced the efficiency of SAD-B19(ΔG) transsynaptic transfer, but there has been little focus on improvements to the core RABV strain. Here we generate a new deletion mutant strain, CVS-N2c(ΔG), and examine its neuronal toxicity and efficiency in directing retrograde transsynaptic transfer. We find that by comparison with SAD-B19(ΔG), the CVS-N2c(ΔG) strain exhibits a reduction in neuronal toxicity and a marked enhancement in transsynaptic neuronal transfer. We conclude that the CVS-N2c(ΔG) strain provides a more effective means of mapping neuronal circuitry and of monitoring and manipulating neuronal activity in vivo in the mammalian CNS. PMID:26804990

  9. The effect of modified polysialic acid based hydrogels on the adhesion and viability of primary neurons and glial cells.

    PubMed

    Haile, Yohannes; Berski, Silke; Dräger, Gerald; Nobre, Andrè; Stummeyer, Katharina; Gerardy-Schahn, Rita; Grothe, Claudia

    2008-04-01

    In this study we present the enzymatic and biological analysis of polysialic acid (polySia) based hydrogel in terms of its degradation and cytocompatibility. PolySia based hydrogel is completely degradable by endosialidase enzyme which may avoid second surgery after tissue recovery. Viability assay showed that soluble components of polySia hydrogel did not cause any toxic effect on cultured Schwann cells. Moreover, green fluorescence protein transfected neonatal and adult Schwann cells, neural stem cells and dorsal root ganglionic cells (unlabelled) were seeded on polySia hydrogel modified with poly-L-lysine (Pll), poly-L-ornithine-laminin (porn-laminin) or collagen. Water soluble tetrazolium salt assay revealed that modification of the hydrogel significantly improved cell adhesion and viability. These results infer that polySia based scaffolds in combination with cell adhesion molecules and cells genetically modified to express growth factors would potentially be promising alternative in reconstructive therapeutic strategies. PMID:18255143

  10. Neuroprotective effects of erythromycin on cerebral ischemia reperfusion-injury and cell viability after oxygen-glucose deprivation in cultured neuronal cells.

    PubMed

    Katayama, Yasuo; Inaba, Toshiki; Nito, Chikako; Ueda, Masayuki; Katsura, Kenichiro

    2014-11-01

    This study aims to determine if erythromycin has neuroprotective effects against transient ischemia and oxygen-glucose deprivation (OGD) in cultured neuronal cells. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 90 min, followed by reperfusion. The animals received a subcutaneous single injection of erythromycin lactobionate (EM, 50mg/kg) or vehicle immediately after ischemia. Infarct volume, edema index, and neurological performance were evaluated at 24 and 72 h after reperfusion. Immunohistochemical analyses for oxidative stress (4-HNE, 8-OHdG) and inflammation (Iba-1, TNF-α) were conducted in the cortex at 24h. Primary cortical neuronal cell cultures were prepared from the cerebral cortices of the animals and then subjected to OGD for 3h. Ten or 100 μM EM was added before OGD to determine the effect of EM on cell viability after OGD. EM significantly reduced infarct volume (p<0.01) and edema volume (p<0.05) and improved neurological deficit scores (p<0.05) at 24 and 72 h. EM significantly suppressed the accumulation of 4-HNE (p<0.01) and 8-OHdG (p<0.01) and markedly reduced Iba-1 (p<0.01) and TNF-α expression (p<0.01). Treatment with 100 μM EM in vitro significantly reduced cell death after OGD. EM reduces neuronal damage following cerebral ischemia and OGD and may have antioxidant and anti-inflammatory effects. PMID:25264351

  11. Compromised NMDA/Glutamate Receptor Expression in Dopaminergic Neurons Impairs Instrumental Learning, But Not Pavlovian Goal Tracking or Sign Tracking1,2,3

    PubMed Central

    James, Alex S.; Pennington, Zachary T.; Tran, Phu

    2015-01-01

    Abstract Two theories regarding the role for dopamine neurons in learning include the concepts that their activity serves as a (1) mechanism that confers incentive salience onto rewards and associated cues and/or (2) contingency teaching signal reflecting reward prediction error. While both theories are provocative, the causal role for dopamine cell activity in either mechanism remains controversial. In this study mice that either fully or partially lacked NMDARs in dopamine neurons exclusively, as well as appropriate controls, were evaluated for reward-related learning; this experimental design allowed for a test of the premise that NMDA/glutamate receptor (NMDAR)-mediated mechanisms in dopamine neurons, including NMDA-dependent regulation of phasic discharge activity of these cells, modulate either the instrumental learning processes or the likelihood of pavlovian cues to become highly motivating incentive stimuli that directly attract behavior. Loss of NMDARs in dopamine neurons did not significantly affect baseline dopamine utilization in the striatum, novelty evoked locomotor behavior, or consumption of a freely available, palatable food solution. On the other hand, animals lacking NMDARs in dopamine cells exhibited a selective reduction in reinforced lever responses that emerged over the course of instrumental learning. Loss of receptor expression did not, however, influence the likelihood of an animal acquiring a pavlovian conditional response associated with attribution of incentive salience to reward-paired cues (sign tracking). These data support the view that reductions in NMDAR signaling in dopamine neurons affect instrumental reward-related learning but do not lend support to hypotheses that suggest that the behavioral significance of this signaling includes incentive salience attribution. PMID:26464985

  12. In vitro cytotoxicity of superparamagnetic iron oxide nanoparticles on neuronal and glial cells. Evaluation of nanoparticle interference with viability tests.

    PubMed

    Costa, Carla; Brandão, Fátima; Bessa, Maria João; Costa, Solange; Valdiglesias, Vanessa; Kiliç, Gözde; Fernández-Bertólez, Natalia; Quaresma, Pedro; Pereira, Eulália; Pásaro, Eduardo; Laffon, Blanca; Teixeira, João Paulo

    2016-03-01

    Superparamagnetic iron oxide nanoparticles (ION) have attracted great interest for use in several biomedical fields. In general, they are considered biocompatible, but little is known of their effects on the human nervous system. The main objective of this work was to evaluate the cytotoxicity of two ION (magnetite), coated with silica and oleic acid, previously determining the possible interference of the ION with the methodological procedures to assure the reliability of the results obtained. Human neuroblastoma SHSY5Y and glioblastoma A172 cells were exposed to different concentrations of ION (5-300 µg ml(-1)), prepared in complete and serum-free cell culture medium for three exposure times (3, 6 and 24 h). Cytotoxicity was evaluated by means of the MTT, neutral red uptake and alamar blue assays. Characterization of the main physical-chemical properties of the ION tested was also performed. Results demonstrated that both ION could significantly alter absorbance readings. To reduce these interferences, protocols were modified by introducing additional washing steps and cell-free systems. Significant decreases in cell viability were observed for both cell lines in specific conditions by all assays. In general, oleic acid-coated ION were less cytotoxic than silica-coated ION; besides, a serum-protective effect was observed for both ION studied and cell lines. These results contribute to increase the knowledge of the potential harmful effects of ION on the human nervous system. Understanding these effects is essential to establish satisfactory regulatory policies on the safe use of magnetite nanoparticles in biomedical applications. PMID:26212026

  13. Ablation of CBP in forebrain principal neurons causes modest memory and transcriptional defects and a dramatic reduction of histone acetylation but does not affect cell viability.

    PubMed

    Valor, Luis M; Pulopulos, Matias M; Jimenez-Minchan, Maria; Olivares, Roman; Lutz, Beat; Barco, Angel

    2011-02-01

    Rubinstein-Taybi syndrome (RSTS) is an inheritable disease associated with mutations in the gene encoding the CREB (cAMP response element-binding protein)-binding protein (CBP) and characterized by growth impairment, learning disabilities, and distinctive facial and skeletal features. Studies in mouse models for RSTS first suggested a direct role for CBP and histone acetylation in cognition and memory. Here, we took advantage of the genetic tools for generating mice in which the CBP gene is specifically deleted in postmitotic principal neurons of the forebrain to investigate the consequences of the loss of CBP in the adult brain. In contrast to the conventional CBP knock-out mice, which exhibit very early embryonic lethality, postnatal forebrain-restricted CBP mutants were viable and displayed no overt abnormalities. We identified the dimer of histones H2A and H2B as the preferred substrate of the histone acetyltransferase domain of CBP. Surprisingly, the loss of CBP and subsequent histone hypoacetylation had a very modest impact in the expression of a number of immediate early genes and did not affect neuronal viability. In addition, the behavioral characterization of these mice dissociated embryonic and postnatal deficits caused by impaired CBP function, narrowed down the anatomical substrate of specific behavioral defects, and confirmed the special sensitivity of object recognition memory to CBP deficiency. Overall, our study provides novel insights into RSTS etiology and clarifies some of the standing questions concerning the role of CBP and histone acetylation in activity-driven gene expression, memory formation, and neurodegeneration. PMID:21289174

  14. Overexpression of the astrocyte glutamate transporter GLT1 exacerbates phrenic motor neuron degeneration, diaphragm compromise, and forelimb motor dysfunction following cervical contusion spinal cord injury.

    PubMed

    Li, Ke; Nicaise, Charles; Sannie, Daniel; Hala, Tamara J; Javed, Elham; Parker, Jessica L; Putatunda, Rajarshi; Regan, Kathleen A; Suain, Valérie; Brion, Jean-Pierre; Rhoderick, Fred; Wright, Megan C; Poulsen, David J; Lepore, Angelo C

    2014-05-28

    A major portion of spinal cord injury (SCI) cases affect midcervical levels, the location of the phrenic motor neuron (PhMN) pool that innervates the diaphragm. While initial trauma is uncontrollable, a valuable opportunity exists in the hours to days following SCI for preventing PhMN loss and consequent respiratory dysfunction that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxic cell death due to dysregulation of extracellular glutamate homeostasis. GLT1, mainly expressed by astrocytes, is responsible for the vast majority of functional uptake of extracellular glutamate in the CNS, particularly in spinal cord. We found that, in bacterial artificial chromosome-GLT1-enhanced green fluorescent protein reporter mice following unilateral midcervical (C4) contusion SCI, numbers of GLT1-expressing astrocytes in ventral horn and total intraspinal GLT1 protein expression were reduced soon after injury and the decrease persisted for ≥6 weeks. We used intraspinal delivery of adeno-associated virus type 8 (AAV8)-Gfa2 vector to rat cervical spinal cord ventral horn for targeting focal astrocyte GLT1 overexpression in areas of PhMN loss. Intraspinal delivery of AAV8-Gfa2-GLT1 resulted in transduction primarily of GFAP(+) astrocytes that persisted for ≥6 weeks postinjury, as well as increased intraspinal GLT1 protein expression. Surprisingly, we found that astrocyte-targeted GLT1 overexpression increased lesion size, PhMN loss, phrenic nerve axonal degeneration, and diaphragm neuromuscular junction denervation, and resulted in reduced functional diaphragm innervation as assessed by phrenic nerve-diaphragm compound muscle action potential recordings. These results demonstrate that GLT1 overexpression via intraspinal AAV-Gfa2-GLT1 delivery exacerbates neuronal damage and increases respiratory impairment following cervical SCI. PMID:24872566

  15. Neuropilin 2 deficiency does not affect cortical neuronal viability in response to oxygen-glucose-deprivation and transient middle cerebral artery occlusion.

    PubMed

    Hou, Sheng T; Jiang, Susan X; Slinn, Jacqueline; O'Hare, Michael; Karchewski, Laurie

    2010-04-01

    Neuropilin 2 (NRP2) is a type I transmembrane protein that binds to distinct members of the class III secreted Semaphorin subfamily. NRP2 plays important roles in repulsive axon guidance, angiogenesis and vasculogenesis through partnering with co-receptors such as vascular endothelial growth factor receptors (VEGFRs) during development. Emerging evidence also suggests that NRP2 contributes to injury response and environment changes in adult brains. In this study, we examined the contribution of NRP2 gene to cerebral ischemia-induced brain injury using NRP2 deficient mouse. To our surprise, the lack of NRP2 expression does not affect the outcome of brain injury induced by transient occlusion of the middle cerebral artery (MCAO) in mouse. The cerebral vasculature in terms of the middle cerebral artery anatomy and microvessel density in the cerebral cortex of NRP2 deficient homozygous (NRP2(-/-)) mice are normal and almost identical to those of the heterozygous (NRP2(+/-)) and wild type (NRP2(+/+)) littermates. MCAO (1h) and 24h reperfusion caused a brain infarction of 23% (compared to the contralateral side) in NRP2(-/-) mice, which is not different from those in NRP2(+/- and +/+) mice at 22 and 21%, respectively (n=19, p>0.05). Correspondingly, NRP2(-/-) mouse also showed a similar level of deterioration of neurological functions after stroke compared with their NRP2(+/- and +/+) littermates. Oxygen-glucose-deprivation (OGD) caused a significant neuronal death in NRP2(-/-) cortical neurons, at the level similar to that in NRP(+/+) cortical neurons (72% death in NRP(-/-) neurons vs. 75% death in NRP2(+/+) neurons; n=4; p>0.05). Together, these loss-of-function studies demonstrated that despite of its critical role in neuronal guidance and vascular formation during development, NRP2 expression dose not affect adult brain response to cerebral ischemia. PMID:20036291

  16. Guiding neuronal development with in situ microfabrication

    NASA Astrophysics Data System (ADS)

    Kaehr, Bryan; Allen, Richard; Javier, David J.; Currie, John; Shear, Jason B.

    2004-11-01

    We report the ability to modify microscopic 3D topographies within dissociated cultures, providing a means to alter the development of neurons as they extend neurites and establish interconnections. In this approach, multiphoton excitation is used to focally excite noncytotoxic photosensitizers that promote protein crosslinking, such as BSA, into matrices having feature sizes 250 nm. Barriers, growth lanes, and pinning structures comprised of crosslinked proteins are fabricated under conditions that do not compromise the viability of neurons both on short time scales and over periods of days. In addition, the ability to fabricate functional microstructures from crosslinked avidin enables submicrometer localization of controllable quantities of biotinylated ligands, such as indicators and biological effectors. Feasibility is demonstrated for using in situ microfabrication to guide the contact position of cortical neurons with micrometer accuracy, opening the possibility for engineering well defined sets of synaptic interactions. biofabrication | multiphoton cell patterning | growth cone

  17. Localization of CdSe/ZnS quantum dots in the lysosomal acidic compartment of cultured neurons and its impact on viability: potential role of ion release.

    PubMed

    Corazzari, Ingrid; Gilardino, Alessandra; Dalmazzo, Simona; Fubini, Bice; Lovisolo, Davide

    2013-03-01

    CdSe Quantum Dots (QDs) are increasingly being employed in both industrial applications and biological imaging, thanks to their numerous advantages over conventional organic and proteic fluorescent markers. On the other hand a growing concern has emerged that toxic elements from the QDs core would render the nanoparticles harmful to cell cultures, animals and humans. The interaction between QDs and neuronal cells in particular needs to be carefully evaluated, since nanoparticles could access the nervous system by several pathways, including the olfactory epithelium, even if no data are presently available about QDs. The pH of the environment to which the nanoparticles are exposed may play a crucial role in the stability of QDs coating. For this reason we investigated the release of metal ions from CdSe/ZnS QDs in artificial media reproducing the cytosolic and lysosomal cellular compartments characterized respectively by a neutral and an acidic pH. In the latter significant amounts of both Cd(2+) and Zn(2+) were released. We provide evidence that these QDs are internalized in the GT1-7 neuronal cell line and located in the lysosomal compartment. These findings can be related to a slight but significant reduction in cell survival and proliferation. PMID:23274769

  18. A compromise on abortion?

    PubMed

    Rhoden, N K

    1989-01-01

    Rhoden's article is one of three on "Abortion: searching for common ground" in this issue of the Hastings Center Report. Her article, together with those by M. Mahowald and M. Glendon, was prompted by the expectation that the impending U.S. Supreme Court decision in Webster v. Reproductive Health Services (3 July 1989) would overturn or restrict Roe v. Wade (1973). Rhoden, an advocate for the pro-choice position, asks whether a compromise leading to an acceptable regulatory policy is possible or desirable among those on opposite sides of the abortion issue. She identifies several reasons why the Roe decision is vulnerable to review, but argues that effective education about sexuality and comprehensive social support of women are better approaches to abortion than restrictive legislation. PMID:2663778

  19. The medically compromised patient.

    PubMed

    Parnell, A G

    1986-06-01

    Diabetes mellitus is found in up to 5 per cent of the population. There is an excess of blood sugar due to a deficiency or diminished effectiveness of insulin. It is a complex disease which, if not controlled, has many major complications including an increased incidence of heart attacks, strokes and vascular changes in many other organs. The management of young onset diabetic patients is directed towards: controlling the carbohydrate intake, testing the blood sugar by the patient and regular insulin injections. Great care must be taken in treating diabetics in the dental surgery. Except for children, any diabetic can be treated for simple dental procedures by ensuring freedom from pain, by eliminating stress and by ensuring that the patient does not miss a meal. Children, unstable diabetic patients and those with infections or requiring multiple extractions should be treated in hospital under the care of an endocrinologist. In hypertension it is only after a number of years that complications begin to appear. The main ones are those of stroke, retinal haemorrhages, renal failure and heart disease. Dentists should be encouraged to take the blood pressure of all adults who present for treatment. Patients with increased blood pressure yet controlled by drugs may be treated as normal patients. Those that are not well controlled should be referred to their physician. Dental appointments must be free of pain and stress should be avoided. A screening method is presented which assists in the evaluation of medically compromised patients. PMID:2941377

  20. [Tuberculosis in compromised hosts].

    PubMed

    2003-11-01

    Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower

  1. Kif5 regulates mitochondrial movement, morphology, function and neuronal survival.

    PubMed

    Iworima, Diepiriye G; Pasqualotto, Bryce A; Rintoul, Gordon L

    2016-04-01

    Due to the unique architecture of neurons, trafficking of mitochondria throughout processes to regions of high energetic demand is critical to sustain neuronal health. It has been suggested that compromised mitochondrial trafficking may play a role in neurodegenerative diseases. We evaluated the consequences of disrupted kif5c-mediated mitochondrial trafficking on mitochondrial form and function in primary rat cortical neurons. Morphological changes in mitochondria appeared to be due to remodelling, a phenomenon distinct from mitochondrial fission, which resulted in punctate-shaped mitochondria. We also demonstrated that neurons displaying punctate mitochondria exhibited relatively decreased ROS and increased cellular ATP levels using ROS-sensitive GFP and ATP FRET probes, respectively. Somewhat unexpectedly, neurons overexpressing the dominant negative form of kif5c exhibited enhanced survival following excitotoxicity, suggesting that the impairment of mitochondrial trafficking conferred some form of neuroprotection. However, when neurons were exposed to H2O2, disruption of kif5c exacerbated cell death indicating that the effect on cell viability was dependent on the mode of toxicity. Our results suggest a novel role of kif5c. In addition to mediating mitochondrial transport, kif5c plays a role in the mechanism of regulating mitochondrial morphology. Our results also suggest that kif5c mediated mitochondrial dynamics may play an important role in regulating mitochondrial function and in turn cellular health. Moreover, our studies demonstrate an interesting interplay between the regulation of mitochondrial motility and morphology. PMID:26767417

  2. Label-Free Characterization of Emerging Human Neuronal Networks

    NASA Astrophysics Data System (ADS)

    Mir, Mustafa; Kim, Taewoo; Majumder, Anirban; Xiang, Mike; Wang, Ru; Liu, S. Chris; Gillette, Martha U.; Stice, Steven; Popescu, Gabriel

    2014-03-01

    The emergent self-organization of a neuronal network in a developing nervous system is the result of a remarkably orchestrated process involving a multitude of chemical, mechanical and electrical signals. Little is known about the dynamic behavior of a developing network (especially in a human model) primarily due to a lack of practical and non-invasive methods to measure and quantify the process. Here we demonstrate that by using a novel optical interferometric technique, we can non-invasively measure several fundamental properties of neural networks from the sub-cellular to the cell population level. We applied this method to quantify network formation in human stem cell derived neurons and show for the first time, correlations between trends in the growth, transport, and spatial organization of such a system. Quantifying the fundamental behavior of such cell lines without compromising their viability may provide an important new tool in future longitudinal studies.

  3. Surviving cancer without compromising aspirations.

    PubMed

    McGregor, Sandra

    2011-07-01

    This short paper is a reflection of how one person coped, survived and grew following numerous metastatic incidences over a 20 year period. Surviving cancer is a complex process but coping with the threat of regular recurrence has required a coping strategy that embraced the disease, set it aside and refused to compromise hopes, dreams and future life. Central to this personal journey has been the need to redefine normality, live with and set aside the fear of future metastases and death and find an answer and meaning in a changing biology, increased morbidity and possible mortality. This paper contends that not compromising the direction of travel and being able to focus on a career has ensured that survival was valuable and valued. A working environment in which students' problems have been immediate has produced different stressors. These have ultimately forced personal worries to be set aside, while living with cancer has become normal and accepted. PMID:21514884

  4. The role of the clinical nurse specialist in tissue viability.

    PubMed

    Flanagan, M

    The development of tissue viability clinical nurse specialists in the UK has occurred rapidly and haphazardly over the last decade. Lack of role definition has created ambiguity and additional demands which are not so apparent within more established specialist nurse roles. Many specialist nurses in tissue viability are currently practising without adequate supervision frameworks which may compromise both personal and professional role satisfaction. Evaluation of the specific contribution of tissue viability specialist nurses is problematic for a variety of reasons. These, together with the identification of those factors thought to contribute to role conflict, will be discussed. PMID:8845674

  5. 48 CFR 432.616 - Compromise actions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Compromise actions. 432.616 Section 432.616 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Contract Debts 432.616 Compromise actions. Compromise of a...

  6. Forensic Analysis of Compromised Computers

    NASA Technical Reports Server (NTRS)

    Wolfe, Thomas

    2004-01-01

    Directory Tree Analysis File Generator is a Practical Extraction and Reporting Language (PERL) script that simplifies and automates the collection of information for forensic analysis of compromised computer systems. During such an analysis, it is sometimes necessary to collect and analyze information about files on a specific directory tree. Directory Tree Analysis File Generator collects information of this type (except information about directories) and writes it to a text file. In particular, the script asks the user for the root of the directory tree to be processed, the name of the output file, and the number of subtree levels to process. The script then processes the directory tree and puts out the aforementioned text file. The format of the text file is designed to enable the submission of the file as input to a spreadsheet program, wherein the forensic analysis is performed. The analysis usually consists of sorting files and examination of such characteristics of files as ownership, time of creation, and time of most recent access, all of which characteristics are among the data included in the text file.

  7. Integrity and compromise in nursing ethics.

    PubMed

    Winslow, B J; Winslow, G R

    1991-06-01

    Nurses are often caught in the middle of what appear to be intractable moral conflicts. For such times, the function and limits of moral compromise need to be explored. Compromise is compatible with moral integrity if a number of conditions are met. Among these are the sharing of a moral language, mutual respect on the part of those who differ, acknowledgement of factual and moral complexities, and recognition of limits to compromise. Nurses are in a position uniquely suited to leadership in fostering an environment that makes compromise with integrity possible. PMID:1880466

  8. Corticosteroids compromise survival in glioblastoma.

    PubMed

    Pitter, Kenneth L; Tamagno, Ilaria; Alikhanyan, Kristina; Hosni-Ahmed, Amira; Pattwell, Siobhan S; Donnola, Shannon; Dai, Charles; Ozawa, Tatsuya; Chang, Maria; Chan, Timothy A; Beal, Kathryn; Bishop, Andrew J; Barker, Christopher A; Jones, Terreia S; Hentschel, Bettina; Gorlia, Thierry; Schlegel, Uwe; Stupp, Roger; Weller, Michael; Holland, Eric C; Hambardzumyan, Dolores

    2016-05-01

    Glioblastoma is the most common and most aggressive primary brain tumour. Standard of care consists of surgical resection followed by radiotherapy and concomitant and maintenance temozolomide (temozolomide/radiotherapy→temozolomide). Corticosteroids are commonly used perioperatively to control cerebral oedema and are frequently continued throughout subsequent treatment, notably radiotherapy, for amelioration of side effects. The effects of corticosteroids such as dexamethasone on cell growth in glioma models and on patient survival have remained controversial. We performed a retrospective analysis of glioblastoma patient cohorts to determine the prognostic role of steroid administration. A disease-relevant mouse model of glioblastoma was used to characterize the effects of dexamethasone on tumour cell proliferation and death, and to identify gene signatures associated with these effects. A murine anti-VEGFA antibody was used in parallel as an alternative for oedema control. We applied the dexamethasone-induced gene signature to The Cancer Genome Atlas glioblastoma dataset to explore the association of dexamethasone exposure with outcome. Mouse experiments were used to validate the effects of dexamethasone on survival in vivo Retrospective clinical analyses identified corticosteroid use during radiotherapy as an independent indicator of shorter survival in three independent patient cohorts. A dexamethasone-associated gene expression signature correlated with shorter survival in The Cancer Genome Atlas patient dataset. In glioma-bearing mice, dexamethasone pretreatment decreased tumour cell proliferation without affecting tumour cell viability, but reduced survival when combined with radiotherapy. Conversely, anti-VEGFA antibody decreased proliferation and increased tumour cell death, but did not affect survival when combined with radiotherapy. Clinical and mouse experimental data suggest that corticosteroids may decrease the effectiveness of treatment and shorten

  9. 49 CFR 1503.425 - Compromise orders.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 9 2014-10-01 2014-10-01 false Compromise orders. 1503.425 Section 1503.425... Assessment of Civil Penalties by TSA § 1503.425 Compromise orders. (a) Issuance. At any time before the issuance of an Order Assessing Civil Penalty under this subpart, an agency attorney and a person subject...

  10. 49 CFR 1503.425 - Compromise orders.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 9 2011-10-01 2011-10-01 false Compromise orders. 1503.425 Section 1503.425... Assessment of Civil Penalties by TSA § 1503.425 Compromise orders. (a) Issuance. At any time before the issuance of an Order Assessing Civil Penalty under this subpart, an agency attorney and a person subject...

  11. 48 CFR 32.610 - Compromising debts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... REQUIREMENTS CONTRACT FINANCING Contract Debts 32.610 Compromising debts. For debts under $100,000, excluding interest, the designated agency official may compromise the debt pursuant to the Federal Claims Collection Standards (31 CFR part 902) and agency regulations. Unless specifically authorized by agency...

  12. 48 CFR 1432.610 - Compromising debts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Compromising debts. 1432.610 Section 1432.610 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Contract Debts 1432.610 Compromising debts. The CO may...

  13. 26 CFR 301.7122-1 - Compromises.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Secretary may, at the Secretary's discretion, compromise any civil or criminal liability arising under the internal revenue laws prior to reference of a case involving such a liability to the Department of Justice for prosecution or defense. (2) An agreement to compromise may relate to a civil or criminal...

  14. Enhancing Osteochondral Allograft Viability: Effects of Storage Media Composition

    PubMed Central

    Teng, Margie S.; Yuen, Audrey S.

    2008-01-01

    Osteochondral allograft transplantation is a well-accepted treatment for articular cartilage damage. However, chondrocyte viability declines during graft storage, which may compromise graft performance. We first tested the hypothesis that the composition of commonly used storage media affects the viability of articular chondrocytes over time; we then tested the hypothesis that the addition of insulin growth factor-1 or the apoptosis inhibitor ZVAD-fmk could enhance the storage properties of serum-free media. Bovine osteochondral grafts were stored at 4°C in lactated Ringer’s, Dulbecco’s modified eagle’s media (DMEM), DMEM supplemented with either insulin growth factor-1 or ZVAD-fmk, and a commercial storage media. Chondrocyte viability in lactated Ringer’s declined rapidly to 20.4% at 2 weeks. Viability in DMEM declined more slowly to 54.8% at 2 weeks and 31.2% at 3 weeks. Viability in commercial storage media was 83.6% at 3 weeks and 44.8% at 4 weeks. Viability was increased in DMEM + insulin growth factor-1 (56.4%) and DMEM + ZVAD (52.4%) at 3 weeks compared with DMEM alone. These results confirm the hypotheses that media composition greatly influences chondrocyte viability during cold storage and that insulin growth factor-1 and ZVAD improve the storage properties of DMEM. PMID:18506560

  15. Enhancing osteochondral allograft viability: effects of storage media composition.

    PubMed

    Teng, Margie S; Yuen, Audrey S; Kim, Hubert T

    2008-08-01

    Osteochondral allograft transplantation is a well-accepted treatment for articular cartilage damage. However, chondrocyte viability declines during graft storage, which may compromise graft performance. We first tested the hypothesis that the composition of commonly used storage media affects the viability of articular chondrocytes over time; we then tested the hypothesis that the addition of insulin growth factor-1 or the apoptosis inhibitor ZVAD-fmk could enhance the storage properties of serum-free media. Bovine osteochondral grafts were stored at 4 degrees C in lactated Ringer's, Dulbecco's modified eagle's media (DMEM), DMEM supplemented with either insulin growth factor-1 or ZVAD-fmk, and a commercial storage media. Chondrocyte viability in lactated Ringer's declined rapidly to 20.4% at 2 weeks. Viability in DMEM declined more slowly to 54.8% at 2 weeks and 31.2% at 3 weeks. Viability in commercial storage media was 83.6% at 3 weeks and 44.8% at 4 weeks. Viability was increased in DMEM + insulin growth factor-1 (56.4%) and DMEM + ZVAD (52.4%) at 3 weeks compared with DMEM alone. These results confirm the hypotheses that media composition greatly influences chondrocyte viability during cold storage and that insulin growth factor-1 and ZVAD improve the storage properties of DMEM. PMID:18506560

  16. Improved two-photon imaging of living neurons in brain tissue through temporal gating

    PubMed Central

    Gautam, Vini; Drury, Jack; Choy, Julian M. C.; Stricker, Christian; Bachor, Hans-A.; Daria, Vincent R.

    2015-01-01

    We optimize two-photon imaging of living neurons in brain tissue by temporally gating an incident laser to reduce the photon flux while optimizing the maximum fluorescence signal from the acquired images. Temporal gating produces a bunch of ~10 femtosecond pulses and the fluorescence signal is improved by increasing the bunch-pulse energy. Gating is achieved using an acousto-optic modulator with a variable gating frequency determined as integral multiples of the imaging sampling frequency. We hypothesize that reducing the photon flux minimizes the photo-damage to the cells. Our results, however, show that despite producing a high fluorescence signal, cell viability is compromised when the gating and sampling frequencies are equal (or effectively one bunch-pulse per pixel). We found an optimum gating frequency range that maintains the viability of the cells while preserving a pre-set fluorescence signal of the acquired two-photon images. The neurons are imaged while under whole-cell patch, and the cell viability is monitored as a change in the membrane’s input resistance. PMID:26504651

  17. Improved two-photon imaging of living neurons in brain tissue through temporal gating.

    PubMed

    Gautam, Vini; Drury, Jack; Choy, Julian M C; Stricker, Christian; Bachor, Hans-A; Daria, Vincent R

    2015-10-01

    We optimize two-photon imaging of living neurons in brain tissue by temporally gating an incident laser to reduce the photon flux while optimizing the maximum fluorescence signal from the acquired images. Temporal gating produces a bunch of ~10 femtosecond pulses and the fluorescence signal is improved by increasing the bunch-pulse energy. Gating is achieved using an acousto-optic modulator with a variable gating frequency determined as integral multiples of the imaging sampling frequency. We hypothesize that reducing the photon flux minimizes the photo-damage to the cells. Our results, however, show that despite producing a high fluorescence signal, cell viability is compromised when the gating and sampling frequencies are equal (or effectively one bunch-pulse per pixel). We found an optimum gating frequency range that maintains the viability of the cells while preserving a pre-set fluorescence signal of the acquired two-photon images. The neurons are imaged while under whole-cell patch, and the cell viability is monitored as a change in the membrane's input resistance. PMID:26504651

  18. Assessment of myocardial viability.

    PubMed

    Travin, Mark I; Bergmann, Steven R

    2005-01-01

    The prevalence of left ventricular (LV) dysfunction and resultant congestive heart failure is increasing. Patients with this condition are at high risk for cardiac death and usually have significant limitations in their lifestyles. Although there have been advances in medical therapy resulting in improved survival and well being, the best and most definitive therapy, when appropriate, is revascularization. In the setting of coronary artery disease, accounting for approximately two thirds of cases of congestive heart failure, LV dysfunction often is not the result of irreversible scar but rather caused by impairment in function and energy use of still viable-myocytes, with the opportunity for improved function if coronary blood flow is restored. Patients with LV dysfunction who have viable myocardium are the patients at highest risk because of the potential for ischemia but at the same time benefit most from revascularization. It is important to identify viable myocardium in these patients, and radionuclide myocardial scintigraphy is an excellent tool for this. Single-photon emission computed tomography perfusion scintigraphy, whether using thallium-201, Tc-99m sestamibi, or Tc-99m tetrofosmin, in stress and/or rest protocols, has consistently been shown to be an effective modality for identifying myocardial viability and guiding appropriate management. Metabolic imaging with positron emission tomography radiotracers frequently adds additional information and is a powerful tool for predicting which patients will have an improved outcome from revascularization, including some patients referred instead for cardiac transplantation. Other noninvasive modalities, such as stress echocardiography, also facilitate the assessment of myocardial viability, but there are advantages and disadvantages compared with the nuclear techniques. Nuclear imaging appears to require fewer viable cells for detection, resulting in a higher sensitivity but a lower specificity than stress

  19. 39 CFR 931.1 - Compromise of obligations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Compromise of obligations. 931.1 Section 931.1 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PROCEDURE GOVERNING THE COMPROMISE OF OBLIGATIONS § 931.1 Compromise of obligations. Any proposition of compromise shall be submitted in writing, and the amount offered in compromise...

  20. Vascular Compromise from Soft Tissue Augmentation

    PubMed Central

    Humphrey, Shannon; Carruthers, Jean D.A.; Carruthers, Alastair

    2014-01-01

    The popularity of soft tissue fillers is, in part, due to their favorable side-effect profile. However, serious complications can occur. The authors describe their extensive clinical experience with soft-tissue augmentation and the rare complication of vascular compromise, which can lead to necrosis and scarring. Over a 10-year period between January 2003 and January 2013, the authors observed a total of 12 cases of vascular compromise. Eight patients in their clinical practice showed evidence of vascular compromise out of a total of 14,355 filler injections (0.05%). In addition, four patients treated with an experimental particulate filler had vascular complications. All cases were examined for filler type, location of complication, risk factors, treatment, and outcomes. Although treatment plans differed for each patient in their series, all cases of vascular compromise resolved fully. The authors believe that an office-based protocol for both immediate and ongoing care—including a thorough individualized assessment and treatment plan for each patient—is critical to timely and effective resolution of side effects. They propose key recommendations for the prevention and management of vascular compromise to improve patient outcomes and reduce the risk of permanent complications. PMID:25276276

  1. Modeling the Dynamics of Compromised Networks

    SciTech Connect

    Soper, B; Merl, D M

    2011-09-12

    Accurate predictive models of compromised networks would contribute greatly to improving the effectiveness and efficiency of the detection and control of network attacks. Compartmental epidemiological models have been applied to modeling attack vectors such as viruses and worms. We extend the application of these models to capture a wider class of dynamics applicable to cyber security. By making basic assumptions regarding network topology we use multi-group epidemiological models and reaction rate kinetics to model the stochastic evolution of a compromised network. The Gillespie Algorithm is used to run simulations under a worst case scenario in which the intruder follows the basic connection rates of network traffic as a method of obfuscation.

  2. Viability of Baylisascaris procyonis Eggs.

    PubMed

    Shafir, Shira C; Sorvillo, Frank J; Sorvillo, Teresa; Eberhard, Mark L

    2011-07-01

    Infection with Baylisascaris procyonis roundworms is rare but often fatal and typically affects children. We attempted to determine parameters of viability and methods of inactivating the eggs of these roundworms. Loss of viability resulted when eggs were heated to 62°C or desiccated for 7 months but not when frozen at -15°C for 6 months. PMID:21762591

  3. Viability of Baylisascaris procyonis Eggs

    PubMed Central

    Sorvillo, Frank J.; Sorvillo, Teresa; Eberhard, Mark L.

    2011-01-01

    Infection with Baylisascaris procyonis roundworms is rare but often fatal and typically affects children. We attempted to determine parameters of viability and methods of inactivating the eggs of these roundworms. Loss of viability resulted when eggs were heated to 62°C or desiccated for 7 months but not when frozen at –15°C for 6 months. PMID:21762591

  4. Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line

    SciTech Connect

    Blusztajn, J.K.; Liscovitch, M.; Richardson, U.I.

    1987-08-01

    Cholinergic neurons are unique among cells since they alone utilize choline not only as a component of major membrane phospholipids, such as phosphatidylcholine (Ptd-Cho), but also as a precursor of their neurotransmitter acetylcholine (AcCho). It has been hypothesized that choline-phospholipids might serve as a storage pool of choline for AcCho synthesis. The selective vulnerability of cholinergic neurons in certain neurodegenerative diseases (e.g., Alzheimer disease, motor neuron disorders) might result from the abnormally accelerated liberation of choline (to be used a precursor of AcCho) from membrane phospholipids, resulting in altered membrane composition and function and compromised neuronal viability. However, the proposed metabolic link between membrane turnover and AcCho synthesis has been difficult to demonstrate because of the heterogeneity of the preparations used. Here the authors used a population of purely cholinergic cells (human neuroblastomas, LA-N-2), incubated in the presence of (methyl-/sup 3/H)methionine to selectively label PtdCho synthesized by methylation of phosphatidylethanolamine, the only pathway of de novo choline synthesis. Three peaks of radioactive material that cochromatographed with authentic AcCho, choline, and phosphocholine were observed when the water-soluble metabolites of the (/sup 3/H)PtdCho were purified by high-performance liquid chromatography. The results demonstrate that AcCho can be synthesized from choline derived from the degradation of endogenous PtdCho formed de novo by methylation of phosphatidylethanolamine.

  5. 48 CFR 232.616 - Compromise actions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Compromise actions. 232.616 Section 232.616 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... actions. Only the department/agency contract financing offices (see 232.070(c)) are authorized...

  6. An Unstructured Workshop as a Training Compromise.

    ERIC Educational Resources Information Center

    Moore, R. J.

    1978-01-01

    Because of its poor labor relations and consequent public image, New Zealand's meat industry asked the University of Otago to provide management training. Describes difficulties in developing effective training acceptable to the industry, the compromise workshop approach involving questionnaires and diaries, and the workshop's qualified success.…

  7. 49 CFR 1503.425 - Compromise orders.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 9 2012-10-01 2012-10-01 false Compromise orders. 1503.425 Section 1503.425 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY ADMINISTRATIVE AND PROCEDURAL RULES INVESTIGATIVE AND ENFORCEMENT PROCEDURES Assessment of Civil Penalties...

  8. 49 CFR 1503.425 - Compromise orders.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Compromise orders. 1503.425 Section 1503.425 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY ADMINISTRATIVE AND PROCEDURAL RULES INVESTIGATIVE AND ENFORCEMENT PROCEDURES Assessment of Civil Penalties...

  9. Political Compromise Makes the World Go 'Round

    ERIC Educational Resources Information Center

    Everett, Diana

    2007-01-01

    Compromise in any context is often hard to accept. It feels like a person is giving up on his or her ideals. This is especially true in dealing with politics. Legislative and congressional bills can be written with the highest of ideals in mind. By the time the bill progresses through committees and the floor debate process, it can look like a…

  10. Vestibular Neuronitis

    MedlinePlus

    ... Prevent Painful Swimmer's Ear Additional Content Medical News Vestibular Neuronitis By Lawrence R. Lustig, MD NOTE: This ... Drugs Herpes Zoster Oticus Meniere Disease Purulent Labyrinthitis Vestibular Neuronitis Vestibular neuronitis is a disorder characterized by ...

  11. 38 CFR 1.931 - Bases for compromise.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Bases for compromise. 1.931 Section 1.931 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS GENERAL PROVISIONS Standards for Compromise of Claims § 1.931 Bases for compromise. (a) VA may compromise a debt if it cannot collect the full amount because:...

  12. 49 CFR 1018.51 - Reasons for compromising a claim.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... compromise in accordance with the guidelines in 4 CFR 103.4. (b) The Board shall determine the debtor's... compromise in accordance with the Federal Claims Collection Standards, 4 CFR part 103. (c) Compromises... 49 Transportation 8 2010-10-01 2010-10-01 false Reasons for compromising a claim. 1018.51...

  13. 40 CFR 13.25 - Standards for compromise.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Standards for compromise. 13.25 Section 13.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL CLAIMS COLLECTION STANDARDS Compromise of Debts § 13.25 Standards for compromise. (a) EPA may compromise a claim pursuant to this...

  14. 31 CFR 902.5 - Further review of compromise offers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Further review of compromise offers... COMPROMISE OF CLAIMS § 902.5 Further review of compromise offers. If an agency is uncertain whether to accept a firm, written, substantive compromise offer on a debt that is within the agency's...

  15. Gender Differences in the Readiness To Accept Career Compromise.

    ERIC Educational Resources Information Center

    Gati, Itamar

    Most career decisions involve compromises. The need to compromise can be attributed to the fact that the characteristics of the options in the occupational world do not necessarily match the ideal career image of the career decision maker. This study examined the readiness to compromise and the content of compromise in 1,252 deliberating women and…

  16. Live imaging of mitochondrial dynamics in CNS dopaminergic neurons in vivo demonstrates early reversal of mitochondrial transport following MPP(+) exposure.

    PubMed

    Dukes, April A; Bai, Qing; Van Laar, Victor S; Zhou, Yangzhong; Ilin, Vladimir; David, Christopher N; Agim, Zeynep S; Bonkowsky, Joshua L; Cannon, Jason R; Watkins, Simon C; Croix, Claudette M St; Burton, Edward A; Berman, Sarah B

    2016-11-01

    Extensive convergent evidence collectively suggests that mitochondrial dysfunction is central to the pathogenesis of Parkinson's disease (PD). Recently, changes in the dynamic properties of mitochondria have been increasingly implicated as a key proximate mechanism underlying neurodegeneration. However, studies have been limited by the lack of a model in which mitochondria can be imaged directly and dynamically in dopaminergic neurons of the intact vertebrate CNS. We generated transgenic zebrafish in which mitochondria of dopaminergic neurons are labeled with a fluorescent reporter, and optimized methods allowing direct intravital imaging of CNS dopaminergic axons and measurement of mitochondrial transport in vivo. The proportion of mitochondria undergoing axonal transport in dopaminergic neurons decreased overall during development between 2days post-fertilization (dpf) and 5dpf, at which point the major period of growth and synaptogenesis of the relevant axonal projections is complete. Exposure to 0.5-1.0mM MPP(+) between 4 and 5dpf did not compromise zebrafish viability or cause detectable changes in the number or morphology of dopaminergic neurons, motor function or monoaminergic neurochemistry. However, 0.5mM MPP(+) caused a 300% increase in retrograde mitochondrial transport and a 30% decrease in anterograde transport. In contrast, exposure to higher concentrations of MPP(+) caused an overall reduction in mitochondrial transport. This is the first time mitochondrial transport has been observed directly in CNS dopaminergic neurons of a living vertebrate and quantified in a PD model in vivo. Our findings are compatible with a model in which damage at presynaptic dopaminergic terminals causes an early compensatory increase in retrograde transport of compromised mitochondria for degradation in the cell body. These data are important because manipulation of early pathogenic mechanisms might be a valid therapeutic approach to PD. The novel transgenic lines and

  17. ESCRT-0 dysfunction compromises autophagic degradation of protein aggregates and facilitates ER stress-mediated neurodegeneration via apoptotic and necroptotic pathways

    PubMed Central

    Oshima, Ryuji; Hasegawa, Takafumi; Tamai, Keiichi; Sugeno, Naoto; Yoshida, Shun; Kobayashi, Junpei; Kikuchi, Akio; Baba, Toru; Futatsugi, Akira; Sato, Ikuro; Satoh, Kennichi; Takeda, Atsushi; Aoki, Masashi; Tanaka, Nobuyuki

    2016-01-01

    Endosomal sorting required for transport (ESCRT) complexes orchestrate endo-lysosomal sorting of ubiquitinated proteins, multivesicular body formation and autophagic degradation. Defects in the ESCRT pathway have been implicated in many neurodegenerative diseases, but the underlying molecular mechanisms that link them to neurodegeneration remain unknown. In this study, we showed that forebrain-specific ablation of ESCRT-0/Hrs induced marked hippocampal neuronal cell loss accompanied by the accumulation of ubiquitinated proteins, including α-synuclein, TDP-43 and huntingtin as well as the autophagic substrate SQSTM1/p62. Consistent with this, silencing of Hrs in cultured cells not only led to α-synuclein and TDP-43 accumulation in addition to impaired autophagic flux but also suppressed cell viability through the induction of ER stress followed by the activation of JNK and RIPK1, a key regulator of necroptosis. Moreover, necrostatin-1, a specific inhibitor of RIPK1, and pan-caspase inhibitors partially reduced the neurotoxicity in the Hrs-silenced cells. Altogether, these findings suggest that the disruption of ESCRT-0/Hrs in the nervous system compromises autophagic/lysosomal degradation of neurodegenerative disease-related proteins, which thereby triggers ER stress-mediated apoptotic and necroptotic cell death. PMID:27112194

  18. Trichobezoar Causing Airway Compromise during Esophagogastroduodenoscopy

    PubMed Central

    Kao, Erica Y.; Scalzitti, Nicholas J.; Dion, Gregory R.; Bowe, Sarah N.

    2015-01-01

    Objectives. (1) Report the case of a 5-year-old female with trichotillomania and trichophagia that suffered airway compromise during esophagogastroduodenoscopy for removal of a trichobezoar. (2) Provide management recommendations for an unusual foreign body causing extubation and partial airway obstruction. Methods. Case report of a rare situation of airway compromise caused by a trichobezoar. Results. A 5-year-old patient underwent endoscopic retrieval of a gastric trichobezoar (hairball) by the gastroenterology service under general endotracheal anesthesia in a sedation unit. During removal, the hairball, due to its large size, dislodged the endotracheal tube, effectively extubating the patient. The bezoar became lodged at the cricopharyngeus muscle. Attempts to remove the bezoar or reintubation were unsuccessful. The child was able to be mask ventilated while the otolaryngology service was called. Direct laryngoscopy revealed a hairball partially obstructing the view of the glottis from its position in the postcricoid area. The hairball, still entrapped in the snare from the esophagoscope, was grasped with Magill forceps and slowly extracted. The patient was then reintubated and the airway and esophagus were reevaluated. Conclusions. Trichobezoar is an uncommon cause of airway foreign body. Careful attention to airway management during these and similar foreign body extractions can prevent inadvertent extubations. PMID:26457086

  19. Trichobezoar Causing Airway Compromise during Esophagogastroduodenoscopy.

    PubMed

    Kao, Erica Y; Scalzitti, Nicholas J; Dion, Gregory R; Bowe, Sarah N

    2015-01-01

    Objectives. (1) Report the case of a 5-year-old female with trichotillomania and trichophagia that suffered airway compromise during esophagogastroduodenoscopy for removal of a trichobezoar. (2) Provide management recommendations for an unusual foreign body causing extubation and partial airway obstruction. Methods. Case report of a rare situation of airway compromise caused by a trichobezoar. Results. A 5-year-old patient underwent endoscopic retrieval of a gastric trichobezoar (hairball) by the gastroenterology service under general endotracheal anesthesia in a sedation unit. During removal, the hairball, due to its large size, dislodged the endotracheal tube, effectively extubating the patient. The bezoar became lodged at the cricopharyngeus muscle. Attempts to remove the bezoar or reintubation were unsuccessful. The child was able to be mask ventilated while the otolaryngology service was called. Direct laryngoscopy revealed a hairball partially obstructing the view of the glottis from its position in the postcricoid area. The hairball, still entrapped in the snare from the esophagoscope, was grasped with Magill forceps and slowly extracted. The patient was then reintubated and the airway and esophagus were reevaluated. Conclusions. Trichobezoar is an uncommon cause of airway foreign body. Careful attention to airway management during these and similar foreign body extractions can prevent inadvertent extubations. PMID:26457086

  20. Identifying genetic relatives without compromising privacy

    PubMed Central

    He, Dan; Furlotte, Nicholas A.; Hormozdiari, Farhad; Joo, Jong Wha J.; Wadia, Akshay; Ostrovsky, Rafail; Sahai, Amit; Eskin, Eleazar

    2014-01-01

    The development of high-throughput genomic technologies has impacted many areas of genetic research. While many applications of these technologies focus on the discovery of genes involved in disease from population samples, applications of genomic technologies to an individual’s genome or personal genomics have recently gained much interest. One such application is the identification of relatives from genetic data. In this application, genetic information from a set of individuals is collected in a database, and each pair of individuals is compared in order to identify genetic relatives. An inherent issue that arises in the identification of relatives is privacy. In this article, we propose a method for identifying genetic relatives without compromising privacy by taking advantage of novel cryptographic techniques customized for secure and private comparison of genetic information. We demonstrate the utility of these techniques by allowing a pair of individuals to discover whether or not they are related without compromising their genetic information or revealing it to a third party. The idea is that individuals only share enough special-purpose cryptographically protected information with each other to identify whether or not they are relatives, but not enough to expose any information about their genomes. We show in HapMap and 1000 Genomes data that our method can recover first- and second-order genetic relationships and, through simulations, show that our method can identify relationships as distant as third cousins while preserving privacy. PMID:24614977

  1. Novel Method for Neuronal Nanosurgical Connection

    PubMed Central

    Katchinskiy, Nir; Goez, Helly R.; Dutta, Indrani; Godbout, Roseline; Elezzabi, Abdulhakem Y.

    2016-01-01

    Neuronal injury may cause an irreversible damage to cellular, organ and organism function. While preventing neural injury is ideal, it is not always possible. There are multiple etiologies for neuronal injury including trauma, infection, inflammation, immune mediated disorders, toxins and hereditary conditions. We describe a novel laser application, utilizing femtosecond laser pulses, in order to connect neuronal axon to neuronal soma. We were able to maintain cellular viability, and demonstrate that this technique is universal as it is applicable to multiple cell types and media. PMID:26846892

  2. 31 CFR 902.2 - Bases for compromise.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Bases for compromise. 902.2 Section 902.2 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FEDERAL CLAIMS COLLECTION STANDARDS (DEPARTMENT OF THE TREASURY-DEPARTMENT OF JUSTICE) STANDARDS FOR THE COMPROMISE OF CLAIMS § 902.2 Bases for compromise....

  3. 49 CFR 89.13 - Documentary evidence of compromise.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Documentary evidence of compromise. 89.13 Section 89.13 Transportation Office of the Secretary of Transportation IMPLEMENTATION OF THE FEDERAL CLAIMS COLLECTION ACT General § 89.13 Documentary evidence of compromise. A compromise of any claim is not final...

  4. 49 CFR 89.13 - Documentary evidence of compromise.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false Documentary evidence of compromise. 89.13 Section 89.13 Transportation Office of the Secretary of Transportation IMPLEMENTATION OF THE FEDERAL CLAIMS COLLECTION ACT General § 89.13 Documentary evidence of compromise. A compromise of any claim is not final...

  5. 26 CFR 300.3 - Offer to compromise fee.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Offer to compromise fee. 300.3 Section 300.3... ADMINISTRATION USER FEES § 300.3 Offer to compromise fee. (a) Applicability. This section applies to the... provided in this section, this fee applies to all offers to compromise accepted for processing. (b) Fee....

  6. 20 CFR 340.13 - Compromise of amounts recoverable.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... INSURANCE ACT RECOVERY OF BENEFITS § 340.13 Compromise of amounts recoverable. The Board or its designee may compromise an amount recoverable, provided such amount does not exceed $100,000, excluding interest, or such... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Compromise of amounts recoverable....

  7. 5 CFR 185.146 - Compromise or settlement.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Compromise or settlement. 185.146 Section 185.146 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PROGRAM FRAUD CIVIL REMEDIES § 185.146 Compromise or settlement. (a) Parties may make offers of compromise...

  8. 49 CFR 1018.71 - Referral of a compromise offer.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false Referral of a compromise offer. 1018.71 Section... § 1018.71 Referral of a compromise offer. The Board may refer a debtor's firm written offer of compromise which is substantial in amount to GAO or to DOJ if the Board is uncertain whether the offer should...

  9. 27 CFR 70.436 - Offers in compromise.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Offers in compromise. 70.436 Section 70.436 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Cigarette Papers and Tubes § 70.436 Offers in compromise. Procedure in the case of offers in compromise...

  10. 27 CFR 70.415 - Offers in compromise.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Offers in compromise. 70.415 Section 70.415 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Beer § 70.415 Offers in compromise. Procedure in the case of offers in compromise of liabilities...

  11. 49 CFR 89.13 - Documentary evidence of compromise.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Documentary evidence of compromise. 89.13 Section 89.13 Transportation Office of the Secretary of Transportation IMPLEMENTATION OF THE FEDERAL CLAIMS COLLECTION ACT General § 89.13 Documentary evidence of compromise. A compromise of any claim is not final...

  12. 49 CFR 89.13 - Documentary evidence of compromise.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Documentary evidence of compromise. 89.13 Section 89.13 Transportation Office of the Secretary of Transportation IMPLEMENTATION OF THE FEDERAL CLAIMS COLLECTION ACT General § 89.13 Documentary evidence of compromise. A compromise of any claim is not final...

  13. 49 CFR 89.13 - Documentary evidence of compromise.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Documentary evidence of compromise. 89.13 Section 89.13 Transportation Office of the Secretary of Transportation IMPLEMENTATION OF THE FEDERAL CLAIMS COLLECTION ACT General § 89.13 Documentary evidence of compromise. A compromise of any claim is not final...

  14. Enhancement of cell viability after treatment with polyunsaturated fatty acids.

    PubMed

    Bartl, J; Walitza, S; Grünblatt, E

    2014-01-24

    Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent in children and adolescents and both environmental and genetic factors play major roles. Polyunsaturated fatty acids (PUFAs) are postulated to contribute to the development of the infant brain and an imbalance in these may increase the risk of ADHD. In recent clinical studies, supplementation with PUFAs improved symptoms of ADHD in some cases. Similarly, some beneficial effects were observed with PUFA treatment in neuronal cell cultures. Therefore, in this study, we hypothesized that a specific PUFA combination (available on the market as Equazen™ [Vifor Pharma, Switzerland]) along with iron, zinc, or vitamin B5 (vitB5) would produce an additive beneficial effect on the viability of rat pheochromocytoma-12 dopaminergic cells. The specific PUFA combination alone, as well as added to each of the three nutrients, was tested in a dose-response manner. The specific PUFAs significantly improved cell viability, starting at very low doses (100pM) from 60h up to 90h; while the combined treatment with vitB5 and minerals did not provide additional benefit. Our results confirmed the beneficial effect of the specific PUFAs on neuronal cell viability; although supplementation with minerals and vitB5 did not enhance this effect. PMID:24269370

  15. Institutional Commitments, Individual Compromises: Identity-Related Responses to Compromise in an Australian University

    ERIC Educational Resources Information Center

    Churchman, Deborah

    2006-01-01

    This study explores compromises by individual academic staff, which reflect their multiple understandings of academic work. I offer a brief overview of the changing Australian tertiary sector environment and the ways in which this has had an impact on the academic role. The discussion centres around the need for investigations of academia to be…

  16. Morgellons: contested illness, diagnostic compromise and medicalisation.

    PubMed

    Fair, Brian

    2010-05-01

    The case of Morgellons illustrates how the emergence of a new medically contested illness intersected with and impacted on the diagnostic processes of an existing uncontested psychiatric condition, Delusional Parasitosis (DP). More specifically, the sociopolitical processes at play in the contested illness, Morgellons, dubiously reflect patient empowerment, as well the resilience and power of medical jurisdiction. This research offers insights into the contested illness and medicalisation literatures, and aims to bridge these two approaches towards the relationship between patient empowerment and medical authority, which I do through the notion of doctor-patient compromise. The data for this research come from a comprehensive qualitative analysis of Morgellons discourse through four key sources: the pro-Morgellons website Morgellons.org; the anti-Morgellons website Morgellonswatch.com; the popular media's portrayal of Morgellons; and the DP and Morgellons articles published in peer-reviewed medical journals, as made available on PubMed. PMID:20149149

  17. Influence of political opposition and compromise on conservation outcomes in the Tongass National Forest, Alaska.

    PubMed

    Beier, Colin M

    2008-12-01

    To understand how a highly contentious policy process influenced a major conservation effort, I examined the origins, compromises, and outcomes of the Alaska National Interest Lands Conservation Act of 1980 (ANILCA) for the Tongass National Forest. Tongass wilderness designation was among the most controversial issues in the ANILCA debate, and it faced strong opposition from influential lawmakers, land managers, and Alaska residents. To investigate the influence of this opposition on Tongass conservation outcomes, I conducted a gap analysis of Tongass reserves and a policy analysis of the ANILCA debate and traced the influence of specific interests through the amendments, negotiations, and resulting compromises needed to enact ANILCA. Overall, I found that Tongass reserves comprise a broadly representative cross-section of ecosystems and species habitats in southeastern Alaska. Redrawn reserve boundaries, industry subsidies, and special access regulations reflected compromises to minimize the impact of wilderness conservation on mining, timber, and local stakeholder interests, respectively. Fragmentation of the Admiralty Island National Monument-the most ecologically valuable and politically controversial reserve-resulted from compromises with Alaskan Native (indigenous peoples of Alaska) corporations and timber interests. Despite language to accommodate "reasonable access" to wilderness reserves, ongoing access limitations highlight the concerns of Alaska residents that opposed ANILCA several decades ago. More broadly, the Tongass case suggests that early and ambitious conservation action may offset strong political opposition; compromises needed to establish key reserves often exacerbate development impacts in unprotected areas; and efforts to minimize social conflicts are needed to safeguard the long-term viability of conservation measures. PMID:18847443

  18. Birth, meaningful viability and abortion.

    PubMed

    Jensen, David

    2015-06-01

    What role does birth play in the debate about elective abortion? Does the wrongness of infanticide imply the wrongness of late-term abortion? In this paper, I argue that the same or similar factors that make birth morally significant with regard to abortion make meaningful viability morally significant due to the relatively arbitrary time of birth. I do this by considering the positions of Mary Anne Warren and José Luis Bermúdez who argue that birth is significant enough that the wrongness of infanticide does not imply the wrongness of late-term abortion. On the basis of the relatively arbitrary timing of birth, I argue that meaningful viability is the point at which elective abortion is prima facie morally wrong. PMID:25012846

  19. In vitro electrochemical corrosion and cell viability studies on nickel-free stainless steel orthopedic implants.

    PubMed

    Salahinejad, Erfan; Hadianfard, Mohammad Jafar; Macdonald, Digby Donald; Sharifi-Asl, Samin; Mozafari, Masoud; Walker, Kenneth J; Rad, Armin Tahmasbi; Madihally, Sundararajan V; Tayebi, Lobat

    2013-01-01

    The corrosion and cell viability behaviors of nanostructured, nickel-free stainless steel implants were studied and compared with AISI 316L. The electrochemical studies were conducted by potentiodynamic polarization and electrochemical impedance spectroscopic measurements in a simulated body fluid. Cytocompatibility was also evaluated by the adhesion behavior of adult human stem cells on the surface of the samples. According to the results, the electrochemical behavior is affected by a compromise among the specimen's structural characteristics, comprising composition, density, and grain size. The cell viability is interpreted by considering the results of the electrochemical impedance spectroscopic experiments. PMID:23630603

  20. In Vitro Electrochemical Corrosion and Cell Viability Studies on Nickel-Free Stainless Steel Orthopedic Implants

    PubMed Central

    Salahinejad, Erfan; Hadianfard, Mohammad Jafar; Macdonald, Digby Donald; Sharifi-Asl, Samin; Mozafari, Masoud; Walker, Kenneth J.; Rad, Armin Tahmasbi; Madihally, Sundararajan V.; Tayebi, Lobat

    2013-01-01

    The corrosion and cell viability behaviors of nanostructured, nickel-free stainless steel implants were studied and compared with AISI 316L. The electrochemical studies were conducted by potentiodynamic polarization and electrochemical impedance spectroscopic measurements in a simulated body fluid. Cytocompatibility was also evaluated by the adhesion behavior of adult human stem cells on the surface of the samples. According to the results, the electrochemical behavior is affected by a compromise among the specimen's structural characteristics, comprising composition, density, and grain size. The cell viability is interpreted by considering the results of the electrochemical impedance spectroscopic experiments. PMID:23630603

  1. Female genital alteration: a compromise solution.

    PubMed

    Arora, Kavita Shah; Jacobs, Allan J

    2016-03-01

    Despite 30 years of advocacy, the prevalence of non-therapeutic female genital alteration (FGA) in minors is stable in many countries. Educational efforts have minimally changed the prevalence of this procedure in regions where it has been widely practiced. In order to better protect female children from the serious and long-term harms of some types of non-therapeutic FGA, we must adopt a more nuanced position that acknowledges a wide spectrum of procedures that alter female genitalia. We offer a revised categorisation for non-therapeutic FGA that groups procedures by effect and not by process. Acceptance of de minimis procedures that generally do not carry long-term medical risks is culturally sensitive, does not discriminate on the basis of gender, and does not violate human rights. More morbid procedures should not be performed. However, accepting de minimis non-therapeutic f FGA procedures enhances the effort of compassionate practitioners searching for a compromise position that respects cultural differences but protects the health of their patients. PMID:26902479

  2. Deficiencies in mitochondrial DNA compromise the survival of yeast cells at critically high temperatures.

    PubMed

    Zubko, Elena I; Zubko, Mikhajlo K

    2014-01-01

    To address possible roles of mitochondrial genes in adaptation of eukaryotic cells to critical temperatures, we compared thermotolerance of mitochondrial rho mutants and wild type cells of six rho positive yeast species: Candida glabrata, Saccharomyces bayanus, Saccharomyces cerevisiae, Saccharomyces eubayanus, Saccharomyces paradoxus and Saccharomyces pastorianus. All rho mutants manifested compromised thermotolerance as a common phenotype. Analysis of viabilities at critical temperatures (32-45 °C) showed the reduction of maximum permissive temperatures (MPTs) in all rho mutants in comparison to their wild type counterparts. Degrees of the compromised thermotolerance depended on maximum permissive temperatures for wild type cells: the highest levels of MPT reductions for rho mutants took place in species and strains with highest MPTs for wild types. Short term exposures of S. cerevisiae cells (up to 3.5h) at non-permissive temperatures (45 °C and 50 °C) also lead to more rapid cell death of rho mutants as compared to wild type cells. We conclude that: (1) compromised thermotolerance could be a generic phenotypic property of rho mutants; (2) the enhanced thermotolerance of cells possessing mitochondrial genomes could be one of selective advantages in adaptation to environmental factors, in particular to enhanced temperatures. PMID:23890722

  3. Neuronal polarization.

    PubMed

    Takano, Tetsuya; Xu, Chundi; Funahashi, Yasuhiro; Namba, Takashi; Kaibuchi, Kozo

    2015-06-15

    Neurons are highly polarized cells with structurally and functionally distinct processes called axons and dendrites. This polarization underlies the directional flow of information in the central nervous system, so the establishment and maintenance of neuronal polarization is crucial for correct development and function. Great progress in our understanding of how neurons establish their polarity has been made through the use of cultured hippocampal neurons, while recent technological advances have enabled in vivo analysis of axon specification and elongation. This short review and accompanying poster highlight recent advances in this fascinating field, with an emphasis on the signaling mechanisms underlying axon and dendrite specification in vitro and in vivo. PMID:26081570

  4. Economic viability of biogas technology

    SciTech Connect

    Agrawal, S.C.; Agrawal, S.; Khare, O.P.

    1983-12-01

    Biogas has emerged as a suitable technology for providing alternative and additional sources of energy, especially for rural areas of developing countries. Although the experience gained in China and India established its technological success, social scientists are still involved in the controversial issue of its economic viability. The available literature presents very contradictory situations, ranging between the two extreme poles of high economic viability and nonviability. Such contradictory conclusions are derived since economic benefits from the technology are influenced by a number of factors. A review of the literature reveals that various factors are either not considered, or that the economics have been worked out assuming a very ideal situation, while biogas plants are operating under very different conditions. Using the coal replacement method even as coal is seldom used by villages is only a single example of this approach. In most of the developing countries, rural populations depend mainly on non-commercial fuels like firewood, dungcakes, agricultural wastes and leaves for cooking and heating purposes. Under the present technological limitations, biogas can most commonly be used for cooking and lighting. For testing the economic viability of biogas systems, a number of authors have considered the benefits in terms of savings in traditional fuels. But considering the actual thermal efficiency of different non-commercial fuel items, as well as biogas, it has still be be decided at what point of the market prices of fuel items that the biogas system becomes economically viable and remains viable. The present paper thus reviews different approaches adopted and suggested for working out the economics or the cost-benefit ratio of the biogas technology at the first stage, and then spells out the factors influencing the economic benefits of the technology under various situations, with the help of empirical

  5. Neurofilament dot blot assays: novel means of assessing axon viability in culture.

    PubMed

    Hares, Kelly; Kemp, Kevin; Gray, Elizabeth; Scolding, Neil; Wilkins, Alastair

    2011-06-15

    Axonal structure and integrity are vital to overall neuronal maintenance and action potential propagation. Neurofilaments (NFs) are one of the main cytoskeletal components of axons and phosphorylation of NF subunits regulates speed of NF transport through axons and determines optimal axonal calibre required for signal propagation. Many previous studies of neuroprotective agents have focussed on neuronal viability in models of neurodegenerative disease, without specifically considering axon function as an indicator of neuronal damage. In this study, we have focused on developing novel assays for determining axon viability by measuring levels of neurofilament phosphorylation in cultured cortical neurons. The nitric oxide donor DETANONOate (NO) was used as an inflammatory insult and glial cell line-derived neurotrophic factor (GDNF) and superoxide dismutase (SOD) were tested as potential axonal protective agents. Using 'dot blot' methodologies, we show a decrease in NF phosphorylation in cortical neurons exposed to NO-mediated cell toxicity and an attenuation of NO-mediated changes in NF phosphorylation associated with GDNF and SOD treatment. These results correlated well with immunocytochemical counts. We propose therefore that the dot blot assay is a novel method for assessing axonal integrity in vitro and may play a useful role in the future for testing the effects of agents on axonal viability, providing a reliable and reproducible screening method for potential therapeutics for neurodegenerative diseases. PMID:21459112

  6. Neuronal arithmetic

    PubMed Central

    Silver, R. Angus

    2016-01-01

    The vast computational power of the brain has traditionally been viewed as arising from the complex connectivity of neural networks, in which an individual neuron acts as a simple linear summation and thresholding device. However, recent studies show that individual neurons utilize a wealth of nonlinear mechanisms to transform synaptic input into output firing. These mechanisms can arise from synaptic plasticity, synaptic noise, and somatic and dendritic conductances. This tool kit of nonlinear mechanisms confers considerable computational power on both morphologically simple and more complex neurons, enabling them to perform a range of arithmetic operations on signals encoded in a variety of different ways. PMID:20531421

  7. 49 CFR 209.109 - Payment of penalty; compromise.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Payment of penalty; compromise. 209.109 Section... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY ENFORCEMENT PROCEDURES Hazardous Materials Penalties Civil Penalties § 209.109 Payment of penalty; compromise. (a) Payment of a civil penalty may be made...

  8. 49 CFR 209.109 - Payment of penalty; compromise.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Payment of penalty; compromise. 209.109 Section... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY ENFORCEMENT PROCEDURES Hazardous Materials Penalties Civil Penalties § 209.109 Payment of penalty; compromise. (a) Payment of a civil penalty may be made...

  9. 49 CFR 107.327 - Compromise and settlement.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Compromise and settlement. 107.327 Section 107.327 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... PROGRAM PROCEDURES Enforcement Compliance Orders and Civil Penalties § 107.327 Compromise and...

  10. 49 CFR 107.327 - Compromise and settlement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Compromise and settlement. 107.327 Section 107.327 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... PROGRAM PROCEDURES Enforcement Compliance Orders and Civil Penalties § 107.327 Compromise and...

  11. 5 CFR 1215.32 - Compromise, suspension and termination.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Compromise, suspension and termination. 1215.32 Section 1215.32 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD ORGANIZATION AND PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.32 Compromise, suspension and termination. (a)...

  12. 10 CFR 429.132 - Compromise and settlement.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Compromise and settlement. 429.132 Section 429.132 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION CERTIFICATION, COMPLIANCE, AND ENFORCEMENT FOR CONSUMER PRODUCTS AND COMMERCIAL AND INDUSTRIAL EQUIPMENT Enforcement § 429.132 Compromise and settlement. (a) DOE may...

  13. 10 CFR 429.132 - Compromise and settlement.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Compromise and settlement. 429.132 Section 429.132 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION CERTIFICATION, COMPLIANCE, AND ENFORCEMENT FOR CONSUMER PRODUCTS AND COMMERCIAL AND INDUSTRIAL EQUIPMENT Enforcement § 429.132 Compromise and settlement. (a) DOE may...

  14. 10 CFR 429.132 - Compromise and settlement.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Compromise and settlement. 429.132 Section 429.132 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION CERTIFICATION, COMPLIANCE, AND ENFORCEMENT FOR CONSUMER PRODUCTS AND COMMERCIAL AND INDUSTRIAL EQUIPMENT Enforcement § 429.132 Compromise and settlement. (a) DOE may...

  15. 38 CFR 1.970 - Standards for compromise.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Standards for compromise. 1.970 Section 1.970 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS GENERAL PROVISIONS Referrals to Gao, Department of Justice, Or Irs § 1.970 Standards for compromise. Decisions of...

  16. 38 CFR 1.970 - Standards for compromise.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Standards for compromise. 1.970 Section 1.970 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS GENERAL PROVISIONS Referrals to Gao, Department of Justice, Or Irs § 1.970 Standards for compromise. Decisions of...

  17. 48 CFR 252.239-7000 - Protection against compromising emanations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Protection against... CLAUSES Text of Provisions And Clauses 252.239-7000 Protection against compromising emanations. As prescribed in 239.7103(a), use the following clause: Protection Against Compromising Emanations (JUN 2004)...

  18. 20 CFR 355.46 - Compromise or settlement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Compromise or settlement. 355.46 Section 355.46 Employees' Benefits RAILROAD RETIREMENT BOARD ADMINISTRATIVE REMEDIES FOR FRAUDULENT CLAIMS OR STATEMENTS REGULATIONS UNDER THE PROGRAM FRAUD CIVIL REMEDIES ACT OF 1986 § 355.46 Compromise or settlement. (a) Parties may make offers of...

  19. 5 CFR 1312.30 - Loss or possible compromise.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DOWNGRADING, DECLASSIFICATION AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION Control and Accountability of Classified Information § 1312.30 Loss or possible compromise. Any person who has knowledge of the loss or possible compromise of classified information shall immediately secure the material and then report...

  20. 27 CFR 70.449 - Offers in compromise.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Offers in compromise. 70.449 Section 70.449 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Cartridges, and Explosives § 70.449 Offers in compromise. The procedures in the case of offers in...

  1. 19 CFR 161.5 - Compromise of Government claims.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Compromise of Government claims. 161.5 Section 161... Government claims. (a) Offer. An offer made pursuant to section 617, Tariff Act of 1930, as amended (19 U.S.C. 1617), in compromise of a Government claim arising under the Customs laws and the terms upon which...

  2. The CCR4-NOT Complex Is Implicated in the Viability of Aneuploid Yeasts

    PubMed Central

    Tange, Yoshie; Kurabayashi, Atsushi; Goto, Bunshiro; Hoe, Kwang-Lae; Kim, Dong-Uk; Park, Han-Oh; Hayles, Jacqueline; Chikashige, Yuji; Tsutumi, Chihiro; Hiraoka, Yasushi; Yamao, Fumiaki; Nurse, Paul; Niwa, Osami

    2012-01-01

    To identify the genes required to sustain aneuploid viability, we screened a deletion library of non-essential genes in the fission yeast Schizosaccharomyces pombe, in which most types of aneuploidy are eventually lethal to the cell. Aneuploids remain viable for a period of time and can form colonies by reducing the extent of the aneuploidy. We hypothesized that a reduction in colony formation efficiency could be used to screen for gene deletions that compromise aneuploid viability. Deletion mutants were used to measure the effects on the viability of spores derived from triploid meiosis and from a chromosome instability mutant. We found that the CCR4-NOT complex, an evolutionarily conserved general regulator of mRNA turnover, and other related factors, including poly(A)-specific nuclease for mRNA decay, are involved in aneuploid viability. Defective mutations in CCR4-NOT complex components in the distantly related yeast Saccharomyces cerevisiae also affected the viability of spores produced from triploid cells, suggesting that this complex has a conserved role in aneuploids. In addition, our findings suggest that the genes required for homologous recombination repair are important for aneuploid viability. PMID:22737087

  3. Hippocampal function is compromised in an animal model of multiple sclerosis.

    PubMed

    Novkovic, T; Shchyglo, O; Gold, R; Manahan-Vaughan, D

    2015-11-19

    Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease that is characterized by demyelination and axonal damage in the nervous system. One obvious consequence is a cumulative loss of muscle control. However, cognitive dysfunction affects roughly half of MS sufferers, sometimes already early in the disease course. Although long-term (remote) memory is typically unaffected, the ability to form new declarative memories becomes compromised. A major structure for the encoding of new declarative memories is the hippocampus. Encoding is believed to be mediated by synaptic plasticity in the form of long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength. Here, in an animal model of MS we explored whether disease symptoms are accompanied by a loss of functional neuronal integrity, synaptic plasticity, or hippocampus-dependent learning ability. In mice that developed MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), passive properties of CA1 pyramidal neurons were unaffected, although the ability to fire action potentials became reduced in the late phase of EAE. LTP remained normal in the early phase of MOG35-55-induced EAE. However, in the late phase, LTP was impaired and LTP-related spatial memory was impaired. In contrast, LTD and hippocampus-dependent object recognition memory were unaffected. These data suggest that in an animal model of MS hippocampal function becomes compromised as the disease progresses. PMID:25795599

  4. Viability of telework at PROCEMPA.

    PubMed

    Fetzner, Maria Amelia de Mesquita

    2003-02-01

    At the end of the 20th century, telework appears as one of the modalities of flexible work, which is related to new organizational structures as well as to increasing use of technology. It revolutionizes the traditional ways of performing work. Its implementation creates a number of questions to be answered by the organizations and the individuals involved. This article presents a case study on the viability of implementing telework at Procempa (The Data Processing Company of the City of Porto Alegre). The case study analyzes the technical, organizational, psychological, legal, and labor union dimensions. As a result of this study, we can identify the organization's stage of readiness for telework, the conditions under which it would be implemented, and the specific issues of an implementation. PMID:12650560

  5. The effect of ultrasound-related stimuli on cell viability in microfluidic channels

    PubMed Central

    2013-01-01

    Background In ultrasonic micro-devices, contrast agent micro-bubbles are known to initiate cavitation and streaming local to cells, potentially compromising cell viability. Here we investigate the effects of US alone by omitting contrast agent and monitoring cell viability under moderate-to-extreme ultrasound-related stimuli. Results Suspended H9c2 cardiac myoblasts were exposed to ultrasonic fields within a glass micro-capillary and their viability monitored under different US-related stimuli. An optimal injection flow rate of 2.6 mL/h was identified in which, high viability was maintained (~95%) and no mechanical stress towards cells was evident. This flow rate also allowed sufficient exposure of cells to US in order to induce bioeffects (~5 sec), whilst providing economical sample collection and processing times. Although the transducer temperature increased from ambient 23°C to 54°C at the maximum experimental voltage (29 Vpp), computational fluid dynamic simulations and controls (absence of US) revealed that the cell medium temperature did not exceed 34°C in the pressure nodal plane. Cells exposed to US amplitudes ranging from 0–29 Vpp, at a fixed frequency sweep period (tsw = 0.05 sec), revealed that viability was minimally affected up to ~15 Vpp. There was a ~17% reduction in viability at 21 Vpp, corresponding to the onset of Rayleigh-like streaming and a ~60% reduction at 29 Vpp, corresponding to increased streaming velocity or the potential onset of cavitation. At a fixed amplitude (29 Vpp) but with varying frequency sweep period (tsw = 0.02-0.50 sec), cell viability remained relatively constant at tsw ≥ 0.08 sec, whilst viability reduced at tsw < 0.08 sec and minimum viability recorded at tsw = 0.05 sec. Conclusion The absence of CA has enabled us to investigate the effect of US alone on cell viability. Moderate-to-extreme US-related stimuli of cells have allowed us to discriminate between stimuli that maintain high viability and stimuli that

  6. Economic viability of anaerobic digestion

    SciTech Connect

    Wellinger, A.

    1996-01-01

    The industrial application of anaerobic digestion is a relatively new, yet proven waste treatment technology. Anaerobic digestion reduces and upgrades organic waste, and is a good way to control air pollution as it reduces methane and nitrous gas emissions. For environmental and energy considerations, anaerobic digestion is a nearly perfect waste treatment process. However, its economic viability is still in question. A number of parameters - type of waste (solid or liquid), digester system, facility size, product quality and end use, environmental requirements, cost of alternative treatments (including labor), and interest rates - define the investment and operating costs of an anaerobic digestion facility. Therefore, identical facilities that treat the same amount and type of waste may, depending on location, legislation, and end product characteristics, reveal radically different costs. A good approach for evaluating the economics of anaerobic digestion is to compare it to treatment techniques such as aeration or conventional sewage treatment (for industrial wastewater), or composting and incineration (for solid organic waste). For example, the cost (per ton of waste) of in-vessel composting with biofilters is somewhat higher than that of anaerobic digestion, but the investment costs 1 1/2 to 2 times more than either composting or anaerobic digestion. Two distinct advantages of anaerobic digestion are: (1) it requires less land than either composting or incinerating, which translates into lower costs and milder environmental and community impacts (especially in densely populated areas); and (2) it produces net energy, which can be used to operate the facility or sold to nearby industries.

  7. Metabolomic assessment of embryo viability.

    PubMed

    Uyar, Asli; Seli, Emre

    2014-03-01

    Preimplantation embryo metabolism demonstrates distinctive characteristics associated with the developmental potential of embryos. On this basis, metabolite content of culture media was hypothesized to reflect the implantation potential of individual embryos. This hypothesis was tested in consecutive studies reporting a significant association between culture media metabolites and embryo development or clinical pregnancy. The need for a noninvasive, reliable, and rapid embryo assessment strategy promoted metabolomics studies in vitro fertilization (IVF) in an effort to increase success rates of single embryo transfers. With the advance of analytical techniques and bioinformatics, commercial instruments were developed to predict embryo viability using spectroscopic analysis of surplus culture media. However, despite the initial promising results from proof-of-principal studies, recent randomized controlled trials using commercial instruments failed to show a consistent benefit in improving pregnancy rates when metabolomics is used as an adjunct to morphology. At present, the application of metabolomics technology in clinical IVF laboratory requires the elimination of factors underlying inconsistent findings, when possible, and development of reliable predictive models accounting for all possible sources of bias throughout the embryo selection process. PMID:24515909

  8. Graphene's Viability for Fusion Applications

    NASA Astrophysics Data System (ADS)

    Navarro, Marcos; Hall, Karla; Rojas, Richard; Santarius, John; Kulcinski, Gerald

    2015-11-01

    Graphene is a source of interest for multiple applications due to its unusual electronic and physical properties. As a coating material, it has reduced oxidation of the main substrate, though no effort has been reported of testing it under fusion conditions. A number of experimental studies have established that defect-free graphene is an excellent barrier material for gases. We explore its viability to maintain a significant pressure difference under ion irradiation. Deuterium is used as a projectile on graphene coated silicon over a range of 10-50 keV energies and various fluences. The vacancy yield (amount of damage) and natural resonance for graphene are found at around 1350 cm-1 and 1550 cm-1, respectively. Damage of each sample is quantified via Raman spectroscopy (RS) using the ratio of the intensities at these wavenumbers. Graphene is also tested here as a coating for some fusion components. Though tungsten is a very promising divertor and first wall candidate, after intense irradiation, it is prone to developing fuzz or grass structures, leading to a diminished lifetime. Graphene grown on tungsten is tested under reactor conditions with 30 keV He ions at several fluences, and the sputtering of both materials is studied via RS and Scanning Electron Microscopy. This work was supported by the Graduate Engineering Research Scholars and the TEAM-Science program at the University of Wisconsin-Madison.

  9. 15 CFR 904.106 - Compromise of civil penalty.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... be sent to Agency counsel at the address specified in the NOVA. (c) Neither the existence of the... which a NOVA becomes final. (d) NOAA will not compromise, modify, or remit a civil penalty assessed,...

  10. 15 CFR 904.106 - Compromise of civil penalty.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... be sent to Agency counsel at the address specified in the NOVA. (c) Neither the existence of the... which a NOVA becomes final. (d) NOAA will not compromise, modify, or remit a civil penalty assessed,...

  11. 15 CFR 904.106 - Compromise of civil penalty.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... be sent to Agency counsel at the address specified in the NOVA. (c) Neither the existence of the... which a NOVA becomes final. (d) NOAA will not compromise, modify, or remit a civil penalty assessed,...

  12. 15 CFR 904.106 - Compromise of civil penalty.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... be sent to Agency counsel at the address specified in the NOVA. (c) Neither the existence of the... which a NOVA becomes final. (d) NOAA will not compromise, modify, or remit a civil penalty assessed,...

  13. 15 CFR 904.106 - Compromise of civil penalty.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... be sent to Agency counsel at the address specified in the NOVA. (c) Neither the existence of the... which a NOVA becomes final. (d) NOAA will not compromise, modify, or remit a civil penalty assessed,...

  14. Arsenic promotes centrosome abnormalities and cell colony formation in p53 compromised human lung cells

    SciTech Connect

    Liao Weiting; Lin Pinpin; Cheng, T.-S.; Yu, H.-S.; Chang, Louis W.

    2007-12-01

    Epidemiological evidence indicated that residents, especially cigarette smokers, in arseniasis areas had significantly higher lung cancer risk than those living in non-arseniasis areas. Thus, an interaction between arsenic and cigarette smoking in lung carcinogenesis was suspected. p53 dysfunction or mutation in lung epithelial cells was frequently observed in cigarette smokers. Our present study was to explore the differential effects by arsenic on H1355 cells (human lung adenocarcinoma cell line with mutation in p53), BEAS-2B (immortalized lung epithelial cell with functional p53) and pifithrin-{alpha}-treated BEAS-2B cells (p53-inhibited cells). These cells were treated with different doses of sodium arsenite (0, 0.1, 1, 5 and 10 {mu}M) for 48 h. A greater reduction in cell viability was observed in the BEAS-2B cells vs. p53 compromised cells (H1355 or p53-inhibited BEAS-2B). Similar observation was also made on 7-day cell survival (growth) study. TUNEL analysis confirmed that there was indeed a significantly reduced arsenite-induced apoptosis found in p53-compromised cells. Centrosomal abnormality has been attributed to eventual chromosomal missegregation, aneuploidy and tumorigenesis. In our present study, reduced p21 and Gadd45a expressions and increased centrosomal abnormality (atopic and multiple centrosomes) were observed in both arsenite-treated H1355 and p53-inhibited BEAS-2B cells as compared with similarly treated BEAS-2B cells. Increased anchorage-independent growth (colony formation) of BEAS-2B cells co-treated with pifithrin-{alpha} and 5 {mu}M sodium arsenite was also observed in soft agar. Our present investigation demonstrated that arsenic would act specifically on p53 compromised cells (either with p53 dysfunction or inhibited) to induce centrosomal abnormality and colony formation. These findings provided strong evidence on the carcinogenic promotional role of arsenic, especially under the condition of p53 dysfunction.

  15. Experiments with the Viability of Chicken Eggs

    ERIC Educational Resources Information Center

    Garigliano, Leonard J.

    1975-01-01

    Presents the results of an experiment designed to test two hypotheses: (1) a delay of two weeks at room temperature will have no effect on the viability of fertile chicken eggs and (2) refrigeration will have no effect on the viability of fertile chicken eggs. Experimenters were the author and two ninth-grade students. (PEB)

  16. Assessing the Financial Viability of Academic Programmes

    ERIC Educational Resources Information Center

    Swift, Lynette

    2012-01-01

    This paper reviews and examines approaches to determining the financial viability of academic programmes as a critical component of assessing a programme's overall sustainability. Key to assessing the financial viability of a programme is understanding the teaching activities required to deliver the programme and the cost of those activities. A…

  17. Motor Neuron Diseases

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Motor Neuron Diseases Information Page Condensed from Motor Neuron Diseases ... and Information Publicaciones en Español What are Motor Neuron Diseases? The motor neuron diseases (MNDs) are a ...

  18. Motor Neuron Diseases

    MedlinePlus

    ... called upper motor neurons ) are transmitted to nerve cells in the brain stem and spinal cord (called lower motor neurons ) and from them to particular muscles. Upper motor neurons direct the lower motor neurons ...

  19. Hijacking microglial glutathione by inorganic arsenic impels bystander death of immature neurons through extracellular cystine/glutamate imbalance.

    PubMed

    Singh, Vikas; Gera, Ruchi; Kushwaha, Rajesh; Sharma, Anuj Kumar; Patnaik, Satyakam; Ghosh, Debabrata

    2016-01-01

    Arsenic-induced altered microglial activity leads to neuronal death, but the causative mechanism remains unclear. The present study showed, arsenic-exposed (10 μM) microglial (N9) culture supernatant induced bystander death of neuro-2a (N2a), which was further validated with primary microglia and immature neuronal cultures. Results indicated that arsenic-induced GSH synthesis by N9 unfavorably modified the extracellular milieu for N2a by lowering cystine and increasing glutamate concentration. Similar result was observed in N9-N2a co-culture. Co-exposure of arsenic and 250 μM glutamate, less than the level (265 μM) detected in arsenic-exposed N9 culture supernatant, compromised N2a viability which was rescued by cystine supplementation. Therefore, microglia executes bystander N2a death by competitive inhibition of system Xc(-) (xCT) through extracellular cystine/glutamate imbalance. We confirmed the role of xCT in mediating bystander N2a death by siRNA inhibition studies. Ex-vivo primary microglia culture supernatant from gestationally exposed mice measured to contain lower cystine and higher glutamate compared to control and N-acetyl cysteine co-treated group. Immunofluorescence staining of brain cryosections from treated group showed more dead immature neurons with no such effect on microglia. Collectively, we showed, in presence of arsenic microglia alters cystine/glutamate balance through xCT in extracellular milieu leading to bystander death of immature neurons. PMID:27477106

  20. Hijacking microglial glutathione by inorganic arsenic impels bystander death of immature neurons through extracellular cystine/glutamate imbalance

    PubMed Central

    Singh, Vikas; Gera, Ruchi; Kushwaha, Rajesh; Sharma, Anuj Kumar; Patnaik, Satyakam; Ghosh, Debabrata

    2016-01-01

    Arsenic-induced altered microglial activity leads to neuronal death, but the causative mechanism remains unclear. The present study showed, arsenic-exposed (10 μM) microglial (N9) culture supernatant induced bystander death of neuro-2a (N2a), which was further validated with primary microglia and immature neuronal cultures. Results indicated that arsenic-induced GSH synthesis by N9 unfavorably modified the extracellular milieu for N2a by lowering cystine and increasing glutamate concentration. Similar result was observed in N9-N2a co-culture. Co-exposure of arsenic and 250 μM glutamate, less than the level (265 μM) detected in arsenic-exposed N9 culture supernatant, compromised N2a viability which was rescued by cystine supplementation. Therefore, microglia executes bystander N2a death by competitive inhibition of system Xc- (xCT) through extracellular cystine/glutamate imbalance. We confirmed the role of xCT in mediating bystander N2a death by siRNA inhibition studies. Ex-vivo primary microglia culture supernatant from gestationally exposed mice measured to contain lower cystine and higher glutamate compared to control and N-acetyl cysteine co-treated group. Immunofluorescence staining of brain cryosections from treated group showed more dead immature neurons with no such effect on microglia. Collectively, we showed, in presence of arsenic microglia alters cystine/glutamate balance through xCT in extracellular milieu leading to bystander death of immature neurons. PMID:27477106

  1. Labeling of neuronal differentiation and neuron cells with biocompatible fluorescent nanodiamonds

    NASA Astrophysics Data System (ADS)

    Hsu, Tzu-Chia; Liu, Kuang-Kai; Chang, Huan-Cheng; Hwang, Eric; Chao, Jui-I.

    2014-05-01

    Nanodiamond is a promising carbon nanomaterial developed for biomedical applications. Here, we show fluorescent nanodiamond (FND) with the biocompatible properties that can be used for the labeling and tracking of neuronal differentiation and neuron cells derived from embryonal carcinoma stem (ECS) cells. The fluorescence intensities of FNDs were increased by treatment with FNDs in both the mouse P19 and human NT2/D1 ECS cells. FNDs were taken into ECS cells; however, FNDs did not alter the cellular morphology and growth ability. Moreover, FNDs did not change the protein expression of stem cell marker SSEA-1 of ECS cells. The neuronal differentiation of ECS cells could be induced by retinoic acid (RA). Interestingly, FNDs did not affect on the morphological alteration, cytotoxicity and apoptosis during the neuronal differentiation. Besides, FNDs did not alter the cell viability and the expression of neuron-specific marker β-III-tubulin in these differentiated neuron cells. The existence of FNDs in the neuron cells can be identified by confocal microscopy and flow cytometry. Together, FND is a biocompatible and readily detectable nanomaterial for the labeling and tracking of neuronal differentiation process and neuron cells from stem cells.

  2. Sloppiness in Spontaneously Active Neuronal Networks

    PubMed Central

    Panas, Dagmara; Amin, Hayder; Maccione, Alessandro; Muthmann, Oliver; van Rossum, Mark; Berdondini, Luca

    2015-01-01

    Various plasticity mechanisms, including experience-dependent, spontaneous, as well as homeostatic ones, continuously remodel neural circuits. Yet, despite fluctuations in the properties of single neurons and synapses, the behavior and function of neuronal assemblies are generally found to be very stable over time. This raises the important question of how plasticity is coordinated across the network. To address this, we investigated the stability of network activity in cultured rat hippocampal neurons recorded with high-density multielectrode arrays over several days. We used parametric models to characterize multineuron activity patterns and analyzed their sensitivity to changes. We found that the models exhibited sloppiness, a property where the model behavior is insensitive to changes in many parameter combinations, but very sensitive to a few. The activity of neurons with sloppy parameters showed faster and larger fluctuations than the activity of a small subset of neurons associated with sensitive parameters. Furthermore, parameter sensitivity was highly correlated with firing rates. Finally, we tested our observations from cell cultures on an in vivo recording from monkey visual cortex and we confirm that spontaneous cortical activity also shows hallmarks of sloppy behavior and firing rate dependence. Our findings suggest that a small subnetwork of highly active and stable neurons supports group stability, and that this endows neuronal networks with the flexibility to continuously remodel without compromising stability and function. PMID:26041916

  3. New perspectives on neuronal development via microfluidic environments

    PubMed Central

    Millet, Larry J.; Gillette, Martha U.

    2012-01-01

    Understanding the signals that guide neuronal development and direct formation of axons, dendrites, and synapses during wiring of the brain is a fundamental challenge of developmental neuroscience. Discovering how local signals shape developing neurons has been impeded by the inability of conventional culture methods to interrogate micro-environments of complex neuronal cytoarchitectures, where different sub-domains encounter distinct chemical, physical, and fluidic features. Micro-fabrication techniques are enabling the creation of micro-environments tailored to neuronal structures and sub-domains, with unprecedented access and control. The design, fabrication, and properties of microfluidic devices offer significant advantages for addressing unresolved issues of neuronal development. These high-resolution approaches are poised to contribute new insights into mechanisms for restoring neuronal function and connectivity compromised by injury, stress, and neurodegeneration. PMID:23031246

  4. Alchemy or Science? Compromising Archaeology in the Deep Sea

    NASA Astrophysics Data System (ADS)

    Adams, Jonathan

    2007-06-01

    In the torrid debate between archaeology and treasure hunting, compromise is often suggested as the pragmatic solution, especially for archaeology carried out either in deep water or beyond the constraints that commonly regulate such activities in territorial seas. Both the wisdom and the need for such compromise have even been advocated by some archaeologists, particularly in forums such as the internet and conferences. This paper argues that such a compromise is impossible, not in order to fuel confrontation but simply because of the nature of any academic discipline. We can define what archaeology is in terms of its aims, theories, methods and ethics, so combining it with an activity founded on opposing principles must transform it into something else. The way forward for archaeology in the deep sea does not lie in a contradictory realignment of archaeology’s goals but in collaborative research designed to mesh with emerging national and regional research and management plans.

  5. LIMITATIONS OF THE FLUORESCENT PROBE VIABILITY ASSAY

    EPA Science Inventory

    Cell viability commonly is determined flow cytometrically by the carboxyfluorescein diacetate (CFDA)/propidium iodide (PI) assay. FDA is taken up by the viable cell and converted via cytoplasmic esterase-catalyzed hydrolysis to carboxyfluorescein (CF). F fluorescence intensity is...

  6. Economic viability of access broadband multiservice networks

    NASA Astrophysics Data System (ADS)

    Castelli, Francesco; Dammicco, Giacinto; Mocci, Ugo

    1995-02-01

    In this paper the economic viability of alternative architectures for optical access networks providing broad band services to different subscriber classes in a metropolitan environment, is investigated by a specific tool, NEVE (Network Economic Viability Evaluator), developed for broad band multiservice network planning, service evolutionary scenarios assessment, evaluation of tariff strategies and other actions taken at stimulating the demand growth. As the viability target can be achieved in different ways, different studies can be carried out by NEVE. In the paper some of them are discussed, particularly the ones addressed: to evaluate the impact on viability of alternative service scenarios; to determine the critical mass of broad band subscribers and the critical joint service adoption cost; to evaluate cross subsidiary policies among different subscriber classes and services; to perform sensitivity analysis with respect to variations of demand parameters and tariffs.

  7. Mitochondrial viability in mouse and human postmortem brain

    PubMed Central

    Barksdale, Keri A.; Perez-Costas, Emma; Gandy, Johanna C.; Melendez-Ferro, Miguel; Roberts, Rosalinda C.; Bijur, Gautam N.

    2010-01-01

    Neuronal function in the brain requires energy in the form of ATP, and mitochondria are canonically associated with ATP production in neurons. The electrochemical gradient, which underlies the mitochondrial transmembrane potential (ΔΨmem), is harnessed for ATP generation. Here we show that ΔΨmem and ATP-production can be engaged in mitochondria isolated from human brains up to 8.5 h postmortem. Also, a time course of postmortem intervals from 0 to 24 h using mitochondria isolated from mouse cortex reveals that ΔΨmem in mitochondria can be reconstituted beyond 10 h postmortem. It was found that complex I of the mitochondrial electron transport chain was affected adversely with increasing postmortem intervals. Mitochondria isolated from postmortem mouse brains maintain the ability to produce ATP, but rates of production decreased with longer postmortem intervals. Furthermore, we show that postmortem brain mitochondria retain their ΔΨmem and ATP-production capacities following cryopreservation. Our finding that ΔΨmem and ATP-generating capacity can be reinitiated in brain mitochondria hours after death indicates that human postmortem brains can be an abundant source of viable mitochondria to study metabolic processes in health and disease. It is also possible to archive these mitochondria for future studies.—Barksdale, K. A., Perez-Costas, E., Gandy, J. C., Melendez-Ferro, M., Roberts, R. C., Bijur, G. N. Mitochondrial viability in mouse and human postmortem brain. PMID:20466876

  8. 26 CFR 601.203 - Offers in compromise.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... STATEMENT OF PROCEDURAL RULES Rulings and Other Specific Matters § 601.203 Offers in compromise. (a) General... Department of Justice for prosecution or defense. Certain functions of the Commissioner with respect to... prosecution are pending in the Office of the Chief Counsel, the Department of Justice, or in an office of...

  9. 49 CFR 209.109 - Payment of penalty; compromise.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Payment of penalty; compromise. 209.109 Section 209.109 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY ENFORCEMENT PROCEDURES Hazardous Materials Penalties Civil Penalties § 209.109 Payment...

  10. Implant surgery in healthy compromised patients-review of literature.

    PubMed

    Gheorghiu, I M; Stoian, I M

    2014-01-01

    Systemic diseases are of major importance in terms of prosthetic restorations supported by dental implants in healthy compromised patients. Each treatment stage from conception of the treatment plan to the long-term monitoring is under the necessity of the interdisciplinary approach to the underlying disease. PMID:25870664

  11. 47 CFR 1.1915 - Exploration of compromise.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Federal Claims Collection Standards (31 CFR part 902). The Commission will also consider a request... justification of the offer and addressing the bases for compromise at 31 CFR 902.2. Debtors will provide full... evaluate an offer, using the factors set forth in 31 CFR 902.2 and, as appropriate, refer the offer...

  12. Evil Searching: Compromise and Recompromise of Internet Hosts for Phishing

    NASA Astrophysics Data System (ADS)

    Moore, Tyler; Clayton, Richard

    Attackers compromise web servers in order to host fraudulent content, such as malware and phishing websites. While the techniques used to compromise websites are widely discussed and categorized, analysis of the methods used by attackers to identify targets has remained anecdotal. In this paper, we study the use of search engines to locate potentially vulnerable hosts. We present empirical evidence from the logs of websites used for phishing to demonstrate attackers’ widespread use of search terms which seek out susceptible web servers. We establish that at least 18% of website compromises are triggered by these searches. Many websites are repeatedly compromised whenever the root cause of the vulnerability is not addressed. We find that 19% of phishing websites are recompromised within six months, and the rate of recompromise is much higher if they have been identified through web search. By contrast, other public sources of information about phishing websites are not currently raising recompromise rates; we find that phishing websites placed onto a public blacklist are recompromised no more frequently than websites only known within closed communities.

  13. Time-to-Compromise Model for Cyber Risk Reduction Estimation

    SciTech Connect

    Miles A. McQueen; Wayne F. Boyer; Mark A. Flynn; George A. Beitel

    2005-09-01

    We propose a new model for estimating the time to compromise a system component that is visible to an attacker. The model provides an estimate of the expected value of the time-to-compromise as a function of known and visible vulnerabilities, and attacker skill level. The time-to-compromise random process model is a composite of three subprocesses associated with attacker actions aimed at the exploitation of vulnerabilities. In a case study, the model was used to aid in a risk reduction estimate between a baseline Supervisory Control and Data Acquisition (SCADA) system and the baseline system enhanced through a specific set of control system security remedial actions. For our case study, the total number of system vulnerabilities was reduced by 86% but the dominant attack path was through a component where the number of vulnerabilities was reduced by only 42% and the time-to-compromise of that component was increased by only 13% to 30% depending on attacker skill level.

  14. CONCENTRATED AMBIENT PARTICULATE STUDIES IN HEALTHY AND COMPROMISED RODENTS

    EPA Science Inventory


    CONCENTRATED AMBIENT PARTICULATE STUDIES IN HEALTHY AND COMPROMISED RODENTS. WP Watkinson1, LB Wichers2, JP Nolan1, DW Winsett1, UP Kodavanti1, MCJ Schladweiler1, LC Walsh1, ER Lappi1, D Terrell1, R Slade1, AD Ledbetter1, and DL Costa1. 1USEPA, ORD/NHEERL/ETD/PTB, RTP, NC, US...

  15. 40 CFR 27.46 - Compromise or settlement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Compromise or settlement. 27.46 Section 27.46 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROGRAM FRAUD CIVIL REMEDIES... at any time after the date on which the reviewing official is permitted to issue a complaint...

  16. 14 CFR 1261.414 - Compromise of claims.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the Claims Collection Litigation Report. See § 1261.417(e) or 4 CFR 105.2(b). Claims for which the... Department of Justice for litigation. The Comptroller General may exercise such compromise authority with... other debtors that resistance to payment is not likely to succeed. (f) Enforcement policy....

  17. 14 CFR 1261.414 - Compromise of claims.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the Claims Collection Litigation Report. See § 1261.417(e) or 4 CFR 105.2(b). Claims for which the... Department of Justice for litigation. The Comptroller General may exercise such compromise authority with... other debtors that resistance to payment is not likely to succeed. (f) Enforcement policy....

  18. 14 CFR 1261.414 - Compromise of claims.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the Claims Collection Litigation Report. See § 1261.417(e) or 4 CFR 105.2(b). Claims for which the... Department of Justice for litigation. The Comptroller General may exercise such compromise authority with... other debtors that resistance to payment is not likely to succeed. (f) Enforcement policy....

  19. 14 CFR § 1261.414 - Compromise of claims.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the Claims Collection Litigation Report. See § 1261.417(e) or 4 CFR 105.2(b). Claims for which the... Department of Justice for litigation. The Comptroller General may exercise such compromise authority with... other debtors that resistance to payment is not likely to succeed. (f) Enforcement policy....

  20. 14 CFR 1261.414 - Compromise of claims.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... the Claims Collection Litigation Report. See § 1261.417(e) or 4 CFR 105.2(b). Claims for which the... Department of Justice for litigation. The Comptroller General may exercise such compromise authority with... other debtors that resistance to payment is not likely to succeed. (f) Enforcement policy....

  1. Whatever It Takes: Health Compromising Behaviors in Female Athletes

    ERIC Educational Resources Information Center

    Waldron, Jennifer J.; Krane, Vikki

    2005-01-01

    The power and performance model of sport stresses a sport ethic of doing "whatever it takes" to win (Coakley, 2004). Uncritical acceptance of this model may lead to various health-compromising behaviors. Employing achievement goal theory, we examine why female athletes may adopt the power and performance approach. An ego motivational climate and a…

  2. An Item Response Model for Characterizing Test Compromise.

    ERIC Educational Resources Information Center

    Segall, Daniel O.

    2002-01-01

    Developed an item response model for characterizing test-compromise that enables the estimation of item preview and score-gain distributions. In the approach, models parameters and posterior distributions are estimated by Markov Chain Monte Carlo procedures. Simulation study results suggest that when at least some test items are known to be…

  3. 32 CFR 2400.33 - Loss or possible compromise.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Loss or possible compromise. 2400.33 Section 2400.33 National Defense Other Regulations Relating to National Defense OFFICE OF SCIENCE AND TECHNOLOGY POLICY REGULATIONS TO IMPLEMENT E.O. 12356; OFFICE OF SCIENCE AND TECHNOLOGY POLICY...

  4. 7 CFR 1956.124 - Compromise and adjustment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 14 2012-01-01 2012-01-01 false Compromise and adjustment. 1956.124 Section 1956.124 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE SERVICE, RURAL UTILITIES SERVICE, AND FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS...

  5. 45 CFR 1177.12 - Compromise, suspension and termination.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION § 1177.12 Compromise, suspension and termination. (a) The Chairperson of the National Endowment for the Humanities or... available to the public. (b) The Chairperson of the National Endowment for the Humanities may...

  6. 45 CFR 1177.12 - Compromise, suspension and termination.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION § 1177.12 Compromise, suspension and termination. (a) The Chairperson of the National Endowment for the Humanities or... available to the public. (b) The Chairperson of the National Endowment for the Humanities may...

  7. 45 CFR 1177.12 - Compromise, suspension and termination.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION § 1177.12 Compromise, suspension and termination. (a) The Chairperson of the National Endowment for the Humanities or... available to the public. (b) The Chairperson of the National Endowment for the Humanities may...

  8. 45 CFR 1177.12 - Compromise, suspension and termination.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION § 1177.12 Compromise, suspension and termination. (a) The Chairperson of the National Endowment for the Humanities or... available to the public. (b) The Chairperson of the National Endowment for the Humanities may...

  9. 45 CFR 1177.12 - Compromise, suspension and termination.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... THE ARTS AND THE HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES CLAIMS COLLECTION § 1177.12 Compromise, suspension and termination. (a) The Chairperson of the National Endowment for the Humanities or... available to the public. (b) The Chairperson of the National Endowment for the Humanities may...

  10. Vehicle influence on permeation through intact and compromised skin.

    PubMed

    Gujjar, Meera; Banga, Ajay K

    2014-09-10

    The purpose of this study was to compare the transdermal permeation of a model compound, diclofenac diethylamine, from a hydrophilic and lipophilic vehicle across in vitro models simulating compromised skin. Mineral oil served as a lipophilic vehicle while 10mM phosphate buffered saline served as a hydrophilic vehicle. Compromised skin was simulated by tape stripping, delipidization, or microneedle application and compared with intact skin as a control. Transepidermal water loss was measured to assess barrier function. Skin compromised with tape stripping and delipidization significantly (p<0.05) increased permeation of diclofenac diethylamine compared to intact and microneedle treated skin with phosphate buffered saline vehicle. A similar trend in permeation was observed with mineral oil as the vehicle. For both vehicles, permeation across skin increased in the same order and correlated with degree of barrier impairment as indicated by transepidermal water loss values: intactcompromised skin. PMID:24979534

  11. 32 CFR 2400.33 - Loss or possible compromise.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 2400.33 National Defense Other Regulations Relating to National Defense OFFICE OF SCIENCE AND TECHNOLOGY POLICY REGULATIONS TO IMPLEMENT E.O. 12356; OFFICE OF SCIENCE AND TECHNOLOGY POLICY INFORMATION... measures taken to negate or minimize any adverse effect of the compromise. (b) The Security Officer...

  12. 32 CFR 2400.33 - Loss or possible compromise.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 2400.33 National Defense Other Regulations Relating to National Defense OFFICE OF SCIENCE AND TECHNOLOGY POLICY REGULATIONS TO IMPLEMENT E.O. 12356; OFFICE OF SCIENCE AND TECHNOLOGY POLICY INFORMATION... measures taken to negate or minimize any adverse effect of the compromise. (b) The Security Officer...

  13. SEMA4D compromises blood-brain barrier, activates microglia, and inhibits remyelination in neurodegenerative disease.

    PubMed

    Smith, Ernest S; Jonason, Alan; Reilly, Christine; Veeraraghavan, Janaki; Fisher, Terrence; Doherty, Michael; Klimatcheva, Ekaterina; Mallow, Crystal; Cornelius, Chad; Leonard, John E; Marchi, Nicola; Janigro, Damir; Argaw, Azeb Tadesse; Pham, Trinh; Seils, Jennifer; Bussler, Holm; Torno, Sebold; Kirk, Renee; Howell, Alan; Evans, Elizabeth E; Paris, Mark; Bowers, William J; John, Gareth; Zauderer, Maurice

    2015-01-01

    Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by immune cell infiltration of CNS, blood-brain barrier (BBB) breakdown, localized myelin destruction, and progressive neuronal degeneration. There exists a significant need to identify novel therapeutic targets and strategies that effectively and safely disrupt and even reverse disease pathophysiology. Signaling cascades initiated by semaphorin 4D (SEMA4D) induce glial activation, neuronal process collapse, inhibit migration and differentiation of oligodendrocyte precursor cells (OPCs), and disrupt endothelial tight junctions forming the BBB. To target SEMA4D, we generated a monoclonal antibody that recognizes mouse, rat, monkey and human SEMA4D with high affinity and blocks interaction between SEMA4D and its cognate receptors. In vitro, anti-SEMA4D reverses the inhibitory effects of recombinant SEMA4D on OPC survival and differentiation. In vivo, anti-SEMA4D significantly attenuates experimental autoimmune encephalomyelitis in multiple rodent models by preserving BBB integrity and axonal myelination and can be shown to promote migration of OPC to the site of lesions and improve myelin status following chemically-induced demyelination. Our study underscores SEMA4D as a key factor in CNS disease and supports the further development of antibody-based inhibition of SEMA4D as a novel therapeutic strategy for MS and other neurologic diseases with evidence of demyelination and/or compromise to the neurovascular unit. PMID:25461192

  14. Comparison of methods used for assessing the viability and vitality of yeast cells.

    PubMed

    Kwolek-Mirek, Magdalena; Zadrag-Tecza, Renata

    2014-11-01

    Determination of cell viability is the most commonly used method for assessing the impact of various types of stressors in toxicity research and in industrial microbiology studies. Viability is defined as a percentage of live cells in a whole population. Although cell death is one of the consequences of toxicity, chemical or physical factors may exert their toxic effects through a number of cellular alterations that may compromise cell ability to divide without necessarily leading to cell death. This aspect represents the term 'cell vitality' defined as physiological capabilities of cells. It is important to note that cell viability and cell vitality represent two different aspects of cell functions, and both are required for the estimation of the physiological state of a cell after exposure to various types of stressors and chemical or physical factors. In this paper, we introduced a classification of available methods for estimating both viability and vitality in Saccharomyces cerevisiae yeast cells (wild-type and Δsod1 mutant) in which the effects of selected oxidants causing oxidative stress is evaluated. We present the advantages as well as disadvantages of the selected methods and assess their usefulness in different types of research. PMID:25154541

  15. Viability and Resilience of Languages in Competition

    PubMed Central

    Chapel, Laetitia; Castelló, Xavier; Bernard, Claire; Deffuant, Guillaume; Eguíluz, Víctor M.; Martin, Sophie; Miguel, Maxi San

    2010-01-01

    We study the viability and resilience of languages, using a simple dynamical model of two languages in competition. Assuming that public action can modify the prestige of a language in order to avoid language extinction, we analyze two cases: (i) the prestige can only take two values, (ii) it can take any value but its change at each time step is bounded. In both cases, we determine the viability kernel, that is, the set of states for which there exists an action policy maintaining the coexistence of the two languages, and we define such policies. We also study the resilience of the languages and identify configurations from where the system can return to the viability kernel (finite resilience), or where one of the languages is lead to disappear (zero resilience). Within our current framework, the maintenance of a bilingual society is shown to be possible by introducing the prestige of a language as a control variable. PMID:20126655

  16. Poxvirus Viability and Signatures in Historical Relics

    PubMed Central

    Li, Yu; Wilkins, Kimberly; Karem, Kevin L.; Davidson, Whitni B.; Paddock, Christopher D.; Reynolds, Mary G.; Damon, Inger K.

    2014-01-01

    Although it has been >30 years since the eradication of smallpox, the unearthing of well-preserved tissue material in which the virus may reside has called into question the viability of variola virus decades or centuries after its original occurrence. Experimental data to address the long-term stability and viability of the virus are limited. There are several instances of well-preserved corpses and tissues that have been examined for poxvirus viability and viral DNA. These historical specimens cause concern for potential exposures, and each situation should be approached cautiously and independently with the available information. Nevertheless, these specimens provide information on the history of a major disease and vaccination against it. PMID:24447382

  17. Electromagnetic limits to radiofrequency (RF) neuronal telemetry

    NASA Astrophysics Data System (ADS)

    Diaz, R. E.; Sebastian, T.

    2013-12-01

    The viability of a radiofrequency (RF) telemetry channel for reporting individual neuron activity wirelessly from an embedded antenna to an external receiver is determined. Comparing the power at the transmitting antenna required for the desired Channel Capacity, to the maximum power that this antenna can dissipate in the body without altering or damaging surrounding tissue reveals the severe penalty incurred by miniaturization of the antenna. Using both Specific Absorption Rate (SAR) and thermal damage limits as constraints, and 300 Kbps as the required capacity for telemetry streams 100 ms in duration, the model shows that conventional antennas smaller than 0.1 mm could not support human neuronal telemetry to a remote receiver (1 m away.) Reducing the antenna to 10 microns in size to enable the monitoring of single human neuron signals to a receiver at the surface of the head would require operating with a channel capacity of only 0.3 bps.

  18. Survival response of hippocampal neurons under low oxygen conditions induced by Hippophae rhamnoides is associated with JAK/STAT signaling.

    PubMed

    Manickam, Manimaran; Tulsawani, Rajkumar

    2014-01-01

    Janus activated kinase/signal transducers and activators of transcription (JAK/STATs) pathway are associated with various neuronal functions including cell survival and inflammation. In the present study, it is hypothesized that protective action of aqueous extract of Hippophae rhamnoides in hippocampal neurons against hypoxia is mediated via JAK/STATs. Neuronal cells exposed to hypoxia (0.5% O2) display higher reactive oxygen species with compromised antioxidant status compared to unexposed control cells. Further, these cells had elevated levels of pro-inflammatory cytokines; tumor necrosis factor α and interleukin 6 and nuclear factor κappa B. Moreover, the expression of JAK1 was found to be highly expressed with phosphorylation of STAT3 and STAT5. Cells treated with JAK1, STAT3 and STAT5 specific inhibitors resulted in more cell death compared to hypoxic cells. Treatment of cells with extract prevented oxidative stress and inflammatory response associated with hypoxia. The extract treated cells had more cell survival than hypoxic cells with induction of JAK1 and STAT5b. Cells treated with extract having suppressed JAK1 or STAT3 or STAT5 expression showed reduced cell viability than the cell treated with extract alone. Overall, the findings from these studies indicate that the aqueous extract of Hippophae rhamnoides treatment inhibited hypoxia induced oxidative stress by altering cellular JAK1, STAT3 and STAT5 levels thereby enhancing cellular survival response to hypoxia and provide a basis for possible use of aqueous extract of Hippophae rhamnoides in facilitating tolerance to hypoxia. PMID:24516559

  19. Creating clones, kids & chimera: liberal democratic compromise at the crossroads.

    PubMed

    Adams, Nathan A

    2004-01-01

    The objective of this article is to find middle ground between the supporters and opponents of biotechnology by perpetuating the existing legal compromise pertaining to the complete range of health and welfare doctrines relevant to the biotechnological industry. The author aspires neither to add to nor detract from this liberal democratic consensus, but to preserve its constitutive balance between positivism and natural law and over-regulation and under-regulation in the hopes of stabilizing new political fault lines developing around the few biotechnological innovations already grabbing headlines. The most feasible solution is to extend the existing liberal democratic compromise with respect to equal protection, reproductive rights, the First Amendment, human subject experimentation, patent law, and parental rights. This includes banning or monopolizing certain biotechnologies and extending substantive special respect to the ex vivo living human embryo. Biotechnology must not be left to regulate itself. PMID:15382747

  20. A technique to salvage endodontically compromised maxillary anterior tooth.

    PubMed

    Comut, Alper; Foran, Denise; Cunningham, Ralph P

    2014-01-01

    A complication of endodontic treatment is over-preparation of the tooth structure in an attempt to access calcified pulp chambers and root canals. This could result in thin root walls that might compromise the long-term prognosis of the tooth. There are various treatment options when such a complication occurs, among them, extraction of the compromised tooth and its replacement with a dental implant. This clinical report describes a nonsurgical, multidisciplinary treatment alternative where a maxillary anterior tooth with a thinned root wall was successfully saved by repairing the damaged root to its original thickness using a composite resin material and subsequently restoring with a cast post and core and a crown. PMID:24654367

  1. Securing Single Points of Compromise (SPoC)

    SciTech Connect

    Belangia, David Warren

    2015-06-25

    Securing the Single Points of Compromise that provide central services to the institution’s environment is paramount to success when trying to protect the business. (Fisk, 2014) Time Based Security mandates protection (erecting and ensuring effective controls) that last longer than the time to detect and react to a compromise. When enterprise protections fail, providing additional layered controls for these central services provides more time to detect and react. While guidance is readily available for securing the individual critical asset, protecting these assets as a group is not often discussed. Using best business practices to protect these resources as individual assets while leveraging holistic defenses for the group increases the opportunity to maximize protection time, allowing detection and reaction time for the SPoCs that is commensurate with the inherent risk of these centralized services.

  2. Potential Soviet compromise on ballistic missile defense. Final report

    SciTech Connect

    Nguyen, H.P.

    1989-11-01

    The body of this research memorandum was written before the Baker-Shevardnadze meeting in Wyoming. It presented evidence suggesting that the Soviet Union might agree to a compromise at the Wyoming meeting that defers the issue of ballistic missile defense (BMD) negotiations to a later stage in arms reductions, thus facilitating a first-stage cut in offensive arms without an explicit Soviet endorsement of the Strategic Defense Initiative (SDI). Through this compromise, offensive arms reductions should first be delinked from an agreement on BMD, and then be relinked during the second stage of deeper cuts. Therefore, negotiations on limiting BMD systems, though deterred, are deemed inevitable if the U.S. persists in deploying a strategic defense system (SDS). Moreover, some Soviet arms controllers already look beyond the first stage to the prospect of negotiated transition into a strategic defense environment (i.e., a reliance on defensive deterrence). In this approach, Wyoming, then, was expected to be only a first move in the Soviet negotiating strategy for a grand compromise on strategic defense. As explained in the afterword added to the paper, the actual events at Wyoming seem consistent with that interpretation.

  3. In situ monitoring of surgical flap viability using THz imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Bajwa, Neha; Sung, Shijun; Grundfest, Warren; Taylor, Zachary

    2016-03-01

    This paper explores the utility of reflective THz imaging to assess the viability of surgical flaps. Flap surgery is a technique where tissue is harvested from a donor site and moved to a recipient while keeping the blood supply intact. This technique is common in head and neck tumor resection surgery where the reconstruction of complex and sensitive anatomic structures is routine following the resection of large and/or invasive tumors. Successful flap surgery results in tissue that is sufficiently perfused with both blood and extracellular water. If insufficient fluid levels are maintained, the flap tissue becomes necrotic and must be excised immediately to prevent infection developing and spreading to the surrounding areas. The goal of this work is to investigate the hydration of surgical flaps and correlate image features to successful graft outcomes. Advancement flaps were created on the abdomens of rat models. One rat model was labeled control and care was taken to ensure a successful flap outcome. The flap on the second rat was compromised with restricted blood flow and allowed to fail. The flaps of both rats were imaged once a day over the course of a week at which point the compromised flap had begun to show signs of necrosis. Significant differences in tissue water content were observed between rats over the experimental period. The results suggest that THz imaging may enable early assessment of flap viability.

  4. Viability of piping plover Charadrius melodus metapopulations

    USGS Publications Warehouse

    Plissner, Jonathan H.; Haig, Susan M.

    2000-01-01

    The metapopulation viability analysis package, VORTEX, was used to examine viability and recovery objectives for piping plovers Charadrius melodus, an endangered shorebird that breeds in three distinct regions of North America. Baseline models indicate that while Atlantic Coast populations, under current management practices, are at little risk of near-term extinction, Great Plains and Great Lakes populations require 36% higher mean fecundity for a significant probability of persisting for the next 100 years. Metapopulation structure (i.e. the delineation of populations within the metapopulation) and interpopulation dispersal rates had varying effects on model results; however, spatially-structured metapopulations exhibited lower viability than that reported for single-population models. The models were most sensitive to variation in survivorship; hence, additional mortality data will improve their accuracy. With this information, such models become useful tools in identifying successful management objectives; and sensitivity analyses, even in the absence of some data, may indicate which options are likely to be most effective. Metapopulation viability models are best suited for developing conservation strategies for achieving recovery objectives based on maintaining an externally derived, target population size and structure.

  5. Viability of nonminimally coupled f (R) gravity

    NASA Astrophysics Data System (ADS)

    Bertolami, Orfeu; Páramos, Jorge

    2016-03-01

    In this work we explore the viability of nonminimally coupled matter-curvature gravity theories, namely the conditions required for the absence of tachyon instabilities and ghost degrees of freedom. We contrast our finds with recent claims of a pathological behaviour of this class of models, which resorted to, in our view, an incorrect analogy with k-essence.

  6. EFFECT OF HALOGENS ON 'GIARDIA' CYST VIABILITY

    EPA Science Inventory

    The objective of this research was to determine the effect of chlorine and other disinfecting agents on Giardia lamblia cyst viability. The agents studied included free residual chlorine and six different methods recommended for emergency disinfection of small quantities of water...

  7. Viability of the Matter Bounce Scenario

    NASA Astrophysics Data System (ADS)

    de Haro, Jaume; Amorós, Jaume

    2015-04-01

    It is shown that teleparallel F(T) theories of gravity combined with Loop Quantum Cosmology support a Matter Bounce Scenario which is an alternative to the inflation scenario in the Big Bang paradigm. It is checked that these bouncing models provide theoretical data that fits well with the current observational data, allowing the viability of the Matter Bounce Scenario.

  8. Extending the viability of sea urchin gametes.

    PubMed

    Spiegler, M A; Oppenheimer, S B

    1995-04-01

    The sea urchin is the material of choice for studying many early developmental events. Methods to extend the viability of sea urchin gametes have not received much attention, but it is well known that the eggs are easily damaged by freezing. This study was designed to extend the viability of Lytechinus pictus eggs and sperm without freezing. Gamete viability measurements were based on relative numbers of fertilized vs unfertilized eggs, percentage fertilization, and on observations of embryonic development. Results indicate that gametes can be stored longer and at lower temperatures than previously described. Sperm were consistently kept viable for at least 12 days with little decrease in viability when stored in glass test tubes or plastic petri dishes and submerged in ice inside a refrigerator at 0 +/- 1 degree C. In one experiment, sperm stored in glass test tubes on ice remained viable up to 20 days after extraction. Eggs were maintained from 1 to 7 days, rather than the 1 day or so previously reported, when stored in glass test tubes submerged in ice in a refrigerator at 0 +/- 1 degree C. Results of egg and sperm experiments varied at different times in the season. Such variations may be caused by seasonal cytoplasmic changes, population differences, or the time mature individuals were maintained unfed in aquaria prior to use. Results from this study should be useful for a variety of research, mariculture, and teaching applications in which sea urchin supplies are limited or when the same gamete population is required for subsequent experiments. PMID:7743818

  9. Observability in strategic models of viability selection.

    PubMed

    Gámez, M; Carreño, R; Kósa, A; Varga, Z

    2003-10-01

    Strategic models of frequency-dependent viability selection, in terms of mathematical systems theory, are considered as a dynamic observation system. Using a general sufficient condition for observability of nonlinear systems with invariant manifold, it is studied whether, observing certain phenotypic characteristics of the population, the development of its genetic state can be recovered, at least near equilibrium. PMID:14563566

  10. Viability of mesenchymal stem cells during electrospinning

    PubMed Central

    Zanatta, G.; Steffens, D.; Braghirolli, D.I.; Fernandes, R.A.; Netto, C.A.; Pranke, P.

    2011-01-01

    Tissue engineering is a technique by which a live tissue can be re-constructed and one of its main goals is to associate cells with biomaterials. Electrospinning is a technique that facilitates the production of nanofibers and is commonly used to develop fibrous scaffolds to be used in tissue engineering. In the present study, a different approach for cell incorporation into fibrous scaffolds was tested. Mesenchymal stem cells were extracted from the wall of the umbilical cord and mononuclear cells from umbilical cord blood. Cells were re-suspended in a 10% polyvinyl alcohol solution and subjected to electrospinning for 30 min under a voltage of 21 kV. Cell viability was assessed before and after the procedure by exclusion of dead cells using trypan blue staining. Fiber diameter was observed by scanning electron microscopy and the presence of cells within the scaffolds was analyzed by confocal laser scanning microscopy. After electrospinning, the viability of mesenchymal stem cells was reduced from 88 to 19.6% and the viability of mononuclear cells from 99 to 8.38%. The loss of viability was possibly due to the high viscosity of the polymer solution, which reduced the access to nutrients associated with electric and mechanical stress during electrospinning. These results suggest that the incorporation of cells during fiber formation by electrospinning is a viable process that needs more investigation in order to find ways to protect cells from damage. PMID:22183245

  11. Elevated non-esterified fatty acid concentrations during bovine oocyte maturation compromise early embryo physiology.

    PubMed

    Van Hoeck, Veerle; Sturmey, Roger G; Bermejo-Alvarez, Pablo; Rizos, Dimitrios; Gutierrez-Adan, Alfonso; Leese, Henry J; Bols, Peter E J; Leroy, Jo L M R

    2011-01-01

    Elevated concentrations of serum non-esterified fatty acids (NEFA), associated with maternal disorders such as obesity and type II diabetes, alter the ovarian follicular micro-environment and have been associated with subfertility arising from reduced oocyte developmental competence. We have asked whether elevated NEFA concentrations during oocyte maturation affect the development and physiology of zygotes formed from such oocytes, using the cow as a model. The zygotes were grown to blastocysts, which were evaluated for their quality in terms of cell number, apoptosis, expression of key genes, amino acid turnover and oxidative metabolism. Oocyte maturation under elevated NEFA concentrations resulted in blastocysts with significantly lower cell number, increased apoptotic cell ratio and altered mRNA abundance of DNMT3A, IGF2R and SLC2A1. In addition, the blastocysts displayed reduced oxygen, pyruvate and glucose consumption, up-regulated lactate consumption and higher amino acid metabolism. These data indicate that exposure of maturing oocytes to elevated NEFA concentrations has a negative impact on fertility not only through a reduction in oocyte developmental capacity but through compromised early embryo quality, viability and metabolism. PMID:21858021

  12. Native Chondrocyte Viability during Cartilage Lesion Progression

    PubMed Central

    Ganguly, Kumkum; McRury, Ian D.; Goodwin, Peter M.; Morgan, Roy E.; Augé, Wayne K.

    2010-01-01

    Objective: Early surgical intervention for articular cartilage disease is desirable before full-thickness lesions develop. As early intervention treatments are designed, native chondrocyte viability at the treatment site before intervention becomes an important parameter to consider. The purpose of this study is to evaluate native chondrocyte viability in a series of specimens demonstrating the progression of articular cartilage lesions to determine if the chondrocyte viability profile changes during the evolution of articular cartilage disease to the level of surface fibrillation. Design: Osteochondral specimens demonstrating various degrees of articular cartilage damage were obtained from patients undergoing knee total joint replacement. Three groups were created within a patient harvest based on visual and tactile cues commonly encountered during surgical intervention: group 1, visually and tactilely intact surfaces; group 2, visually intact, tactilely soft surfaces; and group 3, surface fibrillation. Confocal laser microscopy was performed following live/dead cell viability staining. Results: Groups 1 to 3 demonstrated viable chondrocytes in all specimens, even within the fibrillated portions of articular cartilage, with little to no evidence of dead chondrocytes. Chondrocyte viability profile in articular cartilage does not appear to change as disease lesion progresses from normal to surface fibrillation. Conclusions: Fibrillated partial-thickness articular cartilage lesions are a good therapeutic target for early intervention. These lesions retain a high profile of viable chondrocytes and are readily diagnosed by visual and tactile cues during surgery. Early intervention should be based on matrix failure rather than on more aggressive procedures that further corrupt the matrix and contribute to chondrocyte necrosis of contiguous untargeted cartilage. PMID:26069561

  13. Graphene Oxide Nanosheets Disrupt Lipid Composition, Ca(2+) Homeostasis, and Synaptic Transmission in Primary Cortical Neurons.

    PubMed

    Bramini, Mattia; Sacchetti, Silvio; Armirotti, Andrea; Rocchi, Anna; Vázquez, Ester; León Castellanos, Verónica; Bandiera, Tiziano; Cesca, Fabrizia; Benfenati, Fabio

    2016-07-26

    Graphene has the potential to make a very significant impact on society, with important applications in the biomedical field. The possibility to engineer graphene-based medical devices at the neuronal interface is of particular interest, making it imperative to determine the biocompatibility of graphene materials with neuronal cells. Here we conducted a comprehensive analysis of the effects of chronic and acute exposure of rat primary cortical neurons to few-layer pristine graphene (GR) and monolayer graphene oxide (GO) flakes. By combining a range of cell biology, microscopy, electrophysiology, and "omics" approaches we characterized the graphene-neuron interaction from the first steps of membrane contact and internalization to the long-term effects on cell viability, synaptic transmission, and cell metabolism. GR/GO flakes are found in contact with the neuronal membrane, free in the cytoplasm, and internalized through the endolysosomal pathway, with no significant impact on neuron viability. However, GO exposure selectively caused the inhibition of excitatory transmission, paralleled by a reduction in the number of excitatory synaptic contacts, and a concomitant enhancement of the inhibitory activity. This was accompanied by induction of autophagy, altered Ca(2+) dynamics, and a downregulation of some of the main players in the regulation of Ca(2+) homeostasis in both excitatory and inhibitory neurons. Our results show that, although graphene exposure does not impact neuron viability, it does nevertheless have important effects on neuronal transmission and network functionality, thus warranting caution when planning to employ this material for neurobiological applications. PMID:27359048

  14. Video-assisted thoracoscopy in compromised pediatric patients.

    PubMed

    Gamba, Piergiorgio; Midrio, Paola; Betalli, Pietro; Snijders, Deborah; Leon, Francesco Fascetti

    2010-02-01

    The use of video-assisted techniques (VATs) in the paediatric field has become increasingly more frequent, based on reports of prompter recovery following VATs in respect to standard techniques. Specific advantages have been documented, in particular for pediatric patients undergoing chemioradiotherapic treatment. We retrospectively reviewed data of severely compromised patients who underwent VAT for lung wedge resections and biopsies carried out in our center over a 7-year period. As far as the area of therapeutic tumor resection is concerned, the present data are consistent with the view that thoracoscopy is both an effective and safe tool in diagnostic procedures. PMID:19811063

  15. From function to esthetics: anterior or occlusal compromises to esthetics.

    PubMed

    Guichet, D L; Guichet, N F

    1993-01-01

    Increased patient expectations together with improved diagnostic, material, and surgical advances have expanded the boundaries of esthetic dentistry. To optimize functional and esthetic success, existing techniques are being enhanced through careful patient selection and management of the occlusion. During the period from 1991 to 1992, several areas relating anterior or occlusal compromises to esthetics have been identified. These include: dental and skeletal malocclusion, periodontal esthetic defects, restorative materials and laboratory techniques, tooth arrangement and maxillomandibular relations, and implant dentistry. This paper reviews some of the literature on these areas during this period. PMID:8401825

  16. Expert review--identification of intra-partum fetal compromise.

    PubMed

    Prior, Tomas; Kumar, Sailesh

    2015-07-01

    Whilst most cases of cerebral palsy occur as a consequence of an ante-natal insult, a significant proportion, particularly in the term fetus, are attributable to intra-partum hypoxia. Intra-partum monitoring using continuous fetal heart rate assessment has led to an increased incidence of operative delivery without a concurrent reduction in the incidence of cerebral palsy. Despite this, birth asphyxia remains the strongest and most consistent risk factor for cerebral palsy in term infants. This review evaluates current intra-partum monitoring techniques as well as alternative approaches aimed at better identification of the fetus at risk of compromise in labour. PMID:25917435

  17. [Frostbite injuries causing compromised airway after inhalation of propane].

    PubMed

    Straarup, Therese Simonsen; Fink, Anders Olsen; Larsen, Jens Kjærgaard Rolighed

    2015-01-01

    We describe a case report of a 23-year-old man with acute pharyngeal injuries due to frostbite subsequent to inhalation of propane. He was fiber-optically intubated on admission to hospital since his airways were considered acutely compromised. He was subsequently kept intubated for 11 days due to persistent pharyngeal oedema and frostbite injuries. The latter is caused by low temperature of propane upon release from a pressurized container. Injuries caused by frostbite often gradually progress and thus caution should be exerted in regards to airway management. PMID:25557449

  18. The cybernetics of viability: an overview

    NASA Astrophysics Data System (ADS)

    Nechansky, Helmut

    2011-10-01

    A three-level approach to viability is developed, considering (1) living systems, (2) a niche, understood as the area within the reach of their actions, and (3) an environment. A systematic analysis of the interrelations between these levels shows that living systems emerge with matter/energy processing systems. These can add controller structures when producing excess energy. A three-sensor controller structure enables a living system to deal with unfavourable and scarce environments. Further evolution of these controller structures offers improved ways to act on niches. Maintaining niches in scarce environments can require technology or economy. So social systems emerge, which are understood as aggregates of living systems. Basic patterns of interactions within social systems are analysed. So the introduction of the notion of the niche into the discussion of viability allows us to explain phenomena ranging from properties of single living systems to societal organization.

  19. Skin graft storage and keratinocyte viability.

    PubMed

    Fahmy, F S; Navsaria, H A; Frame, J D; Jones, C R; Leigh, I M

    1993-06-01

    The viability of human split skin grafts stored in four solutions has been assessed by monitoring the percentage of viable keratinocytes in the stored grafts. Skin grafts stored in RM+ (Ready Mix) tissue culture medium remained more viable than those stored in Hartmann's, Marshall's or saline solutions. By day 10 (postoperative), the percentage of viable keratinocytes of those grafts stored in RM+ was around 85%, compared to a value of around 10% for the other media. By day 30, RM+ achieved a value of around 60% keratinocyte viability compared to a value approaching 1% in the other storage media under investigation. RM+ provides mitogens, nutrients, growth factors and physiological pH, all of which are important factors for successful skin graft storage. PMID:8330085

  20. GGGGCC repeat expansion in C9ORF72 compromises nucleocytoplasmic transport

    PubMed Central

    Freibaum, Brian D.; Lu, Yubing; Lopez-Gonzalez, Rodrigo; Kim, Nam Chul; Almeida, Sandra; Lee, Kyung-Ha; Badders, Nisha; Valentine, Marc; Miller, Bruce L.; Wong, Philip C.; Petrucelli, Leonard; Kim, Hong Joo; Gao, Fen-Biao; Taylor, J. Paul

    2015-01-01

    GGGGCC (G4C2) repeat expansion in a noncoding region of C9ORF72 is the most common cause of sporadic and familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)1,2. The basis for pathogenesis is unknown. To capture the consequences of G4C2 repeat expansion in a tractable genetic system, we generated transgenic fly lines expressing 8, 28 or 58 G4C2 repeat-containing transcripts that do not have a translation start site (AUG) but contain an open-reading frame for green fluorescent protein (GFP) to detect repeat-associated non-AUG (RAN) translation. These transgenic animals show dosage-dependent, repeat length-dependent degeneration in neuronal tissues and RAN translation of dipeptide repeat (DPR) proteins as observed in patients. This model was used in a large-scale, unbiased genetic screen ultimately leading to the identification of 18 genetic modifiers that encode components of the nuclear pore complex (NPC) as well as the machinery that coordinates the export of nuclear RNA and the import of nuclear proteins. Consistent with these results we found morphological abnormalities in the architecture of the nuclear envelope in cells expressing expanded G4C2 repeats in vitro and in vivo. Moreover, we identified a substantial defect in RNA export resulting in retention of RNA in the nuclei of Drosophila cells expressing expanded G4C2 repeats and also in mammalian cells, including aged iPSC-derived neurons from C9ORF72 patients. These studies show that a primary consequence of G4C2 repeat expansion is the compromise of nucleocytoplasmic transport through the nuclear pore, revealing a novel mechanism of neurodegeneration. PMID:26308899

  1. Anthropogenic noise compromises antipredator behaviour in European eels.

    PubMed

    Simpson, Stephen D; Purser, Julia; Radford, Andrew N

    2015-02-01

    Increases in noise-generating human activities since the Industrial Revolution have changed the acoustic landscape of many terrestrial and aquatic ecosystems. Anthropogenic noise is now recognized as a major pollutant of international concern, and recent studies have demonstrated impacts on, for instance, hearing thresholds, communication, movement and foraging in a range of species. However, consequences for survival and reproductive success are difficult to ascertain. Using a series of laboratory-based experiments and an open-water test with the same methodology, we show that acoustic disturbance can compromise antipredator behaviour--which directly affects survival likelihood--and explore potential underlying mechanisms. Juvenile European eels (Anguilla anguilla) exposed to additional noise (playback of recordings of ships passing through harbours), rather than control conditions (playback of recordings from the same harbours without ships), performed less well in two simulated predation paradigms. Eels were 50% less likely and 25% slower to startle to an 'ambush predator' and were caught more than twice as quickly by a 'pursuit predator'. Furthermore, eels experiencing additional noise had diminished spatial performance and elevated ventilation and metabolic rates (indicators of stress) compared with control individuals. Our results suggest that acoustic disturbance could have important physiological and behavioural impacts on animals, compromising life-or-death responses. PMID:25098970

  2. Progress in Pain Assessment: The Cognitively Compromised Patient

    PubMed Central

    Chapman, C. Richard

    2009-01-01

    Purpose of review Pain assessment is essential for patient care in many settings, but it proves difficult when the patient is cognitively compromised or otherwise unable to produce a conventional pain report. This review describes progress in pain assessment technology that involves the coding of human facial expression. Recent findings It is possible to quantify facial expression by coding patterns of facial muscle contraction and relaxation. These patterns are action units, and they can gauge the intensity of pain as well as signal its occurrence. The experience of pain seems to generate a unique facial expression comprising several action units. Concerns have existed about whether demented patients produce diagnostically meaningful facial expressions of pain because they tend to generate more non-specific facial expressions and perhaps code pain intensity less well than normals. Recent work shows that facial expression reflects pain as well or better in demented patients compared to normals. Summary Although still nascent, coded facial expression appears to work reliably as a pain assessment tool with cognitively compromised patients. Clinical application awaits the development of technology that can automate facial coding and scoring. PMID:18784487

  3. Hint1 knockout results in a compromised activation of protein kinase C gamma in the brain.

    PubMed

    Zhang, Fan; Fang, Zhenfei; Wang, Jia Bei

    2015-10-01

    Previous studies have implicated a role of the histidine triad nucleotide-binding protein 1 (Hint1) in the pathogenesis of schizophrenia. Protein kinase C gamma (PKCγ) could be potentially involved in the Hint1-implicated pathogenesis since PKCγ was identified as a Hint1 interacting protein. Recently, a debate was brought forward from the understanding how Hint1 affects the expression and activity of PKCγ in the brain. In the present study, we use Hint1 knockout mice and biochemical analysis to define the effect of Hint1 on protein PKCγ. Our data reveal that Hint1-deficiency in mouse brains led to increased protein levels of PKCγ in the cortex and hippocampus, the striatum and thalamus and amygdala. Without stimulation, PKCγ protein in Hint1-deficient brain displayed a basal activity that was reflected by control-leveled phosphorylations of PKCγ T514 and T674 at its kinase domain. Upon psycho-stimulation, both sites of PKCγ T514 and T674 were activated in these brain structures via phosphorylation; however, the phosphorylation level at the site of PKCγ T674 apparently attenuated in Hint1-deficient mice compared to wild-type control. Thus, we conclude that Hint1 deficiency leads to an increased protein level of PKCγ in the brain and a compromised activation response of PKCγ upon stimulation. These findings suggest an inhibitory role of Hint1 on the protein PKCγ in the brain and an impaired PKCγ-mediated phosphorylation signal in Hint1-deficient neuron. PMID:26133792

  4. Atypical cadherins Celsr1-3 differentially regulate migration of facial branchiomotor neurons in mice.

    PubMed

    Qu, Yibo; Glasco, Derrick M; Zhou, Libing; Sawant, Anagha; Ravni, Aurélia; Fritzsch, Bernd; Damrau, Christine; Murdoch, Jennifer N; Evans, Sylvia; Pfaff, Samuel L; Formstone, Caroline; Goffinet, André M; Chandrasekhar, Anand; Tissir, Fadel

    2010-07-14

    During hindbrain development, facial branchiomotor neurons (FBM neurons) migrate from medial rhombomere (r) 4 to lateral r6. In zebrafish, mutations in planar cell polarity genes celsr2 and frizzled3a block caudal migration of FBM neurons. Here, we investigated the role of cadherins Celsr1-3, and Fzd3 in FBM neuron migration in mice. In Celsr1 mutants (knock-out and Crash alleles), caudal migration was compromised and neurons often migrated rostrally into r2 and r3, as well as laterally. These phenotypes were not caused by defects in hindbrain patterning or neuronal specification. Celsr1 is expressed in FBM neuron precursors and the floor plate, but not in FBM neurons. Consistent with this, conditional inactivation showed that the function of Celsr1 in FBM neuron migration was non-cell autonomous. In Celsr2 mutants, FBM neurons initiated caudal migration but moved prematurely into lateral r4 and r5. This phenotype was enhanced by inactivation of Celsr3 in FBM neurons and mimicked by inactivation of Fzd3. Furthermore, Celsr2 was epistatic to Celsr1. These data indicate that Celsr1-3 differentially regulate FBM neuron migration. Celsr1 helps to specify the direction of FBM neuron migration, whereas Celsr2 and 3 control its ability to migrate. PMID:20631168

  5. Mechanism of soluble beta-amyloid 25-35 neurotoxicity in primary cultured rat cortical neurons.

    PubMed

    Wang, Yong; Liu, Lili; Hu, Weimin; Li, Guanglai

    2016-04-01

    This study aimed to determine the effects of different concentrations of soluble beta-amyloid 25-35 (Aβ25-35) on cell viability, calcium overload, and PI3K-p85 expression in cultured cortical rat neurons. Primary cultured cerebral cortical neurons of newborn rats were divided randomly into six groups. Five groups were treated with soluble Aβ25-35 at concentrations of 10nmol/L, 100nmol/L, 1μmol/L, 10μmol/L, or 30μmol/L. Cell Counting Kit-8 staining was used to measure cell viability, laser-scanning confocal imaging was used to detect changes in intracellular free calcium concentration, and western blot assay was used to measure neuronal PI3K-p85 expression. Soluble Aβ25-35 was found to reduce cell viability and induce calcium overload in primary cultured rat cerebral cortical neurons, in a concentration-dependent manner. At certain concentrations, soluble Aβ25-35 also increased neuronal PI3K-p85 expression. These findings reveal that soluble Aβ25-35 reduces the viability of cultured cerebral cortical rat neurons. The neurotoxicity mechanism may involve calcium overload and disruption of insulin signal transduction pathways. PMID:26940239

  6. 40 CFR 1620.6 - Authority to adjust, determine, compromise, and settle.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., compromise, and settle. 1620.6 Section 1620.6 Protection of Environment CHEMICAL SAFETY AND HAZARD..., determine, compromise, and settle. The General Counsel of CSB, or his or her designee, is delegated authority to consider, ascertain, adjust, determine, compromise and settle claims under the provision of...

  7. 40 CFR 1620.6 - Authority to adjust, determine, compromise, and settle.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., compromise, and settle. 1620.6 Section 1620.6 Protection of Environment CHEMICAL SAFETY AND HAZARD..., determine, compromise, and settle. The General Counsel of CSB, or his or her designee, is delegated authority to consider, ascertain, adjust, determine, compromise and settle claims under the provision of...

  8. 7 CFR 3550.253 - Settlement of a debt by compromise or adjustment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Settlement of a debt by compromise or adjustment. 3550.253 Section 3550.253 Agriculture Regulations of the Department of Agriculture (Continued) RURAL... Actions § 3550.253 Settlement of a debt by compromise or adjustment. Compromise or adjustment offers...

  9. 7 CFR 3550.253 - Settlement of a debt by compromise or adjustment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Settlement of a debt by compromise or adjustment. 3550.253 Section 3550.253 Agriculture Regulations of the Department of Agriculture (Continued) RURAL... Actions § 3550.253 Settlement of a debt by compromise or adjustment. Compromise or adjustment offers...

  10. Perceived Career Compromise, Affect and Work-Related Satisfaction in College Students

    ERIC Educational Resources Information Center

    Tsaousides, Theodore; Jome, LaRae

    2008-01-01

    The objective of this study was to investigate the effects of career compromise on positive affect (PA), negative affect (NA), and work-related satisfaction (WRS). Career compromise refers to the modification of occupational preferences under pressing external circumstances [Gottfredson, L. S. (1981). Circumscription and compromise: A…

  11. Compromises along the Way: Balancing Speed To Market with Sustainability while Delivering Knowledge Management Services.

    ERIC Educational Resources Information Center

    Heyman, Martha K.

    This paper will discuss some of the compromises, and the path to those compromises, that must be made while implementing a successful knowledge management program within a for-profit enterprise. Specifically the following compromises are addressed: (1) manage knowledge where it is created, but do that within a global system; (2) no single scope…

  12. Impact of ZnO and Ag Nanoparticles on Bacterial Growth and Viability

    NASA Astrophysics Data System (ADS)

    Olson, M. S.; Digiovanni, K. A.

    2007-12-01

    Hundreds of consumer products containing nanomaterials are currently available in the U.S., including computers, clothing, cosmetics, sports equipment, medical devices and product packaging. Metallic nanoparticles can be embedded in or coated on product surfaces to provide antimicrobial, deodorizing, and stain- resistant properties. Although these products have the potential to provide significant benefit to the user, the impact of these products on the environment remains largely unknown. The purpose of this project is to study the effect of metallic nanoparticles released to the environment on bacterial growth and viability. Inhibition of bacterial growth was tested by adding doses of suspended ZnO and Ag nanoparticles into luria broth prior to inoculation of Escherichia coli cells. ZnO particles (approximately 40 nm) were obtained commercially and Ag particles (12-14 nm) were fabricated by reduction of silver nitrate with sodium borohydride. Toxicity assays were performed to test the viability of E. coli cells exposed to both ZnO and Ag nanoparticles using the LIVE/DEAD BacLight bacterial viability kit (Invitrogen). Live cells stain green whereas cells with compromised membranes that are considered dead or dying stain red. Cells were first grown, stained, and exposed to varying doses of metallic nanoparticles, and then bacterial viability was measured hourly using fluorescence microscopy. Results indicate that both ZnO and Ag nanoparticles inhibit the growth of E. coli in liquid media. Preliminary results from toxicity assays confirm the toxic effect of ZnO and Ag nanoparticles on active cell cultures. Calculated death rates resulting from analyses of toxicity studies will be presented.

  13. Effects of purification and fluorescent staining on viability of Mycobacterium leprae.

    PubMed

    Lahiri, Ramanuj; Randhawa, Baljit; Krahenbuhl, James L

    2005-09-01

    Over the years, researchers have carried out experiments with Mycobacterium leprae obtained from either human multibacillary lesions, or infected armadillo tissues, or infected footpad tissues of conventional mice as well as athymic nu/nu mice. In general, these sources of leprosy bacilli are satisfactory for most biochemical and mouse footpad studies, but less than satisfactory for studies in cell biology and immunology where contaminating host tissues pose a serious problem. We examined the utility of a procedure for eliminating mouse footpad tissue from M. leprae suspension using sodium hydroxide solution and its subsequent effect on the viability of the organism by determining the rate of palmitic acid oxidation, bacterial membrane integrity, and growth in the mouse footpad. We found that treating M. leprae suspension, obtained from infected nu/nu mouse footpad, with 0.1N NaOH for 3 min was sufficient to remove the majority of mouse tissue without adversely affecting the viability of the organism. This is a simple and rapid method to get suspensions of nu/nu footpad-derived viable M. leprae essentially free of host tissues, which can be a research reagent for studying the host-pathogen relationship in leprosy. We also report here a method for labeling M. leprae with the fluorescent dye PKH26, without compromising on the viability of the organism. This method may be useful in intracellular trafficking studies of M. leprae or in other cell biology studies that require tracking of the bacteria using fluorescent tag. We observed the staining to be stable in vitro over considerable lengths of time and did not affect the viability of the bacteria. PMID:16830641

  14. Conflict and Compromise: Catholic and Public Hospital Partnerships

    PubMed Central

    Wall, Barbra Mann

    2010-01-01

    This article analyzes the tensions and uneasy negotiations, based on a case study, that occurred among Catholic sisters, administrators, bishops, physicians, and the Vatican for more than seven years at a hospital in Austin, Texas. Here, the largest health care system in the city, which was Catholic, joined with the local public, tax-supported hospital that provided the majority of reproductive health care services in the region. A clash resulted over whether the hospital could continue providing sterilization and contraceptive services to its primarily poor patients. This article examines the fierce debates that occurred, especially over emergency contraception and attempts to develop creative solutions after a hierarchical crackdown from the Vatican. The end result was a compromise that included the creation of a “hospital within a hospital.” PMID:20067093

  15. Protecting Privacy of Shared Epidemiologic Data without Compromising Analysis Potential

    DOE PAGESBeta

    Cologne, John; Grant, Eric J.; Nakashima, Eiji; Chen, Yun; Funamoto, Sachiyo; Katayama, Hiroaki

    2012-01-01

    Objective . Ensuring privacy of research subjects when epidemiologic data are shared with outside collaborators involves masking (modifying) the data, but overmasking can compromise utility (analysis potential). Methods of statistical disclosure control for protecting privacy may be impractical for individual researchers involved in small-scale collaborations. Methods . We investigated a simple approach based on measures of disclosure risk and analytical utility that are straightforward for epidemiologic researchers to derive. The method is illustrated using data from the Japanese Atomic-bomb Survivor population. Results . Masking by modest rounding did not adequately enhance security but rounding to remove several digits ofmore » relative accuracy effectively reduced the risk of identification without substantially reducing utility. Grouping or adding random noise led to noticeable bias. Conclusions . When sharing epidemiologic data, it is recommended that masking be performed using rounding. Specific treatment should be determined separately in individual situations after consideration of the disclosure risks and analysis needs.« less

  16. Enhanced susceptibility to predation in corals of compromised condition

    PubMed Central

    Cameron, Caitlin M.; Miller, Margaret W.

    2015-01-01

    The marine gastropod, Coralliophila abbreviata, is an obligate corallivore that causes substantial mortality in Caribbean Acropora spp. Considering the imperiled status of Acropora cervicornis and A. palmata, a better understanding of ecological interactions resulting in tissue loss may enable more effective conservation strategies. We examined differences in susceptibility of A. cervicornis to C. abbreviata predation based on coral tissue condition. Coral tissue condition was a strong determinant of snail prey choice, with snails preferring A. cervicornis fragments that were diseased or mechanically damaged over healthy fragments. In addition, snails always chose fragments undergoing active predation by another snail, while showing no preference for a non-feeding snail when compared with an undisturbed prey fragment. These results indicate that the condition of A. cervicornis prey influenced foraging behavior of C. abbreviata, creating a potential feedback that may exacerbate damage from predation in coral populations compromised by other types of disturbance. PMID:26734500

  17. Suppression of Mic60 compromises mitochondrial transcription and oxidative phosphorylation

    PubMed Central

    Yang, Rui-Feng; Sun, Li-Hong; Zhang, Ran; Zhang, Yuan; Luo, Yu-Xuan; Zheng, Wei; Zhang, Zhu-Qin; Chen, Hou-Zao; Liu, De-Pei

    2015-01-01

    Precise regulation of mtDNA transcription and oxidative phosphorylation (OXPHOS) is crucial for human health. As a component of mitochondrial contact site and cristae organizing system (MICOS), Mic60 plays a central role in mitochondrial morphology. However, it remains unclear whether Mic60 affects mitochondrial transcription. Here, we report that Mic60 interacts with mitochondrial transcription factors TFAM and TFB2M. Furthermore, we found that Mic60 knockdown compromises mitochondrial transcription and OXPHOS activities. Importantly, Mic60 deficiency decreased TFAM binding and mitochondrial RNA polymerase (POLRMT) recruitment to the mtDNA promoters. In addition, through mtDNA immunoprecipitation (mIP)-chromatin conformation capture (3C) assays, we found that Mic60 interacted with mtDNA and was involved in the architecture of mtDNA D-loop region. Taken together, our findings reveal a previously unrecognized important role of Mic60 in mtDNA transcription. PMID:25612828

  18. Glycan Side Reaction May Compromise ETD-Based Glycopeptide Identification

    NASA Astrophysics Data System (ADS)

    Darula, Zsuzsanna; Medzihradszky, Katalin F.

    2014-06-01

    Tris(hydroxymethyl)aminomethane (Tris) is one of the most frequently used buffer ingredients. Among other things, it is recommended and is usually used for lectin-based affinity enrichment of glycopeptides. Here we report that sialic acid, a common `capping' unit in both N- and O-linked glycans may react with this chemical, and this side reaction may compromise glycopeptide identification when ETD spectra are the only MS/MS data used in the database search. We show that the modification may alter N- as well as O-linked glycans, the Tris-derivative is still prone to fragmentation both in `beam-type' CID (HCD) and ETD experiments, at the same time—since the acidic carboxyl group was `neutralized'—it will display a different retention time than its unmodified counterpart. We also suggest solutions that—when incorporated into existing search engines—may significantly improve the reliability of glycopeptide assignments.

  19. Protecting Privacy of Shared Epidemiologic Data without Compromising Analysis Potential

    PubMed Central

    Cologne, John; Grant, Eric J.; Nakashima, Eiji; Chen, Yun; Funamoto, Sachiyo; Katayama, Hiroaki

    2012-01-01

    Objective. Ensuring privacy of research subjects when epidemiologic data are shared with outside collaborators involves masking (modifying) the data, but overmasking can compromise utility (analysis potential). Methods of statistical disclosure control for protecting privacy may be impractical for individual researchers involved in small-scale collaborations. Methods. We investigated a simple approach based on measures of disclosure risk and analytical utility that are straightforward for epidemiologic researchers to derive. The method is illustrated using data from the Japanese Atomic-bomb Survivor population. Results. Masking by modest rounding did not adequately enhance security but rounding to remove several digits of relative accuracy effectively reduced the risk of identification without substantially reducing utility. Grouping or adding random noise led to noticeable bias. Conclusions. When sharing epidemiologic data, it is recommended that masking be performed using rounding. Specific treatment should be determined separately in individual situations after consideration of the disclosure risks and analysis needs. PMID:22505949

  20. Thiamine absorption is not compromised in folate-deficient rats

    SciTech Connect

    Walzem, R.L.; Clifford, A.J.

    1988-11-01

    Thiamine absorption and excretion were assessed in rats with severe folate deficiency (FD) by determining the fate of oral TH-labeled and intravenous UC-labeled thiamine over a 6-h test period. Thiamine status was evaluated in these same rats by measuring transketolase activity levels of blood before (TKA) and after (TPPE) addition of thiamine pyrophosphate to the incubation mixture of the assay procedure. Two additional experiments assessed active transport of thiamine and the effect of dietary succinylsulfathiazole (SST) on TKA and TPPE in rats with moderate FD. Intestinal absorption in general and thiamine absorption in particular and thiamine status were unaltered in rats with severe FD. Inanition associated with severe FD may impair thiamine status. Thiamine absorption by active transport was not compromised in FD, and dietary succinylsulfathiazole did not affect thiamine status.

  1. [Nicotinamide influence on pancreatic cells viability].

    PubMed

    Kuchmerovs'ka, T M; Donchenko, H V; Tykhonenko, T M; Huzyk, M M; Stavniĭchuk, R V; Ianits'ka, L V; Stepanenko, S P; Klymenko, A P

    2012-01-01

    The study was undertaken to investigate the modulating effect of nicotinamide (NAm) in different concentrations and under different glucose concentrations on the viability and oxidative stress induced by streptozotocin (STZ, 5 mmol/l) and hydrogen peroxide (H2O2, 100 micromol/l) on isolated rat pancreatic cells of the Langerhans islets in vitro. Cell viability did not depend on the concentration of glucose in the range of 5-20 mmol/l, and in subsequent studies we used glucose in concentration of 10 mmol/l to protect cells against its hypo- and hyperglycemic action. Cytoprotective effect of NAm in concentrations from 5 to 20 mmol/l on cells survival was the same. It was found that the destructive action of STZ and H2O2 during 24 hours on isolated cells of the pancreas resulted in the significant cell death. It was revealed that NAm in concentration of 5 mmol/l not only had cytoprotective effects against STZ and H2O2 but also partially reduced the level of oxidative stress in the investigated cells induced by these compounds. High concentration of NAm, 35 mmol/l, causes cytotoxic effect on the viability of pancreatic islet cells and increase of oxidative stress induced by STZ and H2O2. Most likely these effects could be associated with direct modulatory action of NAm on important effector mechanisms involved in cell death, including PARP-dependent processes, or/and indirectly, through metabolic and antioxidant effects of the compound. PMID:22642125

  2. Echinococcus metacestode: in search of viability markers

    PubMed Central

    Gottstein, Bruno; Wang, Junhua; Blagosklonov, Oleg; Grenouillet, Frédéric; Millon, Laurence; Vuitton, Dominique A.; Müller, Norbert

    2014-01-01

    Epidemiological studies have demonstrated that most humans infected with Echinococcus spp. exhibit resistance to disease. When infection leads to disease, the parasite is partially controlled by host immunity: in case of immunocompetence, the normal alveolar echinococcosis (AE) or cystic echinococcosis (CE) situation, the metacestode grows slowly, and first clinical signs appear years after infection; in case of impaired immunity (AIDS; other immunodeficiencies), uncontrolled proliferation of the metacestode leads to rapidly progressing disease. Assessing Echinococcus multilocularis viability in vivo following therapeutic interventions in AE patients may be of tremendous benefit when compared with the invasive procedures used to perform biopsies. Current options are F18-fluorodeoxyglucose-positron emission tomography (FDG-PET), which visualizes periparasitic inflammation due to the metabolic activity of the metacestode, and measurement of antibodies against recEm18, a viability-associated protein, that rapidly regresses upon metacestode inactivation. For Echinococcus granulosus, similar prognosis-associated follow-up parameters are still lacking but a few candidates may be listed. Other possible markers include functional and diffusion-weighted Magnetic Resonance Imaging (MRI), and measurement of products from the parasite (circulating antigens or DNA), and from the host (inflammation markers, cytokines, or chemokines). Even though some of them have been promising in pilot studies, none has been properly validated in an appropriate number of patients until now to be recommended for further use in clinical settings. There is therefore still a need to develop reliable tools for improved viability assessment to provide the sufficient information needed to reliably withdraw anti-parasite benzimidazole chemotherapy, and a basis for the development of new alternative therapeutic tools. PMID:25429386

  3. Rapid onsite assessment of spore viability.

    SciTech Connect

    Branda, Steven; Lane, Todd W.; VanderNoot, Victoria A.; Gaucher, Sara P.; Jokerst, Amanda S.

    2005-12-01

    This one year LDRD addresses problems of threat assessment and restoration of facilities following a bioterror incident like the incident that closed down mail facilities in late 2001. Facilities that are contaminated with pathogenic spores such as B. anthracis spores must be shut down while they are treated with a sporicidal agent and the effectiveness of the treatment is ascertained. This process involves measuring the viability of spore test strips, laid out in a grid throughout the facility; the CDC accepted methodologies require transporting the samples to a laboratory and carrying out a 48 hr outgrowth experiment. We proposed developing a technique that will ultimately lead to a fieldable microfluidic device that can rapidly assess (ideally less than 30 min) spore viability and effectiveness of sporicidal treatment, returning facilities to use in hours not days. The proposed method will determine viability of spores by detecting early protein synthesis after chemical germination. During this year, we established the feasibility of this approach and gathered preliminary results that should fuel a future more comprehensive effort. Such a proposal is currently under review with the NIH. Proteomic signatures of Bacillus spores and vegetative cells were assessed by both slab gel electrophoresis as well as microchip based gel electrophoresis employing sensitive laser-induced fluorescence detection. The conditions for germination using a number of chemical germinants were evaluated and optimized and the time course of protein synthesis was ascertained. Microseparations were carried out using both viable spores and spores inactivated by two different methods. A select number of the early synthesis proteins were digested into peptides for analysis by mass spectrometry.

  4. Mitigating Reptile Road Mortality: Fence Failures Compromise Ecopassage Effectiveness

    PubMed Central

    Baxter-Gilbert, James H.; Riley, Julia L.; Lesbarrères, David; Litzgus, Jacqueline D.

    2015-01-01

    Roadways pose serious threats to animal populations. The installation of roadway mitigation measures is becoming increasingly common, yet studies that rigorously evaluate the effectiveness of these conservation tools remain rare. A highway expansion project in Ontario, Canada included exclusion fencing and ecopassages as mitigation measures designed to offset detrimental effects to one of the most imperial groups of vertebrates, reptiles. Taking a multispecies approach, we used a Before-After-Control-Impact study design to compare reptile abundance on the highway before and after mitigation at an Impact site and a Control site from 1 May to 31 August in 2012 and 2013. During this time, radio telemetry, wildlife cameras, and an automated PIT-tag reading system were used to monitor reptile movements and use of ecopassages. Additionally, a willingness to utilize experiment was conducted to quantify turtle behavioral responses to ecopassages. We found no difference in abundance of turtles on the road between the un-mitigated and mitigated highways, and an increase in the percentage of both snakes and turtles detected dead on the road post-mitigation, suggesting that the fencing was not effective. Although ecopassages were used by reptiles, the number of crossings through ecopassages was lower than road-surface crossings. Furthermore, turtle willingness to use ecopassages was lower than that reported in previous arena studies, suggesting that effectiveness of ecopassages may be compromised when alternative crossing options are available (e.g., through holes in exclusion structures). Our rigorous evaluation of reptile roadway mitigation demonstrated that when exclusion structures fail, the effectiveness of population connectivity structures is compromised. Our project emphasizes the need to design mitigation measures with the biology and behavior of the target species in mind, to implement mitigation designs in a rigorous fashion, and quantitatively evaluate road

  5. Blood–Retinal Barrier Compromise and Endogenous Staphylococcus aureus Endophthalmitis

    PubMed Central

    Coburn, Phillip S.; Wiskur, Brandt J.; Astley, Roger A.; Callegan, Michelle C.

    2015-01-01

    Purpose To test the hypothesis that blood–retinal barrier compromise is associated with the development of endogenous Staphylococcus aureus endophthalmitis. Methods To compromise the blood–retinal barrier in vivo, streptozotocin-induced diabetes was induced in C57BL/6J mice for 1, 3, or 5 months. Diabetic and age-matched nondiabetic mice were intravenously injected with 108 colony-forming units (cfu) of S. aureus, a common cause of endogenous endophthalmitis in diabetics. After 4 days post infection, electroretinography, histology, and bacterial counts were performed. Staphylococcus aureus–induced alterations in in vitro retinal pigment epithelial (RPE) cell barrier structure and function were assessed by anti–ZO-1 immunohistochemistry, FITC-dextran conjugate diffusion, and bacterial transmigration assays. Results We observed one bilateral infection in a control, nondiabetic animal (mean = 1.54 × 103 ± 1.78 × 102 cfu/eye, 7% incidence). Among the 1-month diabetic mice, we observed culture-confirmed unilateral infections in two animals (mean = 5.54 × 102 ± 7.09 × 102 cfu/eye, 12% incidence). Among the 3-month diabetic mice, infections were observed in 11 animals, three with bilateral infections (mean = 2.67 × 102 ± 2.49 × 102 cfu/eye, 58% incidence). Among the 5-month diabetic mice, we observed infections in five animals (mean = 7.88 × 102 ± 1.08 × 103 cfu/eye, 33% incidence). In vitro, S. aureus infection reduced ZO-1 immunostaining and disrupted the barrier function of cultured RPE cells, resulting in diffusion of fluorophore-conjugated dextrans and transmigration of live bacteria across a permeabilized RPE barrier. Conclusions Taken together, these results indicated that S. aureus is capable of inducing blood–retinal barrier permeability and causing endogenous bacterial endophthalmitis in normal and diabetic animals. PMID:26559476

  6. Quintessence reconstructed: New constraints and tracker viability

    SciTech Connect

    Sahlen, Martin; Liddle, Andrew R.; Parkinson, David

    2007-01-15

    We update and extend our previous work reconstructing the potential of a quintessence field from current observational data. We extend the cosmological data set to include new supernova data, plus information from the cosmic microwave background and from baryon acoustic oscillations. We extend the modeling by considering Pade approximant expansions as well as Taylor series, and by using observations to assess the viability of the tracker hypothesis. We find that parameter constraints have improved by a factor of 2, with a strengthening of the preference of the cosmological constant over evolving quintessence models. Present data show some signs, though inconclusive, of favoring tracker models over nontracker models under our assumptions.

  7. Chitin and carbon nanotube composites as biocompatible scaffolds for neuron growth

    NASA Astrophysics Data System (ADS)

    Singh, Nandita; Chen, Jinhu; Koziol, Krzysztof K.; Hallam, Keith R.; Janas, Dawid; Patil, Avinash J.; Strachan, Ally; G. Hanley, Jonathan; Rahatekar, Sameer S.

    2016-04-01

    The design of biocompatible implants for neuron repair/regeneration ideally requires high cell adhesion as well as good electrical conductivity. Here, we have shown that plasma-treated chitin carbon nanotube composite scaffolds show very good neuron adhesion as well as support of synaptic function of neurons. The addition of carbon nanotubes to a chitin biopolymer improved the electrical conductivity and the assisted oxygen plasma treatment introduced more oxygen species onto the chitin nanotube scaffold surface. Neuron viability experiments showed excellent neuron attachment onto plasma-treated chitin nanotube composite scaffolds. The support of synaptic function was evident on chitin/nanotube composites, as confirmed by PSD-95 staining. The biocompatible and electrically-conducting chitin nanotube composite scaffold prepared in this study can be used for in vitro tissue engineering of neurons and, potentially, as an implantable electrode for stimulation and repair of neurons.

  8. Membrane potential dye imaging of ventromedial hypothalamus neurons from adult mice to study glucose sensing.

    PubMed

    Vazirani, Reema P; Fioramonti, Xavier; Routh, Vanessa H

    2013-01-01

    Studies of neuronal activity are often performed using neurons from rodents less than 2 months of age due to the technical difficulties associated with increasing connective tissue and decreased neuronal viability that occur with age. Here, we describe a methodology for the dissociation of healthy hypothalamic neurons from adult-aged mice. The ability to study neurons from adult-aged mice allows the use of disease models that manifest at a later age and might be more developmentally accurate for certain studies. Fluorescence imaging of dissociated neurons can be used to study the activity of a population of neurons, as opposed to using electrophysiology to study a single neuron. This is particularly useful when studying a heterogeneous neuronal population in which the desired neuronal type is rare such as for hypothalamic glucose sensing neurons. We utilized membrane potential dye imaging of adult ventromedial hypothalamic neurons to study their responses to changes in extracellular glucose. Glucose sensing neurons are believed to play a role in central regulation of energy balance. The ability to study glucose sensing in adult rodents is particularly useful since the predominance of diseases related to dysfunctional energy balance (e.g. obesity) increase with age. PMID:24326343

  9. Membrane Potential Dye Imaging of Ventromedial Hypothalamus Neurons From Adult Mice to Study Glucose Sensing

    PubMed Central

    Vazirani, Reema P.; Fioramonti, Xavier; Routh, Vanessa H.

    2013-01-01

    Studies of neuronal activity are often performed using neurons from rodents less than 2 months of age due to the technical difficulties associated with increasing connective tissue and decreased neuronal viability that occur with age. Here, we describe a methodology for the dissociation of healthy hypothalamic neurons from adult-aged mice. The ability to study neurons from adult-aged mice allows the use of disease models that manifest at a later age and might be more developmentally accurate for certain studies. Fluorescence imaging of dissociated neurons can be used to study the activity of a population of neurons, as opposed to using electrophysiology to study a single neuron. This is particularly useful when studying a heterogeneous neuronal population in which the desired neuronal type is rare such as for hypothalamic glucose sensing neurons. We utilized membrane potential dye imaging of adult ventromedial hypothalamic neurons to study their responses to changes in extracellular glucose. Glucose sensing neurons are believed to play a role in central regulation of energy balance. The ability to study glucose sensing in adult rodents is particularly useful since the predominance of diseases related to dysfunctional energy balance (e.g. obesity) increase with age. PMID:24326343

  10. Directed Evolution of a Novel Adeno-associated Virus (AAV) Vector That Crosses the Seizure-compromised Blood–Brain Barrier (BBB)

    PubMed Central

    Gray, Steven J; Blake, Bonita L; Criswell, Hugh E; Nicolson, Sarah C; Samulski, R Jude; McCown, Thomas J

    2009-01-01

    DNA shuffling and directed evolution were employed to develop a novel adeno-associated virus (AAV) vector capable of crossing the seizure-compromised blood–brain barrier (BBB) and transducing cells in the brain. Capsid DNA from AAV serotypes 1–6, 8, and 9 were shuffled and recombined to create a library of chimeric AAVs. One day after kainic acid–induced limbic seizure activity in rats, the virus library was infused intravenously (i.v.), and 3 days later, neuron-rich cells were mechanically dissociated from seizure-sensitive brain sites, collected and viral DNA extracted. After three cycles of selection, green fluorescent protein (GFP)–packaged clones were administered directly into brain or i.v. 1 day after kainic acid–induced seizures. Several clones that were effective after intracranial administration did not transduce brain cells after the i.v. administration. However, two clones (32 and 83) transduced the cells after direct brain infusion and after i.v. administration transduced the cells that were localized to the piriform cortex and ventral hippocampus, areas exhibiting a seizure-compromised BBB. No transduction occurred in areas devoid of BBB compromise. Only one parental serotype (AAV8) exhibited a similar expression profile, but the biodistribution of 32 and 83 diverged dramatically from this parental serotype. Thus, novel AAV vectors have been created that can selectively cross the seizure-compromised BBB and transduce cells. PMID:20040913

  11. Compromised paraspeckle formation as a pathogenic factor in FUSopathies

    PubMed Central

    Shelkovnikova, Tatyana A.; Robinson, Hannah K.; Troakes, Claire; Ninkina, Natalia; Buchman, Vladimir L.

    2014-01-01

    Paraspeckles are nuclear bodies formed by a set of specialized proteins assembled on the long non-coding RNA NEAT1; they have a role in nuclear retention of hyperedited transcripts and are associated with response to cellular stress. Fused in sarcoma (FUS) protein, linked to a number of neurodegenerative disorders, is an essential paraspeckle component. We have shown that its recruitment to these nuclear structures is mediated by the N-terminal region and requires prion-like activity. FUS interacts with p54nrb/NONO, a major constituent of paraspeckles, in an RNA-dependent manner and responds in the same way as other paraspeckle proteins to alterations in cellular homeostasis such as changes in transcription rates or levels of protein methylation. FUS also regulates NEAT1 levels and paraspeckle formation in cultured cells, and FUS deficiency leads to loss of paraspeckles. Pathological gain-of-function FUS mutations might be expected to affect paraspeckle function in human diseases because mislocalized amyotrophic lateral sclerosis (ALS)-linked FUS variants sequester other paraspeckle proteins into aggregates formed in cultured cells and into neuronal inclusions in a transgenic mouse model of FUSopathy. Furthermore, we detected abundant p54nrb/NONO-positive inclusions in motor neurons of patients with familial forms of ALS caused by FUS mutations, but not in other ALS cases. Our results suggest that both loss and gain of FUS function can trigger disruption of paraspeckle assembly, which may impair protective responses in neurons and thereby contribute to the pathogenesis of FUSopathies. PMID:24334610

  12. Limit of viability: The Swiss experience.

    PubMed

    Berger, T M; Roth-Kleiner, M

    2016-09-01

    Progress made in the field of perinatology over the past four decades has led to unprecedented low mortality rates for extremely low birth weight infants. However, because rates of important short-term complications and neurodevelopmental impairment among survivors have remained high, the best approach to borderline viable infants continues to be debated. Not surprisingly, guidelines from various national medical societies for the care of infants born at the limit of viability vary considerably. In 2002, the first Swiss recommendations for the care of borderline viable infants were published. They had been developed by a multidisciplinary team of experts from the fields of obstetrics, pediatrics, and neonatology. Despite the availability of national guidelines, center-to-center outcome variability has since persisted, suggesting that care for the most immature infants is not only evidence-based and guideline-driven but also strongly influenced by local neonatal intensive care unit (NICU) culture. In 2011, revised national recommendations for perinatal care at the limit of viability between 22 and 26 completed weeks of gestation were published. It remains to be seen whether this has led to more uniform outcomes across the Swiss centers in the years that followed. PMID:27476994

  13. Population Viability Analysis of Riverine Fishes

    SciTech Connect

    Bates, P.; Chandler, J.; Jager, H.I.; Lepla, K.; Van Winkle, W.

    1999-04-12

    Many utilities face conflkts between two goals: cost-efficient hydropower generation and protecting riverine fishes. Research to develop ecological simulation tools that can evaluate alternative mitigation strategies in terms of their benefits to fish populations is vital to informed decision-making. In this paper, we describe our approach to population viability analysis of riverine fishes in general and Snake River white sturgeon in particular. We are finding that the individual-based modeling approach used in previous in-stream flow applications is well suited to addressing questions about the viability of species of concern for several reasons. Chief among these are: (1) the abiIity to represent the effects of individual variation in life history characteristics on predicted population viabili~, (2) the flexibili~ needed to quanti~ the ecological benefits of alternative flow management options by representing spatial and temporal variation in flow and temperaturty and (3) the flexibility needed to quantifi the ecological benefits of non-flow related manipulations (i.e., passage, screening and hatchery supplementation).

  14. Cell viability in a wet silica gel.

    PubMed

    Nieto, Alejandra; Areva, Sami; Wilson, Timothy; Viitala, Reeta; Vallet-Regi, Maria

    2009-11-01

    A modified two-step sol-gel route using silicon ethoxide (TEOS) has been used to synthesize amorphous sol-gel-derived silica, which has been successfully used as a cell encapsulation matrix for 3T3 mouse fibroblasts and CRL-2595 epithelial cells due to its non-toxicity. The sol-gel procedure comprised a first, low pH hydrolysis step, followed by a neutral condensation-gelation step. A high water-to-TEOS ratio and the addition of d-glucose as a porogen and source of nutrients were chosen to minimize silica dissolution and improve the biocompatibility of the process. Indeed, the cell integrity in the encapsulation process was preserved by alcohol removal from the starting solution. Cells were then added in a buffered medium, causing rapid gelation and entrapment of the cells within a randomly structured siloxane matrix in the shape of a monolith, which was maintained in the wet state. MTT and alamarBlue assays were used to check the cytotoxicity of the silica gels and the viability of entrapped cells at initial times in contact with silica. To improve cell attachment, cell clumping experiments - where groups of cells were formed - were designed, rendering improved viability. The obtained materials are therefore excellent candidates for designing tissue-culture scaffolds and implantable bioreactors for biomedical applications. PMID:19481618

  15. Toxicity of neurons treated with herbicides and neuroprotection by mitochondria-targeted antioxidant SS31.

    PubMed

    Reddy, Tejaswini P; Manczak, Maria; Calkins, Marcus J; Mao, Peizhong; Reddy, Arubala P; Shirendeb, Ulziibat; Park, Byung; Reddy, P Hemachandra

    2011-01-01

    The purpose of this study was to determine the neurotoxicity of two commonly used herbicides: picloram and triclopyr and the neuroprotective effects of the mitochondria-targeted antioxidant, SS31. Using mouse neuroblastoma (N2a) cells and primary neurons from C57BL/6 mice, we investigated the toxicity of these herbicides, and protective effects of SS1 peptide against picloram and triclopyr toxicity. We measured total RNA content, cell viability and mRNA expression of peroxiredoxins, neuroprotective genes, mitochondrial-encoded electron transport chain (ETC) genes in N2a cells treated with herbicides and SS31. Using primary neurons from C57BL/6 mice, neuronal survival was studied in neurons treated with herbicides, in neurons pretreated with SS31 plus treated with herbicides, neurons treated with SS31 alone, and untreated neurons. Significantly decreased total RNA content, and cell viability in N2a cells treated with picloram and triclopyr were found compared to untreated N2a cells. Decreased mRNA expression of neuroprotective genes, and ETC genes in cells treated with herbicides was found compared to untreated cells. Decreased mRNA expression of peroxiredoxins 1-6 in N2a cells treated with picloram was found, suggesting that picloram affects the antioxidant enzymes in N2a cells. Immunofluorescence analysis of primary neurons revealed that decreased neuronal branching and degenerating neurons in neurons treated with picloram and triclopyr. However, neurons pretreated with SS31 prevented degenerative process caused by herbicides. Based on these results, we propose that herbicides--picloram and triclopyr appear to damage neurons, and the SS31 peptide appears to protect neurons from herbicide toxicity. PMID:21318024

  16. Toxicity of Neurons Treated with Herbicides and Neuroprotection by Mitochondria-Targeted Antioxidant SS31

    PubMed Central

    Reddy, Tejaswini P.; Manczak, Maria; Calkins, Marcus J.; Mao, Peizhong; Reddy, Arubala P.; Shirendeb, Ulziibat; Park, Byung; Reddy, P. Hemachandra

    2011-01-01

    The purpose of this study was to determine the neurotoxicity of two commonly used herbicides: picloram and triclopyr and the neuroprotective effects of the mitochondria-targeted antioxidant, SS31. Using mouse neuroblastoma (N2a) cells and primary neurons from C57BL/6 mice, we investigated the toxicity of these herbicides, and protective effects of SS1 peptide against picloram and triclopyr toxicity. We measured total RNA content, cell viability and mRNA expression of peroxiredoxins, neuroprotective genes, mitochondrial-encoded electron transport chain (ETC) genes in N2a cells treated with herbicides and SS31. Using primary neurons from C57BL/6 mice, neuronal survival was studied in neurons treated with herbicides, in neurons pretreated with SS31 plus treated with herbicides, neurons treated with SS31 alone, and untreated neurons. Significantly decreased total RNA content, and cell viability in N2a cells treated with picloram and triclopyr were found compared to untreated N2a cells. Decreased mRNA expression of neuroprotective genes, and ETC genes in cells treated with herbicides was found compared to untreated cells. Decreased mRNA expression of peroxiredoxins 1–6 in N2a cells treated with picloram was found, suggesting that picloram affects the antioxidant enzymes in N2a cells. Immunofluorescence analysis of primary neurons revealed that decreased neuronal branching and degenerating neurons in neurons treated with picloram and triclopyr. However, neurons pretreated with SS31 prevented degenerative process caused by herbicides. Based on these results, we propose that herbicides—picloram and triclopyr appear to damage neurons, and the SS31 peptide appears to protect neurons from herbicide toxicity. PMID:21318024

  17. The RNA-binding protein SFPQ orchestrates an RNA regulon to promote axon viability.

    PubMed

    Cosker, Katharina E; Fenstermacher, Sara J; Pazyra-Murphy, Maria F; Elliott, Hunter L; Segal, Rosalind A

    2016-05-01

    To achieve accurate spatiotemporal patterns of gene expression, RNA-binding proteins (RBPs) guide nuclear processing, intracellular trafficking and local translation of target mRNAs. In neurons, RBPs direct transport of target mRNAs to sites of translation in remote axons and dendrites. However, it is not known whether an individual RBP coordinately regulates multiple mRNAs within these morphologically complex cells. Here we identify SFPQ (splicing factor, poly-glutamine rich) as an RBP that binds and regulates multiple mRNAs in dorsal root ganglion sensory neurons and thereby promotes neurotrophin-dependent axonal viability. SFPQ acts in nuclei, cytoplasm and axons to regulate functionally related mRNAs essential for axon survival. Notably, SFPQ is required for coassembly of LaminB2 (Lmnb2) and Bclw (Bcl2l2) mRNAs in RNA granules and for axonal trafficking of these mRNAs. Together these data demonstrate that SFPQ orchestrates spatial gene expression of a newly identified RNA regulon essential for axonal viability. PMID:27019013

  18. Cold shock induces apoptosis of dorsal root ganglion neurons plated on infrared windows.

    PubMed

    Aboualizadeh, Ebrahim; Mattson, Eric C; O'Hara, Crystal L; Smith, Amanda K; Stucky, Cheryl L; Hirschmugl, Carol J

    2015-06-21

    The chemical status of live sensory neurons is accessible with infrared microspectroscopy of appropriately prepared cells. In this paper, individual dorsal root ganglion (DRG) neurons have been prepared with two different protocols, and plated on glass cover slips, BaF2 and CaF2 substrates. The first protocol exposes the intact DRGs to 4 °C for between 20-30 minutes before dissociating individual neurons and plating 2 hours later. The second protocol maintains the neurons at 23 °C for the entire duration of the sample preparation. The visual appearance of the neurons is similar. The viability was assessed by means of trypan blue exclusion method to determine the viability of the neurons. The neurons prepared under the first protocol (cold exposure) and plated on BaF2 reveal a distinct chemical signature and chemical distribution that is different from the other sample preparations described in the paper. Importantly, results for other sample preparation methods, using various substrates and temperature protocols, when compared across the overlapping spectral bandwidth, present normal chemical distribution within the neurons. The unusual chemically specific spatial variation is dominated by a lack of protein and carbohydrates in the center of the neurons and signatures of unraveling DNA are detected. We suggest that cold shock leads to apoptosis of DRGs, followed by osmotic stress originating from ion gradients across the cell membrane leading to cell lysis. PMID:26000346

  19. Inkjet printing Schwann cells and neuronal analogue NG108-15 cells.

    PubMed

    Tse, Christopher; Whiteley, Robert; Yu, Tong; Stringer, Jonathan; MacNeil, Sheila; Haycock, John W; Smith, Patrick J

    2016-03-01

    Porcine Schwann cells and neuronal analogue NG108-15 cells were printed using a piezoelectric-inkjet-printer with a nozzle diameter of 60 μm, within the range of 70-230 V, with analysis of viability and quality after printing. Neuronal and glial cell viabilities of >86% and >90% were detected immediately after printing and no correlation between voltage applied and cell viability could be seen. Printed neuronal cells were shown to produce neurites earlier compared to controls, and over several days, produced longer neurites which become most evident by day 7. The number of neurites becomes similar by day 7 also, and cells proliferate with a similar viability to that of non-printed cells (controls). This method of inkjet printing cells provides a technical platform for investigating neuron-glial cell interactions with no significant difference to cell viability than standard cell seeding. Such techniques can be utilized for lab-on-a-chip technologies and to create printed neural networks for neuroscience applications. PMID:26930268

  20. Compromised central tolerance of ICA69 induces multiple organ autoimmunity

    PubMed Central

    Fan, Yong; Gualtierotti, Giulio; Tajima, Asako; Grupillo, Maria; Coppola, Antonina; He, Jing; Bertera, Suzanne; Owens, Gregory; Pietropaolo, Massimo; Rudert, William A.; Trucco, Massimo

    2015-01-01

    For reasons not fully understood, patients with an organ-specific autoimmune disease have increased risks of developing autoimmune responses against other organs/tissues. We identified ICA69, a known β-cell autoantigen in Type 1 diabetes, as a potential common target in multi-organ autoimmunity. NOD mice immunized with ICA69 polypeptides exhibited exacerbated inflammation not only in the islets, but also in the salivary glands. To further investigate ICA69 autoimmunity, two genetically modified mouse lines were generated to modulate thymic ICA69 expression: the heterozygous ICA69del/wt line and the thymic medullary epithelial cell-specific deletion Aire-ΔICA69 line. Suboptimal central negative selection of ICA69-reactive T-cells was observed in both lines. Aire-ΔICA69 mice spontaneously developed coincident autoimmune responses to the pancreas, the salivary glands, the thyroid, and the stomach. Our findings establish a direct link between compromised thymic ICA69 expression and autoimmunity against multiple ICA69-expressing organs, and identify a potential novel mechanism for the development of multi-organ autoimmune diseases. PMID:25088457

  1. Protection characteristics of a Faraday cage compromised by lightning burnthrough.

    SciTech Connect

    Warne, Larry Kevin; Bystrom, Edward; Jorgenson, Roy Eberhardt; Montoya, Sandra L.; Merewether, Kimball O.; Coats, Rebecca Sue; Martinez, Leonard E.; Jojola, John M.

    2012-01-01

    A lightning flash consists of multiple, high-amplitude but short duration return strokes. Between the return strokes is a lower amplitude, continuing current which flows for longer duration. If the walls of a Faraday cage are made of thin enough metal, the continuing current can melt a hole through the metal in a process called burnthrough. A subsequent return stroke can couple energy through this newly-formed hole. This LDRD is a study of the protection provided by a Faraday cage when it has been compromised by burnthrough. We initially repeated some previous experiments and expanded on them in terms of scope and diagnostics to form a knowledge baseline of the coupling phenomena. We then used a combination of experiment, analysis and numerical modeling to study four coupling mechanisms: indirect electric field coupling, indirect magnetic field coupling, conduction through plasma and breakdown through the hole. We discovered voltages higher than those encountered in the previous set of experiments (on the order of several hundreds of volts).

  2. Contribution of consultants to care of compromised pregnancies.

    PubMed Central

    Bird, J. S.; Taslimi, M. M.; Gonzales, A. R.; Duggan, M.

    1996-01-01

    Obstetricians often seek consultative services of other specialists in the management of compromised pregnancies. However, the extent of such consultations and the contribution of these consultants have not been addressed in the literature. This study is addresses the contribution of consultants to the care of complicated pregnancies at a tertiary care center. During the 2 1/2 years of this retrospective study, 2263 antepartum admissions were made for pregnancy complications. One hundred sixty-six of those patients were hospitalized 176 times and were treated by one or more consulting physicians for a consultation rate of 7.8%. Eighteen specialties were consulted, including 54 (32%) consultations from maternal fetal medicine, 44 (24%) from internal medicine, 28 (16%) from general surgery, and 22 (12%) from endocrinology. Of the initial admission diagnoses, 87.9% were confirmed and 46 new diagnoses were made by the consultants. A significant positive correlation was noted between the number of consultants, maternal length of hospital stay, and maternal hospitalization cost. PMID:8776065

  3. Physiologic assessment of fetal compromise: biomarkers of toxic exposure

    SciTech Connect

    Longo, L.D.

    1987-10-01

    Understanding the physiologic and endocrinologic basis of fetal development is a major goal of perinatal biology. During the past decade a number of technological developments have allowed more precise evaluation of the fetus in utero and diagnosis of abnormalities. Despite these methodological achievements, however, there are no specific biological markers currently available to indicate that exposure to a given xenobiotic is associated with a cellular, subcellular, or pharmacodynamic event. This paper evaluates the following issues: what are some of the unique physiologic and endocrinologic features of the fetal milieu interieur. What problems are peculiar to fetal assessment. What are some examples of validated biomarkers and their applicability. What promising biomarkers are on the horizon. How may molecular probes be of value as biological markers of fetal compromise. What are some of the major research gaps and needs, and how should research priorities be set. Some of these topics are addressed. Moreover, the more general role(s) that various diagnostic methods and biological markers can have in an understanding of the regulation of fetal growth and differentiation and the role of xenobiotics in affecting the normal course of events are discussed.

  4. Risk Factors for Uteroplacental Vascular Compromise and Inflammation

    PubMed Central

    BAKER, Arthur M.; BRAUN, Joe M.; SALAFIA, Carolyn M.; HERRING, Amy H.; DANIELS, Julie; RANKINS, Nicole; THORP, John M.

    2008-01-01

    Objective To identify potentially modifiable risk factors of placental injury reflecting maternal uteroplacental vascular compromise (UPVC) and acute and chronic placental inflammation. Study design A prospective epidemiologic study was conducted. A total of 1270 placentas were characterized by gross and microscopic examination. Placental pathology was coded for features of amniotic fluid infection syndrome (AFIS), chronic villitis, UPVC, and fetal vascular obstructive lesions. Odds ratios between UPVC, the acute and the chronic inflammatory lesions, and risk factors of interest were calculated. Results After adjusting for confounders, women with a history of preterm birth had 1.60 times the odds of chronic inflammation (95% CI: 1.10, 2.55). Women with a previous elective termination had 3.28 times the odds of acute inflammation (95% CI: 1.89, 5.70). The odds of chronic villitis increased with parity, while the odds of AFIS decreased with parity. Conclusion We have identified several predictors of UPVC, AFIS and chronic villitis. Further studies are needed to examine whether interventions to alter UPVC, AFIS and chronic villitis will lead to improved pregnancy outcomes. PMID:18771974

  5. GABA-CREB signalling regulates maturation and survival of newly generated neurons in the adult hippocampus

    PubMed Central

    Jagasia, Ravi; Steib, Kathrin; Englberger, Elisabeth; Herold, Sabine; Faus-Kessler, Theresa; Saxe, Michael; Gage, Fred H.; Song, Hongjun; Lie, D. Chichung

    2009-01-01

    Survival and integration of new neurons in the hippocampal circuit are rate-limiting steps in adult hippocampal neurogenesis. Neuronal network activity is a major regulator of these processes, yet little is known about the respective downstream signalling pathways. Here, we investigate the role of CREB signalling in adult hippocampal neurogenesis. CREB is activated in new granule neurons during a distinct developmental period. Loss of CREB function in a cell-autonomous fashion impairs dendritic development, decreases the expression of the neurogenic transcription factor NeuroD and of the neuronal microtubule associated protein, DCX, and compromises the survival of newborn neurons. In addition, GABA-mediated excitation regulates CREB activation at early developmental stages. Importantly, developmental defects following loss of GABA-mediated excitation can be compensated by enhanced CREB signalling. These results indicate that CREB signalling is a central pathway in adult hippocampal neurogenesis, regulating the development and survival of new hippocampal neurons downstream of GABA-mediated excitation. PMID:19553437

  6. Incorporating evolutionary processes into population viability models.

    PubMed

    Pierson, Jennifer C; Beissinger, Steven R; Bragg, Jason G; Coates, David J; Oostermeijer, J Gerard B; Sunnucks, Paul; Schumaker, Nathan H; Trotter, Meredith V; Young, Andrew G

    2015-06-01

    We examined how ecological and evolutionary (eco-evo) processes in population dynamics could be better integrated into population viability analysis (PVA). Complementary advances in computation and population genomics can be combined into an eco-evo PVA to offer powerful new approaches to understand the influence of evolutionary processes on population persistence. We developed the mechanistic basis of an eco-evo PVA using individual-based models with individual-level genotype tracking and dynamic genotype-phenotype mapping to model emergent population-level effects, such as local adaptation and genetic rescue. We then outline how genomics can allow or improve parameter estimation for PVA models by providing genotypic information at large numbers of loci for neutral and functional genome regions. As climate change and other threatening processes increase in rate and scale, eco-evo PVAs will become essential research tools to evaluate the effects of adaptive potential, evolutionary rescue, and locally adapted traits on persistence. PMID:25494697

  7. Extending the viability of acute brain slices.

    PubMed

    Buskila, Yossi; Breen, Paul P; Tapson, Jonathan; van Schaik, André; Barton, Matthew; Morley, John W

    2014-01-01

    The lifespan of an acute brain slice is approximately 6-12 hours, limiting potential experimentation time. We have designed a new recovery incubation system capable of extending their lifespan to more than 36 hours. This system controls the temperature of the incubated artificial cerebral spinal fluid (aCSF) while continuously passing the fluid through a UVC filtration system and simultaneously monitoring temperature and pH. The combination of controlled temperature and UVC filtering maintains bacteria levels in the lag phase and leads to the dramatic extension of the brain slice lifespan. Brain slice viability was validated through electrophysiological recordings as well as live/dead cell assays. This system benefits researchers by monitoring incubation conditions and standardizing this artificial environment. It further provides viable tissue for two experimental days, reducing the time spent preparing brain slices and the number of animals required for research. PMID:24930889

  8. Artificial evolution by viability rather than competition.

    PubMed

    Maesani, Andrea; Fernando, Pradeep Ruben; Floreano, Dario

    2014-01-01

    Evolutionary algorithms are widespread heuristic methods inspired by natural evolution to solve difficult problems for which analytical approaches are not suitable. In many domains experimenters are not only interested in discovering optimal solutions, but also in finding the largest number of different solutions satisfying minimal requirements. However, the formulation of an effective performance measure describing these requirements, also known as fitness function, represents a major challenge. The difficulty of combining and weighting multiple problem objectives and constraints of possibly varying nature and scale into a single fitness function often leads to unsatisfactory solutions. Furthermore, selective reproduction of the fittest solutions, which is inspired by competition-based selection in nature, leads to loss of diversity within the evolving population and premature convergence of the algorithm, hindering the discovery of many different solutions. Here we present an alternative abstraction of artificial evolution, which does not require the formulation of a composite fitness function. Inspired from viability theory in dynamical systems, natural evolution and ethology, the proposed method puts emphasis on the elimination of individuals that do not meet a set of changing criteria, which are defined on the problem objectives and constraints. Experimental results show that the proposed method maintains higher diversity in the evolving population and generates more unique solutions when compared to classical competition-based evolutionary algorithms. Our findings suggest that incorporating viability principles into evolutionary algorithms can significantly improve the applicability and effectiveness of evolutionary methods to numerous complex problems of science and engineering, ranging from protein structure prediction to aircraft wing design. PMID:24489790

  9. EFFECTS OF SUSTAINED PRONGF BLOCKADE ON ATTENTIONAL CAPACITIES IN AGED RATS WITH COMPROMISED CHOLINERGIC SYSTEM

    PubMed Central

    YEGLA, BRITTNEY; PARIKH, VINAY

    2014-01-01

    Disruption in nerve growth factor (NGF) signaling via trkA receptors compromises the integrity of the basal forebrain (BF) cholinergic system, yielding cognitive, specifically attentional, impairments in Alzheimer’s disease (AD). Although normal aging is considered a risk factor for AD, the mechanisms underlying the selective vulnerability of the aging cholinergic system to trkA disruption is not clear. The levels of proNGF, a proneurotrophin that possesses higher affinity for p75 receptors, increase in aging. The present study was designed to test the hypothesis that cholinergic and attentional dysfunction in aged rats with reduced BF trkA receptors occurs due to the overactivation of endogenous proNGF signaling. We employed a viral vector that produced trkA shRNA to suppress trkA receptors in the corticopetal cholinergic neurons of aged rats. BF trkA suppression impaired animals’ performance on signal trials in both the sustained attention task (SAT) and the cognitively-taxing distractor version of SAT (dSAT) and these deficits were normalized by chronic intracerebroventricular administration of proNGF antibody. Moreover, depolarization-evoked ACh release and the density of cortical cholinergic fibers were partially restored in these animals. However, SAT/dSAT scores reflecting overall performance did not improve following proNGF blockade in trkA knockdown rats due to impaired performance in non-signal trials. Sustained proNGF blockade alone did not alter baseline attentional performance but produced moderate impairments during challenging conditions. Collectively, our findings indicate that barring proNGF-p75 signaling may exert some beneficial effects on attentional capacities specifically when BF trkA signaling is abrogated. However, endogenous proNGF may also possess neurotrophic effects and blockade of this proneurotrophin may not completely ameliorate attentional impairments in AD and potentially hinder performance during periods of high cognitive load

  10. Neuron changes in a mollusk in response to proteolytic enzymes.

    PubMed

    Sotnikov, O S; Lukovnikova, M V; Vasyagina, N Yu; Laktionova, A A; Paramonova, N M

    2010-09-01

    The aims of the present work were to investigate the structure of neurons after treatment with proteases and to identify possible recovery of interneuronal syncytial connections. In the first series of experiments, phase-contrast microscopy studies of live dissociated neurons from ganglia of the mollusk Lymnaea stagnalis treated with 0.4% pronase solution demonstrated retraction of nerve processes and biphasic changes in cell body volume. At stage I, at an average of 82.5 min, neuron body volume decreased by 12.1%, after which it increased by a mean of 14.1%. Signs of neuron viability in Ringer's solution were seen for an average of 828 min; survival time in pronase solution was 1.4 times shorter. In the second series of experiments, studies of neuron ultrastructure showed many cases of persistence of mitochondria, the rough and smooth endoplasmic reticulum (ER), Golgi complex, light and granular vesicles, nuclear structure, and neuroplasm optical density. Cells coming close together after centrifugation formed intracellular clefts of uniform width (about 20 nm). There were very rare cases of points at which membranes came into contact. There were no signs of syncytial connections. Lengthening and fusion of smooth ER cisterns separated fragments of neuron bodies from relatively undamaged cells. Some neurons were damaged, with multiple vacuoles formed form swollen mitochondria and ER cisterns. Fragments of nerve processes formed on dissociation were surrounded by a normal outer cell membrane. PMID:20652422