Activation of neurotensin receptor type 1 attenuates locomotor activity.

PubMed

Vadnie, Chelsea A; Hinton, David J; Choi, Sun; Choi, YuBin; Ruby, Christina L; Oliveros, Alfredo; Prieto, Miguel L; Park, Jun Hyun; Choi, Doo-Sup

2014-10-01

Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF-81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

Activation of Neurotensin Receptor Type 1 Attenuates Locomotor Activity

PubMed Central

Vadnie, Chelsea A.; Hinton, David J.; Choi, Sun; Choi, YuBin; Ruby, Christina L.; Oliveros, Alfredo; Prieto, Miguel L.; Park, Jun Hyun; Choi, Doo-Sup

2014-01-01

Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders. PMID:24929110

Dietary Neurotransmitters: A Narrative Review on Current Knowledge

PubMed Central

Dell’Osso, Bernardo; Malgaroli, Antonio; Banfi, Giuseppe; Zanaboni Dina, Carlotta; Galentino, Roberta; Porta, Mauro

2018-01-01

Foods are natural sources of substances that may exert crucial effects on the nervous system in humans. Some of these substances are the neurotransmitters (NTs) acetylcholine (ACh), the modified amino acids glutamate and γ-aminobutyric acid (GABA), and the biogenic amines dopamine, serotonin (5-HT), and histamine. In neuropsychiatry, progressive integration of dietary approaches in clinical routine made it necessary to discern the more about some of these dietary NTs. Relevant books and literature from PubMed and Scopus databases were searched for data on food sources of Ach, glutamate, GABA, dopamine, 5-HT, and histamine. Different animal foods, fruits, edible plants, roots, and botanicals were reported to contain NTs. These substances can either be naturally present, as part of essential metabolic processes and ecological interactions, or derive from controlled/uncontrolled food technology processes. Ripening time, methods of preservation and cooking, and microbial activity further contributes to NTs. Moreover, gut microbiota are considerable sources of NTs. However, the significance of dietary NTs intake needs to be further investigated as there are no significant data on their bioavailability, neuronal/non neuronal effects, or clinical implications. Evidence-based interventions studies should be encouraged. PMID:29748506

Loss of Action via Neurotensin-Leptin Receptor Neurons Disrupts Leptin and Ghrelin-Mediated Control of Energy Balance.

PubMed

Brown, Juliette A; Bugescu, Raluca; Mayer, Thomas A; Gata-Garcia, Adriana; Kurt, Gizem; Woodworth, Hillary L; Leinninger, Gina M

2017-05-01

The hormones ghrelin and leptin act via the lateral hypothalamic area (LHA) to modify energy balance, but the underlying neural mechanisms remain unclear. We investigated how leptin and ghrelin engage LHA neurons to modify energy balance behaviors and whether there is any crosstalk between leptin and ghrelin-responsive circuits. We demonstrate that ghrelin activates LHA neurons expressing hypocretin/orexin (OX) to increase food intake. Leptin mediates anorectic actions via separate neurons expressing the long form of the leptin receptor (LepRb), many of which coexpress the neuropeptide neurotensin (Nts); we refer to these as NtsLepRb neurons. Because NtsLepRb neurons inhibit OX neurons, we hypothesized that disruption of the NtsLepRb neuronal circuit would impair both NtsLepRb and OX neurons from responding to their respective hormonal cues, thus compromising adaptive energy balance. Indeed, mice with developmental deletion of LepRb specifically from NtsLepRb neurons exhibit blunted adaptive responses to leptin and ghrelin that discoordinate the mesolimbic dopamine system and ingestive and locomotor behaviors, leading to weight gain. Collectively, these data reveal a crucial role for LepRb in the proper formation of LHA circuits, and that NtsLepRb neurons are important neuronal hubs within the LHA for hormone-mediated control of ingestive and locomotor behaviors. Copyright © 2017 Endocrine Society.

Efficient removal of herbicide 2,4-dichlorophenoxyacetic acid from water using Ag/reduced graphene oxide co-decorated TiO2 nanotube arrays.

PubMed

Tang, Yanhong; Luo, Shenglian; Teng, Yarong; Liu, Chengbin; Xu, Xiangli; Zhang, Xilin; Chen, Liang

2012-11-30

A new photocatalyst, Ag nanoparticles (NPs) and reduced graphene oxide (RGO) co-decorated TiO(2) nanotube arrays (NTs) (Ag/RGO-TiO(2) NTs), was designed and facilely produced by combining electrodeposition and photoreduction processes. The structures and properties of the photocatalysts were characterized. The ternary catalyst exhibited almost 100% photocatalytic removal efficiency of typical herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) from water under simulated solar light irradiation. The photodegradation rate toward 2,4-D over Ag/RGO-TiO(2) NTs is 11.3 times that over bare TiO(2) NTs. After 10 successive cycles with 1600 min of irradiation, Ag/RGO-TiO(2) NTs maintained as high 2,4-D removal efficiency as 97.3% with excellent stability and easy recovery, which justifies the photocatalytic system a promising application for herbicide removal from water. Copyright © 2012 Elsevier B.V. All rights reserved.

Clinical Uses of Botulinum Neurotoxins: Current Indications, Limitations and Future Developments

PubMed Central

Chen, Sheng

2012-01-01

Botulinum neurotoxins (BoNTs) cause flaccid paralysis by interfering with vesicle fusion and neurotransmitter release in the neuronal cells. BoNTs are the most widely used therapeutic proteins. BoNT/A was approved by the U.S. FDA to treat strabismus, blepharospam, and hemificial spasm as early as 1989 and then for treatment of cervical dystonia, glabellar facial lines, axillary hyperhidrosis, chronic migraine and for cosmetic use. Due to its high efficacy, longevity of action and satisfactory safety profile, it has been used empirically in a variety of ophthalmological, gastrointestinal, urological, orthopedic, dermatological, secretory, and painful disorders. Currently available BoNT therapies are limited to neuronal indications with the requirement of periodic injections resulting in immune-resistance for some indications. Recent understanding of the structure-function relationship of BoNTs prompted the engineering of novel BoNTs to extend therapeutic interventions in non-neuronal systems and to overcome the immune-resistance issue. Much research still needs to be done to improve and extend the medical uses of BoNTs. PMID:23162705

An integrated decision-making framework for transportation architectures: Application to aviation systems design

NASA Astrophysics Data System (ADS)

Lewe, Jung-Ho

The National Transportation System (NTS) is undoubtedly a complex system-of-systems---a collection of diverse 'things' that evolve over time, organized at multiple levels, to achieve a range of possibly conflicting objectives, and never quite behaving as planned. The purpose of this research is to develop a virtual transportation architecture for the ultimate goal of formulating an integrated decision-making framework. The foundational endeavor begins with creating an abstraction of the NTS with the belief that a holistic frame of reference is required to properly study such a multi-disciplinary, trans-domain system. The culmination of the effort produces the Transportation Architecture Field (TAF) as a mental model of the NTS, in which the relationships between four basic entity groups are identified and articulated. This entity-centric abstraction framework underpins the construction of a virtual NTS couched in the form of an agent-based model. The transportation consumers and the service providers are identified as adaptive agents that apply a set of preprogrammed behavioral rules to achieve their respective goals. The transportation infrastructure and multitude of exogenous entities (disruptors and drivers) in the whole system can also be represented without resorting to an extremely complicated structure. The outcome is a flexible, scalable, computational model that allows for examination of numerous scenarios which involve the cascade of interrelated effects of aviation technology, infrastructure, and socioeconomic changes throughout the entire system.

Summary of Resources for the International Space Station Environmental Control and Life Support System

NASA Technical Reports Server (NTRS)

Williams, David E.

2003-01-01

The assembly complete Environmental Control and Life Support (ECLS) s ystem for the International Space Station (ISS) will consist of compo nents and subsystems in both the U.S. and International partner eleme nts which together will perform the functions of Temperature and Hum idity Control (THC), Atmosphere Control and Supply (ACS), Atmosphere Revitalization (AR), Water Recovery and Management (WRM), Fire Detect ion and Suppression (FDS), and Vacuum System (VS) for the station. D ue to limited resources available on ISS, detailed attention is given to minimizing and tracking all resources associated with all systems , beginning with estimates during the hardware development phase thr ough measured actuals when flight hardware is built and delivered. A summary of resources consumed by the current on-orbit U.S. ECLS syste m hardware is presented, including launch weight, average continuous and peak power loads, on-orbit volume and resupply logistics. ..

[Involvement of cross interaction between central cholinergic and histaminergic systems in the nucleus tractus solitarius in regulating carotid sinus baroreceptor reflex].

PubMed

Hu, Li-Xun; Zhang, Guo-Xing; Zhang, Yu-Ying; Zhao, Hong-Fen; Yu, Kang-Ying; Wang, Guo-Qing

2013-12-25

The carotid sinus baroreceptor reflex (CSR) is an important approach for regulating arterial blood pressure homeostasis instantaneously and physiologically. Activation of the central histaminergic or cholinergic systems results in CSR functional inhibitory resetting. However, it is unclear whether two systems at the nucleus tractus solitarius (NTS) level display cross interaction to regulate the CSR or not. In the present study, the left or right carotid sinus region was isolated from the systemic circulation in Sprague-Dawley rats (sinus nerve was reserved) anesthetized with pentobarbital sodium. Respective intubation was conducted into one side isolated carotid sinus and into the femoral artery for recording the intracarotid sinus pressure (ISP) and mean arterial pressure (MAP) simultaneously with pressure transducers connection in vivo. ISP was set at the level of 0 mmHg to eliminate the effect of initial internal pressure of the carotid sinus on the CSR function. To trigger CSR, the ISP was quickly elevated from 0 mmHg to 280 mmHg in a stepwise manner (40 mmHg) which was added at every step for over 4 s, and then ISP returned to 0 mmHg in similar steps. The original data of ISP and corresponding MAP were fitted to a modified logistic equation with five parameters to obtain the ISP-MAP, ISP-Gain relationship curves and the CSR characteristic parameters, which were statistically compared and analyzed separately. Under the precondition of no influence on the basic levels of the artery blood pressure, the effects and potential regulatory mechanism of preceding microinjection with different cholinoceptor antagonists, the selective cholinergic M1 receptor antagonist, i.e., pirenzepine (PRZ), the M2 receptor antagonist, i.e., methoctramine (MTR) or the N1 receptor antagonist, i.e., hexamethonium (HEX) into the NTS on the changes in function of CSR induced by intracerebroventricular injection (i.c.v.) of histamine (HA) in rats were observed. Meanwhile, the actions and possible modulatory mechanism of preceding microinjection with different histaminergic receptor antagonists, the selective histaminergic H1 receptor antagonist, i.e., chlorpheniramine (CHL) or the H2 receptor antagonist, i.e., cimetidine (CIM) into the NTS on the changes in function of CSR resulted from the i.c.v. cholinesterase inhibitor, physostigmine (PHY) were also examined in order to confirm and to analyze effects of cross interaction between central histaminergic and cholinergic systems on CSR. The main results obtained are as follows. (1) Standalone microinjection of different selective cholinergic receptor antagonists (PRZ, MTR or HEX) or different selective histaminergic receptor antagonists (CHL or CIM) into the NTS with each given dose had no effects on the CSR function and on the basic levels of the artery blood pressure, respectively (P > 0.05). (2) The pretreatment of PRZ or MTR into the NTS with each corresponding dose could attenuate CSR resetting resulted from i.c.v. HA in some degrees, which remarkably moved the posterior half range of ISP-MAP relationship curve downwards (P < 0.05), shifted the middle part of ISP-Gain relationship curve upwards (P < 0.05), and increased reflex parameters such as the MAP range and maximum gain (P < 0.05), but decreased parameters such as saturation pressure and intracarotid sinus pressure at maximum gain (P < 0.05). The catabatic effects of pretreatment with MTR into the NTS on CSR resetting induced by i.c.v. HA were more obvious than those with PRZ (P < 0.05), but pretreatment of HEX with given dose into the NTS had no effects on CSR resetting induced by i.c.v. HA (P > 0.05). (3) The effects of pretreatment of CHL or CIM into the NTS with each corresponding dose on CSR resetting made by i.c.v. PHY were similar to those of pretreatment of PRZ or MTR into the NTS on CSR resetting resulted from i.c.v. HA, and the decreasing effects of pretreatment with CHL into the NTS on CSR resetting induced by i.c.v. PHY were more remarkable than those with CIM (P < 0.05). These findings suggest that CSR resetting resulted from either HA or PHY into the lateral ventricle may partly involve the descending histaminergic or cholinergic pathway from the hypothalamus to NTS, which might evoke a cross activation of the cholinergic system in the NTS, via cholinergic M1 and M2 receptors mediation, especially the M2 receptors showing actions, or trigger another cross activation of the histaminergic system in the NTS, by histaminergic H1 and H2 receptors mediation, especially the H1 receptors displaying effects.

Non-technical skills and health care provision in low- and middle-income countries: a systematic review.

PubMed

Scott, John; Revera Morales, Dianali; McRitchie, Andrew; Riviello, Robert; Smink, Douglas; Yule, Steven

2016-04-01

Health care workers must possess high levels of medical knowledge, technical skills and also non-technical skills (NTS) in order to provide safe, effective and patient-centred care. Although there has been a recent proliferation of NTS assessment and training tools developed in high-income countries, little is known about NTS in low- and middle-income countries (LMICs), which face a variety of provider-level and system-level challenges. The aim of this study was to identify the NTS used by providers in LMICs that have been studied, describe how they are assessed and taught, and explain the contextual factors in LMICs that affect their use. We conducted a systematic literature review in accordance with preferred reporting items for systematic reviews and meta-analyses guidelines for primary research publications from January 1994 to December 2013 on evaluation or teaching of NTS used by health care workers in LMICs using MEDLINE, Embase, CIHHAL and Web of Science. Bibliographies of relevant manuscripts were also hand-searched to identify all potentially eligible manuscripts. We identified 21 manuscripts from 17 LMICs involving eight types of health care providers and trainees. These studies covered five NTS categories: decision making, communication, teamwork, leadership and stress management. The most commonly used methods were questionnaires, interviews and observations, and 43% (n = 9) scored > 10 points using the Medical Education Research Study Quality Instrument. Although many studies highlighted the ways in which overburdened health care systems, lack of provider empowerment and deficiencies in provider training had an impact on providers' use of these NTS, no context-specific assessment or educational tools were identified. There is growing worldwide interest in understanding and teaching critical non-technical skills to health care providers. This review highlights several studies describing a variety of important non-technical skills. However, these skills must be further characterised in order to develop context-specific tools for assessing and teaching NTS that are sensitive to the local challenges that are common across a variety of LMIC contexts. © 2016 John Wiley & Sons Ltd.

8-OH-DPAT abolishes the pulmonary C-fiber-mediated apneic response to fentanyl largely via acting on 5HT1A receptors in the nucleus tractus solitarius

PubMed Central

Zhuang, Jianguo; Zhang, Zhenxiong; Zhang, Cancan

2012-01-01

Intravenous bolus injection of morphine causes a vagal-mediated brief apnea (∼3 s), while continuous injection, via action upon central μ-opioid receptor (MOR), arrests ventilation (>20 s) that is eliminated by stimulating central 5-hydroxytryptamine 1A receptors (5HT1ARs). Bronchopulmonary C-fibers (PCFs) are essential for triggering a brief apnea, and their afferents terminate at the caudomedial region of the nucleus tractus solitarius (mNTS) that densely expresses 5HT1ARs. Thus we asked whether the vagal-mediated apneic response to MOR agonists was PCF dependent, and if so, whether this apnea was abolished by systemic administration of 8-hydroxy-2-(di-n-propylamino)tetral (8-OH-DPAT) largely through action upon mNTS 5HT1ARs. Right atrial bolus injection of fentanyl (5.0 μg/kg, a MOR agonist) was performed in the anesthetized and spontaneously breathing rats before and after: 1) selective blockade of PCFs' conduction and subsequent bivagotomy; 2) intravenous administration of 5HT1AR agonist 8-OH-DPAT; 3) intra-mNTS injection of 8-OH-DPAT; and 4) intra-mNTS injection of 5HT1AR antagonist WAY-100635 followed by 8-OH-DPAT (iv). We found the following: First, fentanyl evoked an immediate apnea (2.5 ± 0.4 s, ∼6-fold longer than the baseline expiratory duration, TE), which was abolished by either blocking PCFs' conduction or bivagotomy. Second, this apnea was prevented by systemic 8-OH-DPAT challenge. Third, intra-mNTS injection of 8-OH-DPAT greatly attenuated the apnea by 64%. Finally, intra-mNTS microinjection of WAY-100635 significantly attenuated (58%) the apneic blockade by 8-OH-DPAT (iv). We conclude that the vagal-mediated apneic response to MOR activation depends on PCFs, which is fully antagonized by systemic 8-OH-DPAT challenge largely via acting on mNTS 5HT1ARs. PMID:22696579

Antimicrobial residues and resistance against critically important antimicrobials in non-typhoidal Salmonella from meat sold at wet markets and supermarkets in Vietnam.

PubMed

Nhung, Nguyen Thi; Van, Nguyen Thi Bich; Cuong, Nguyen Van; Duong, Truong Thi Quy; Nhat, Tran Thi; Hang, Tran Thi Thu; Nhi, Nguyen Thi Hong; Kiet, Bach Tuan; Hien, Vo Be; Ngoc, Pham Thi; Campbell, James; Thwaites, Guy; Carrique-Mas, Juan

2018-02-02

Excessive antimicrobial usage and deficiencies in hygiene in meat production systems may result in undesirable human health hazards, such as the presence of antimicrobial drug residues and non-typhoidal Salmonella (NTS), including antimicrobial resistant (AMR) NTS. Recently, Vietnam has witnessed the emergence of integrated intensive animal production systems, coexisting with more traditional, locally-sourced wet markets. To date no systematic studies have been carried out to compare health hazards in beef, pork and chicken in different production systems. We aimed to: (1) estimate the prevalence of antimicrobial residues in beef, pork and chicken meat; (2) investigate the prevalence and levels of NTS contamination; and (3) investigate serovar distribution and AMR against critically important antimicrobials by animal species and type of retail (wet market vs. supermarket) in Vietnam. Fresh pork, beef and chicken meat samples (N=357) sourced from wet markets and supermarkets in Ho Chi Minh City (HCMC), Hanoi and Dong Thap were screened for antimicrobial residues by PremiTest, and were further investigated by Charm II. Samples from HCMC (N=113) were cultured using ISO 6579:2002/Amd 1:2007. NTS bacteria were quantified using a minimum probable number (MPN) technique. NTS isolates were assigned to serovar by Multilocus Sequence Typing (MLST), and were investigated for their phenotypic susceptibility against 32 antimicrobials. A total of 26 (7.3%) samples tested positive by PremiTest (9.5% beef, 4.1% pork and 8.4% chicken meat). Sulfonamides, tetracyclines and macrolides were detected by Charm in 3.1%, 2.8% and 2.0% samples, respectively. Overall, meat samples from wet markets had a higher prevalence of residues than those from supermarkets (9.6% vs. 2.6%) (p=0.016). NTS were isolated from 68.4% samples from HCMC. Chicken samples from wet markets had by far the highest NTS counts (median 3.2 logMPN/g). NTS isolates displayed high levels of resistance against quinolones (52.2%) and β-lactams (49.6%), but low levels against 3rd generation cephalosporins (4.4%) and aminoglycosides (0.8%). The highest adjusted prevalence of multidrug resistance (MDR) corresponded to isolates from chicken meat and pork (OR 8.3 and 1.8, respectively) (baseline=beef). S. Kentucky was the most common serovar identified (11 from chicken, 1 from beef) and 91.7% isolates was MDR. 11/12 isolates corresponded to ST198, a worldwide-disseminated multi-resistant NTS clone. We recommend stepping up policy measures to promote responsible antimicrobial use in animal production, as well as awareness about withdrawal periods to limit the hazard of residues in animal products, and improving slaughtering/hygiene procedures to limit cross-contamination with NTS, particularly in poultry wet markets. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Switching control of sympathetic activity from forebrain to hindbrain in chronic dehydration

PubMed Central

Colombari, Débora S A; Colombari, Eduardo; Freiria-Oliveira, Andre H; Antunes, Vagner R; Yao, Song T; Hindmarch, Charles; Ferguson, Alastair V; Fry, Mark; Murphy, David; Paton, Julian F R

2011-01-01

Abstract We investigated the mechanisms responsible for increased blood pressure and sympathetic nerve activity (SNA) caused by 2–3 days dehydration (DH) both in vivo and in situ preparations. In euhydrated (EH) rats, systemic application of the AT1 receptor antagonist Losartan and subsequent pre-collicular transection (to remove the hypothalamus) significantly reduced thoracic (t)SNA. In contrast, in DH rats, Losartan, followed by pre-collicular and pontine transections, failed to reduce tSNA, whereas transection at the medulla–spinal cord junction massively reduced tSNA. In DH but not EH rats, selective inhibition of the commissural nucleus tractus solitarii (cNTS) significantly reduced tSNA. Comparable data were obtained in both in situ and in vivo (anaesthetized/conscious) rats and suggest that following chronic dehydration, the control of tSNA transfers from supra-brainstem structures (e.g. hypothalamus) to the medulla oblongata, particularly the cNTS. As microarray analysis revealed up-regulation of AP1 transcription factor JunD in the dehydrated cNTS, we tested the hypothesis that AP1 transcription factor activity is responsible for dehydration-induced functional plasticity. When AP1 activity was blocked in the cNTS using a viral vector expressing a dominant negative FosB, cNTS inactivation was ineffective. However, tSNA was decreased after pre-collicular transection, a response similar to that seen in EH rats. Thus, the dehydration-induced switch in control of tSNA from hypothalamus to cNTS seems to be mediated via activation of AP1 transcription factors in the cNTS. If AP1 activity is blocked in the cNTS during dehydration, sympathetic activity control reverts back to forebrain regions. This unique reciprocating neural structure-switching plasticity between brain centres emphasizes the multiple mechanisms available for the adaptive response to dehydration. PMID:21708906

Leptin Acts via Lateral Hypothalamic Area Neurotensin Neurons to Inhibit Orexin Neurons by Multiple GABA-Independent Mechanisms

PubMed Central

Goforth, Paulette B.; Leinninger, Gina M.; Patterson, Christa M.

2014-01-01

The adipocyte-derived hormone leptin modulates neural systems appropriately for the status of body energy stores. Leptin inhibits lateral hypothalamic area (LHA) orexin (OX; also known as hypocretin)-producing neurons, which control feeding, activity, and energy expenditure, among other parameters. Our previous results suggest that GABAergic LHA leptin receptor (LepRb)-containing and neurotensin (Nts)-containing (LepRbNts) neurons lie in close apposition with OX neurons and control Ox mRNA expression. Here, we show that, similar to leptin, activation of LHA Nts neurons by the excitatory hM3Dq DREADD (designer receptor exclusively activated by designer drugs) hyperpolarizes membrane potential and suppresses action potential firing in OX neurons in mouse hypothalamic slices. Furthermore, ablation of LepRb from Nts neurons abrogated the leptin-mediated inhibition, demonstrating that LepRbNts neurons mediate the inhibition of OX neurons by leptin. Leptin did not significantly enhance GABAA-mediated inhibitory synaptic transmission, and GABA receptor antagonists did not block leptin-mediated inhibition of OX neuron activity. Rather, leptin diminished the frequency of spontaneous EPSCs onto OX neurons. Furthermore, leptin indirectly activated an ATP-sensitive potassium (KATP) channel in OX neurons, which was required for the hyperpolarization of OX neurons by leptin. Although Nts did not alter OX activity, galanin, which is coexpressed in LepRbNts neurons, inhibited OX neurons, whereas the galanin receptor antagonist M40 (galanin-(1–12)-Pro3-(Ala-Leu)2-Ala amide) prevented the leptin-induced hyperpolarization of OX cells. These findings demonstrate that leptin indirectly inhibits OX neurons by acting on LHA LepRbNts neurons to mediate two distinct GABA-independent mechanisms of inhibition: the presynaptic inhibition of excitatory neurotransmission and the opening of KATP channels. PMID:25143620

Concentrating versus non-concentrating reactors for solar photocatalytic degradation of p-nitrotoluene-o-sulfonic acid.

PubMed

Parra, S; Malato, S; Blanco, J; Péringer, P; Pulgari, C

2001-01-01

The photocatalytic oxidation of the non-biodegradable p-nitrotoluene-o-sulfonic acid (p-NTS) in homogeneous (photo-Fenton reactions) and heterogeneous (with TiO2) solutions has been studied at a pilot-scale under solar irradiation at the Plataforma Solar de Almeria (PSA). In this study two different reactors were tested: a medium concentrating radiation system (Heliomans, HM) and a non-concentrating radiation system (CPC). Their advantages and disadvantages for p-NTS degradation have been compared and discussed. The degradation rates obtained in the CPC collector are around three times more efficient than in the HM collectors. However, in both systems, 100% of the initial concentration of p-NTS was removed. Kinetic experiments were performed in both systems using TiO2 suspensions. During the photodegradation, the disappearance of p-NTS was followed by HPLC, the mineralization of the solution by the TOC technique, the evolution of NO3-, NO2-, and SO4(2-) concentration by ionic chromatography, the toxicity by the standard Microtox test, and the biodegradability by BOD5 and COD measurements. The obtained results demonstrated the utility of the heterogeneous catalysis (using TiO2 as catalyst) as a pretreatment method that can be followed by a biological process.

Atoxic derivative of botulinum neurotoxin A as a prototype vehicle for targeted delivery to neuronal cytoplasm

USDA-ARS?s Scientific Manuscript database

We have previously described genetic constructs and expression systems that enable facile production of recombinant derivatives of botulinum neurotoxins (BoNTs) that retain the structural and trafficking properties of wt BoNTs. In this report we describe the properties of one such derivative, BoNT/A...

BDNF - A key player in cardiovascular system.

PubMed

Pius-Sadowska, Ewa; Machaliński, Bogusław

2017-09-01

Neurotrophins (NTs) were first identified as target-derived survival factors for neurons of the central and peripheral nervous system (PNS). They are known to control neural cell fate, development and function. Independently of their neuronal properties, NTs exert unique cardiovascular activity. The heart is innervated by sensory, sympathetic and parasympathetic neurons, which require NTs during early development and in the establishment of mature properties, contributing to the maintenance of cardiovascular homeostasis. The identification of molecular mechanisms regulated by NTs and involved in the crosstalk between cardiac sympathetic nerves, cardiomyocytes, cardiac fibroblasts, and vascular cells, has a fundamental importance in both normal heart function and disease. The article aims to review the recent data on the effects of Brain-Derived Neurotrophic Factor (BDNF) on various cardiovascular neuronal and non-neuronal functions such as the modulation of synaptic properties of autonomic neurons, axonal outgrowth and sprouting, formation of the vascular and neural networks, smooth muscle migration, and control of endothelial cell survival and cardiomyocytes. Understanding these mechanisms may be crucial for developing novel therapeutic strategies, including stem cell-based therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes.

PubMed

Pérez-Isidoro, Rosendo; Ruiz-Suárez, J C

2016-09-01

We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH conditions. As NTs we used acetylcholine (ACh), γ-aminobutyric acid (GABA), and l-glutamic acid (LGlu). As ATs, tetracaine (TC), and pentobarbital (PB) were employed. By using differential scanning calorimetry (DSC), we analyzed the changes such molecules produce in the thermal properties of the membranes. We found that calcium and pH play important roles in the interactions of NTs and ATs with the anionic lipid membranes. Changes in pH promote deprotonation of the phosphate groups in anionic phospholipids inducing electrostatic interactions between them and NTs; but if Ca(2+) ions are in the system, these act as bridges. Such interactions impact the physical properties of the membranes in a similar manner that anesthetics do. Beyond the usual biochemical approach, we claim that these effects should be taken into account to understand the excitatory-inhibitory orchestrated balance in the nervous system. Copyright © 2016 Elsevier B.V. All rights reserved.

Identifying the nontechnical skills required of nurses in general surgical wards.

PubMed

Marshall, Dianne C; Finlayson, Mary P

2018-04-01

To identify the nontechnical skills (NTS) required of nurses in general surgical wards for safe and effective care. As the largest occupational group, nurses are in an ideal position to block the vulnerabilities of patient adverse events in a surgical ward. Previous studies in the surgical environment have identified the NTS required of nurses for safe care in operating rooms; however, these skills have not been identified for nurses in general surgical wards. A nonparticipant observational descriptive design was used. A purposive sample of 15 registered nurses was recruited from four surgical wards and observed for a full shift on a morning, afternoon or night shift. Nonparticipant observations were conducted using field notes to collect data. A coding frame was developed, and an inductive process was used to analyse the data. A taxonomy comprising seven NTS required of nurses in their roles in surgical ward teams emerged from the data analysis. They are communication, leadership and management, planning, decision-making, situation awareness, teamwork and patient advocacy. Patient care provided by general surgical nurses involved the seven identified key NTS. These particular NTS are an important component of safe nursing practice as they underpin the provision of safe and effective care for general surgical patients. Nurses block the trajectory of error by using NTS to address the vulnerabilities in the system that can lead to adverse patient events. Identifying general surgical nurses' NTS enables the development of teaching strategies that target the learning of those skills to achieve successful work outcomes and improve patient safety. © 2018 John Wiley & Sons Ltd.

Behaviour of bentazon as influenced by water and tillage management in rice-growing conditions.

PubMed

López-Piñeiro, Antonio; Peña, David; Albarrán, Ángel; Sánchez-Llerena, Javier; Rato-Nunes, José Manuel; Rozas, María Ángeles

2017-06-01

Bentazon is a widely used herbicide in rice agroecosystems that has commonly been found in water resources. To assess how tillage and water regimes affect sorption/desorption, dissipation and leaching of bentazon in Mediterranean rice-growing conditions, field experiments were carried out using tillage and flooding (TF), tillage and sprinkler irrigation (TS), no-tillage and sprinkler irrigation (NTS) and long-term no-tillage and sprinkler irrigation (NTS7). After 3 years, the K d values in TS were 2.3, 1.6 and 1.7 times lower than the values in NTS7, NTS and TF respectively. Greater sorption of bentazon was related to higher contents in total organic carbon and, although to a lesser extent, in humic acids and dissolved organic carbon. The persistence of bentazon was significantly greater under anaerobic (half-life DT 50 = 94.1-135 days) than under aerobic (DT 50 = 42.4-91.3 days) incubation conditions for all management regimes. Leaching losses of bentazon were reduced from 78 and 74% in TS and TF to 61 and 62% in NTS7 and NTS respectively. The mid- and long-term implementation of sprinkler irrigation in combination with no-tillage could be considered a management system that is effective at reducing water contamination by bentazon in Mediterranean rice-growing agroecosystems. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Novel therapeutic uses and formulations of botulinum neurotoxins: a patent review (2012 - 2014).

PubMed

Kane, Christopher D; Nuss, Jonathan E; Bavari, Sina

2015-06-01

Botulinum neurotoxins (BoNTs) are among the most toxic of known biological molecules and function as acetylcholine release inhibitors and neuromuscular blocking agents. Paradoxically, these properties also make them valuable therapeutic agents for the treatment of movement disorders, urological conditions and hypersecretory disorders. Greater understanding of their molecular mechanism of action and advances in protein engineering has led to significant efforts to improve and expand their function with a view towards broadening their therapeutic potential. Searches of Espacenet and Google Patent have revealed a number of patents related to BoNTs. This review will focus on novel therapeutic uses and formulations disclosed during 2012 - 2014. The seven patents discussed will include nanoformulations of FDA-approved BoNTs, additional BoNT subtypes and novel BoNT variants and chimeras created through protein engineering. Supporting patents and related publications are also briefly discussed. The clinical and commercial success of BoNTs has prompted investigation into novel BoNTs or BoNT-mediated chimeras with promising in vitro results. Distinct strategies including the use of nanoformulations and targeted delivery have been implemented to identify new indication and improved functionality. Greater understanding of their systemic exposure, efficacy and safety profiles will be required for further development.

Evaluation of antimicrobial resistance phenotypes for predicting multidrug-resistant Salmonella recovered from retail meats and humans in the United States.

PubMed

Whichard, Jean M; Medalla, Felicita; Hoekstra, Robert M; McDermott, Patrick F; Joyce, Kevin; Chiller, Tom; Barrett, Timothy J; White, David G

2010-03-01

Although multidrug-resistant (MDR) non-Typhi Salmonella (NTS) strains are a concern in food production, determining resistance to multiple antimicrobial agents at slaughter or processing may be impractical. Single antimicrobial resistance results for predicting multidrug resistance are desirable. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were used to determine each antimicrobial agent's ability to predict MDR phenotypes of human health significance: ACSSuT (resistance to at least ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, tetracycline) in NTS isolates, and MDR-AmpC-SN (resistance to ACSSuT, additional resistance to amoxicillin-clavulanate and to ceftiofur, and decreased susceptibility [MIC >= 2 microg/ml] to ceftriaxone) in NTS serotype Newport. The U.S. National Antimicrobial Resistance Monitoring System determined MICs to 15 or more antimicrobial agents for 9,955 NTS isolates from humans from 1999 to 2004 and 689 NTS isolates from retail meat from 2002 to 2004. A total of 847 (8.5%) human and 26 (3.8%) retail NTS isolates were ACSSuT; 995 (10.0%) human and 16 (2.3%) retail isolates were serotype Newport. Among Salmonella Newport, 204 (20.5%) human and 9 (56.3%) retail isolates were MDR-AmpC-SN. Chloramphenicol resistance provided the highest PPVs for ACSSuT among human (90.5%; 95% confidence interval, 88.4 to 92.3) and retail NTS isolates (96.3%; 95% confidence interval, 81.0 to 99.9). Resistance to ceftiofur and to amoxicillin-clavulanate and decreased susceptibility to ceftriaxone provided the highest PPVs (97.1, 98.1, and 98.6%, respectively) for MDR-AmpC-SN from humans. High PPVs for these agents applied to retail meat MDR-AmpC-SN, but isolate numbers were lower. Variations in MIC results may complicate ceftriaxone's predictive utility. Selecting specific antimicrobial resistance offers practical alternatives for predicting MDR phenotypes. Chloramphenicol resistance works best for ACSSuT-NTS, and resistance to ceftiofur, amoxicillin-clavulanate, or chloramphenicol works best for MDR-AmpC-SN.

Leptin acts via lateral hypothalamic area neurotensin neurons to inhibit orexin neurons by multiple GABA-independent mechanisms.

PubMed

Goforth, Paulette B; Leinninger, Gina M; Patterson, Christa M; Satin, Leslie S; Myers, Martin G

2014-08-20

The adipocyte-derived hormone leptin modulates neural systems appropriately for the status of body energy stores. Leptin inhibits lateral hypothalamic area (LHA) orexin (OX; also known as hypocretin)-producing neurons, which control feeding, activity, and energy expenditure, among other parameters. Our previous results suggest that GABAergic LHA leptin receptor (LepRb)-containing and neurotensin (Nts)-containing (LepRb(Nts)) neurons lie in close apposition with OX neurons and control Ox mRNA expression. Here, we show that, similar to leptin, activation of LHA Nts neurons by the excitatory hM3Dq DREADD (designer receptor exclusively activated by designer drugs) hyperpolarizes membrane potential and suppresses action potential firing in OX neurons in mouse hypothalamic slices. Furthermore, ablation of LepRb from Nts neurons abrogated the leptin-mediated inhibition, demonstrating that LepRb(Nts) neurons mediate the inhibition of OX neurons by leptin. Leptin did not significantly enhance GABAA-mediated inhibitory synaptic transmission, and GABA receptor antagonists did not block leptin-mediated inhibition of OX neuron activity. Rather, leptin diminished the frequency of spontaneous EPSCs onto OX neurons. Furthermore, leptin indirectly activated an ATP-sensitive potassium (K(ATP)) channel in OX neurons, which was required for the hyperpolarization of OX neurons by leptin. Although Nts did not alter OX activity, galanin, which is coexpressed in LepRb(Nts) neurons, inhibited OX neurons, whereas the galanin receptor antagonist M40 (galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide) prevented the leptin-induced hyperpolarization of OX cells. These findings demonstrate that leptin indirectly inhibits OX neurons by acting on LHA LepRb(Nts) neurons to mediate two distinct GABA-independent mechanisms of inhibition: the presynaptic inhibition of excitatory neurotransmission and the opening of K(ATP) channels. Copyright © 2014 the authors 0270-6474/14/3411405-11$15.00/0.

Contributions of long-term tillage systems on crop production and soil properties in the semi-arid Loess Plateau of China.

PubMed

Niu, Yining; Zhang, Renzhi; Luo, Zhuzhu; Li, Lingling; Cai, Liqun; Li, Guang; Xie, Junhong

2016-06-01

This study determined the long-term effect of tillage systems on soil properties and crop yields in a semi-arid environment. Field pea (Pisum sativum L.) and spring wheat (Triticum aestivum L.) were alternately grown in six tillage systems at Dingxi (35° 28' N, 104° 44' E), north-west China starting in 2001. After the first 6 years of experiments, conventional tillage with stubble incorporating (TS) and no-till with stubble cover (NTS) increased soil organic matter by 9.9% and 13.0%, respectively, compared to the conventional tillage with stubble removed (T); both TS and NTS also increased soil microbial counts, available K and P, and total N. No-till with stubble removed (NT), NTS and NTP (no-till with plastic mulching) had 20.7%, 62.6% and 43.7% greater alkaline phosphatase activity compared to the T treatment. Soil catalase, urease and invertase activities were all greater in the no-till treatments than in the T treatment. Averaged across 6 years, both wheat and pea achieved highest grain yields under NTS treatment. No-till with stubble retention is the most promising system for improving soil physical, biological and chemical properties, and increasing crop yields, and thus, this system can be adopted in areas with conditions similar to the semi-arid north-west China. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Antimicrobial resistance among invasive nontyphoidal Salmonella enterica isolates in the United States: National Antimicrobial Resistance Monitoring System, 1996 to 2007.

PubMed

Crump, John A; Medalla, Felicita M; Joyce, Kevin W; Krueger, Amy L; Hoekstra, R Michael; Whichard, Jean M; Barzilay, Ezra J

2011-03-01

Nontyphoidal salmonellae (NTS) are important causes of community-acquired bloodstream infection. We describe patterns of antimicrobial resistance among invasive NTS in the United States. We compared bloodstream NTS isolates with those from stool submitted to the National Antimicrobial Resistance Monitoring System (NARMS) from 1996 to 2007. We describe antimicrobial resistance among invasive strains by serogroup and serotype. Of the 19,302 NTS isolates, 17,804 (92.2%) were from stool or blood. Of these, 1,050 (5.9%) were bloodstream isolates. The median ages (ranges) of patients with and without bacteremia were 36 (<1 to 97) years and 20 (<1 to 105) years, respectively (P < 0.001). Males (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.06 to 1.38) and those ≥65 years of age were at greater risk for invasive disease. Salmonella enterica serotypes Enteritidis, Typhimurium, and Heidelberg were the most common serotypes isolated from blood; S. enterica serotypes Dublin, Sandiego, and Schwarzengrund were associated with the greatest risk for bloodstream isolation. Of invasive isolates, 208 (19.8%) were resistant to ampicillin, 117 (11.1%) to chloramphenicol, and 26 (2.5%) to trimethoprim-sulfamethoxazole; 28 (2.7%) isolates were resistant to nalidixic acid and 26 (2.5%) to ceftriaxone. Antimicrobial resistance to traditional agents is common. However, the occurrence of nalidixic acid and ceftriaxone resistance among invasive NTS is cause for clinical and public health vigilance.

Antimicrobial Resistance among Invasive Nontyphoidal Salmonella enterica Isolates in the United States: National Antimicrobial Resistance Monitoring System, 1996 to 2007 ▿

PubMed Central

Crump, John A.; Medalla, Felicita M.; Joyce, Kevin W.; Krueger, Amy L.; Hoekstra, R. Michael; Whichard, Jean M.; Barzilay, Ezra J.

2011-01-01

Nontyphoidal salmonellae (NTS) are important causes of community-acquired bloodstream infection. We describe patterns of antimicrobial resistance among invasive NTS in the United States. We compared bloodstream NTS isolates with those from stool submitted to the National Antimicrobial Resistance Monitoring System (NARMS) from 1996 to 2007. We describe antimicrobial resistance among invasive strains by serogroup and serotype. Of the 19,302 NTS isolates, 17,804 (92.2%) were from stool or blood. Of these, 1,050 (5.9%) were bloodstream isolates. The median ages (ranges) of patients with and without bacteremia were 36 (<1 to 97) years and 20 (<1 to 105) years, respectively (P < 0.001). Males (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.06 to 1.38) and those ≥65 years of age were at greater risk for invasive disease. Salmonella enterica serotypes Enteritidis, Typhimurium, and Heidelberg were the most common serotypes isolated from blood; S. enterica serotypes Dublin, Sandiego, and Schwarzengrund were associated with the greatest risk for bloodstream isolation. Of invasive isolates, 208 (19.8%) were resistant to ampicillin, 117 (11.1%) to chloramphenicol, and 26 (2.5%) to trimethoprim-sulfamethoxazole; 28 (2.7%) isolates were resistant to nalidixic acid and 26 (2.5%) to ceftriaxone. Antimicrobial resistance to traditional agents is common. However, the occurrence of nalidixic acid and ceftriaxone resistance among invasive NTS is cause for clinical and public health vigilance. PMID:21199924

Nevada Test Site Environmental Report 2007

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

Cathy Wills

2008-09-01

The Nevada Test Site Environmental Report 2007 (NTSER) was prepared to meet the information needs of the public and the requirements and guidelines of the U.S. Department of Energy (DOE) for annual site environmental reports. It was prepared by National Security Technologies, LLC (NSTec). This Executive Summary presents the purpose of the document, the major programs conducted at the Nevada Test Site (NTS), NTS key environmental initiatives, radiological releases and potential doses to the public resulting from site operations, a summary of nonradiological releases, implementation status of the NTS Environmental Management System, a summary of compliance with environmental regulations, pollutionmore » prevention and waste minimization accomplishments, and significant environmental accomplishments. Much of the content of this Executive Summary is also presented in a separate stand-alone pamphlet titled Nevada Test Site Environmental Report Summary 2007. This NTSER was prepared to satisfy DOE Order 231.1A, Environment, Safety and Health Reporting. Its purpose is to (1) report compliance status with environmental standards and requirements, (2) present results of environmental monitoring of radiological and nonradiological effluents, (3) report estimated radiological doses to the public from releases of radioactive material, (4) summarize environmental incidents of noncompliance and actions taken in response to them, (5) describe the NTS Environmental Management System and characterize its performance, and (6) highlight significant environmental programs and efforts. This report meets these objectives for the NTS and three offsite Nevada facilities mentioned in this report.« less

Development of an Accelerated Hydrogen Embrittlement Test for Manganese Phosphated Steels

DTIC Science & Technology

2011-05-01

from the same vendor (RSL Testing Systems) and lot (HT/ HTP ) were used. See Appendix B for the certifications for lots HT/ HTP . Note: lot HTP is...Based on the vendor certification of the notched tensile specimens from RSL lot HT/ HTP , the NTS was 373 ksi and the average load at failure was...Systems Lot HT/ HTP ). Note that use of a higher reference NTS and load to failure is a conservative approach since the specimens will experience

Emerging role of neurotensin in regulation of the cardiovascular system.

PubMed

Osadchii, Oleg E

2015-09-05

There is increasing evidence in support of an important role played by neurotensin (NT), a tridecapeptide originally found in bovine hypothalamus, in regulation of cardiovascular system. Elevated systemic levels of NT may contribute to pathogenesis of acute circulatory disoders, and predict the risk for cardiovascular morbidity and mortality in population-based studies. Within cardiovascular system, NT-containing neural fibers are found in close contact with atrial and ventricular cardiac myocytes, cardiac conduction system, intracardiac ganglia, as well as coronary vessels in humans and various animal species. The density of NT-immunoreactive innervation is reduced in cardiac disease. NT produces a variety of cardiovascular actions including effects on heart rate, myocardial contractility, systemic blood pressure, coronary vascular tone, venous smooth muscle tone, and regional blood flow in gastrointestinal tract, cutaneous and adipose tissue. NT could trigger cardiovascular reflexes by stimulating primary visceral afferents synaptically connected with preganglionic sympathetic neurons at the spinal cord. Structural determinants of biological activity of NT reside primarily in the C-terminal portion of its molecule which is responsible for receptor activation. NT effects are mediated via activation of NT receptors, or produced indirectly via stimulation of release of various endogenous neuromodulators/neurotransmitters such as histamine, catecholamines and prostaglandins. Three subtypes of NT receptor (NTS1, NTS2 and NTS3) have been shown to be expressed in the myocardium. NTS1, a high-affinity NT binding site coupled to phospholipase C-inositoltrisphosphate transduction pathway, is thought to mediate NT-induced cardiovascular responses. Copyright © 2015 Elsevier B.V. All rights reserved.

Letter Report: Yucca Mountain Environmental Monitoring Systems Initiative - Air Quality Scoping Study for Caliente, Lincoln County, Nevada

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

J. Englebrecht; I. Kavouras; D. Campbell

2008-08-01

The Desert Research Institute (DRI) is performing a scoping study as part of the U.S. Department of Energy's Yucca Mountain Environmental Monitoring Systems Initiative (EMSI). The main objective is to obtain baseline air quality information for Yucca Mountain and an area surrounding the Nevada Test Site (NTS). Air quality and meteorological monitoring and sampling equipment housed in a mobile trailer (shelter) is collecting data at eight sites outside the NTS, including Ash Meadows National Wildlife Refuge (NWR), Beatty, Sarcobatus Flats, Rachel, Caliente, Pahranagat NWR, Crater Flat, and Tonopah Airport, and at four sites on the NTS (Engelbrecht et al., 2007a-d).more » The trailer is stationed at any one site for approximately eight weeks at a time. This letter report provides a summary of air quality and meteorological data, on completion of the site's sampling program.« less

Letter Report: Yucca Mountain Environmental Monitoring Systems Initiative - Air Quality Scoping Study for Pahranagat National Wildlife Refuge, Lincoln County, Nevada

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

J. Englebrecht; I. Kavouras; D. Campbell

2008-08-01

The Desert Research Institute (DRI) is performing a scoping study as part of the U.S. Department of Energy's Yucca Mountain Environmental Monitoring Systems Initiative (EMSI). The main objective is to obtain baseline air quality information for Yucca Mountain and an area surrounding the Nevada Test Site (NTS). Air quality and meteorological monitoring and sampling equipment housed in a mobile trailer (shelter) is collecting data at eight sites outside the NTS, including Ash Meadows National Wildlife Refuge (NWR), Pahranagat NWR, Beatty, Rachel, Caliente, Crater Flat, and Tonopah Airport, and at four sites on the NTS (Engelbrecht et al., 2007a-d). The trailermore » is stationed at any one site for approximately eight weeks at a time. This letter report provides a summary of air quality and meteorological data on completion of the site's sampling program.« less

Letter Report Yucca Mountain Environmental Monitoring Systems Initiative - Air Quality Scoping Study for Pahranagat National Wildlife Refuge, Lincoln County, Nevada

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

J. Engelbrecht; I. Kavouras; D. Campbell

2009-04-02

The Desert Research Institute (DRI) is performing a scoping study as part of the U.S. Department of Energy's Yucca Mountain Environmental Monitoring Systems Initiative (EMSI). The main objective is to obtain baseline air quality information for Yucca Mountain and an area surrounding the Nevada Test Site (NTS). Air quality and meteorological monitoring and sampling equipment housed in a mobile trailer (shelter) is collecting data at eight sites outside the NTS, including Ash Meadows National Wildlife Refuge (NWR), Pahranagat NWR, Beatty, Rachel, Caliente, Crater Flat, and Tonopah Airport, and at four sites on the NTS (Engelbrecht et al., 2007a-d). The trailermore » is stationed at any one site for approximately eight weeks at a time. This letter report provides a summary of air quality and meteorological data on completion of the site's sampling program.« less

DOE/NV/26383-LTR2008-01 Letter Report Yucca Mountain Environmental Monitoring Systems Initiative - Air Quality Scoping Study for Caliente, Lincoln County, Nevada

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

J. Engelbrecht; I. Kavouras; D. Campbell

2009-04-02

The Desert Research Institute (DRI) is performing a scoping study as part of the U.S. Department of Energy's Yucca Mountain Environmental Monitoring Systems Initiative (EMSI). The main objective is to obtain baseline air quality information for Yucca Mountain and an area surrounding the Nevada Test Site (NTS). Air quality and meteorological monitoring and sampling equipment housed in a mobile trailer (shelter) is collecting data at eight sites outside the NTS, including Ash Meadows National Wildlife Refuge (NWR), Beatty, Sarcobatus Flats, Rachel, Caliente, Pahranagat NWR, Crater Flat, and Tonopah Airport, and at four sites on the NTS (Engelbrecht et al., 2007a-d).more » The trailer is stationed at any one site for approximately eight weeks at a time. This letter report provides a summary of air quality and meteorological data, on completion of the site's sampling program.« less

Letter Report Yucca Mountain Environmental Monitoring Systems Initiative - Air Quality Scoping Study for Tonopah Airport, Nye County, Nevada

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

J. Engelbrecht; I. Kavouras; D. Campbell

2009-04-02

The Desert Research Institute (DRI) is performing a scoping study as part of the U.S. Department of Energy's Yucca Mountain Environmental Monitoring Systems Initiative (EMSI). The main objective is to obtain baseline air quality information for Yucca Mountain and an area surrounding the Nevada Test Site (NTS). Air quality and meteorological monitoring and sampling equipment housed in a mobile trailer (shelter) is collecting data at eight sites outside the NTS, including Ash Meadows National Wildlife Refuge (NWR), Tonopah Airport, Beatty, Rachel, Caliente, Pahranagat NWR, Crater Flat, and the Tonopah Airport, and at four sites on the NTS (Engelbrecht et al.,more » 2007a-d). The trailer is stationed at any one site for approximately eight weeks at a time. This letter report provides a summary of air quality and meteorological data, on completion of the site's sampling program.« less

Letter Report: Yucca Mountain Environmental Monitoring Systems Initiative - Air Quality Scoping Study for Tonopah Airport, Nye County, Nevada

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

J. Engelbrecht; I. Kavouras; D Campbell

2008-08-01

The Desert Research Institute (DRI) is performing a scoping study as part of the U.S. Department of Energy's Yucca Mountain Environmental Monitoring Systems Initiative (EMSI). The main objective is to obtain baseline air quality information for Yucca Mountain and an area surrounding the Nevada Test Site (NTS). Air quality and meteorological monitoring and sampling equipment housed in a mobile trailer (shelter) is collecting data at eight sites outside the NTS, including Ash Meadows National Wildlife Refuge (NWR), Tonopah Airport, Beatty, Rachel, Caliente, Pahranagat NWR, Crater Flat, and the Tonopah Airport, and at four sites on the NTS (Engelbrecht et al.,more » 2007a-d). The trailer is stationed at any one site for approximately eight weeks at a time. This letter report provides a summary of air quality and meteorological data, on completion of the site's sampling program.« less

An integrative assessment of the commercial air transportation system via adaptive agents

NASA Astrophysics Data System (ADS)

Lim, Choon Giap

The overarching research objective is to address the tightly-coupled interactions between the demand-side and supply-side components of the United States Commercial Air Transportation System (CATS) in a time-variant environment. A system-of-system perspective is adopted, where the scope is extended beyond the National Airspace System (NAS) level to the National Transportation System (NTS) level to capture the intermodal and multimodal relationships between the NTS stakeholders. The Agent-Based Modeling and Simulation technique is employed where the NTS/NAS is treated as an integrated Multi-Agent System comprising of consumer and service provider agents, representing the demand-side and supply-side components respectively. Successful calibration and validation of both model components against the observable real world data resulted in a CATS simulation tool where the aviation demand is estimated from socioeconomic and demographic properties of the population instead of merely based on enplanement growth multipliers. This valuable achievement enabled a 20-year outlook simulation study to investigate the implications of a global fuel price hike on the airline industry and the U.S. CATS at large. Simulation outcomes revealed insights into the airline competitive behaviors and the subsequent responses from transportation consumers.

Continuity of neuropil threads with tangle-bearing and tangle-free neurons in Alzheimer disease cortex. A confocal laser scanning microscopy study.

PubMed

Schmidt, M L; Murray, J M; Trojanowski, J Q

1993-04-01

Neuropil threads (NTs) are abnormal processes that are associated with tangle-bearing neurons in gray matter areas of Alzheimer disease (AD) brains. Although NTs contain paired helical filaments (PHFs) and share multiple tau epitopes with neurobrillary tangles (NFTs), the relationship between NTs and tangle-bearing neurons is unclear. For this reason, we assessed the continuity of NTs with tangle-bearing and tangle-free neurons. Since astrocytes express low levels of tau and rarely have been shown to contain PHFs, we also examined the relationship of NTs to cortical astrocytes. This was done using histochemical and immunochemical methods in conjunction with confocal laser scanning microscopy to examine NTs in amygdala and entorhinal cortex of seven AD brains. Only a small fraction of NTs (< 1%) in 3.5 x 10(6) microns 3 of amygdala and entorhinal cortex could be traced to local neurons with NFTs or to neurons that did not contain NFTs, and no NTs were continuous with cortical astrocytes. These results indicate that only a very small percentage of NTs in entorhinal cortex and amygdala occur in the most proximal segments of processes that emanate from tangle-bearing or tangle-free neurons. This implies that the majority of NTs reside in the distal parts of dendrites and/or the terminal arborizations of axons or that NTs are discontinuous abnormalities. Taken together, these data suggest that NTs could disrupt local and long distance neuronal circuitry and thereby contribute to the cognitive impairments seen in AD patients.

Rapid, conformal gas-phase formation of silica (SiO2) nanotubes from water condensates

NASA Astrophysics Data System (ADS)

Bae, Changdeuck; Kim, Hyunchul; Yang, Yunjeong; Yoo, Hyunjun; Montero Moreno, Josep M.; Bachmann, Julien; Nielsch, Kornelius; Shin, Hyunjung

2013-06-01

An innovative atomic layer deposition (ALD) concept, with which nanostructures of water condensates with high aspect ratio at equilibrium in cylindrical nanopores can be transformed uniformly into silica (SiO2) at near room temperature and ambient pressure, has been demonstrated for the first time. As a challenging model system, we first prove the conversion of cylindrical water condensates in porous alumina membranes to silica nanotubes (NTs) by introducing SiCl4 as a metal reactant without involving any catalytic reaction. Surprisingly, the water NTs reproducibly transformed into silica NTs, where the wall thickness of the silica NTs deposited per cycle was found to be limited by the amount of condensed water, and it was on the orders of ten nanometers per cycle (i.e., over 50 times faster than that of conventional ALD). More remarkably, the reactions only took place for 10-20 minutes or less without vacuum-related equipment. The thickness of initially adsorbed water layers in cylindrical nanopores was indirectly estimated from the thickness of formed SiO2 layers. With systematic experimental designs, we tackle the classical Kelvin equation in the nanosized pores, and the role of van der Waals forces in the nanoscale wetting phenomena, which is a long-standing issue lacking experimental insight. Moreover, we show that the present strategy is likely generalized to other oxide systems such as TiO2. Our approach opens up a new avenue for ultra-simple preparation of porous oxides and allows for the room temperature formation of dielectric layers toward organic electronic and photovoltaic applications.An innovative atomic layer deposition (ALD) concept, with which nanostructures of water condensates with high aspect ratio at equilibrium in cylindrical nanopores can be transformed uniformly into silica (SiO2) at near room temperature and ambient pressure, has been demonstrated for the first time. As a challenging model system, we first prove the conversion of cylindrical water condensates in porous alumina membranes to silica nanotubes (NTs) by introducing SiCl4 as a metal reactant without involving any catalytic reaction. Surprisingly, the water NTs reproducibly transformed into silica NTs, where the wall thickness of the silica NTs deposited per cycle was found to be limited by the amount of condensed water, and it was on the orders of ten nanometers per cycle (i.e., over 50 times faster than that of conventional ALD). More remarkably, the reactions only took place for 10-20 minutes or less without vacuum-related equipment. The thickness of initially adsorbed water layers in cylindrical nanopores was indirectly estimated from the thickness of formed SiO2 layers. With systematic experimental designs, we tackle the classical Kelvin equation in the nanosized pores, and the role of van der Waals forces in the nanoscale wetting phenomena, which is a long-standing issue lacking experimental insight. Moreover, we show that the present strategy is likely generalized to other oxide systems such as TiO2. Our approach opens up a new avenue for ultra-simple preparation of porous oxides and allows for the room temperature formation of dielectric layers toward organic electronic and photovoltaic applications. Electronic supplementary information (ESI) available: TEM gallery of silica NTs under different experimental conditions, detailed calculation of estimating the thickness of condensed water and Hamaker constants, and a comparison of processing times. See DOI: 10.1039/c3nr00906h

Detection of Respiratory Viruses in Sputum from Adults by Use of Automated Multiplex PCR

PubMed Central

Walsh, Edward E.; Formica, Maria A.; Falsey, Ann R.

2014-01-01

Respiratory tract infections (RTI) frequently cause hospital admissions among adults. Diagnostic viral reverse transcriptase PCR (RT-PCR) of nose and throat swabs (NTS) is useful for patient care by informing antiviral use and appropriate isolation. However, automated RT-PCR systems are not amenable to utilizing sputum due to its viscosity. We evaluated a simple method of processing sputum samples in a fully automated respiratory viral panel RT-PCR assay (FilmArray). Archived sputum and NTS samples collected in 2008-2012 from hospitalized adults with RTI were evaluated. A subset of sputum samples positive for 10 common viruses by a uniplex RT-PCR was selected. A sterile cotton-tip swab was dunked in sputum, swirled in 700 μL of sterile water (dunk and swirl method) and tested by the FilmArray assay. Quantitative RT-PCR was performed on “dunked” sputum and NTS samples for influenza A (Flu A), respiratory syncytial virus (RSV), coronavirus OC43 (OC43), and human metapneumovirus (HMPV). Viruses were identified in 31% of 965 illnesses using a uniplex RT-PCR. The sputum sample was the only sample positive for 105 subjects, including 35% (22/64) of influenza cases and significantly increased the diagnostic yield of NTS alone (302/965 [31%] versus 197/965 [20%]; P = 0.0001). Of 108 sputum samples evaluated by the FilmArray assay using the dunk and swirl method, 99 (92%) were positive. Quantitative RT-PCR revealed higher mean viral loads in dunked sputum samples compared to NTS samples for Flu A, RSV, and HMPV (P = 0.0001, P = 0.006, and P = 0.011, respectively). The dunk and swirl method is a simple and practical method for reliably processing sputum samples in a fully automated PCR system. The higher viral loads in sputa may increase detection over NTS testing alone. PMID:25056335

Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection.

PubMed

Mooney, Jason P; Lokken, Kristen L; Byndloss, Mariana X; George, Michael D; Velazquez, Eric M; Faber, Franziska; Butler, Brian P; Walker, Gregory T; Ali, Mohamed M; Potts, Rashaun; Tiffany, Caitlin; Ahmer, Brian M M; Luckhart, Shirley; Tsolis, Renée M

2015-10-05

Childhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection. Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory macrophages and T cells into the intestinal mucosa and increased expression of inflammatory cytokines. These mucosal responses were also observed in germ-free mice, showing that they are independent of the resident microbiota. Remarkably, P. yoelii infection reduced colonization resistance of mice against S. enterica serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal microbiota revealed marked changes in the community structure. Shifts in the microbiota increased susceptibility to intestinal colonization by S. Typhimurium, as demonstrated by microbiota reconstitution of germ-free mice. These results show that P. yoelii infection, via alterations to the microbial community in the intestine, decreases resistance to intestinal colonization with NTS. Further they raise the possibility that decreased colonization resistance may synergize with effects of malaria on systemic immunity to increase susceptibility to disseminated NTS infections.

Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection

PubMed Central

Mooney, Jason P.; Lokken, Kristen L.; Byndloss, Mariana X.; George, Michael D.; Velazquez, Eric M.; Faber, Franziska; Butler, Brian P.; Walker, Gregory T.; Ali, Mohamed M.; Potts, Rashaun; Tiffany, Caitlin; Ahmer, Brian M. M.; Luckhart, Shirley; Tsolis, Renée M.

2015-01-01

Childhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection. Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory macrophages and T cells into the intestinal mucosa and increased expression of inflammatory cytokines. These mucosal responses were also observed in germ-free mice, showing that they are independent of the resident microbiota. Remarkably, P. yoelii infection reduced colonization resistance of mice against S. enterica serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal microbiota revealed marked changes in the community structure. Shifts in the microbiota increased susceptibility to intestinal colonization by S. Typhimurium, as demonstrated by microbiota reconstitution of germ-free mice. These results show that P. yoelii infection, via alterations to the microbial community in the intestine, decreases resistance to intestinal colonization with NTS. Further they raise the possibility that decreased colonization resistance may synergize with effects of malaria on systemic immunity to increase susceptibility to disseminated NTS infections. PMID:26434367

Substance P in the nucleus of the solitary tract augments bronchopulmonary C fiber reflex output.

PubMed

Mutoh, T; Bonham, A C; Joad, J P

2000-10-01

Bronchopulmonary C fibers defend the lungs against injury from inhaled agents by a central nervous system reflex consisting of apnea, cough, bronchoconstriction, hypotension, and bradycardia. Glutamate is the putative neurotransmitter at the first central synapses in the nucleus of the solitary tract (NTS), but substance P, also released in the NTS, may modulate the transmission. To test the hypothesis that substance P in the NTS augments bronchopulmonary C fiber input and hence reflex output, we stimulated the C fibers with left atrial capsaicin (LA CAP) injections and compared the changes in phrenic nerve discharge, tracheal pressure (TP), arterial blood pressure (ABP), and heart rate (HR) in guinea pigs before and after substance P injections (200 microM, 25 nl) in the NTS. Substance P significantly augmented LA CAP-evoked increases in expiratory time by 10-fold and increases in TP and decreases in ABP and HR by threefold, effects prevented by neurokinin-1 (NK1) receptor antagonism. Thus substance P acting at NTS NK1 receptors can exaggerate bronchopulmonary C fiber reflex output. Because substance P synthesis in vagal airway C fibers may be enhanced in pathological conditions such as allergic asthma, the findings may help explain some of the associated respiratory symptoms including cough and bronchoconstriction.

Astrocytes Regulate GLP-1 Receptor-Mediated Effects on Energy Balance

PubMed Central

Reiner, David J.; Mietlicki-Baase, Elizabeth G.; McGrath, Lauren E.; Zimmer, Derek J.; Bence, Kendra K.; Sousa, Gregory L.; Konanur, Vaibhav R.; Krawczyk, Joanna; Burk, David H.; Kanoski, Scott E.; Hermann, Gerlinda E.; Rogers, Richard C.

2016-01-01

Astrocytes are well established modulators of extracellular glutamate, but their direct influence on energy balance-relevant behaviors is largely understudied. As the anorectic effects of glucagon-like peptide-1 receptor (GLP-1R) agonists are partly mediated by central modulation of glutamatergic signaling, we tested the hypothesis that astrocytic GLP-1R signaling regulates energy balance in rats. Central or peripheral administration of a fluorophore-labeled GLP-1R agonist, exendin-4, localizes within astrocytes and neurons in the nucleus tractus solitarius (NTS), a hindbrain nucleus critical for energy balance control. This effect is mediated by GLP-1R, as the uptake of systemically administered fluorophore-tagged exendin-4 was blocked by central pretreatment with the competitive GLP-1R antagonist exendin-(9–39). Ex vivo analyses show prolonged exendin-4-induced activation (live cell calcium signaling) of NTS astrocytes and neurons; these effects are also attenuated by exendin-(9–39), indicating mediation by the GLP-1R. In vitro analyses show that the application of GLP-1R agonists increases cAMP levels in astrocytes. Immunohistochemical analyses reveal that endogenous GLP-1 axons form close synaptic apposition with NTS astrocytes. Finally, pharmacological inhibition of NTS astrocytes attenuates the anorectic and body weight-suppressive effects of intra-NTS GLP-1R activation. Collectively, data demonstrate a role for NTS astrocytic GLP-1R signaling in energy balance control. SIGNIFICANCE STATEMENT Glucagon-like peptide-1 receptor (GLP-1R) agonists reduce food intake and are approved by the Food and Drug Administration for the treatment of obesity, but the cellular mechanisms underlying the anorectic effects of GLP-1 require further investigation. Astrocytes represent a major cellular population in the CNS that regulates neurotransmission, yet the role of astrocytes in mediating energy balance is largely unstudied. The current data provide novel evidence that astrocytes within the NTS are relevant for energy balance control by GLP-1 signaling. Here, we report that GLP-1R agonists activate and internalize within NTS astrocytes, while behavioral data suggest the pharmacological relevance of NTS astrocytic GLP-1R activation for food intake and body weight. These findings support a previously unknown role for CNS astrocytes in energy balance control by GLP-1 signaling. PMID:27013681

Non-Typhoidal Salmonella Colonization in Chickens and Humans in the Mekong Delta of Vietnam.

PubMed

Trung, N V; Carrique-Mas, J J; Nghia, N H; Tu, L T P; Mai, H H; Tuyen, H T; Campbell, J; Nhung, N T; Nhung, H N; Minh, P V; Chieu, T T B; Hieu, T Q; Mai, N T N; Baker, S; Wagenaar, J A; Hoa, N T; Schultsz, C

2017-03-01

Salmonellosis is a public health concern in both the developed and developing countries. Although the majority of human non-typhoidal Salmonella enterica (NTS) cases are the result of foodborne infections or person-to-person transmission, NTS infections may also be acquired by environmental and occupational exposure to animals. While a considerable number of studies have investigated the presence of NTS in farm animals and meat/carcasses, very few studies have investigated the risk of NTS colonization in humans as a result of direct animal exposure. We investigated asymptomatic NTS colonization in 204 backyard chicken farms, 204 farmers and 306 matched individuals not exposed to chicken farming, in southern Vietnam. Pooled chicken faeces, collected using boot or handheld swabs on backyard chicken farms, and rectal swabs from human participants were tested. NTS colonization prevalence was 45.6%, 4.4% and 2.6% for chicken farms, farmers and unexposed individuals, respectively. Our study observed a higher prevalence of NTS colonization among chicken farmers (4.4%) compared with age-, sex- and location- matched rural and urban individuals not exposed to chickens (2.9% and 2.0%). A total of 164 chicken NTS strains and 17 human NTS strains were isolated, and 28 serovars were identified. Salmonella Weltevreden was the predominant serovar in both chickens and humans. NTS isolates showed resistance (20-40%) against tetracycline, chloramphenicol, sulfamethoxazole-trimethoprim and ampicillin. Our study reflects the epidemiology of NTS colonization in chickens and humans in the Mekong delta of Vietnam and emphasizes the need of larger, preferably longitudinal studies to study the transmission dynamics of NTS between and within animal and human host populations. © 2016 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.

Pathogenesis of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea: A Hypothesis with Emphasis on the Nucleus Tractus Solitarius

PubMed Central

Daulatzai, Mak Adam

2012-01-01

OSA is characterized by the quintessential triad of intermittent apnea, hypoxia, and hypoxemia due to pharyngeal collapse. This paper highlights the upstream mechanisms that may trigger cognitive decline in OSA. Three interrelated steps underpin cognitive dysfunction in OSA patients. First, several risk factors upregulate peripheral inflammation; these crucial factors promote neuroinflammation, cerebrovascular endothelial dysfunction, and oxidative stress in OSA. Secondly, the neuroinflammation exerts negative impact globally on the CNS, and thirdly, important foci in the neocortex and brainstem are rendered inflamed and dysfunctional. A strong link is known to exist between neuroinflammation and neurodegeneration. A unique perspective delineated here underscores the importance of dysfunctional brainstem nuclei in etiopathogenesis of cognitive decline in OSA patients. Nucleus tractus solitarius (NTS) is the central integration hub for afferents from upper airway (somatosensory/gustatory), respiratory, gastrointestinal, cardiovascular (baroreceptor and chemoreceptor) and other systems. The NTS has an essential role in sympathetic and parasympathetic systems also; it projects to most key brain regions and modulates numerous physiological functions. Inflamed and dysfunctional NTS and other key brainstem nuclei may play a pivotal role in triggering memory and cognitive dysfunction in OSA. Attenuation of upstream factors and amelioration of the NTS dysfunction remain important challenges. PMID:23470865

The Role of Neurotrophins in Neurotransmitter Release

PubMed Central

Tyler, William J.; Perrett, Stephen P.; Pozzo-Miller, Lucas D.

2009-01-01

The neurotrophins (NTs) have recently been shown to elicit pronounced effects on quantal neurotransmitter release at both central and peripheral nervous system synapses. Due to their activity-dependent release, as well as the subcellular localization of both protein and receptor, NTs are ideally suited to modify the strength of neuronal connections by “fine-tuning” synaptic activity through direct actions at presynaptic terminals. Here, using BDNF as a prototypical example, the authors provide an update of recent evidence demonstrating that NTs enhance quantal neurotransmitter release at synapses through presynaptic mechanisms. The authors further propose that a potential target for NT actions at presynaptic terminals is the mechanism by which terminals retrieve synaptic vesicles after exocytosis. Depending on the temporal demands placed on synapses during high-frequency synaptic transmission, synapses may use two alternative modes of synaptic vesicle retrieval, the conventional slow endosomal recycling or a faster rapid retrieval at the active zone, referred to as “kiss-and-run.” By modulating Ca2+ microdomains associated with voltage-gated Ca2+ channels at active zones, NTs may elicit a switch from the slow to the fast mode of endocytosis of vesicles at presynaptic terminals during high-frequency synaptic transmission, allowing more reliable information transfer and neuronal signaling in the central nervous system. PMID:12467374

The role of neurotrophins in neurotransmitter release.

PubMed

Tyler, William J; Perrett, Stephen P; Pozzo-Miller, Lucas D

2002-12-01

The neurotrophins (NTs) have recently been shown to elicit pronounced effects on quantal neurotransmitter release at both central and peripheral nervous system synapses. Due to their activity-dependent release, as well as the subcellular localization of both protein and receptor, NTs are ideally suited to modify the strength of neuronal connections by "fine-tuning" synaptic activity through direct actions at presynaptic terminals. Here, using BDNF as a prototypical example, the authors provide an update of recent evidence demonstrating that NTs enhance quantal neurotransmitter release at synapses through presynaptic mechanisms. The authors further propose that a potential target for NT actions at presynaptic terminals is the mechanism by which terminals retrieve synaptic vesicles after exocytosis. Depending on the temporal demands placed on synapses during high-frequency synaptic transmission, synapses may use two alternative modes of synaptic vesicle retrieval, the conventional slow endosomal recycling or a faster rapid retrieval at the active zone, referred to as "kiss-and-run." By modulating Ca2+ microdomains associated with voltage-gated Ca2+ channels at active zones, NTs may elicit a switch from the slow to the fast mode of endocytosis of vesicles at presynaptic terminals during high-frequency synaptic transmission, allowing more reliable information transfer and neuronal signaling in the central nervous system.

Sustained neurotensin exposure promotes cell surface recruitment of NTS2 receptors

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

Perron, Amelie; Sharif, Nadder; Gendron, Louis

2006-05-12

In this study, we investigated whether persistent agonist stimulation of NTS2 receptors gives rise to down-regulation, in light of reports that their activation induced long-lasting effects. To address this issue, we incubated COS-7 cells expressing the rat NTS2 with neurotensin (NT) for up to 24 h and measured resultant cell surface [{sup 125}I]-NT binding. We found that NTS2-expressing cells retained the same surface receptor density despite efficient internalization mechanisms. This preservation was neither due to NTS2 neosynthesis nor recycling since it was not blocked by cycloheximide or monensin. However, it appeared to involve translocation of spare receptors from internal stores,more » as NT induced NTS2 migration from trans-Golgi network to endosome-like structures. This stimulation-induced regulation of cell surface NTS2 receptors was even more striking in rat spinal cord neurons. Taken together, these results suggest that sustained NTS2 activation promotes recruitment of intracellular receptors to the cell surface, thereby preventing functional desensitization.« less

Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling.

PubMed

Resch, Jon M; Fenselau, Henning; Madara, Joseph C; Wu, Chen; Campbell, John N; Lyubetskaya, Anna; Dawes, Brian A; Tsai, Linus T; Li, Monica M; Livneh, Yoav; Ke, Qingen; Kang, Peter M; Fejes-Tóth, Géza; Náray-Fejes-Tóth, Anikó; Geerling, Joel C; Lowell, Bradford B

2017-09-27

Sodium deficiency increases angiotensin II (ATII) and aldosterone, which synergistically stimulate sodium retention and consumption. Recently, ATII-responsive neurons in the subfornical organ (SFO) and aldosterone-sensitive neurons in the nucleus of the solitary tract (NTS HSD2 neurons) were shown to drive sodium appetite. Here we investigate the basis for NTS HSD2 neuron activation, identify the circuit by which NTS HSD2 neurons drive appetite, and uncover an interaction between the NTS HSD2 circuit and ATII signaling. NTS HSD2 neurons respond to sodium deficiency with spontaneous pacemaker-like activity-the consequence of "cardiac" HCN and Na v 1.5 channels. Remarkably, NTS HSD2 neurons are necessary for sodium appetite, and with concurrent ATII signaling their activity is sufficient to produce rapid consumption. Importantly, NTS HSD2 neurons stimulate appetite via projections to the vlBNST, which is also the effector site for ATII-responsive SFO neurons. The interaction between angiotensin signaling and NTS HSD2 neurons provides a neuronal context for the long-standing "synergy hypothesis" of sodium appetite regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimizing the photochemical conversion of UV-vis light of silver-nanoparticles decorated TiO2 nanotubes based photoanodes.

PubMed

Gaidi, M; Trabelsi, K; Hajjaji, A; Chourou, M L; Alhazaa, A N; Bessais, B; El Khakani, M A

2018-01-05

Homogeneous decoration of TiO 2 nanotubes (NTs) by Ag metallic nanoparticles (NPs) was carried out by a relatively simple photoreduction process. This Ag-NPs decoration was found to improve the photoconversion efficiency of the TiO 2 -NTs based photoanodes. The x-ray photoelectron spectroscopy and x-ray diffraction analyses confirmed that all the Ag-NPs are metallic and the underlying TiO 2 -NTs crystallize in the anatase phase after their annealing at 400 °C, respectively. Transmission electron microscopy observations have confirmed the effective decoration of the TiO 2 -NTs' surface by Ag-NPs, and allowed to measure the average Ag-NPs size, which was found to increase linearly from (4 ± 2) nm to (16 ± 4) nm when the photoreduction time is increased from 5 to 20 min. The diffuse reflectivity of the Ag-NPs decorated TiO 2 -NTs was found to decrease significantly as compared to the undecorated TiO 2 -NTs. Interestingly, the Ag-NPs decorated TiO 2 -NTs exhibited a significantly enhanced photochemical response, under visible radiation, with regards to the undecorated NTs. This enhancement was found to reach its maximum for the TiO 2 -NTs decorated with Ag-NPs having the optimal average diameter of ∼8.5 nm. The maximum photoconversion efficiency of Ag-NPs decorated TiO 2 -NTs was about two times greater than for the undecorated ones. This improved photo-electro-chemical response is believed to be associated with the additional absorption of visible light of Ag-NPs through the localized surface plasmon resonance phenomenon. This interpretation is supported by the fact that the photoluminescence intensity of the Ag-NPs decorated TiO 2 -NTs was found to decrease significantly as compared to undecorated NTs, due to charge carriers trapping in the Ag NPs. This demonstrates that Ag-NPs decoration promotes photogenerated charges separation in the TiO 2 -NTs, increasing thereby their capacity for current photogeneration. The surface decoration of TiO 2 NTs by noble metals NPs is expected to impact positively the use of TiO 2 -NTs based photoanodes in some energetic applications such as hydrogen generation and photo-electrochemical solar cells.

Antibiotic resistance and molecular characterization of diarrheagenic Escherichia coli and non-typhoidal Salmonella strains isolated from infections in Southwest China.

PubMed

Zhang, Shun-Xian; Zhou, Yong-Ming; Tian, Li-Guang; Chen, Jia-Xu; Tinoco-Torres, Rita; Serrano, Emmanuel; Li, Shi-Zhu; Chen, Shao-Hong; Ai, Lin; Chen, Jun-Hu; Xia, Shang; Lu, Yan; Lv, Shan; Teng, Xue-Jiao; Xu, Wen; Gu, Wen-Peng; Gong, Si-Tang; Zhou, Xiao-Nong; Geng, Lan-Lan; Hu, Wei

2018-05-07

Bacterial diarrhea is one of the most common causes for medical consultations, mortality and morbidity in the world. Diarrheagenic Escherichia coli (DEC) and non-typhoidal Salmonella (NTS) are major intestinal pathogens in developing countries, and the indiscriminate use of antibiotics has greatly contributed to resistant strains. Hence, the aim of the present study is to identify the antimicrobial resistance patterns and the molecular characteristics of DEC and NTS in southwest, China. 1121 diarrheal patients and 319 non-diarrheal subjects across all age groups were recruited from four sentinel hospitals from June 2014 to July 2015 in Kunming City, Yunnan Province. Each stool specimen was collected to detect DEC and NTS with standard microbiological and molecular methods. Antimicrobial resistance testing was performed with the Kirby-Bauer disk diffusion method, and the standards for antimicrobial susceptibility testing complied with the Clinical and Laboratory Standards Institute (CLSI). Molecular characterization of strains was carried out using pulsed-field gel electrophoresis (PFGE). A structured questionnaire was used to record basic epidemiological data (e.g. sex, age, residence, season, etc.). Data were analyzed using Chi-square or Fisher's exact test. DEC was detected in 127 (11.33%) diarrhea cases and 9 (2.82%) non-diarrheal cases (χ 2  = 20.69, P < 0.001, OR = 4.36, 95% CI: 2.19-8.65), and the prevalence of NTS isolated from diarrhea cases was higher than that of non-diarrheal cases across all age groups (n = 42, 3.75%, n = 1, 0.31%, χ 2  = 10.10, P = 0.002, OR = 12.38, 95% CI: 1.70-90.29). The rates of resistance to ten antibiotics of DEC and NTS showed significant differences (χ 2  = 386.77, P < 0.001; χ 2  = 191.16, P < 0.001). The rates of resistance to Amoxicillin and Clavulafiate (AMC), Cephalothin (CEP), Gentamicin (GEN) and Sulfamethoxazole-Trimethoprim (SXT) of DEC isolated from diarrhea cases were higher than those of NTS isolated from diarrhea patients (37.01% vs 14.29%, χ 2  = 7.57, P = 0.006; 29.92% vs 11.90%, χ 2  = 5.40, P = 0.02; 37.01% vs 11.90%, χ 2  = 5.80, P = 0.016; 62.20% vs 26.19%, χ 2  = 16.44, P < 0.001; respectively). Ciprofloxacin (CIP) was the most sensitive antibiotic for DEC and NTS strains isolated from diarrhea cases. Resistance rates of DEC isolates from cases and controls to more than three kinds antimicrobials (multidrug resistance, MDR) showed no significant differences (81.10% vs 88.89%, P = 0.33). Pulsotype patterns of DEC strains were highly diverse; however, the pulsotype pattern of NTS strains was closely related to the serotype. The pattern of S. enteritidis was highly similar, but the S. enterica Typhimurium strain was discrete. Antibiotic resistance of Enterobacteriaceae is of great concern. The societal effects of antibiotic use justify strict monitoring to combat increases in antimicrobial resistance. Molecular epidemiology and systematic epidemiological investigation can provide accurate evidence for tracking the infection source.

Modelling the Contributions of Malaria, HIV, Malnutrition and Rainfall to the Decline in Paediatric Invasive Non-typhoidal Salmonella Disease in Malawi.

PubMed

Feasey, Nicholas A; Everett, Dean; Faragher, E Brian; Roca-Feltrer, Arantxa; Kang'ombe, Arthur; Denis, Brigitte; Kerac, Marko; Molyneux, Elizabeth; Molyneux, Malcolm; Jahn, Andreas; Gordon, Melita A; Heyderman, Robert S

2015-01-01

Nontyphoidal Salmonellae (NTS) are responsible for a huge burden of bloodstream infection in Sub-Saharan African children. Recent reports of a decline in invasive NTS (iNTS) disease from Kenya and The Gambia have emphasised an association with malaria control. Following a similar decline in iNTS disease in Malawi, we have used 9 years of continuous longitudinal data to model the interrelationships between iNTS disease, malaria, HIV and malnutrition. Trends in monthly numbers of childhood iNTS disease presenting at Queen's Hospital, Blantyre, Malawi from 2002 to 2010 were reviewed in the context of longitudinal monthly data describing malaria slide-positivity among paediatric febrile admissions, paediatric HIV prevalence, nutritional rehabilitation unit admissions and monthly rainfall over the same 9 years, using structural equation models (SEM). Analysis of 3,105 iNTS episodes identified from 49,093 blood cultures, showed an 11.8% annual decline in iNTS (p < 0.001). SEM analysis produced a stable model with good fit, revealing direct and statistically significant seasonal effects of malaria and malnutrition on the prevalence of iNTS disease. When these data were smoothed to eliminate seasonal cyclic changes, these associations remained strong and there were additional significant effects of HIV prevalence. These data suggest that the overall decline in iNTS disease observed in Malawi is attributable to multiple public health interventions leading to reductions in malaria, HIV and acute malnutrition. Understanding the impacts of public health programmes on iNTS disease is essential to plan and evaluate interventions.

Digital geologic map of the Nevada Test Site and vicinity, Nye, Lincoln, and Clark Counties, Nevada, and Inyo County, California

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

Slate, J.L.; Berry, M.E.; Rowley, P.D.

2000-03-08

This digital geologic map of the Nevada Test Site (NTS) and vicinity, as well as its accompanying digital geophysical maps, are compiled at 1:100,000 scale. The map area covers two 30 {times} 60-minute quadrangles-the Pahute Mesa quadrangle to the north and the Beatty quadrangle to the south-plus a strip of 7 1/2-minute quadrangles on the east side. In addition to the NTS, the map area includes the rest of the southwest Nevada volcanic field, part of the Walker Lane, most of the Amargosa Desert, part of the Funeral and Grapevine Mountains, some of Death Valley, and the northern Spring Mountains.more » This geologic map improves on previous geologic mapping of the same area by providing new and updated Quaternary and bedrock geology, new geophysical interpretations of faults beneath the basins, and improved GIS coverages. This publication also includes a new isostatic gravity map and a new aeromagnetic map. The primary purpose of the three maps is to provide an updated geologic framework to aid interpretation of ground-water flow through and off the NTS. The NTS is centrally located within the area of the Death Valley regional ground-water flow system of southwestern Nevada and adjacent California. During the last 40 years, DOE and its predecessor agencies have conducted about 900 nuclear tests on the NTS, of which 100 were atmospheric tests and the rest were underground tests. More than 200 of the tests were detonated at or beneath the water table, which commonly is about 500 to 600 m below the surface. Because contaminants introduced by these test may move into water supplies off the NTS, rates and directions of ground-water flow must be determined. Knowledge about the ground water also is needed to properly appraise potential future effects of the possible nuclear waste repository at Yucca Mountain, adjacent to the NTS.« less

Effect of substance P injection into the nucleus tractus solitarius of rats on cricothyroid and thyroarytenoid motor activity and cardiovascular and respiratory systems.

PubMed

Bauman, Nancy M; Wang, DeQiang; Luschei, Erich S; Talman, William T

2002-10-01

Identification of central neurotransmitters that mediate laryngeal adductor and/or tensor activity may prove useful in managing pathological laryngeal adduction as occurs in laryngospasm or apparent life-threatening events. The putative transmitter substance P (SP) is found in the nucleus tractus solitarius (NTS), in which laryngeal afferents terminate. Therefore, we studied the laryngeal, cardiovascular, and respiratory effects of SP injected into the NTS of rats. We completed bilateral stereotactic injections of 20 nL of SP (15 micromol) or control solution into the region of the NTS, the dorsal motor nucleus (DMN), or the nucleus gracilis (GR) in 30 anesthetized rats. Changes in diaphragm, cricothyroid (CT), and thyroarytenoid (TA) electromyography (EMG), as well as blood pressure (BP), were compared. The injection sites were verified histologically. Injection of SP into the NTS altered CT and/or TA EMG activity in all animals. The change ranged from complete inhibition, to a phasic increase, to a tonic increase. No change in laryngeal adductor EMG activity was seen in 8 of 9 animals after SP injections into the DMN (4/5) or GR (4/4), but 1 animal demonstrated brief inhibition of CT and TA EMG activity after SP injection into the DMN. Injection of SP into the NTS induced central apnea and a significant decrease in BP in all animals. The duration of apnea tended to be longer after NTS injections than after DMN or GR injections (p < .10 and p < .05, respectively). We conclude that stereotactic injections of putative neurotransmitters in rats may be accomplished to identify effects on laryngeal motor activity. Direct application of SP into the NTS consistently elicits a change in CT and/or TA EMG activity, ranging from inhibition to excitation. This model may prove useful in evaluating pharmacological targets of central reflex activity to manage life-threatening laryngeal reflex activity.

Risk of nontyphoidal Salmonella bacteraemia in African children is modified by STAT4.

PubMed

Gilchrist, James J; Rautanen, Anna; Fairfax, Benjamin P; Mills, Tara C; Naranbhai, Vivek; Trochet, Holly; Pirinen, Matti; Muthumbi, Esther; Mwarumba, Salim; Njuguna, Patricia; Mturi, Neema; Msefula, Chisomo L; Gondwe, Esther N; MacLennan, Jenny M; Chapman, Stephen J; Molyneux, Malcolm E; Knight, Julian C; Spencer, Chris C A; Williams, Thomas N; MacLennan, Calman A; Scott, J Anthony G; Hill, Adrian V S

2018-03-09

Nontyphoidal Salmonella (NTS) is a major cause of bacteraemia in Africa. The disease typically affects HIV-infected individuals and young children, causing substantial morbidity and mortality. Here we present a genome-wide association study (180 cases, 2677 controls) and replication analysis of NTS bacteraemia in Kenyan and Malawian children. We identify a locus in STAT4, rs13390936, associated with NTS bacteraemia. rs13390936 is a context-specific expression quantitative trait locus for STAT4 RNA expression, and individuals carrying the NTS-risk genotype demonstrate decreased interferon-γ (IFNγ) production in stimulated natural killer cells, and decreased circulating IFNγ concentrations during acute NTS bacteraemia. The NTS-risk allele at rs13390936 is associated with protection against a range of autoimmune diseases. These data implicate interleukin-12-dependent IFNγ-mediated immunity as a determinant of invasive NTS disease in African children, and highlight the shared genetic architecture of infectious and autoimmune disease.

Neurotrophin Signaling and Stem Cells-Implications for Neurodegenerative Diseases and Stem Cell Therapy.

PubMed

Pramanik, Subrata; Sulistio, Yanuar Alan; Heese, Klaus

2017-11-01

Neurotrophins (NTs) are members of a neuronal growth factor protein family whose action is mediated by the tropomyosin receptor kinase (TRK) receptor family receptors and the p75 NT receptor (p75NTR), a member of the tumor necrosis factor (TNF) receptor family. Although NTs were first discovered in neurons, recent studies have suggested that NTs and their receptors are expressed in various types of stem cells mediating pivotal signaling events in stem cell biology. The concept of stem cell therapy has already attracted much attention as a potential strategy for the treatment of neurodegenerative diseases (NDs). Strikingly, NTs, proNTs, and their receptors are gaining interest as key regulators of stem cells differentiation, survival, self-renewal, plasticity, and migration. In this review, we elaborate the recent progress in understanding of NTs and their action on various stem cells. First, we provide current knowledge of NTs, proNTs, and their receptor isoforms and signaling pathways. Subsequently, we describe recent advances in the understanding of NT activities in various stem cells and their role in NDs, particularly Alzheimer's disease (AD) and Parkinson's disease (PD). Finally, we compile the implications of NTs and stem cells from a clinical perspective and discuss the challenges with regard to transplantation therapy for treatment of AD and PD.

Predictors of Attitudes Toward Non-Technical Skills in Farming.

PubMed

Irwin, Amy; Poots, Jill

2018-01-01

Farming is a high-risk sector with up to 170,000 worldwide fatalities reported per year; it is therefore vital to identify methods of mitigating the dangers of this industry. Research within high-risk industries, such as aviation, shipping, and agriculture, has identified the importance of non-technical skills (NTS) in maintaining effective, safe performance and reducing error and injury. However, there is a lack of research evaluating factors that may contribute to NTS attitudes and behaviors. As a first step to address this literature gap, the current study evaluated a range of individual and environmental factors as potential predictors of attitudes toward NTS in agriculture. A sample of 170 farmers from within the United Kingdom and Ireland were surveyed using an online questionnaire. The questionnaire included measures of personality, stress, attitudes toward safety (safety climate, motivation, and risk), environmental stressors (workload, work-life imbalance), and non-technical skills (team and lone worker). Attitudes toward safety climate, compliance, and motivation showed a significant association with both team-based and lone worker NTS. Conscientiousness correlated positively with the majority of the NTS elements. Multiple regression analysis indicated neuroticism and conscientiousness demonstrated capacity to predict NTS attitudes. Concerns about costs and equipment, attitudes toward safety climate, and safety motivation were also found to be significant predictors of NTS attitudes. The results indicate the utility of individual characteristics and environmental factors when predicting farming NTS attitudes. As a result, these elements could be important when evaluating engagement with NTS and developing NTS training initiatives in agriculture.

Clonal Differences between Non-Typhoidal Salmonella (NTS) Recovered from Children and Animals Living in Close Contact in The Gambia

PubMed Central

Dione, Michel M.; Ikumapayi, Usman N.; Saha, Debasish; Mohammed, Nuredin I.; Geerts, Stanny; Ieven, Margareta; Adegbola, Richard A.; Antonio, Martin

2011-01-01

Background Non-Typhoidal Salmonella (NTS) is an important cause of invasive bacterial disease and associated with mortality in Africa. However, little is known about the environmental reservoirs and predominant modes of transmission. Our study aimed to study the role of domestic animals in the transmission of NTS to humans in rural area of The Gambia. Methodology Human NTS isolates were obtained through an active population-based case-control surveillance study designated to determine the aetiology and epidemiology of enteric infections covering 27,567 Gambian children less than five years of age in the surveillance area. Fourteen children infected with NTS were traced back to their family compounds and anal swabs collected from 210 domestic animals present in their households. Identified NTSs were serotyped and genotyped by multi-locus sequencing typing. Principal Findings NTS was identified from 21/210 animal sources in the households of the 14 infected children. Chickens carried NTS more frequently than sheep and goats; 66.6%, 28.6% and 4.8% respectively. The most common NTS serovars were S. Colindale in humans (21.42%) and S. Poona in animals (14.28%). MLST on the 35 NTS revealed four new alleles and 24 sequence types (ST) of which 18 (75%) STs were novel. There was no overlap in serovars or genotypes of NTS recovered from humans or animal sources in the same household. Conclusion Our results do not support the hypothesis that humans and animals in close contact in the same household carry genotypically similar Salmonella serovars. These findings form an important baseline for future studies of transmission of NTS in humans and animals in Africa. PMID:21655353

Optimizing the photochemical conversion of UV-vis light of silver-nanoparticles decorated TiO2 nanotubes based photoanodes

NASA Astrophysics Data System (ADS)

Gaidi, M.; Trabelsi, K.; Hajjaji, A.; Chourou, M. L.; Alhazaa, A. N.; Bessais, B.; El Khakani, M. A.

2018-01-01

Homogeneous decoration of TiO2 nanotubes (NTs) by Ag metallic nanoparticles (NPs) was carried out by a relatively simple photoreduction process. This Ag-NPs decoration was found to improve the photoconversion efficiency of the TiO2-NTs based photoanodes. The x-ray photoelectron spectroscopy and x-ray diffraction analyses confirmed that all the Ag-NPs are metallic and the underlying TiO2-NTs crystallize in the anatase phase after their annealing at 400 °C, respectively. Transmission electron microscopy observations have confirmed the effective decoration of the TiO2-NTs’ surface by Ag-NPs, and allowed to measure the average Ag-NPs size, which was found to increase linearly from (4 ± 2) nm to (16 ± 4) nm when the photoreduction time is increased from 5 to 20 min. The diffuse reflectivity of the Ag-NPs decorated TiO2-NTs was found to decrease significantly as compared to the undecorated TiO2-NTs. Interestingly, the Ag-NPs decorated TiO2-NTs exhibited a significantly enhanced photochemical response, under visible radiation, with regards to the undecorated NTs. This enhancement was found to reach its maximum for the TiO2-NTs decorated with Ag-NPs having the optimal average diameter of ˜8.5 nm. The maximum photoconversion efficiency of Ag-NPs decorated TiO2-NTs was about two times greater than for the undecorated ones. This improved photo-electro-chemical response is believed to be associated with the additional absorption of visible light of Ag-NPs through the localized surface plasmon resonance phenomenon. This interpretation is supported by the fact that the photoluminescence intensity of the Ag-NPs decorated TiO2-NTs was found to decrease significantly as compared to undecorated NTs, due to charge carriers trapping in the Ag NPs. This demonstrates that Ag-NPs decoration promotes photogenerated charges separation in the TiO2-NTs, increasing thereby their capacity for current photogeneration. The surface decoration of TiO2 NTs by noble metals NPs is expected to impact positively the use of TiO2-NTs based photoanodes in some energetic applications such as hydrogen generation and photo-electrochemical solar cells.

Cardiovascular actions of L-cysteine and L-cysteine sulfinic acid in the nucleus tractus solitarius of the rat.

PubMed

Takemoto, Yumi

2014-07-01

The sulfur-containing excitatory amino acid (EAA) L-cysteine sulfinic acid (CSA), a neurotransmitter candidate, is endogenously synthesized from L-cysteine (Cys). Exogenous Cys administration into the brain produces cardiovascular effects; these effects likely occur via synaptic stimulation of central nervous system (CNS) neurons that regulate peripheral cardiovascular function. However, the cardiovascular responses produced by CNS Cys administration could result from CSA biosynthesized in synapse. The present study examined the role of CSA in Cys-induced cardiovascular responses within the nucleus tractus solitarius (NTS) of anesthetized rats. The NTS receives input from various visceral afferents that gate autonomic reflexes, including cardiovascular reflexes. Within the NTS, both Cys and CSA microinjections produced decrease responses in arterial blood pressure and heart rate that were similar to those produced by L-glutamate. Co-injection of the ionotropic EAA receptor antagonist kynurenic acid abolished Cys-, but not CSA-, induced cardiovascular responses. This finding suggests that only Cys-induced cardiovascular responses are mediated by kynurenate-sensitive receptors. This study provides the first demonstration that Cys- and CSA-induced cardiovascular responses occur via different mechanisms in the NTS of rats. Further, this study also indicates that Cys-induced cardiovascular responses do not occur via CSA. Thus, within the NTS, endogenous Cys and/or CSA might be involved in cardiovascular regulation.

Administration of IL-1beta to the 4th ventricle causes anorexia that is blocked by agouti-related peptide and that coincides with activation of tyrosine-hydroxylase neurons in the nucleus of the solitary tract.

PubMed

DeBoer, Mark D; Scarlett, Jarrad M; Levasseur, Peter R; Grant, Wilmon F; Marks, Daniel L

2009-02-01

Inflammation-associated cachexia is associated with multiple chronic diseases and involves activation of appetite regulating centers in the arcuate nucleus of the hypothalamus (ARH). The nucleus of the solitary tract (NTS) in the brainstem has also been implicated as an important nucleus involved in appetite regulation. We set out to determine whether the NTS may be involved in inflammation-associated anorexia by injecting IL-1 beta into the 4th ventricle and assessing food intake and NTS neuronal activation. Injection of IL-1 beta produced a decrease in food intake at 3 and 12h after injection which was ameliorated at the 12h time point by a sub-threshold dose of agouti-related peptide (AgRP). Investigation into neuron types in the NTS revealed that IL-1 beta injection was associated with an increase in c-Fos activity in NTS neurons expressing tyrosine hydroxylase (TH). Additionally, injection of IL-1 beta into the 4th ventricle did not produce c-Fos activation of neurons expressing pro-opiomelanocortin (POMC) in the ARH, cells known to be involved in producing anorexia in response to systemic inflammation. Double-label in situ hybridization revealed that TH neurons did not express IL-1 receptor I (IL1-RI) transcript, demonstrating that c-Fos activation of TH neurons in this setting was not via direct stimulation of IL-1 beta on TH neurons themselves. We conclude that IL-1 beta injection into the 4th ventricle produces anorexia and is accompanied by an increase in activation in TH neurons in the NTS. This provides evidence that the brainstem may be an important mediator of anorexia in the setting of inflammation.

The thioredoxin reductase--Thioredoxin redox system cleaves the interchain disulphide bond of botulinum neurotoxins on the cytosolic surface of synaptic vesicles.

PubMed

Pirazzini, Marco; Azarnia Tehran, Domenico; Zanetti, Giulia; Lista, Florigio; Binz, Thomas; Shone, Clifford C; Rossetto, Ornella; Montecucco, Cesare

2015-12-01

Botulinum neurotoxins (BoNTs) are Janus toxins, as they are at the same time the most deadly substances known and one of the safest drugs used in human therapy. They specifically block neurotransmission at peripheral nerves through the proteolysis of SNARE proteins, i.e. the essential proteins which are the core of the neuroexocytosis machinery. Even if BoNTs are traditionally known as seven main serotypes, their actual number is much higher as each serotype exists in many different subtypes, with individual biological properties and little antigenic relations. Since BoNTs can be used as biological weapons, and the only currently available therapy is based on immunological approaches, the existence of so many different subtypes is a major safety problem. Nevertheless, all BoNT isoforms are structurally similar and intoxicate peripheral nerve endings via a conserved mechanism. They consist of two chains linked by a unique disulphide bond which must be reduced to enable their toxicity. We found that thioredoxin 1 and its reductase compose the cell redox system responsible for this reduction, and its inhibition via specific chemicals significantly reduces BoNTs activity, in vitro as well as in vivo. Such molecules can be considered as lead compounds for the development of pan-inhibitors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Highly ordered Fe3+/TiO2 nanotube arrays for efficient photocataltyic degradation of nitrobenzene

NASA Astrophysics Data System (ADS)

Zhang, Yiyang; Gu, Di; Zhu, Lingyue; Wang, Baohui

2017-10-01

Highly ordered TiO2 nanotube arrays (TiO2 NTs) were prepared through a facile two-step electrochemical anodization, subsequently, active iron ions were introduced into the TiO2 NTs via a direct impregnation method. The XPS results showed that the iron elements existed in TiO2 NTs in the form of Fe3+ ions. Compared with the undoped TiO2 NTs, the absorption edge of Fe3+/TiO2 NTs showed an overt red shift and the photocurrent improved obviously, which indicated that Fe3+/TiO2 had a much higher photocatalytic activity. The optimal doping content was tested to be 0.1 mol/L which could make the photocatalytic activity of TiO2 NTs obviously improves under both visible and ultraviolent light. The prepared samples were adopted as photocatalyst to degrade nitrobenzene (NB). The reaction rate constants ks under UV light were in the order kone-stepTiO2NTs = 0.00338

Solitosynthesis: Cosmological evolution of non-topological solitons

NASA Technical Reports Server (NTRS)

Griest, Kim; Kolb, Edward W.

1989-01-01

The thermal creation, fusion, evaporation, and destruction of non-topological solitons (NTS) after a phase transition in the early universe is considered. By defining and following NTS statistical equilibrium and departures from it, and depending on particle physics parameters, one of three possible scenarios occurs. If reaction rates are high enough, a period of equilibrium occurs and relic abundances are determined by the freeze-out temperature. Equilibrium first drives most NTS's into their constituents (free phi particles) and then causes rapid fusion into large NTS's. If freeze-out occurs during the first phase, the NTS's are almost entirely destroyed, while if it occurs during the second phase, solitosynthesis occurs and NTS's may be cosmically relevant. For slow reaction rates the NTS's are born frozen out and have the abundance determined by the phase transition. Analytic approximations for determining the abundances are developed, and tested by numerically integrating a reaction network in an expanding universe. Unfortunately, for most of the parameter space considered, solito-destruction/evaporation occurs.

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

Zhang, Da-Quan; Sun, Tian-Ying; Yu, Xue-Feng, E-mail: yxf@whu.edu.cn

Highlights: • The morphology and properties of Ce-doped yttrium hydroxide fluoride nanotubes (YHF:Ce NTs) were investigated. • YHF:Ce NTs were conjugated with Au nanoparticles to produce Au-YHF:Ce nanocomposites. • Au-YHF:Ce NTs showed excellent capability and efficiency in removing Congo red from solutions. • Au-YHF:Ce NTs were utilized to determine the concentration of Congo red based on SERS. - Abstract: Ce-doped yttrium hydroxide fluoride nanotubes (YHF:Ce NTs) with large surface area are synthesized and conjugated with Au nanoparticles (NPs) to produce Au-YHF:Ce nanocomposites. The Au-YHF:Ce NTs have a hollow structure, rough surface, polymer coating, and good surface-enhanced Raman spectroscopy (SERS) properties.more » They are applied to wastewater treatment to remove Congo red as a typical pollutant. The materials not only remove pollutants rapidly from the wastewater, but also detect trace amounts of the pollutants quantitatively. The multifunctional Au-YHF:Ce NTs have commercial potential as nano-absorbents and nano-detectors in water treatment and environmental monitoring.« less

[Effects of Short-time Conservation Tillage Managements on Greenhouse Gases Emissions from Soybean-Winter Wheat Rotation System].

PubMed

Xie, Yan; Chen, Xi; Hu, Zheng-hua; Chen, Shu-tao; Zhang, Han; Ling, Hui; Shen, Shuang-he

2016-04-15

Field experiments including one soybean growing season and one winter-wheat growing season were adopted. The experimental field was divided into four equal-area sub-blocks which differed from each other only in tillage managements, which were conventional tillage (T) , no-tillage with no straw cover ( NT) , conventional tillage with straw cover (TS) , and no-tillage with straw cover (NTS). CO₂ and N₂O emission fluxes from soil-crop system were measured by static chamber-gas chromatograph technique. The results showed that: compared with T, in the soybean growing season, NTS significantly increased the cumulative amount of CO₂ (CAC) from soil-soybean system by 27.9% (P = 0.045) during the flowering-podding stage, while NT significantly declined CAC by 28.9% (P = 0.043) during the grain filling-maturity stage. Compared with T, NT significantly declined the cumulative amount of N₂O (CAN) by 28.3% (P = 0.042) during the grain filling-maturity stage. In the winter-wheat growing season, compared with T, TS and NT significantly declined CAC by 24.3% (P = 0.032) and 36.0% (P = 0.041) during the elongation-booting stage, and also declined CAC by 26.8% (P = 0.027) and 33.1% (P = 0.038) during the maturity stage. During the turning-green stage, compared with T treatment, NT, NTS, and TS treatments had no significant effect on CAN, while NTS significant declined CAN by 42.0% (P = 0.035) compared with NT. Our findings suggested that conservation tillage managements had a more significant impact on CO₂ emission than 20 emission from soil-crop system.

Simulation-Based Training of Non-Technical Skills in Colonoscopy: Protocol for a Randomized Controlled Trial.

PubMed

Khan, Rishad; Scaffidi, Michael A; Walsh, Catharine M; Lin, Peter; Al-Mazroui, Ahmed; Chana, Barinder; Kalaichandran, Ruben; Lee, Woojin; Grantcharov, Teodor P; Grover, Samir C

2017-08-04

Non-technical skills (NTS), such as communication and professionalism, contribute to the safe and effective completion of procedures. NTS training has previously been shown to improve surgical performance. Moreover, increases in NTS have been associated with improved clinical endoscopic performance. Despite this evidence, NTS training has not been tested as an intervention in endoscopy. The aim of this study is to evaluate the effectiveness of a simulation-based training (SBT) curriculum of NTS on novice endoscopists' performance of clinical colonoscopy. Novice endoscopists were randomized to 2 groups. The control group received 4 hours of interactive didactic sessions on colonoscopy theory and 6 hours of SBT. Hours 5 and 6 of the SBT were integrated scenarios, wherein participants interacted with a standardized patient and nurse, while performing a colonoscopy on the virtual reality (VR) simulator. The NTS (intervention) group received the same teaching sessions but the last hour was focused on NTS teaching. The NTS group also reviewed a checklist of tasks relevant to NTS concepts prior to each integrated scenario case and was provided with dedicated feedback on their NTS performance during the integrated scenario practice. All participants were assessed at baseline, immediately after training, and 4 to 6 weeks post-training. The primary outcome measure is colonoscopy-specific performance in the clinical setting. In total, 42 novice endoscopists completed the study. Data collection and analysis is ongoing. We anticipate completion of all assessments by August 2017. Data analysis, manuscript writing, and subsequent submission for publication is expected to be completed by December 2017. Results from this study may inform the implementation of NTS training into postgraduate gastrointestinal curricula. NTS curricula may improve attitudes towards patient safety and self-reflection among trainees. Moreover, enhanced NTS may lead to superior clinical performance and outcomes in colonoscopy. Clinicaltrial.gov NCT02877420; https://www.clinicaltrials.gov/ct2/show/NCT02877420 (Archived by WebCite at http://www.webcitation.org/6rw94ubXX NCT02877420). ©Rishad Khan, Michael A Scaffidi, Catharine M Walsh, Peter Lin, Ahmed Al-Mazroui, Barinder Chana, Ruben Kalaichandran, Woojin Lee, Teodor P Grantcharov, Samir C Grover. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 04.08.2017.

Natural treatment system models for wastewater management: a study from Hyderabad, India.

PubMed

Sonkamble, Sahebrao; Wajihuddin, Md; Jampani, Mahesh; Sarah, S; Somvanshi, V K; Ahmed, Shakeel; Amerasinghe, Priyanie; Boisson, Alexandre

2018-01-01

Wastewater generated on a global scale has become a significant source of water resources which necessitates appropriate management strategies. However, the complexities associated with wastewater are lack of economically viable treatment systems, especially in low- and middle-income countries. While many types of treatment systems are needed to serve the various local issues, we propose natural treatment systems (NTS) such as natural wetlands that are eco-friendly, cost-effective, and can be jointly driven by public bodies and communities. In order for it to be part of wastewater management, this study explores the NTS potential for removal of pollutants, cost-effectiveness, and reuse options for the 1.20 million m 3 /day of wastewater generated in Hyderabad, India. The pilot study includes hydro-geophysical characterization of natural wetland to determine pollutant removal efficiency and its effective utilization for treated wastewater in the peri-urban habitat. The results show the removal of organic content (76-78%), nutrients (77-97%), and microbes (99.5-99.9%) from the wetland-treated wastewater and its suitability for agriculture applications. Furthermore, the wetland efficiency integrated with engineered interventions led to the development of NTS models with different application scenarios: (i) constructed wetlands, (ii) minimized community wetlands, and (iii) single outlet system, suitable for urban, peri-urban and rural areas, respectively.

[Sequencing and analysis of complete genome of rabies viruses isolated from Chinese Ferret-Badger and dog in Zhejiang province].

PubMed

Lei, Yong-Liang; Wang, Xiao-Guang; Tao, Xiao-Yan; Li, Hao; Meng, Sheng-Li; Chen, Xiu-Ying; Liu, Fu-Ming; Ye, Bi-Feng; Tang, Qing

2010-01-01

Based on sequencing the full-length genomes of four Chinese Ferret-Badger and dog, we analyze the properties of rabies viruses genetic variation in molecular level, get the information about rabies viruses prevalence and variation in Zhejiang, and enrich the genome database of rabies viruses street strains isolated from China. Rabies viruses in suckling mice were isolated, overlapped fragments were amplified by RT-PCR and full-length genomes were assembled to analyze the nucleotide and deduced protein similarities and phylogenetic analyses from Chinese Ferret-Badger, dog, sika deer, vole, used vaccine strain were determined. The four full-length genomes were sequenced completely and had the same genetic structure with the length of 11, 923 nts or 11, 925 nts including 58 nts-Leader, 1353 nts-NP, 894 nts-PP, 609 nts-MP, 1575 nts-GP, 6386 nts-LP, and 2, 5, 5 nts- intergenic regions(IGRs), 423 nts-Pseudogene-like sequence (psi), 70 nts-Trailer. The four full-length genomes were in accordance with the properties of Rhabdoviridae Lyssa virus by BLAST and multi-sequence alignment. The nucleotide and amino acid sequences among Chinese strains had the highest similarity, especially among animals of the same species. Of the four full-length genomes, the similarity in amino acid level was dramatically higher than that in nucleotide level, so the nucleotide mutations happened in these four genomes were most synonymous mutations. Compared with the reference rabies viruses, the lengths of the five protein coding regions had no change, no recombination, only with a few point mutations. It was evident that the five proteins appeared to be stable. The variation sites and types of the four genomes were similar to the reference vaccine or street strains. And the four strains were genotype 1 according to the multi-sequence and phylogenetic analyses, which possessed the distinct district characteristics of China. Therefore, these four rabies viruses are likely to be street viruses already existing in the natural world.

Neurotensin (NTS) and its receptor (NTSR1) causes EGFR, HER2 and HER3 over-expression and their autocrine/paracrine activation in lung tumors, confirming responsiveness to erlotinib

PubMed Central

Lupo, Audrey Mansuet; Mourra, Najat; Takahashi, Takashi; Fléjou, Jean François; Trédaniel, Jean; Régnard, Jean François; Damotte, Diane; Alifano, Marco; Forgez, Patricia

2014-01-01

Alterations in the signaling pathways of epidermal growth factor receptors (HERs) are associated with tumor aggressiveness. Neurotensin (NTS) and its high affinity receptor (NTSR1) are up regulated in 60% of lung cancers. In a previous clinical study, NTSR1 overexpression was shown to predict a poor prognosis for 5 year overall survival in a selected population of stage I lung adenocarcinomas treated by surgery alone. In a second study, shown here, the frequent and high expression of NTSR1 was correlated with a pejorative prognosis in 389 patients with stage I to III lung adenocarcinoma, and was an independent prognosis marker. Interactions between NTS and NTSR1 induce pro-oncogenic biological effects associated with neoplastic processes and tumor progression. Here we highlight the cellular mechanisms activated by Neurotensin (NTS) and its high affinity receptor (NTSR1) contributing to lung cancer cell aggressiveness. We show that the NTS autocrine and/or paracrine regulation causes EGFR, HER2, and HER3 over-expression and activation in lung tumor cells. The EGFR and HER3 autocrine activation is mediated by MMP1 activation and EGF “like” ligands (HB-EGF, Neuregulin 1) release. By establishing autocrine and/or paracrine NTS regulation, we show that tumor growth is modulated according to NTS expression, with a low growth rate in those tumors that do not express NTS. Accordingly, xenografted tumors expressing NTS and NTSR1 showed a positive response to erlotinib, whereas tumors void of NTSR1 expression had no detectable response. This is consistent with the presence of a NTS autocrine loop, leading to the sustained activation of EGFR and responsible for cancer aggressiveness. We propose the use of NTS/NTSR1 tumor expression, as a biomarker for the use of EGFR tyrosine kinase inhibitors in patients lacking EGFR mutation. PMID:25249545

Neurotensin (NTS) and its receptor (NTSR1) causes EGFR, HER2 and HER3 over-expression and their autocrine/paracrine activation in lung tumors, confirming responsiveness to erlotinib.

PubMed

Younes, Mohamad; Wu, Zherui; Dupouy, Sandra; Lupo, Audrey Mansuet; Mourra, Najat; Takahashi, Takashi; Fléjou, Jean François; Trédaniel, Jean; Régnard, Jean François; Damotte, Diane; Alifano, Marco; Forgez, Patricia

2014-09-30

Alterations in the signaling pathways of epidermal growth factor receptors (HERs) are associated with tumor aggressiveness. Neurotensin (NTS) and its high affinity receptor (NTSR1) are up regulated in 60% of lung cancers. In a previous clinical study, NTSR1 overexpression was shown to predict a poor prognosis for 5 year overall survival in a selected population of stage I lung adenocarcinomas treated by surgery alone. In a second study, shown here, the frequent and high expression of NTSR1 was correlated with a pejorative prognosis in 389 patients with stage I to III lung adenocarcinoma, and was an independent prognosis marker. Interactions between NTS and NTSR1 induce pro-oncogenic biological effects associated with neoplastic processes and tumor progression. Here we highlight the cellular mechanisms activated by Neurotensin (NTS) and its high affinity receptor (NTSR1) contributing to lung cancer cell aggressiveness. We show that the NTS autocrine and/or paracrine regulation causes EGFR, HER2, and HER3 over-expression and activation in lung tumor cells. The EGFR and HER3 autocrine activation is mediated by MMP1 activation and EGF "like" ligands (HB-EGF, Neuregulin 1) release. By establishing autocrine and/or paracrine NTS regulation, we show that tumor growth is modulated according to NTS expression, with a low growth rate in those tumors that do not express NTS. Accordingly, xenografted tumors expressing NTS and NTSR1 showed a positive response to erlotinib, whereas tumors void of NTSR1 expression had no detectable response. This is consistent with the presence of a NTS autocrine loop, leading to the sustained activation of EGFR and responsible for cancer aggressiveness. We propose the use of NTS/NTSR1 tumor expression, as a biomarker for the use of EGFR tyrosine kinase inhibitors in patients lacking EGFR mutation.

Clinical features and outcome of typhoid fever and invasive non-typhoidal salmonellosis in a tertiary hospital in Belgium: analysis and review of the literature.

PubMed

Yombi, J C; Martins, L; Vandercam, B; Rodriguez-Villalobos, H; Robert, A

2015-08-01

Typhoid fever (TF) occurs rarely in industrialized countries because of advances in health care and improvement of drinking water. Conversely, non-typhoid salmonellosis (NTS) remains widespread, because of food contamination or asymptomatic carriage. Non-typhoid salmonellosis can be severe when becoming invasive non-typhoid salmonellosis (iNTS). Although established prognostic indicators of the two pathologies are different, direct comparisons between iNTS and TF in the literature remain scarce. The purpose of this study was to analyse and compare demographic, clinical features and outcome of hospitalized patients with TF and iNTS. Demographic, clinical features and outcome were retrospectively analysed in a series of patients hospitalized between 2007 and 2012. A total of 33 patients were enrolled, including 13 with established TF and 20 with iNTS. No differences between TF and iNTS patients were observed in incidence of fever, abdominal cramps, diarrhoea, headache, nausea and vomiting and duration of antibiotic therapy (≤ 7 days in both groups). Although the clinical outcome of TF patients was identical to that of iNTS patients, including incidence of complications, length of hospitalization and mortality (1/13 (7.7%) vs 2/20 (10%), P = 0.43), comorbidities were less frequent in the TF group than in the iNTS group (2/13 vs 15/20, P = 0.003). The clinical profile and outcome of TF patients are similar to those with iNTS. Although comorbidities are more often associated with iNTS, the results of our study suggest that clinical management of these two diseases should remain similar.

A Systematic Review of the Incidence, Risk Factors and Case Fatality Rates of Invasive Nontyphoidal Salmonella (iNTS) Disease in Africa (1966 to 2014)

PubMed Central

Uche, Ifeanyi Valentine; MacLennan, Calman A.

2017-01-01

This study systematically reviews the literature on the occurrence, incidence and case fatality rate (CFR) of invasive nontyphoidal Salmonella (iNTS) disease in Africa from 1966 to 2014. Data on the burden of iNTS disease in Africa are sparse and generally have not been aggregated, making it difficult to describe the epidemiology that is needed to inform the development and implementation of effective prevention and control policies. This study involved a comprehensive search of PubMed and Embase databases. It documents the geographical spread of iNTS disease over time in Africa, and describes its reported incidence, risk factors and CFR. We found that Nontyphoidal Salmonella (NTS) have been reported as a cause of bacteraemia in 33 out of 54 African countries, spanning the five geographical regions of Africa, and especially in sub-Saharan Africa since 1966. Our review indicates that NTS have been responsible for up to 39% of community acquired blood stream infections in sub-Saharan Africa with an average CFR of 19%. Salmonella Typhimurium and Enteritidis are the major serovars implicated and together have been responsible for 91%% of the cases of iNTS disease, (where serotype was determined), reported in Africa. The study confirms that iNTS disease is more prevalent amongst Human Immunodeficiency Virus (HIV)-infected individuals, infants, and young children with malaria, anaemia and malnutrition. In conclusion, iNTS disease is a substantial cause of community-acquired bacteraemia in Africa. Given the high morbidity and mortality of iNTS disease in Africa, it is important to develop effective prevention and control strategies including vaccination. PMID:28056035

BDNF and AMPA receptors in the cNTS modulate the hyperglycemic reflex after local carotid body NaCN stimulation.

PubMed

Cuéllar, R; Montero, S; Luquín, S; García-Estrada, J; Melnikov, V; Virgen-Ortiz, A; Lemus, M; Pineda-Lemus, M; de Álvarez-Buylla, E

2017-07-01

The application of sodium cyanide (NaCN) to the carotid body receptors (CBR) (CBR stimulation) induces rapid blood hyperglycemia and an increase in brain glucose retention. The commissural nucleus tractus solitarius (cNTS) is an essential relay nucleus in this hyperglycemic reflex; it receives glutamatergic afferents (that also release brain derived neurotrophic factor, BDNF) from the nodose-petrosal ganglia that relays CBR information. Previous work showed that AMPA in NTS blocks hyperglycemia and brain glucose retention after CBR stimulation. In contrast, BDNF, which attenuates glutamatergic AMPA currents in NTS, enhances these glycemic responses. Here we investigated the combined effects of BDNF and AMPA (and their antagonists) in NTS on the glycemic responses to CBR stimulation. Microinjections of BDNF plus AMPA into the cNTS before CBR stimulation in anesthetized rats, induced blood hyperglycemia and an increase in brain arteriovenous (a-v) of blood glucose concentration difference, which we infer is due to increased brain glucose retention. By contrast, the microinjection of the TrkB antagonist K252a plus AMPA abolished the glycemic responses to CBR stimulation similar to what is observed after AMPA pretreatments. In BDNF plus AMPA microinjections preceding CBR stimulation, the number of c-fos immunoreactive cNTS neurons increased. In contrast, in the rats microinjected with K252a plus AMPA in NTS, before CBR stimulation, c-fos expression in cNTS decreased. The expression of AMPA receptors GluR2/3 did not change in any of the studied groups. These results indicate that BDNF in cNTS plays a key role in the modulation of the hyperglycemic reflex initiated by CBR stimulation. Copyright © 2017. Published by Elsevier B.V.

Gas Transport Properties of Polybenzimidazole and Poly(Phenylene Oxide) Mixed Matrix Membranes Incorporated with PDA-Functionalised Titanate Nanotubes

NASA Astrophysics Data System (ADS)

Giel, V.; Perchacz, M.; Kredatusová, J.; Pientka, Z.

2017-01-01

Functionalised titanate nanotubes (TiNTs) were incorporated to poly(5,5-bisbenzimidazole-2,2-diyl-1,3-phenylene) (PBI) or poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) for improving the interfacial compatibility between the polymer matrix and inorganic material and for altering the gas separation performance of the neat polymer membranes. Functionalisation consisted in oxidative polymerisation of dopamine-hydrochloride on the surface of non-functionalised TiNTs. Transmission electron microscopy (TEM) confirmed that a thin polydopamine (PDA) layer was created on the surface of TiNTs. 1.5, 3, 6, and 9 wt.% of PDA-functionalised TiNTs (PDA-TiNTs) were dispersed to each type of polymer matrix to create so-called mixed matrix membranes (MMMs). Infrared spectroscopy confirmed that -OH and -NH groups exist on the surface of PDA-TiNTs and that the nanotubes interact via H-bonding with PBI but not with PPO. The distribution of PDA-TiNTs in the MMMs was to some extent uniform as scanning electron microscope (SEM) studies showed. Beyond, PDA-TiNTs exhibit positive effect on gas transport properties, resulting in increased selectivities of MMMs. The addition of nanotubes caused a decrease in permeabilities but an increase in selectivities. It is shown that 9 wt.% of PDA-TiNTs in PBI gave a rise to CO2/N2 and CO2/CH4 selectivities of 112 and 63 %, respectively. In case of PPO-PDA-TiNT MMMs, CO2/N2 and CO2/CH4 selectivity increased about 25 and 17 %, respectively. Sorption measurement showed that the presence of PDA-TiNTs in PBI caused an increase in CO2 sorption, whereas the influence on other gases is less noticeable.

Commissural NTS lesions enhance the pressor response to central cholinergic and adrenergic activation.

PubMed

Vieira, Alexandre A; De Luca, Laurival A; Colombari, Eduardo; Colombari, Debora S A; Menani, José V

2012-07-11

Electrolytic lesions of the commissural nucleus of the solitary tract (commNTS) in rats enhance the pressor response to bilateral carotid occlusion or to intravenous infusion of hypertonic NaCl without changing baroreflex responses. In an opposite direction, commNTS lesions abolish the pressor responses to peripheral chemoreflex activation. These opposite effects of commNTS lesions apparently result from an impairment of sympathetic activation in one case and in a facilitation of vasopressin secretion in the others. In the present study, we investigated the effects of the electrolytic lesions of the commNTS in the pressor responses that depend on sympathetic activation and vasopressin secretion produced by central cholinergic or adrenergic activation with intracerebroventricular (i.c.v.) injections of carbachol or noradrenaline, respectively, in unanesthetized rats. Male Holtzman rats (280-320 g, n=8-15/group) with acute (1 day) or chronic (21 days) sham or commNTS lesions (1 mA×10 s) and a stainless steel cannula implanted in the lateral ventricle were used. Acute commNTS lesions increased the pressor response to i.c.v. injection of carbachol (0.5 nmol/1μ1) (52 ± 2, vs. sham: 37 ± 2mm Hg) or noradrenaline (80 nmol/1μl) (45 ± 6, vs. sham: 30 ± 3 mm Hg), whereas chronic commNTS lesions did not affect the pressor responses to the same treatments. Lesions of the commNTS impaired chemoreflex responses produced by intravenous KCN, without changing baroreflex responses. The results suggest that commNTS-dependent inhibitory signals are involved in the modulation of the pressor responses to central cholinergic and adrenergic activation, probably limiting vasopressin secretion. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Electronic Properties of SiNTs Under External Electric and Magnetic Fields Using the Tight-Binding Method

NASA Astrophysics Data System (ADS)

Chegel, Raad; Behzad, Somayeh

2014-02-01

We investigated the electronic properties of silicon nanotubes (SiNTs) under external transverse electric fields and axial magnetic fields using the tight-binding approximation. It was found that, after switching on the electric and magnetic fields, band modifications such as distortion of degeneracy, change in energy dispersion and subband spacing, and bandgap size reduction occur. The bandgap of silicon gear-like nanotubes (Si g-NTs) decreases linearly with increasing electric field strength, but the bandgap for silicon hexagonal nanotubes (Si h-NTs) first increases and then decreases (metallic) or first remains constant and then decreases (semiconducting). Our results show that the bandgap of Si h-NTs is very sensitive to both electric and magnetic fields, unlike Si g-NTs, which are more sensitive to electric than magnetic fields.

NTS2-selective neurotensin mimetics with tetrahydrofuran amino acids.

PubMed

Simeth, Nadja A; Bause, Manuel; Dobmeier, Michael; Kling, Ralf C; Lachmann, Daniel; Hübner, Harald; Einsiedel, Jürgen; Gmeiner, Peter; König, Burkhard

2017-01-01

Stimulation of the NTS2 neurotensin receptor causes antipsychotic effects and leads to a promotion of the μ-opioid-independent antinociception, which is important in the modulation of tonic pain sensitivity. We report the synthesis and properties of a small library of peptidic agonists based on the active neurotensin fragment NT(8-13). Two tetrahydrofuran amino acid derivatives were synthesized to replace Tyr 11 in NT(8-13). Additionally, Arg 8 , Arg 9 , and Ile 12 of the lead peptide were exchanged by Lys, Lys, and Gly, respectively. The new compounds showed substantial NTS2 binding affinity and up to 1000-fold selectivity over NTS1. The highest selectivity (K i (NTS2): 29nM, K i (NTS1): 35,000nM) was observed for the peptide analog 17R trans . Copyright © 2016 Elsevier Ltd. All rights reserved.

Multi-drug resistant non-typhoidal Salmonella associated with invasive disease in western Kenya.

PubMed

Akullian, Adam; Montgomery, Joel M; John-Stewart, Grace; Miller, Samuel I; Hayden, Hillary S; Radey, Matthew C; Hager, Kyle R; Verani, Jennifer R; Ochieng, John Benjamin; Juma, Jane; Katieno, Jim; Fields, Barry; Bigogo, Godfrey; Audi, Allan; Walson, Judd

2018-01-01

Non-typhoidal Salmonella (NTS) is a leading cause of bloodstream infections in Africa, but the various contributions of host susceptibility versus unique pathogen virulence factors are unclear. We used data from a population-based surveillance platform (population ~25,000) between 2007-2014 and NTS genome-sequencing to compare host and pathogen-specific factors between individuals presenting with NTS bacteremia and those presenting with NTS diarrhea. Salmonella Typhimurium ST313 and Salmonella Enteritidis ST11 were the most common isolates. Multi-drug resistant strains of NTS were more commonly isolated from patients presenting with NTS bacteremia compared to NTS diarrhea. This relationship was observed in patients under age five [aOR = 15.16, 95% CI (2.84-81.05), P = 0.001], in patients five years and older, [aOR = 6.70 95% CI (2.25-19.89), P = 0.001], in HIV-uninfected patients, [aOR = 21.61, 95% CI (2.53-185.0), P = 0.005], and in patients infected with Salmonella serogroup B [aOR = 5.96, 95% CI (2.28-15.56), P < 0.001] and serogroup D [aOR = 14.15, 95% CI (1.10-182.7), P = 0.042]. Thus, multi-drug-resistant NTS was strongly associated with bacteremia compared to diarrhea among children and adults. This association was seen in HIV-uninfected individuals infected with either S. Typhimurium or S. Enteritidis. Risk of developing bacteremia from NTS infection may be driven by virulence properties of the Salmonella pathogen.

Invasive Non-typhoidal Salmonella Disease – epidemiology, pathogenesis and diagnosis

PubMed Central

Gordon, Melita A

2012-01-01

Purpose of review To highlight and discuss important publications over the past 12 months providing new insights on invasive non-typhoidal Salmonella disease (iNTS). Recent findings There have been informative new estimates of the burden of iNTS in Asia and in high-resource low-incidence settings. Important information has emerged in the last year about the relationships between HIV, malaria, iNTS and typhoid fever in adults and children in Africa. HIV causes susceptibility to iNTS disease, but has been shown to be protective against typhoid fever. Clinical guidelines for presumptive diagnosis frequently fail to identify iNTS disease in Africa, and there remains a need for improved diagnostic tools. Experimental studies in humans have helped us to understand the intracellular pathogenesis of iNTS and to direct the search for appropriate protein vaccine targets. Summary The most important remaining gap in our knowledge is probably an understanding of how NTS are transmitted, and the nature of the relationship between diarrhoeal disease, carriage and invasive disease in Africa, so that diagnostic and prevention tools can be appropriately directed. PMID:21844803

Glutamatergic Receptor Activation in the Commisural Nucleus Tractus Solitarii (cNTS) Mediates Brain Glucose Retention (BGR) Response to Anoxic Carotid Chemoreceptor (CChr) Stimulation in Rats.

PubMed

Cuéllar, R; Montero, S; Luquín, S; García-Estrada, J; Dobrovinskaya, O; Melnikov, V; Lemus, M; de Álvarez-Buylla, E Roces

2015-01-01

Glutamate, released from central terminals of glossopharyngeal nerve, is a major excitatory neurotransmitter of commissural nucleus tractus solitarii (cNTS) afferent terminals, and brain derived neurotrophic factor (BDNF) has been shown to attenuate glutamatergic AMPA currents in NTS neurons. To test the hypothesis that AMPA contributes to glucose regulation in vivo modulating the hyperglycemic reflex with brain glucose retention (BGR), we microinjected AMPA and NBQX (AMPA antagonist) into the cNTS before carotid chemoreceptor stimulation in anesthetized normal Wistar rats, while hyperglycemic reflex an brain glucose retention (BGR) were analyzed. To investigate the underlying mechanisms, GluR2/3 receptor and c-Fos protein expressions in cNTS neurons were determined. We showed that AMPA in the cNTS before CChr stimulation inhibited BGR observed in aCSF group. In contrast, NBQX in similar conditions, did not modify the effects on glucose variables observed in aCSF control group. These experiments suggest that glutamatergic pathways, via AMPA receptors, in the cNTS may play a role in glucose homeostasis.

Incubation period for outbreak-associated, non-typhoidal salmonellosis cases, Minnesota, 2000-2015.

PubMed

Eikmeier, D; Medus, C; Smith, K

2018-03-01

Incubation period for non-typhoidal Salmonella (NTS) infections is generally reported as 6-72 h despite numerous reports of foodborne NTS outbreaks with median incubation periods >3 days. We summarised 16 years of Minnesota foodborne NTS outbreaks to better estimate the expected range of incubation periods for NTS infections. Of the 1517 NTS outbreak cases, 725 had enough data to calculate a precise incubation period. The median incubation period was 45 h; 77 (11%) cases had incubations ⩽12 h and 211 (29%) cases had incubations >72 h. Incubation period length varied by outbreak vehicle type, Salmonella serotype and outbreak setting. Based on our data, a more accurate description would be that the incubation of NTS infection is usually from 12 to 96 h, that incubations in >96 to 144 h (>4 to 6-day) range are not unusual and that incubations from 7 to 9 days and occasionally longer also occur.

Multi-drug resistant non-typhoidal Salmonella associated with invasive disease in western Kenya

PubMed Central

Montgomery, Joel M.; Miller, Samuel I.; Hayden, Hillary S.; Radey, Matthew C.; Hager, Kyle R.; Verani, Jennifer R.; Ochieng, John Benjamin; Juma, Jane; Katieno, Jim; Fields, Barry; Bigogo, Godfrey; Audi, Allan; Walson, Judd

2018-01-01

Non-typhoidal Salmonella (NTS) is a leading cause of bloodstream infections in Africa, but the various contributions of host susceptibility versus unique pathogen virulence factors are unclear. We used data from a population-based surveillance platform (population ~25,000) between 2007–2014 and NTS genome-sequencing to compare host and pathogen-specific factors between individuals presenting with NTS bacteremia and those presenting with NTS diarrhea. Salmonella Typhimurium ST313 and Salmonella Enteritidis ST11 were the most common isolates. Multi-drug resistant strains of NTS were more commonly isolated from patients presenting with NTS bacteremia compared to NTS diarrhea. This relationship was observed in patients under age five [aOR = 15.16, 95% CI (2.84–81.05), P = 0.001], in patients five years and older, [aOR = 6.70 95% CI (2.25–19.89), P = 0.001], in HIV-uninfected patients, [aOR = 21.61, 95% CI (2.53–185.0), P = 0.005], and in patients infected with Salmonella serogroup B [aOR = 5.96, 95% CI (2.28–15.56), P < 0.001] and serogroup D [aOR = 14.15, 95% CI (1.10–182.7), P = 0.042]. Thus, multi-drug-resistant NTS was strongly associated with bacteremia compared to diarrhea among children and adults. This association was seen in HIV-uninfected individuals infected with either S. Typhimurium or S. Enteritidis. Risk of developing bacteremia from NTS infection may be driven by virulence properties of the Salmonella pathogen. PMID:29329299

Bacterial adhesion and inactivation on Ag decorated TiO2-nanotubes under visible light: Effect of the nanotubes geometry on the photocatalytic activity.

PubMed

Hajjaji, A; Elabidi, M; Trabelsi, K; Assadi, A A; Bessais, B; Rtimi, S

2018-06-05

This study investigates the effect of the diameter of TiO 2 nanotubes and silver decorated nanotubes on optical properties and photocatalytic inactivation of Escherichia coli under visible light. The TiO 2 nanotubes (TiO 2 -NTs) were prepared using the electrochemical method varying the anodization potential starting from 20 V until 70 V. The Ag nanoparticles were carried out using the photoreduction process under the same experimental conditions. The diameter size was determined using the scanning electronic microscopy (SEM). TiO 2 -NTs diameter reached ∼100 nm at 70 V. Transmission electronic microscopy (TEM) imaging confirmed the TiO 2 -NTs surface decoration by silver nanoparticles. The Ag-NPs average size was found to be equal to 8 nm. The X-Ray diffraction (XRD) analysis confirm that all TiO 2 -NTs crystallize in the anatase phases regardless the used anodization potential. The decrease of the photoluminescence (PL) intensity of Ag NPs decorated TiO 2 -NTs indicates the decrease of the specific area when the nanotubes diameter increases. The UV-vis absorbance show that the absorption edges was bleu shifted with the increasing of nanotubes diameter, which can be explained by the increase of the crystallites average size. The bacterial adhesion and inactivation tests were carried in the dark and under light. Bacteria were seen to adhere on TiO 2 -NTs in the dark; however, under light the bacteria were killed before they establish a strong contact with the TiO 2 -NTs and Ag/TiO 2 -NTs surfaces. Bacterial inactivation kinetics were faster when the anodizing potential of the NTs-preparation increases. A total bacterial inactivation was obtained on ∼100 nm nanotubes diameter within 90 min. This result was attributed to the enhancement of the TNTs crystallinity leading to reduced surface defects. Redox catalysis was seen to occur under light on the TiO 2 -NTs and Ag/TiO 2 -NTs. the photo-induced antibacterial activity on the AgO/Ag 2 O decorated TiO 2 -NTs was attributed to the interfacial charge transfer mechanism (IFCT). Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis of silicon nanotubes with cobalt silicide ends using anodized aluminum oxide template.

PubMed

Zhang, Zhang; Liu, Lifeng; Shimizu, Tomohiro; Senz, Stephan; Gösele, Ulrich

2010-02-05

Silicon nanotubes (SiNTs) are compatible with Si-based semiconductor technology. In particular, the small diameters and controllable structure of such nanotubes are remaining challenges. Here we describe a method to fabricate SiNTs intrinsically connected with cobalt silicide ends based on highly ordered anodic aluminum oxide (AAO) templates. Size and growth direction of the SiNTs can be well controlled via the templates. The growth of SiNTs is catalyzed by the Co nanoparticles reduced on the pore walls of the AAO after annealing, with a controllable thickness at a given growth temperature and time. Simultaneously, cobalt silicide forms on the bottom side of the SiNTs.

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

Cathy Wills

The Nevada Test Site Environmental Report 2006 (NTSER) was prepared to meet the information needs of the public and the requirements and guidelines of the U.S. Department of Energy (DOE) for annual site environmental reports. It was prepared by National Security Technologies, LLC (NSTec). This Executive Summary presents the purpose of the document, the major programs conducted at the Nevada Test Site (NTS), NTS key environmental initiatives, radiological releases and potential doses to the public resulting from site operations, a summary of nonradiological releases, implementation status of the NTS Environmental Management System, a summary of compliance with environmental regulations, pollutionmore » prevention and waste minimization accomplishments, and significant environmental accomplishments. Much of the content of this Executive Summary is also presented in a separate stand-alone pamphlet titled Nevada Test Site Environmental Report Summary 2006 produced to be a more cost-effective means of distributing information contained in the NTSER to interested DOE stakeholders.« less

Title: Experimental and analytical study of frictional anisotropy of nanotubes

NASA Astrophysics Data System (ADS)

Riedo, Elisa; Gao, Yang; Li, Tai-De; Chiu, Hsiang-Chih; Kim, Suenne; Klinke, Christian; Tosatti, Erio

The frictional properties of Carbon and Boron Nitride nanotubes (NTs) are very important in a variety of applications, including composite materials, carbon fibers, and micro/nano-electromechanical systems. Atomic force microscopy (AFM) is a powerful tool to investigate with nanoscale resolution the frictional properties of individual NTs. Here, we report on an experimental study of the frictional properties of different types of supported nanotubes by AFM. We also propose a quantitative model to describe and then predict the frictional properties of nanotubes sliding on a substrate along (longitudinal friction) or perpendicular (transverse friction) their axis. This model provides a simple but general analytical relationship that well describes the acquired experimental data. As an example of potential applications, this experimental method combined with the proposed model can guide to design better NTs-ceramic composites, or to self-assemble the nanotubes on a surface in a given direction. M. Lucas et al., Nature Materials 8, 876-881 (2009).

Do technical skills correlate with non-technical skills in crisis resource management: a simulation study.

PubMed

Riem, N; Boet, S; Bould, M D; Tavares, W; Naik, V N

2012-11-01

Both technical skills (TS) and non-technical skills (NTS) are key to ensuring patient safety in acute care practice and effective crisis management. These skills are often taught and assessed separately. We hypothesized that TS and NTS are not independent of each other, and we aimed to evaluate the relationship between TS and NTS during a simulated intraoperative crisis scenario. This study was a retrospective analysis of performances from a previously published work. After institutional ethics approval, 50 anaesthesiology residents managed a simulated crisis scenario of an intraoperative cardiac arrest secondary to a malignant arrhythmia. We used a modified Delphi approach to design a TS checklist, specific for the management of a malignant arrhythmia requiring defibrillation. All scenarios were recorded. Each performance was analysed by four independent experts. For each performance, two experts independently rated the technical performance using the TS checklist, and two other experts independently rated NTS using the Anaesthetists' Non-Technical Skills score. TS and NTS were significantly correlated to each other (r=0.45, P<0.05). During a simulated 5 min resuscitation requiring crisis resource management, our results indicate that TS and NTS are related to one another. This research provides the basis for future studies evaluating the nature of this relationship, the influence of NTS training on the performance of TS, and to determine whether NTS are generic and transferrable between crises that require different TS.

TiO2 nanotubes with different spacing, Fe2O3 decoration and their evaluation for Li-ion battery application.

PubMed

Ozkan, Selda; Cha, Gihoon; Mazare, Anca; Schmuki, Patrik

2018-05-11

In the present work, we report on the use of organized TiO 2 nanotube (NT) layers with a regular intertube spacing for the growth of highly defined α-Fe 2 O 3 nano-needles in the interspace. These α-Fe 2 O 3 decorated TiO 2 NTs are then explored for Li-ion battery applications and compared to classic close-packed (CP) NTs that are decorated with various amounts of nanoscale α-Fe 2 O 3 . We show that NTs with tube-to-tube spacing allow uniform decoration of individual NTs with regular arrangements of hematite nano-needles. The tube spacing also facilitates the electrolyte penetration as well as yielding better ion diffusion. While bare CP NTs show a higher capacitance of 71 μAh cm -2 compared to bare spaced NTs with a capacitance of 54 μAh cm -2 , the hierarchical decoration with secondary metal oxide, α-Fe 2 O 3 , remarkably enhances the Li-ion battery performance. Namely, spaced NTs with α-Fe 2 O 3 decoration have an areal capacitance of 477 μAh cm -2 , i.e. they have nearly ∼8 times higher capacitance. However, the areal capacitance of CP NTs with α-Fe 2 O 3 decoration saturates at 208 μAh cm -2 , i.e. is limited to ∼3 times increase.

TiO2 nanotubes with different spacing, Fe2O3 decoration and their evaluation for Li-ion battery application

NASA Astrophysics Data System (ADS)

Ozkan, Selda; Cha, Gihoon; Mazare, Anca; Schmuki, Patrik

2018-05-01

In the present work, we report on the use of organized TiO2 nanotube (NT) layers with a regular intertube spacing for the growth of highly defined α-Fe2O3 nano-needles in the interspace. These α-Fe2O3 decorated TiO2 NTs are then explored for Li-ion battery applications and compared to classic close-packed (CP) NTs that are decorated with various amounts of nanoscale α-Fe2O3. We show that NTs with tube-to-tube spacing allow uniform decoration of individual NTs with regular arrangements of hematite nano-needles. The tube spacing also facilitates the electrolyte penetration as well as yielding better ion diffusion. While bare CP NTs show a higher capacitance of 71 μAh cm-2 compared to bare spaced NTs with a capacitance of 54 μAh cm-2, the hierarchical decoration with secondary metal oxide, α-Fe2O3, remarkably enhances the Li-ion battery performance. Namely, spaced NTs with α-Fe2O3 decoration have an areal capacitance of 477 μAh cm-2, i.e. they have nearly ˜8 times higher capacitance. However, the areal capacitance of CP NTs with α-Fe2O3 decoration saturates at 208 μAh cm-2, i.e. is limited to ˜3 times increase.

Differing Burden and Epidemiology of Non-Typhi Salmonella Bacteremia in Rural and Urban Kenya, 2006–2009

PubMed Central

Tabu, Collins; Breiman, Robert F.; Ochieng, Benjamin; Aura, Barrack; Cosmas, Leonard; Audi, Allan; Olack, Beatrice; Bigogo, Godfrey; Ongus, Juliette R.; Fields, Patricia; Mintz, Eric; Burton, Deron; Oundo, Joe; Feikin, Daniel R.

2012-01-01

Background The epidemiology of non-Typhi Salmonella (NTS) bacteremia in Africa will likely evolve as potential co-factors, such as HIV, malaria, and urbanization, also change. Methods As part of population-based surveillance among 55,000 persons in malaria-endemic, rural and malaria-nonendemic, urban Kenya from 2006–2009, blood cultures were obtained from patients presenting to referral clinics with fever ≥38.0°C or severe acute respiratory infection. Incidence rates were adjusted based on persons with compatible illnesses, but whose blood was not cultured. Results NTS accounted for 60/155 (39%) of blood culture isolates in the rural and 7/230 (3%) in the urban sites. The adjusted incidence in the rural site was 568/100,000 person-years, and the urban site was 51/100,000 person-years. In both sites, the incidence was highest in children <5 years old. The NTS-to-typhoid bacteremia ratio in the rural site was 4.6 and in the urban site was 0.05. S. Typhimurium represented >85% of blood NTS isolates in both sites, but only 21% (urban) and 64% (rural) of stool NTS isolates. Overall, 76% of S. Typhimurium blood isolates were multi-drug resistant, most of which had an identical profile in Pulse Field Gel Electrophoresis. In the rural site, the incidence of NTS bacteremia increased during the study period, concomitant with rising malaria prevalence (monthly correlation of malaria positive blood smears and NTS bacteremia cases, Spearman's correlation, p = 0.018 for children, p = 0.16 adults). In the rural site, 80% of adults with NTS bacteremia were HIV-infected. Six of 7 deaths within 90 days of NTS bacteremia had HIV/AIDS as the primary cause of death assigned on verbal autopsy. Conclusions NTS caused the majority of bacteremias in rural Kenya, but typhoid predominated in urban Kenya, which most likely reflects differences in malaria endemicity. Control measures for malaria, as well as HIV, will likely decrease the burden of NTS bacteremia in Africa. PMID:22363591

Neurotrophins and Migraine.

PubMed

Martins, L B; Teixeira, A L; Domingues, R B

2017-01-01

Neurotrophins (NTs) have been implicated in generation and modulation of nociceptive pathways. Change in NTs levels is associated with painful conditions and neurological diseases such as migraine. Currently, it is generally recognized that migraine headaches result from the activation and sensitization of trigeminal sensory afferent fibers leading to neuropeptides release such as calcitonin gene-related peptide (CGRP) and substance P (SP). This triggers an inflammatory cascade causing a neurogenic inflammation. The agents responsible for trigeminal activation and release of neuropeptides are still unclear. It is known that the transient receptor potential vanilloid receptor-1 (TRPV1) is an important mediator of CGRP and SP release. TRPV1 is closely associated with tyrosine receptors kinases (Trk), which are NTs receptors. NTs can act on TRPV1 increasing its sensitivity to painful stimuli, therefore predisposing to hyperalgesia. Upregulation of ion channels and pain receptors in dorsal root ganglion neurons may be alternative mechanisms by which NTs contribute to pain development. Only a few studies have been performed to investigate the role of NTs in migraine. These studies have reported changes in NTs levels in migraine patients either during the migraine attack or in free-headache periods. © 2017 Elsevier Inc. All rights reserved.

No GIST-type c-kit gain of function mutations in neuroblastic tumours

PubMed Central

Korja, M; Finne, J; Salmi, T T; Haapasalo, H; Tanner, M; Isola, J

2005-01-01

Aims: Neuroblastic tumours (NTs) have been shown to respond to imatinib treatment in vivo and in vitro, possibly via inactivating the c-kit receptor. The purpose of this study was to identify gastrointestinal stromal tumour (GIST)-type c-kit gene associated mutations in exons 9, 11, 13, and 17 in NTs to recognise a subset of tumours that would probably respond to imatinib treatment. Methods: Expression of the c-kit protein was detected immunohistochemically in a total of 37 archival paraffin wax embedded NTs using polyclonal rabbit antihuman c-kit antibody. After immunohistochemistry, c-kit gene associated chromosomal mutations in all cases of NT were detected with denaturing high performance liquid chromatography (HPLC). Results: Denaturing HLPC analysis did not reveal GIST-type mutations in four immunohistochemically detected c-kit positive or in 33 c-kit negative NTs. Conclusions: c-kit receptor expression and GIST-type c-kit gene mutations are rare events in NTs. Oncogenic activation of c-kit in NTs presumably differs from that of GISTs, which may influence their responsiveness to imatinib treatment. Whether c-kit has an essential role in the pathogenesis of NTs remains to be investigated. PMID:15976348

Administration of IL-1β to the 4th ventricle causes anorexia that is blocked by agouti-related peptide and that coincides with activation of tyrosine-hydroxylase neurons in the nucleus of the solitary tract

PubMed Central

DeBoer, Mark D.; Scarlett, Jarrad M.; Levasseur, Peter R.; Grant, Wilmon F.; Marks, Daniel L.

2010-01-01

Inflammation-associated cachexia is associated with multiple chronic diseases and involves activation of appetite regulating centers in the arcuate nucleus of the hypothalamus (ARH). The nucleus of the solitary tract (NTS) in the brainstem has also been implicated as an important nucleus involved in appetite regulation. We set out to determine whether the NTS may be involved in inflammation-associated anorexia by injecting IL-1β into the 4th ventricle and assessing food intake and NTS neuronal activation. Injection of IL-1β produced a decrease in food intake at 3 and 12 h after injection which was ameliorated at the 12 h time point by a sub-threshold dose of agouti-related peptide (AgRP). Investigation into neuron types in the NTS revealed that IL-1β injection was associated with an increase in c-Fos activity in NTS neurons expressing tyrosine hydroxylase (TH). Additionally, injection of IL-1β into the 4th ventricle did not produce c-Fos activation of neurons expressing pro-opiomelanocortin (POMC) in the ARH, cells known to be involved in producing anorexia in response to systemic inflammation. Double-label in situ hybridization revealed that TH neurons did not express IL-1 receptor I (IL1-RI) transcript, demonstrating that c-Fos activation of TH neurons in this setting was not via direct stimulation of IL-1β on TH neurons themselves. We conclude that IL-1β injection into the 4th ventricle produces anorexia and is accompanied by an increase in activation in TH neurons in the NTS. This provides evidence that the brainstem may be an important mediator of anorexia in the setting of inflammation. PMID:19028534

Stability of the neurotensin receptor NTS1 free in detergent solution and immobilized to affinity resin.

PubMed

White, Jim F; Grisshammer, Reinhard

2010-09-07

Purification of recombinant membrane receptors is commonly achieved by use of an affinity tag followed by an additional chromatography step if required. This second step may exploit specific receptor properties such as ligand binding. However, the effects of multiple purification steps on protein yield and integrity are often poorly documented. We have previously reported a robust two-step purification procedure for the recombinant rat neurotensin receptor NTS1 to give milligram quantities of functional receptor protein. First, histidine-tagged receptors are enriched by immobilized metal affinity chromatography using Ni-NTA resin. Second, remaining contaminants in the Ni-NTA column eluate are removed by use of a subsequent neurotensin column yielding pure NTS1. Whilst the neurotensin column eluate contained functional receptor protein, we observed in the neurotensin column flow-through misfolded NTS1. To investigate the origin of the misfolded receptors, we estimated the amount of functional and misfolded NTS1 at each purification step by radio-ligand binding, densitometry of Coomassie stained SDS-gels, and protein content determination. First, we observed that correctly folded NTS1 suffers damage by exposure to detergent and various buffer compositions as seen by the loss of [(3)H]neurotensin binding over time. Second, exposure to the neurotensin affinity resin generated additional misfolded receptor protein. Our data point towards two ways by which misfolded NTS1 may be generated: Damage by exposure to buffer components and by close contact of the receptor to the neurotensin affinity resin. Because NTS1 in detergent solution is stabilized by neurotensin, we speculate that the occurrence of aggregated receptor after contact with the neurotensin resin is the consequence of perturbations in the detergent belt surrounding the NTS1 transmembrane core. Both effects reduce the yield of functional receptor protein.

Acid-sensing ion channels contribute to chemosensitivity of breathing-related neurons of the nucleus of the solitary tract.

PubMed

Huda, Rafiq; Pollema-Mays, Sarah L; Chang, Zheng; Alheid, George F; McCrimmon, Donald R; Martina, Marco

2012-10-01

Cellular mechanisms of central pH chemosensitivity remain largely unknown. The nucleus of the solitary tract (NTS) integrates peripheral afferents with central pathways controlling breathing; NTS neurons function as central chemosensors, but only limited information exists concerning the ionic mechanisms involved. Acid-sensing ion channels (ASICs) mediate chemosensitivity in nociceptive terminals, where pH values ∼6.5 are not uncommon in inflammation, but are also abundantly expressed throughout the brain where pHi s tightly regulated and their role is less clear. Here we test the hypothesis that ASICs are expressed in NTS neurons and contribute to intrinsic chemosensitivity and control of breathing. In electrophysiological recordings from acute rat NTS slices, ∼40% of NTS neurons responded to physiological acidification (pH 7.0) with a transient depolarization. This response was also present in dissociated neurons suggesting an intrinsic mechanism. In voltage clamp recordings in slices, a pH drop from 7.4 to 7.0 induced ASIC-like inward currents (blocked by 100 μM amiloride) in ∼40% of NTS neurons, while at pH ≤ 6.5 these currents were detected in all neurons tested; RT-PCR revealed expression of ASIC1 and, less abundantly, ASIC2 in the NTS. Anatomical analysis of dye-filled neurons showed that ASIC-dependent chemosensitive cells (cells responding to pH 7.0) cluster dorsally in the NTS. Using in vivo retrograde labelling from the ventral respiratory column, 90% (9/10) of the labelled neurons showed an ASIC-like response to pH 7.0, suggesting that ASIC currents contribute to control of breathing. Accordingly, amiloride injection into the NTS reduced phrenic nerve activity of anaesthetized rats with an elevated arterial P(CO(2)) .

Ghrelin fibers from lateral hypothalamus project to nucleus tractus solitaries and are involved in gastric motility regulation in cisplatin-treated rats.

PubMed

Gong, Yanling; Liu, Yang; Liu, Fei; Wang, Shasha; Jin, Hong; Guo, Feifei; Xu, Luo

2017-03-15

Ghrelin can alleviate cancer chemotherapy-induced dyspepsia in rodents, though the neural mechanisms involved are not known. Therefore, ghrelin projections from the lateral hypothalamus (LH) and its involvement in the regulation of gastric motility in cisplatin-treated rats were investigated with a multi-disciplined approach. Retrograde tracing combined with fluoro-immunohistochemical staining were used to investigate ghrelin fiber projections arising from LH and projecting to nucleus tractus solitaries (NTS). Results revealed that ghrelin fibers originating in LH project to NTS. Expression of ghrelin and its receptor growth hormone secretagogue receptor (GHS-R1a) in LH and NTS were detected by Western Blot. 2days after cisplatin dosing, expression of ghrelin in LH decreased while GHS-R1a in both LH and NTS increased. In electrophysiological experiments, the effects of N-methyl-d-aspartate (NMDA) microinjection in LH on neuronal discharge of gastric distension-responsive neurons in NTS and gastric motility were assessed. NMDA in LH excited most of ghrelin-responsive gastric distension (GD)-sensitive neurons in NTS and promoted gastric motility. This effect was partially blocked by ghrelin antibody in NTS. Furthermore, the excitatory effects of NMDA in cisplatin-treated rats were weaker than those in saline-treated rats. Behaviorally, cisplatin induced a significant increase of kaolin consumption and decrease of food intake. These studies reveal a decreased expression of ghrelin in LH and up-regulation of GHS-R1a in LH and NTS, which are involved in the regulation of GD neuronal discharge in NTS and gastric motility. Copyright © 2017 Elsevier B.V. All rights reserved.

Fabrication of uniformly dispersed Ag nanoparticles loaded TiO{sub 2} nanotube arrays for enhancing photoelectrochemical and photocatalytic performances under visible light irradiation

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

Yi, Junhui; Zhang, Shengsen; Wang, Hongjuan

2014-12-15

Graphical abstract: Uniformly dispersed Ag nanoparticles (NPs) were successfully loaded on both the outer and inner surface of the TiO{sub 2} nanotube arrays (NTs) through a simple polyol method, which exhibited the enhanced photoelectrochemical and photocatalytic performances under visible-light irradiation due to the more effective separation of photo-generated electron–hole pairs and faster interfacial charge transfer. - Highlights: • Highly dispersed Ag nanoparticles (NPs) are successfully prepared by polyol method. • Ag NPs are uniformly loaded on the surface of the TiO{sub 2} nanotube arrays (NTs). • Ag/TiO{sub 2}-NTs exhibit the enhanced photocatalytic activity under visible-light. • The enhanced photocurrent ismore » explained by electrochemical impedance spectroscopy. - Abstract: Uniformly dispersed Ag nanoparticles (NPs) were successfully loaded on both the outer and inner surface of the TiO{sub 2} nanotube arrays (NTs) through a simple polyol method. The as-prepared Ag/TiO{sub 2}-NTs were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and UV–vis diffusion reflectance spectroscopy. Photoelectrochemical behaviors were investigated via photocurrent response and electrochemical impedance spectroscopy (EIS). Photocatalytic activity of Ag/TiO{sub 2}-NTs was evaluated by degradation of acid orange II under visible light irradiation. The results showed that photocatalytic efficiency of Ag/TiO{sub 2}-NTs is more than 5 times higher than that of pure TiO{sub 2} NTs. Comparing with the electrochemical deposition method, the photocatalytic activity of Ag/TiO{sub 2}-NTs prepared by polyol method has been obviously increased.« less

Genomic insights into the evolution and ecology of botulinum neurotoxins.

PubMed

Mansfield, Michael J; Doxey, Andrew C

2018-06-01

Clostridial neurotoxins, which include botulinum neurotoxins (BoNTs) and tetanus neurotoxins, have evolved a remarkably sophisticated structure and molecular mechanism fine-tuned for the targeting and cleavage of vertebrate neuron substrates leading to muscular paralysis. How and why did this toxin evolve? From which ancestral proteins are BoNTs derived? And what is, or was, the primary ecological role of BoNTs in the environment? In this article, we examine these questions in light of recent studies identifying homologs of BoNTs in the genomes of non-clostridial bacteria, including Weissella, Enterococcus and Chryseobacterium. Genomic and phylogenetic analysis of these more distantly related toxins suggests that they are derived from ancient toxin lineages that predate the evolution of BoNTs and are not limited to the Clostridium genus. We propose that BoNTs have therefore evolved from a precursor family of BoNT-like toxins, and ultimately from non-neurospecific toxins that cleaved different substrates (possibly non-neuronal SNAREs). Comparison of BoNTs with these related toxins reveals several unique molecular features that underlie the evolution of BoNT's unique function, including functional shifts involving all four domains, and gain of the BoNT gene cluster associated proteins. BoNTs then diversified to produce the existing serotypes, including TeNT, and underwent repeated substrate shifts from ancestral VAMP2 specificity to SNAP25 specificity at least three times in their history. Finally, similar to previous proposals, we suggest that one ecological role of BoNTs could be to create a paralytic phase in vertebrate decomposition, which provides a competitive advantage for necrophagous scavengers that in turn facilitate the spread of Clostridium botulinum and its toxin.

Reduction of CO2 to low carbon alcohols on CuO FCs/Fe2O3 NTs catalyst with photoelectric dual catalytic interfaces

NASA Astrophysics Data System (ADS)

Li, Peiqiang; Wang, Huying; Xu, Jinfeng; Jing, Hua; Zhang, Jun; Han, Haixiang; Lu, Fusui

2013-11-01

In this paper, the CuO FCs/Fe2O3 NTs catalyst was obtained after Fe2O3 nanotubes (Fe2O3 NTs) were decorated with CuO flower clusters (CuO FCs) by the pulse electrochemical deposition method. The in situ vertically aligned Fe2O3 NTs were prepared on the ferrous substrate by a potentiostatic anodization method. The SEM result showed the volcano-like Fe2O3 NTs were arranged in order and the CuO FCs constituted of flaky CuO distributed on the Fe2O3 NTs surface uniformly. After CuO FCs were loaded on Fe2O3 NTs, the absorption of visible light was enhanced noticeably, and its band gap narrowed to 1.78 eV from 2.03 eV. The conduction band and valence band locating at -0.73 eV and 1.05 eV, respectively were further obtained. In the PEC reduction of CO2 process, methanol and ethanol were two major products identified by chromatography. Their contents reached 1.00 mmol L-1 cm-2 and 107.38 μmol L-1 cm-2 after 6 h, respectively. This high-efficiency catalyst with photoelectric dual catalytic interfaces has a great guidance and reference significance for CO2 reduction to liquid carbon fuels.In this paper, the CuO FCs/Fe2O3 NTs catalyst was obtained after Fe2O3 nanotubes (Fe2O3 NTs) were decorated with CuO flower clusters (CuO FCs) by the pulse electrochemical deposition method. The in situ vertically aligned Fe2O3 NTs were prepared on the ferrous substrate by a potentiostatic anodization method. The SEM result showed the volcano-like Fe2O3 NTs were arranged in order and the CuO FCs constituted of flaky CuO distributed on the Fe2O3 NTs surface uniformly. After CuO FCs were loaded on Fe2O3 NTs, the absorption of visible light was enhanced noticeably, and its band gap narrowed to 1.78 eV from 2.03 eV. The conduction band and valence band locating at -0.73 eV and 1.05 eV, respectively were further obtained. In the PEC reduction of CO2 process, methanol and ethanol were two major products identified by chromatography. Their contents reached 1.00 mmol L-1 cm-2 and 107.38 μmol L-1 cm-2 after 6 h, respectively. This high-efficiency catalyst with photoelectric dual catalytic interfaces has a great guidance and reference significance for CO2 reduction to liquid carbon fuels. Electronic supplementary information (ESI) available: Reduction of CO2 to low carbon alcohols on CuO FCs/Fe2O3 NTs catalyst with photoelectric dual catalytic interfaces. See DOI: 10.1039/c3nr03352j

Nevada Test Site Resource Management Plan

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

NONE

1998-12-01

The Nevada Test Site (NTS) Resource Management Plan (RMP) describes the NTS Stewardship Mission and how its accomplishment will preserve the resources of the ecoregion while accomplishing the objectives of the mission. The NTS Stewardship Mission is to manage the land and facilities at the NTS as a unique and valuable national resource. The RMP has defined goals for twelve resource areas based on the principles of ecosystem management. These goals were established using an interdisciplinary team of DOE/NV resource specialists with input from surrounding land managers, private parties, and representatives of Native American governments. The overall goal of themore » RMP is to facilitate improved NTS land use management decisions within the Great Basin and Mojave Desert ecoregions.« less

Nevada Test Site Wetlands Assessment

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

D. J. Hansen

1997-05-01

This report identifies 16 Nevada Test Site (NTS) natural water sources that may be classified by the U.S. Army Corps of Engineers (USACE) as jurisdictional wetlands and identifies eight water sources that may be classified as waters of the United States. These water sources are rare, localized habitats on the NTS that are important to regional wildlife and to isolated populations of water tolerant plants and aquatic organisms. No field investigations on the NTS have been conducted in the past to identify those natural water sources which would be protected as rare habitats and which may fall under regulatory authoritymore » of the Clean Water Act (CWA) of 1997. This report identifies and summarizes previous studies of NTS natural water sources, and identifies the current DOE management practices related to the protection of NTS wetlands. This report also presents management goals specific for NTS wetlands that incorporate the intent of existing wetlands legislation, the principles of ecosystem management, and the interests of regional land managers and other stakeholders.« less

Hybrid biocomposites based on titania nanotubes and a hydroxyapatite coating deposited by RF-magnetron sputtering: Surface topography, structure, and mechanical properties

NASA Astrophysics Data System (ADS)

Chernozem, Roman V.; Surmeneva, Maria A.; Krause, Bärbel; Baumbach, Tilo; Ignatov, Viktor P.; Tyurin, Alexander I.; Loza, Kateryna; Epple, Matthias; Surmenev, Roman A.

2017-12-01

In this study, biocomposites based on porous titanium oxide structures and a calcium phosphate (CaP) or hydroxyapatite (HA) coating are described and prepared. Nanotubes (NTs) with different pore dimensions were processed using anodic oxidation of Ti substrates in a NH4F-containing electrolyte solution at anodization voltages of 30 and 60 V with a DC power supply. The external diameters of the nanotubes prepared at 30 V and 60 V were 53 ± 10 and 98 ± 16 nm, respectively. RF-magnetron sputtering of the HA target in a single deposition run was performed to prepare a coating on the surface of TiO2 NTs prepared at 30 and 60 V. The thickness of the CaP coating deposited on the mirror-polished Si substrate in the same deposition run with TiO2 NTs was determined by optical ellipsometry (SE) 95 ± 5 nm. Uncoated and CaP-coated NTs were annealed at 500 °C in air. Afterwards, the presence of TiO2 (anatase) was observed. The scanning electron microscopy (SEM), X-ray diffraction (XRD), photoelectron spectroscopy (XPS) and nanoindentation results revealed the influence that the NT dimensions had on the CaP coating deposition process. The tubular surfaces of the NTs were completely coated with the HA coating when prepared at 30 V, and no homogeneous CaP coating was observed when prepared at 60 V. The XRD patterns show peaks assigned to crystalline HA only for the coated TiO2 NTs prepared at 30 V. High-resolution XPS spectra show binding energies (BE) of Ca 2p, P 2p and O 1s core-levels corresponding to HA and amorphous calcium phosphate on TiO2 NTs prepared at 30 V and 60 V, respectively. Fabrication of TiO2 NTs results in a significant decrease to the elastic modulus and nanohardness compared to the Ti substrate. The porous structure of the NTs causes an increase in the elastic strain to failure of the coating (H/E) and the parameter used to describe the resistance of the material to plastic deformation (H3/E2) at the nanoscale level compared to the Ti substrate. Furthermore, only the HA coating on the NTs exhibits a significantly increased H/E ratio and H3/E2 factor compared to the NTs and Ti substrate. Increases in resistance to penetration for the indenter were also observed for HA-coated TiO2 NTs prepared at 30 V compared to uncoated and CaP-coated NTs prepared at 60 V.

Cardiovascular responses to microinjection of L-glutamate into the NTS in AV3V-lesioned rats.

PubMed

Vieira, Alexandre Antonio; Colombari, Eduardo; De Luca, Laurival A; de Almeida Colombari, Débora Simões; Menani, José V

2004-10-29

The excitatory amino acid L-glutamate injected into the nucleus of the solitary tract (NTS) in unanesthetized rats similar to peripheral chemoreceptor activation increases mean arterial pressure (MAP) and reduces heart rate. In this study, we investigated the effects of acute (1 day) and chronic (15 days) electrolytic lesions of the preoptic-periventricular tissue surrounding the anteroventral third ventricle (AV3V region) on the pressor and bradycardic responses induced by injections of L-glutamate into the NTS or peripheral chemoreceptor activation in unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions and a stainless steel cannula implanted into the NTS were used. Differently from the pressor responses (28+/-3 mm Hg) produced by injections into the NTS of sham-lesioned rats, L-glutamate (5 nmol/100 nl) injected into the NTS reduced MAP (-26+/-8 mm Hg) or produced no effect (2+/-7 mm Hg) in acute and chronic AV3V-lesioned rats, respectively. The bradycardia to l-glutamate into the NTS and the cardiovascular responses to chemoreflex activation with intravenous potassium cyanide or to baroreflex activation with intravenous phenylephrine or sodium nitroprusside were not modified by AV3V lesions. The results show that the integrity of the AV3V region is essential for the pressor responses to L-glutamate into the NTS but not for the pressor responses to chemoreflex activation, suggesting dissociation between the central mechanisms involved in these responses.

The evaluation of a framework for measuring the non-technical ward round skills of final year nursing students: An observational study.

PubMed

Murray, Kara; McKenzie, Karen; Kelleher, Michael

2016-10-01

The importance of non-technical skills (NTS) to patient outcomes is increasingly being recognised, however, there is limited research into how such skills can be taught and evaluated in student nurses in relation toward rounds. This pilot study describes an evaluation of a NTS framework that could potentially be used to measure ward round skills of student nurses. The study used an observational design. Potential key NTS were identified from existing literature and NTS taxonomies. The proposed framework was then used to evaluate whether the identified NTS were evident in a series of ward round simulations that final year general nursing students undertook as part of their training. Finally, the views of a small group of qualified nurse educators, qualified nurses and general nursing students were sought about whether the identified NTS were important and relevant to practice. The proposed NTS framework included seven categories: Communication, Decision Making, Situational Awareness, Teamwork and Task Management, Student Initiative and Responsiveness to Patient. All were rated as important and relevant to practice. The pilot study suggests that the proposed NTS framework could be used as a means of evaluating student nurse competencies in respect of many non-technical skills required for a successful ward round. Further work is required to establish the validity of the framework in educational settings and to determine the extent to which it is of use in a non-simulated ward round setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of a G protein-coupled receptor for neurotensin by liquid chromatography-electrospray ionization-mass spectrometry.

PubMed

Ho, Jenny T C; White, Jim F; Grisshammer, Reinhard; Hess, Sonja

2008-05-01

The type 1 neurotensin receptor (NTS1) belongs to the G protein-coupled receptor (GPCR) family. GPCRs are involved in important physiological processes, but for many GPCRs ligand binding sites and other structural features have yet to be elucidated. Comprehensive analyses by mass spectrometry (MS) could address such issues, but they are complicated by the hydrophobic nature of the receptors. Recombinant NTS1 must be purified in the presence of detergents to maintain solubility and functionality of the receptor, to allow testing of ligand, or to allow G protein interaction. However, detergents are detrimental to MS analyses. Hence, steps need to be taken to substitute the detergents with MS-compatible polar/organic solvents. Here we report the characterization of NTS1 by electrospray ionization (ESI)-MS with emphasis on methods to transfer intact NTS1 or its proteolytic peptides into compatible solvents by protein precipitation and liquid chromatography (LC) prior to ESI-MS analyses. Molecular mass measurement of intact recombinant NTS1 was performed using a mixture of chloroform/methanol/aqueous trifluoroacetic acid as the mobile phase for size exclusion chromatography-ESI-MS analysis. In a separate experiment, NTS1 was digested with a combination of cyanogen bromide and trypsin and/or chymotrypsin. Subsequent reversed phase LC-ESI-tandem MS analysis resulted in greater than 80% sequence coverage of the NTS1 protein, including all seven transmembrane domains. This work represents the first comprehensive analysis of recombinant NTS1 using MS.

Emergence and serovar profiling of non-typhoidal Salmonellae (NTS) isolated from gastroenteritis cases-A study from South India.

PubMed

Ballal, Mamatha; Devadas, Suganthi Martena; Shetty, Vignesh; Bangera, Sohan Rodney; Ramamurthy, Thandavarayan; Sarkar, Anirban

2016-01-01

Human infection with non-typhoidal Salmonella (NTS) serovars is often a neglected and undiagnosed infection in the developing world. Invasive NTS is now being established as having a new and emerging pathogenic role. There is not sufficient data on the prevalence of NTS serovars and their antibiotic susceptibility pattern from India. Faecal specimens collected from patients with acute gastroenteritis were processed to isolate Salmonella according to the standard protocol for a period from January 2011-December 2014. Salmonella isolates were serotyped and tested for antibiotic susceptibility. Of the total 320 (10.04%) bacterial enteric pathogens isolated, 64 (20%) were non-typhoidal Salmonella. Among the serogroup, O:4 (B) (n = 26; 40.6%) was found to be the commonest followed by O:7 (C1) (n = 11; 17.1%) and O:3,10 (E1) (n = 11; 17.1%). NTS infection in cancer patients could also be termed as nosocomial NTS diarrhoea due to primary community infection with prolonged incubation periods, consumption of contaminated food during hospital stay or Nosocomially acquired infection. Serovar Oslo has been predominant (9/17) in NTS isolates from cancer patients, whereas serovars Bovismorbificans, Wangata and Schleissheim have been reported for the first time in the country. The isolates were mostly susceptible to antibiotics except Salmonella ser Kentucky, which showed resistance to ciprofloxacin is reported for the first time in the country. Continuous surveillance is required to monitor resistance of NTS isolates.

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

Sekizawa, Shin-ichi, E-mail: ssekizawa@ucdavis.ed; Bechtold, Andrea G.; Tham, Rick C.

Allergic airway diseases in children are a common and a growing health problem. Changes in the central nervous system (CNS) have been implicated in contributing to some of the symptoms. We hypothesized that airway allergic diseases are associated with altered histamine H3 receptor expression in the nucleus tractus solitarius (NTS) and caudal spinal trigeminal nucleus, where lung/airway and nasal sensory afferents terminate, respectively. Immunohistochemistry for histamine H3 receptors was performed on brainstem sections containing the NTS and the caudal spinal trigeminal nucleus from 6- and 12-month-old rhesus monkeys who had been exposed for 5 months to house dust mite allergenmore » (HDMA) + O{sub 3} or to filtered air (FA). While histamine H3 receptors were found exclusively in astrocytes in the caudal spinal trigeminal nucleus, they were localized to both neuronal terminals and processes in the NTS. HDMA + O{sub 3} exposure significantly decreased histamine H3 receptor immunoreactivity in the NTS at 6 months and in the caudal spinal trigeminal nucleus at 12 months of age. In conclusion, exposing young primates to HDMA + O{sub 3} changed histamine H3 receptor expression in CNS pathways involving lung and nasal afferent nerves in an age-related manner. Histamine H3 receptors may be a therapeutic target for allergic asthma and rhinitis in children.« less

Atmospheric Radioxenon Measurements in North Las Vegas, NV

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

Milbrath, Brian D.; Cooper, Matthew W.; Lidey, Lance S.

2006-07-31

PNNL deployed the ARSA radioxenon measurement system in North Las Vegas for two weeks in February and March 2006 for the purpose of measuring the radioxenon background at a level of sensitivity much higher than previously done in the vicinity of the NTS. The measurements establish what might be expected if future measurements are taken at NTS itself. The measurements are also relevant to test site readiness. A second detector, the PEMS, built and operated by DRI, was deployed in conjunction with the ARSA and contained a PIC, aerosol collection filters, and meteorological sensors. Originally, measurements were also to bemore » performed at Mercury, NV on the NTS, but these were canceled due to initial equipment problems with the ARSA detector. Some of the radioxenon measurements detected 133Xe at levels up to 3 mBq/m3. This concentration of radioxenon is consistent with the observation of low levels of radioxenon emanating from distance nuclear reactors. Previous measurements in areas of high nuclear reactor concentration have shown similar results, but the western US, in general, does not have many nuclear reactors. Measurements of the wind direction indicate that the air carrying the radioxenon came from south of the detector and not from the NTS.« less

Biosecurity through Public Health System Design.

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

Beyeler, Walter E.; Finley, Patrick D.; Arndt, William

We applied modeling and simulation to examine the real-world tradeoffs between developingcountry public-health improvement and the need to improve the identification, tracking, and security of agents with bio-weapons potential. Traditionally, the international community has applied facility-focused strategies for improving biosecurity and biosafety. This work examines how system-level assessments and improvements can foster biosecurity and biosafety. We modeled medical laboratory resources and capabilities to identify scenarios where biosurveillance goals are transparently aligned with public health needs, and resource are distributed in a way that maximizes their ability to serve patients while minimizing security a nd safety risks. Our modeling platform simulatesmore » key processes involved in healthcare system operation, such as sample collection, transport, and analysis at medical laboratories. The research reported here extends the prior art by provided two key compone nts for comparative performance assessment: a model of patient interaction dynamics, and the capability to perform uncertainty quantification. In addition, we have outlined a process for incorporating quantitative biosecurity and biosafety risk measures. Two test problems were used to exercise these research products examine (a) Systemic effects of technological innovation and (b) Right -sizing of laboratory networks.« less

Air pollutants and cough.

PubMed

Joad, Jesse P; Sekizawa, Shin-ichi; Chen, Chao-Yin; Bonham, Ann C

2007-01-01

Epidemiological studies have shown that exposure to air pollution is associated with respiratory symptoms and decreases in lung function. This paper reviews recent literature showing that exposure to particulate matter, irritant gases, environmental tobacco smoke (ETS), mixed pollutants, and molds is associated with an increase in cough and wheeze. Some pollutants, like particulate matter and mixed pollutants, appear to increase cough at least as much as wheeze. Others, like irritant gases, appear to increase wheeze more than cough. For ETS, exposure during childhood is associated with cough and wheeze in adulthood, suggesting that the pollutant permanently alters some important aspect of the lungs, immune system or nervous system. We have shown in animal studies that pollutants change the neural control of airways and cough. Second hand smoke (SHS) exposure lengthened stimulated apnoea, increased the number of stimulated coughs, and augmented the degree of stimulated bronchoconstriction. The mechanisms included enhanced reactivity of the peripheral sensory neurones and second-order neurones in the nucleus tractus solitarius (NTS). NTS effects were due to a substance P mechanism at least in part. Ozone and allergen increased the intrinsic excitability of second-order neurones in the NTS. The animal studies suggest that the cough and wheeze experienced by humans exposed to pollutants may involve plasticity in the nervous system.

Organization of 5S rDNA in species of the fish Leporinus: two different genomic locations are characterized by distinct nontranscribed spacers.

PubMed

Martins, C; Galetti, P M

2001-10-01

To address understanding the organization of the 5S rRNA multigene family in the fish genome, the nucleotide sequence and organization array of 5S rDNA were investigated in the genus Leporinus, a representative freshwater fish group of South American fauna. PCR, subgenomic library screening, genomic blotting, fluorescence in situ hybridization, and DNA sequencing were employed in this study. Two arrays of 5S rDNA were identified for all species investigated, one consisting of monomeric repeat units of around 200 bp and another one with monomers of 900 bp. These 5S rDNA arrays were characterized by distinct NTS sequences (designated NTS-I and NTS-II for the 200- and 900-bp monomers, respectively); however, their coding sequences were nearly identical. The 5S rRNA genes were clustered in two chromosome loci, a major one corresponding to the NTS-I sites and a minor one corresponding to the NTS-II sites. The NTS-I sequence was variable among Leporinus spp., whereas the NTS-II was conserved among them and even in the related genus Schizodon. The distinct 5S rDNA arrays might characterize two 5S rRNA gene subfamilies that have been evolving independently in the genome.

Study of the highly ordered TiO2 nanotubes physical properties prepared with two-step anodization

NASA Astrophysics Data System (ADS)

Pishkar, Negin; Ghoranneviss, Mahmood; Ghorannevis, Zohreh; Akbari, Hossein

2018-06-01

Highly ordered hexagonal closely packed titanium dioxide nanotubes (TiO2 NTs) were successfully grown by a two-step anodization process. The TiO2 NTs were synthesized by electrochemical anodization of titanium foils in an ethylene glycol based electrolyte solution containing 0.3 wt% NH4F and 2 vol% deionized (DI) water at constant potential (50 V) for 1 h at room temperature. Physical properties of the TiO2 NTs, which were prepared via one and two-step anodization, were investigated. Atomic Force Microscopy (AFM) analysis revealed that anodization and subsequently peeled off the TiO2 NTs caused to the periodic pattern on the Ti surface. In order To study the nanotubes morphology, Field Emission Scanning Electron Microscopy (FESEM) was used, which was revealed that the two-step anodization resulted highly ordered hexagonal TiO2 NTs. Crystal structures of the TiO2 NTs were mainly anatase, determined by X-ray diffraction analysis. Optical studies were performed by Diffuse Reflection Spectra (DRS) and Photoluminescence (PL) analysis showed that the band gap of TiO2 NTs prepared via two-step anodization was lower than the band gap of samples prepared by one-step anodization process.

Rapid, conformal gas-phase formation of silica (SiO2) nanotubes from water condensates.

PubMed

Bae, Changdeuck; Kim, Hyunchul; Yang, Yunjeong; Yoo, Hyunjun; Montero Moreno, Josep M; Bachmann, Julien; Nielsch, Kornelius; Shin, Hyunjung

2013-07-07

An innovative atomic layer deposition (ALD) concept, with which nanostructures of water condensates with high aspect ratio at equilibrium in cylindrical nanopores can be transformed uniformly into silica (SiO2) at near room temperature and ambient pressure, has been demonstrated for the first time. As a challenging model system, we first prove the conversion of cylindrical water condensates in porous alumina membranes to silica nanotubes (NTs) by introducing SiCl4 as a metal reactant without involving any catalytic reaction. Surprisingly, the water NTs reproducibly transformed into silica NTs, where the wall thickness of the silica NTs deposited per cycle was found to be limited by the amount of condensed water, and it was on the orders of ten nanometers per cycle (i.e., over 50 times faster than that of conventional ALD). More remarkably, the reactions only took place for 10-20 minutes or less without vacuum-related equipment. The thickness of initially adsorbed water layers in cylindrical nanopores was indirectly estimated from the thickness of formed SiO2 layers. With systematic experimental designs, we tackle the classical Kelvin equation in the nanosized pores, and the role of van der Waals forces in the nanoscale wetting phenomena, which is a long-standing issue lacking experimental insight. Moreover, we show that the present strategy is likely generalized to other oxide systems such as TiO2. Our approach opens up a new avenue for ultra-simple preparation of porous oxides and allows for the room temperature formation of dielectric layers toward organic electronic and photovoltaic applications.

Inhibition of botulinum neurotoxins interchain disulfide bond reduction prevents the peripheral neuroparalysis of botulism.

PubMed

Zanetti, Giulia; Azarnia Tehran, Domenico; Pirazzini, Marcon; Binz, Thomas; Shone, Clifford C; Fillo, Silvia; Lista, Florigio; Rossetto, Ornella; Montecucco, Cesare

2015-12-01

Botulinum neurotoxins (BoNTs) form a growing family of metalloproteases with a unique specificity either for VAMP, SNAP25 or syntaxin. The BoNTs are grouped in seven different serotypes indicated by letters from A to G. These neurotoxins enter the cytosol of nerve terminals via a 100 kDa chain which binds to the presynaptic membrane and assists the translocation of a 50 kDa metalloprotease chain. These two chains are linked by a single disulfide bridge which plays an essential role during the entry of the metalloprotease chain in the cytosol, but thereafter it has to be reduced to free the proteolytic activity. Its reduction is mediated by thioredoxin which is continuously regenerated by its reductase. Here we show that inhibitors of thioredoxin reductase or of thioredoxin prevent the specific proteolysis of VAMP by the four VAMP-specific BoNTs: type B, D, F and G. These compounds are effective not only in primary cultures of neurons, but also in preventing the in vivo mouse limb neuroparalysis. In addition, one of these inhibitors, Ebselen, largely protects mice from the death caused by a systemic injection. Together with recent results obtained with BoNTs specific for SNAP25 and syntaxin, the present data demonstrate the essential role of the thioredoxin-thioredoxin reductase system in reducing the interchain disulfide during the nerve intoxication mechanism of all serotypes. Therefore its inhibitors should be considered for a possible use to prevent botulism and for treating infant botulism. Copyright © 2015 Elsevier Inc. All rights reserved.

[Complete genome sequencing and analyses of rabies viruses isolated from wild animals (Chinese Ferret-Badger) in Zhejiang province].

PubMed

Lei, Yong-Liang; Wang, Xiao-Guang; Liu, Fu-Ming; Chen, Xiu-Ying; Ye, Bi-Feng; Mei, Jian-Hua; Lan, Jin-Quan; Tang, Qing

2009-08-01

Based on sequencing the full-length genomes of two Chinese Ferret-Badger, we analyzed the properties of rabies viruses genetic variation in molecular level to get information on prevalence and variation of rabies viruses in Zhejiang, and to enrich the genome database of rabies viruses street strains isolated from Chinese wildlife. Overlapped fragments were amplified by RT-PCR and full-length genomes were assembled to analyze the nucleotide and deduced protein similarities and phylogenetic analyses of the N genes from Chinese Ferret-Badger, sika deer, vole, dog. Vaccine strains were then determined. The two full-length genomes were completely sequenced to find out that they had the same genetic structure with 11 923 nts including 58 nts-Leader, 1353 nts-NP, 894 nts-PP, 609 nts-MP, 1575 nts-GP, 6386 nts-LP, and 2, 5, 5 nts- intergenic regions (IGRs), 423 nts-Pseudogene-like sequence (Psi), 70 nts-Trailer. The two full-length genomes were in accordance with the properties of Rhabdoviridae Lyssa virus by blast and multi-sequence alignment. The nucleotide and amino acid sequences among Chinese strains had the highest similarity, especially among animals of the same species. Of the two full-length genomes, the similarity in amino acid level was dramatically higher than that in nucleotide level, so that the nucleotide mutations happened in these two genomes were most probably as synonymous mutations. Compared to the referenced rabies viruses, the lengths of the five protein coding regions did not show any changes or recombination, but only with a few-point mutations. It was evident that the five proteins appeared to be stable. The variation sites and types of the two ferret badgers genomes were similar to the referenced vaccine or street strains. The two strains were genotype 1 according to the multi-sequence and phylogenetic analyses, which possessing the distinct geographyphic characteristics of China. All the evidence suggested a cue that these two ferret badgers rabies viruses were likely to be street virus that already circulating in wildlife.

The Neurotensin NTS1 Receptor Agonist PD149163 Produces Antidepressant-Like Effects in the Forced Swim Test: Further Support for Neurotensin as a Novel Pharmacologic Strategy for Antidepressant Drugs.

PubMed

Carey, Lawrence M; Rice, Remington J; Prus, Adam J

2017-08-01

Preclinical Research Neurotensin is a nonbrain penetrant neuropeptide neurotransmitter that alters dopaminergic and serotonergic neurotransmission. Previous animal behavioral studies have demonstrated that intra-ventral tegmental administration of neurotensin and system administration of the selective neurotensin NTS 1 receptor agonist, PD149163 produce antidepressant-like effects in a forced swim test and a differential reinforcement of low rate task, respectively. The present study sought to expand upon these past findings by assessing systemic administration of PD149163 in a forced swim test, a primary antidepressant preclinical screening model, in mice. The tricyclic antidepressant drug imipramine was tested for comparison, and both compounds were also assessed in an open field test. Both PD149163 and imipramine reduced time spent immobile, an antidepressant-like effect, in the forced swim test. The highest dose of each compound significantly reduced locomotor activity. These findings provide further evidence for the putative antidepressant effects for PD149163 and suggest that NTS 1 receptor activation may be a novel pharmacologic strategy for antidepressant drug development. Drug Dev Res 78 : 196-202, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Coaxial electrospinning of WO3 nanotubes functionalized with bio-inspired Pd catalysts and their superior hydrogen sensing performance

NASA Astrophysics Data System (ADS)

Choi, Seon-Jin; Chattopadhyay, Saptarshi; Kim, Jae Jin; Kim, Sang-Joon; Tuller, Harry L.; Rutledge, Gregory C.; Kim, Il-Doo

2016-04-01

Macroporous WO3 nanotubes (NTs) functionalized with nanoscale catalysts were fabricated using coaxial electrospinning combined with sacrificial templating and protein-encapsulated catalysts. The macroporous thin-walled nanotubular structures were obtained by introducing colloidal polystyrene (PS) particles to a shell solution of W precursor and poly(vinylpyrrolidone). After coaxial electrospinning with a core liquid of mineral oil and subsequent calcination, open pores with an average diameter of 173 nm were formed on the surface of WO3 NTs due to decomposition of the PS colloids. In addition, catalytic Pd nanoparticles (NPs) were synthesized using bio-inspired protein cages, i.e., apoferritin, and uniformly dispersed within the shell solution and subsequently on the WO3 NTs. The resulting Pd functionalized macroporous WO3 NTs were demonstrated to be high performance hydrogen (H2) sensors. In particular, Pd-functionalized macroporous WO3 NTs exhibited a very high H2 response (Rair/Rgas) of 17.6 at 500 ppm with a short response time. Furthermore, the NTs were shown to be highly selective for H2 compared to other gases such as carbon monoxide (CO), ammonia (NH3), and methane (CH4). The results demonstrate a new synthetic method to prepare highly porous nanotubular structures with well-dispersed nanoscale catalysts, which can provide improved microstructures for chemical sensing.Macroporous WO3 nanotubes (NTs) functionalized with nanoscale catalysts were fabricated using coaxial electrospinning combined with sacrificial templating and protein-encapsulated catalysts. The macroporous thin-walled nanotubular structures were obtained by introducing colloidal polystyrene (PS) particles to a shell solution of W precursor and poly(vinylpyrrolidone). After coaxial electrospinning with a core liquid of mineral oil and subsequent calcination, open pores with an average diameter of 173 nm were formed on the surface of WO3 NTs due to decomposition of the PS colloids. In addition, catalytic Pd nanoparticles (NPs) were synthesized using bio-inspired protein cages, i.e., apoferritin, and uniformly dispersed within the shell solution and subsequently on the WO3 NTs. The resulting Pd functionalized macroporous WO3 NTs were demonstrated to be high performance hydrogen (H2) sensors. In particular, Pd-functionalized macroporous WO3 NTs exhibited a very high H2 response (Rair/Rgas) of 17.6 at 500 ppm with a short response time. Furthermore, the NTs were shown to be highly selective for H2 compared to other gases such as carbon monoxide (CO), ammonia (NH3), and methane (CH4). The results demonstrate a new synthetic method to prepare highly porous nanotubular structures with well-dispersed nanoscale catalysts, which can provide improved microstructures for chemical sensing. Electronic supplementary information (ESI) available: Coaxial electrospinning with different feeding rates, additional TEM analysis for pore size analysis, XPS analysis of Pd-loaded macroporous WO3 NTs, and dynamic response transition properties of sensors. See DOI: 10.1039/c5nr06611e

Electrodeposition of Ni and CeO₂/Ni Nanotubes for Hydrogen Evolution Reaction Electrode.

PubMed

Du, Xiaoqing; Yang, Yumeng; Yi, Chenxi; Chen, Yu; Cai, Chao; Zhang, Zhao

2018-07-01

Ni NTs and CeO2-Ni nanotubes (NTs) have been prepared by galvanostatic electrodeposition in anodic aluminum oxide (AAO) Templates. Scanning electron microscope (SEM), high resolution transmission electron microscopy (HRTEM), energy dispersive X-ray spectroscopic (EDS) and X-ray Diffraction (XRD) are used to characterize the prepared NTs. The results showed that the preparation process of CeO2-Ni NTs was accompanied by the formation of many new phases CeNix (x = 1, 2, 3.5 or 5) and preferential orientation crystal face of Ni in CeO2-Ni NTs is 〈111〉, which is different from that Ni 〈200〉 in Ni NTs. Then linear scan voltammetry (LSV) is applied to test the electrocatalytic activity for hydrogen revolution reaction (HER) of the two electrodes in 1 M NaCl aqueous solution and find that both of the two materials exhibited good performance. Finally, the kinetics analyses from the HER process showed that Tafel slope b was mainly dependent on phase composition and electric conductivity of the electrode, while j0 was mainly dependent on its real specific surface area.

National Emission Standards for Hazardous Air Pollutants Submittal - 1998

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

Stuart Black; Yvonne Townsend

1999-06-01

The Nevada Test Site (NTS) is operated by the U.S. Department of Energy Nevada Operations Office (DOE/NV) as the site for nuclear weapons testing, now limited to readiness activities and experiments in support of the national Stockpile Stewardship Management Program. It is located in Nye County, Nevada, with the southeast corner about 105 km (65 mi) northwest of Las Vegas, Nevada. The NTS covers about 3,500 km2 (1,350 mi2), an area larger than Rhode Island. Its size is about 46 to 56 km (28 to 35 mi) east to west and from 64 to 88 km (40 to 55 mi)northmore » to south. The NTS is surrounded, except on the south side, by public exclusion areas (Nellis Air Force Range) that provide another 24 to 104 km (15 to 65 mi) between the NTS and public lands. The NTS is characterized by desert valley and Great Basin mountain topography, with a climate, flora, and fauna typical of the southwest deserts. Surface waters are scarce on the NTS and there is great depth to slow-moving groundwater.« less

The evolutionary origin of the need to sleep: an inevitable consequence of synaptic neurotransmission?

PubMed

Cantor, Robert S

2015-01-01

It is proposed that the evolutionary origin of the need to sleep is the removal of neurotransmitters (NTs) that escape reuptake and accumulate in brain interstitial fluid (ISF). Recent work suggests that the activity of ionotropic postsynaptic receptors, rapidly initiated by binding of NTs to extracellular sites, is modulated over longer times by adsorption of these NTs to the lipid bilayers in which the receptors are embedded. This bilayer-mediated mechanism is far less molecularly specific than binding, so bilayer adsorption of NTs that have diffused into synapses for other receptors would modulate their activity as well. Although NTs are recycled by membrane protein reuptake, the process is less than 100% efficient; a fraction escapes the region in which these specific reuptake proteins are localized and eventually diffuses throughout the ISF. It is estimated that even if only 0.1% of NTs escape reuptake, they would accumulate and adsorb to bilayers in synapses of other receptors sufficiently to affect receptor activity, the harmful consequences of which are avoided by sleep: a period of efficient convective clearance of solutes together with greatly reduced synaptic activity.

Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse.

PubMed

Carter, D A; Choong, Y-T; Connelly, A A; Bassi, J K; Hunter, N O; Thongsepee, N; Llewellyn-Smith, I J; Fong, A Y; McDougall, S J; Allen, A M

2017-10-01

Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT 1A R) most widely expressed in adult neurons. Activation of the AT 1 R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT 1 R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT 1A R-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT 1A R promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT 1A R-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT 1A R-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT 1A R-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT 1A R-GFP neurons and TH-GFP neurons showed similar AT 1A R-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT 1A R-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing. Copyright © 2017 the American Physiological Society.

Structural and electronic properties of chiral single-wall copper nanotubes

NASA Astrophysics Data System (ADS)

Duan, YingNi; Zhang, JianMin; Xu, KeWei

2014-04-01

The structural, energetic and electronic properties of chiral ( n, m) (3⩽ n⩽6, n/2⩽ m⩽ n) single-wall copper nanotubes (CuNTs) have been investigated by using projector-augmented wave method based on density-functional theory. The (4, 3) CuNT is energetically stable and should be observed experimentally in both free-standing and tip-suspended conditions, whereas the (5, 5) and (6, 4) CuNTs should be observed in free-standing and tip-suspended conditions, respectively. The number of conductance channels in the CuNTs does not always correspond to the number of atomic strands comprising the nanotube. Charge density contours show that there is an enhanced interatomic interaction in CuNTs compared with Cu bulk. Current transporting states display different periods and chirality, the combined effects of which lead to weaker chiral currents on CuNTs.

Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A.

PubMed

Masuyer, Geoffrey; Thiyagarajan, Nethaji; James, Peter L; Marks, Philip M H; Chaddock, John A; Acharya, K Ravi

2009-03-27

Botulinum neurotoxins (BoNTs) modulate cholinergic nerve terminals to result in neurotransmitter blockade. BoNTs consists of catalytic (LC), translocation (Hn) and cell-binding domains (Hc). The binding function of the Hc domain is essential for BoNTs to bind the neuronal cell membrane, therefore, removal of the Hc domain results in a product that retains the endopeptidase activity of the LC but is non-toxic. Thus, a molecule consisting of LC and Hn domains of BoNTs, termed LHn, is a suitable molecule for engineering novel therapeutics. The structure of LHA at 2.6 A reported here provides an understanding of the structural implications and challenges of engineering therapeutic molecules that combine functional properties of LHn of BoNTs with specific ligand partners to target different cell types.

A Hydrostratigraphic System for Modeling Groundwater Flow and Radionuclide Migration at the Corrective Action Unit Scale, Nevada Test Site and Surrounding Areas, Clark, Lincoln, and Nye Counties, Nevada

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

Prothro, Lance; Drellack Jr., Sigmund; Mercadante, Jennifer

2009-01-31

Underground Test Area (UGTA) corrective action unit (CAU) groundwater flow and contaminant transport models of the Nevada Test Site (NTS) and vicinity are built upon hydrostratigraphic framework models (HFMs) that utilize the hydrostratigraphic unit (HSU) as the fundamental modeling component. The delineation and three-dimensional (3-D) modeling of HSUs within the highly complex geologic terrain that is the NTS requires a hydrostratigraphic system that is internally consistent, yet flexible enough to account for overlapping model areas, varied geologic terrain, and the development of multiple alternative HFMs. The UGTA CAU-scale hydrostratigraphic system builds on more than 50 years of geologic and hydrologicmore » work in the NTS region. It includes 76 HSUs developed from nearly 300 stratigraphic units that span more than 570 million years of geologic time, and includes rock units as diverse as marine carbonate and siliciclastic rocks, granitic intrusives, rhyolitic lavas and ash-flow tuffs, and alluvial valley-fill deposits. The UGTA CAU-scale hydrostratigraphic system uses a geology-based approach and two-level classification scheme. The first, or lowest, level of the hydrostratigraphic system is the hydrogeologic unit (HGU). Rocks in a model area are first classified as one of ten HGUs based on the rock’s ability to transmit groundwater (i.e., nature of their porosity and permeability), which at the NTS is mainly a function of the rock’s primary lithology, type and degree of postdepositional alteration, and propensity to fracture. The second, or highest, level within the UGTA CAU-scale hydrostratigraphic system is the HSU, which is the fundamental mapping/modeling unit within UGTA CAU-scale HFMs. HSUs are 3-D bodies that are represented in the finite element mesh for the UGTA groundwater modeling process. HSUs are defined systematically by stratigraphically organizing HGUs of similar character into larger HSUs designations. The careful integration of stratigraphic information in the development of HSUs is important to assure individual HSUs are internally consistent, correlatable, and mappable throughout all the model areas.« less

Photoelectrocatalytic Synthesis of Hydrogen Peroxide by Molecular Copper-Porphyrin Supported on Titanium Dioxide Nanotubes.

PubMed

Apaydin, Dogukan H; Seelajaroen, Hathaichanok; Pengsakul, Orathip; Thamyongkit, Patchanita; Sariciftci, Niyazi Serdar; Kunze-Liebhäuser, Julia; Portenkirchner, Engelbert

2018-04-24

We report on a self-assembled system comprising a molecular copper-porphyrin photoelectrocatalyst, 5-(4-carboxy-phenyl)-10,15,20-triphenylporphyrinatocopper(II) (CuTPP-COOH), covalently bound to self-organized, anodic titania nanotube arrays (TiO 2 NTs) for photoelectrochemical reduction of oxygen. Visible light irradiation of the porphyrin-covered TiO 2 NTs under cathodic polarization up to -0.3 V vs. Normal hydrogen electrode (NHE) photocatalytically produces H 2 O 2 in pH neutral electrolyte, at room temperature and without need of sacrificial electron donors. The formation of H 2 O 2 upon irradiation is proven and quantified by direct colorimetric detection using 4-nitrophenyl boronic acid ( p -NPBA) as a reactant. This simple approach for the attachment of a small molecular catalyst to TiO 2 NTs may ultimately allow for the preparation of a low-cost H 2 O 2 evolving cathode for efficient photoelectrochemical energy storage under ambient conditions.

Electrochemical biosensor for Mycobacterium tuberculosis DNA detection based on gold nanotubes array electrode platform.

PubMed

Torati, Sri Ramulu; Reddy, Venu; Yoon, Seok Soo; Kim, CheolGi

2016-04-15

The template assisted electrochemical deposition technique was used for the synthesis of gold nanotubes array (AuNTsA). The morphological structure of the synthesized AuNTsA was observed by scanning electron microscopy and found that the individual nanotubes are around 1.5 μm in length with a diameter of 200 nm. Nanotubes are vertically aligned to the Au thick film, which is formed during the synthesis process of nanotubes. The electrochemical performance of the AuNTsA was compared with the bare Au electrode and found that AuNTsA has better electron transfer surface than bare Au electrode which is due to the high surface area. Hence, the AuNTsA was used as an electrode for the fabrication of DNA hybridization biosensor for detection of Mycobacterium Tuberculosis DNA. The DNA hybridization biosensor constructed by AuNTsA electrode was characterized by cyclic voltammetry technique with Fe(CN)6(3-/4-) as an electrochemical redox indicator. The selectivity of the fabricated biosensor was illustrated by hybridization with complementary DNA and non-complementary DNA with probe DNA immobilized AuNTsA electrode using methylene blue as a hybridization indicator. The developed electrochemical DNA biosensor shows good linear range of complementary DNA concentration from 0.01 ng/μL to 100 ng/μL with high detection limit. Copyright © 2015 Elsevier B.V. All rights reserved.

pH modulation of glial glutamate transporters regulates synaptic transmission in the nucleus of the solitary tract

PubMed Central

McCrimmon, Donald R.; Martina, Marco

2013-01-01

The nucleus of the solitary tract (NTS) is the major site for termination of visceral sensory afferents contributing to homeostatic regulation of, for example, arterial pressure, gastric motility, and breathing. Whereas much is known about how different neuronal populations influence these functions, information about the role of glia remains scant. In this article, we propose that glia may contribute to NTS functions by modulating excitatory neurotransmission. We found that acidification (pH 7.0) depolarizes NTS glia by inhibiting K+-selective membrane currents. NTS glia also showed functional expression of voltage-sensitive glutamate transporters, suggesting that extracellular acidification regulates synaptic transmission by compromising glial glutamate uptake. To test this hypothesis, we evoked glutamatergic slow excitatory potentials (SEPs) in NTS neurons with repetitive stimulation (20 pulses at 10 Hz) of the solitary tract. This SEP depends on accumulation of glutamate following repetitive stimulation, since it was potentiated by blocking glutamate uptake with dl-threo-β-benzyloxyaspartic acid (TBOA) or a glia-specific glutamate transport blocker, dihydrokainate (DHK). Importantly, extracellular acidification (pH 7.0) also potentiated the SEP. This effect appeared to be mediated through a depolarization-induced inhibition of glial transporter activity, because it was occluded by TBOA and DHK. In agreement, pH 7.0 did not directly alter d-aspartate-induced responses in NTS glia or properties of presynaptic glutamate release. Thus acidification-dependent regulation of glial function affects synaptic transmission within the NTS. These results suggest that glia play a modulatory role in the NTS by integrating local tissue signals (such as pH) with synaptic inputs from peripheral afferents. PMID:23615553

Involvement of ERK phosphorylation in brainstem neurons in modulation of swallowing reflex in rats

PubMed Central

Tsujimura, Takanori; Kondo, Masahiro; Kitagawa, Junichi; Tsuboi, Yoshiyuki; Saito, Kimiko; Tohara, Haruka; Ueda, Koichiro; Sessle, Barry J; Iwata, Koichi

2009-01-01

In order to evaluate the neuronal mechanisms underlying functional abnormalities of swallowing in orofacial pain patients, this study investigated the effects of noxious orofacial stimulation on the swallowing reflex, phosphorylated extracellular signal-regulated kinase (pERK) and γ-aminobutyric acid (GABA) immunohistochemical features in brainstem neurons, and also analysed the effects of brainstem lesioning and of microinjection of GABA receptor agonist or antagonist into the nucleus tractus solitarii (NTS) on the swallowing reflex in anaesthetized rats. The swallowing reflex elicited by topical administration of distilled water to the pharyngolaryngeal region was inhibited after capsaicin injection into the facial (whisker pad) skin or lingual muscle. The capsaicin-induced inhibitory effect on the swallowing reflex was itself depressed after the intrathecal administration of MAPK kinase (MEK) inhibitor. No change in the capsaicin-induced inhibitory effect was observed after trigeminal spinal subnucleus caudalis lesioning, but the inhibitory effect was diminished by paratrigeminal nucleus (Pa5) lesioning. Many pERK-like immunoreactive neurons in the NTS showed GABA immunoreactivity. The local microinjection of the GABAA receptor agonist muscimol into the NTS produced a significant reduction in swallowing reflex, and the capsaicin-induced depression of the swallowing reflex was abolished by microinjection of the GABAA receptor antagonist bicuculline into the NTS. The present findings suggest that facial skin–NTS, lingual muscle–NTS and lingual muscle–Pa5–NTS pathways are involved in the modulation of swallowing reflex by facial and lingual pain, respectively, and that the activation of GABAergic NTS neurons is involved in the inhibition of the swallowing reflex following noxious stimulation of facial and intraoral structures. PMID:19124539

Aligned TiO₂ nanotube/nanoparticle heterostructures with enhanced electrochemical performance as three-dimensional anode for lithium-ion microbatteries.

PubMed

Xie, Keyu; Guo, Min; Lu, Wei; Huang, Haitao

2014-11-14

A novel TiO₂ three-dimensional (3D) anode with an aligned TiO₂ nanotube/nanoparticle heterostructure (TiO₂ NTs/NPs) is developed by simply immersing as-anodized TiO₂ NTs into water and further crystallizing the TiO₂ NTs by post-annealing. The heterostructure, with its core in a tubular morphology and with both the outer and inner surface consisting of nanoparticles, is confirmed by FESEM and TEM. A reversible areal capacity of 0.126 mAh · cm(-2) is retained after 50 cycles for the TiO₂ NTs/NPs heterostructure electrode, which is higher than that of the TiO₂ NTs electrode (0.102 mAh · cm(-2) after 50 cycles). At the current densities of 0.02, 0.04, 0.06, 0.08, 0.10 and 0.20 mA · cm(-2), the areal capacities are 0.142, 0.127, 0.117, 0.110, 0.104 and 0.089 mAh · cm(-2), respectively, for the TiO₂ NTs/NPs heterostructure electrode compared to the areal capacities of 0.123, 0.112, 0.105, 0.101, 0.094 and 0.083 mAh · cm(-2), respectively, for the the TiO₂ NTs electrode. The enhanced electrochemical performance is attributed to the unique microstructure of the TiO₂ NTs/NPs heterostructure electrode with the TiO₂ NT core used as a straight pathway for electronic transport and with TiO₂ NP offering enhanced surface areas for facile Li+ insertion/extraction. The results described here inspire a facile approach to fabricate a 3D anode with an enhanced electrochemical performance for lithium-ion microbattery applications.

Sudden Death and Myocardial Lesions after Damage to Catecholamine Neurons of the Nucleus Tractus Solitarii in Rat

PubMed Central

Talman, William T.; Dragon, Deidre Nitschke; Jones, Susan Y.; Moore, Steven A.; Lin, Li-Hsien

2015-01-01

Lesions that remove neurons expressing neurokinin-1 (NK1) receptors from the nucleus tractus solitarii (NTS) without removing catecholaminergic neurons lead to loss of baroreflexes, labile arterial pressure, myocardial lesions and sudden death. Because destruction of NTS catecholaminergic neurons expressing tyrosine hydroxylase (TH) may also cause lability of arterial pressure and loss of baroreflexes, we sought to test the hypothesis that cardiac lesions associated with lability are not dependent on damage to neurons with NK1 receptors but would also occur when TH neurons in NTS are targeted. To rid the NTS of TH neurons we microinjected anti-dopamine β-hydroxylase conjugated to saporin (anti-DBH-SAP, 42ng/200nl) into the NTS. After injection of the toxin unilaterally, immunofluorescent staining confirmed that anti-DBH-SAP decreased the number of neurons and fibers that contain TH and DBH in the injected side of the NTS while sparing neuronal elements expressing NK1 receptors. Bilateral injections in 8 rats led to significant lability of arterial pressure. For example, on day 8 standard deviation of mean arterial pressure was 16.8 ± 2.5 mmHg when compared with a standard deviation of 7.83 ± 0.33 mmHg in 6 rats in which phosphate buffered saline (PBS) had been injected bilaterally. Two rats died suddenly at 5 and 8 days after anti-DBH-SAP injection. Seven treated animals demonstrated microscopic myocardial necrosis as reported in animals with lesions of NTS neurons expressing NK1 receptors. Thus, cardiac and cardiovascular effects of lesions directed toward catecholamine neurons of the NTS are similar to those following damage directed toward NK1 receptor containing neurons. PMID:22484855

Glycemic state regulates melanocortin, but not nesfatin-1, responsiveness of glucose-sensing neurons in the nucleus of the solitary tract.

PubMed

Mimee, Andrea; Ferguson, Alastair V

2015-04-15

The nucleus of the solitary tract (NTS) is a medullary integrative center with critical roles in the coordinated control of energy homeostasis. Here, we used whole cell current-clamp recordings on rat NTS neurons in slice preparation to identify the presence of physiologically relevant glucose-sensing neurons. The majority of NTS neurons (n = 81) were found to be glucose-responsive, with 35% exhibiting a glucose-excited (GE) phenotype (mean absolute change in membrane potential: 9.5 ± 1.1 mV), and 21% exhibiting a glucose-inhibited (GI) response (mean: 6.3 ± 0.7 mV). Furthermore, we found glucose-responsive cells are preferentially influenced by the anorexigenic peptide α-melanocyte-stimulating hormone (α-MSH), but not nesfatin-1. Accordingly, alterations in glycemic state have profound effects on the responsiveness of NTS neurons to α-MSH, but not to nesfatin-1. Indeed, NTS neurons showed increasing responsiveness to α-MSH as extracellular glucose concentrations were decreased, and in hypoglycemic conditions, all NTS neurons were depolarized by α-MSH (mean 10.6 ± 3.2 mV; n = 8). Finally, decreasing levels of extracellular glucose correlated with a significant hyperpolarization of the baseline membrane potential of NTS neurons, highlighting the modulatory effect of glucose on the baseline excitability of cells in this region. Our findings reveal individual NTS cells are capable of integrating multiple sources of metabolically relevant inputs, highlight the rapid capacity for plasticity in medullary melanocortin circuits, and emphasize the critical importance of physiological recording conditions for electrophysiological studies pertaining to the central control of energy homeostasis. Copyright © 2015 the American Physiological Society.

Glycemic state regulates melanocortin, but not nesfatin-1, responsiveness of glucose-sensing neurons in the nucleus of the solitary tract

PubMed Central

Mimee, Andrea

2015-01-01

The nucleus of the solitary tract (NTS) is a medullary integrative center with critical roles in the coordinated control of energy homeostasis. Here, we used whole cell current-clamp recordings on rat NTS neurons in slice preparation to identify the presence of physiologically relevant glucose-sensing neurons. The majority of NTS neurons (n = 81) were found to be glucose-responsive, with 35% exhibiting a glucose-excited (GE) phenotype (mean absolute change in membrane potential: 9.5 ± 1.1 mV), and 21% exhibiting a glucose-inhibited (GI) response (mean: 6.3 ± 0.7 mV). Furthermore, we found glucose-responsive cells are preferentially influenced by the anorexigenic peptide α-melanocyte-stimulating hormone (α-MSH), but not nesfatin-1. Accordingly, alterations in glycemic state have profound effects on the responsiveness of NTS neurons to α-MSH, but not to nesfatin-1. Indeed, NTS neurons showed increasing responsiveness to α-MSH as extracellular glucose concentrations were decreased, and in hypoglycemic conditions, all NTS neurons were depolarized by α-MSH (mean 10.6 ± 3.2 mV; n = 8). Finally, decreasing levels of extracellular glucose correlated with a significant hyperpolarization of the baseline membrane potential of NTS neurons, highlighting the modulatory effect of glucose on the baseline excitability of cells in this region. Our findings reveal individual NTS cells are capable of integrating multiple sources of metabolically relevant inputs, highlight the rapid capacity for plasticity in medullary melanocortin circuits, and emphasize the critical importance of physiological recording conditions for electrophysiological studies pertaining to the central control of energy homeostasis. PMID:25695291

Viscerosensory input drives angiotensin II type 1A receptor-expressing neurons in the solitary tract nucleus.

PubMed

Carter, D A; Guo, H; Connelly, A A; Bassi, J K; Fong, A Y; Allen, A M; McDougall, S J

2018-02-01

Homeostatic regulation of visceral organ function requires integrated processing of neural and neurohormonal sensory signals. The nucleus of the solitary tract (NTS) is the primary sensory nucleus for cranial visceral sensory afferents. Angiotensin II (ANG II) is known to modulate peripheral visceral reflexes, in part, by activating ANG II type 1A receptors (AT 1A R) in the NTS. AT 1A R-expressing NTS neurons occur throughout the NTS with a defined subnuclear distribution, and most of these neurons are depolarized by ANG II. In this study we determined whether AT 1A R-expressing NTS neurons receive direct visceral sensory input, and whether this input is modulated by ANG II. Using AT 1A R-GFP mice to make targeted whole cell recordings from AT 1A R-expressing NTS neurons, we demonstrate that two-thirds (37 of 56) of AT 1A R-expressing neurons receive direct excitatory, visceral sensory input. In half of the neurons tested (4 of 8) the excitatory visceral sensory input was significantly reduced by application of the transient receptor potential vallinoid type 1 receptor agonist, capsaicin, indicating AT 1A R-expressing neurons can receive either C- or A-fiber-mediated input. Application of ANG II to a subset of second-order AT 1A R-expressing neurons did not affect spontaneous, evoked, or asynchronous glutamate release from visceral sensory afferents. Thus it is unlikely that AT 1A R-expressing viscerosensory neurons terminate on AT 1A R-expressing NTS neurons. Our data suggest that ANG II is likely to modulate multiple visceral sensory modalities by altering the excitability of second-order AT 1A R-expressing NTS neurons.

Antihypertensive effects of central ablations in spontaneously hypertensive rats.

PubMed

Moreira, Thiago S; Takakura, Ana C; Colombari, Eduardo; Menani, José V

2009-06-01

Commissural nucleus of the solitary tract (commNTS) lesions transitorily (first 5 days) reduce mean arterial pressure (MAP) in spontaneously hypertensive rats (SHR), and lesions of the tissue surrounding the anteroventral third ventricle (AV3V region) chronically reduce MAP in other models of hypertension. In the present study, we investigated the effects of combined AV3V+commNTS electrolytic lesions on MAP and heart rate (HR) in conscious SHR. Baseline MAP and HR were recorded in male SHR before and for the next 40 days after sham or AV3V lesions combined with sham or commNTS lesions. The AV3V lesions produced no change in MAP in SHR, while commNTS lesions reduced MAP acutely (121 +/- 2 to 127 +/- 3 mmHg in the 1st and 5th days, respectively, vs. prelesion: 192 +/- 4 mmHg) but not chronically (from 10 to 40 days). However, combined AV3V+commNTS lesions reduced MAP of SHR chronically (119 +/- 2 to 161 +/- 4 mmHg, in the 1st and 40th day, respectively, vs. prelesion levels: 186 +/- 4 mmHg) or sham-lesioned SHR (187 +/- 4 to 191 +/- 6 mmHg). Sympathetic and angiotensinergic blockade produced less reduction in MAP in SHR with AV3V+commNTS-lesions, and there was no relationship between changes on water and food intake, body weight, or urinary excretion produced by AV3V+commNTS lesions with the changes in MAP. The present findings suggest that in the absence of the commNTS, the AV3V region contributes to the hypertension observed in SHR by mechanisms that appear to involve enhanced angiotensinergic and sympathetic activity.

Fabrication of polypyrrole/vanadium oxide nanotube composite with enhanced electrochemical performance as cathode in rechargeable batteries

NASA Astrophysics Data System (ADS)

Zhou, Xiaowei; Chen, Xu; He, Taoling; Bi, Qinsong; Sun, Li; Liu, Zhu

2017-05-01

Vanadium oxide nanotubes (VOxNTs) with hollow as well as multi-walled features were fabricated under hydrothermal condition by soft-template method. This novel VOxNTs can be used as cathode material for lithium ion batteries (LIBs), but displaying low specific capacity and poor cycling performance owing to the residual of a mass of soft-template (C12H27N) and intrinsic low conductivity of VOx. Cation exchange technique and oxidative polymerization process of pyrrole monomers were conducted to wipe off partial soft-template without electrochemical activity within VOxNTs and simultaneously form polypyrrole coating on VOxNTs, respectively. The resulting polypyrrole/VOxNTs nanocomposite delivers much improved capacity and cyclic stability. Further optimizations, such as complete elimination of organic template and enhancing the crystallinity, can make this unique nanostructure a promising cathode for LIBs.

Blood invasiveness of Salmonella enterica as a function of age and serotype.

PubMed Central

Weinberger, M.; Andorn, N.; Agmon, V.; Cohen, D.; Shohat, T.; Pitlik, S. D.

2004-01-01

We explored the dual influence of the patient's age and the infecting serotype on the blood invasiveness patterns of non-Typhi Salmonella enterica (NTS). Blood invasiveness ratio (BIR) was calculated as the ratio between the number of blood and blood + stool isolates. Analysis of 14,951 NTS isolates showed that the BIR increased drastically above the age of 60 years, reaching levels 3.5-7 times higher compared to age group < 2 years. Different patterns of age-related invasiveness were observed for the five most common NTS serotypes (Enteritidis, Typhimurium, Virchow, Hadar, Infantis). Among children < 2 years, the BIR was highest for serotype Virchow and lowest for serotype Hadar, while in persons > or = 60 years it was highest for serotypes Enteritidis and lowest for serotype Infantis. The tendency of NTS serotypes to invade the bloodstream was significantly influenced by the patient's age, however the impact of age differed for various NTS serotypes. PMID:15635958

Selective effect of cell membrane on synaptic neurotransmission

NASA Astrophysics Data System (ADS)

Postila, Pekka A.; Vattulainen, Ilpo; Róg, Tomasz

2016-01-01

Atomistic molecular dynamics simulations were performed with 13 non-peptidic neurotransmitters (NTs) in three different membrane environments. The results provide compelling evidence that NTs are divided into membrane-binding and membrane-nonbinding molecules. NTs adhere to the postsynaptic membrane surface whenever the ligand-binding sites of their synaptic receptors are buried in the lipid bilayer. In contrast, NTs that have extracellular ligand-binding sites do not have a similar tendency to adhere to the membrane surface. This finding is a seemingly simple yet important addition to the paradigm of neurotransmission, essentially dividing it into membrane-independent and membrane-dependent mechanisms. Moreover, the simulations also indicate that the lipid composition especially in terms of charged lipids can affect the membrane partitioning of NTs. The revised paradigm, highlighting the importance of cell membrane and specific lipids for neurotransmission, should to be of interest to neuroscientists, drug industry and the general public alike.

Electrical transport properties of individual WS2 nanotubes and their dependence on water and oxygen absorption

NASA Astrophysics Data System (ADS)

Zhang, Chaoying; Ning, Zhiyuan; Liu, Yang; Xu, Tingting; Guo, Yao; Zak, Alla; Zhang, Zhiyong; Wang, Sheng; Tenne, Reshef; Chen, Qing

2012-09-01

The electrical properties of WS2 nanotubes (NTs) were studied through measuring 59 devices. Important electrical parameters, such as the carrier concentration, mobility, and effective barrier height at the contacts, were obtained through fitting experimental non-linear I-V curves using a metal-semiconductor-metal model. The carrier mobility was found to be several orders of magnitude higher than that have been reported previously for WS2 NTs. Water absorption was found to decrease the conductivity and carrier mobility of the NTs, and could be removed when the sample was dried. Oxygen absorption also slightly decreased the conductivity of WS2 NTs.

Nanometer Scale Confined Growth of Single-Crystalline Gold Nanowires via Photocatalytic Reduction.

PubMed

Lee, Seonhee; Bae, Changdeuck; Shin, Hyunjung

2018-06-20

Single-crystalline gold nanowires (Au NWs) are directly synthesized by the photocatalytic reduction of an aqueous HAuCl 4 solution inside high-aspect-ratio TiO 2 nanotubes (NTs). Crystalline TiO 2 (anatase) NTs are prepared by the template-assisted atomic layer deposition technique with a subsequent annealing. Under the irradiation of ultraviolet light, photoexcited electrons are formed on the surfaces of TiO 2 NTs and could reduce Au ions to create nuclei without using any surfactant, reducing agent, and/or seed. Once nucleation occurred, high-aspect-ratio Au NWs are grown inside the TiO 2 NTs in a diffusion-controlled manner. As the solution pH increased, the nucleation/growth rate decreased and twin-free (or not observed), single-crystalline Au NWs are formed. At a pH above 6, the nucleation/growth rates increased and Au nanoparticles are observed both inside and outside of the TiO 2 NTs. The confined nanoscale geometries of the interior of the TiO 2 NTs are found to play a key role in the controlled diffusion of Au species and in determining the crystal morphology of the resulting Au NWs.

Photocatalytic performance of freestanding tetragonal zirconia nanotubes formed in H2O2/NH4F/ethylene glycol electrolyte by anodisation of zirconium

NASA Astrophysics Data System (ADS)

Rozana, Monna; Izza Soaid, Nurul; Kian, Tan Wai; Kawamura, Go; Matsuda, Atsunori; Lockman, Zainovia

2017-04-01

ZrO2 nanotubes (ZrNTs) were produced by anodisation of zirconium foil in H2O2/NH4F/ethylene glycol electrolyte. The as-anodised foils were then soaked in the anodising electrolyte for 12 h. Soaking weakens the adherence of the anodic layer from the substrate resulting in freestanding ZrNTs (FS-ZrNTs). Moreover, the presence of H2O2 in the electrolyte also aids in weakening the adhesion of the film from the foil, as foil anodised in electrolyte without H2O2 has good film adherence. The as-anodised FS-ZrNTs film was amorphous and crystallised to predominantly tetragonal phase upon annealing at >300 °C. Annealing must, however, be done at <500 °C to avoid monoclinic ZrO2 formation and nanotubes disintegration. FS-ZrNTs annealed at 450 °C exhibited the highest photocatalytic ability to degrade methyl orange (MO), whereby 82% MO degradation was observed after 5 h, whereas FS-ZrNTs with a mixture of monoclinic and tetragonal degraded 70% of MO after 5 h.

BaTiO3-based nanolayers and nanotubes: first-principles calculations.

PubMed

Evarestov, Robert A; Bandura, Andrei V; Kuruch, Dmitrii D

2013-01-30

The first-principles calculations using hybrid exchange-correlation functional and localized atomic basis set are performed for BaTiO(3) (BTO) nanolayers and nanotubes (NTs) with the structure optimization. Both the cubic and the ferroelectric BTO phases are used for the nanolayers and NTs modeling. It follows from the calculations that nanolayers of the different ferroelectric BTO phases have the practically identical surface energies and are more stable than nanolayers of the cubic phase. Thin nanosheets composed of three or more dense layers of (0 1 0) and (0 1 1[overline]) faces preserve the ferroelectric displacements inherent to the initial bulk phase. The structure and stability of BTO single-wall NTs depends on the original bulk crystal phase and a wall thickness. The majority of the considered NTs with the low formation and strain energies has the mirror plane perpendicular to the tube axis and therefore cannot exhibit ferroelectricity. The NTs folded from (0 1 1[overline]) layers may show antiferroelectric arrangement of Ti-O bonds. Comparison of stability of the BTO-based and SrTiO(3)-based NTs shows that the former are more stable than the latter. Copyright © 2012 Wiley Periodicals, Inc.

Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children.

PubMed

Gilchrist, James J; Heath, Jennifer N; Msefula, Chisomo L; Gondwe, Esther N; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M; Molyneux, Elizabeth M; Graham, Stephen M; Drayson, Mark T; Molyneux, Malcolm E; MacLennan, Calman A

2016-07-01

Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis. Copyright © 2016 Gilchrist et al.

Invasive Infections with Nontyphoidal Salmonella in Sub-Saharan Africa.

PubMed

Mahon, Barbara E; Fields, Patricia I

2016-06-01

Invasive nontyphoidal Salmonella (NTS) infections in Africa cause an enormous burden of illness. These infections are often devastating, with mortality estimated at 20%, even with appropriate antimicrobial therapy. Two major groups-young children and HIV-infected adults-suffer the great majority of these infections. In children, younger age itself, as well as malaria, malnutrition, and HIV infection, are prominent risk factors. In adults, HIV infection is by far the most important risk factor. The most common serotypes in invasive infections are Salmonella enterica serotypes Typhimurium and Enteritidis. In recent years, a specific strain of Salmonella Typhimurium, multilocus sequence type 313, has caused epidemics of invasive disease. Little is known about risk factors for exposure to NTS, making the design of rational interventions to decrease exposure difficult. Antimicrobial therapy is critically important for treatment of invasive NTS infections. Thus, the emergence and spread of resistance to agents commonly used for treatment of invasive NTS infection, now including third-generation cephalosporins, is an ominous development. Already, many invasive NTS infections are essentially untreatable in many health care facilities in sub-Saharan Africa. Several candidate vaccines are in early development and, if safe and effective, could be promising. Interventions to prevent exposure to NTS (e.g., improved sanitation), to prevent the occurrence of disease if exposure does occur (e.g., vaccination, malaria control), and to prevent severe disease and death in those who become ill (e.g., preserving antimicrobial effectiveness) are all important in reducing the toll of invasive NTS disease in sub-Saharan Africa.

Current distribution, habitat, and status of Category 2 candidate plant species on and near the U.S. Department of Energy's Nevada Test Site

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

Blomquist, Kevin W.; Lindemann, Tim A.; Lyon, Glen E.

1995-12-31

Results of surveys conducted between 1991 and 1995 were used to document the distribution and habitat of 11 Category 2 candidate plant species known to occur on or near the Nevada Test Site (NTS). Approximately 200 areas encompassing about 13,000 ha were surveyed. Distributions of all species except Frasera-pahutensis and Phaceliaparishii were increased, and the ranges of Camissonia megalantha, Galium hilendiae ssp. kingstonense, Penstemon albomarginatus, and Penstemon pahutensis were expanded. The status of each species was assessed based on current distribution population trends, and potential threats. Recommendations were made to reclassi& the following five species to Category 3C: Arctomecon merriamii,more » F. pahutensis, P. pahutensis, Phacelia beatleyae, and Phaceliaparishii. Two species, C. megalantha and Cymopterus ripIeyi var. saniculoides, were recommended for reclassification to Category 3B status. No recommendation was made to reclassify Astragalus funereus, G. hilendiae ssp. kingstonense, P. albomarginatus, or Penstemon fruticiformis var. amargosae from their current Category 2 status. Populations of these four species are not threatened on NTS, but the NTS populations represent only a.small portion of each species’ range and the potential threats of mining or grazing activities off NTS on these species was notassessed. Conservation measures recommended included the development of an NTS ecosystem conservation plan, continued conduct of preactivity and plant surveys on NTS, and protection of plant type localities on NTS.« less

Protein-based nanotubes for biomedical applications

NASA Astrophysics Data System (ADS)

Komatsu, Teruyuki

2012-03-01

This review presents highlights of our latest results of studies directed at developing protein-based smart nanotubes for biomedical applications. These practical biocylinders were prepared using an alternate layer-by-layer (LbL) assembly of protein and oppositely charged poly(amino acid) into a nanoporous polycarbonate (PC) membrane (pore diameter, 400 nm), with subsequent dissolution of the template. The tube wall typically comprises six layers of poly-l-arginine (PLA) and human serum albumin (HSA) [(PLA/HSA)3]. The obtained (PLA/HSA)3 nanotubes (NTs) can be dispersed in aqueous medium and are hydrated significantly. Several ligands for HSA, such as zinc(ii) protoporphyrin IX (ZnPP), were bound to the HSA component in the cylindrical wall. Similar NTs comprising recombinant HSA mutant, which has a strong binding affinity for ZnPP, captured the ligand more tightly. The Fe3O4-coated NTs can be collected easily by exposure to a magnetic field. The hybrid NTs bearing a single avidin layer as an internal wall captured biotin-labeled nanoparticles into the central channel when their particle size is sufficiently small to enter the pores. The NTs with an antibody surface interior entrapped human hepatitis B virus with size selectivity. It is noteworthy that the infectious Dane particles were encapsulated completely into the hollows. Other HSA-based NTs having an α-glucosidase inner wall hydrolysed a glucopyranoside to yield α-d-glucose. A perspective of the practical use of the protein-based NTs is also described.

Resident Physicians Improve Nontechnical Skills When on Operating Room Management and Leadership Rotation.

PubMed

Cole, Devon C; Giordano, Christopher R; Vasilopoulos, Terrie; Fahy, Brenda G

2017-01-01

Anesthesiology residency primarily emphasizes the development of medical knowledge and technical skills. Yet, nontechnical skills (NTS) are also vital to successful clinical practice. Elements of NTS are communication, teamwork, situational awareness, and decision making. The first 10 consecutive senior residents who chose to participate in this 2-week elective rotation of operating room (OR) management and leadership training were enrolled in this study, which spanned from March 2013 to March 2015. Each resident served as the anesthesiology officer of the day (AOD) and was tasked with coordinating OR assignments, managing care for 2 to 4 ORs, and being on call for the trauma OR; all residents were supervised by an attending AOD. Leadership and NTS techniques were taught via a standardized curriculum consisting of leadership and team training articles, crisis management text, and daily debriefings. Resident self-ratings and attending AOD and charge nurse raters used the Anaesthetists' Non-Technical Skills (ANTS) scoring system, which involved task management, situational awareness, teamwork, and decision making. For each of the 10 residents in their third year of clinical anesthesiology training (CA-3) who participated in this elective rotation, there were 14 items that required feedback from resident self-assessment and OR raters, including the daily attending AOD and charge nurse. Results for each of the items on the questionnaire were compared between the beginning and the end of the rotation with the Wilcoxon signed-rank test for matched samples. Comparisons were run separately for attending AOD and charge nurse assessments and resident self-assessments. Scaled rankings were analyzed for the Kendall coefficient of concordance (ω) for rater agreement with associated χ and P value. Common themes identified by the residents during debriefings were recurrence of challenging situations and the skills residents needed to instruct and manage clinical teams. For attending AOD and charge nurse assessments, resident performance of NTS improved from the beginning to the end of the rotation on 12 of the 14 NTS items (P < .05), whereas resident self-assessment improved on 3 NTS items (P < .05). Interrater reliability (across the charge nurse, resident, and AOD raters) ranged from ω = .36 to .61 at the beginning of the rotation and ω = .27 to .70 at the end of the rotation. This rotation allowed for teaching and resident assessment to occur in a way that facilitated resident education in several of the skills required to meet specific milestones. Resident physicians are able to foster NTS and build a framework for clinical leadership when completing a 2-week senior elective as an OR manager.

Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

PubMed

Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

2012-01-01

Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

Ameliorative effects of bombesin and neurotensin on trinitrobenzene sulphonic acid-induced colitis, oxidative damage and apoptosis in rats.

PubMed

Akcan, Alper; Muhtaroglu, Sebahattin; Akgun, Hulya; Akyildiz, Hizir; Kucuk, Can; Sozuer, Erdogan; Yurci, Alper; Yilmaz, Namik

2008-02-28

To investigate the effects of bombesin (BBS) and neurotensin (NTS) on apoptosis and colitis in an ulcerative colitis model. In this study, a total of 50 rats were divided equally into 5 groups. In the control group, no colitis induction or drug administration was performed. Colitis was induced in all other groups. Following the induction of colitis, BBS, NTS or both were applied to three groups of rats. The remaining group (colitis group) received no treatment. On the 11th d after induction of colitis and drug treatment, blood samples were collected for TNF-alpha and IL-6 level studies. Malondialdehyde (MDA), carbonyl, myeloperoxidase (MPO) and caspase-3 activities, as well as histopathological findings, evaluated in colonic tissues. According to the macroscopic and microscopic findings, the study groups treated with BBS, NTS and BBS + NTS showed significantly lower damage and inflammation compared with the colitis group (macroscopic score, 2.1 +/- 0.87, 3.7 +/- 0.94 and 2.1 +/- 0.87 vs 7.3 +/- 0.94; microscopic score, 2.0 +/- 0.66, 3.3 +/- 0.82 and 1.8 +/- 0.63 vs 5.2 +/- 0.78, P < 0.01). TNF-alpha and IL-6 levels were increased significantly in all groups compared with the control group. These increases were significantly smaller in the BBS, NTS and BBS + NTS groups compared with the colitis group (TNF-alpha levels, 169.69 +/- 53.56, 245.86 +/- 64.85 and 175.54 +/- 42.19 vs 556.44 +/- 49.82; IL-6 levels, 443.30 +/- 53.99, 612.80 +/- 70.39 and 396.80 +/- 78.43 vs 1505.90 +/- 222.23, P < 0.05). The colonic MPO and MDA levels were significantly lower in control, BBS, NTS and BBS + NTS groups than in the colitis group (MPO levels, 24.36 +/- 8.10, 40.51 +/- 8.67 and 25.83 +/- 6.43 vs 161.47 +/- 38.24; MDA levels, 4.70 +/- 1.41, 6.55 +/- 1.12 and 4.51 +/- 0.54 vs 15.60 +/- 1.88, P < 0.05). Carbonyl content and caspase-3 levels were higher in the colitis and NTS groups than in control, BBS and BBS + NTS groups (carbonyl levels, 553.99 +/- 59.58 and 336.26 +/- 35.72 vs 209.76 +/- 30.92, 219.76 +/- 25.77 and 220.34 +/- 36.95; caspase-3 levels, 451.70 +/- 68.27 and 216.20 +/- 28.17 vs 28.60 +/- 6.46, 170.50 +/- 32.37 and 166.50 +/- 30.95, P < 0.05). The results of this study suggest BBS and NTS, through their anti-inflammatory actions, support the maintenance of colonic integrity and merit consideration as potential agents for ameliorating colonic inflammation.

CLOSURE REPORT FOR CORRECTIVE ACTION UNIT165: AREA 25 AND 26 DRY WELL AND WASH DOWN AREAS, NEVADA TEST SITE, NEVADA

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

BECHTEL NEVADA

This Closure Report (CR) documents the closure activities for Corrective Action Unit (CAU) 165, Area 25 and 26 Dry Well and Washdown Areas, according to the Federal Facility Agreement and Consent Order (FFACO) of 1996. CAU 165 consists of 8 Corrective Action Sites (CASs) located in Areas 25 and 26 of the Nevada Test Site (NTS). The NTS is located approximately 105 kilometers (65 miles) northwest of Las Vegas, nevada. Site closure activities were performed according to the Nevada Division of Environmental Protection (NDEP)-approved Corrective Action Plan (CAP) for CAU 165. CAU 165 consists of the following CASs: (1) CASmore » 25-07-06, Train Decontamination Area; (2) CAS 25-07-07, Vehicle Washdown; (3) CAS 25-20-01, Lab Drain Dry Well; (4) CAS 25-47-01, Reservoir and French Drain; (5) CAS 25-51-02, Drywell; (6) CAS 25-59-01, Septic System; (7) CAS 26-07-01, Vehicle Washdown Station; and (8) CAS 26-59-01, Septic System. CAU 165, Area 25 and 26 Dry Well and Washdown Areas, consists of eight CASs located in Areas 25 and 26 of the NTS. The approved closure alternatives included No Further Action, Clean Closure, and Closure in Place with Administrative Controls.« less

Serotonin: A mediator of the gut-brain axis in multiple sclerosis.

PubMed

Malinova, Tsveta S; Dijkstra, Christine D; de Vries, Helga E

2017-11-01

The significance of the gut microbiome for the pathogenesis of multiple sclerosis (MS) has been established, although the underlying signaling mechanisms of this interaction have not been sufficiently explored. We address this point and use serotonin (5-hydroxytryptamine (5-HT))-a microbial-modulated neurotransmitter (NT) as a showcase to demonstrate that NTs regulated by the gut microbiome are potent candidates for mediators of the gut-brain axis in demyelinating disorders. Methods, Results, and Conclusion: Our comprehensive overview of literature provides evidence that 5-HT levels in the gut are controlled by the microbiome, both via secretion and through regulation of metabolites. In addition, we demonstrate that the gut microbiome can influence the formation of the serotonergic system (SS) in the brain. We also show that SS alterations have been related to MS directly-altered expression of 5-HT transporters in central nervous system (CNS) and indirectly-beneficial effects of 5-HT modulating drugs on the course of the disease and higher prevalence of depression in patients with MS. Finally, we discuss briefly the role of other microbiome-modulated NTs such as γ-aminobutyric acid and dopamine in MS to highlight a new direction for future research aiming to relate microbiome-regulated NTs to demyelinating disorders.

Microelectronics-Based Biosensors Dedicated to the Detection of Neurotransmitters: A Review

PubMed Central

Mirzaei, Maryam; Sawan, Mohamad

2014-01-01

Dysregulation of neurotransmitters (NTs) in the human body are related to diseases such as Parkinson's and Alzheimer's. The mechanisms of several neurological disorders, such as epilepsy, have been linked to NTs. Because the number of diagnosed cases is increasing, the diagnosis and treatment of such diseases are important. To detect biomolecules including NTs, microtechnology, micro and nanoelectronics have become popular in the form of the miniaturization of medical and clinical devices. They offer high-performance features in terms of sensitivity, as well as low-background noise. In this paper, we review various devices and circuit techniques used for monitoring NTs in vitro and in vivo and compare various methods described in recent publications. PMID:25264957

Value of blood culture time to positivity in identifying complicated nontyphoidal Salmonella bacteremia.

PubMed

Chen, Shang-Yu; Weng, Tzu-Hua; Tseng, Wen-Pin; Fu, Chia-Ming; Lin, Hui-Wen; Liao, Chun-Hsing; Lee, Tai-Fen; Hsueh, Po-Ren; Fang, Cheng-Chung; Chen, Shey-Ying

2018-02-13

Few studies analyzed the association between blood culture time to positivity (TTP) and risk of complicated nontyphoidal Salmonella (NTS) bacteremia. We conducted a retrospective study of 206 patients (aged 60.4 ± 17.4 years) with NTS bacteremia during a 30-month period. Complicated NTS bacteremia was defined as the presence of 30-day mortality, complicated infection requiring surgery or abscess drainage, or requirement of intensive care unit admission. Serogroup D (75.7%) was the predominant isolates. Malignancy (44.7%) was the most prevalent comorbidity. Patients with rapid TTP (<10 h) were more likely to have thrombocytopenia, septic shock, persistent bacteremia, complicated infection, and a higher intensive care unit admission rate. In multivariate logistic regression model, a TTP <10 h was an independent predictor for complicated NTS bacteremia (adjusted odd ratio, 5.683, 95% confidence interval, 2.396-13.482). Our study showed that blood culture TTP provides important diagnostic and prognostic information in the treatment of NTS bacteremia patients. Copyright © 2018. Published by Elsevier Inc.

Mast cells and histamine alter intestinal permeability during malaria parasite infection.

PubMed

Potts, Rashaun A; Tiffany, Caitlin M; Pakpour, Nazzy; Lokken, Kristen L; Tiffany, Connor R; Cheung, Kong; Tsolis, Renée M; Luckhart, Shirley

2016-03-01

Co-infections with malaria and non-typhoidal Salmonella serotypes (NTS) can present as life-threatening bacteremia, in contrast to self-resolving NTS diarrhea in healthy individuals. In previous work with our mouse model of malaria/NTS co-infection, we showed increased gut mastocytosis and increased ileal and plasma histamine levels that were temporally associated with increased gut permeability and bacterial translocation. Here, we report that gut mastocytosis and elevated plasma histamine are also associated with malaria in an animal model of falciparum malaria, suggesting a broader host distribution of this biology. In support of mast cell function in this phenotype, malaria/NTS co-infection in mast cell-deficient mice was associated with a reduction in gut permeability and bacteremia. Further, antihistamine treatment reduced bacterial translocation and gut permeability in mice with malaria, suggesting a contribution of mast cell-derived histamine to GI pathology and enhanced risk of bacteremia during malaria/NTS co-infection. Copyright © 2015 Elsevier GmbH. All rights reserved.

Assembly and function of the botulinum neurotoxin progenitor complex.

PubMed

Gu, Shenyan; Jin, Rongsheng

2013-01-01

Botulinum neurotoxins (BoNTs) are among the most poisonous substances known to man, but paradoxically, BoNT-containing medicines and cosmetics have been used with great success in the clinic. Accidental BoNT poisoning mainly occurs through oral ingestion of food contaminated with Clostridium botulinum. BoNTs are naturally produced in the form of progenitor toxin complexes (PTCs), which are high molecular weight (up to ~900 kDa) multiprotein complexes composed of BoNT and several non-toxic neurotoxin-associated proteins (NAPs). NAPs protect the inherently fragile BoNTs against the hostile environment of the gastrointestinal (GI) tract and help BoNTs pass through the intestinal epithelial barrier before they are released into the general circulation. These events are essential for ingested BoNTs to gain access to motoneurons, where they inhibit neurotransmitter release and cause muscle paralysis. In this review, we discuss the structural basis for assembly of NAPs and BoNT into the PTC that protects BoNT and facilitate its delivery into the bloodstream.

Altered respiratory response to substance P and reduced NK1 receptor binding in the nucleus of the solitary tract of aged rats.

PubMed

Mazzone, S B; Geraghty, D P

1999-04-24

The respiratory response to microinjection of substance P (SP) into the commissural nucleus of the solitary tract (cNTS) and binding of [125I]-Bolton-Hunter SP ([125I]-BHSP) to brain stem NK1 receptors were compared in young and aged rats. Injection of SP (750 pmol) into the cNTS of young rats (2 months) increased tidal volume (VT) but had no effect on respiratory rate (f). In aged rats (19-21 months), injection of SP had no significant effect on f or VT. The NTS of aged rats displayed significantly lower specific [125I]-BHSP binding than young rats, indicating a reduction in the number in NK1 receptors. These findings show that the respiratory response to microinjection of SP into the cNTS of aged rats is severely blunted and that this phenomenon may be due to a decrease in the number of NK1 receptors in the NTS. Copyright 1999 Elsevier Science B.V.

Challenges in searching for therapeutics against Botulinum Neurotoxins.

PubMed

Pirazzini, Marco; Rossetto, Ornella

2017-05-01

Botulinum neurotoxins (BoNTs) are the most potent toxins known. BoNTs are responsible for botulism, a deadly neuroparalytic syndrome caused by the inactivation of neurotransmitter release at peripheral nerve terminals. Thanks to their specificity and potency, BoNTs are both considered potential bio-weapons and therapeutics of choice for a variety of medical syndromes. Several variants of BoNTs have been identified with individual biological properties and little antigenic relation. This expands greatly the potential of BoNTs as therapeutics but poses a major safety problem, increasing the need for finding appropriate antidotes. Areas covered: The authors describe the multi-step molecular mechanism through which BoNTs enter nerve terminals and discuss the many levels at which the toxins can be inhibited. They review the outcomes of the different strategies adopted to limit neurotoxicity and counter intoxication. Potential new targets arising from the last discoveries of the mechanism of action and the approaches to promote neuromuscular junction recovery are also discussed. Expert opinion: Current drug discovery efforts have mainly focused on BoNT type A and addressed primarily light chain proteolytic activity. Development of pan-BoNT inhibitors acting independently of BoNT immunological properties and targeting a common step of the intoxication process should be encouraged.

"Hand-it-on": an innovative simulation on the relation of non-technical skills to healthcare.

PubMed

Dieckmann, Peter; Zeltner, Louise Graae; Helsø, Anne-Mette

2016-01-01

Non-technical skills (NTS) are an integral part of the abilities healthcare professionals need to optimally care for patients. Integrating NTS into the already complex tasks of healthcare can be a challenge for clinicians. Integrating NTS into simulation-based training increases the demands for simulation instructors with regard to scenario design, conduct, and debriefing. We introduce a simulation game, Hand-it-on , that can trigger discussions on how NTS can influence work processes. Hand-it-on aims to help clinicians and simulation instructors alike to improve their understanding of NTS concepts and where they can apply them in their work. It complements existing approaches to teaching NTS by limiting the complexity of the game and by removing medical content, allowing learners to concentrate on NTS. Hand-it-on is relevant for groups and teams working across the range of different healthcare contexts. During Hand-it-on, participants stand in a circle and hand on everyday objects to each other according to simple rules, resulting in many events that can be debriefed in relation to safe patient care. We describe both the conduct of Hand-it-on and ideas on how to debrief participants. We provide variations that can be used in different contexts, focusing the exercise on different learning goals. We also offer the theoretical rationale for using an out-of-context simulation in combination with other forms of teaching. Although we did not evaluate Hand-it-on formally, oral feedback from participants and the replication of Hand-it-on by many simulation teams support its value.

Modulation of Neurally Mediated Vasodepression and Bradycardia by Electroacupuncture through Opioids in Nucleus Tractus Solitarius.

PubMed

Tjen-A-Looi, Stephanie C; Fu, Liang-Wu; Guo, Zhi-Ling; Longhurst, John C

2018-01-30

Stimulation of vagal afferent endings with intravenous phenylbiguanide (PBG) causes both bradycardia and vasodepression, simulating neurally mediated syncope. Activation of µ-opioid receptors in the nucleus tractus solitarius (NTS) increases blood pressure. Electroacupuncture (EA) stimulation of somatosensory nerves underneath acupoints P5-6, ST36-37, LI6-7 or G37-39 selectively but differentially modulates sympathoexcitatory responses. We therefore hypothesized that EA-stimulation at P5-6 or ST36-37, but not LI6-7 or G37-39 acupoints, inhibits the bradycardia and vasodepression through a µ-opioid receptor mechanism in the NTS. We observed that stimulation at acupoints P5-6 and ST36-37 overlying the deep somatosensory nerves and LI6-7 and G37-39 overlying cutaneous nerves differentially evoked NTS neural activity in anesthetized and ventilated animals. Thirty-min of EA-stimulation at P5-6 or ST36-37 reduced the depressor and bradycardia responses to PBG while EA at LI6-7 or G37-39 did not. Congruent with the hemodynamic responses, EA at P5-6 and ST36-37, but not at LI6-7 and G37-39, reduced vagally evoked activity of cardiovascular NTS cells. Finally, opioid receptor blockade in the NTS with naloxone or a specific μ-receptor antagonist reversed P5-6 EA-inhibition of the depressor, bradycardia and vagally evoked NTS activity. These data suggest that point specific EA stimulation inhibits PBG-induced vasodepression and bradycardia responses through a μ-opioid mechanism in the NTS.

Learning health 'safety' within non-technical skills interprofessional simulation education: a qualitative study.

PubMed

Gordon, Morris; Fell, Christopher W R; Box, Helen; Farrell, Michael; Stewart, Alison

2017-01-01

Healthcare increasingly recognises and focusses on the phenomena of 'safe practice' and 'patient safety.' Success with non-technical skills (NTS) training in other industries has led to widespread transposition to healthcare education, with communication and teamwork skills central to NTS frameworks. This study set out to identify how the context of interprofessional simulation learning influences NTS acquisition and development of 'safety' amongst learners. Participants receiving a non-technical skills (NTS) safety focussed training package were invited to take part in a focus group interview which set out to explore communication, teamwork, and the phenomenon of safety in the context of the learning experiences they had within the training programme. The analysis was aligned with a constructivist paradigm and took an interactive methodological approach. The analysis proceeded through three stages, consisting of open, axial, and selective coding, with constant comparisons taking place throughout each phase. Each stage provided categories that could be used to explore the themes of the data. Additionally, to ensure thematic saturation, transcripts of observed simulated learning encounters were then analysed. Six themes were established at the axial coding level, i.e., analytical skills, personal behaviours, communication, teamwork, context, and pedagogy. Underlying these themes, two principal concepts emerged, namely: intergroup contact anxiety - as both a result of and determinant of communication - and teamwork, both of which must be considered in relation to context. These concepts have subsequently been used to propose a framework for NTS learning. This study highlights the role of intergroup contact anxiety and teamwork as factors in NTS behaviour and its dissipation through interprofessional simulation learning. Therefore, this should be a key consideration in NTS education. Future research is needed to consider the role of the affective non-technical attributes of intergroup contact anxiety and teamwork as focuses for education and determinants of safe behaviour. AUM: Anxiety/uncertainty management; NTS: Non-technical skills; TINSELS: Training in non-technical skills to enhance levels of medicines safety.

A novel method for photodegradation of high-chroma dye wastewater via electrochemical pre-oxidation.

PubMed

Zhao, Kunjiao; Zhao, Guohua; Li, Peiqiang; Gao, Junxia; Lv, Baoying; Li, Dongming

2010-06-01

A new two-step process involving the electrocatalytic (EC) pre-oxidation and the following photoelectrocatalytic synergistic (PEC) oxidation is proposed to treat the high concentration and high-chroma methyl orange dye wastewater, which cannot be degraded by photocatalytic oxidation (PC) directly. The SnO(2)/TiO(2)-NTs/Ti electrode simultaneously possessing the outstanding PC oxidation properties of TiO(2)-NTs and the excellent EC oxidation abilities of the Sb doped SnO(2) was synthesized by impregnating Sb doped SnO(2) nanoparticles into TiO(2)-NTs. In the pre-oxidation process as the first stage, the high-color dye wastewater is decolorized with electrochemical method to some extent. Then, the wastewater becomes a light transmission system. It provides a suitable condition for PC oxidation reaction in the second stage. The synergistic effects of PC and EC oxidation led to the high PEC efficiency and the complete mineralization of dye wastewater is achieved. This two-step process is fast and efficient, which is worthy to study and explore in the practical environmental treatment.

Training for Defense? From Stochastic Traits to Synchrony in Giant Honey Bees (Apis dorsata).

PubMed

Weihmann, Frank; Hoetzl, Thomas; Kastberger, Gerald

2012-08-30

In Giant Honey Bees, abdomen flipping happens in a variety of contexts. It can be either synchronous or cascaded, such as in the collective defense traits of shimmering and rearing-up, or it can happen as single-agent behavior. Abdomen flipping is also involved in flickering behavior, which occurs regularly under quiescent colony state displaying singular or collective traits, with stochastic, and (semi-) synchronized properties. It presumably acts via visual, mechanoceptive, and pheromonal pathways and its goals are still unknown. This study questions whether flickering is preliminary to shimmering which is subject of the fs (flickering-shimmering)-transition hypothesis? We tested the respective prediction that trigger sites (ts) at the nest surface (where shimmering waves had been generated) show higher flickering activity than the alternative non-trigger sites (nts). We measured the flickering activity of ts- and nts-surface bees from two experimental nests, before and after the colony had been aroused by a dummy wasp. Arousal increased rate and intensity of the flickering activity of both ts- and nts cohorts (P < 0.05), whereby the flickering intensity of ts-bees were higher than that of nts-bees (P < 0.05). Under arousal, the colonies also increased the number of flickering-active ts- and nts-cohorts (P < 0.05). This provides evidence that cohorts which are specialist at launching shimmering waves are found across the quiescent nest zone. It also proves that arousal may reinforce the responsiveness of quiescent curtain bees for participating in shimmering, practically by recruiting additional trigger site bees for expanding repetition of rate and intensity of shimmering waves. This finding confirms the fs-transition hypothesis and constitutes evidence that flickering is part of a basal colony-intrinsic information system. Furthermore, the findings disprove that the muscle activity associated with flickering would heat up the surface bees. Hence, surface bees are not actively contributing to thermoregulation.

Training for Defense? From Stochastic Traits to Synchrony in Giant Honey Bees (Apis dorsata)

PubMed Central

Weihmann, Frank; Hoetzl, Thomas; Kastberger, Gerald

2012-01-01

In Giant Honey Bees, abdomen flipping happens in a variety of contexts. It can be either synchronous or cascaded, such as in the collective defense traits of shimmering and rearing-up, or it can happen as single-agent behavior. Abdomen flipping is also involved in flickering behavior, which occurs regularly under quiescent colony state displaying singular or collective traits, with stochastic, and (semi-) synchronized properties. It presumably acts via visual, mechanoceptive, and pheromonal pathways and its goals are still unknown. This study questions whether flickering is preliminary to shimmering which is subject of the fs (flickering-shimmering)-transition hypothesis? We tested the respective prediction that trigger sites (ts) at the nest surface (where shimmering waves had been generated) show higher flickering activity than the alternative non-trigger sites (nts). We measured the flickering activity of ts- and nts-surface bees from two experimental nests, before and after the colony had been aroused by a dummy wasp. Arousal increased rate and intensity of the flickering activity of both ts- and nts cohorts (P < 0.05), whereby the flickering intensity of ts-bees were higher than that of nts-bees (P < 0.05). Under arousal, the colonies also increased the number of flickering-active ts- and nts-cohorts (P < 0.05). This provides evidence that cohorts which are specialist at launching shimmering waves are found across the quiescent nest zone. It also proves that arousal may reinforce the responsiveness of quiescent curtain bees for participating in shimmering, practically by recruiting additional trigger site bees for expanding repetition of rate and intensity of shimmering waves. This finding confirms the fs-transition hypothesis and constitutes evidence that flickering is part of a basal colony-intrinsic information system. Furthermore, the findings disprove that the muscle activity associated with flickering would heat up the surface bees. Hence, surface bees are not actively contributing to thermoregulation. PMID:26466631

Ameliorative effects of bombesin and neurotensin on trinitrobenzene sulphonic acid-induced colitis, oxidative damage and apoptosis in rats

PubMed Central

Akcan, Alper; Muhtaroglu, Sebahattin; Akgun, Hulya; Akyildiz, Hizir; Kucuk, Can; Sozuer, Erdogan; Yurci, Alper; Yilmaz, Namik

2008-01-01

AIM: To investigate the effects of bombesin (BBS) and neurotensin (NTS) on apoptosis and colitis in an ulcerative colitis model. METHODS: In this study, a total of 50 rats were divided equally into 5 groups. In the control group, no colitis induction or drug administration was performed. Colitis was induced in all other groups. Following the induction of colitis, BBS, NTS or both were applied to three groups of rats. The remaining group (colitis group) received no treatment. On the 11th d after induction of colitis and drug treatment, blood samples were collected for TNF-α and IL-6 level studies. Malondialdehyde (MDA), carbonyl, myeloperoxidase (MPO) and caspase-3 activities, as well as histopathological findings, evaluated in colonic tissues. RESULTS: According to the macroscopic and microscopic findings, the study groups treated with BBS, NTS and BBS + NTS showed significantly lower damage and inflammation compared with the colitis group (macroscopic score, 2.1 ± 0.87, 3.7 ± 0.94 and 2.1 ± 0.87 vs 7.3 ± 0.94; microscopic score, 2.0 ± 0.66, 3.3 ± 0.82 and 1.8 ± 0.63 vs 5.2 ± 0.78, P < 0.01). TNF-α and IL-6 levels were increased significantly in all groups compared with the control group. These increases were significantly smaller in the BBS, NTS and BBS + NTS groups compared with the colitis group (TNF-α levels, 169.69 ± 53.56, 245.86 ± 64.85 and 175.54 ± 42.19 vs 556.44 ± 49.82; IL-6 levels, 443.30 ± 53.99, 612.80 ± 70.39 and 396.80 ± 78.43 vs 1505.90 ± 222.23, P < 0.05). The colonic MPO and MDA levels were significantly lower in control, BBS, NTS and BBS + NTS groups than in the colitis group (MPO levels, 24.36 ± 8.10, 40.51 ± 8.67 and 25.83 ± 6.43 vs 161.47 ± 38.24; MDA levels, 4.70 ± 1.41, 6.55 ± 1.12 and 4.51 ± 0.54 vs 15.60 ± 1.88, P < 0.05). Carbonyl content and caspase-3 levels were higher in the colitis and NTS groups than in control, BBS and BBS + NTS groups (carbonyl levels, 553.99 ± 59.58 and 336.26 ± 35.72 vs 209.76 ± 30.92, 219.76 ± 25.77 and 220.34 ± 36.95; caspase-3 levels, 451.70 ± 68.27 and 216.20 ± 28.17 vs 28.60 ± 6.46, 170.50 ± 32.37 and 166.50 ± 30.95, P < 0.05). CONCLUSION: The results of this study suggest BBS and NTS, through their anti-inflammatory actions, support the maintenance of colonic integrity and merit consideration as potential agents for ameliorating colonic inflammation. PMID:18300348

What is the best immunization strategy for protecting African children against invasive Salmonella disease?

PubMed

Jeon, Hyon Jin; Pak, Gi Deok; Im, Justin; Owusu-Dabo, Ellis; Adu-Sarkodie, Yaw; Gassama Sow, Amy; Bassiahi, Abdramane Soura; Gasmelseed, Nagla; Keddy, Karen H; Bjerregaard-Andersen, Morten; Konings, Frank; Aseffa, Abraham; Crump, John A; Chon, Yun; Breiman, Robert F; Park, Se Eun; Cruz Espinoza, Ligia Maria; Seo, Hye Jin; May, Jürgen; Meyer, Christian G; Andrews, Jason R; Panzner, Ursula; von Kalckreuth, Vera; Wierzba, Thomas F; Rakotozandrindrainy, Raphaël; Dougan, Gordon; Levine, Myron M; Hombach, Joachim; Kim, Jerome H; Clemens, John D; Baker, Stephen; Marks, Florian

2018-05-09

The WHO recently prequalified a typhoid conjugate vaccine (TCV), recommending its use in persons aged ≥6 months to 45 years residing in typhoid fever (TF)-endemic areas. We now need to consider how TCVs can have the greatest impact in the most vulnerable populations in Africa. The Typhoid Fever Surveillance in Africa Program (TSAP) in 10 sub-Saharan African countries included blood culture-based surveillance in febrile people presenting at healthcare-facilities originating from defined catchment areas. The TF/invasive non-typhoidal Salmonella (iNTS) disease incidences were estimated for 0-10 year-old children in yearly increments. Salmonella Typhi and iNTS were the most frequently isolated pathogens, 135 and 94 cases were identified, respectively. Isolates (12 and 4, respectively) from Ethiopia, Senegal and South Africa were excluded due to person-years of observation (PYO) data absence. 37/123 (30.1%) TF and 71/90 (78.9%) iNTS disease cases occurred among individuals aged <5 years. No TF and 8/90 (8.9%) iNTS-infections were observed in children aged <9 months. The TF incidences (/100,000 PYO) for children aged <1 year and 1-<2 years were 5 and 39, respectively; the highest incidence was 304/100,000 PYO in 4-<5 year-old children. The iNTS incidence in the defined age groups ranged between 81 and 233/100,000 PYO, with the highest incidence in 1-<2 year-old children. Higher TF/iNTS disease incidences were observed in West Africa. The high TF burden observed in TSAP merits TCV introductions. Considering the additional iNTS disease burden, a trivalent vaccine targeting S. Typhi, S. Typhimurium, and S. Enteritidis may be a future solution.

Ponto-medullary nuclei involved in the generation of sequential pharyngeal swallowing and concomitant protective laryngeal adduction in situ

PubMed Central

Bautista, Tara G; Dutschmann, Mathias

2014-01-01

Both swallowing and respiration involve postinspiratory laryngeal adduction. Swallowing-related postinspiratory neurons are likely to be located in the nucleus of the solitary tract (NTS) and those involved in respiration are found in the Kölliker–Fuse nucleus (KF). The function of KF and NTS in the generation of swallowing and its coordination with respiration was investigated in perfused brainstem preparations of juvenile rats (n = 41). Orally injected water evoked sequential pharyngeal swallowing (s-PSW) seen as phasic, spindle-shaped bursting of vagal nerve activity (VNA) against tonic postinspiratory discharge. KF inhibition by microinjecting isoguvacine (GABAA receptor agonist) selectively attenuated tonic postinspiratory VNA (n = 10, P < 0.001) but had no effect on frequency or timing of s-PSW. KF disinhibition after bicuculline (GABAA receptor antagonist) microinjections caused an increase of the tonic VNA (n = 8, P < 0.01) resulting in obscured and delayed phasic s-PSW. Occurrence of spontaneous PSW significantly increased after KF inhibition (P < 0.0001) but not after KF disinhibition (P = 0.14). NTS isoguvacine microinjections attenuated the occurrence of all PSW (n = 5, P < 0.01). NTS bicuculline microinjections (n = 6) resulted in spontaneous activation of a disordered PSW pattern and long-lasting suppression of respiratory activity. Pharmacological manipulation of either KF or NTS also triggered profound changes in respiratory postinspiratory VNA. Our results indicate that the s-PSW comprises two functionally distinct components. While the primary s-PSW is generated within the NTS, a KF-mediated laryngeal adductor reflex safeguards the lower airways from aspiration. Synaptic interaction between KF and NTS is required for s-PSW coordination with respiration as well as for proper gating and timing of s-PSW. PMID:24639482

Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat.

PubMed

Korim, Willian Seiji; Ferreira-Neto, Marcos L; Pedrino, Gustavo R; Pilowsky, Paul M; Cravo, Sergio L

2012-12-01

In the nucleus tractus solitarii (NTS) of rats, blockade of extracellular ATP breakdown to adenosine reduces arterial blood pressure (AP) increases that follow stimulation of the hypothalamic defense area (HDA). The effects of ATP on NTS P2 receptors, during stimulation of the HDA, are still unclear. The aim of this study was to determine whether activation of P2 receptors in the NTS mediates cardiovascular responses to HDA stimulation. Further investigation was taken to establish if changes in hindlimb vascular conductance (HVC) elicited by electrical stimulation of the HDA, or activation of P2 receptors in the NTS, are relayed in the rostral ventrolateral medulla (RVLM); and if those responses depend on glutamate release by ATP acting on presynaptic terminals. In anesthetized and paralyzed rats, electrical stimulation of the HDA increased AP and HVC. Blockade of P2 or glutamate receptors in the NTS, with bilateral microinjections of suramin (10 mM) or kynurenate (50 mM) reduced only the evoked increase in HVC by 75 % or more. Similar results were obtained with the blockade combining both antagonists. Blockade of P2 and glutamate receptors in the RVLM also reduced the increases in HVC to stimulation of the HDA by up to 75 %. Bilateral microinjections of kynurenate in the RVLM abolished changes in AP and HVC to injections of the P2 receptor agonist α,β-methylene ATP (20 mM) into the NTS. The findings suggest that HDA-NTS-RVLM pathways in control of HVC are mediated by activation of P2 and glutamate receptors in the brainstem in alerting-defense reactions.

Analytical evidence of heterogeneous lead accumulation in the hypothalamic defence area and nucleus tractus solitarius.

PubMed

Guimarães, D; Santos, J P; Carvalho, M L; Diniz, M S; House, B; Miller, V M

2014-09-01

Lead is a potent toxicant associated with adverse cardiovascular effects and hypertension in children. Yet, few studies have determined if autonomic dysfunction associated with lead exposure involves brain regions which regulate autonomic responses. Central autonomic nuclei such as the nucleus tractus solitarius (NTS) and hypothalamic defence area (HDA) may be particularly sensitive to lead infiltration because they are adjacent to ventricles and areas with semi-permeable blood-brain-barriers. To understand if autonomic nuclei are sensitive to lead accumulation Wistar rats were exposed to lead from the gestational period and lead levels were quantified in brain regions that regulate arterial pressure: the NTS and the HDA. Energy dispersive X-ray fluorescence (EDXRF) was used to quantify total brain lead levels and revealed no differences between exposed and control tissues; measured values were close to the detection limit (2μg/g). Electrothermal atomic absorption spectrometry (ETAAS) was also used, which has a greater sensitivity, to quantify lead. There was ∼2.1μg/g lead in the NTS and ∼3.1μg/g lead in the HDA of exposed rats, and no lead in the control rats. There were greater lead levels in the HDA (∼50%) as compared with the NTS. Pathology studies revealed more prominent lead granules in the HDA as compared with the NTS. Increased microglia and astrocyte activation was also noted in the NTS of lead exposed rats as compared with the HDA. Regional differences in neuro-inflammatory responses likely contribute to heterogeneous lead accumulation, with enhanced clearance of lead in the NTS. Future studies will resolve the mechanisms underpinning tissue-specific lead accumulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Substance P immunoreactive nerve terminals in the dorsolateral nucleus of the tractus solitarius: roles in the baroreceptor reflex.

PubMed

Massari, V J; Shirahata, M; Johnson, T A; Lauenstein, J M; Gatti, P J

1998-03-02

Physiological and light microscopic evidence suggest that substance P (SP) may be a neurotransmitter contained in first-order sensory baroreceptor afferents; however, ultrastructural support for this hypothesis is lacking. We have traced the central projections of the carotid sinus nerve (CSN) in the cat by utilizing the transganglionic transport of horseradish peroxidase (HRP). The dorsolateral subnucleus of the nucleus tractus solitarius (dlNTS) was processed for the histochemical visualization of transganglionically labeled CSN afferents and for the immunocytochemical visualization of SP by dual labeling light and electron microscopic methods. Either HRP or SP was readily identified in single-labeled unmyelinated axons, myelinated axons, and nerve terminals in the dlNTS. SP immunoreactivity was also identified in unmyelinated axons, myelinated axons, and nerve terminals in the dlNTS, which were simultaneously identified as CSN primary afferents. However, only 15% of CSN terminals in the dlNTS were immunoreactive for SP. Therefore, while the ultrastructural data support the hypothesis that SP immunoreactive first-order neurons are involved in the origination of the baroreceptor reflex, they suggest that only a modest part of the total sensory input conveyed from the carotid sinus baroreceptors to the dlNTS is mediated by SP immunoreactive CSN terminals. Five types of axo-axonic synapses were observed in the dlNTS. SP immunoreactive CSN afferents were very rarely involved in these synapses. Furthermore, SP terminals were never observed to form the presynaptic element in an axo-axonic synapse with a CSN afferent. Therefore, SP does not appear to be involved in the modulation of the baroreceptor reflex in the dlNTS. Copyright 1998 Elsevier Science B.V.

High glucose increases action potential firing of catecholamine neurons in the nucleus of the solitary tract by increasing spontaneous glutamate inputs.

PubMed

Roberts, Brandon L; Zhu, Mingyan; Zhao, Huan; Dillon, Crystal; Appleyard, Suzanne M

2017-09-01

Glucose is a crucial substrate essential for cell survival and function. Changes in glucose levels impact neuronal activity and glucose deprivation increases feeding. Several brain regions have been shown to respond to glucoprivation, including the nucleus of the solitary tract (NTS) in the brain stem. The NTS is the primary site in the brain that receives visceral afferent information from the gastrointestinal tract. The catecholaminergic (CA) subpopulation within the NTS modulates many homeostatic functions including cardiovascular reflexes, respiration, food intake, arousal, and stress. However, it is not known if they respond to changes in glucose. Here we determined whether NTS-CA neurons respond to changes in glucose concentration and the mechanism involved. We found that decreasing glucose concentrations from 5 mM to 2 mM to 1 mM, significantly decreased action potential firing in a cell-attached preparation, whereas increasing it back to 5 mM increased the firing rate. This effect was dependent on glutamate release from afferent terminals and required presynaptic 5-HT 3 Rs. Decreasing the glucose concentration also decreased both basal and 5-HT 3 R agonist-induced increase in the frequency of spontaneous glutamate inputs onto NTS-CA neurons. Low glucose also blunted 5-HT-induced inward currents in nodose ganglia neurons, which are the cell bodies of vagal afferents. The effect of low glucose in both nodose ganglia cells and in NTS slices was mimicked by the glucokinase inhibitor glucosamine. This study suggests that NTS-CA neurons are glucosensing through a presynaptic mechanism that is dependent on vagal glutamate release, 5-HT 3 R activity, and glucokinase. Copyright © 2017 the American Physiological Society.

Immunological bases of increased susceptibility to invasive nontyphoidal Salmonella infection in children with malaria and anaemia.

PubMed

Nyirenda, Tonney S; Mandala, Wilson L; Gordon, Melita A; Mastroeni, Pietro

2017-12-15

Malaria and anaemia are key underlying factors for iNTS disease in African children. Knowledge of clinical and epidemiological risk-factors for iNTS disease has not been paralleled by an in-depth knowledge of the immunobiology of the disease. Herein, we review human and animal studies on mechanisms of increased susceptibility to iNTS in children. Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Binding of plasma proteins to titanium dioxide nanotubes with different diameters

PubMed Central

Kulkarni, Mukta; Flašker, Ajda; Lokar, Maruša; Mrak-Poljšak, Katjuša; Mazare, Anca; Artenjak, Andrej; Čučnik, Saša; Kralj, Slavko; Velikonja, Aljaž; Schmuki, Patrik; Kralj-Iglič, Veronika; Sodin-Semrl, Snezna; Iglič, Aleš

2015-01-01

Titanium and titanium alloys are considered to be one of the most applicable materials in medical devices because of their suitable properties, most importantly high corrosion resistance and the specific combination of strength with biocompatibility. In order to improve the biocompatibility of titanium surfaces, the current report initially focuses on specifying the topography of titanium dioxide (TiO2) nanotubes (NTs) by electrochemical anodization. The zeta potential (ζ-potential) of NTs showed a negative value and confirmed the agreement between the measured and theoretically predicted dependence of ζ-potential on salt concentration, whereby the absolute value of ζ-potential diminished with increasing salt concentrations. We investigated binding of various plasma proteins with different sizes and charges using the bicinchoninic acid assay and immunofluorescence microscopy. Results showed effective and comparatively higher protein binding to NTs with 100 nm diameters (compared to 50 or 15 nm). We also showed a dose-dependent effect of serum amyloid A protein binding to NTs. These results and theoretical calculations of total available surface area for binding of proteins indicate that the largest surface area (also considering the NT lengths) is available for 100 nm NTs, with decreasing surface area for 50 and 15 nm NTs. These current investigations will have an impact on increasing the binding ability of biomedical devices in the body leading to increased durability of biomedical devices. PMID:25733829

Inorganic Nanotubes and Fullerene-like Nanoparticles at the Crossroads between Solid-State Chemistry and Nanotechnology.

PubMed

Višić, Bojana; Panchakarla, Leela Srinivas; Tenne, Reshef

2017-09-20

Inorganic nanotubes (NTs) and fullerene-like nanoparticles (NPs) of WS 2 were discovered some 25 years ago and are produced now on a commercial scale for various applications. This Perspective provides a brief description of recent progress in this scientific discipline. The conceptual evolution leading to the discovery of these NTs and NPs is briefly discussed. Subsequently, recent progress in the synthesis of such NPs from a variety of inorganic compounds with layered (2D) structure is described. In particular, we discuss the synthesis of NTs from chalcogenide- and oxide-based ternary misfit layered compounds, as well as their structure and different growth mechanisms. Next we deliberate on the mechanical, optical, electrical, and electromechanical properties, which delineate them from their bulk counterparts and also from their graphene-like analogues. Here, different experiments with individual NTs coupled with first-principles and molecular dynamics calculations demonstrate the unique physical nature of these quasi-1D nanostructures. Finally, the various applications of the fullerene-like NPs of WS 2 and NTs formed therefrom are deliberated. Foremost among the possibilities are their extensive uses as superior solid lubricants. Combined with their nontoxicity and their facile dispersion, these NTs, with an ultimate strength of about 20 GPa, are likely to find numerous applications in reinforcing polymers, adhesives, textiles, medical devices, metallic alloys, and even concrete. Other potential applications in energy-harvesting and catalysis are discussed in brief.

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

PubMed Central

Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto

2017-01-01

The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. PMID:28356439

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.

PubMed

Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto; Montecucco, Cesare

2017-04-01

The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. Copyright © 2017 by The Author(s).

Fracture Toughness and Shear Strength of the Bonded Interface Between an Aluminium Alloy Skin and a FRP Patch

NASA Astrophysics Data System (ADS)

Kumar, Prashant; Shinde, Prakash Sonyabapu; Bhoyar, Gaurav

2018-05-01

The existing techniques to determine the fracture properties such as critical energy release rate in mode I (GIc) and mode II (GIIc) of an interface between two sheets of same material were modified to determine these properties between the sheets of dissimilar materials and thickness. In addition, the interface shear strength (ISS) was also determined. Experiments were carried out on the specimens made of a pre-cracked thin aluminium alloy skin and a Fiber reinforced polymer (FRP) patch. Two kinds of surface preparation of the aluminium skin were employed; (i) emery-paper roughened surface (ERS) and (ii) Sodium Hydroxide (NaOH) treated surface (NTS). GIc of ERS specimen was found to be 36.1 J/m2, while it was found to be much higher for NTS specimens, that is, 87.3 J/m2. GIIc was found to be 282.4 J/m2 for ERS specimens and much higher as 734.5 J/m2 for NTS specimens. ISS was determined as 32.6 MPa for ERS specimen and significantly higher for NTS specimen, that is, 44.5 MPa. The micrographs obtained from a field emission-scanning electron microscope (FE-SEM) and the surface roughness test showed that the NTS was significantly rougher than the ERS, explaining the higher values of all the three kinds of NTS specimens.

An adenosine A(2A) antagonist injected in the NTS reverses thermal prolongation of the LCR in decerebrate piglets.

PubMed

Xia, Luxi; Bartlett, Donald; Leiter, J C

2008-12-31

Hyperthermia prolongs the laryngeal chemoreflex (LCR). Under normothermic conditions, adenosine antagonists shorten and adenosine A(2A) (Ad-A(2A)) agonists prolong the LCR. Therefore, we tested the hypothesis that SCH-58261, an Ad-A(2A) receptor antagonist, would prevent thermal prolongation of the LCR when injected unilaterally within the nucleus of the solitary tract (NTS). We studied decerebrate piglets aged 4-13 days. We elicited the LCR by injecting 0.1ml of water into the larynx and recorded integrated phrenic nerve activity. The laryngeal chemoreflex was prolonged when the body temperature of each piglet was raised approximately 2.5 degrees C, and SCH-58261 reversed the thermal prolongation of the LCR when injected into the NTS (n=13), but not when injected in the nucleus ambiguus (n=9). Injections of vehicle alone into the NTS did not alter the thermal prolongation of the LCR (n=9). We conclude that activation of adenosine receptors, perhaps located on GABAergic neurons in the NTS, contributes to thermal prolongation of the LCR.

Mechanical properties of sol–gel derived SiO2 nanotubes

PubMed Central

Antsov, Mikk; Vlassov, Sergei; Dorogin, Leonid M; Vahtrus, Mikk; Zabels, Roberts; Lange, Sven; Lõhmus, Rünno

2014-01-01

Summary The mechanical properties of thick-walled SiO2 nanotubes (NTs) prepared by a sol–gel method while using Ag nanowires (NWs) as templates were measured by using different methods. In situ scanning electron microscopy (SEM) cantilever beam bending tests were carried out by using a nanomanipulator equipped with a force sensor in order to investigate plasticity and flexural response of NTs. Nanoindentation and three point bending tests of NTs were performed by atomic force microscopy (AFM) under ambient conditions. Half-suspended and three-point bending tests were processed in the framework of linear elasticity theory. Finite element method simulations were used to extract Young’s modulus values from the nanoindentation data. Finally, the Young’s moduli of SiO2 NTs measured by different methods were compared and discussed. PMID:25383292

Unguided Rocket Employment: Why We Must Update Marine Corps Rotary Wing Attack Training

DTIC Science & Technology

2008-03-01

100 meters of target area from a range of 1500m or less during the initial.engagement. Using NTS video , validate an effective HELLFIRE engagement of a...as stipulated by the terminal controller) using 5.00 inch rockets or 20mm within 30 seconds of TOT during the initial engagement. Using NTS video ...Standards. Achievement of desired illumination effects (as stipulated in OAS brief) will be debriefed by flight lead. Using NTS video , validate an

Improved tribocorrosion performance of bio-functionalized TiO2 nanotubes under two-cycle sliding actions in artificial saliva.

PubMed

Alves, Sofia A; Rossi, André L; Ribeiro, Ana R; Toptan, Fatih; Pinto, Ana M; Shokuhfar, Tolou; Celis, Jean-Pierre; Rocha, Luís A

2018-04-01

After insertion into bone, dental implants may be subjected to tribocorrosive conditions resulting in the release of metallic ions and solid wear debris, which can induce to peri-implant inflammatory reactions accompanied by bone loss, and ultimately implant loosening. Despite the promising ability of TiO 2 nanotubes (NTs) to improve osseointegration and avoid infection-related failures, the understanding of their degradation under the simultaneous action of wear and corrosion (tribocorrosion) is still very limited. This study aims, for the first time, to study the tribocorrosion behavior of bio-functionalized TiO 2 NTs submitted to two-cycle sliding actions, and compare it with conventional TiO 2 NTs. TiO 2 NTs grown by anodization were doped with bioactive elements, namely calcium (Ca), phosphorous (P), and zinc (Zn), through reverse polarization anodization treatments. Characterization techniques such as scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and scanning transmission electron microscopy (STEM), were used to characterize the films. Tribocorrosion tests were carried out in artificial saliva (AS) by applying two cycles of reciprocating sliding actions. The open circuit potential (OCP) was monitored before, during, and after both cycles of sliding, during which the coefficient of friction (COF) was calculated. The resulting wear scars were analyzed by SEM and EDS, and wear volume measurements were performed by 2D profilometry. Finally, the mechanical features of TiO 2 NTs were accessed by nanoindentation. The results show that bio-functionalized TiO 2 NTs display an enhanced tribocorrosion performance, ascribed to the growth of a nano-thick oxide film at Ti/TiO 2 NTs interface, which significantly increased their adhesion strength to the substrate and consequently their hardness. Furthermore, it was discovered that during tribo-electrochemical solicitations, the formation of a P-rich tribofilm takes place, which grants both electrochemical protection and resistance to mechanical wear. This study provides fundamental and new insights for the development of multifunctional TiO 2 NTs with long-term biomechanical stability and improved clinical outcomes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular Epidemiology of Nontyphoidal Salmonella in Poultry and Poultry Products in India: Implications for Human Health.

PubMed

Saravanan, Sellappan; Purushothaman, Venketaraman; Murthy, Thippichettypalayam Ramasamy Gopala Krishna; Sukumar, Kuppannan; Srinivasan, Palani; Gowthaman, Vasudevan; Balusamy, Mohan; Atterbury, Robert; Kuchipudi, Suresh V

2015-09-01

Human infections with non-typhoidal Salmonella (NTS) serovars are increasingly becoming a threat to human health globally. While all motile Salmonellae have zoonotic potential, Salmonella Enteritidis and Salmonella Typhimurium are most commonly associated with human disease, for which poultry are a major source. Despite the increasing number of human NTS infections, the epidemiology of NTS in poultry in India has not been fully understood. Hence, as a first step, we carried out epidemiological analysis to establish the incidence of NTS in poultry to evaluate the risk to human health. A total of 1215 samples (including poultry meat, tissues, egg and environmental samples) were collected from 154 commercial layer farms from southern India and screened for NTS. Following identification by cultural and biochemical methods, Salmonella isolates were further characterized by multiplex PCR, allele-specific PCR, enterobacterial repetitive intergenic consensus (ERIC) PCR and pulse field gel electrophoresis (PFGE). In the present study, 21/1215 (1.73 %) samples tested positive for NTS. We found 12/392 (3.06 %) of tissue samples, 7/460 (1.52 %) of poultry products, and 2/363 (0.55 %) of environmental samples tested positive for NTS. All the Salmonella isolates were resistant to oxytetracycline, which is routinely used as poultry feed additive. The multiplex PCR results allowed 16/21 isolates to be classified as S. Typhimurium, and five isolates as S. Enteritidis. Of the five S. Enteritidis isolates, four were identified as group D Salmonella by allele-specific PCR. All of the isolates produced different banding patterns in ERIC PCR. Of the thirteen macro restriction profiles (MRPs) obtained by PFGE, MRP 6 was predominant which included 6 (21 %) isolates. In conclusion, the findings of the study revealed higher incidence of contamination of NTS Salmonella in poultry tissue and animal protein sources used for poultry. The results of the study warrants further investigation on different type of animal feed sources, food market chains, processing plants, live bird markets etc., to evaluate the risk factors, transmission and effective control measures of human Salmonella infection from poultry products.

Hydrogeologic characterization of wells HTH-1, UE18r, UE6e, and HTH-3, Nevada Test Site

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

Lyles, B.F.; McKay, W.A.; Chapman, J.B.

1991-06-01

Monitoring for the migration of contaminants in groundwater or for the proper design of nuclear test emplacement holes at the Nevada Test Site (NTS) requires proper placement and completion of monitoring wells. This is only possible if the hydrogeologic system is understood in a regional and local context, necessitating data from existing wells and boreholes. Though the NTS Groundwater Characterization Project will be drilling wells, their great expense limits the number of new wells. However, there are many existing boreholes and wells on the NTS which have not been completely evaluated hydrologically. Some of these are incorporated in the Longmore » Term Hydrologic Monitoring Program (LTHMP) of the US Environmental Protection Agency (EPA), others are related to the testing programs. In all cases, additional site investigation in necessary to properly interpret the hydrogeologic data from these wells. Monitoring wells on the NTS are poorly characterized with regard to aquifers penetrated, vertical hydraulic gradients, and vertical variations in water quality. One of the goals of the well validation program was to gain a thorough understanding of the parameters needed to interpret the source and fate potential hazardous and radioactive substances that may be detected in these wells in the future. One of the most critical parameters for monitoring is the knowledge of what aquifer or geologic unit is being sampled when a water sample is collected. Pumped water samples are weighted most heavily to the water quality of the most productive (highest transmissivity) aquifer penetrated by the well.« less

Identification of the Critical Nontechnical Skills for Surgeons Needed for High Performance in a Variable-resource Context (NOTSS-VRC).

PubMed

Scott, John W; Lin, Yihan; Ntakiyiruta, Georges; Mutabazi, Zeta; Davis, William A; Morris, Megan A; Smink, Douglas S; Riviello, Robert; Yule, Steven

2018-05-17

To identify the critical nontechnical skills (NTS) required for high performance in variable-resource contexts (VRC). As surgical training and capacity increase in low- and middle-income countries (LMICs), new strategies for improving surgical education and care in these settings are required. NTS are critical for high performance in surgery around the world. However, the essential NTS used by surgeons operating in LMICs to overcome the challenges specific to their contexts have never been described. Using a constructivist grounded theory approach, 52 intraoperative team observations as well as 34 critical incident interviews with surgical providers (surgeons, anesthetists, and nurses) were performed at the 4 tertiary referral hospitals in Rwanda. Interview transcripts and field notes from observations were analyzed using line-by-line coding to identify emerging themes until thematic saturation was achieved. Four skill categories of situation awareness, decision-making, communication/teamwork, and leadership emerged. This provided the framework for a contextually informed skills taxonomy consisting of 12 skill elements with examples of specific behaviors indicative of high performance. While the main skill categories were consistent with those encountered in high-income countries, the specific behaviors associated with these skills often focused on overcoming the frequently encountered variability in resources, staff, systems support, and language in this context. This is the first description of the critical nontechnical skills, and associated example behaviors, used by surgeons in a VRC to overcome common challenges to safe and effective surgical patient care. Improvements in the NTS used by surgeons operating in VRCs have the potential to improve surgical care delivery worldwide.

Ranges of applicability for the continuum beam model in the mechanics of carbon nanotubes and nanorods

NASA Technical Reports Server (NTRS)

Harik, V. M.

2001-01-01

Limitations in the validity of the continuum beam model for carbon nanotubes (NTs) and nanorods are examined. Applicability of all assumptions used in the model is restricted by the two criteria for geometric parameters that characterize the structure of NTs. The key non-dimensional parameters that control the NT buckling behavior are derived via dimensional analysis of the nanomechanical problem. A mechanical law of geometric similitude for NT buckling is extended from continuum mechanics for different molecular structures. A model applicability map, where two classes of beam-like NTs are identified, is constructed for distinct ranges of non-dimensional parameters. Expressions for the critical buckling loads and strains are tailored for two classes of NTs and compared with the data provided by the molecular dynamics simulations. copyright 2001 Elsevier Science Ltd. All rights reserved.

The Human Transcriptome During Nontyphoid Salmonella and HIV Coinfection Reveals Attenuated NFκB-Mediated Inflammation and Persistent Cell Cycle Disruption

PubMed Central

Schreiber, Fernanda; Lynn, David J.; Houston, Angela; Peters, Joanna; Mwafulirwa, Gershom; Finlay, Brett B.; Brinkman, Fiona S. L.; Hancock, Robert E. W.; Heyderman, Robert S.; Dougan, Gordon

2011-01-01

Background. Invasive nontyphoid Salmonella (iNTS) disease is common and severe in adults with human immunodeficiency virus (HIV) infection in Africa. We previously observed that ex vivo macrophages from HIV-infected subjects challenged with Salmonella Typhimurium exhibit dysregulated proinflammatory cytokine responses. Methods. We studied the transcriptional response in whole blood from HIV-positive patients during acute and convalescent iNTS disease compared to other invasive bacterial diseases, and to HIV-positive and -negative controls. Results. During iNTS disease, there was a remarkable lack of a coordinated inflammatory or innate immune signaling response. Few interferon γ (IFNγ)--induced genes or Toll-like receptor/transcription factor nuclear factor κB (TLR/NFκB) gene pathways were upregulated in expression. Ex vivo lipopolysacharide (LPS) or flagellin stimulation of whole blood, however, showed that convalescent iNTS subjects and controls were competent to mount prominent TLR/NFκB-associated patterns of mRNA expression. In contrast, HIV-positive patients with other invasive bacterial infections (Escherichia coli and Streptococcus pneumoniae) displayed a pronounced proinflammatory innate immune transcriptional response. There was also upregulated mRNA expression in cell cycle, DNA replication, translation and repair, and viral replication pathways during iNTS. These patterns persisted for up to 2 months into convalescence. Conclusions. Attenuation of NFκB-mediated inflammation and dysregulation of cell cycle and DNA-function gene pathway expression are key features of the interplay between iNTS and HIV. PMID:21917897

Prevalence and Correlates of Skin Cancer Screening Among Indoor Tanners and Nontanners.

PubMed

Heckman, Carolyn J; Handorf, Elizabeth; Auerbach, Melissa V

2018-04-04

The US Food and Drug Administration recommends that indoor tanners (ITs) be screened regularly for skin cancer (SC). To investigate the association between indoor tanning and SC screening. The 2015 National Health Interview Survey was a multistage, clustered, cross-sectional design with 30 352 US adults participating. The response rate for the sample adult data used in this study was 55.20% after excluding 1099 individuals who reported a history of SC and 2221 individuals with unknown SC screening or indoor tanning history. To examine the independent correlates of screening, we conducted multiple logistic regressions separately for ITs and nontanners (NTs), simultaneously including all preselected variables of interest as potential predictors. Formal interaction analyses were also performed to determine if the covariate effects differed significantly between ITs and NTs. Indoor tanning as well as sociodemographic, health care, and SC risk and sun protection factors. The primary outcome was self-reported full-body SC screening by a physician. Univariable and multivariable analyses were conducted to determine the secondary outcome, correlates of SC screening among ITs and NTs. A total of 15 777 participants (51.98%) were female, and 23 823 (78.49%) were white; 4987 (16.43%) of the sample had indoor tanned, and 1077 (21.59%) of these had tanned last year. A total of 1505 ITs (30.18%) and 4951 NTs (19.52%) had been screened for SC. Correlates of screening for ITs and NTs were older age (ITs: odds ratio [OR], 4.29 [95% CI, 2.72-6.76]; NTs, OR, 5.14 [95% CI, 4.01-6.58], age ≥65 years vs 18-29 years), higher income (ITs: OR, 2.08 [95% CI, 1.50-2.88]; NTs: OR, 1.79 [95% CI, 1.51-2.12]; >$100 000 vs $0-34 999), seeking online health information (ITs, OR, 0.71 [95% CI. 0.56-0.91; NTs, OR, 0.65 [95% CI, 0.58-0.72], for not looking up health info online), family history of melanoma (ITs: OR, 1.92 [95% CI, 1.26-2.93]; NTs: OR, 1.58 [95% CI, 1.21-2.05]) or SC (ITs: OR, 1.59 [95% CI, 1.17-2.17; NTs: OR, 1.61 [95% CI, 1.33-1.94]), very high SPF sunscreen use (ITs: OR, 0.57 [95% CI, 0.42-0.78]; NTs: OR, 0.71 [95% CI, 0.61-0.82], use of SPF of 1-14 vs SPF of >50), and receipt of a professional spray-on tan (ITs: OR, 0.60 [ 95% CI, 0.41-0.88]; NTs: OR, 0.51 [95% CI, 0.32-0.81], for not receiving a salon spray-on tan). Correlates for NTs only were white race (blacks: OR, 0.45 [95% CI, 0.37-0.54], others: OR, 0.40 [95% CI, 0.33-0.48]), non-Hispanic ethnicity (Hispanics: OR, 0.42 [95% CI, 0.36-0.50]), email use (no email: OR, 0.67 [95% CI, 0.56-0.80]), having a usual clinic/or physician's office (no usual place: OR, 0.56 [95% CI, 0.40-0.78]), emergency department visits (OR, 1.20 [95% CI, 1.06-1.35]), having had a previous cancer diagnosis (no cancer diagnosis: OR, 0.67 [95% CI, 0.57-0.79]), not being worried about medical bills (OR, 1.37 [95% CI, 1.15-1.63] vs very worried), sun protection (rarely/never: OR, 0.43 [95% CI, 0.34-0.56]), and sunless self-tanning (not using: OR, 0.62 [95% CI, 0.47-0.83]). Few ITs have been screened for SC, although SC rates are higher than among NTs. It is not surprising that SC screening is associated with SC risk factors (eg, family history of SC and age) among ITs. However, some unscreened ITs may be putting themselves at even greater risk of SC by also being more likely to use low SPF sunscreen than ITs who have been screened for SC.

Liquid chromatography-mass spectrometry platform for both small neurotransmitters and neuropeptides in blood, with automatic and robust solid phase extraction

NASA Astrophysics Data System (ADS)

Johnsen, Elin; Leknes, Siri; Wilson, Steven Ray; Lundanes, Elsa

2015-03-01

Neurons communicate via chemical signals called neurotransmitters (NTs). The numerous identified NTs can have very different physiochemical properties (solubility, charge, size etc.), so quantification of the various NT classes traditionally requires several analytical platforms/methodologies. We here report that a diverse range of NTs, e.g. peptides oxytocin and vasopressin, monoamines adrenaline and serotonin, and amino acid GABA, can be simultaneously identified/measured in small samples, using an analytical platform based on liquid chromatography and high-resolution mass spectrometry (LC-MS). The automated platform is cost-efficient as manual sample preparation steps and one-time-use equipment are kept to a minimum. Zwitter-ionic HILIC stationary phases were used for both on-line solid phase extraction (SPE) and liquid chromatography (capillary format, cLC). This approach enabled compounds from all NT classes to elute in small volumes producing sharp and symmetric signals, and allowing precise quantifications of small samples, demonstrated with whole blood (100 microliters per sample). An additional robustness-enhancing feature is automatic filtration/filter back-flushing (AFFL), allowing hundreds of samples to be analyzed without any parts needing replacement. The platform can be installed by simple modification of a conventional LC-MS system.

Defining modeling parameters for juniper trees assuming pleistocene-like conditions at the NTS

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

Tarbox, S.R.; Cochran, J.R.

1994-12-31

This paper addresses part of Sandia National Laboratories` (SNL) efforts to assess the long-term performance of the Greater Confinement Disposal (GCD) facility located on the Nevada Test Site (NTS). Of issue is whether the GCD site complies with 40 CFR 191 standards set for transuranic (TRU) waste burial. SNL has developed a radionuclide transport model which can be used to assess TRU radionuclide movement away from the GCD facility. An earlier iteration of the model found that radionuclide uptake and release by plants is an important aspect of the system to consider. Currently, the shallow-rooted plants at the NTS domore » not pose a threat to the integrity of the GCD facility. However, the threat increases substantially it deeper-rooted woodland species migrate to the GCD facility, given a shift to a wetter climate. The model parameters discussed here will be included in the next model iteration which assumes a climate shift will provide for the growth of juniper trees at the GCD facility. Model parameters were developed using published data and wherever possible, data were taken from juniper and pinon-juniper studies that mirrored as many aspects of the GCD facility as possible.« less

Non-carbon titanium cobalt nitride nanotubes supported platinum catalyst with high activity and durability for methanol oxidation reaction

NASA Astrophysics Data System (ADS)

Chen, Xiaoxiang; Li, Wuyi; Pan, Zhanchang; Xu, Yanbin; Liu, Gen; Hu, Guanghui; Wu, Shoukun; Li, Jinghong; Chen, Chun; Lin, Yingsheng

2018-05-01

Titanium cobalt nitride nanotubes (Ti0.95Co0.05N NTs) hybrid support, a novel robust non-carbon support material prepared by solvothermal and post-nitriding processes, is further decorated with Pt nanoparticles for the electrooxidation of methanol. The catalyst is characterized by X-ray diffraction (XRD), nitrogen adsorption/desorption, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and electrochemical measurements. The morphology, structure and composition of the synthesized Ti0.95Co0.05N NTs suggest that the nanotube wall is porous and consists of homogeneous cohesively attached nitrides nanocube particles. Notable, Ti0.95Co0.05N NTs supported Pt catalyst exhibits significantly improved catalytic activity and durability for methanol electrooxidation compared with the conventional JM Pt/C catalyst. The experimental data indicate that enhanced catalytic activity and stability of Pt/Ti0.95Co0.05N NTs towards methanol electrooxidation might be mainly attributed to the tubular nanostructures and synergistic effect introduced by the Co doping. Both of them are playing an important role in improving the activity and durability of the Ti0.95Co0.05N NTs catalyst.

Magnetic properties of superparamagnetic nanoparticles loaded into silicon nanotubes.

PubMed

Granitzer, Petra; Rumpf, Klemens; Gonzalez, Roberto; Coffer, Jeffery; Reissner, Michael

2014-01-01

In this work, the magnetic properties of silicon nanotubes (SiNTs) filled with Fe3O4 nanoparticles (NPs) are investigated. SiNTs with different wall thicknesses of 10 and 70 nm and an inner diameter of approximately 50 nm are prepared and filled with superparamagnetic iron oxide nanoparticles of 4 and 10 nm in diameter. The infiltration process of the NPs into the tubes and dependence on the wall-thickness is described. Furthermore, data from magnetization measurements of the nanocomposite systems are analyzed in terms of iron oxide nanoparticle size dependence. Such biocompatible nanocomposites have potential merit in the field of magnetically guided drug delivery vehicles. 61.46.Fg; 62.23.Pq; 75.75.-c; 75.20.-g.

Explosion Source Model Development in Support of Seismic Monitoring Technologies: New Models Accounting for Shock-Induced Tensile Failure

DTIC Science & Technology

2008-09-01

values for nuclear explosions at the Semipalatinsk Test Site (STS) will be inferred in the same way they were for NTS. Comparisons between K values...K > ~3 in Poisson media. Most Nevada Test Site (NTS) observations support ~1 < K < 3, and as such the new model predicts lower Ms compared to the...explosions at the two test sites and for two different containment rules are summarized in Table 1 below. F1 is found to be positive for NTS, as we

Lesion of the commissural nucleus of the solitary tract/A2 noradrenergic neurons facilitates the activation of angiotensinergic mechanisms in response to hemorrhage.

PubMed

Freiria-Oliveira, A H; Blanch, G T; De Paula, P M; Menani, J V; Colombari, D S A

2013-12-19

In the present study, we investigated the effects of lesions of A2 neurons of the commissural nucleus of the solitary tract (cNTS) alone or combined with the blockade of angiotensinergic mechanisms on the recovery of arterial pressure (AP) to hemorrhage in conscious rats. Male Holtzman rats (280-320g) received an injection of anti-dopamine-beta-hydroxylase-saporin (12.6ng/60nl; cNTS/A2-lesion, n=28) or immunoglobulin G (IgG)-saporin (12.6ng/60nl, sham, n=24) into the cNTS and 15-21days later had a stainless steel cannula implanted in the lateral ventricle. After 6days, rats were submitted to hemorrhage (four blood withdrawals, 2ml/300g of body weight every 10min). Both cNTS/A2-lesioned and sham rats had similar hypotension to hemorrhage (-62±7 and -73±7mmHg, respectively), however cNTS/A2-lesioned rats rapidly recovered from hypotension (-5±3mmHg at 30min), whereas sham rats did not completely recover until the end of the recording (-20±3mmHg at 60min). Losartan (angiotensin type 1 receptor antagonist) injected intracerebroventricularly (100μg/1μl) or intravenously (i.v.) (10mg/kg of body weight) impaired the recovery of AP in cNTS/A2-lesioned rats (-24±6 and -35±7mmHg at 30min, respectively). In sham rats, only i.v. losartan affected the recovery of AP (-39±6mmHg at 60min). The results suggest that lesion of the A2 neurons in the cNTS facilitates the activation of the angiotensinergic pressor mechanisms in response to hemorrhage. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Prevalence and Predictors of Neoadjuvant Therapy for Stage IIIA Non-Small Cell Lung Cancer in the National Cancer Database: Importance of Socioeconomic Status and Treating Institution

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

Sher, David J., E-mail: david_sher@rush.edu; Liptay, Michael J.; Fidler, Mary Jo

Purpose: The optimal locoregional therapy for stage IIIA non-small cell lung cancer (NSCLC) is controversial, with definitive chemoradiation therapy (CRT) and neoadjuvant therapy followed by surgery (NT-S) serving as competing strategies. In this study, we used the National Cancer Database to determine the prevalence and predictors of NT in a large, modern cohort of patients. Methods and Materials: Patients with stage IIIA NSCLC treated with CRT or NT-S between 2003 and 2010 at programs accredited by the Commission on Cancer were included. Predictors were categorized as clinical, time/geographic, socioeconomic, and institutional. In accord with the National Cancer Database, institutions were classifiedmore » as academic/research program and as comprehensive and noncomprehensive community cancer centers. Logistic regression and random effects multilevel logistic regression were performed for univariable and multivariable analyses, respectively. Results: The cohort consisted of 18,581 patients, 3,087 (16.6%) of whom underwent NT-S (10.6% induction CRT, 6% induction chemotherapy). The prevalence of NT-S was constant over time, but there were significant relative 31% and 30% decreases in pneumonectomy and right-sided pneumonectomy, respectively, over time (P trend <.02). In addition to younger age, lower T stage, and favorable comorbidity score, indicators of higher socioeconomic status were strong independent predictors of NT-S, including white race, higher income, and private/managed insurance. The type of institution (academic/research program vs comprehensive or noncomprehensive community cancer centers, odds ratio 1.54 and 2.08, respectively) strongly predicted NT-S, but treatment volume did not. Conclusions: Neoadjuvant therapy followed by surgery was an uncommon treatment approach in Commission on Cancer programs, and the prevalence of postinduction pneumonectomy decreased over time. Higher socioeconomic status and treatment at academic institutions were significant predictors of NT-S. Further research should be performed to enable a better understanding of these disparities.« less

Nanotetrapods: quantum dot hybrid for bulk heterojunction solar cells

PubMed Central

2013-01-01

Hybrid thin film solar cell based on all-inorganic nanoparticles is a new member in the family of photovoltaic devices. In this work, a novel and performance-efficient inorganic hybrid nanostructure with continuous charge transportation and collection channels is demonstrated by introducing CdTe nanotetropods (NTs) and CdSe quantum dots (QDs). Hybrid morphology is characterized, demonstrating an interpenetration and compacted contact of NTs and QDs. Electrical measurements show enhanced charge transfer at the hybrid bulk heterojunction interface of NTs and QDs after ligand exchange which accordingly improves the performance of solar cells. Photovoltaic and light response tests exhibit a combined optic-electric contribution from both CdTe NTs and CdSe QDs through a formation of interpercolation in morphology as well as a type II energy level distribution. The NT and QD hybrid bulk heterojunction is applicable and promising in other highly efficient photovoltaic materials such as PbS QDs. PMID:24139059

Graphene/vanadium oxide nanotubes composite as electrode material for electrochemical capacitors

NASA Astrophysics Data System (ADS)

Fu, Meimei; Ge, Chongyong; Hou, Zhaohui; Cao, Jianguo; He, Binhong; Zeng, Fanyan; Kuang, Yafei

2013-07-01

Graphene/vanadium oxide nanotubes (VOx-NTs) composite was successfully synthesized through the hydrothermal process in which acetone as solvent and 1-hexadecylamine (HDA) as structure-directing template were used. Morphology, structure and composition of the as-obtained composite were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy, nitrogen isothermal adsorption/desorption and thermo gravimetric analysis (TGA). The composite with the VOx-NTs amount of 69.0 wt% can deliver a specific capacitance of 210 F/g at a current density of 1 A/g in 1 M Na2SO4 aqueous solution, which is nearly twice as that of pristine graphene (128 F/g) or VOx-NTs (127 F/g), and exhibit a good performance rate. Compared with pure VOx-NTs, the cycle stability of the composite was also greatly improved due to the enhanced conductivity of the electrode and the structure buffer role of graphene.

National Emission Standards for Hazardous Air Pollutants Calendar Year 2001

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

Y. E. Townsend

2002-06-01

The Nevada Test Site (NTS) is operated by the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Operations Office (NNSA/NV) as the site for nuclear weapons testing, now limited to readiness activities, experiments in support of the national Stockpile Stewardship Program, and the activities listed below. Located in Nye County, Nevada, the site's southeast corner is about 88 km (55 mi) northwest of the major population center, Las Vegas, Nevada. The NTS covers about 3,561 km2 (1,375 mi2), an area larger than Rhode Island. Its size is 46 to 56 km (28 to 35 mi) east to westmore » and from 64 to 88 km (40 to 55 mi) north to south. The NTS is surrounded, except on the south side, by public exclusion areas (Nellis Air Force Range [NAFR]) that provide another 24 to 104 km (15 to 65 mi) between the NTS and public lands (Figure 1.0). The NTS is characterized by desert valley and Great Basin mountain topography, with a climate, flora, and fauna typical of the southwest deserts. Population density within 150 km (93 mi) of the NTS is only about 0.2 persons per square kilometer, excluding the Las Vegas area. Restricted access, low population density in the surrounding area, and extended wind transport times are advantageous factors for the activities conducted at the NTS. Surface waters are scarce on the NTS, and slow-moving groundwater is present hundreds to thousands of feet below the land surface. The sources of radionuclides include current and previous activities conducted on the NTS (Figure 2.0). The NTS was the primary location for testing of nuclear explosives in the Continental U.S. between 1951 and 1992. Historical testing above or at ground surface has included (1) atmospheric testing in the 1950s and early 1960s, (2) earth-cratering experiments, and (3) open-air nuclear reactor and rocket engine testing. Since the mid-1950s, testing of nuclear explosive devices has occurred underground in drilled vertical holes or in mined tunnels (DOE 1996a). No such tests have been conducted since September 23, 1992 (DOE 2000). Limited non-nuclear testing includes spills of hazardous materials at the Hazardous Materials Spill Center, private technology development, aerospace and demilitarization activities, and site remediating activities. Processing of radioactive materials is limited to laboratory analyses, and handling is restricted to transport, storage, and assembly of nuclear explosive devices and operation of radioactive waste management sites (RWMSs) for low-level radioactive and mixed waste (DOE 1996a). Monitoring and evaluation of the various activities conducted onsite indicate that the potential sources of offsite radiation exposure in CY 2001 were releases from (1) evaporation of tritiated water (HTO) from containment ponds that receive drainage water from E Tunnel in Area 12 and from discharges of two wells (Well U-3cn PS No. 2 and Well ER-20-5 No.3) into lined ponds, (2) onsite radio analytical laboratories, (3) the Area 5 RWMS (RWMS-5) facility, and (4) diffuse sources of tritium and re- suspension of plutonium and americium. The following sections present a general description of the present sources on the NTS and at the North Las Vegas Facility.« less

Timeliness of electronic reporting and acceptability of public health follow-up of routine nonparatyphoidal and nontyphoidal Salmonella infections, London and South East England, 2010 to 2011.

PubMed

Severi, E; Dabrera, G; Boxall, N; Harvey-Vince, L; Booth, L; Balasegaram, S

2014-01-01

Nonparatyphoidal and nontyphoidal Salmonella (NTS) infections are major causes of food poisoning in England. Diagnostic laboratories and clinicians have a statutory responsibility to report NTS infection cases to the Health Protection Agency via various means, with electronic reporting encouraged as the universal method. The Health Protection Agency (Public Health England since 1 April 2013) refers cases to environmental health departments for follow-up. Timeliness of reporting and adequacy of NTS infection case follow-up are key factors in the implementation of public health actions. Laboratories, health protection units, and environmental health departments in London and South East (SE) regions of England completed three surveys between December 2010 and April 2011, collecting data about the NTS infection case reporting methods and the time elapsed between symptom onset and public health actions. The median period between symptom onset and public health investigation was 25 days in London and 23 days in SE when electronic reporting was used and 12 days in London and 11 days in SE when other means of reporting were used. The most common follow-up method was a telephone questionnaire in London (53%) and a postal questionnaire in SE (52%). The telephone questionnaire had the highest response rate (98% in London; 96% in SE). Timeliness and efficiency of electronic NTS infection case reports can be improved by decreasing the electronic laboratory report period and using telephone-administered questionnaires to maximize the public health benefit when following up single cases of NTS infection.

US Department of Energy Nevada Operations Office annual site environmental report: 1993. Volume 1

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

Black, S.C.; Glines, W.M.; Townsend, Y.E.

1994-09-01

Monitoring and surveillance on and around the Nevada Test Site (NTS) by DOE contractors and NTS user organizations during 1993 indicated that operations on the NTS were conducted in compliance with applicable federal and DOE guidelines, i.e., the dose the maximally exposed offsite individual could have received was less than 0.04 percent of the 10 mrem per year guide for air exposure. No nuclear tests were conducted due to the moratorium. All discharges of radioactive liquids remained onsite in containment ponds, and there was no indication of potential migration of radioactivity to the offsite area through groundwater. Surveillance around themore » NTS indicated that airborne radioactivity from diffusion, evaporation of effluents, or resuspension was not detectable offsite, and no measurable net exposure to members of the offsite population was detected through the offsite dosimetry program. Using the CAP88-PC model and NTS radionuclide emissions data, the calculated effective dose equivalent to the maximally exposed individual offsite would have been 0.004 mrem. Any person receiving this dose would also have received 97 mrem from natural background radiation. There were no nonradiological releases to the offsite area. Hazardous wastes were shipped offsite to approved disposal facilities. Compliance with the various regulations stemming from the National Environmental Policy Act is being achieved and, where mandated, permits for air and water discharges and waste management have been obtained from the appropriate agencies. Support facilities at off-NTS locations compiled with the requirements of air quality permits and state or local wastewater discharge and hazardous waste permits.« less

Trpv4 involvement in the sex differences in blood pressure regulation in spontaneously hypertensive rats.

PubMed

Onishi, Makiko; Yamanaka, Ko; Miyamoto, Yasunori; Waki, Hidefumi; Gouraud, Sabine

2018-04-01

Arterial pressure (AP) is lower in premenopausal women than in men of a similar age. Premenopausal women exhibit a lower sympathetic activity and a greater baroreceptor reflex; however, mechanisms controlling sex differences in blood pressure regulation are not well understood. We hypothesized that different neuronal functions in the cardiovascular centers of the brains of men and women may contribute to the sex difference in cardiovascular homeostasis. Our previous studies on male spontaneously hypertensive rats (SHRs) and their normotensive counterparts, Wistar Kyoto (WKY) rats, revealed that the gene-expression profile of the nucleus tractus solitarius (NTS), a region of the medulla oblongata that is pivotal for regulating the set point of AP, is strongly associated with AP. Thus, we hypothesized that gene-expression profiles in the rat NTS are related to sex differences in AP regulation. Because female SHRs clearly exhibit lower AP than their male counterparts of a similar age, we investigated whether SHR NTS exhibits sex differences in gene expression by using microarray and RT-qPCR experiments. The transcript for transient receptor potential cation channel subfamily V member 4 ( Trpv4) was found to be upregulated in SHR NTS in females compared with that in males. The channel was expressed in neurons and glial cells within NTS. The TRPV4 agonist 4-alpha-phorbol-12,13-didecanoate (4α-PDD) decreased blood pressure when injected into NTS of rats. These findings suggest that altered TRPV4 expression might be involved in the sex differences in blood pressure regulation.

Au nanoparticles-ZnO composite nanotubes using natural silk fibroin fiber as template for electrochemical non-enzymatic sensing of hydrogen peroxide.

PubMed

Chen, Liangliang; Xu, Xiaolong; Cui, Feng; Qiu, Qianying; Chen, Xiaojun; Xu, Jinzhong

2018-05-23

A novel electrochemical sensor based on the composite of gold nanoparticles/zinc oxide nanotube (AuNPs/ZnO-NTs) was constructed and its application as hydrogen peroxide (H 2 O 2 ) non-enzymatic sensor was investigated. ZnO-NTs were prepared by a biomineralization strategy in which silk fibroin fiber (SFF) was used as template, and thus the ZnO-NTs inherited the advantages of SFF such as mechanical stability, flexible biomimetic morphology and biocompatibility. The AuNPs/ZnO-NTs was further prepared by the electrostatic absorption of AuNPs onto the surface of ZnO-NTs, and found to be capable to catalyze the reduction of H 2 O 2 . The working potential was 0.05 V, which was far higher than those in literatures, indicating the strong anti-interference ability in the real application. The catalytic current was linearly proportional in the concentration range of 1 μM-3.0 mM with a sensitivity of 1336.7 μA mM -1  cm -2 . The detection limit was estimated to be 0.1 μM (S/N = 3). Such a high sensitivity was attributed to the electrocatalytic property of ZnO and high electron transfer ability of AuNPs/ZnO-NTs structure. Moreover, the final detection results of H 2 O 2 in real samples showed the acceptable accuracy compared with the traditional potassium permanganate titration, exhibiting the prospect to be used as an applicable sensor in actual detections. Copyright © 2018 Elsevier Inc. All rights reserved.

Neonatal tactile stimulation reverses the effect of neonatal isolation on open-field and anxiety-like behavior, and pain sensitivity in male and female adult Sprague-Dawley rats.

PubMed

Imanaka, A; Morinobu, S; Toki, S; Yamamoto, S; Matsuki, A; Kozuru, T; Yamawaki, S

2008-01-10

It is well known that early life events induce long-lasting psychophysiological and psychobiological influences in later life. In rodent studies, environmental enrichment after weaning prevents the adulthood behavioral and emotional disturbances in response to early adversities. We compared the behavioral effect of neonatal isolation (NI) with the effect of NI accompanied by tactile stimulation (NTS) to determine whether NTS could reverse or prevent the effects of NI on the adulthood behavioral and emotional responses to environmental stimuli. In addition, we also examined the sex difference of the NTS effect. Measurements of body weights, an open-field locomotor test, an elevated plus maze test, a hot-plate test, and a contextual fear-conditioning test were performed on postnatal day 60. As compared with rats subjected to NI, rats subjected to NTS showed significantly higher activity and exploration in the open-field locomotor test, lower anxiety-like behavior in the elevated plus maze test, and significantly prolonged latencies in the hot-plate test, and this effect was equal among males and females. In the contextual fear-conditioning test, whereas NTS significantly reduced the enhanced freezing time due to NI in females, no significant difference in the freezing time between NI and NTS was found in males. These findings indicate that adequate tactile stimulation in early life plays an important role in the prevention of disturbances in the behavioral and emotional responses to environmental stimuli in adulthood induced by early adverse experiences.

HMC-1 human mast cells synthesize neurotensin (NT) precursor, secrete bioactive NT-like peptide(s) and express NT receptor NTS1.

PubMed

Cochrane, David E; Carraway, Robert E; Harrington, Kimberly; Laudano, Melissa; Rawlings, Stephen; Feldberg, Ross S

2011-12-01

To determine if mast cells synthesize the inflammatory peptide, neurotensin (NT), secrete immunoreactive and bioactive NT, and express the NT receptor NTS1. HMC-1 cells, pleural mast cells from Sprague-Dawley rats, LAD2 mast cells, and human cord blood mast cells were used. HMC-1 cells were stimulated with NT, C48/80, mastoparan, or PGE(2). For changes in cutaneous vascular permeability, anesthetized rats were injected intravenously with Evans Blue dye and intradermally with saline, NT, histamine, diphenhydramine, and C48/80. RT-PCR was used to identify RNA transcripts. Histamine was measured by fluorometric assay. In vivo cutaneous vascular permeability assays, radio-immunoassays for NT, Western blotting for the NT precursor protein and NTS1 protein from HMC-1 cells and tissues from rats were used. Immunohistochemistry was used to identify NT precursor-like proteins in HMC-1 mast cells. HMC-1 cells express mRNAs for NT precursor, PC5A processing enzyme and NTS1 receptor. Human cord blood mast cells and LAD2 mast cells express mRNA transcripts for NT precursor and NTS1. Western blotting showed NT precursor and NTS1 receptor in HMC1. Rat tissues with high numbers of mast cells contained NT precursor proteins. NT-like peptides from HMC-1 displayed NT-like bioactivity. HMC-1 mast cells synthesize and secrete immunoreactive and bioactive NT-like peptide(s) and express the NT receptor, suggesting that NT from mast cells might serve autocrine and paracrine roles.

Serotonin in the solitary tract nucleus shortens the laryngeal chemoreflex in anesthetized neonatal rats

PubMed Central

Donnelly, William T.; Bartlett, Donald; Leiter, J.C.

2017-01-01

The laryngeal chemoreflex (LCR), an airway protective reflex that causes apnea and bradycardia, has long been suspected as an initiating event in the sudden infant death syndrome (SIDS). Serotonin (5-HT) and 5-HT receptors may be deficient in the brainstems of babies who die of SIDS, and 5-HT seems to be important in terminating apneas directly or in causing arousals or as part of the process of autoresuscitation. We hypothesized that 5-HT in the brainstem would limit the duration of the LCR. We studied anesthetized rat pups between 7 and 21 days of age and made microinjections into the cisterna magna or into the nucleus of the solitary tract (NTS). Focal, bilateral microinjections of 5-HT into the caudal NTS significantly shortened the LCR. The 5-HT 1a receptor antagonist, WAY 100635, did not affect the LCR consistently, nor did a 5-HT2 receptor antagonist, ketanserin, alter the duration of the LCR. The 5-HT3 specific agonist, 1-(3-chlorophenyl)-biguanide, microinjected bilaterally into the caudal NTS significantly shortened the LCR. Thus, endogenous 5-HT released within the NTS may curtail the respiratory depression that is part of the LCR, and serotonergic shortening of the LCR may be attributed to activation of 5-HT3 receptors within the NTS. 5-HT3 receptors are expressed presynaptically on C-fiber afferents of the superior laryngeal nerve, and serotonergic shortening of the LCR may be mediated presynaptically by enhanced activation of inhibitory interneurons within the NTS that terminate during the LCR. PMID:27121960

Ecological Monitoring and Compliance Program Fiscal Year 2000 Report

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

Wills, C.A.

2000-12-01

The Ecological Monitoring and Compliance program, funded through the U.S. Department of Energy, Nevada Operations Office, monitors the ecosystem of he Nevada Test Site (NTS) and ensures compliance with laws and regulations pertaining to NTS biota. This report summarizes the program's activities conducted by Bechtel Nevada during fiscal year 2000. Program activities included: (1) biological surveys at proposed construction sites, (2) desert tortoise compliance,(3) ecosystem mapping, (4) sensitive species and unique habitat monitoring, and (5) biological monitoring at the HAZMAT Spill Center. Biological surveys for the presence of sensitive species were conducted for 24 NTS projects. Seventeen sites were inmore » desert tortoise habitat, and six acres of tortoise habitat were documented as being disturbed this year. No tortoises were found in or displaced from project areas, and no tortoises were accidentally injured or killed. A topical report describing the classification of habitat types o n the NTS was completed. The report is the culmination of three years of field vegetation mapping and the analysis of vegetation data from over 1,500 ecological landform units. A long-term monitoring plan for important plant species that occur on the NTS was completed. Sitewide inventories were conducted for the western burrowing owl, bat species of concern, wild horses, raptor nests, and mule deer. Fifty-nine of 69 known owl burrows were monitored. Forty-four of the known burrows are in disturbed habitat. As in previous years, some owls were present year round on the NTS. An overall decrease in active owl burrows was observed within all three ecoregions (Mojave Desert, Transition, Great Basin Desert) from October through January. An increase in active owl burrows was observed from mid-March to early April. A total of 45 juvenile owls was detected from eight breeding pairs. One nest burrow was detected in the Mojave Desert,one in the Great Basin Desert, and six in the Transition ecoregion. Seventy bats, representing four bat species of concern, were captured in mist-nets at water sources in the Great Basin Desert ecoregion. Bats were detected with the Anabat II call-recording system at selected tunnel and mine entrances verifying that some NTS mines and tunnels are used as bat roosts. Thirty-seven adult horses and 11 foals were counted this year. Four of the five foals observed last year have survived to yearlings. A monitoring plan for NTS horses was completed. Six active red-tailed hawk nests and 10 nestling red-tailed hawks were detected this year. Two spotlighting surveys for mule deer were conducted, each over three consecutive nights in October 1999 and August 2000. The mean sighting rate in October was 1.2 deer/10 kilometers (km) and 1.6 deer/10 km in August. Selected wetlands and man-made water sources were monitored for physical parameters and wildlife use. No dead animals were observed this year in any plastic-lined sump. Pahute Mesa Pond was confirmed to have vegetation,hydrology, and soil indicators that qualify the site as a jurisdictional wetland. The chemical spill test plan for one experiment at the HAZMAT Spill Center was reviewed for its potential to impact biota downwind of spills on Frenchman Lake playa.« less

Burden of Invasive Nontyphoidal Salmonella Disease in a Rural and Urban Site in Kenya, 2009-2014.

PubMed

Verani, Jennifer R; Toroitich, Samuel; Auko, Joshua; Kiplang'at, Samuel; Cosmas, Leonard; Audi, Allan; Mogeni, Ondari D; Aol, George; Oketch, Dismas; Odiembo, Herine; Katieno, Jim; Wamola, Newton; Onyango, Clayton O; Juma, Bonventure W; Fields, Barry S; Bigogo, Godfrey; Montgomery, Joel M

2015-11-01

Invasive infections with nontyphoidal Salmonella (NTS) lead to bacteremia in children and adults and are an important cause of illness in Africa; however, few data on the burden of NTS bacteremia are available. We sought to determine the burden of invasive NTS disease in a rural and urban setting in Kenya. We conducted the study in a population-based surveillance platform in a rural setting in western Kenya (Lwak), and an informal urban settlement in Nairobi (Kibera) from 2009 to 2014. We obtained blood culture specimens from participants presenting with acute lower respiratory tract illness or acute febrile illness to a designated outpatient facility in each site, or any hospital admission for a potentially infectious cause (rural site only). Incidence was calculated using a defined catchment population and adjusting for specimen collection and healthcare-seeking practices. A total of 12 683 and 9524 blood cultures were analyzed from Lwak and Kibera, respectively. Of these, 428 (3.4%) and 533 (5.6%) grew a pathogen; among those, 208 (48.6%) and 70 (13.1%) were positive for NTS in Lwak and Kibera, respectively. Overall, the adjusted incidence of invasive NTS disease was higher in Lwak (839.4 per 100,000 person-years of observation [PYO]) than in Kibera (202.5 per 100,000 PYO). The highest adjusted incidences were observed in children <5 years of age (Lwak 3914.3 per 100,000 PYO and Kibera 997.9 per 100,000 PYO). The highest adjusted annual incidence was 1927.3 per 100,000 PYO (in 2010) in Lwak and 220.5 per 100,000 PYO (in 2011) in Kibera; the lowest incidences were 303.3 and 62.5 per 100,000 PYO, respectively (in 2012). In both sites, invasive NTS disease incidence generally declined over the study period. We observed an extremely high burden of invasive NTS disease in a rural area of Kenya and a lesser, but still substantial, burden in an urban slum. Although the incidences in both sites declined during the study period, invasive NTS infections remain an important cause of morbidity in these settings, particularly among children <5 years old. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Burden of invasive non-typhoidal Salmonella disease in a rural and urban site in Kenya, 2009–2014

PubMed Central

Verani, Jennifer R.; Toroitich, Samuel; Auko, Joshua; Kiplang’at, Samuel; Cosmas, Leonard; Audi, Allan; Mogeni, Ondari D.; Aol, George; Oketch, Dismas; Odiembo, Herine; Katieno, Jim; Wamola, Newton; Onyango, Clayton O.; Juma, Bonventure W.; Fields, Barry S.; Bigogo, Godfrey; Montgomery, Joel M.

2016-01-01

Background Invasive infections with non-typhoidal Salmonella (NTS) lead to bacteremia in children and adults and are an important cause of illness in Africa; however, few data on the burden of NTS bacteremia are available. We sought to determine the burden of invasive NTS disease in a rural and urban setting in Kenya. Methods We conducted the study in a population-based surveillance platform in a rural setting in western Kenya (Lwak), and an informal urban settlement in Nairobi (Kibera) from 2009 to 2014. We obtained blood culture specimens from participants presenting with acute lower respiratory tract illness, or acute febrile illness to a designated outpatient facility in each site, or any hospital admission for a potentially infectious cause (rural site only). Incidence was calculated using a defined catchment population and adjusting for specimen collection and healthcare seeking practices. Results A total of 12,683 and 9,524 blood cultures were analyzed from Lwak and Kibera, respectively. Of these, 428 (3.4%) and 533 (5.6%) grew a pathogen; among those 208 (48.6%) and 70 (13.1%) were positive for NTS in Lwak and Kibera, respectively. Overall, the adjusted incidence of invasive NTS disease was higher in Lwak (839.4 per 100,000 person-years observation [pyo]) compared with Kibera (202.5 per 100,000 pyo). The highest adjusted incidences were observed in children <5 years of age (Lwak 3,914.3 per 100,000 pyo and Kibera 997.9 per 100,000 pyo). In Lwak the highest adjusted annual incidence was 1,927.3 per 100,000 pyo (in 2010) and in Kibera 220.5 per 100,000 pyo (in 2011); the lowest incidences were 303.3 and 62.5 per 100,000 pyo respectively (in 2012). In both sites, invasive NTS disease incidence generally declined over the study period. Conclusion We observed an extremely high burden of invasive NTS disease in a rural area of Kenya and a lesser, but still substantial, burden in an urban slum. Although the incidences in both sites declined during the study period, invasive NTS infections remain an important cause of morbidity in these settings, particularly among children < 5 years old. PMID:26449945

Prevalence, antimicrobial susceptibility and risk factors associated with non-typhoidal Salmonella on Ugandan layer hen farms.

PubMed

Odoch, Terence; Wasteson, Yngvild; L'Abée-Lund, Trine; Muwonge, Adrian; Kankya, Clovice; Nyakarahuka, Luke; Tegule, Sarah; Skjerve, Eystein

2017-11-29

Non-typhoidal Salmonella (NTS) are among the leading global foodborne pathogens and a significant public health threat. Their occurrence in animal reservoirs and their susceptibilities to commonly used antimicrobials are poorly understood in developing countries. The aim of this study was to estimate the prevalence, determine antimicrobial susceptibility and identify risk factors associated with NTS presence in laying hen farms in Uganda through a cross-sectional study. Pooled faecal samples were collected from 237 laying hen farms and these were analysed for NTS following standard laboratory procedures. In total, 49 farms (20.7%; 95% Confidence interval (CI): 15.6-25.6%) were positive for NTS presence. Altogether, ten Salmonella serotypes were identified among the confirmed 78 isolates, and the predominant serotypes were Salmonella Newport (30.8%), S. Hadar (14.1%), S. Aberdeen (12.8%), S. Heidelberg (12.8%), and S. Bolton (12.8%). Phenotypic antimicrobial resistance was detected in 45(57.7%) of the isolates and the highest resistance was against ciprofloxacin (50.0%) followed by sulphonamides (26.9%) and sulphamethoxazole/trimethoprim (7.7%). Resistance was significantly associated with sampled districts (p = 0.034). Resistance to three or more drugs, multi-drug resistance (MDR) was detected in 12 (15.4%) of the isolates, 9 (75%) of these were from Wakiso district. A multivariable logistic model identified large farm size (OR = 7.0; 95% CI: 2.5-19.8) and the presence of other animal species on the farm (OR = 5.9; 95% CI: 2.1-16.1) as risk factors for NTS prevalence on farms. Having a separate house for birds newly brought to the farms was found to be protective (OR = 0,4; 95% CI: 0.2-0.8). This study has highlighted a high prevalence and diversity of NTS species in laying hen farms in Uganda and identified associated risk factors. In addition, it has demonstrated high levels of antimicrobial resistance in isolates of NTS. This could be because of overuse or misuse of antimicrobials in poultry production. Also importantly, the insights provided in this study justifies a strong case for strengthening One Health practices and this will contribute to the development of NTS control strategies at local, national and international levels.

Serotonin in the solitary tract nucleus shortens the laryngeal chemoreflex in anaesthetized neonatal rats.

PubMed

Donnelly, William T; Bartlett, Donald; Leiter, J C

2016-07-01

What is the central question of this study? Failure to terminate apnoea and arouse is likely to contribute to sudden infant death syndrome (SIDS). Serotonin is deficient in the brainstems of babies who died of SIDS. Therefore, we tested the hypothesis that serotonin in the nucleus of the solitary tract (NTS) would shorten reflex apnoea. What is the main finding and its importance? Serotonin microinjected into the NTS shortened the apnoea and respiratory inhibition associated with the laryngeal chemoreflex. Moreover, this effect was achieved through a 5-HT3 receptor. This is a new insight that is likely to be relevant to the pathogenesis of SIDS. The laryngeal chemoreflex (LCR), an airway-protective reflex that causes apnoea and bradycardia, has long been suspected as an initiating event in the sudden infant death syndrome. Serotonin (5-HT) and 5-HT receptors may be deficient in the brainstems of babies who die of sudden infant death syndrome, and 5-HT seems to be important in terminating apnoeas directly or in causing arousals or as part of the process of autoresuscitation. We hypothesized that 5-HT in the brainstem would limit the duration of the LCR. We studied anaesthetized rat pups between 7 and 21 days of age and made microinjections into the cisterna magna or into the nucleus of the solitary tract (NTS). Focal, bilateral microinjections of 5-HT into the caudal NTS significantly shortened the LCR. The 5-HT1a receptor antagonist, WAY 100635, did not affect the LCR consistently, nor did a 5-HT2 receptor antagonist, ketanserin, alter the duration of the LCR. The 5-HT3 specific agonist, 1-(3-chlorophenyl)-biguanide, microinjected bilaterally into the caudal NTS significantly shortened the LCR. Thus, endogenous 5-HT released within the NTS may curtail the respiratory depression that is part of the LCR, and serotonergic shortening of the LCR may be attributed to activation of 5-HT3 receptors within the NTS. 5-HT3 receptors are expressed presynaptically on C fibre afferents of the superior laryngeal nerve, and serotonergic shortening of the LCR may be mediated presynaptically by enhanced activation of inhibitory interneurons within the NTS. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Thin-walled SnO2 nanotubes functionalized with Pt and Au catalysts via the protein templating route and their selective detection of acetone and hydrogen sulfide molecules

NASA Astrophysics Data System (ADS)

Jang, Ji-Soo; Kim, Sang-Joon; Choi, Seon-Jin; Kim, Nam-Hoon; Hakim, Meggie; Rothschild, Avner; Kim, Il-Doo

2015-10-01

Bio-inspired Pt (~2 nm) and Au (~2.7 nm) catalysts encapsulated by a protein shell, i.e., Pt-apoferritin (Pt@AF) and Au-apoferriten (Au@AF), were synthesized via the hollow protein nanocage (apoferritin) templating route and directly functionalized on the interior and exterior walls of electrospun SnO2 nanotubes (NTs) during controlled single-nozzle electrospinning followed by high temperature calcination with heating rate control. Fast crystallization of the exterior shell and outward diffusion of the interior Sn precursors and crystallites result in the continued growth of a tubular wall, which is related to rapid heating driven Ostwald-ripening behavior. Very importantly, the Pt and Au nanoparticles (NPs) were immobilized onto thin-walled SnO2 NTs with a diameter of ~350 nm and a shell thickness of ~40 nm without any aggregation of catalysts due to high dispersibility, which originated from repulsive electrostatic (Coulombic) forces acting on the surface charged protein shells, leading to an enhanced catalytic effect and outstanding gas sensing properties. Pt-loaded SnO2 NTs exhibited superior acetone response (Rair/Rgas = 92 at 5 ppm) compared to pure SnO2 NFs (Rair/Rgas = 4.8 at 5 ppm) and SnO2 NTs (Rair/Rgas = 11 at 5 ppm) while Au-loaded SnO2 NTs showed a high response when exposed to hydrogen sulfide (Rair/Rgas = 34 at 5 ppm), offering selective gas detection with minimal cross-sensitivity against other interfering gases such as NH3, CO, NO, C6H5CH3, and C5H12. Our results provide a new insight into facile, cost-effective, and highly dispersible catalyst loading on the interior and exterior walls of hollow metal oxide NTs via simple electrospinning as a potential breath analyzer.Bio-inspired Pt (~2 nm) and Au (~2.7 nm) catalysts encapsulated by a protein shell, i.e., Pt-apoferritin (Pt@AF) and Au-apoferriten (Au@AF), were synthesized via the hollow protein nanocage (apoferritin) templating route and directly functionalized on the interior and exterior walls of electrospun SnO2 nanotubes (NTs) during controlled single-nozzle electrospinning followed by high temperature calcination with heating rate control. Fast crystallization of the exterior shell and outward diffusion of the interior Sn precursors and crystallites result in the continued growth of a tubular wall, which is related to rapid heating driven Ostwald-ripening behavior. Very importantly, the Pt and Au nanoparticles (NPs) were immobilized onto thin-walled SnO2 NTs with a diameter of ~350 nm and a shell thickness of ~40 nm without any aggregation of catalysts due to high dispersibility, which originated from repulsive electrostatic (Coulombic) forces acting on the surface charged protein shells, leading to an enhanced catalytic effect and outstanding gas sensing properties. Pt-loaded SnO2 NTs exhibited superior acetone response (Rair/Rgas = 92 at 5 ppm) compared to pure SnO2 NFs (Rair/Rgas = 4.8 at 5 ppm) and SnO2 NTs (Rair/Rgas = 11 at 5 ppm) while Au-loaded SnO2 NTs showed a high response when exposed to hydrogen sulfide (Rair/Rgas = 34 at 5 ppm), offering selective gas detection with minimal cross-sensitivity against other interfering gases such as NH3, CO, NO, C6H5CH3, and C5H12. Our results provide a new insight into facile, cost-effective, and highly dispersible catalyst loading on the interior and exterior walls of hollow metal oxide NTs via simple electrospinning as a potential breath analyzer. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04487a

Fear extinction can be made state-dependent on peripheral epinephrine: role of norepinephrine in the nucleus tractus solitarius.

PubMed

Rosa, Jessica; Myskiw, Jociane C; Furini, Cristiane R G; Sapiras, Gerson G; Izquierdo, Ivan

2014-09-01

We investigate whether the extinction of inhibitory avoidance (IA) learning can be subjected to endogenous state-dependence with systemic injections of epinephrine (E), and whether endogenous norepinephrine (NE) and the nucleus tractus solitarius (NTS)→locus coeruleus→hippocampus/amygdala (HIPP/BLA) pathway participate in this. Rats trained in IA were submitted to two sessions of extinction 24 h apart: In the first, the animals were submitted to a training session of extinction, and in the second they were tested for the retention of extinction. Saline or E were given i.p. immediately after the extinction training (post-extinction training injections) and/or 6 min before the extinction test (pre-extinction test). Post-extinction training E (50 or 100 μg/kg) induced a poor retrieval of extinction in the test session of this task unless an additional E injection (50 μg/kg) was given prior to the extinction test. This suggested state-dependence. Muscimol (0.01 μg/side) microinfused into the NTS prior to the extinction test session blocked E-induced state-dependence. Norepinephrine (NE, 1 μg/side) infused bilaterally into NTS restores the extinction impairment caused by post-extinction training i.p. E. In animals with bilateral NTS blockade induced by muscimol, NE (1 μg/side) given prior to the extinction test into the CA1 region of the dorsal hippocampus or into the basolateral amygdala restored the normal extinction levels that had been impaired by muscimol. These results suggest a role for the NTS→locus coeruleus→HIPP/BLA pathway in the retrieval of extinction, as it has been shown to have in the consolidation of inhibitory avoidance and of object recognition learning. Copyright © 2013 Elsevier Inc. All rights reserved.

Activation of hindbrain neurons in response to gastrointestinal lipid is attenuated by high fat, high energy diets in mice prone to diet-induced obesity.

PubMed

Donovan, Michael J; Paulino, Gabriel; Raybould, Helen E

2009-01-12

Food intake is controlled by peripheral signals from the gastrointestinal tract and adipocytes, which are integrated within the central nervous system. There is evidence that signals from the GI tract are modulated by long term changes in diet, possibly leading to hyperphagia and increased body weight. We tested the hypothesis that diet-induced obese-prone (DIO-P) and obese-resistant (DIO-R) mice strains differ in the long term adaptive response of the gut-brain pathway to a high fat diet. Immunochemical detection of Fos protein was used as a measure of neuronal activation in the nucleus of the solitary tract (NTS) in response to intragastric administration of lipid in DIO-P (C57Bl6) and DIO-R (129sv) mouse strains maintained on chow or high fat, high energy diets (45% or 60% kcal from fat). Intragastric lipid administration activated neurons in the NTS in both DIO-P and DIO-R mice; the number of activated neurons was significantly greater in DIO-P than in DIO-R mice (P<0.001). However, lipid-induced activation of NTS neurons in DIO-P mice was attenuated by approximately 30% after maintenance on either 45% or 60% HF diet, for 4 or 8 weeks, compared to chow fed controls (P<0.05). In contrast, in DIO-R mice, maintenance on a HF diet (45% or 60%) had no effect on lipid-induced activation of NTS neurons. These results demonstrate that DIO-P and DIO-R mice strains differ in the adaptation of the pathway to long term ingestion of high fat diets, which may contribute to decrease satiation and increased food intake.

The nucleus raphe magnus suppresses vomiting, and the solitary nucleus and 5-HT are not involved in this suppression.

PubMed

Hattori, Yuka; Hamaguchi, Chie; Yamada, Yuko; Urayama, Yukiko; Nakamura, Emi; Koga, Tomoshige; Fukuda, Hiroyuki

2010-01-15

In previous paper, we reported that stimulation of the nucleus raphe magnus (stim-NRM) inhibits the induction of retching by afferent vagal fibers (VAs). We performed the present study to identity the transmitter of inhibition and then the site. The following results were obtained in decerebrated and paralyzed dogs. 1) The induction of fictive retching was suppressed by i.v. injection of 5-HT, and by 4th ventricular administration of 5-HT or a 5-HT3-receptor (R) agonist, 1-(m-chlorophenyl)-biguanade hydrochloride (m-CPBG). 2) Both forms of suppression were antagonized by i.v. injection of ondansetron, a 5-HT3-R antagonist. 3) Administration of the antagonist into the 4th ventricle did not affect the induction or its suppression by stim-NRM. These results suggest that the transmission from VAs to neurons in the nucleus solitarius (NTS) is suppressed by 5-HT via 5-HT3-R. However, these results also suggest that both the transmitter and receptor are not involved in the induction of retching by VAs or in its suppression by the NRM. Next, we examined the site of suppression. Unitary firings of NTS neurons in response to pulse-train stimulation of VAs were not inhibited by NRM stimulation. Moreover, the firing of NTS neurons during the induction of retching by vagal stimulation did not significantly decrease with the superimposition of stim-NRM, although the induction of retching was completely suppressed. These results suggest that suppression of the induction of retching by the descending inhibitory system of pain did not occur in the synapse between afferent vagal fibers and NTS neurons. The site of suppression is discussed.

Glutamate receptors in the nucleus tractus solitarius contribute to ventilatory acclimatization to hypoxia in rat

PubMed Central

Pamenter, Matthew E; Carr, J Austin; Go, Ariel; Fu, Zhenxing; Reid, Stephen G; Powell, Frank L

2014-01-01

When exposed to a hypoxic environment the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time-dependent increase in ventilation occurs, which increases the HVR. This secondary increase persists after exposure to CSH and involves plasticity within the circuits in the central nervous system that control breathing. Currently these mechanisms of HVR plasticity are unknown and we hypothesized that they involve glutamatergic synapses in the nucleus tractus solitarius (NTS), where afferent endings from arterial chemoreceptors terminate. To test this, we treated rats held in normoxia (CON) or 10% O2 (CSH) for 7 days and measured ventilation in conscious, unrestrained animals before and after microinjecting glutamate receptor agonists and antagonists into the NTS. In normoxia, AMPA increased ventilation 25% and 50% in CON and CSH, respectively, while NMDA doubled ventilation in both groups (P < 0.05). Specific AMPA and NMDA receptor antagonists (NBQX and MK801, respectively) abolished these effects. MK801 significantly decreased the HVR in CON rats, and completely blocked the acute HVR in CSH rats but had no effect on ventilation in normoxia. NBQX decreased ventilation whenever it was increased relative to normoxic controls; i.e. acute hypoxia in CON and CSH, and normoxia in CSH. These results support our hypothesis that glutamate receptors in the NTS contribute to plasticity in the HVR with CSH. The mechanism underlying this synaptic plasticity is probably glutamate receptor modification, as in CSH rats the expression of phosphorylated NR1 and GluR1 proteins in the NTS increased 35% and 70%, respectively, relative to that in CON rats. PMID:24492841

Glutamate receptors in the nucleus tractus solitarius contribute to ventilatory acclimatization to hypoxia in rat.

PubMed

Pamenter, Matthew E; Carr, J Austin; Go, Ariel; Fu, Zhenxing; Reid, Stephen G; Powell, Frank L

2014-04-15

When exposed to a hypoxic environment the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time-dependent increase in ventilation occurs, which increases the HVR. This secondary increase persists after exposure to CSH and involves plasticity within the circuits in the central nervous system that control breathing. Currently these mechanisms of HVR plasticity are unknown and we hypothesized that they involve glutamatergic synapses in the nucleus tractus solitarius (NTS), where afferent endings from arterial chemoreceptors terminate. To test this, we treated rats held in normoxia (CON) or 10% O2 (CSH) for 7 days and measured ventilation in conscious, unrestrained animals before and after microinjecting glutamate receptor agonists and antagonists into the NTS. In normoxia, AMPA increased ventilation 25% and 50% in CON and CSH, respectively, while NMDA doubled ventilation in both groups (P < 0.05). Specific AMPA and NMDA receptor antagonists (NBQX and MK801, respectively) abolished these effects. MK801 significantly decreased the HVR in CON rats, and completely blocked the acute HVR in CSH rats but had no effect on ventilation in normoxia. NBQX decreased ventilation whenever it was increased relative to normoxic controls; i.e. acute hypoxia in CON and CSH, and normoxia in CSH. These results support our hypothesis that glutamate receptors in the NTS contribute to plasticity in the HVR with CSH. The mechanism underlying this synaptic plasticity is probably glutamate receptor modification, as in CSH rats the expression of phosphorylated NR1 and GluR1 proteins in the NTS increased 35% and 70%, respectively, relative to that in CON rats.

An Apprenticeship Rotation Teaches Chief Residents Nontechnical Skills and ACGME Core Competencies.

PubMed

Kwakye, Gifty; Chen, Xiaodong Phoenix; Havens, Joaquim M; Irani, Jennifer L; Yule, Steven; Smink, Douglas S

2015-01-01

Traditionally, surgical training has used an apprenticeship model but has more recently moved to a service-based model, with groups of residents working with groups of attending surgeons. We developed an apprenticeship rotation to enhance one-on-one interaction between chief residents and selected faculty. We hypothesized that the apprenticeship rotation would be effective for teaching nontechnical skills (NTS) and core competencies. An apprenticeship rotation was created at a university-based surgery residency in which each chief resident selected a single attending surgeon with whom to work exclusively with for a 4-week period. Emphasis was placed on teaching intraoperative NTS as well as the 4 difficult-to-teach Accreditation Council for Graduate Medical Education core competencies (DCC): Interpersonal and Communication Skills, Practice-Based Learning and Improvement, Professionalism, and Systems-Based Practice. Participants were surveyed afterwards about their rotation using a 5-point Likert scale. A Wilcoxon signed rank test was used to compare differences depending on data distribution. All (13/13) the chief residents and 67% (8/12) faculty completed the survey. Overall, 85% of residents and 87.5% of faculty would recommend the rotation to other residents/faculty members. Both residents and faculty reported improvement in trainees' technical skills and NTS. Residents reported improvement in all 4 DCC, particularly, Practice-Based Learning and Improvement, Professionalism, and Interpersonal and Communication Skills. The apprenticeship rotation is an effective means of teaching residents both NTS and DCC essential for independent practice. Consideration should be given to introducing this program into surgical curricula nationally. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Surface modification of thin film composite membrane by nanoporous titanate nanoparticles for improving combined organic and inorganic antifouling properties.

PubMed

Emadzadeh, D; Ghanbari, M; Lau, W J; Rahbari-Sisakht, M; Rana, D; Matsuura, T; Kruczek, B; Ismail, A F

2017-06-01

In this study, nanoporous titanate (NT) nanoparticle synthesized by the solvothermal method was used to modify polyamide layer of thin film composite membranes with the aim of improving membrane resistances against organic and inorganic fouling. Thin film nanocomposite membranes (NMs) were synthesized by adding mNTs (modified nanoparticles) into polyamide selective layer followed by characterization using different analytical instruments. The results of XPS and XRD confirmed the presence of mNTs in the polyamide layer of NMs, while FESEM, AFM, zeta potential and contact angle measurement further supported the changes in physical and chemical properties of the membrane surface upon mNTs incorporation. Results of fouling showed that NM1 (the membrane incorporated with 0.01w/v% mNTs) always demonstrated lower degree of flux decline compared to the control membrane when membranes were tested with organic, inorganic and multicomponent synthesized water, brackish water or seawater. Besides showing greater antifouling resistance, the NM also displayed significantly higher water flux compared to the control M membrane. The findings of this work confirmed the positive impact of mNTs in improving the properties of NM with respect to fouling mitigation and flux improvement. Copyright © 2017. Published by Elsevier B.V.

Role of neurotrophic factors in attention deficit hyperactivity disorder.

PubMed

Tsai, Shih-Jen

2017-04-01

Neurotrophins (NTs), a family of proteins including nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4, are essential for neural growth, survival, and differentiation, and are therefore crucial for brain development. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by problems of inattention and/or hyperactivity-impulsivity. ADHD is one of the most common childhood onset psychiatric disorders. Studies have suggested that both genetic and environmental factors influence the development of the disorder, although the precise causes of ADHD have not yet been identified. In this review, we assess the role of NTs in the pathophysiology of ADHD. Preclinical evidence indicates that BDNF knockout mice are hyperactive, and an ADHD rodent model exhibited decreased cerebral BDNF levels. Several lines of evidence from clinical studies, including blood level and genetic studies, have suggested that NTs are involved in the pathogenesis of ADHD and in the mechanism of biological treatments for ADHD. Future directions for research are proposed, such as using blood NTs as ADHD biomarkers, optimizing NT genetic studies in ADHD, considering NTs as a link between ADHD and other comorbid mental disorders, and investigating methods for optimally modulating NT signaling to discover novel therapeutics for treating ADHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tuning Nanowires and Nanotubes for Efficient Fuel-Cell Electrocatalysis.

PubMed

Wang, Wei; Lv, Fan; Lei, Bo; Wan, Sheng; Luo, Mingchuan; Guo, Shaojun

2016-12-01

Developing new synthetic methods for the controlled synthesis of Pt-based or non-Pt nanocatalysts with low or no Pt loading to facilitate sluggish cathodic oxygen reduction reaction (ORR) and organics oxidation reactions is the key in the development of fuel-cell technology. Various nanoparticles (NPs), with a range of size, shape, composition, and structure, have shown good potential to catalyze the sluggish cathodic and anodic reactions. In contrast to NPs, one-dimensional (1D) nanomaterials such as nanowires (NWs), and nanotubes (NTs), exhibit additional advantages associated with their anisotropy, unique structure, and surface properties. The prominent characteristics of NWs and NTs include fewer lattice boundaries, a lower number of surface defect sites, and easier electron and mass transport for better electrocatalytic activity and lower vulnerability to dissolution, Ostwald ripening, and aggregation than Pt NPs for enhanced stability. An overview of recent advances in tuning 1D nanostructured Pt-based, Pd-based, or 1D metal-free nanomaterials as advanced electrocatalysts is provided here, for boosting fuel-cell reactions with high activity and stability, including the oxygen reduction reaction (ORR), methanol oxidation reaction (MOR), and ethanol oxidation reaction (EOR). After highlighting the different strategies developed so far for the synthesis of Pt-based 1D nanomaterials with controlled size, shape, and composition, special emphasis is placed on the rational design of diverse NWs and NTs catalysts such as Pt-based NWs or NTs, non-Pt NTs, and carbon NTs with molecular engineering, etc. for enhancing the ORR, MOR, and EOR. Finally, some perspectives are highlighted on the development of more efficient fuel-cell electrocatalysts featuring high stability, low cost, and enhanced performance, which are the key factors in accelerating the commercialization of fuel-cell technology. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Monosynaptic inputs from the nucleus tractus solitarii to the laryngeal motoneurons in the nucleus ambiguus of the rat.

PubMed

Hayakawa, T; Takanaga, A; Maeda, S; Ito, H; Seki, M

2000-11-01

The cricothyroid (CT) and the posterior cricoarytenoid (PCA) muscles in the larynx are activated by the laryngeal motoneurons located within the nucleus ambiguus; these motoneurons receive the laryngeal sensory information from the nucleus tractus solitarii (NTS) during respiration and swallowing. We investigated whether the neurons in the NTS projected directly to the laryngeal motoneurons, and what is the synaptic organization of their nerve terminals on the laryngeal motoneurons using the electron microscope. When wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the NTS after cholera toxin subunit B-conjugated HRP (CT-HRP) was injected into the CT muscle or the PCA muscle, the anterogradely WGA-HRP-labeled terminals from the NTS were found to directly contact the retrogradely CT-HRP-labeled dendrites and soma of both the CT and the PCA motoneurons. The labeled NTS terminals comprised about 4% of the axosomatic terminals in a section through the CT motoneurons, and about 9% on both the small (PCA-A) and the large (PCA-B) PCA motoneurons. The number of labeled axosomatic terminals containing round vesicles and making asymmetric synaptic contacts (Gray's type I) was almost equal to that of the labeled terminals containing pleomorphic vesicles and making symmetric synaptic contacts (Gray's type II) on the CT motoneurons. The labeled axosomatic terminals were mostly Gray's type II on the PCA-A motoneurons, while the majority of them were Gray's type I on the PCA-B motoneurons. These results indicate that the laryngeal CT and PCA motoneurons receive a few direct excitatory and inhibitory inputs from the neurons in the NTS.

Extracellular synthesis gold nanotriangles using biomass of Streptomyces microflavus.

PubMed

Soltani Nejad, Meysam; Khatami, Mehrdad; Shahidi Bonjar, Gholam Hosein

2016-02-01

Applications of nanotechnology and nano-science have ever-expanding breakthroughs in medicine, agriculture and industries in recent years; therefore, synthesis of metals nanoparticle (NP) has special significance. Synthesis of NPs by chemical methods are long, costly and hazardous for environment so biosynthesis has been developing interest for researchers. In this regard, the extracellular biosynthesis of gold nanotriangles (AuNTs) performed by use of the soil Streptomycetes. Streptomycetes isolated from rice fields of Guilan Province, Iran, showed biosynthetic activity for producing AuNTs via in vitro experiments. Among all 15 Streptomyces spp. isolates, isolate No. 5 showed high biosynthesis activity. To determine the bacterium taxonomical identity at genus level, its colonies characterised morphologically by use of scanning electron microscope. The polymerase chain reaction (PCR) molecular analysis of active isolate represented its identity partially. In this regard, 16S rRNA gene of the isolate was amplified using universal bacterial primers FD1 and RP2. The PCR products were purified and sequenced. Sequence analysis of 16S rDNA was then conducted using National Center for Biotechnology Information Basic Local Alignment Search Tool method. The AuNTs obtained were characterised by ultraviolet-visible spectroscopy, atomic force microscopy, transmission electron microscopy and energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction spectroscopy analyses. The authors results indicated that Streptomyces microflavus isolate 5 bio-synthesises extracellular AuNTs in the range of 10-100 nm. Synthesised SNPs size ranged from 10 to 100 nm. In comparison with chemical methods for synthesis of metal NPs, the biosynthesis of AuNTs by Streptomyces source is a fast, simple and eco-friendly method. The isolate is a good candidate for further investigations to optimise its production efficacy for further industrial goals in biosynthesis of AuNTs.

Metabolome analysis of esophageal cancer tissues using capillary electrophoresis-time-of-flight mass spectrometry.

PubMed

Tokunaga, Masanori; Kami, Kenjiro; Ozawa, Soji; Oguma, Junya; Kazuno, Akihito; Miyachi, Hayato; Ohashi, Yoshiaki; Kusuhara, Masatoshi; Terashima, Masanori

2018-06-01

Reports of the metabolomic characteristics of esophageal cancer are limited. In the present study, we thus conducted metabolome analysis of paired tumor tissues (Ts) and non-tumor esophageal tissues (NTs) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The Ts and surrounding NTs were surgically excised pair-wise from 35 patients with esophageal cancer. Following tissue homogenization and metabolite extraction, a total of 110 compounds were absolutely quantified by CE-TOFMS. We compared the concentrations of the metabolites between Ts and NTs, between pT1 or pT2 (pT1-2) and pT3 or pT4 (pT3-4) stage, and between node-negative (pN-) and node-positive (pN+) samples. Principal component analysis and hierarchical clustering analysis revealed clear metabolomic differences between Ts and NTs. Lactate and citrate levels in Ts were significantly higher (P=0.001) and lower (P<0.001), respectively, than those in NTs, which corroborated with the Warburg effect in Ts. The concentrations of most amino acids apart from glutamine were higher in Ts than in NTs, presumably due to hyperactive glutaminolysis in Ts. The concentrations of malic acid (P=0.015) and citric acid (P=0.008) were significantly lower in pT3-4 than in pT1-2, suggesting the downregulation of tricarboxylic acid (TCA) cycle activity in pT3-4. On the whole, in this study, we demonstrate significantly different metabolomic characteristics between tumor and non-tumor tissues and identified a novel set of metabolites that were strongly associated with the degree of tumor progression. A further understanding of cancer metabolomics may enable the selection of more appropriate treatment strategies, thereby contributing to individualized medicine.

O-Serotype Conversion in Salmonella Typhimurium Induces Protective Immune Responses against Invasive Non-Typhoidal Salmonella Infections.

PubMed

Li, Pei; Liu, Qing; Luo, Hongyan; Liang, Kang; Yi, Jie; Luo, Ying; Hu, Yunlong; Han, Yue; Kong, Qingke

2017-01-01

Salmonella infections remain a big problem worldwide, causing enteric fever by Salmonella Typhi (or Paratyphi) or self-limiting gastroenteritis by non-typhoidal Salmonella (NTS) in healthy individuals. NTS may become invasive and cause septicemia in elderly or immuno-compromised individuals, leading to high mortality and morbidity. No vaccines are currently available for preventing NTS infection in human. As these invasive NTS are restricted to several O-antigen serogroups including B1, D1, C1, and C2, O-antigen polysaccharide is believed to be a good target for vaccine development. In this study, a strategy of O-serotype conversion was investigated to develop live attenuated S . Typhimurium vaccines against the major serovars of NTS infections. The immunodominant O4 serotype of S . Typhimurium was converted into O9, O7, and O8 serotypes through unmarked chromosomal deletion-insertion mutations. O-serotype conversion was confirmed by LPS silver staining and western blotting. All O-serotype conversion mutations were successfully introduced into the live attenuated S . Typhimurium vaccine S738 (Δ crp Δ cya ) to evaluate their immunogenicity in mice model. The vaccine candidates induced high amounts of heterologous O-polysaccharide-specific functional IgG responses. Vaccinated mice survived a challenge of 100 times the 50% lethality dose (LD 50 ) of wild-type S . Typhimurium. Protective efficacy against heterologous virulent Salmonella challenges was highly O-serotype related. Furthermore, broad-spectrum protection against S . Typhimurium, S . Enteritidis, and S . Choleraesuis was observed by co-vaccination of O9 and O7 O-serotype-converted vaccine candidates. This study highlights the strategy of expressing heterologous O-polysaccharides via genetic engineering in developing live attenuated S . Typhimurium vaccines against NTS infections.

Nevada Test Site annual site environmental report for calendar year 1996

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

Black, S.C.; Townsend, Y.E.

1997-10-01

Monitoring and surveillance on and around the Nevada Test Site (NTS) by US Department of Energy (DOE) contractors and NTS user organizations during 1996 indicated that operations on the NTS were conducted in compliance with applicable DOE, state, and federal regulations and guidelines. All discharges of radioactive liquids remained onsite in containment ponds, and there was no indication of potential migration of radioactivity to the offsite area through groundwater. Surveillance around the NTS indicated that airborne radioactivity from diffusion, evaporation of liquid effluents, or resuspension of soil was not detectable offsite, and exposure above background to members of the offsitemore » population was not measured by the offsite monitoring program. Using the US Environmental Protection Agency`s (EPA) Clean Air Package 1988 (CAP88)PC model and NTS radionuclide emissions and environmental monitoring data, the calculated effective dose equivalent (EDE) to the maximally exposed individual offsite would have been 0.11 mrem. This value is less than 2 percent of the federal dose limit prescribed for radionuclide air emissions. Any person receiving this dose would also have received 144 mrem from natural background radiation. There were no nonradiological releases to the offsite area. Hazardous wastes were shipped offsite to approved disposal facilities. Compliance with the various regulations stemming from the National Environmental Policy Act (NEPA) is being achieved and, where mandated, permits for air and water effluents and waste management have been obtained from the appropriate agencies. Cooperation with other agencies has resulted in seven different consent orders and agreements. Support facilities at off-NTS locations have complied with the requirements of air quality permits and state or local wastewater discharge and hazardous waste permits as mandated for each location.« less

Kv4 channels underlie A-currents with highly variable inactivation time courses but homogeneous other gating properties in the nucleus tractus solitarii.

PubMed

Strube, Caroline; Saliba, Layal; Moubarak, Estelle; Penalba, Virginie; Martin-Eauclaire, Marie-France; Tell, Fabien; Clerc, Nadine

2015-04-01

In the nucleus of the tractus solitarii (NTS), a large proportion of neurones express transient A-type potassium currents (I KA) having deep influence on the fidelity of the synaptic transmission of the visceral primary afferent inputs to second-order neurones. Up to now, the strong impact of I KA within the NTS was considered to result exclusively from its variation in amplitude, and its molecular correlate(s) remained unknown. In order to identify which Kv channels underlie I KA in NTS neurones, the gating properties and the pharmacology of this current were determined using whole cell patch clamp recordings in slices. Complementary information was brought by immunohistochemistry. Strikingly, two neurone subpopulations characterized by fast or slow inactivation time courses (respectively about 50 and 200 ms) were discriminated. Both characteristics matched those of the Kv4 channel subfamily. The other gating properties, also matching the Kv4 channel ones, were homogeneous through the NTS. The activation and inactivation occurred at membrane potentials around the threshold for generating action potentials, and the time course of recovery from inactivation was rapid. Pharmacologically, I KA in NTS neurones was found to be resistant to tetraethylammonium (TEA), sea anemone toxin blood-depressing substance (BDS) and dendrotoxin (DTX), whereas Androctonus mauretanicus mauretanicus toxin 3 (AmmTX3), a scorpion toxin of the α-KTX 15 family that has been shown to block all the members of the Kv4 family, inhibited 80 % of I KA irrespectively of its inactivation time course. Finally, immunohistochemistry data suggested that, among the Kv4 channel subfamily, Kv4.3 is the prevalent subunit expressed in the NTS.

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

Chen, K.; Tsai, H.; Decision and Information Sciences

The technical basis for extending the Model 9977 shipping package periodic maintenance beyond the one-year interval to a maximum of five years is based on the performance of the O-ring seals and the environmental conditions. The DOE Packaging Certification Program (PCP) has tasked Argonne National Laboratory to develop a Radio-Frequency Identification (RFID) temperature monitoring system for use by the facility personnel at DAF/NTS. The RFID temperature monitoring system, depicted in the figure below, consists of the Mk-1 RFId tags, a reader, and a control computer mounted on a mobile platform that can operate as a stand-alone system, or it canmore » be connected to the local IT network. As part of the Conditions of Approval of the CoC, the user must complete the prescribed training to become qualified and be certified for operation of the RFID temperature monitoring system. The training course will be administered by Argonne National Laboratory on behalf of the Headquarters Certifying Official. This is a complete documentation package for the RFID temperature monitoring system of the Model 9977 packagings at NTS. The documentation package will be used for training and certification. The table of contents are: Acceptance Testing Procedure of MK-1 RFID Tags for DOE/EM Nuclear Materials Management Applications; Acceptance Testing Result of MK-1 RFID Tags for DOE/EM Nuclear Materials Management Applications; Performance Test of the Single Bolt Seal Sensor for the Model 9977 Packaging; Calibration of Built-in Thermistors in RFID Tags for Nevada Test Site; Results of Calibration of Built-in Thermistors in RFID Tags; Results of Thermal Calibration of Second Batch of MK-I RFID Tags; Procedure for Installing and Removing MK-1 RFID Tag on Model 9977 Drum; User Guide for RFID Reader and Software for Temperature Monitoring of Model 9977 Drums at NTS; Software Quality Assurance Plan (SQAP) for the ARG-US System; Quality Category for the RFID Temperature Monitoring System; The Documentation Package for the RFID Temperature Monitoring System; Software Test Plan and Results for ARG-US OnSite; Configuration Management Plan (CMP) for the ARG-US System; Requirements Management Plan for the ARG-US System; and Design Management Plan for ARG-US.« less

Phenotypical resistance correlation networks for 10 non-typhoidal Salmonella subpopulations in an active antimicrobial surveillance programme.

PubMed

Love, W J; Zawack, K A; Booth, J G; Gröhn, Y T; Lanzas, C

2018-06-01

Antimicrobials play a critical role in treating cases of invasive non-typhoidal salmonellosis (iNTS) and other diseases, but efficacy is hindered by resistant pathogens. Selection for phenotypical resistance may occur via several mechanisms. The current study aims to identify correlations that would allow indirect selection of increased resistance to ceftriaxone, ciprofloxacin and azithromycin to improve antimicrobial stewardship. These are medically important antibiotics for treating iNTS, but these resistances persist in non-Typhi Salmonella serotypes even though they are not licensed for use in US food animals. A set of 2875 Salmonella enterica isolates collected from animal sources by the National Antimicrobial Resistance Monitoring System were stratified in to 10 subpopulations based on serotype and host species. Collateral resistances in each subpopulation were estimated as network models of minimum inhibitory concentration partial correlations. Ceftriaxone sensitivity was correlated with other β-lactam resistances, and less commonly resistances to tetracycline, trimethoprim-sulfamethoxazole or kanamycin. Azithromycin resistance was frequently correlated with chloramphenicol resistance. Indirect selection for ciprofloxacin resistance via collateral selection appears unlikely. Density of the ACSSuT subgraph resistance aligned well with the phenotypical frequency. The current study identifies several important resistances in iNTS serotypes and further research is needed to identify the causative genetic correlations.

An optimized method for neurotransmitters and their metabolites analysis in mouse hypothalamus by high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry.

PubMed

Yang, Zong-Lin; Li, Hui; Wang, Bing; Liu, Shu-Ying

2016-02-15

Neurotransmitters (NTs) and their metabolites are known to play an essential role in maintaining various physiological functions in nervous system. However, there are many difficulties in the detection of NTs together with their metabolites in biological samples. A new method for NTs and their metabolites detection by high performance liquid chromatography coupled with Q Exactive hybrid quadruple-orbitrap high-resolution accurate mass spectrometry (HPLC-HRMS) was established in this paper. This method was a great development of the applying of Q Exactive MS in the quantitative analysis. This method enabled a rapid quantification of ten compounds within 18min. Good linearity was obtained with a correlation coefficient above 0.99. The concentration range of the limit of detection (LOD) and the limit of quantitation (LOQ) level were 0.0008-0.05nmol/mL and 0.002-25.0nmol/mL respectively. Precisions (relative standard deviation, RSD) of this method were at 0.36-12.70%. Recovery ranges were between 81.83% and 118.04%. Concentrations of these compounds in mouse hypothalamus were detected by Q Exactive LC-MS technology with this method. Copyright © 2016 Elsevier B.V. All rights reserved.

Detecting Anthrax, Botulinum Toxin, and Ricin – Immunoassay Test Strips

EPA Pesticide Factsheets

This assay is listed as Tier I for presumptive analysis of BoNTs in drinking water samples and Tier II for presumptive analysis of BoNTs in other environmental sample types. The lateral flow immunochromatographic assay uses two antibodies in combination to

The Need for an Information Communication and Advocacy Strategy to Guide a Research Agenda to Address Burden of Invasive Nontyphoidal Salmonella Infections in Africa.

PubMed

Imran Khan, M; Freeman, Alexander J; Gessner, Bradford D; Sahastrabuddhe, Sushant

2015-11-01

Invasive nontyphoidal salmonellosis (iNTS) is often not recognized clinically, and prevention of iNTS is largely ignored by policy planners and decision makers. During 2010, an estimated 3.4 million cases and 681,316 deaths occurred worldwide due to iNTS, with the largest estimated disease burden in resource-limited areas of sub-Saharan Africa. These figures likely underestimate global burden for several reasons, further complicating efforts to raise awareness of iNTS. To increase disease recognition and facilitate development of interventions, a communication and advocacy plan should be developed and implemented by actors in different sectors of global health, including researchers and scientists, funders, vaccine manufacturers, civil society organizations, and government officials from highly affected countries. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Immunology, epidemiology and mathematical modelling towards a better understanding of invasive non-typhoidal Salmonella disease and rational vaccination approaches.

PubMed

Mastroeni, Pietro; Rossi, Omar

2016-12-01

Invasive non-typhoidal Salmonella (iNTS) infections cause a high burden of lethal sepsis in young children and HIV patients, often associated with malaria, anaemia, malnutrition and sickle-cell disease. Vaccines against iNTS are urgently needed but none are licensed yet. Areas covered: This review illustrates how immunology, epidemiology and within-host pathogen behaviour affect invasive Salmonella infections and highlights how this knowledge can assist the improvement and choice of vaccines. Expert Commentary: Control of iNTS disease requires approaches that reduce transmission and improve diagnosis and treatment. These are often difficult to implement due to the fragile ecology and economies in endemic countries. Vaccines will be key tools in the fight against iNTS disease. To optimise vaccine design, we need to better define protective antigens and mechanisms of resistance to disease in susceptible populations even in those individuals where innate immunity may be impaired by widespread comorbidities.

The Receptor Binding Domain of Botulinum Neurotoxin Stereotype C Binds Phosphoinositides

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

Zhang, Yanfeng; Varnum, Susan M.

2012-03-01

Botulinum neurotoxins (BoNTs) are the most toxic proteins known for humans and animals with an extremely low LD50 of {approx} 1 ng/kg. BoNTs generally require a protein and a ganglioside on the cell membrane surface for binding, which is known as a 'dual receptor' mechanism for host intoxication. Recent studies have suggested that in addition to gangliosides, other membrane lipids such as phosphoinositides may be involved in the interactions with the receptor binding domain (HCR) of BoNTs for better membrane penetration. Here, using two independent lipid-binding assays, we tested the interactions of BoNT/C-HCR with lipids in vitro. BoNT/C-HCR was foundmore » to bind negatively charged phospholipids, preferentially phosphoinositides. Additional interactions to phosphoinositides may help BoNT/C bind membrane more tightly and transduct signals for subsequent steps of intoxication. Our results provide new insights into the mechanisms of host cell membrane recognition by BoNTs.« less

The Neurotensin Receptor-1 Pathway Contributes to Human Ductal Breast Cancer Progression

PubMed Central

Dupouy, Sandra; Viardot-Foucault, Véronique; Alifano, Marco; Souazé, Frédérique; Plu-Bureau, Geneviève; Chaouat, Marc; Lavaur, Anne; Hugol, Danielle; Gespach, Christian

2009-01-01

Background The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. Methods and Results we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. Conclusion these data support the activation of neurotensinergic deleterious pathways in breast cancer progression. PMID:19156213

The neurotensin receptor-1 pathway contributes to human ductal breast cancer progression.

PubMed

Dupouy, Sandra; Viardot-Foucault, Véronique; Alifano, Marco; Souazé, Frédérique; Plu-Bureau, Geneviève; Chaouat, Marc; Lavaur, Anne; Hugol, Danielle; Gespach, Christian; Gompel, Anne; Forgez, Patricia

2009-01-01

The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

Neuronal modelling of baroreflex response to orthostatic stress

NASA Astrophysics Data System (ADS)

Samin, Azfar

The accelerations experienced in aerial combat can cause pilot loss of consciousness (GLOC) due to a critical reduction in cerebral blood circulation. The development of smart protective equipment requires understanding of how the brain processes blood pressure (BP) information in response to acceleration. We present a biologically plausible model of the Baroreflex to investigate the neural correlates of short-term BP control under acceleration or orthostatic stress. The neuronal network model, which employs an integrate-and-fire representation of a biological neuron, comprises the sensory, motor, and the central neural processing areas that form the Baroreflex. Our modelling strategy is to test hypotheses relating to the encoding mechanisms of multiple sensory inputs to the nucleus tractus solitarius (NTS), the site of central neural processing. The goal is to run simulations and reproduce model responses that are consistent with the variety of available experimental data. Model construction and connectivity are inspired by the available anatomical and neurophysiological evidence that points to a barotopic organization in the NTS, and the presence of frequency-dependent synaptic depression, which provides a mechanism for generating non-linear local responses in NTS neurons that result in quantifiable dynamic global baroreflex responses. The entire physiological range of BP and rate of change of BP variables is encoded in a palisade of NTS neurons in that the spike responses approximate Gaussian 'tuning' curves. An adapting weighted-average decoding scheme computes the motor responses and a compensatory signal regulates the heart rate (HR). Model simulations suggest that: (1) the NTS neurons can encode the hydrostatic pressure difference between two vertically separated sensory receptor regions at +Gz, and use changes in that difference for the regulation of HR; (2) even though NTS neurons do not fire with a cardiac rhythm seen in the afferents, pulse-rhythmic activity is regained downstream provided the input phase information in preserved centrally; (3) frequency-dependent synaptic depression, which causes temporal variations in synaptic strength due to changes in input frequency, is a possible mechanism of non-linear dynamic baroreflex gain control. Synaptic depression enables the NTS neuron to encode dBP/dt but to lose information about the steady state firing of the afferents.

Microinjection of kynurenic acid in the rostral nucleus of the tractus solitarius disrupts spatiotemporal aspects of mechanically induced tracheobronchial cough.

PubMed

Poliacek, Ivan; Pitts, Teresa; Rose, Melanie J; Davenport, Paul W; Simera, Michal; Veternik, Marcel; Kotmanova, Zuzana; Bolser, Donald C

2017-06-01

The importance of neurons in the nucleus of the solitary tract (NTS) in the production of coughing was tested by microinjections of the nonspecific glutamate receptor antagonist kynurenic acid (kyn; 100 mM in artificial cerebrospinal fluid) in 15 adult spontaneously breathing anesthetized cats. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airway. Electromyograms (EMG) were recorded from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles. Bilateral microinjections of kyn into the NTS rostral to obex [55 ± 4 nl total in 2 locations ( n = 6) or 110 ± 4 nl total in 4 locations ( n = 5)], primarily the ventrolateral subnucleus, reduced cough number and expiratory cough efforts (amplitudes of ABD EMG and maxima of esophageal pressure) compared with control. These microinjections also markedly prolonged the inspiratory phase, all cough-related EMG activation, and the total cough cycle duration as well as some other cough-related time intervals. In response to microinjections of kyn into the NTS rostral to the obex respiratory rate decreased, and there were increases in the durations of the inspiratory and postinspiratory phases and mean blood pressure. However, bilateral microinjections of kyn into the NTS caudal to obex as well as control vehicle microinjections in the NTS location rostral to obex had no effect on coughing or cardiorespiratory variables. These results are consistent with the existence of a critical component of the cough rhythmogenic circuit located in the rostral ventral and lateral NTS. Neuronal structures of the rostral NTS are significantly involved specifically in the regulation of cough magnitude and phase timing. NEW & NOTEWORTHY The nucleus of the solitary tract contains significant neuronal structures responsible for control of 1 ) cough excitability, 2 ) motor drive during cough, 3 ) cough phase timing, and 4 ) cough rhythmicity. Significant elimination of neurons in the solitary tract nucleus results in cough apraxia (incomplete and/or disordered cough pattern). The mechanism of the cough impairment is different from that for the concomitant changes in breathing. Copyright © 2017 the American Physiological Society.

Evaluation of options for improving Amtrak’s passenger accountability system

DOT National Transportation Integrated Search

2005-12-01

In investigating the derailment of Amtrak's Auto Train on April 18, 2002, the National Transportation Safety Board (NTSB) reported that an accurate count of persons on the train at the time of the accident was not available at the accident scene. NTS...

The scope and limitations of intramolecular Nicholas and Pauson-Khand reactions for the synthesis of tricyclic oxygen- and nitrogen-containing heterocycles.

PubMed

Closser, Kristina D; Quintal, Miriam M; Shea, Kevin M

2009-05-15

We studied the scope and limitations of a tandem intramolecular Nicholas/Pauson-Khand strategy for the synthesis of tricyclic oxygen- and nitrogen-containing heterocycles. This methodology enables conversion of simple acyclic starting materials into a series of previously unknown heterocyclic architectures. For the preparation of cyclic ethers (Z = O), tricyclic [5,6,5]- through [5,9,5]-systems (m = 1, n = 1-4) are available with the [5,7,5]- and [5,8,5]-systems amenable to quick and efficient synthesis. Tricyclic [5,7,5]- and [5,8,5]-amine-containing (Z = NTs) heterocycles can be successfully prepared. Attempts to make larger ring systems (Z = O, m = 2; Z = O, n = 5; or Z = NTs, n = 4-5) or prepare lactones via Nicholas reactions with carboxylic acid nucleophiles (available via oxidation of alcohol nucleophiles, Z = O) result in decomposition or dimerization. The latter process enables formation of 14-, 16-, and 18-membered ring diolides when using carboxylic acid nucleophiles. We also investigated the use of chiral amine promoters in the Pauson-Khand step but found no asymmetric induction.

Multi-Use seismic stations offer strong deterrent to clandestine nuclear weapons testing

NASA Astrophysics Data System (ADS)

Hennet, C. B.; Van der Vink, G. E.; Richards, P. G.; Adushkin, V. V.; Kopnichev, Y. F.; Geary, R.

As the United States and other nations push for the signing of a Comprehensive Test Ban Treaty, representatives are meeting in Geneva this year to develop an International Seismic Monitoring System to verify compliance with the treaty's restrictions. In addition to the official monitoring system, regional networks developed for earthquake studies and basic research can provide a strong deterrent against clandestine testing. The recent release of information by the U.S. Department of Energy (DoE) on previously unannounced nuclear tests provides an opportunity to assess the ability of multi-use seismic networks to help monitor nuclear testing across the globe.Here we look at the extent to which the formerly unannounced tests were recorded and identified on the basis of publicly available seismographic data recorded by five seismic networks. The data were recorded by networks in southern Nevada and northern California at stations less than 1500 km from the Nevada Test Site (NTS), and two networks in the former Soviet Union at stations farther than 1500 km from the NTS.

Tunable Fano Resonance and Plasmon-Exciton Coupling in Single Au Nanotriangles on Monolayer WS2 at Room Temperature.

PubMed

Wang, Mingsong; Krasnok, Alex; Zhang, Tianyi; Scarabelli, Leonardo; Liu, He; Wu, Zilong; Liz-Marzán, Luis M; Terrones, Mauricio; Alù, Andrea; Zheng, Yuebing

2018-05-01

Tunable Fano resonances and plasmon-exciton coupling are demonstrated at room temperature in hybrid systems consisting of single plasmonic nanoparticles deposited on top of the transition metal dichalcogenide monolayers. By using single Au nanotriangles (AuNTs) on monolayer WS 2 as model systems, Fano resonances are observed from the interference between a discrete exciton band of monolayer WS 2 and a broadband plasmonic mode of single AuNTs. The Fano lineshape depends on the exciton binding energy and the localized surface plasmon resonance strength, which can be tuned by the dielectric constant of surrounding solvents and AuNT size, respectively. Moreover, a transition from weak to strong plasmon-exciton coupling with Rabi splitting energies of 100-340 meV is observed by rationally changing the surrounding solvents. With their tunable plasmon-exciton interactions, the proposed WS 2 -AuNT hybrids can open new pathways to develop active nanophotonic devices. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Temporal and Spatial Development of dB/dt During Substorms

NASA Astrophysics Data System (ADS)

Weygand, J. M.; Chu, X.

2017-12-01

Ground induced currents (GICs) due to space weather are a threat to high voltage power transmission systems. However, knowledge of ground conductivity is the largest source of errors in the determination of GICs. A good proxy for GICs is dB/dt obtained from the Bx and By components of the magnetic field fluctuations. It is known that dB/dt values associated with magnetic storms can reach dangerous levels for power transmission systems. On the other hand, it is not uncommon for dB/dt values associated with substorms to exceed critical thresholds of 1.5 nT/s [Pulkkinen et al., 2011; 2013] and 5 nT/s [Molinski et al., 2000] and the temporal and spatial changes of the dB/dt associated with substorms, unlike storms, are not well understood. Using two dimensional maps of dB/dt over North America and Greenland derived from the spherical elementary currents [Weygand et al., 2011], we investigate the temporal and spatial change of dB/dt for both a single substorm event and a two dimensional superposed epoch analysis of many substorms. Both the single event and the statistical analysis show a sudden increase of dB/dt at substorm onset followed by an expansion poleward, westward, and eastward after the onset during the expansion phase. This temporal and spatial development of the dB/dt resembles the temporal and spatial change of the auroral emissions. Substorm values of dB/dt peak shortly after the auroral onset time and in at least one event exceeded 6.5 nT/s for a non-storm time substorm. In many of our 24 cases the area that exceeds the Pulkkinen et al. [2011; 2013] threshold of 1.5 nT/s over several million square kilometers and after about 30 minutes the dB/dt values fall below the threshold level. These results address one of goals of the Space Weather Action Plan, which are to establish benchmarks for space weather events and improve modeling and prediction of their impacts on infrastructure.

Botulinum neurotoxin detection methods for public health response and surveillance

USDA-ARS?s Scientific Manuscript database

A single suspected case of foodborne botulism caused by food contaminated with botulinum neurotoxin (BoNTs) could evoke public health emergency. The threat of bioterrorism through deliberate distribution in food sources and/or aerosolization of BoNTs raises global public health and security concerns...

Inflammation and pancreatic cancer: molecular and functional interactions between S100A8, S100A9, NT-S100A8 and TGFβ1

PubMed Central

2014-01-01

Background In order to gain further insight on the crosstalk between pancreatic cancer (PDAC) and stromal cells, we investigated interactions occurring between TGFβ1 and the inflammatory proteins S100A8, S100A9 and NT-S100A8, a PDAC-associated S100A8 derived peptide, in cell signaling, intracellular calcium (Cai2+) and epithelial to mesenchymal transition (EMT). NF-κB, Akt and mTOR pathways, Cai2+ and EMT were studied in well (Capan1 and BxPC3) and poorly differentiated (Panc1 and MiaPaCa2) cell lines. Results NT-S100A8, one of the low molecular weight N-terminal peptides from S100A8 to be released by PDAC-derived proteases, shared many effects on NF-κB, Akt and mTOR signaling with S100A8, but mainly with TGFβ1. The chief effects of S100A8, S100A9 and NT-S100A8 were to inhibit NF-κB and stimulate mTOR; the molecules inhibited Akt in Smad4-expressing, while stimulated Akt in Smad4 negative cells. By restoring Smad4 expression in BxPC3 and silencing it in MiaPaCa2, S100A8 and NT-S100A8 were shown to inhibit NF-κB and Akt in the presence of an intact TGFβ1 canonical signaling pathway. TGFβ1 counteracted S100A8, S100A9 and NT-S100A8 effects in Smad4 expressing, not in Smad4 negative cells, while it synergized with NT-S100A8 in altering Cai2+ and stimulating PDAC cell growth. The effects of TGFβ1 on both EMT (increased Twist and decreased N-Cadherin expression) and Cai2+ were antagonized by S100A9, which formed heterodimers with TGFβ1 (MALDI-TOF/MS and co-immuno-precipitation). Conclusions The effects of S100A8 and S100A9 on PDAC cell signaling appear to be cell-type and context dependent. NT-S100A8 mimics the effects of TGFβ1 on cell signaling, and the formation of complexes between TGFβ1 with S100A9 appears to be the molecular mechanism underlying the reciprocal antagonism of these molecules on cell signaling, Cai2+ and EMT. PMID:24670043

Effects of cigarette smoke exposure on nicotinic acetylcholine receptor subunits {alpha}7 and {beta}2 in the sudden infant death syndrome (SIDS) brainstem

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

Machaalani, Rita, E-mail: rita.machaalani@sydney.edu.au; Bosch Institute, The University of Sydney, NSW 2006; The Children's Hospital at Westmead, NSW 2145

It is postulated that nicotine, as the main neurotoxic constituent of cigarette smoke, influences SIDS risk through effects on nicotinic acetylcholine receptors (nAChRs) in brainstem nuclei that control respiration and arousal. This study compared {alpha}7 and {beta}2 nAChR subunit expression in eight nuclei of the caudal and rostral medulla and seven nuclei of the pons between SIDS (n = 46) and non-SIDS infants (n = 14). Evaluation for associations with known SIDS risk factors included comparison according to whether infants had a history of exposure to cigarette smoke in the home, and stratification for sleep position and gender. Compared tomore » non-SIDS infants, SIDS infants had significantly decreased {alpha}7 in the caudal nucleus of the solitary tract (cNTS), gracile and cuneate nuclei, with decreased {beta}2 in the cNTS and increased {beta}2 in the facial. When considering only the SIDS cohort: 1-cigarette smoke exposure was associated with increased {alpha}7 in the vestibular nucleus and increased {beta}2 in the rostral dorsal motor nucleus of the vagus, rNTS and Cuneate, 2-there was a gender interaction for {alpha}7 in the gracile and cuneate, and {beta}2 in the cNTS and rostral arcuate nucleus, and 3-there was no effect of sleep position on {alpha}7, but prone sleep was associated with decreased {beta}2 in three nuclei of the pons. In conclusion, SIDS infants demonstrate differences in expression of {alpha}7 and {beta}2 nAChRs within brainstem nuclei that control respiration and arousal, which is independent on prior history of cigarette smoke exposure, especially for the NTS, with additional differences for smoke exposure ({beta}2), gender ({alpha}7 and {beta}2) and sleep position ({beta}2) evident. -- Highlights: Black-Right-Pointing-Pointer The 'normal' response to smoke exposure is decreased {alpha}7 and {beta}2 in certain nuclei. Black-Right-Pointing-Pointer SIDS infants have decreased {alpha}7 in cNTS, Grac and Cun. Black-Right-Pointing-Pointer SIDS infants have decreased {beta}2 in cNTS and increased {beta}2 in facial. Black-Right-Pointing-Pointer The NTS is more sensitive to both {alpha}7 and {beta}2 regulation in SIDS. Black-Right-Pointing-Pointer Smoke exposure amongst SIDS induces a different response; increased {alpha}7 and {beta}2.« less

Inflammation and pancreatic cancer: molecular and functional interactions between S100A8, S100A9, NT-S100A8 and TGFβ1.

PubMed

Basso, Daniela; Bozzato, Dania; Padoan, Andrea; Moz, Stefania; Zambon, Carlo-Federico; Fogar, Paola; Greco, Eliana; Scorzeto, Michele; Simonato, Francesca; Navaglia, Filippo; Fassan, Matteo; Pelloso, Michela; Dupont, Sirio; Pedrazzoli, Sergio; Fassina, Ambrogio; Plebani, Mario

2014-03-26

In order to gain further insight on the crosstalk between pancreatic cancer (PDAC) and stromal cells, we investigated interactions occurring between TGFβ1 and the inflammatory proteins S100A8, S100A9 and NT-S100A8, a PDAC-associated S100A8 derived peptide, in cell signaling, intracellular calcium (Cai2+) and epithelial to mesenchymal transition (EMT). NF-κB, Akt and mTOR pathways, Cai2+ and EMT were studied in well (Capan1 and BxPC3) and poorly differentiated (Panc1 and MiaPaCa2) cell lines. NT-S100A8, one of the low molecular weight N-terminal peptides from S100A8 to be released by PDAC-derived proteases, shared many effects on NF-κB, Akt and mTOR signaling with S100A8, but mainly with TGFβ1. The chief effects of S100A8, S100A9 and NT-S100A8 were to inhibit NF-κB and stimulate mTOR; the molecules inhibited Akt in Smad4-expressing, while stimulated Akt in Smad4 negative cells. By restoring Smad4 expression in BxPC3 and silencing it in MiaPaCa2, S100A8 and NT-S100A8 were shown to inhibit NF-κB and Akt in the presence of an intact TGFβ1 canonical signaling pathway. TGFβ1 counteracted S100A8, S100A9 and NT-S100A8 effects in Smad4 expressing, not in Smad4 negative cells, while it synergized with NT-S100A8 in altering Cai2+ and stimulating PDAC cell growth. The effects of TGFβ1 on both EMT (increased Twist and decreased N-Cadherin expression) and Cai2+ were antagonized by S100A9, which formed heterodimers with TGFβ1 (MALDI-TOF/MS and co-immuno-precipitation). The effects of S100A8 and S100A9 on PDAC cell signaling appear to be cell-type and context dependent. NT-S100A8 mimics the effects of TGFβ1 on cell signaling, and the formation of complexes between TGFβ1 with S100A9 appears to be the molecular mechanism underlying the reciprocal antagonism of these molecules on cell signaling, Cai2+ and EMT.

TRPV1 channels in the nucleus of the solitary tract mediate thermal prolongation of the LCR in decerebrate piglets

PubMed Central

Xia, Luxi; Bartlett, Donald; Leiter, J.C.

2011-01-01

Elevating body temperature or just the temperature of the dorsal medulla by approximately 2 °C prolongs the laryngeal chemoreflex (LCR) in decerebrate neonatal piglets. We tested the hypothesis that transient receptor potential vanilloid 1 (TRPV1) receptors in the nucleus of the solitary tract (NTS) mediate thermal prolongation of the LCR. We studied the effect of a selective TRPV1 receptor antagonist on thermal prolongation of the LCR, and we tested the effect of a TRPV1 agonist on the duration of the LCR under normothermic conditions. We studied 37 decerebrate neonatal piglets between the ages of post-natal days 4 and 7. The TRPV1 receptor antagonist, 5−iodoresiniferatoxin (65 microM/L in 100 nL), blocked thermal prolongation of the LCR when injected bilaterally into the region of the NTS. The TRPV1 agonist, resiniferatoxin (0.65-1.0 mM/L in 100 nL), prolonged the LCR after bilateral injection into the NTS even when the body temperature of each piglet was normal. The effect of the TRPV1 agonists could be blocked by treatment with the GABAA receptor antagonist, bicuculline, whether given intravenously (0.3 mg/kg) or focally injected bilaterally into the NTS (10 mM in 100nL). We conclude that TRPV1 receptors in the NTS mediate thermal prolongation of the LCR. PMID:21276877

Fructose induced neurogenic hypertension mediated by overactivation of p38 MAPK to impair insulin signaling transduction caused central insulin resistance.

PubMed

Cheng, Pei-Wen; Lin, Yu-Te; Ho, Wen-Yu; Lu, Pei-Jung; Chen, Hsin-Hung; Lai, Chi-Cheng; Sun, Gwo-Ching; Yeh, Tung-Chen; Hsiao, Michael; Tseng, Ching-Jiunn; Liu, Chun-Peng

2017-11-01

Type 2 diabetes are at a high risk of complications related to hypertension, and reports have indicated that insulin levels may be associated with blood pressure (BP). Fructose intake has recently been reported to promote insulin resistance and superoxide formation. The aim of this study is to investigate whether fructose intake can enhance superoxide generation and impair insulin signaling in the NTS and subsequently elevate BP in rats with fructose-induced hypertension. Treatment with fructose for 4 weeks increased the BP, serum fasting insulin, glucose, homeostatic model assessment-insulin resistance, and triglyceride levels and reduced the serum direct high-density lipoprotein level in the fructose group. The Tempol treatment recovered the fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that fructose increased the p38- and fructose-induced phosphorylation of insulin receptor substrate 1 (IRS1 S307 ) and suppressed Akt S473 and neuronal nitric oxide synthase phosphorylation. Similarly, fructose was able to impair insulin sensitivity and increase insulin levels in the NTS. Fructose intake also increased the production of superoxide in the NTS. The results of this study suggest that fructose might induce central insulin resistance and elevate BP by enhancing superoxide production and activating p38 phosphorylation in the NTS. Copyright © 2017 Elsevier Inc. All rights reserved.

In Vitro Assessment of Early Bacterial Activity on Micro/Nanostructured Ti6Al4V Surfaces.

PubMed

Valdez-Salas, Benjamin; Beltrán-Partida, Ernesto; Castillo-Uribe, Sandra; Curiel-Álvarez, Mario; Zlatev, Roumen; Stoytcheva, Margarita; Montero-Alpírez, Gisela; Vargas-Osuna, Lidia

2017-05-18

It is imperative to understand and systematically compare the initial interactions between bacteria genre and surface properties. Thus, we fabricated a flat, anodized with 80 nm TiO₂ nanotubes (NTs), and a rough Ti6Al4V surface. The materials were characterized using field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX) and atomic force microscopy (AFM). We cultured in vitro Staphylococcus epidermidis ( S. epidermidis ) and Pseudomonas aeruginosa ( P. aeruginosa ) to evaluate the bacterial-surface behavior by FE-SEM and viability calculation. In addition, the initial effects of human osteoblasts were tested on the materials. Gram-negative bacteria showed promoted adherence and viability over the flat and rough surface, while NTs displayed opposite activity with altered morphology. Gram-positive bacteria illustrated similar cellular architecture over the surfaces but with promoted surface adhesion bonds on the flat alloy. Rough surfaces supported S. epidermidis viability, whilst NTs exhibited lower vitality. NTs advocated promoted better osteoblast organization with enhanced vitality. Gram-positive bacteria suggested preferred adhesion capability over flat and carbon-rich surfaces. Gram-negative bacteria were strongly disturbed by NTs but largely stimulated by flat and rough materials. Our work proposed that the chemical profile of the material surface and the bacterial cell wall characteristics might play an important role in the bacteria-surface interactions.

The effect of the GLP‐1 analogue Exenatide on functional connectivity within an NTS‐based network in women with and without obesity

PubMed Central

Coveleskie, K.; Kilpatrick, L. A.; Gupta, A.; Stains, J.; Connolly, L.; Labus, J. S.; Sanmiguel, C.

2017-01-01

Summary Objective The differential effect of GLP‐1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite‐related behaviours was investigated in women with normal weight compared with women with obesity. Methods Following an 8‐h fast, 19 female subjects (11 lean, 8 obese) participated in a 2‐d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30‐min post subcutaneous injection of 5 μg of Exenatide or placebo. Functional connectivity was examined with the NTS. Drug‐induced functional connectivity changes within and between groups and correlations with appetite measures were examined in a region of interest approach focusing on the thalamus and hypothalamus. Results Women with obesity reported less hunger after drug injection. Exenatide administration increased functional connectivity of the left NTS with the left thalamus and hypothalamus in the obese group only and increased the correlation between NTS functional connectivity and hunger scores in all subjects, but more so in the obese. Conclusions Obesity can impact the effects of Exenatide on brain connectivity, specifically in the NTS and is linked to changes in appetite control. This has implications for the use of GLP‐1 analogues in therapeutic interventions. PMID:29259802

Aldosterone induces rapid sodium intake by a nongenomic mechanism in the nucleus tractus solitarius.

PubMed

Qiao, Hu; Hu, Bo; Zhou, Hong; Yan, Jianqun; Jia, Ru; Lu, Bo; Sun, Bo; Luo, Xiao; Fan, Yuanyuan; Wang, Nan

2016-12-09

The purpose of this study was to determine whether aldosterone has a rapid action in the nucleus tractus solitarius (NTS) that increases sodium intake, and to examine whether this effect of aldosterone, if present, is mediated by G protein-coupled estrogen receptor (GPER). Adult male Sprague-Dawley rats with a stainless-steel cannula in the NTS were used. Aldosterone was injected into the NTS at the doses of 1, 5, 10 and 20 ng 0.1 μl -1 . A rapid dose-related increase of 0.3 M NaCl intake was induced within 30 min and this increase was not suppressed by the mineralocorticoid receptor (MR) antagonist spironolactone (10 ng 0.1 μl -1 ). Water intake was not affected by aldosterone. The GPER agonist G-1 produced a parallel and significant increase in sodium intake, while pre-treatment with GPER antagonist G15 (10 ng 0.1 μl -1 ) blocked the G-1 or aldosterone-induced rapid sodium intake. In addition, sodium intake induced by sodium depletion or low-sodium diet fell within 30 min after injection into the NTS of the MR antagonist spironolactone, while G15 had no effect. Our results confirm previous reports, and support the hypothesis that aldosterone evokes rapid sodium intake through a non-genomic mechanism involving GPER in NTS.

Breakthrough indicator for aromatic VOCs using needle trap samplers for activated carbon adsorbent.

PubMed

Cheng, Wen-Hsi; Jiang, Jia-Rong; Huang, Yi-Ning; Huang, Shiun-Chian; Yu, Yan-Pin

2012-08-01

Internal circulation cabinets equipped with granular activated carbon (GAC) for adsorbing volatile organic compounds (VOCs) are widely used to store bottles containing organic solvents in universities, colleges, and hospital laboratories throughout Taiwan. This work evaluates the VOC adsorption capacities of GAC using various adsorption times for gas stream mixtures of 100 ppm toluene and 100 ppm o-xylene. Additionally, needle trap sampling (NTS) technology was used to indicate the time for renewing the GAC to avoid VOC breakthrough from adsorbents. Experimental results demonstrate that the proposed models can linearly express toluene and o-xylene adsorption capacities as the natural logarithm of adsorption time (ln(t)) and can accurately simulate the equilibrium adsorption capacities (Qe, g VOCs/g GAC) for gaseous toluene and o-xylene. The NTS, packed with 60-80 mesh divinylbenzene (DVB) particles, was compared in terms of extraction efficiency by simultaneously using the 75-microm Carboxen/polydimethylsiloxane-solid-phase microextraction (Carboxen/PDMS-SPME) fiber for time-weighted average (TWA) sampling, and experimental results indicated that the packed DVB-NTS achieved higher toluene extraction rates. Additionally, the NTS installed in the outlet air stream for adsorbing toluene and o-xylene exhausted through GAC accurately indicated toluene and o-xylene breakthrough times of 4700-5000 min. The GAC-NTS operational instructions to indicate the replacing time of adsorbent in the internal circulation cabinets are also included in this paper.

Phase transitions in the common brainstem and related systems investigated by nonstationary time series analysis.

PubMed

Lambertz, M; Vandenhouten, R; Grebe, R; Langhorst, P

2000-01-14

Neuronal activities of the reticular formation (RF) of the lower brainstem and the nucleus tractus solitarii (NTS, first relay station of baroreceptor afferents) were recorded together in the anesthized dog with related parameters of EEG, respiration and cardiovascular system. The RF neurons are part of the common brainstem system (CBS) which participates in regulation and coordination of cardiovascular, respiratory, somatomotor systems, and vigilance. Multiple time series of these physiological subsystems yield useful information about internal dynamic coordination of the organism. Essential problems are nonlinearity and instationarity of the signals, due to the dynamic complexity of the systems. Several time-resolving methods are presented to describe nonlinear dynamic couplings in the time course, particularly during phase transitions. The methods are applied to the recorded signals representing the complex couplings of the physiological subsystems. Phase transitions in these systems are detected by recurrence plots of the instationary signals. The pointwise transinformation and the pointwise conditional coupling divergence are measures of the mutual interaction of the subsystems in the state space. If the signals show marked rhythms, instantaneous frequencies and their shiftings are demonstrated by time frequency distributions, and instantaneous phase differences show couplings of oscillating subsystems. Transient signal components are reconstructed by wavelet packet time selective transient reconstruction. These methods are useful means for analyzing coupling characteristics of the complex physiological system, and detailed analyses of internal dynamic coordination of subsystems become possible. During phase transitions of the functional organization (a) the rhythms of the central neuronal activities and the peripheral systems are altered, (b) changes in the coupling between CBS neurons and cardiovascular signals, respiration and the EEG, and (c) between NTS neurons (influenced by baroreceptor afferents) and CBS neurons occur, and (d) the processing of baroreceptor input at the NTS neurons changes. The results of this complex analysis, which could not be done formerly in this manner, confirm and complete former investigations on the dynamic organization of the CBS with its changing relations to peripheral and other central nervous subsystems.

Comparison of oral toxicological properties of botulinum neurotoxin

USDA-ARS?s Scientific Manuscript database

Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated ...

Optical transfer function of NTS-1 retroreflector array

NASA Technical Reports Server (NTRS)

Arnold, D. A.

1974-01-01

An optical transfer function was computed for the retroreflector array carried by the NTS-1 satellite. Range corrections are presented for extrapolating laser range measurements to the center of mass of the satellite. The gain function of the array was computed for use in estimating laser-echo signal strengths.

OFFSITE ENVIRONMENTAL MONITORING REPORT: RADIATION MONITORING AROUND UNITED STATES NUCLEAR TEST AREAS, CALENDAR YEAR 1980

EPA Science Inventory

The U.S. Environmental Protection Agency's Environmental Monitoring Systems Laboratory in Las Vegas continued its Offsite Radiological Safety Program for the Nevada Test Site (NTS) and other sites of past underground nuclear tests. For each test, the Laboratory provided airborne ...

14 CFR Special Federal Aviation... - Mitsubishi MU-2B Series Special Training, Experience, and Operating Requirements

Code of Federal Regulations, 2010 CFR

2010-01-01

.... Fuselage 2. Wing 3. Empennage 4. Doors 5. Windshield and Windows C. Airplane Systems 1. Electrical Power 2... System 1. Navigation Lights 2. Anti-Collision Lights 3. Wing Inspection Lights 4. Taxi Lights 5. Landing... Operations 3. Synchronization 4. De-Ice D. Ground Checks 1. Overspeed Governor 2. SRL and Delta P/P 3. NTS...

14 CFR Special Federal Aviation... - Mitsubishi MU-2B Series Special Training, Experience, and Operating Requirements

Code of Federal Regulations, 2011 CFR

2011-01-01

.... Fuselage 2. Wing 3. Empennage 4. Doors 5. Windshield and Windows C. Airplane Systems 1. Electrical Power 2... System 1. Navigation Lights 2. Anti-Collision Lights 3. Wing Inspection Lights 4. Taxi Lights 5. Landing... Operations 3. Synchronization 4. De-Ice D. Ground Checks 1. Overspeed Governor 2. SRL and Delta P/P 3. NTS...

OFFSITE ENVIRONMENTAL MONITORING REPORT. RADIATION MONITORING AROUND UNITED STATES NUCLEAR TEST AREAS, CALENDAR YEAR 1981

EPA Science Inventory

This report, prepared in accordance with the guidelines in DOE/E-0023 (DOE 1981), covers the program activities conducted around Nevada Test Site (NTS) for calendar year 1981. It contains descriptions of pertinent features of the NTS and its environs, summaries of the dosimetry a...

Translocation of botulinum neurotoxins and associated proteins across intestinal epithelial cells(Abstract)

USDA-ARS?s Scientific Manuscript database

Botulinum neurotoxins(BoNTs)secreted by Clostridium botulinum are some of the most poisonous toxins in nature and considered to be major bioterrorism threats. To date, seven BoNT subtypes (A to G) have been identified. When secreted from bacteria, some BoNTs associate with a non-toxic, non hemagglu...

Translocation of botulinum neurotoxin serotype a and associated proteins across the intestinal epithelia

USDA-ARS?s Scientific Manuscript database

Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins and considered to be a major venue of bioterrorist threat. BoNTs associate with neurotoxin associated proteins (NAPs), forming large complexes. NAPs have been shown to shield the BoNT holotoxin from the harsh environment of ...

Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity

USDA-ARS?s Scientific Manuscript database

Botulinum neurotoxins (BoNTs) are highly potent oral poisons produced by Clostridium botulinum. BoNTs are secreted along with several auxiliary proteins forming progenitor toxin complexes (PTC). Here, we report the structure of a ~760 kDa 14-subunit PTC using a combination of X-ray crystallography a...

Rapid microfluidic assay for the detection of botulinum neurotoxin in animal sera

USDA-ARS?s Scientific Manuscript database

The potent botulinum neurotoxins (BoNTs) represent a threat to public health and safety. Botulism is a disease caused by BoNT intoxication that results in muscle paralysis that can be fatal. Sensitive assays capable of detecting BoNTs from different substrates and settings are essential to limit f...

Discrimination of Earthquakes and Explosions at Regional Distances Using Complexity

DTIC Science & Technology

1993-06-17

and Bennett and Murphy (1986) present several NTS explosion and near-NTS earthquake signals as recorded at single elements of the Tonto Forest, Uinta ... Basin , and Blue Mountain Vela Array Observatories (TFO, UBO, and BMO). As they point out, the S/N for Pn is poor (These authors therefore rested their

Current methods for detecting the presence of botulinum neurotoxins in food and other biological samples

USDA-ARS?s Scientific Manuscript database

Current methods for detecting the presence of botulinum neurotoxins in food and other biological samples Botulinum neurotoxins (BoNTs), the causative agents of botulism, are among the most lethal human bacterial toxins and the causative agent of botulism. BoNTs are also classified as Select Agents ...

Genetic identification of a hindbrain nucleus essential for innate vocalization.

PubMed

Hernandez-Miranda, Luis Rodrigo; Ruffault, Pierre-Louis; Bouvier, Julien C; Murray, Andrew J; Morin-Surun, Marie-Pierre; Zampieri, Niccolò; Cholewa-Waclaw, Justyna B; Ey, Elodie; Brunet, Jean-Francois; Champagnat, Jean; Fortin, Gilles; Birchmeier, Carmen

2017-07-25

Vocalization in young mice is an innate response to isolation or mechanical stimulation. Neuronal circuits that control vocalization and breathing overlap and rely on motor neurons that innervate laryngeal and expiratory muscles, but the brain center that coordinates these motor neurons has not been identified. Here, we show that the hindbrain nucleus tractus solitarius (NTS) is essential for vocalization in mice. By generating genetically modified newborn mice that specifically lack excitatory NTS neurons, we show that they are both mute and unable to produce the expiratory drive required for vocalization. Furthermore, the muteness of these newborns results in maternal neglect. We also show that neurons of the NTS directly connect to and entrain the activity of spinal (L1) and nucleus ambiguus motor pools located at positions where expiratory and laryngeal motor neurons reside. These motor neurons control expiratory pressure and laryngeal tension, respectively, thereby establishing the essential biomechanical parameters used for vocalization. In summary, our work demonstrates that the NTS is an obligatory component of the neuronal circuitry that transforms breaths into calls.

Russian national time scale long-term stability

NASA Astrophysics Data System (ADS)

Alshina, A. P.; Gaigerov, B. A.; Koshelyaevsky, N. B.; Pushkin, S. B.

1994-05-01

The Institute of Metrology for Time and Space NPO 'VNIIFTRI' generates the National Time Scale (NTS) of Russia -- one of the most stable time scales in the world. Its striking feature is that it is based on a free ensemble of H-masers only. During last two years the estimations of NTS longterm stability based only on H-maser intercomparison data gives a flicker floor of about (2 to 3) x 10(exp -15) for averaging times from 1 day to 1 month. Perhaps the most significant feature for a time laboratory is an extremely low possible frequency drift -- it is too difficult to estimate it reliably. The other estimations, free from possible inside the ensemble correlation phenomena, are available based on the time comparison of NTS relative to the stable enough time scale of outer laboratories. The data on NTS comparison relative to the time scale of secondary time and frequency standards at Golitzino and Irkutsk in Russia and relative to NIST, PTB and USNO using GLONASS and GPS time transfer links gives stability estimations which are close to that based on H-maser intercomparisons.

Techniques Employed to Conduct Postshot Drilling at the former Nevada Test Site

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

Dekin, W D

2011-04-14

Postshot drilling provided essential data on the results of the underground nuclear tests conducted at the Nevada Test Site (NTS), now identified as the Nevada National Security Site (NNSS). It was the means by which samples from the zone of interest were obtained for radiochemical analysis. This handbook describes how Lawrence Livermore National Laboratory (LLNL) conducted postshot drilling operations at the NTS, and it provides a general understanding of the process. Postshot drilling is a specialized application of rotary drilling. Accordingly, this handbook gives a brief description of rotary drilling in Section 2 to acquaint the reader with the generalmore » subject before proceeding to the specialized techniques used in postshot drilling. In Section 3, the handbook describes the typical postshot drilling situation at the former NTS and the drilling methods used. Section 4 describes the typical sequence of operations in postshot drilling at the former NTS. Detailed information on special equipment and techniques is given in a series of appendices (A through F) at the end of the handbook.« less

The acquisition process of musical tonal schema: implications from connectionist modeling.

PubMed

Matsunaga, Rie; Hartono, Pitoyo; Abe, Jun-Ichi

2015-01-01

Using connectionist modeling, we address fundamental questions concerning the acquisition process of musical tonal schema of listeners. Compared to models of previous studies, our connectionist model (Learning Network for Tonal Schema, LeNTS) was better equipped to fulfill three basic requirements. Specifically, LeNTS was equipped with a learning mechanism, bound by culture-general properties, and trained by sufficient melody materials. When exposed to Western music, LeNTS acquired musical 'scale' sensitivity early and 'harmony' sensitivity later. The order of acquisition of scale and harmony sensitivities shown by LeNTS was consistent with the culture-specific acquisition order shown by musically westernized children. The implications of these results for the acquisition process of a tonal schema of listeners are as follows: (a) the acquisition process may entail small and incremental changes, rather than large and stage-like changes, in corresponding neural circuits; (b) the speed of schema acquisition may mainly depend on musical experiences rather than maturation; and (c) the learning principles of schema acquisition may be culturally invariant while the acquired tonal schemas are varied with exposed culture-specific music.

Identification of a Unique Ganglioside Binding Loop within Botulinum Neurotoxins C and D-SA

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

Karalewitz, Andrew P.-A.; Kroken, Abby R.; Fu, Zhuji

2010-09-22

The botulinum neurotoxins (BoNTs) are the most potent protein toxins for humans. There are seven serotypes of BoNTs (A-G) based on a lack of cross antiserum neutralization. BoNTs utilize gangliosides as components of the host receptors for binding and entry into neurons. Members of BoNT/C and BoNT/D serotypes include mosaic toxins that are organized in D/C and C/D toxins. One D/C mosaic toxin, BoNT/D-South Africa (BoNT/D-SA), was not fully neutralized by immunization with BoNT serotype C or D, which stimulated this study. Here the crystal structures of the receptor binding domains of BoNT/C, BoNT/D, and BoNT/D-SA are presented. Biochemical andmore » cell binding studies show that BoNT/C and BoNT/D-SA possess unique mechanisms for ganglioside binding. These studies provide new information about how the BoNTs can enter host cells as well as a basis for understanding the immunological diversity of these neurotoxins.« less

Russian national time scale long-term stability

NASA Technical Reports Server (NTRS)

Alshina, A. P.; Gaigerov, B. A.; Koshelyaevsky, N. B.; Pushkin, S. B.

1994-01-01

The Institute of Metrology for Time and Space NPO 'VNIIFTRI' generates the National Time Scale (NTS) of Russia -- one of the most stable time scales in the world. Its striking feature is that it is based on a free ensemble of H-masers only. During last two years the estimations of NTS longterm stability based only on H-maser intercomparison data gives a flicker floor of about (2 to 3) x 10(exp -15) for averaging times from 1 day to 1 month. Perhaps the most significant feature for a time laboratory is an extremely low possible frequency drift -- it is too difficult to estimate it reliably. The other estimations, free from possible inside the ensemble correlation phenomena, are available based on the time comparison of NTS relative to the stable enough time scale of outer laboratories. The data on NTS comparison relative to the time scale of secondary time and frequency standards at Golitzino and Irkutsk in Russia and relative to NIST, PTB and USNO using GLONASS and GPS time transfer links gives stability estimations which are close to that based on H-maser intercomparisons.

The acquisition process of musical tonal schema: implications from connectionist modeling

PubMed Central

Matsunaga, Rie; Hartono, Pitoyo; Abe, Jun-ichi

2015-01-01

Using connectionist modeling, we address fundamental questions concerning the acquisition process of musical tonal schema of listeners. Compared to models of previous studies, our connectionist model (Learning Network for Tonal Schema, LeNTS) was better equipped to fulfill three basic requirements. Specifically, LeNTS was equipped with a learning mechanism, bound by culture-general properties, and trained by sufficient melody materials. When exposed to Western music, LeNTS acquired musical ‘scale’ sensitivity early and ‘harmony’ sensitivity later. The order of acquisition of scale and harmony sensitivities shown by LeNTS was consistent with the culture-specific acquisition order shown by musically westernized children. The implications of these results for the acquisition process of a tonal schema of listeners are as follows: (a) the acquisition process may entail small and incremental changes, rather than large and stage-like changes, in corresponding neural circuits; (b) the speed of schema acquisition may mainly depend on musical experiences rather than maturation; and (c) the learning principles of schema acquisition may be culturally invariant while the acquired tonal schemas are varied with exposed culture-specific music. PMID:26441725

Plasticity of vagal brainstem circuits in the control of gastrointestinal function

PubMed Central

Browning, Kirsteen N; Travagli, R. Alberto

2010-01-01

The afferent vagus transmits sensory information from the gastrointestinal (GI) tract and other viscera to the brainstem via a glutamatergic synapse at the level of the nucleus of the solitary tract (NTS). Second order NTS neurons integrate this sensory information with inputs from other CNS regions that regulate autonomic functions and homeostasis. Glutamatergic and GABAergic neurons are responsible for conveying the integrated response to other nuclei, including the adjacent dorsal motor nucleus of the vagus (DMV). The preganglionic neurons in the DMV are the source of the parasympathetic motor response back to the GI tract. The glutamatergic synapse between the NTS and DMV is unlikely to be tonically active in regulating gastric motility and tone although almost all neurotransmitters tested so far modulate transmission at this synapse. In contrast, the tonic inhibitory GABAergic input from the NTS to the DMV appears to be critical in setting the tone of gastric motility and, under basal conditions, is unaffected by many neurotransmitters or neurohormones. This review is based, in part, on a presentation by Dr Browning at the 2009 ISAN meeting in Sydney, Australia and discusses how neurohormones and macronutrients modulate glutamatergic transmission to NTS neurons and GABAergic transmission to DMV neurons in relation to sensory information that is received from the GI tract. These neurohormones and macronutrients appear to exert efficient “on-demand” control of the motor output from the DMV in response to ever-changing demands required to maintain homeostasis. PMID:21147043

Identification of a novel therapeutic target for head and neck squamous cell carcinomas: a role for the neurotensin-neurotensin receptor 1 oncogenic signaling pathway.

PubMed

Shimizu, Satoya; Tsukada, Jun; Sugimoto, Takashi; Kikkawa, Naoko; Sasaki, Keita; Chazono, Hideaki; Hanazawa, Toyoyuki; Okamoto, Yoshitaka; Seki, Naohiko

2008-10-15

Distant metastasis is a major factor associated with poor prognosis in head and neck squamous cell carcinomas (HNSCC), but little is known of its molecular mechanisms. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Based on a genome-wide gene expression analysis using clinical specimens of HNSCC, we narrowed our focus to the analysis of the neurotensin (NTS) and neurotensin receptor 1 (NTSR1) oncogenic signal pathways. Kaplan-Meier curves and log rank tests revealed that high mRNA expression levels of NTS and NTSR1 had a significant adverse effect on metastasis-free survival rate, suggesting a contribution of this pathway in HNSCC cancer progression. In HNSCC cells, which expressed NTSR1, a NTS agonist promoted cellular invasion, migration and induction of several mRNAs, such as interleukin 8 and matrix metalloproteinase 1 transcripts. In addition, knock down of NTSR1 expression with small interfering RNAs resulted in reduction of cellular invasion and migration in HNSCC cell lines. Our findings suggest a critical role for the NTS and NTSR1 oncogenic pathways in invasion and migration of HNSCC cells during the metastatic process. Our study raises the possibility that NTS and NTSR1 could be a useful predictive marker of poor prognosis in patients with HNSCC and a molecular therapeutic target in antimetastatic strategies for HNSCCs.

TRPV1 channels in the nucleus of the solitary tract mediate thermal prolongation of the LCR in decerebrate piglets.

PubMed

Xia, Luxi; Bartlett, Donald; Leiter, J C

2011-04-30

Elevating body temperature or just the temperature of the dorsal medulla by approximately 2°C prolongs the laryngeal chemoreflex (LCR) in decerebrate neonatal piglets. We tested the hypothesis that transient receptor potential vanilloid 1 (TRPV1) receptors in the nucleus of the solitary tract (NTS) mediate thermal prolongation of the LCR. We studied the effect of a selective TRPV1 receptor antagonist on thermal prolongation of the LCR, and we tested the effect of a TRPV1 agonist on the duration of the LCR under normothermic conditions. We studied 37 decerebrate neonatal piglets between the ages of post-natal days 4 and 7. The TRPV1 receptor antagonist, 5'-iodoresiniferatoxin (65μM/L in 100nL), blocked thermal prolongation of the LCR when injected bilaterally into the region of the NTS. The TRPV1 agonist, resiniferatoxin (0.65-1.0mM/L in 100nL), prolonged the LCR after bilateral injection into the NTS even when the body temperature of each piglet was normal. The effect of the TRPV1 agonists could be blocked by treatment with the GABA(A) receptor antagonist, bicuculline, whether given intravenously (0.3mg/kg) or focally injected bilaterally into the NTS (10mM in 100nL). We conclude that TRPV1 receptors in the NTS mediate thermal prolongation of the LCR. Copyright © 2011 Elsevier B.V. All rights reserved.

Evidence for an excitatory amino acid pathway in the brainstem and for its involvement in cardiovascular control.

PubMed

Somogyi, P; Minson, J B; Morilak, D; Llewellyn-Smith, I; McIlhinney, J R; Chalmers, J

1989-09-04

The source and possible role of excitatory amino acid projections to areas of the ventrolateral medulla (VLM) involved in cardiovascular control were studied. Following the injection of [3H]D-aspartate ([3H]D-Asp), a selective tracer for excitatory amino acid pathways, into vasopressor or vasodepressor areas of the VLM in rats, more than 90% of retrogradely labelled neurones were found in the nucleus of the solitary tract (NTS). Very few of the [3H]D-Asp-labelled cells were immunoreactive for tyrosine hydroxylase, none for phenylethanolamine-N-methyltransferase or gamma-aminobutyric acid. The density of labelled cells in the NTS was similar to that obtained with the non-selective tracers wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and WGA-colloidal gold, but these tracers also labelled other cell groups in the medulla. Furthermore, the decrease in blood pressure, caused by pharmacological activation of neurones in the NTS of rats, or by electrical stimulation of the aortic depressor nerve in rabbits could be blocked by the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate injected into the caudal vasodepressor area of the VLM. This area corresponds to the termination of [3H]D-Asp transporting NTS neurones. These results provide evidence that a population of NTS neurones projecting to the VLM use excitatory amino acids as transmitters. Among other possible functions, this pathway may mediate tonic and reflex control of blood pressure via NMDA receptors in the VLM.

Potent neutralization of botulinum neurotoxin/B by synergistic action of antibodies recognizing protein and ganglioside receptor binding domain.

PubMed

Chen, Changchun; Wang, Shuhui; Wang, Huajing; Mao, Xiaoyan; Zhang, Tiancheng; Ji, Guanghui; Shi, Xin; Xia, Tian; Lu, Weijia; Zhang, Dapeng; Dai, Jianxin; Guo, Yajun

2012-01-01

Botulinum neurotoxins (BoNTs), the causative agents for life-threatening human disease botulism, have been recognized as biological warfare agents. Monoclonal antibody (mAb) therapeutics hold considerable promise as BoNT therapeutics, but the potencies of mAbs against BoNTs are usually less than that of polyclonal antibodies (or oligoclonal antibodies). The confirmation of key epitopes with development of effective mAb is urgently needed. We selected 3 neutralizing mAbs which recognize different non-overlapping epitopes of BoNT/B from a panel of neutralizing antibodies against BoNT/B. By comparing the neutralizing effects among different combination groups, we found that 8E10, response to ganglioside receptor binding site, could synergy with 5G10 and 2F4, recognizing non-overlapping epitopes within Syt II binding sites. However, the combination of 5G10 with 2F4 blocking protein receptor binding sites did not achieve synergistical effects. Moreover, we found that the binding epitope of 8E10 was conserved among BoNT A, B, E, and F, which might cross-protect the challenge of different serotypes of BoNTs in vivo. The combination of two mAbs recognizing different receptors' binding domain in BoNTs has a synergistic effect. 8E10 is a potential universal partner for the synergistical combination with other mAb against protein receptor binding domain in BoNTs of other serotypes.

Summary of tectonic and structural evidence for stress orientation at the Nevada Test Site

USGS Publications Warehouse

Carr, Wilfred James

1974-01-01

A tectonic synthesis of the NTS (Nevada Test Site) region, when combined with seismic data and a few stress and strain measurements, suggests a tentative model for stress orientation. This model proposes that the NTS is undergoing extension in a N. 50 ? W.-S. 50 ? E. direction coincident with the minimum principal stress direction. The model is supported by (1) a tectonic similarity between a belt of NTS Quaternary faulting and part of the Nevada-California seismic belt, for which northwest-southeast extension has been suggested; (2) historic northeast- trending natural- and explosion-produced fractures in the NTS; (3) the virtual absence in the NTS of northwest-trending Quaternary faults; (4) the character of north-trending faults and basin configuration in the Yucca Flat area, which suggest a component of right-lateral displacement and post-10 m.y. (million year) oblique separation of the sides of the north-trending depression; (5) seismic evidence suggesting a north- to northwest-trending tension axis; (6) strain measurements, which indicate episodes of northwest-southeast extension within a net northeast-southwest compression; (7) a stress estimate based on tectonic cracking that indicates near-surface northwest-southeast-directed tension, and two stress measurements indicating an excess (tectonic) maximum principal compressive stress in a northeast-southwest direction at depths of about 1,000 feet (305 m); and (8) enlargement of some drill holes in Yucca Flat in a northwest-southeast direction. It is inferred that the stress episode resulting in the formation of deep alluvium-filled trenches began somewhere between 10 and possibly less than 4 m.y. ago in the NTS and is currently active. In the Walker Lane of western Nevada, crystallization of plutons associated with Miocene volcanism may have increased the competency and thickness of the crust and its ability to propagate stress, thereby modulating the frequency (spacing) of basin-range faults.

Third-Generation Cephalosporin-Resistant Non-Typhoidal Salmonella Isolated from Human Feces in Japan.

PubMed

Saito, Satomi; Koori, Yoshio; Ohsaki, Yusuke; Osaka, Shunsuke; Oana, Kozue; Nagano, Yukiko; Arakawa, Yoshichika; Nagano, Noriyuki

2017-05-24

β-lactamase genes were detected and characterized from 10 non-typhoidal Salmonella (NTS) clinical isolates resistant to third-generation cephalosporins collected between 2012 and 2014 in Japan. Five strains showed cefotaxime minimum inhibitory concentration (MIC) ≥ 64 μg/ml and positive clavulanic acid inhibition results. The bla CTX-M-2 was detected in 3 strains (serotypes Stanley and Muenchen), whereas bla TEM-52 (serotype Manhattan) and bla SHV-12 (serotype Infantis) were each found in 1 strain. bla CMY-2 was detected in the remaining 5 strains (serotypes Infantis, Rissen, Newport, and Saintpaul) with cefotaxime MICs of 4-32 μg/ml and positive cloxacillin- and 3-aminophenylboronic acid- based inhibition tests. ISEcp1 was located upstream of the bla CMY-2 in 4 strains and of the bla CTX-M-2 in 1 strain. Incompatibility (Inc)A/C, IncP, and IncI1 plasmids were present in the strains harboring bla CMY-2 , which were detected predominantly in this study. Acquisition of resistance to third-generation cephalosporins by invasive NTS may limit therapeutic options for severe systemic infections and causing serious public health problems. Though such resistant clinical isolates are still rare in Salmonella species in Japan, our findings reveal the presence of cephem-resistant NTS in food handlers, thus emphasizing the necessity of more systematic nationwide investigations.

Role of GABAergic neurones in the nucleus tractus solitarii in modulation of cardiovascular activity.

PubMed

Zubcevic, Jasenka; Potts, Jeffrey T

2010-09-01

GABAergic neurones are interspersed throughout the nucleus tractus solitarii (NTS), and their tonic activity is crucial to the maintenance of cardiorespiratory homeostasis. However, the mechanisms that regulate the magnitude of GABAergic inhibition in the NTS remain unknown. We hypothesized that the level of GABAergic inhibition is proportionally regulated by the level of excitatory synaptic input to the NTS from baroreceptors. Using the in situ working heart-brainstem preparation in normotensive and spontaneously hypertensive rats, we blocked GABA(A) receptor-mediated neurotransmission in the NTS with gabazine (a specific GABA(A) receptor antagonist) at two levels of perfusion pressure (low PP, 60-70 mmHg; and high PP, 105-125 mmHg) while monitoring the immediate changes in cardiorespiratory variables. In normotensive rats, gabazine produced an immediate bradycardia consistent with disinhibition of NTS circuit neurones that regulate heart rate (HR) which was proportional to the level of arterial pressure (HR at low PP, 57 +/- 9 beats min(1); at high PP, 177 +/- 9 beats min(1); P < 0.001), suggesting that GABAergic circuitry in the NTS modulating heart rate was arterial pressure dependent. In contrast, there was no significant difference in the magnitude of gabazine-induced bradycardia in spontaneously hypertensive rats at low or high PP (HR at low PP, 45 +/- 10 beats min(1); at high PP, 58 +/- 7 beats min(1)). With regard to thoracic sympathetic nerve activity (tSNA), at high PP there was a significant reduction in tSNA during the inspiratory (I) phase of the respiratory cycle, but only in the normotensive rat (tSNA = 18.7 +/- 10%). At low PP, gabazine caused an elevation of the postinspiration phase of tSNA in both normotensive (tSNA = 23.7 +/- 2.9%) and hypertensive rats (tSNA = 44.2 +/- 14%). At low PP, gabazine produced no change in tSNA during the mid-expiration phase in either rat strain, but at high PP we observed a significant reduction in the mid-expiration phase tSNA, but only in the spontaneously hypertensive rat (tSNA = 25.2 +/- 8%). Gabazine at both low and high PP produced a reduction in the late expiration phase of tSNA in the hypertensive rat (low PP, tSNA = 29.4 +/- 4.4%; high PP, tSNA = 22.8 +/- 3%), whereas in the normotensive rat this was only significant at high PP (tSNA = 42.5 +/- 6.1%). Therefore, in the spontaneously hypertensive rat, contrary to the GABA(A) receptor-mediated control of HR, it appears that GABA(A) receptor-mediated control of tSNA in the NTS is arterial pressure dependent. This study provides new insight into the origin of GABAergic inhibition in NTS circuitry affecting heart rate and sympathetic activity.

Genetic signature analysis of Perkinsus marinus in Mexico suggests possible translocation from the Atlantic Ocean to the Pacific coast of Mexico.

PubMed

Ek-Huchim, Juan Pablo; Aguirre-Macedo, Ma Leopoldina; Améndola-Pimenta, Monica; Vidal-Martínez, Victor Manuel; Pérez-Vega, Juan Antonio; Simá-Alvarez, Raúl; Jiménez-García, Isabel; Zamora-Bustillos, Roberto; Rodríguez-Canul, Rossanna

2017-08-02

The protozoan Perkinsus marinus (Mackin, Owen & Collier) Levine, 1978 causes perkinsosis in the American oyster Crassostrea virginica Gmelin, 1791. This pathogen is present in cultured C. virginica from the Gulf of Mexico and has been reported recently in Saccostrea palmula (Carpenter, 1857), Crassostrea corteziensis (Hertlein, 1951) and Crassostrea gigas (Thunberg, 1793) from the Mexican Pacific coast. Transportation of fresh oysters for human consumption and repopulation could be implicated in the transmission and dissemination of this parasite across the Mexican Pacific coast. The aim of this study was two-fold. First, we evaluated the P. marinus infection parameters by PCR and RFTM (Ray's fluid thioglycollate medium) in C. virginica from four major lagoons (Términos Lagoon, Campeche; Carmen-Pajonal-Machona Lagoon complex, Tabasco; Mandinga Lagoon, Veracruz; and La Pesca Lagoon, Tamaulipas) from the Gulf of Mexico. Secondly, we used DNA sequence analyses of the ribosomal non-transcribed spacer (rNTS) region of P. marinus to determine the possible translocation of this species from the Gulf of Mexico to the Mexican Pacific coast. Perkinsus marinus prevalence by PCR was 57.7% (338 out of 586 oysters) and 38.2% (224 out of 586 oysters) by RFTM. The highest prevalence was observed in the Carmen-Pajonal-Machona Lagoon complex in the state of Tabasco (73% by PCR and 58% by RFTM) and the estimated weighted prevalence (WP) was less than 1.0 in the four lagoons. Ten unique rDNA-NTS sequences of P. marinus [termed herein the "P. marinus (Pm) haplotype"] were identified in the Gulf of Mexico sample. They shared 96-100% similarity with 18 rDNA-NTS sequences from the GenBank database which were derived from 16 Mexican Pacific coast infections and two sequences from the USA. The phylogenetic tree and the haplotype network showed that the P. marinus rDNA-NTS sequences from Mexico were distant from the rDNA-NTS sequences of P. marinus reported from the USA. The ten rDNA-NTS sequences described herein were restricted to specific locations displaying different geographical connections within the Gulf of Mexico; the Carmen-Pajonal-Machona Pm1 haplotype from the state of Tabasco shared a cluster with P. marinus isolates reported from the Mexican Pacific coast. The rDNA-NTS sequences of P. marinus from the state of Tabasco shared high similarity with the reference rDNA-NTS sequences from the Mexican Pacific coast. The high similarity suggests a transfer of oysters infected with P. marinus from the Mexican part of the Gulf of Mexico into the Mexican Pacific coast.

Contribution of Central μ-Receptors to Switching Pulmonary C-Fibers-Mediated Rapid Shallow Breathing into An Apnea by Fentanyl in Anesthetized Rats

PubMed Central

Zhang, Zhenxiong; Zhang, Cancan; Zhuang, Jianguo; Xu, Fadi

2012-01-01

Our previous study has shown that activating peripheral μ-receptors is necessary for switching the bronchopulmonary C-fibers (PCFs)-mediated rapid shallow breathing (RSB) into an apnea by systemic administration of fentanyl. The brainstem nuclei, such as the medial nucleus tractus solitarius (mNTS) and the Pre-Botzinger Complex (PBC), are required for completing the PCF-mediated respiratory reflexes. Moreover, these areas contain abundant μ-receptors and their activation prolongs expiratory duration (TE). Thus, we asked if central μ-receptors, especially those in the mNTS and PBC, are involved in fully expressing this RSB-apnea switch by fentanyl. In anesthetized rats, the cardiorespiratory responses to right atrial injection of phenylbiguanide (PBG, 3–6 μg/kg) were repeated after: 1) fentanyl (iv), a μ-receptor agonist, alone (8 μg/kg, iv); 2) fentanyl following microinjection of naloxone methiodide (NXM, an opioid receptor antagonist) into the cisterna magna (10 μg/4 μl); 3) the bilateral mNTS (10 mM, 20 nl); or 4) PBC (10 mM, 20 nl). Our results showed that PBG shortened TE by 37 ± 6 % (RSB, from 0.41 ± 0.05 to 0.26 ± 0.03 s, P < 0.01), but it markedly prolonged TE by 5.8-fold (an apnea, from 0.50 ± 0.04 s to 2.9 ± 0.57 s, P < 0.01) after fentanyl (iv). Pretreatment with NXM injected into the cisterna magna or the PBC, but not the mNTS, prevented the fentanyl-induced switch. This study, along with our previous results mentioned above, suggests that although peripheral μ-receptors are essential for triggering the fentanyl-induced switch, central μ-receptors, especially those in the PBC, are required to fully exhibit such switch. PMID:22759907

The role of nontechnical skills in simulated trauma resuscitation.

PubMed

Briggs, Alexandra; Raja, Ali S; Joyce, Maurice F; Yule, Steven J; Jiang, Wei; Lipsitz, Stuart R; Havens, Joaquim M

2015-01-01

Trauma team training provides instruction on crisis management through debriefing and discussion of teamwork and leadership skills during simulated trauma scenarios. The effects of team leader's nontechnical skills (NTSs) on technical performance have not been thoroughly studied. We hypothesized that team's and team leader's NTSs correlate with technical performance of clinical tasks. Retrospective cohort study. Brigham and Women's Hospital, STRATUS Center for Surgical Simulation A total of 20 teams composed of surgical residents, emergency medicine residents, emergency department nurses, and emergency services assistants underwent 2 separate, high-fidelity, simulated trauma scenarios. Each trauma scenario was recorded on video for analysis and divided into 4 consecutive sections. For each section, 2 raters used the Non-Technical Skills for Surgeons framework to assess NTSs of the team. To evaluate the entire team's NTS, 2 additional raters used the Modified Non-Technical Skills Scale for Trauma system. Clinical performance measures including adherence to guidelines and time to perform critical tasks were measured independently. NTSs performance by both teams and team leaders in all NTS categories decreased from the beginning to the end of the scenario (all p < 0.05). There was significant correlation between team's and team leader's cognitive skills and critical task performance, with correlation coefficients between 0.351 and 0.478 (p < 0.05). The NTS performance of the team leader highly correlated with that of the entire team, with correlation coefficients between 0.602 and 0.785 (p < 0.001). The NTSs of trauma teams and team leaders deteriorate as clinical scenarios progress, and the performance of team leaders and teams is highly correlated. Cognitive NTS scores correlate with critical task performance. Increased attention to NTSs during trauma team training may lead to sustained performance throughout trauma scenarios. Decision making and situation awareness skills are critical for both team leaders and teams and should be specifically addressed to improve performance. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

The non-neuronal and nonmuscular effects of botulinum toxin: an opportunity for a deadly molecule to treat disease in the skin and beyond.

PubMed

Grando, S A; Zachary, C B

2018-05-01

There is growing evidence that botulinum neurotoxins (BoNTs) exhibit biological effects on various human cell types with a host of associated clinical implications. This review aims to provide an update on the non-neuronal and nonmuscular effects of botulinum toxin. We critically analysed recent reports on the structure and function of cellular signalling systems subserving biological effects of BoNTs. The BoNT receptors and intracellular targets are not unique for neurotransmission. They have been found in both neuronal and non-neuronal cells, but there are differences in how BoNT binds to, and acts on, neuronal vs. non-neuronal cells. The non-neuronal cells that express one or more BoNT/A-binding proteins, and/or cleavage target synaptosomal-associated protein 25, include: epidermal keratinocytes; mesenchymal stem cells from subcutaneous adipose; nasal mucosal cells; urothelial cells; intestinal, prostate and alveolar epithelial cells; breast cell lines; neutrophils; and macrophages. Serotype BoNT/A can also elicit specific biological effects in dermal fibroblasts, sebocytes and vascular endothelial cells. Nontraditional applications of BoNT have been reported for the treatment of the following dermatological conditions: hyperhidrosis, Hailey-Hailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenita, multiple eccrine hydrocystomas, eccrine angiomatous hamartoma, eccrine sweat gland naevi, congenital eccrine naevus, Raynaud phenomenon and cutaneous leiomyomas. Experimental studies have demonstrated the ability of BoNT/A to protect skin flaps, facilitate wound healing, decrease thickness of hypertrophic scars, produce an anti-ageing effect, improve a mouse model of psoriasiform dermatitis, and have also revealed extracutaneous effects of BoNT arising from its anti-inflammatory and anticancer properties. BoNTs have a much wider range of applications than originally understood, and the individual cellular responses to the cholinergic impacts of BoNTs could provide fertile ground for future studies. © 2017 British Association of Dermatologists.

Interactions between Brainstem Noradrenergic Neurons and the Nucleus Accumbens Shell in Modulating Memory for Emotionally Arousing Events

ERIC Educational Resources Information Center

Kerfoot, Erin C.; Williams, Cedric L.

2011-01-01

The nucleus accumbens shell (NAC) receives axons containing dopamine-[beta]-hydroxylase that originate from brainstem neurons in the nucleus of the solitary tract (NTS). Recent findings show that memory enhancement produced by stimulating NTS neurons after learning may involve interactions with the NAC. However, it is unclear whether these…

Prevalence of antimicrobial resistance in Salmonella serotype Hadar isolated from humans, retail meat, and food animals at slaughter, United States, NARMS 1996-2008

USDA-ARS?s Scientific Manuscript database

Background Non-Typhi Salmonella (NTS) is a leading cause of bacterial gastroenteritis in the United States. Although most infections are self-limited, antibiotic treatment is essential for severe illness. Use of antimicrobial agents in food animals contributes to resistance in NTS. Multidrug resis...

14 CFR Special Federal Aviation... - Mitsubishi MU-2B Series Special Training, Experience, and Operating Requirements

Code of Federal Regulations, 2013 CFR

2013-01-01

... maintenance test flight with a second pilot or certificated mechanic, and no passengers or cargo are carried... are distributed by Turbine Aircraft Services, Inc. You may obtain a copy from Turbine Aircraft.... Supplementary NTS E. In Flight Post Maintenance Checks 1. NTS In-Flight 2. Flight Idle Fuel Flow F. Limitations...

14 CFR Special Federal Aviation... - Mitsubishi MU-2B Series Special Training, Experience, and Operating Requirements

Code of Federal Regulations, 2012 CFR

2012-01-01

... maintenance test flight with a second pilot or certificated mechanic, and no passengers or cargo are carried... are distributed by Turbine Aircraft Services, Inc. You may obtain a copy from Turbine Aircraft.... Supplementary NTS E. In Flight Post Maintenance Checks 1. NTS In-Flight 2. Flight Idle Fuel Flow F. Limitations...

14 CFR Special Federal Aviation... - Mitsubishi MU-2B Series Special Training, Experience, and Operating Requirements

Code of Federal Regulations, 2014 CFR

2014-01-01

... maintenance test flight with a second pilot or certificated mechanic, and no passengers or cargo are carried... are distributed by Turbine Aircraft Services, Inc. You may obtain a copy from Turbine Aircraft.... Supplementary NTS E. In Flight Post Maintenance Checks 1. NTS In-Flight 2. Flight Idle Fuel Flow F. Limitations...

Use of Source-Region-Station Time Corrections at NTS for Depth Estimation

DTIC Science & Technology

1975-07-15

Pahute Mesa events. 4 Tracings of P or PKP arrivals from NTS at RKON, 19 BUL, PRE. 5 Core-phase travel times, from Qamar (1973). 21 6...19-36. Qamar , 1973. Revised velocities in the earth’s core. Bull. Seism. Soc. Am. vol. 63, no. 3, p. 1073-1106. Richter, C F., 1958. Elementary

Motivations for Participation in Higher Education: Narratives of Non-Traditional Students at Makerere University in Uganda

ERIC Educational Resources Information Center

Tumuheki, Peace Buhwamatsiko; Zeelen, Jacques; Openjuru, George Ladaah

2016-01-01

The objective of this qualitative study was to establish motivations for participation of non-traditional students (NTS) in university education. The findings are drawn from empirical data collected from 15 unstructured in-depth interviews with NTS of the School of Computing and Informatics Technology at Makerere University, and analysed with the…

Synthesis of a 68Ga-Labeled Peptoid−Peptide Hybrid for Imaging of Neurotensin Receptor Expression in Vivo

PubMed Central

2010-01-01

The neurotensin receptor subtype 1 (NTS1) represents an attractive molecular target for imaging various tumors. Positron emission tomography (PET) gained widespread importance due to its sensitivity. We combined the design of a metabolically stable neurotensin analogue with a 68Ga-radiolabeling approach. The 68Ga-labeled peptoid−peptide hybrid [68Ga]3 revealed high stability, specific tumor uptake (0.7%ID/g, 65 min p.i.), and advantageous biokinetics in vivo using HT29 tumor-bearing nude mice. Because of the ability to internalize into NTS1-expressing tumor cells, [68Ga]3 proved to be highly suitable for a reliable and practical visualization of NTS1-expressing tumors in vivo by small animal PET. PMID:24900199

Synthesis of a (68)ga-labeled peptoid-Peptide hybrid for imaging of neurotensin receptor expression in vivo.

PubMed

Maschauer, Simone; Einsiedel, Jürgen; Hocke, Carsten; Hübner, Harald; Kuwert, Torsten; Gmeiner, Peter; Prante, Olaf

2010-08-12

The neurotensin receptor subtype 1 (NTS1) represents an attractive molecular target for imaging various tumors. Positron emission tomography (PET) gained widespread importance due to its sensitivity. We combined the design of a metabolically stable neurotensin analogue with a (68)Ga-radiolabeling approach. The (68)Ga-labeled peptoid-peptide hybrid [(68)Ga]3 revealed high stability, specific tumor uptake (0.7%ID/g, 65 min p.i.), and advantageous biokinetics in vivo using HT29 tumor-bearing nude mice. Because of the ability to internalize into NTS1-expressing tumor cells, [(68)Ga]3 proved to be highly suitable for a reliable and practical visualization of NTS1-expressing tumors in vivo by small animal PET.

Mechanical properties investigation on single-wall ZrO2 nanotubes: A finite element method with equivalent Poisson's ratio for chemical bonds

NASA Astrophysics Data System (ADS)

Yang, Xiao; Li, Huijian; Hu, Minzheng; Liu, Zeliang; Wärnå, John; Cao, Yuying; Ahuja, Rajeev; Luo, Wei

2018-04-01

A method to obtain the equivalent Poisson's ratio in chemical bonds as classical beams with finite element method was proposed from experimental data. The UFF (Universal Force Field) method was employed to calculate the elastic force constants of Zrsbnd O bonds. By applying the equivalent Poisson's ratio, the mechanical properties of single-wall ZrNTs (ZrO2 nanotubes) were investigated by finite element analysis. The nanotubes' Young's modulus (Y), Poisson's ratio (ν) of ZrNTs as function of diameters, length and chirality have been discussed, respectively. We found that the Young's modulus of single-wall ZrNTs is calculated to be between 350 and 420 GPa.

Large-Scale Transport Model Uncertainty and Sensitivity Analysis: Distributed Sources in Complex Hydrogeologic Systems

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

Sig Drellack, Lance Prothro

2007-12-01

The Underground Test Area (UGTA) Project of the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office is in the process of assessing and developing regulatory decision options based on modeling predictions of contaminant transport from underground testing of nuclear weapons at the Nevada Test Site (NTS). The UGTA Project is attempting to develop an effective modeling strategy that addresses and quantifies multiple components of uncertainty including natural variability, parameter uncertainty, conceptual/model uncertainty, and decision uncertainty in translating model results into regulatory requirements. The modeling task presents multiple unique challenges to the hydrological sciences as a result ofmore » the complex fractured and faulted hydrostratigraphy, the distributed locations of sources, the suite of reactive and non-reactive radionuclides, and uncertainty in conceptual models. Characterization of the hydrogeologic system is difficult and expensive because of deep groundwater in the arid desert setting and the large spatial setting of the NTS. Therefore, conceptual model uncertainty is partially addressed through the development of multiple alternative conceptual models of the hydrostratigraphic framework and multiple alternative models of recharge and discharge. Uncertainty in boundary conditions is assessed through development of alternative groundwater fluxes through multiple simulations using the regional groundwater flow model. Calibration of alternative models to heads and measured or inferred fluxes has not proven to provide clear measures of model quality. Therefore, model screening by comparison to independently-derived natural geochemical mixing targets through cluster analysis has also been invoked to evaluate differences between alternative conceptual models. Advancing multiple alternative flow models, sensitivity of transport predictions to parameter uncertainty is assessed through Monte Carlo simulations. The simulations are challenged by the distributed sources in each of the Corrective Action Units, by complex mass transfer processes, and by the size and complexity of the field-scale flow models. An efficient methodology utilizing particle tracking results and convolution integrals provides in situ concentrations appropriate for Monte Carlo analysis. Uncertainty in source releases and transport parameters including effective porosity, fracture apertures and spacing, matrix diffusion coefficients, sorption coefficients, and colloid load and mobility are considered. With the distributions of input uncertainties and output plume volumes, global analysis methods including stepwise regression, contingency table analysis, and classification tree analysis are used to develop sensitivity rankings of parameter uncertainties for each model considered, thus assisting a variety of decisions.« less

Autonomic control of the heart is altered in Sprague-Dawley rats with spontaneous hydronephrosis

PubMed Central

Arnold, Amy C.; Shaltout, Hossam A.; Gilliam-Davis, Shea; Kock, Nancy D.

2011-01-01

The renal medulla plays an important role in cardiovascular regulation, through interactions with the autonomic nervous system. Hydronephrosis is characterized by substantial loss of renal medullary tissue. However, whether alterations in autonomic control of the heart are observed in this condition is unknown. Thus we assessed resting hemodynamics and baroreflex sensitivity (BRS) for control of heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats with normal or hydronephrotic kidneys. While resting arterial pressure was similar, heart rate was higher in rats with hydronephrosis (290 ± 12 normal vs. 344 ± 11 mild/moderate vs. 355 ± 13 beats/min severe; P < 0.05). The evoked BRS to increases, but not decreases, in pressure was lower in hydronephrotic rats (1.06 ± 0.06 normal vs. 0.72 ± 0.10 mild/moderate vs. 0.63 ± 0.07 ms/mmHg severe; P < 0.05). Spectral analysis methods confirmed reduced parasympathetic function in hydronephrosis, with no differences in measures of indirect sympathetic activity among conditions. As a secondary aim, we investigated whether autonomic dysfunction in hydronephrosis is associated with activation of the renin-angiotensin system (RAS). There were no differences in circulating angiotensin peptides among conditions, suggesting that the impaired autonomic function in hydronephrosis is independent of peripheral RAS activation. A possible site for angiotensin II-mediated BRS impairment is the solitary tract nucleus (NTS). In normal and mild/moderate hydronephrotic rats, NTS administration of the angiotensin II type 1 receptor antagonist candesartan significantly improved the BRS, suggesting that angiotensin II provides tonic suppression to the baroreflex. In contrast, angiotensin II blockade produced no significant effect in severe hydronephrosis, indicating that at least within the NTS baroreflex suppression in these animals is independent of angiotensin II. PMID:21460193

Glutamatergic transmission in the nucleus of the solitary tract modulates memory through influences on amygdala noradrenergic systems.

PubMed

Miyashita, Teiko; Williams, Cedric L

2002-02-01

The authors examined whether glutamate release from the vagus nerve onto the nucleus of the solitary tract (NTS) is one mechanism by which the vagus influences memory and neural activity in limbic structures. Rats trained to drink from a spout were given a footshock (0.35 mA) on Day 5 after approaching the spout. Phosphate-buffered saline or 5.0, 50.0, or 100.0 nmol/0.5 microl glutamate was then infused into the NTS. Glutamate (5.0 or 50.0 nmol) significantly enhanced memory on the retention test. In Experiment 2, this effect was attenuated by blocking noradrenergic receptors in the amygdala with propranolol (0.3 microg/0.5 microl). Experiment 3 used in vivo microdialysis to determine whether footshock plus glutamate (50.0 nmol) alters noradrenergic output in the amygdala. These treatments caused a significant and long-lasting increase in amygdala noradrenergic concentrations. The results indicate that glutamate may be one transmitter that conveys the effects of vagal activation on brain systems that process memory.

Ecological Monitoring and Compliance Program Fiscal Year 2001

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

C. A. Wills

The Ecological Monitoring and Compliance program, funded through the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office, monitors the ecosystem of the Nevada Test Site (NTS) and ensures compliance with laws and regulations pertaining to NTS biota. This report summarizes the program's activities conducted by Bechtel Nevada during fiscal year 2001. Program activities included: (1) biological surveys at proposed construction sites, (2) desert tortoise compliance, (3) ecosystem mapping and data management, (4) sensitive species and unique habitat monitoring, and (5) biological monitoring at the HAZMAT Spill Center. Biological surveys for the presence of sensitive species were conductedmore » for 23 NTS projects. Eleven sites were in desert tortoise habitat. These projects have the potential to disturb a total of 588 acres, where 568 acres of disturbance would be off-road driving. No tortoises were found in or displaced from project areas, and no tortoise s were accidentally injured or killed at project areas. One tortoise was crushed by a vehicle on a paved road. A topical report describing the classification of habitat types on the NTS was completed and distributed. The report is the culmination of three years of field vegetation mapping and the analysis of vegetation data from over 1,500 ecological landform units. Compilation of historical wildlife data was initiated. A long-term monitoring plan for important plant species that occur on the NTS was completed. Site-wide monitoring was conducted for the western burrowing owl, bat species of concern, wild horses, and raptor nests. Sixty-nine of 77 known owl burrows were monitored. As in previous years, some owls were present year round on the NTS. An overall decrease in active owl burrows was observed within all three ecoregions (Mojave Desert, Transition, Great Basin Desert) from October through January. An increase in active owl burrows was observed from mid March to early April. A total of 55 juvenile owls was detected from 11 breeding pairs. Pellet analysis of burrowing owls was completed which identified key prey species. A total of 272 bats, representing 10 bat species were captured in mist-nets at water sources in the Great Basin Desert ecoregion. Bats were detected with the Anabat II call-recording system at water sources and selected tunnel and mine entrances. Thirty-seven adult horses and 11 foals were counted this year. Two of the eleven foals observed last year survived to yearlings. Seven active raptor nests were found and monitored this year. These included two Great-horned Owl nests, three Barn Owl nests, and two Red-tailed Hawk nests. Selected wetlands and man-made water sources were monitored for physical parameters and wildlife use. No dead animals were observed this year in any plastic-lined sump. The chemical spill test plans for four experiments at the HAZMAT Spill Center were reviewed for their potential to impact biota downwind of spills on Frenchman Lake playa.« less

Glucose sensing by GABAergic neurons in the mouse nucleus tractus solitarii

PubMed Central

Boychuk, Carie R.; Gyarmati, Peter; Xu, Hong

2015-01-01

Changes in blood glucose concentration alter autonomic function in a manner consistent with altered neural activity in brain regions controlling digestive processes, including neurons in the brain stem nucleus tractus solitarii (NTS), which process viscerosensory information. With whole cell or on-cell patch-clamp recordings, responses to elevating glucose concentration from 2.5 to 15 mM were assessed in identified GABAergic NTS neurons in slices from transgenic mice that express EGFP in a subset of GABA neurons. Single-cell real-time RT-PCR was also performed to detect glutamic acid decarboxylase (GAD67) in recorded neurons. In most identified GABA neurons (73%), elevating glucose concentration from 2.5 to 15 mM resulted in either increased (40%) or decreased (33%) neuronal excitability, reflected by altered membrane potential and/or action potential firing. Effects on membrane potential were maintained when action potentials or fast synaptic inputs were blocked, suggesting direct glucose sensing by GABA neurons. Glucose-inhibited GABA neurons were found predominantly in the lateral NTS, whereas glucose-excited cells were mainly in the medial NTS, suggesting regional segregation of responses. Responses were prevented in the presence of glucosamine, a glucokinase (GCK) inhibitor. Depolarizing responses were prevented when KATP channel activity was blocked with tolbutamide. Whereas effects on synaptic input to identified GABAergic neurons were variable in GABA neurons, elevating glucose increased glutamate release subsequent to stimulation of tractus solitarius in unlabeled, unidentified neurons. These results indicate that GABAergic NTS neurons act as GCK-dependent glucose sensors in the vagal complex, providing a means of modulating central autonomic signals when glucose is elevated. PMID:26084907

Fine structural survey of the intermediate subnucleus of the nucleus tractus solitarii and its glossopharyngeal afferent terminals.

PubMed

Hayakawa, Tetsu; Maeda, Seishi; Tanaka, Koichi; Seki, Makoto

2005-10-01

The intermediate subnucleus of the nucleus tractus solitarii (imNTS) receives somatosensory inputs from the soft palate and pharynx, and projects onto the nucleus ambiguus, thus serving as a relay nucleus for swallowing. The ultrastructure and synaptology of the rat imNTS, and its glossopharyngeal afferent terminals, have been examined with cholera toxin-conjugated horseradish peroxidase (CT-HRP) as an anterograde tracer. The imNTS contained oval or ellipsoid-shaped, small to medium-sized neurons (18.2 x 11.4 microm) with little cytoplasm, few cell organelles and an irregularly shaped nucleus. The cytoplasm often contained one or two nucleolus-like stigmoid bodies. The average number of axosomatic terminals was 1.8 per profile. About 83% of them contained round vesicles and formed asymmetric synaptic contacts (Gray's type I), while about 17% contained pleomorphic vesicles and formed symmetric synaptic contacts (Gray's type II). The neuropil contained small or large axodendritic terminals, and about 92% of them were Gray's type I. When CT-HRP was injected into the nodose ganglion, many labeled terminals were found in the imNTS. All anterogradely labeled terminals contacted dendrites but not somata. The labeled terminals were usually large (2.69+/-0.09 mum) and exclusively of Gray's type I. They often contacted more than two dendrites, were covered with glial processes, and formed synaptic glomeruli. A small unlabeled terminal occasionally made an asymmetric synaptic contact with a large labeled terminal. The large glossopharyngeal afferent terminals and the neurons containing stigmoid bodies characterized the imNTS neurons that received pharyngeal afferents.

Ultrastructure of the central subnucleus of the nucleus tractus solitarii and the esophageal afferent terminals in the rat.

PubMed

Hayakawa, Tetsu; Takanaga, Akinori; Tanaka, Koichi; Maeda, Seishi; Seki, Makoto

2003-03-01

The central subnucleus of the nucleus tractus solitarii (ceNTS) receives afferent projections from the esophageal wall and projects to the nucleus ambiguus, thus serving as a relay nucleus for peristalsis of the esophagus. Here we examine the synaptic organization of the ceNTS, and its esophageal afferents by using transganglionic anterograde transport of cholera toxin-conjugated horseradish peroxidase (CT-HRP). When CT-HRP was injected into the subdiaphragmatic esophagus, many anterogradely labeled terminals were found only in the ceNTS. The ceNTS was composed of round or oval-shaped, small neurons (14.7x8.7 micro m) containing sparse organelles and an irregularly shaped nucleus. The average number of axosomatic terminals was only 1.3 per section cut through the nucleolus. Most of them (92%) contained round vesicles and formed asymmetric synaptic contacts (Gray's type I), and a few (8%) contained pleomorphic vesicles and formed symmetric synaptic contacts (Gray's type II). All anterogradely labeled terminals contacted dendrites but not the neuronal somata. The labeled terminals were large (2.55+/-0.07 micro m) and exclusively Gray's type I. More than half of them (60%) contacted small dendrites (less than 1 micro m in diameter), and contained dense-cored vesicles. More than 40% of the labeled terminals contacted two to four dendrites, thus forming a synaptic glomerulus. Sometimes a labeled terminal that contacted an unlabeled terminal by an adherent junction was found within the glomerulus. The large terminals and these complex synaptic relations appeared to characterize the esophageal afferent projections in the ceNTS.

Photodynamic Effect of Ni Nanotubes on an HeLa Cell Line

PubMed Central

Hammad Aziz, Muhammad; Fakhar-e-Alam, M.; Fatima, Mahvish; Shaheen, Fozia; Iqbal, Seemab; Atif, M.; Talha, Muhammad; Mansoor Ali, Syed; Afzal, Muhammad; Majid, Abdul; Shelih Al.Harbi, Thamir; Ismail, Muhammad; Wang, Zhiming M.; AlSalhi, M. S.; Alahmed, Z. A.

2016-01-01

Nickel nanomaterials are promising in the biomedical field, especially in cancer diagnostics and targeted therapy, due to their distinctive chemical and physical properties. In this experiment, the toxicity of nickel nanotubes (Ni NTs) were tested in an in vitro cervical cancer model (HeLa cell line) to optimize the parameters of photodynamic therapy (PDT) for their greatest effectiveness. Ni NTs were synthesized by electrodeposition. Morphological analysis and magnetic behavior were examined using a Scanning electron microscope (SEM), an energy dispersive X-ray analysis (EDAX) and a vibrating sample magnetometer (VSM) analysis. Phototoxic and cytotoxic effects of nanomaterials were studied using the Ni NTs alone as well as in conjugation with aminolevulinic acid (5-ALA); this was performed both in the dark and under laser exposure. Toxic effects on the HeLa cell model were evaluated by a neutral red assay (NRA) and by detection of intracellular reactive oxygen species (ROS) production. Furthermore, 10–200 nM of Ni NTs was prepared in solution form and applied to HeLa cells in 96-well plates. Maximum toxicity of Ni NTs complexed with 5-ALA was observed at 100 J/cm2 and 200 nM. Up to 65–68% loss in cell viability was observed. Statistical analysis was performed on the experimental results to confirm the worth and clarity of results, with p-values = 0.003 and 0.000, respectively. Current results pave the way for a more rational strategy to overcome the problem of drug bioavailability in nanoparticulate targeted cancer therapy, which plays a dynamic role in clinical practice. PMID:26990435

Yield and depth Estimation of Selected NTS Nuclear and SPE Chemical Explosions Using Source Equalization by modeling Local and Regional Seismograms (Invited)

NASA Astrophysics Data System (ADS)

Saikia, C. K.; Roman-nieves, J. I.; Woods, M. T.

2013-12-01

Source parameters of nuclear and chemical explosions are often estimated by matching either the corner frequency and spectral level of a single event or the spectral ratio when spectra from two events are available with known source parameters for one. In this study, we propose an alternative method in which waveforms from two or more events can be simultaneously equalized by setting the differential of the processed seismograms at one station from any two individual events to zero. The method involves convolving the equivalent Mueller-Murphy displacement source time function (MMDSTF) of one event with the seismogram of the second event and vice-versa, and then computing their difference seismogram. MMDSTF is computed at the elastic radius including both near and far-field terms. For this method to yield accurate source parameters, an inherent assumption is that green's functions for the any paired events from the source to a receiver are same. In the frequency limit of the seismic data, this is a reasonable assumption and is concluded based on the comparison of green's functions computed for flat-earth models at various source depths ranging from 100m to 1Km. Frequency domain analysis of the initial P wave is, however, sensitive to the depth phase interaction, and if tracked meticulously can help estimating the event depth. We applied this method to the local waveforms recorded from the three SPE shots and precisely determined their yields. These high-frequency seismograms exhibit significant lateral path effects in spectrogram analysis and 3D numerical computations, but the source equalization technique is independent of any variation as long as their instrument characteristics are well preserved. We are currently estimating the uncertainty in the derived source parameters assuming the yields of the SPE shots as unknown. We also collected regional waveforms from 95 NTS explosions at regional stations ALQ, ANMO, CMB, COR, JAS LON, PAS, PFO and RSSD. We are currently employing a station based analysis using the equalization technique to estimate depth and yields of many relative to those of the announced explosions; and to develop their relationship with the Mw and Mo for the NTS explosions.

A survey of vegetation and wildland fire hazards on the Nevada Test Site

Treesearch

Dennis J. Hansen; W. Kent Ostler

2008-01-01

In the springs of 2004, 2005, and 2006, surveys were conducted on the Nevada Test Site (NTS) to characterize vegetation resources and climatic components of the environment that contribute to wildland fires. The NTS includes both Great Basin Desert and Mojave Desert ecosystems and a transitional zone between these two deserts. The field surveys assessed 211 sites along...

Botulinum toxin treatment of pain syndromes -an evidence based review.

PubMed

Safarpour, Yasaman; Jabbari, Bahman

2018-06-01

This review evaluates the existing level of evidence for efficacy of BoNTs in different pain syndromes using the recommended efficacy criteria from the Assessment and Therapeutic Subcommittee of the American Academy of Neurology. There is a level A evidence (effective) for BoNT therapy in post-herpetic neuralgia, trigeminal neuralgia, and posttraumatic neuralgia. There is a level B evidence (probably effective) for diabetic neuropathy, plantar fasciitis, piriformis syndrome, pain associated with total knee arthroplasty, male pelvic pain syndrome, chronic low back pain, male pelvic pain, and neuropathic pain secondary to traumatic spinal cord injury. BoNTs are possibly effective (Level C -one class II study) for female pelvic pain, painful knee osteoarthritis, post-operative pain in children with cerebral palsy after adductor release surgery, anterior knee pain with vastus lateralis imbalance. There is a level B evidence (one class I study) that BoNT treatment is probably ineffective in carpal tunnel syndrome. For myofascial pain syndrome, the level of evidence is U (undetermined) due to contradicting results. More high quality (Class I) studies and studies with different types of BoNTs are needed for better understanding of the role of BoNTs in pain syndromes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats

PubMed Central

Fu, Zhenxing; Powell, Frank L.

2011-01-01

During ventilatory acclimatization to hypoxia (VAH), time-dependent increases in ventilation lower Pco2 levels, and this persists on return to normoxia. We hypothesized that plasticity in the caudal nucleus tractus solitarii (NTS) contributes to VAH, as the NTS receives the first synapse from the carotid body chemoreceptor afferents and also contains CO2-sensitive neurons. We lesioned cells in the caudal NTS containing the neurokinin-1 receptor by microinjecting the neurotoxin saporin conjugated to substance P and measured ventilatory responses in awake, unrestrained rats 18 days later. Lesions did not affect hypoxic or hypercapnic ventilatory responses in normoxic control rats, in contrast to published reports for similar lesions in other central chemosensitive areas. Also, lesions did not affect the hypercapnic ventilatory response in chronically hypoxic rats (inspired Po2 = 90 Torr for 7 days). These results suggest functional differences between central chemoreceptor sites. However, lesions significantly increased ventilation in normoxia or acute hypoxia in chronically hypoxic rats. Hence, chronic hypoxia increases an inhibitory effect of neurokinin-1 receptor neurons in the NTS on ventilatory drive, indicating that these neurons contribute to plasticity during chronic hypoxia, although such plasticity does not explain VAH. PMID:21593425

The Adenosinergic System as a Therapeutic Target in the Vasculature: New Ligands and Challenges.

PubMed

Sousa, Joana Beatriz; Diniz, Carmen

2017-05-06

Adenosine is an adenine base purine with actions as a modulator of neurotransmission, smooth muscle contraction, and immune response in several systems of the human body, including the cardiovascular system. In the vasculature, four P1-receptors or adenosine receptors-A₁, A 2A , A 2B and A₃-have been identified. Adenosine receptors are membrane G-protein receptors that trigger their actions through several signaling pathways and present differential affinity requirements. Adenosine is an endogenous ligand whose extracellular levels can reach concentrations high enough to activate the adenosine receptors. This nucleoside is a product of enzymatic breakdown of extra and intracellular adenine nucleotides and also of S-adenosylhomocysteine. Adenosine availability is also dependent on the activity of nucleoside transporters (NTs). The interplay between NTs and adenosine receptors' activities are debated and a particular attention is given to the paramount importance of the disruption of this interplay in vascular pathophysiology, namely in hypertension., The integration of important functional aspects of individual adenosine receptor pharmacology (such as in vasoconstriction/vasodilation) and morphological features (within the three vascular layers) in vessels will be discussed, hopefully clarifying the importance of adenosine receptors/NTs for modulating peripheral mesenteric vascular resistance. In recent years, an increase interest in purine physiology/pharmacology has led to the development of new ligands for adenosine receptors. Some of them have been patented as having promising therapeutic activities and some have been chosen to undergo on clinical trials. Increased levels of endogenous adenosine near a specific subtype can lead to its activation, constituting an indirect receptor targeting approach either by inhibition of NT or, alternatively, by increasing the activity of enzymes responsible for ATP breakdown. These findings highlight the putative role of adenosinergic players as attractive therapeutic targets for cardiovascular pathologies, namely hypertension, heart failure or stroke. Nevertheless, several aspects are still to be explored, creating new challenges to be addressed in future studies, particularly the development of strategies able to circumvent the predicted side effects of these therapies.

TTSS2-deficient hha mutant of Salmonella Typhimurium exhibits significant systemic attenuation in immunocompromised hosts

PubMed Central

Vishwakarma, Vikalp; Pati, Niladri Bhusan; Ray, Shilpa; Das, Susmita; Suar, Mrutyunjay

2014-01-01

Non-typhoidal Salmonella (NTS) infections are emerging as leading problem worldwide and the variations in host immune status append to the concern of NTS. Salmonella enterica serovar Typhimurium is one of the causative agents of NTS infections and has been extensively studied. The inactivation of Salmonella pathogenicity island 2 (SPI2) encoded type-III secretion system 2 (TTSS2) has been reported rendering the strain incapable for systemic dissemination to host sites and has also been proposed as live-attenuated vaccine. However, infections from TTSS2-deficient Salmonella have also been reported. In this study, mutant strain MT15 was developed by inactivation of the hemolysin expression modulating protein (hha) in TTSS2-deficient S. Typhimurium background. The MT15 strain showed significant level of attenuation in immune-deprived murine colitis model when tested in iNos−/−, IL10−/−, and CD40L−/− mice groups in C57BL/6 background. Further, the mutation in hha does not implicate any defect in bacterial colonization to the host gut. The long-term infection of developed mutant strain conferred protective immune responses to suitably immunized streptomycin pre-treated C57BL/6 mice. The immunization enhanced the CD4+ and CD8+ cell types involved in bacterial clearance. The serum IgG and luminal secretory IgA (sIgA) was also found to be elevated after the due course of infection. Additionally, the immunized C57BL/6 mice were protected from the subsequent lethal infection of Salmonella Typhimurium. Collectively, these findings implicate the involvement of hemolysin expression modulating protein (Hha) in establishment of bacterial infection. In light of the observed attenuation of the developed mutant strain, this study proposes the possible significance of SPI2-deficient hha mutant as an alternative live-attenuated vaccine strain for use against lethal Salmonella infections. PMID:24401482

Ultrasound Guidance for Botulinum Neurotoxin Chemodenervation Procedures.

PubMed

Alter, Katharine E; Karp, Barbara I

2017-12-28

Injections of botulinum neurotoxins (BoNTs) are prescribed by clinicians for a variety of disorders that cause over-activity of muscles; glands; pain and other structures. Accurately targeting the structure for injection is one of the principle goals when performing BoNTs procedures. Traditionally; injections have been guided by anatomic landmarks; palpation; range of motion; electromyography or electrical stimulation. Ultrasound (US) based imaging based guidance overcomes some of the limitations of traditional techniques. US and/or US combined with traditional guidance techniques is utilized and or recommended by many expert clinicians; authors and in practice guidelines by professional academies. This article reviews the advantages and disadvantages of available guidance techniques including US as well as technical aspects of US guidance and a focused literature review related to US guidance for chemodenervation procedures including BoNTs injection.

Application of zone-folding approach to the first-principles estimation of thermodynamic properties of carbon and ZrS2 -based nanotubes.

PubMed

Bandura, Andrei V; Porsev, Vitaly V; Evarestov, Robert A

2016-03-15

A zone-folding (ZF) approach is applied for the estimation of the phonon contributions to thermodynamic properties of carbon-and ZrS2 -based nanotubes (NTs) of hexagonal morphology with different chiralities. The results obtained are compared with those from the direct calculation of the thermodynamic properties of NTs using PBE0 hybrid exchange-correlation functional. The phonon contribution to the stability of NTs proved to be negligible for the internal energy and small for the Helmholtz free energy. It is found that the ZF approach allows us an accurate estimation of phonon contributions to internal energy, but slightly overestimates the phonon contributions to entropy. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study.

PubMed

Marks, Florian; von Kalckreuth, Vera; Aaby, Peter; Adu-Sarkodie, Yaw; El Tayeb, Muna Ahmed; Ali, Mohammad; Aseffa, Abraham; Baker, Stephen; Biggs, Holly M; Bjerregaard-Andersen, Morten; Breiman, Robert F; Campbell, James I; Cosmas, Leonard; Crump, John A; Espinoza, Ligia Maria Cruz; Deerin, Jessica Fung; Dekker, Denise Myriam; Fields, Barry S; Gasmelseed, Nagla; Hertz, Julian T; Van Minh Hoang, Nguyen; Im, Justin; Jaeger, Anna; Jeon, Hyon Jin; Kabore, Leon Parfait; Keddy, Karen H; Konings, Frank; Krumkamp, Ralf; Ley, Benedikt; Løfberg, Sandra Valborg; May, Jürgen; Meyer, Christian G; Mintz, Eric D; Montgomery, Joel M; Niang, Aissatou Ahmet; Nichols, Chelsea; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Jin Kyung; Park, Se Eun; Rabezanahary, Henintsoa; Rakotozandrindrainy, Raphaël; Raminosoa, Tiana Mirana; Razafindrabe, Tsiriniaina Jean Luco; Sampo, Emmanuel; Schütt-Gerowitt, Heidi; Sow, Amy Gassama; Sarpong, Nimako; Seo, Hye Jin; Sooka, Arvinda; Soura, Abdramane Bassiahi; Tall, Adama; Teferi, Mekonnen; Thriemer, Kamala; Warren, Michelle R; Yeshitela, Biruk; Clemens, John D; Wierzba, Thomas F

2017-03-01

Available incidence data for invasive salmonella disease in sub-Saharan Africa are scarce. Standardised, multicountry data are required to better understand the nature and burden of disease in Africa. We aimed to measure the adjusted incidence estimates of typhoid fever and invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, and the antimicrobial susceptibility profiles of the causative agents. We established a systematic, standardised surveillance of blood culture-based febrile illness in 13 African sentinel sites with previous reports of typhoid fever: Burkina Faso (two sites), Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar (two sites), Senegal, South Africa, Sudan, and Tanzania (two sites). We used census data and health-care records to define study catchment areas and populations. Eligible participants were either inpatients or outpatients who resided within the catchment area and presented with tympanic (≥38·0°C) or axillary temperature (≥37·5°C). Inpatients with a reported history of fever for 72 h or longer were excluded. We also implemented a health-care utilisation survey in a sample of households randomly selected from each study area to investigate health-seeking behaviour in cases of self-reported fever lasting less than 3 days. Typhoid fever and iNTS disease incidences were corrected for health-care-seeking behaviour and recruitment. Between March 1, 2010, and Jan 31, 2014, 135 Salmonella enterica serotype Typhi (S Typhi) and 94 iNTS isolates were cultured from the blood of 13 431 febrile patients. Salmonella spp accounted for 33% or more of all bacterial pathogens at nine sites. The adjusted incidence rate (AIR) of S Typhi per 100 000 person-years of observation ranged from 0 (95% CI 0-0) in Sudan to 383 (274-535) at one site in Burkina Faso; the AIR of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar (Isotry site), and South Africa to 237 (178-316) at the second site in Burkina Faso. The AIR of iNTS and typhoid fever in individuals younger than 15 years old was typically higher than in those aged 15 years or older. Multidrug-resistant S Typhi was isolated in Ghana, Kenya, and Tanzania (both sites combined), and multidrug-resistant iNTS was isolated in Burkina Faso (both sites combined), Ghana, Kenya, and Guinea-Bissau. Typhoid fever and iNTS disease are major causes of invasive bacterial febrile illness in the sampled locations, most commonly affecting children in both low and high population density settings. The development of iNTS vaccines and the introduction of S Typhi conjugate vaccines should be considered for high-incidence settings, such as those identified in this study. Bill & Melinda Gates Foundation. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats.

PubMed

Belugin, Sergei; Mifflin, Steve

2005-12-01

Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltage-dependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 +/- 5 mmHg, n = 26, P < 0.001) rats compared with normotensive (NT) rats (109 +/- 3 mmHg measured in 10 of 69 rats). Transient outward currents (TOCs) were observed in 67-82% of NTS neurons from NT and HT rats. At activation voltages from -10 to +10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P < 0.001). There were no differences in the voltage-dependent activation kinetics, the voltage dependence of steady-state inactivation, and the rise and decay time constants of the TOCs comparing neurons isolated from NT and HT rats. The 4-aminopyridine-sensitive component of the TOC was significantly less in neurons from HT compared with NT rats (P < 0.001), whereas steady-state outward currents, whether or not sensitive to 4-aminopyridine or tetraethylammonium, were not different. Delayed excitation, studied under current clamp, was observed in 60-80% of NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n = 8 cells, P = 0.022) than DiA-labeled neurons from NT rats (n = 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P = 0.016 and P = 0.014, respectively). The number of APs in the first 200 ms of a sustained depolarization was greater in HT than NT neurons (P = 0.012). These results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this contributes to reduced delayed excitation and increased AP responses to depolarizing inputs. Such changes could alter baroreflex function in hypertension.

FITC-modified PPy nanotubes embedded in nanoporous AAO membrane can detect trace PCB20 via fluorescence ratiometric measurement.

PubMed

Wang, Meiling; Meng, Guowen; Huang, Qing; Xu, Qiaoling; Chu, Zhaoqin; Zhu, Chuhong

2011-04-07

A highly sensitive and selective fluorescence ratiometric sensor membrane for 2,3,3'-trichlorobiphenyl has been achieved, via depositing polypyrrole nanotubes (PPyNTs, the fluorescence indicator) in nano-porous anodic aluminium oxide (NPAAO) template and subsequently immobilizing fluorescein isothiocyanate (as an internal reference) onto the inner walls of the PPyNTs embedded in the NPAAO.

76 FR 8730 - Desert Southwest Customer Service Region-Rate Order No. WAPA-151

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

..., DSW- GI1, PD-NTS3, and INT-NTS3 would go into effect on October 1, 2011, and would remain in effect... Schedule DSW-GI1, would go into effect and coincide with the other ancillary service rates in this rate...-based rates would, if adopted, go into effect October 1, 2011, and remain in effect through September 30...

A Comparison of Motivational Factors and Barriers to Physical Activity among Traditional versus Nontraditional College Students

ERIC Educational Resources Information Center

Kulavic, Kimberly; Hultquist, Cherilyn N.; McLester, John R.

2013-01-01

Objective: To investigate the motivational factors and the barriers to physical activity (PA) in traditional college students (TS) and nontraditional college students (NTS) and determine if differences exist between these 2 groups. Participants: A total of 746 college students; 628 were TS (19.1 [plus-minus] 1.2 years), and 118 were NTS (31.2…

Aqueous synthesis of porous platinum nanotubes at room temperature and their intrinsic peroxidase-like activity.

PubMed

Cai, Kai; Lv, Zhicheng; Chen, Kun; Huang, Liang; Wang, Jing; Shao, Feng; Wang, Yanjun; Han, Heyou

2013-07-11

Platinum nanotubes (PtNTs) exhibiting high porosity were constructed by sacrificing the exterior of tellurium nanowires (TeNWs) and disintegrating the inner part spontaneously in aqueous solution at room temperature, in which the Kirkendall effect may play an important role. The present PtNTs exhibited intrinsic peroxidase-like activity in the presence of H2O2.

Distribution of cells responsive to 5-HT₆ receptor antagonist-induced hypophagia.

PubMed

Garfield, Alastair S; Burke, Luke K; Shaw, Jill; Evans, Mark L; Heisler, Lora K

2014-06-01

The central 5-hydroxytryptamine (5-HT; serotonin) system is well established as an important regulator of appetite and continues to remain a focus of obesity research. While much emphasis has focussed on the 5-HT(2C) receptor (5-HT(2C)R) in 5-HT's anorectic effect, pharmacological manipulation of the 5-HT₆ receptor (5-HT₆R) also reduces appetite and body weight and may be amenable to obesity treatment. However, the neurological circuits that underlie 5-HT₆R-induced hypophagia remain to be identified. Using c-fos immunoreactivity (FOS-IR) as a marker of neuronal activation, here we mapped the neuroanatomical targets activated by an anorectic dose of the 5-HT₆R antagonist SB-399885 throughout the brain. Furthermore, we quantified SB-399855 activated cells within brain appetitive nuclei, the hypothalamus, dorsal raphe nucleus (DRN) and nucleus of the solitary tract (NTS). Our results reveal that 5-HT₆R antagonist-induced hypophagia is associated with significantly increased neuronal activation in two nuclei with an established role in the central control of appetite, the paraventricular nucleus of the hypothalamus (PVH) and the NTS. In contrast, no changes in FOS-IR were observed between treatment groups within other hypothalamic nuclei or DRN. The data presented here provide a first insight into the neural circuitry underlying 5-HT₆R antagonist-induced appetite suppression and highlight the PVH and NTS in the coordination of 5-HT₆R hypophagia. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Engineering a nanotubular mesoporous cobalt phosphide electrocatalyst by the Kirkendall effect towards highly efficient hydrogen evolution reactions.

PubMed

Miao, Yue-E; Li, Fei; Zhou, Yu; Lai, Feili; Lu, Hengyi; Liu, Tianxi

2017-11-02

Tailoring the size and controlling the morphology of particular nano-architectures are considered as two promising strategies to improve the catalytic performance of metal nanocrystals towards hydrogen evolution reactions (HERs). Herein, mesoporous cobalt phosphide nanotubes (CoP-NTs) with a three-dimensional network structure have been obtained through a facile and efficient electrospinning technique combined with thermal stabilization and phosphorization treatments. The thermal stabilization process has been demonstrated to play a key role in the morphological tailoring of Co 3 O 4 nanotubes (Co 3 O 4 -NTs). As a result, the CoP-NTs show one-dimensional hollow tubular architecture instead of forming a worm-like tubular CoP structure (W-CoP-NTs) or severely aggregated CoP powder (CoP-NPs) which originate from the Co 3 O 4 nanotubes without thermal stabilization treatment and Co 3 O 4 nanoparticles, respectively. Satisfyingly, under an optimized phosphorization degree, the CoP-NT electrode exhibits a low onset overpotential of 53 mV with a low Tafel slope of 50 mV dec -1 during the HER process. Furthermore, the CoP-NT electrode is capable of driving a large cathodic current density of 10 mA cm -2 at an overpotential of 152 mV, which is much lower than those of its contrast samples, i.e. CoP-NPs (211 mV) and W-CoP-NTs (230 mV). Therefore, this work provides a feasible and general strategy for constructing three-dimensionally organized mesoporous non-noble metal phosphide nanotubes as promising alternative high-performance electrocatalysts for the commercial platinum ones.

A-type potassium channels differentially tune afferent pathways from rat solitary tract nucleus to caudal ventrolateral medulla or paraventricular hypothalamus

PubMed Central

Bailey, T W; Hermes, S M; Whittier, K L; Aicher, S A; Andresen, M C

2007-01-01

The solitary tract nucleus (NTS) conveys visceral information to diverse central networks involved in homeostatic regulation. Although afferent information content arriving at various CNS sites varies substantially, little is known about the contribution of processing within the NTS to these differences. Using retrograde dyes to identify specific NTS projection neurons, we recently reported that solitary tract (ST) afferents directly contact NTS neurons projecting to caudal ventrolateral medulla (CVLM) but largely only indirectly contact neurons projecting to the hypothalamic paraventricular nucleus (PVN). Since intrinsic properties impact information transmission, here we evaluated potassium channel expression and somatodendritic morphology of projection neurons and their relation to afferent information output directed to PVN or CVLM pathways. In slices, tracer-identified projection neurons were classified as directly or indirectly (polysynaptically) coupled to ST afferents by EPSC latency characteristics (directly coupled, jitter < 200 μs). In each neuron, voltage-dependent potassium currents (IK) were evaluated and, in representative neurons, biocytin-filled structures were quantified. Both CVLM- and PVN-projecting neurons had similar, tetraethylammonium-sensitive IK. However, only PVN-projecting NTS neurons displayed large transient, 4aminopyridine-sensitive, A-type currents (IKA). PVN-projecting neurons had larger cell bodies with more elaborate dendritic morphology than CVLM-projecting neurons. ST shocks faithfully (> 75%) triggered action potentials in CVLM-projecting neurons but spike output was uniformly low (< 20%) in PVN-projecting neurons. Pre-conditioning hyperpolarization removed IKA inactivation and attenuated ST-evoked spike generation along PVN but not CVLM pathways. Thus, multiple differences in structure, organization, synaptic transmission and ion channel expression tune the overall fidelity of afferent signals that reach these destinations. PMID:17510187

Knockdown of tyrosine hydroxylase in the nucleus of the solitary tract reduces elevated blood pressure during chronic intermittent hypoxia.

PubMed

Bathina, Chandra Sekhar; Rajulapati, Anuradha; Franzke, Michelle; Yamamoto, Kenta; Cunningham, J Thomas; Mifflin, Steve

2013-11-01

Noradrenergic A2 neurons in nucleus tractus solitarius (NTS) respond to stressors such as hypoxia. We hypothesize that tyrosine hydroxylase (TH) knockdown in NTS reduces cardiovascular responses to chronic intermittent hypoxia (CIH), a model of the arterial hypoxemia observed during sleep apnea in humans. Adult male Sprague-Dawley rats were implanted with radiotelemetry transmitters and adeno-associated viral constructs with green fluorescent protein (GFP) reporter having either short hairpin RNA (shRNA) for TH or scrambled virus (scRNA) were injected into caudal NTS. Virus-injected rats were exposed to 7 days of CIH (alternating periods of 10% O2 and of 21% O2 from 8 AM to 4 PM; from 4 PM to 8 AM rats were exposed to 21% O2). CIH increased mean arterial pressure (MAP) and heart rate (HR) during the day in both the scRNA (n = 14, P < 0.001 MAP and HR) and shRNA (n = 13, P < 0.001 MAP and HR) groups. During the night, MAP and HR remained elevated in the scRNA rats (P < 0.001 MAP and HR) but not in the shRNA group. TH immunoreactivity and protein were reduced in the shRNA group. FosB/ΔFosB immunoreactivity was decreased in paraventricular nucleus (PVN) of shRNA group (P < 0.001). However, the shRNA group did not show any change in the FosB/ΔFosB immunoreactivity in the rostral ventrolateral medulla. Exposure to CIH increased MAP which persisted beyond the period of exposure to CIH. Knockdown of TH in the NTS reduced this CIH-induced persistent increase in MAP and reduced the transcriptional activation of PVN. This indicates that NTS A2 neurons play a role in the cardiovascular responses to CIH.

Cognitive training for technical and non-technical skills in robotic surgery: a randomised controlled trial.

PubMed

Raison, Nicholas; Ahmed, Kamran; Abe, Takashige; Brunckhorst, Oliver; Novara, Giacomo; Buffi, Nicolò; McIlhenny, Craig; van der Poel, Henk; van Hemelrijck, Mieke; Gavazzi, Andrea; Dasgupta, Prokar

2018-05-07

To investigate the effectiveness of motor imagery (MI) for technical skill and non-technical skill (NTS) training in minimally invasive surgery (MIS). A single-blind, parallel-group randomised controlled trial was conducted at the Vattikuti Institute of Robotic Surgery, King's College London. Novice surgeons were recruited by open invitation in 2015. After basic robotic skills training, participants underwent simple randomisation to either MI training or standard training. All participants completed a robotic urethrovesical anastomosis task within a simulated operating room. In addition to the technical task, participants were required to manage three scripted NTS scenarios. Assessment was performed by five blinded expert surgeons and a NTS expert using validated tools for evaluating technical skills [Global Evaluative Assessment of Robotic Skills (GEARS)] and NTS [Non-Technical Skills for Surgeons (NOTSS)]. Quality of MI was assessed using a revised Movement Imagery Questionnaire (MIQ). In all, 33 participants underwent MI training and 29 underwent standard training. Interrater reliability was high, Krippendorff's α = 0.85. After MI training, the mean (sd) GEARS score was significantly higher than after standard training, at 13.1 (3.25) vs 11.4 (2.97) (P = 0.03). There was no difference in mean NOTSS scores, at 25.8 vs 26.4 (P = 0.77). MI training was successful with significantly higher imagery scores than standard training (mean MIQ score 5.1 vs 4.5, P = 0.04). Motor imagery is an effective training tool for improving technical skill in MIS even in novice participants. No beneficial effect for NTS was found. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Role of nucleus of the solitary tract noradrenergic neurons in post-stress cardiovascular and hormonal control in male rats.

PubMed

Bundzikova-Osacka, Jana; Ghosal, Sriparna; Packard, Benjamin A; Ulrich-Lai, Yvonne M; Herman, James P

2015-01-01

Chronic stress causes hypothalamo-pituitary-adrenal (HPA) axis hyperactivity and cardiovascular dyshomeostasis. Noradrenergic (NA) neurons in the nucleus of the solitary tract (NTS) are considered to play a role in these changes. In this study, we tested the hypothesis that NTS NA A2 neurons are required for cardiovascular and HPA axis responses to both acute and chronic stress. Adult male rats received bilateral microinjection into the NTS of 6-hydroxydopamine (6-OHDA) to lesion A2 neurons [cardiovascular study, n = 5; HPA study, n = 5] or vehicle [cardiovascular study, n = 6; HPA study, n = 4]. Rats were exposed to acute restraint stress followed by 14 d of chronic variable stress (CVS). On the last day of testing, rats were placed in a novel elevated plus maze (EPM) to test post-CVS stress responses. Lesions of NTS A2 neurons reduced the tachycardic response to acute restraint, confirming that A2 neurons promote sympathetic activation following acute stress. In addition, CVS increased the ratio of low-frequency to high-frequency power for heart rate variability, indicative of sympathovagal imbalance, and this effect was significantly attenuated by 6-OHDA lesion. Lesions of NTS A2 neurons reduced acute restraint-induced corticosterone secretion, but did not affect the corticosterone response to the EPM, indicating that A2 neurons promote acute HPA axis responses, but are not involved in CVS-mediated HPA axis sensitization. Collectively, these data indicate that A2 neurons promote both cardiovascular and HPA axis responses to acute stress. Moreover, A2 catecholaminergic neurons may contribute to the potentially deleterious enhancement of sympathetic drive following chronic stress.

Hypothalamic modulation of the arterial chemoreceptor reflex in the anaesthetized cat: role of the nucleus tractus solitarii.

PubMed Central

Silva-Carvalho, L; Dawid-Milner, M S; Goldsmith, G E; Spyer, K M

1995-01-01

1. There is evidence in the literature of a mutual facilitatory interaction between the arterial chemoreceptor reflex and the alerting stage of the defence reaction, particularly in relation to the patterning of cardiorespiratory activity. The present study has been designed to test the hypothesis that a portion of this interaction involves synaptic interactions within the nucleus tractus solitarii (NTS). 2. The study has involved an analysis of the effective interactions between the stimulation of the arterial chemoreceptors and the hypothalamic defence area (HDA) on the activity of NTS neurones recorded in anaesthetized, paralysed and artificially ventilated cats. 3. A group of eighteen NTS neurones was classified as chemosensitive, on the basis of displaying EPSPs on sinus nerve stimulation (SN) and their failure to show an excitatory response to baroreceptor stimulation. Thirteen of these neurones displayed pronounced excitatory responses to chemoreceptor stimulation. In sixteen of these neurones HDA stimulation elicited an EPSP; in four of these sixteen neurones this early EPSP was followed by an IPSP. In the remaining two (of 18) neurones HDA stimulation provoked no obvious synaptic response but facilitated the efficacy of both chemoreceptor inputs and SN stimulation. 4. Neurones shown to receive convergent inputs from the arterial chemoreceptors (and SN stimulation) and HDA, often displayed excitatory responses to stimulation of other peripheral inputs. Vagally evoked EPSPs were observed in nine neurones, SLN-evoked responses in seven neurones and aortic nerve-evoked EPSPs in three neurones. 5. The organization of these synaptic interactions is discussed and these data are used to explain the pattern of interaction between chemoreceptor, baroreceptor and HDA inputs within the NTS. Conclusions are drawn regarding the functional role of different classes of NTS neurone, based on the findings in this and the accompanying two papers. PMID:8544136

Influence of nanotopography on periodontal ligament stem cell functions and cell sheet based periodontal regeneration

PubMed Central

Gao, Hui; Li, Bei; Zhao, Lingzhou; Jin, Yan

2015-01-01

Periodontal regeneration is an important part of regenerative medicine, with great clinical significance; however, the effects of nanotopography on the functions of periodontal ligament (PDL) stem cells (PDLSCs) and on PDLSC sheet based periodontal regeneration have never been explored. Titania nanotubes (NTs) layered on titanium (Ti) provide a good platform to study this. In the current study, the influence of NTs of different tube size on the functions of PDLSCs was observed. Afterward, an ectopic implantation model using a Ti/cell sheets/hydroxyapatite (HA) complex was applied to study the effect of the NTs on cell sheet based periodontal regeneration. The NTs were able to enhance the initial PDLSC adhesion and spread, as well as collagen secretion. With the Ti/cell sheets/HA complex model, it was demonstrated that the PDLSC sheets were capable of regenerating the PDL tissue, when combined with bone marrow mesenchymal stem cell (BMSC) sheets and HA, without the need for extra soluble chemical cues. Simultaneously, the NTs improved the periodontal regeneration result of the ectopically implanted Ti/cell sheets/HA complex, giving rise to functionally aligned collagen fiber bundles. Specifically, much denser collagen fibers, with abundant blood vessels as well as cementum-like tissue on the Ti surface, which well-resembled the structure of natural PDL, were observed in the NT5 and NT10 sample groups. Our study provides the first evidence that the nanotopographical cues obviously influence the functions of PDLSCs and improve the PDLSC sheet based periodontal regeneration size dependently, which provides new insight to the periodontal regeneration. The Ti/cell sheets/HA complex may constitute a good model to predict the effect of biomaterials on periodontal regeneration. PMID:26150714

Molecular Strain Typing of Clinical Isolates, Trichophyton rubrum using Non Transcribed Spacer (NTS) Region as a Molecular Marker

PubMed Central

Ramaraj, Vijayakumar; Vijayaraman, Rajyoganandh S; Elavarashi, Elangovan; Rangarajan, Sudha

2017-01-01

Introduction Dermatophytes are a group of fungi which infect keratinized tissues and causes superficial mycoses in humans and animals. The group comprises of three major genera, Trichophyton, Microsporum and Epidermophyton. Among them Trichophyton rubrum is a predominant anthropophilic fungi which causes chronic infections. Although, the infection is superficial and treatable, reinfection/coinfection causes inflation in the treatment cost. Identifying the source and mode of transmission is essential to prevent its transmission. Accurate discrimination is required to understand the clinical (relapse or reinfection) and epidemiological implications of the genetic heterogeneity of this species. Polymorphism in the Non Transcribed Spacer (NTS) region of ribosomal DNA (rDNA) clusters renders an effective way to discriminate strains among T. rubrum. Aim To carry out the strain typing of the clinical isolates, Trichophyton rubrum using NTS as a molecular marker. Materials and Methods Seventy T.rubrum clinical isolates obtained from April-2011-March 2013, from Sri Ramachandra Medical Centre, Chennai, Tamil Nadu, India, were identified by conventional phenotypic methods and included in this prospective study. The isolates were then subjected to Polymerase Chain Reaction (PCR) targeting two subrepeat elements (SREs), TRS-1 and TRS-2 of the NTS region. Results Strain-specific polymorphism was observed in both subrepeat loci. Total, nine different strains were obtained on combining both TRS-1 and TRS-2, SREs. Conclusion The outcome has given a strong representation for using NTS region amplification in discriminating the T. rubrum clinical isolates. The method can be adapted as a tool for conducting epidemiology and population based study in T. rubrum infections. This will help in future exploration of the epidemiology of T. rubrum. PMID:28658757

Probing defect emissions in bulk, micro- and nano-sized α-Al2O3 via X-ray excited optical luminescence

NASA Astrophysics Data System (ADS)

Wang, Zhiqiang; Li, Chunlei; Liu, Lijia; Sham, Tsun-Kong

2013-02-01

The electronic structure and optical properties of bulk, micro-sized, and nano-sized α-Al2O3 (wafer, microparticles (MPs), nanowires (NWs), and nanotubes (NTs)) have been investigated using X-ray absorption near-edge structures (XANES) and X-ray excited optical luminescence (XEOL). XANES results show that the wafer, MPs, and NTs have characteristic features of α-Al2O3. The NWs have a core/shell structure with a single crystalline α-Al2O3 core surrounded by an amorphous shell, which is consistent with transmission electron microscopy result. It is found that some Al3+ in the shell and core/shell interface of the NWs as well as the surface of the NTs were reduced to Al2+ or Al1+ during the growth process. XEOL results show that the wafer and MPs have a broad emission at 325 nm and a sharp emission at 694 nm, which are attributed to F+ center and Cr3+ impurities, respectively. The NWs exhibit an intense emission at 404 nm that comes from F center, while the NTs show relatively weak luminescence at 325, 433, and 694 nm, which are attributed to F+ center, F center, and Cr3+ impurities, respectively. The O K-edge XEOL confirms that the emissions of α-Al2O3 in the range of 250-550 nm are related to the oxygen site. Furthermore, on the basis of XEOL and photoluminescence yield, the strong luminescence of the NWs (404 nm) is related to the Al2+ or Al1+ in the shell and core/shell interface, while the luminescence of the NTs at 325 and 433 nm are related to the bulk and the Al2+ or Al1+ on the surface, respectively.

Influence of nanotopography on periodontal ligament stem cell functions and cell sheet based periodontal regeneration.

PubMed

Gao, Hui; Li, Bei; Zhao, Lingzhou; Jin, Yan

2015-01-01

Periodontal regeneration is an important part of regenerative medicine, with great clinical significance; however, the effects of nanotopography on the functions of periodontal ligament (PDL) stem cells (PDLSCs) and on PDLSC sheet based periodontal regeneration have never been explored. Titania nanotubes (NTs) layered on titanium (Ti) provide a good platform to study this. In the current study, the influence of NTs of different tube size on the functions of PDLSCs was observed. Afterward, an ectopic implantation model using a Ti/cell sheets/hydroxyapatite (HA) complex was applied to study the effect of the NTs on cell sheet based periodontal regeneration. The NTs were able to enhance the initial PDLSC adhesion and spread, as well as collagen secretion. With the Ti/cell sheets/HA complex model, it was demonstrated that the PDLSC sheets were capable of regenerating the PDL tissue, when combined with bone marrow mesenchymal stem cell (BMSC) sheets and HA, without the need for extra soluble chemical cues. Simultaneously, the NTs improved the periodontal regeneration result of the ectopically implanted Ti/cell sheets/HA complex, giving rise to functionally aligned collagen fiber bundles. Specifically, much denser collagen fibers, with abundant blood vessels as well as cementum-like tissue on the Ti surface, which well-resembled the structure of natural PDL, were observed in the NT5 and NT10 sample groups. Our study provides the first evidence that the nanotopographical cues obviously influence the functions of PDLSCs and improve the PDLSC sheet based periodontal regeneration size dependently, which provides new insight to the periodontal regeneration. The Ti/cell sheets/HA complex may constitute a good model to predict the effect of biomaterials on periodontal regeneration.

Role of nucleus of the solitary tract noradrenergic neurons in post-stress cardiovascular and hormonal control in male rats

PubMed Central

Bundzikova-Osacka, Jana; Ghosal, Sriparna; Packard, Benjamin A.; Ulrich-Lai, Yvonne M.; Herman, James P.

2015-01-01

Chronic stress causes hypothalamo-pituitary-adrenal (HPA) axis hyperactivity and cardiovascular dyshomeostasis. Noradrenergic neurons in the nucleus of the solitary tract (NTS) are considered to play a role in these changes. Here, we tested the hypothesis that NTS noradrenergic A2 neurons are required for cardiovascular and HPA axis responses to both acute and chronic stress. Adult male rats received bilateral microinjection into the NTS of 6-hydroxydopamine (6-OHDA) to lesion A2 neurons [cardiovascular study, n= 5; HPA study, n= 5], or vehicle [cardiovascular study, n= 6; HPA study, n= 4]. Rats were exposed to acute restraint stress followed by 14 days of chronic variable stress (CVS). On the last day of testing, rats were placed in a novel elevated plus maze (EPM) to test post-CVS stress responses. Lesions of NTS A2 neurons reduced the tachycardic response to acute restraint, confirming that A2 neurons promote sympathetic activation following acute stress. In addition, CVS increased the ratio of low frequency to high frequency power for heart rate variability, indicative of sympathovagal imbalance, and this effect was significantly attenuated by 6-OHDA lesion. Lesions of NTS A2 neurons reduced acute restraint-induced corticosterone secretion, but did not affect the corticosterone response to the EPM, indicating that A2 neurons promote acute HPA axis responses, but are not involved in CVS-mediated HPA axis sensitization. Collectively, these data indicate that A2 neurons promote both cardiovascular and HPA axis responses to acute stress. Moreover, A2 catecholaminergic neurons may contribute to the potentially deleterious enhancement of sympathetic drive following chronic stress. PMID:25765732

Chronic intermittent hypoxia reduces neurokinin-1 (NK(1)) receptor density in small dendrites of non-catecholaminergic neurons in mouse nucleus tractus solitarius.

PubMed

Lessard, Andrée; Coleman, Christal G; Pickel, Virginia M

2010-06-01

Chronic intermittent hypoxia (CIH) is a frequent concomitant of sleep apnea, which can increase sympathetic nerve activity through mechanisms involving chemoreceptor inputs to the commissural nucleus of the solitary tract (cNTS). These chemosensory inputs co-store glutamate and substance P (SP), an endogenous ligand for neurokinin-1 (NK(1)) receptors. Acute hypoxia results in internalization of NK(1) receptors, suggesting that CIH also may affect the subcellular distribution of NK(1) receptors in subpopulations of cNTS neurons, some of which may express tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis (TH). To test this hypothesis, we examined dual immunolabeling for the NK(1) receptor and TH in the cNTS of male mice subjected to 10days or 35days of CIH or intermittent air. Electron microscopy revealed that NK(1) receptors and TH were almost exclusively localized within separate somatodendritic profiles in cNTS of control mice. In dendrites, immunogold particles identifying NK(1) receptors were prevalent in the cytoplasm and on the plasmalemmal surface. Compared with controls, CIH produced a significant region-specific decrease in the cytoplasmic (10 and 35days, P<0.05, unpaired Student t-test) and extrasynaptic plasmalemmal (35days, P<0.01, unpaired Student t-test) density of NK(1) immunogold particles exclusively in small (<0.1microm) dendrites without TH immunoreactivity. These results suggest that CIH produces a duration-dependent reduction in the availability of NK(1) receptors preferentially in small dendrites of non-catecholaminergic neurons in the cNTS. The implications of our findings are discussed with respect to their potential involvement in the slowly developing hypertension seen in sleep apnea patients. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Chronic intermittent hypoxia reduces neurokinin-1 (NK1) receptor density in small dendrites of non-catecholaminergic neurons in mouse nucleus tractus solitarius

PubMed Central

Lessard, Andrée; Coleman, Christal G.; Pickel, Virginia M.

2010-01-01

Chronic intermittent hypoxia (CIH) is a frequent concomitant of sleep apnea, which can increase sympathetic nerve activity through mechanisms involving chemoreceptor inputs to the commissural nucleus of the solitary tract (cNTS). These chemosensory inputs co-store glutamate and substance P (SP), an endogenous ligand for neurokinin-1 (NK1) receptors. Acute hypoxia results in internalization of NK1 receptors, suggesting that CIH also may affect the subcellular distribution of NK1 receptors in subpopulations of cNTS neurons, some of which may express tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis (TH). To test this hypothesis, we examined dual immunolabeling for the NK1 receptor and TH in the cNTS of male mice subjected to 10 days or 35 days of CIH or intermittent air. Electron microscopy revealed that NK1 receptors and TH were almost exclusively localized within separate somatodendritic profiles in cNTS of control mice. In dendrites, immunogold particles identifying NK1 receptors were prevalent in the cytoplasm and on the plasmalemmal surface. Compared with controls, CIH produced a significant region-specific decrease in the cytoplasmic (10 and 35 days, P< 0.05, unpaired Student t-test) and extrasynaptic plasmalemmal (35 days, P< 0.01, unpaired Student t-test) density of NK1 immunogold particles exclusively in small (<0.1 µm) dendrites without TH immunoreactivity. These results suggest that CIH produces a duration-dependent reduction in the availability of NK1 receptors preferentially in small dendrites of non-catecholaminergic neurons in the cNTS. The implications of our findings are discussed with respect to their potential involvement in the slowly developing hypertension seen in sleep apnea patients. PMID:20206166

Review of present groundwater monitoring programs at the Nevada Test Site

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

Hershey, R.L.; Gillespie, D.

1993-09-01

Groundwater monitoring at the Nevada Test Site (NTS) is conducted to detect the presence of radionuclides produced by underground nuclear testing and to verify the quality and safety of groundwater supplies as required by the State of Nevada and federal regulations, and by U.S. Department of Energy (DOE) Orders. Groundwater is monitored at water-supply wells and at other boreholes and wells not specifically designed or located for traditional groundwater monitoring objectives. Different groundwater monitoring programs at the NTS are conducted by several DOE Nevada Operations Office (DOE/NV) contractors. Presently, these individual groundwater monitoring programs have not been assessed or administeredmore » under a comprehensive planning approach. Redundancy exists among the programs in both the sampling locations and the constituents analyzed. Also, sampling for certain radionuclides is conducted more frequently than required. The purpose of this report is to review the existing NTS groundwater monitoring programs and make recommendations for modifying the programs so a coordinated, streamlined, and comprehensive monitoring effort may be achieved by DOE/NV. This review will be accomplished in several steps. These include: summarizing the present knowledge of the hydrogeology of the NTS and the potential radionuclide source areas for groundwater contamination; reviewing the existing groundwater monitoring programs at the NTS; examining the rationale for monitoring and the constituents analyzed; reviewing the analytical methods used to quantify tritium activity; discussing monitoring network design criteria; and synthesizing the information presented and making recommendations based on the synthesis. This scope of work was requested by the DOE/NV Hydrologic Resources Management Program (HRMP) and satisfies the 1993 (fiscal year) HRMP Groundwater Monitoring Program Review task.« less

Potential Sources and Transmission of Salmonella and Antimicrobial Resistance in Kampala, Uganda

PubMed Central

Afema, Josephine A.; Byarugaba, Denis K.; Shah, Devendra H.; Atukwase, Esther; Nambi, Maria; Sischo, William M.

2016-01-01

In sub‒Saharan Africa, non‒typhoidal Salmonellae (NTS) cause invasive disease particularly in children and HIV infected adults, but the disease epidemiology is poorly understood. Between 2012 and 2013, we investigated NTS sources and transmission in Kampala. We detected Salmonella in 60% of the influent and 60% of the effluent samples from a wastewater treatment plant and 53.3% of the influent and 10% of the effluent samples from waste stabilization ponds that serve the human population; 40.9% of flush‒water samples from ruminant slaughterhouses, 6.6% of the poultry fecal samples from live bird markets and 4% of the fecal samples from swine at slaughter; and in 54.2% of the water samples from a channel that drains storm–water and effluents from the city. We obtained 775 Salmonella isolates, identified 32 serovars, and determined resistance to 15 antimicrobials. We genotyped common serovars using multiple‒locus variable number tandem repeats analysis or pulsed‒field gel electrophoresis. In addition, we analyzed 49 archived NTS isolates from asymptomatic livestock and human clinical cases. Salmonella from ruminant and swine sources were mostly pan‒susceptible (95%) while poultry isolates were generally more resistant. Salmonella Kentucky isolated from poultry exhibited extensive drug resistance characterized by resistance to 10 antimicrobials. Interestingly, similar genotypes of S. Kentucky but with less antimicrobial resistance (AMR) were found in poultry, human and environmental sources. The observed AMR patterns could be attributed to host or management factors associated with production. Alternatively, S. Kentucky may be prone to acquiring AMR. The factors driving AMR remain poorly understood and should be elucidated. Overall, shared genotypes and AMR phenotypes were found in NTS from human, livestock and environmental sources, suggesting zoonotic and environmental transmissions most likely occur. Information from this study could be used to control NTS transmission. PMID:26999788

Responses to GABA(A) receptor activation are altered in NTS neurons isolated from chronic hypoxic rats.

PubMed

Tolstykh, Gleb; Belugin, Sergei; Mifflin, Steve

2004-04-23

The inhibitory amino acid GABA is released within the nucleus of the solitary tract (NTS) during hypoxia and modulates the respiratory response to hypoxia. To determine if responses of NTS neurons to activation of GABA(A) receptors are altered following exposure to chronic hypoxia, GABA(A) receptor-evoked whole cell currents were measured in enzymatically dispersed NTS neurons from normoxic and chronic hypoxic rats. Chronic hypoxic rats were exposed to 10% O(2) for 9-12 days. Membrane capacitance was the same in neurons from normoxic (6.9+/-0.5 pF, n=16) and hypoxic (6.3+/-0.5 pF, n=15) rats. The EC(50) for peak GABA-evoked current density was significantly greater in neurons from hypoxic (21.7+/-2.2 microM) compared to normoxic rats (12.2+/-0.9 microM) (p<0.001). Peak and 5-s adapted GABA currents evoked by 1, 3 and 10 microM were greater in neurons from normoxic compared to hypoxic rats (p<0.05) whereas peak and 5-s adapted responses to 30 and 100 microM GABA were not different comparing normoxic to hypoxic rats. Desensitization of GABA(A)-evoked currents was observed at concentrations greater than 3 microM and, measured as the ratio of the current 5 s after the onset of 100 microM GABA application to the peak GABA current, was the same in neurons from normoxic (0.37+/-0.03) and hypoxic rats (0.33+/-0.04). Reduced sensitivity to GABA(A) receptor-evoked inhibition in chronic hypoxia could influence chemoreceptor afferent integration by NTS neurons.

Neurotensin enhances glutamatergic EPSCs in VTA neurons by acting on different neurotensin receptors.

PubMed

Bose, Poulomee; Rompré, Pierre-Paul; Warren, Richard A

2015-11-01

Neurotensin (NT) is an endogenous neuropeptide that modulates dopamine and glutamate neurotransmission in several limbic regions innervated by neurons located in the ventral tegmental area (VTA). While several studies showed that NT exerted a direct modulation on VTA dopamine neurons less is known about its role in the modulation of glutamatergic neurotransmission in this region. The present study was aimed at characterising the effects of NT on glutamate-mediated responses in different populations of VTA neurons. Using whole cell patch clamp recording technique in horizontal rat brain slices, we measured the amplitude of glutamatergic excitatory post-synaptic currents (EPSCs) evoked by electrical stimulation of VTA afferents before and after application of different concentrations of NT1-13 or its C-terminal fragment, NT8-13. Neurons were classified as either Ih(+) or Ih(-) based on the presence or absence of a hyperpolarisation activated cationic current (Ih). We found that NT1-13 and NT8-13 produced comparable concentration dependent increase in the amplitude of EPSCs in both Ih(+) and Ih(-) neurons. In Ih(+) neurons, the enhancement effect of NT8-13 was blocked by both antagonists, while in Ih(-) neurons it was blocked by the NTS1/NTS2 antagonist, SR142948A, but not the preferred NTS1 antagonist, SR48692. In as much as Ih(-) neurons are non-dopaminergic neurons and Ih(+) neurons represent both dopamine and non-dopamine neurons, we can conclude that NT enhances glutamatergic mediated responses in dopamine, and in a subset of non-dopamine, neurons by acting respectively on NTS1 and an NT receptor other than NTS1. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular Strain Typing of Clinical Isolates, Trichophyton rubrum using Non Transcribed Spacer (NTS) Region as a Molecular Marker.

PubMed

Ramaraj, Vijayakumar; Vijayaraman, Rajyoganandh S; Elavarashi, Elangovan; Rangarajan, Sudha; Kindo, Anupma Jyoti

2017-05-01

Dermatophytes are a group of fungi which infect keratinized tissues and causes superficial mycoses in humans and animals. The group comprises of three major genera, Trichophyton , Microsporum and Epidermophyton . Among them Trichophyton rubrum is a predominant anthropophilic fungi which causes chronic infections. Although, the infection is superficial and treatable, reinfection/coinfection causes inflation in the treatment cost. Identifying the source and mode of transmission is essential to prevent its transmission. Accurate discrimination is required to understand the clinical (relapse or reinfection) and epidemiological implications of the genetic heterogeneity of this species. Polymorphism in the Non Transcribed Spacer (NTS) region of ribosomal DNA (rDNA) clusters renders an effective way to discriminate strains among T. rubrum . To carry out the strain typing of the clinical isolates, Trichophyton rubrum using NTS as a molecular marker. Seventy T.rubrum clinical isolates obtained from April-2011-March 2013, from Sri Ramachandra Medical Centre, Chennai, Tamil Nadu, India, were identified by conventional phenotypic methods and included in this prospective study. The isolates were then subjected to Polymerase Chain Reaction (PCR) targeting two subrepeat elements (SREs), TRS-1 and TRS-2 of the NTS region. Strain-specific polymorphism was observed in both subrepeat loci. Total, nine different strains were obtained on combining both TRS-1 and TRS-2, SREs. The outcome has given a strong representation for using NTS region amplification in discriminating the T. rubrum clinical isolates. The method can be adapted as a tool for conducting epidemiology and population based study in T. rubrum infections. This will help in future exploration of the epidemiology of T. rubrum .

Comparison of the global gene expression profiles in the bovine endometrium between summer and autumn

PubMed Central

SAKUMOTO, Ryosuke; HAYASHI, Ken-Go; SAITO, Shiori; KANAHARA, Hiroko; KIZAKI, Keiichiro; IGA, Kosuke

2015-01-01

Heat stress compromises fertility during summer in dairy and beef cows by causing nutritional, physiological and reproductive damages. To examine the difference in endometrial conditions in cows between summer and autumn, gene expression profiles were compared using a 15 K bovine oligo DNA microarray. The trial was conducted in the summer (early in September) and autumn (mid-November) seasons of two consecutive years (2013–2014) in Morioka, Japan. Endometrial samples were collected from the cows using a biopsy technique. The expressions of 268 genes were significantly higher in the endometrium collected in summer than those collected in autumn, whereas the expressions of 369 genes were lower (P<0.05 or lower). Messenger RNA expressions of glycoprotein 2 (GP2), neurotensin (NTS),E-cadherin (CDH1) and heat shock 105kDa/110kDa protein 1 (HSPH1) were validated by quantitative real-time PCR. Transcripts of GP2 and NTS were more abundant in the endometrium from summer than in the endometrium from autumn (P < 0.05). In contrast, the mRNA expressions of CDH1 were lower (P < 0.05) and those of HSPH1 tended to be low (P = 0.09) in the endometrium from summer. Immunohistochemical staining showed that GP2, NTS and HSPH1 were expressed in the endometrial epithelial or glandular epithelial cells. The serum concentrations of NTS collected from the cows in summer were higher than those collected from cows in autumn (P < 0.05). Collectively, the different gene expression profiles may contribute to functional differences in the endometrium between summer and autumn, and the increases in GP2 and NTS may have a relationship with the endometrial deficiency that causes infertility of cows in summer. PMID:25994242

Comparison of the global gene expression profiles in the bovine endometrium between summer and autumn.

PubMed

Sakumoto, Ryosuke; Hayashi, Ken-Go; Saito, Shiori; Kanahara, Hiroko; Kizaki, Keiichiro; Iga, Kosuke

2015-01-01

Heat stress compromises fertility during summer in dairy and beef cows by causing nutritional, physiological and reproductive damages. To examine the difference in endometrial conditions in cows between summer and autumn, gene expression profiles were compared using a 15 K bovine oligo DNA microarray. The trial was conducted in the summer (early in September) and autumn (mid-November) seasons of two consecutive years (2013-2014) in Morioka, Japan. Endometrial samples were collected from the cows using a biopsy technique. The expressions of 268 genes were significantly higher in the endometrium collected in summer than those collected in autumn, whereas the expressions of 369 genes were lower (P<0.05 or lower). Messenger RNA expressions of glycoprotein 2 (GP2), neurotensin (NTS),E-cadherin (CDH1) and heat shock 105kDa/110kDa protein 1 (HSPH1) were validated by quantitative real-time PCR. Transcripts of GP2 and NTS were more abundant in the endometrium from summer than in the endometrium from autumn (P < 0.05). In contrast, the mRNA expressions of CDH1 were lower (P < 0.05) and those of HSPH1 tended to be low (P = 0.09) in the endometrium from summer. Immunohistochemical staining showed that GP2, NTS and HSPH1 were expressed in the endometrial epithelial or glandular epithelial cells. The serum concentrations of NTS collected from the cows in summer were higher than those collected from cows in autumn (P < 0.05). Collectively, the different gene expression profiles may contribute to functional differences in the endometrium between summer and autumn, and the increases in GP2 and NTS may have a relationship with the endometrial deficiency that causes infertility of cows in summer.

Different interactions of prolyl oligopeptidase and neurotensin in dopaminergic function of the rat nigrostriatal and mesolimbic pathways.

PubMed

Peltonen, I; Myöhänen, T T; Männistö, P T

2012-09-01

Prolyl oligopeptidase (PREP) is an intracellular enzyme digesting small proline-containing peptides. Since PREP resides the same brain areas as neurotensin in the nigrostriatal and mesolimbic dopaminergic pathways, we were interested to study if there is an intracellular interaction between them. A colocalization of PREP with neurotensin and neurotensin receptor 1 (NTS1) in the rat striatum, nucleus accumbens (NAcc), substantia nigra (SN) and ventral tegmental area (VTA) was studied with immunofluorescence. From the same brain areas, the levels of dopamine and its metabolites were measured 1 h after the injection of saline, NTS1 ligands (JMV-449; 5 μg) or antagonist (SR142948; 5 μg) to the rat striatum or NAcc. We also studied whether an intraperitoneal injection of a PREP inhibitor (KYP-2047; 5 mg/kg) affects the levels of dopamine and its metabolites alone or modifies the effects of the NTS1 ligands. PREP was highly colocalized with neurotensin and NTS1 in the VTA, and with NTS1 in the SN. Colocalization was moderate or low in other brain areas. When injected to the striatum, JMV-449 had a tendency to increase dopamine (p = 0.052) and metabolite levels in the striatum and SN, whereas SR142948 did not. After the injection to the NAcc, JMV-449 but not SR142948, increased dopamine levels in the VTA and dopamine metabolite levels in the NAcc and VTA. KYP-2047 decreased the dopamine levels in the striatum, but increased dopamine metabolite levels in the NAcc and VTA. Our results suggest a novel role for PREP in the modulation of dopaminergic transmission, which may be different in nigrostriatal and mesolimbic pathways.

Evaluation of a Simpler Tool to Assess Nontechnical Skills During Simulated Critical Events.

PubMed

Watkins, Scott C; Roberts, David A; Boulet, John R; McEvoy, Matthew D; Weinger, Matthew B

2017-04-01

Management of critical events requires teams to employ nontechnical skills (NTS), such as teamwork, communication, decision making, and vigilance. We sought to estimate the reliability and provide evidence for the validity of the ratings gathered using a new tool for assessing the NTS of anesthesia providers, the behaviorally anchored rating scale (BARS), and compare its scores with those of an established NTS tool, the Anaesthetists' Nontechnical Skills (ANTS) scale. Six previously trained raters (4 novices and 2 experts) reviewed and scored 18 recorded simulated pediatric crisis management scenarios using a modified ANTS and a BARS tool. Pearson correlation coefficients were calculated separately for the novice and expert raters, by scenario, and overall. The intrarater reliability of the ANTS total score was 0.73 (expert, 0.57; novice, 0.84); for the BARS tool, it was 0.80 (expert, 0.79; novice, 0.81). The average interrater reliability of BARS scores (0.58) was better than ANTS scores (0.37), and the interrater reliabilities of scores from novices (0.69 BARS and 0.52 ANTS) were better than those obtained from experts (0.47 BARS and 0.21 ANTS) for both scoring instruments. The Pearson correlation between the ANTS and BARS total scores was 0.74. Overall, reliability estimates were better for the BARS scores than the ANTS scores. For both measures, the intrarater and interrater reliability was better for novices compared with domain experts, suggesting that properly trained novices can reliably assess the NTS of anesthesia providers managing a simulated critical event. There was substantial correlation between the 2 scoring instruments, suggesting that the tools measured similar constructs. The BARS tool can be an alternative to the ANTS scale for the formative assessment of NTS of anesthesia providers.

α-Fe2O3 nanotubes-reduced graphene oxide composites as synergistic electrochemical capacitor materials.

PubMed

Lee, K K; Deng, S; Fan, H M; Mhaisalkar, S; Tan, H R; Tok, E S; Loh, K P; Chin, W S; Sow, C H

2012-04-28

We present a facile approach for the fabrication of a nanocomposite comprising α-Fe(2)O(3) nanotubes (NTs) anchored on reduced graphene oxide (rGO) for electrochemical capacitors (ECs). The hollow tubular structure of the α-Fe(2)O(3) NTs presents a high surface area for reaction, while the incorporation of rGO provides an efficient two-dimensional conductive pathway to allow fast, reversible redox reaction. As a result, the nanocomposite materials exhibit a specific capacitance which is remarkably higher (~7 times) than α-Fe(2)O(3) NTs alone. In addition, the nanocomposites show excellent cycling life and large negative potential window. These findings suggest that such nanocomposites are a promising candidate as negative electrodes in asymmetrical capacitors with neutral electrolytes. This journal is © The Royal Society of Chemistry 2012

Thermodynamics Study of Removal of Heavy Metal by TiN-Nanotubes

NASA Astrophysics Data System (ADS)

Mahdavian, Leila

2015-12-01

The ability of TiN-nanotube to remove lead (Pb(II)) and arsenic (As(III)) ions from aqueous solutions is investigated. The thermodynamics properties of Pb(II) and As(III) ions passing through TiN-nanotubes (TiN-NTs) is calculated in basis set (B3LYP/6-31G**) DFT-IR method by Gaussian program package. The results showed, Pb(II) and As(III) passing through had low potential in middle nanotubes, and are trapped in this place. The thermodynamic properties showed; the passing through are spontaneous and favorable because ΔGele (MJ/mol) is negative for them. The goal of this study is the detection of surface species of TiN-NTs for metal ions removal by using computer calculations. The structural and thermodynamic properties studied ions absorption on TiN-NTs at room temperature.

Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip.

PubMed

Tehran, Domenico Azarnia; Pirazzini, Marco

2018-05-10

Botulinum neurotoxins (BoNTs), the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

Emetic Mechanism in Acute Radiation Sickness

DTIC Science & Technology

1987-08-20

humans renders the subjects refractory to a wide variety of chemical emetic agents, now numbering more than 25 substances of both exogenous and endogenous...tractus solitarius with each of three neurons (shown as large triangles) in the nucleus of the tractus solitarius (NTS). These hells of NTS connect...Outputs are innervated through autonomic ganglia or by direct efferent connections. I4 Acute radiation-induced vomiting is generally typified by the

Innate and adaptive immunity in experimental glomerulonephritis: a pathfinder tale.

PubMed

Artinger, Katharina; Kirsch, Alexander H; Aringer, Ida; Moschovaki-Filippidou, Foteini; Eller, Philipp; Rosenkranz, Alexander R; Eller, Kathrin

2017-06-01

The role of innate and adaptive immune cells in the experimental model of nephrotoxic serum nephritis (NTS) has been rigorously studied in recent years. The model is dependent on kidney-infiltrating T helper (TH) 17 and TH1 cells, which recruit neutrophils and macrophages, respectively, and cause sustained kidney inflammation. In a later phase of disease, regulatory T cells (Tregs) infiltrate the kidney in an attempt to limit disease activity. In the early stage of NTS, lymph node drainage plays an important role in disease initiation since dendritic cells present the antigen to T cells in the T cell zones of the draining lymph nodes. This results in the differentiation and proliferation of TH17 and TH1 cells. In this setting, immune regulatory cells (Tregs), namely, CCR7-expressing Tregs and mast cells (MCs), which are recruited by Tregs via the production of interleukin-9, exert their immunosuppressive capacity. Together, these two cell populations inhibit T cell differentiation and proliferation, thereby limiting disease activity by as yet unknown mechanisms. In contrast, the spleen plays no role in immune activation in NTS, but constitutes a place of extramedullary haematopoiesis. The complex interactions of immune cells in NTS are still under investigation and might ultimately lead to targeted therapies in glomerulonephritis.

Effects of sintering temperature on the pyrochlore phase in PZT nanotubes and their transformation to the perovskite phase by coating with PbO multilayers.

PubMed

Han, Jin Kyu; Choi, Yong Chan; Jeon, Do Hyen; Lee, Min Ku; Bu, Sang Don

2014-11-01

We report the phase evolution of Pb(Zr0.52Ti0.48)O3 nanotubes (PZT-NTs), from the pyrochlore to perovskite phase, with an outer diameter of about 420 nm and a wall thickness of about 10 nm. The PZT-NTs were fabricated in pores of porous anodic alumina membrane (PAM) using a spin coating of PZT sol-gel solution and subsequent annealing at 500-700 degrees C in oxygen gas. The pyrochlore phase was found to be formed at 500 degrees C, and also found not to be transformed into the perovskite phase, even though annealing was performed at higher temperatures to 700 degrees C. Elementary distribution analysis of PZT-NTs embedded in PAM reveal that Pb diffusion from nanotubes into pore walls of PAM is one of the main reasons. By employing firstly an additional PbO coating on the pyrochlore nanotubes and then subsequent annealing at 700 degrees C, we have successfully achieved an almost pure perovskite phase in nanotubes. These results suggest that PbO acts as a Pb-compensation agent in the Pb- deficient PZT-NTs. Moreover, our method can be used in the synthesis of all metal-oxide materials, including volatile elements.

Cloning of the genome of a goose parvovirus vaccine strain SYG61v and rescue of infectious virions from recombinant plasmid in embryonated goose eggs.

PubMed

Wang, Jianye; Duan, Jinkun; Meng, Xia; Gong, Jiansen; Jiang, Zhiwei; Zhu, Guoqiang

2014-05-01

The SYG61v is an attenuated goose parvovirus (GPV) that has been used as a vaccine strain in China. The genome of SYG61v was sequenced to attempt to identify the genetic basis for the attenuation of this strain. The entire genome consists of 5102 nucleotides (nts), with four nt deletions compared to that of virulent strain B. The inverted terminal repeats (ITR) are 442 nts in length, of which 360 nts form a stem region, and 43 nts constitute the bubble region. Although mutations were observed throughout the ITR, no mismatch was found in the stem. Alignment with other pathogenic GPV strains (B, 82-0321, 06-0329, and YZ99-5) indicated that there are 10 and 11 amino acid mutations in the Rep1 and VP1 proteins of SYG61v, respectively. The complete genome of SYG61v was cloned into the pBluescript II vector and an infectious plasmid pSYG61v was generated. Infectious progeny virus was successfully rescued through transfection of the plasmid pSYG61v in embryonated goose eggs and yielded viral titers similar to its parental virus, as evaluated by ELD50. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of Multicomponent Exercise on Functional and Cognitive Parameters of Hypertensive Patients: A Quasi-Experimental Study

PubMed Central

Feriani, Daniele Jardim; Gonçalves, Ivan de Oliveira; Asano, Ricardo Yukio; Aguiar, Samuel da Silva; Uchida, Marco Carlos

2017-01-01

Purpose. The present study aimed to investigate the impact of a 6-month multicomponent exercise program (MCEP) on physical function and cognitive parameters of normotensive (NTS) and hypertensive (HTS) older patients and verify if age can influence the adaptations in response to the exercise. Methods. A total of 218 subjects, 101 NTS and 117 HTS, were recruited and underwent functional and cognitive evaluations before and after six months of a MCEP. The program of exercise was performed twice a week, for 26 weeks. The physical exercises were thought to mimic the activities of daily living and, therefore, aggregated functional and walking exercises. Exercise sessions were performed at moderate intensity. Results. Data indicated that HTS and NST patients showed a similar increase in the performance of walking speed test and one-leg stand test after the MCEP. Regarding age, results did not show differences in the magnitude of adaptations between old and young HTS and NTS patients. Conclusions. Data of the present study indicated that a 6-month MCEP was able to increase equally balance and mobility in NTS and HTS patients. Moreover, data demonstrated that aging did not seem to impair the capacity to adapt in response to exercise in both groups. PMID:28409030

Salmonella isolates with decreased susceptibility to extended-spectrum cephalosporins in the United States.

PubMed

Sjölund-Karlsson, Maria; Rickert, Regan; Matar, Caline; Pecic, Gary; Howie, Rebecca L; Joyce, Kevin; Medalla, Felicita; Barzilay, Ezra J; Whichard, Jean M

2010-12-01

We describe the antimicrobial susceptibility to extended-spectrum cephalosporins in non-Typhi Salmonella (NTS) isolated from humans in the United States and explore resistance mechanisms for isolates displaying decreased susceptibility to ceftriaxone or ceftiofur. We further explore the concordance between the newly revised Clinical and Laboratory Standards Institute (CLSI) breakpoints for ceftriaxone and the presence of a β-lactamase. In 2005 and 2006, public health laboratories in all U.S. state health departments forwarded every 20th NTS isolate from humans to Centers for Disease Control and Prevention as part of the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Isolates displaying decreased susceptibility (MIC ≥ 2 mg/L) to ceftriaxone or ceftiofur were included in the study. The presence of β-lactamase genes was investigated by polymerase chain reaction amplification and sequencing, targeting six different genes (bla(TEM), bla(OXA), bla(SHV), bla(CTX-M), bla(PSE), and bla(CMY)). Plasmid location of bla(CMY) was confirmed by transforming plasmids into Escherichia coli. Among the 4236 isolates of NTS submitted to NARMS in 2005 and 2006, 175 (4.1%) displayed decreased susceptibility to either ceftriaxone or ceftiofur. By polymerase chain reaction screening, one or more β-lactamase genes could be detected in 139 (80.8%) isolates. The most prevalent resistance mechanism detected was the AmpC β-lactamase gene bla(CMY.) Other β-lactamase genes detected included 11 bla(TEM-1), 3 bla(PSE-1), 2 bla(OXA-1), and 1 bla(CTX-M-15). The ceftriaxone MIC values for the bla(CMY)-containing isolates ranged from 4 to 64 mg/L; all bla(CMY)-bearing isolates were classified as ceftriaxone resistant according to current CLSI guidelines. Among NTS isolates submitted to NARMS in 2005 and 2006, cephamycinase β-lactamases are the predominant cause of decreased susceptibility to ceftriaxone. The fact that all bla(CMY)-containing isolates were classified as resistant to ceftriaxone (MIC ≥ 4 mg/L) supports the newly revised CLSI breakpoints for cephalosporins and Enterobacteriaceae.

Corrective Action Investigation Plan for Corrective Action Unit 99: Rainier Mesa/Shoshone Mountain, Nevada Test Site, Nevada with Errata and ROTC 1, Rev. No. 0

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

McCord, John; Marutzky, Sam

2004-12-01

This Corrective Action Investigation Plan (CAIP) was developed for Corrective Action Unit (CAU) 99, Rainier Mesa/Shoshone Mountain. The CAIP is a requirement of the ''Federal Facility Agreement and Consent Order'' (FFACO) agreed to by the State of Nevada, the U.S. Department of Energy (DOE), and the U.S. Department of Defense (DoD) (FFACO, 1996). The FFACO addresses environmental restoration activities at U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) facilities and sites including the underground testing area(s) of the Nevada Test Site (NTS). This CAIP describes the investigation activities currently planned for the Rainier Mesa/Shoshone Mountain CAU.more » These activities are consistent with the current Underground Test Area (UGTA) Project strategy described in Section 3.0 of Appendix VI, Revision No. 1 (December 7, 2000) of the FFACO (1996) and summarized in Section 2.1.2 of this plan. The Rainier Mesa/Shoshone Mountain CAU extends over several areas of the NTS (Figure 1-1) and includes former underground nuclear testing locations in Areas 12 and 16. The area referred to as ''Rainier Mesa'' includes the geographical area of Rainier Mesa proper and the contiguous Aqueduct Mesa. Figure 1-2 shows the locations of the tests (within tunnel complexes) conducted at Rainier Mesa. Shoshone Mountain is located approximately 20 kilometers (km) south of Rainier Mesa, but is included within the same CAU due to similarities in their geologic setting and in the nature and types of nuclear tests conducted. Figure 1-3 shows the locations of the tests conducted at Shoshone Mountain. The Rainier Mesa/Shoshone Mountain CAU falls within the larger-scale Rainier Mesa/Shoshone Mountain Investigation Area, which also includes the northwest section of the Yucca Flat CAU as shown in Figure 1-1. Rainier Mesa and Shoshone Mountain lie adjacent to the Timber Mountain Caldera Complex and are composed of volcanic rocks that erupted from the caldera as well as from more distant sources. This has resulted in a layered volcanic stratigraphy composed of thick deposits of welded and nonwelded ash-flow tuff and lava flows. These deposits are proximal to the source caldera and are interstratified with the more distal facies of fallout tephra and bedded reworked tuff from more distant sources. In each area, a similar volcanic sequence was deposited upon Paleozoic carbonate and siliciclastic rocks that are disrupted by various thrust faults, normal faults, and strike-slip faults. In both Rainier Mesa (km) to the southwest, and Tippipah Spring, 4 km to the north, and the tunnel complex is dry. Particle-tracking simulations performed during the value of information analysis (VOIA) (SNJV, 2004b) indicate that most of the regional groundwater that underlies the test locations at Rainier Mesa and Shoshone Mountain eventually follows similar and parallel paths and ultimately discharges in Death Valley and the Amargosa Desert. Particle-tracking simulations conducted for the regional groundwater flow and risk assessment indicated that contamination from Rainier Mesa and Shoshone Mountain were unlikely to leave the NTS during the 1,000-year period of interest (DOE/NV, 1997a). It is anticipated that CAU-scale modeling will modify these results somewhat, but it is not expected to radically alter the outcome of these previous particle-tracking simulations within the 1,000-year period of interest. The Rainier Mesa/Shoshone Mountain CAIP describes the corrective action investigation (CAI) to be conducted at the Rainier Mesa/Shoshone Mountain CAU to evaluate the extent of contamination in groundwater due to the underground nuclear testing. The CAI will be conducted by the UGTA Project, which is part of the NNSA/NSO Environmental Restoration Project (ERP). The purpose and scope of the CAI are presented in this section, followed by a summary of the entire document.« less

GLP-1 acts on habenular avoidance circuits to control nicotine intake.

PubMed

Tuesta, Luis M; Chen, Zuxin; Duncan, Alexander; Fowler, Christie D; Ishikawa, Masago; Lee, Brian R; Liu, Xin-An; Lu, Qun; Cameron, Michael; Hayes, Matthew R; Kamenecka, Theodore M; Pletcher, Matthew; Kenny, Paul J

2017-05-01

Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake. Conversely, Glp1r knockout mice consumed greater quantities of nicotine than wild-type mice. Using optogenetic stimulation, we show that GLP-1 excites medial habenular (MHb) projections to the interpeduncular nucleus (IPN). Activation of GLP-1 receptors in the MHb-IPN circuit abolished nicotine reward and decreased nicotine intake, whereas their knockdown or pharmacological blockade increased intake. GLP-1 neurons may therefore serve as 'satiety sensors' for nicotine that stimulate habenular systems to promote nicotine avoidance before its aversive effects are encountered.

Variation in genotype and higher virulence of a strain of Sporothrix schenckii causing disseminated cutaneous sporotrichosis.

PubMed

Zhang, Zhenying; Liu, Xiaoming; Lv, Xuelian; Lin, Jingrong

2011-12-01

Sporotrichosis is usually a localized, lymphocutaneous disease, but its disseminated type was rarely reported. The main objective of this study was to identify specific DNA sequence variation and virulence of a strain of Sporothrix schenckii isolated from the lesion of disseminated cutaneous sporotrichosis. We confirmed this strain to be S. schenckii by(®) tubulin and chitin synthase gene sequence analysis in addition to the routine mycological and partial ITS and NTS sequencing. We found a 10-bp deletion in the ribosomal NTS region of this strain, in reference to the sequence of control strains isolated from fixed cutaneous sporotrichosis. After inoculated into immunosuppressed mice, this strain caused more extensive system involvement and showed stronger virulence than the control strain isolated from a fixed cutaneous sporotrichosis. Our study thus suggests that different clinical manifestation of sporotrichosis may be associated with variation in genotype and virulence of the strain, independent of effects due to the immune status of the host.

Ab-initio study of structural, electronic, and transport properties of zigzag GaP nanotubes.

PubMed

Srivastava, Anurag; Jain, Sumit Kumar; Khare, Purnima Swarup

2014-03-01

Stability and electronic properties of zigzag (3 ≤ n ≤ 16) gallium phosphide nanotubes (GaP NTs) have been analyzed by employing a systematic ab-intio approach based on density functional theory using generalized gradient approximation with revised Perdew Burke Ernzerhoff type parameterization. Diameter dependence of bond length, buckling, binding energy, and band gap has been investigated and the analysis shows that the bond length and buckling decreases with increasing diameter of the tube, highest binding energy of (16, 0) confirms this as the most stable amongst all the NTs taken into consideration. The present GaP NTs shows direct band gap and it increases with diameter of the tubes. Using a two probe model for (4, 0) NT the I-V relationship shows an exponential increase in current on applying bias voltage beyond 1.73 volt.

Sensitive and quantitative detection of botulinum neurotoxin in neurons derived from mouse embryonic stem cells.

PubMed

Pellett, Sabine; Du, Zhong-wei; Pier, Christina L; Tepp, William H; Zhang, Su-chun; Johnson, Eric A

2011-01-07

Botulinum neurotoxins (BoNTs), the most poisonous protein toxins known, represent a serious bioterrorism threat but are also used as a unique and important bio-pharmaceutical to treat an increasing myriad of neurological disorders. The only currently accepted detection method by the United States Food and Drug Administration for biological activity of BoNTs and for potency determination of pharmaceutical preparations is the mouse bioassay (MBA). Recent advances have indicated that cell-based assays using primary neuronal cells can provide an equally sensitive and robust detection platform as the MBA to reliably and quantitatively detect biologically active BoNTs. This study reports for the first time a BoNT detection assay using mouse embryonic stem cells to produce a neuronal cell culture. The data presented indicate that this assay can reliably detect BoNT/A with a similar sensitivity as the MBA. Published by Elsevier Inc.

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

Hunter, R.B.

This is the final progress report of a Department of Energy (DOE), Nevada operations Office (NV), program to monitor the ecology of the Nevada Test Site (NTS). The eight-year Basic Environmental Compliance and Monitoring Program (BECAMP) included meeting goals of understanding the spatial and temporal changes of plants and animals on the NTS, and determining the effects of DOE operations on those plants and animals. Determination of the changes was addressed through monitoring the most common plant and animal species at undisturbed (baseline) plots located in the major NTS valleys and mesas. One plot in Yucca Flat, the site ofmore » most nuclear weapons tests, was monitored annually, while other baseline plots were censused on a three- or four-year cycle. Effects of DOE operations were examined at sites of major disturbances, related to both DOE operations and natural disturbance mechanisms, censused on a three-year cycle. This report concentrates on work completed in 1994.« less

Toward better assessment of tornado potential in typhoons: Significance of considering entrainment effects for CAPE

NASA Astrophysics Data System (ADS)

Sueki, Kenta; Niino, Hiroshi

2016-12-01

The characteristics of typhoons that spawned tornadoes (tornadic typhoons: TTs) in Japan from 1991 to 2013 were investigated by composite analysis using the Japanese 55 year Reanalysis and compared with those of typhoons that did not spawn tornadoes (nontornadic typhoons: NTs). We found that convective available potential energy (CAPE), which considers the effects of entrainment (entraining CAPE: E-CAPE), and storm-relative environmental helicity (SREH) are significantly large in the northeast quadrant of TTs where tornadoes frequently occur and that E-CAPE and SREH in that quadrant for TTs are larger than those for NTs. On the other hand, ordinary CAPE without entrainment does not account for the spatial distribution of tornado occurrences nor does it distinguish TTs from NTs. E-CAPE is sensitive to humidity in the midtroposphere; thus, it is effective for detecting a conditionally unstable layer up to about 550 hPa, which is distinctive of TTs.

Flight experiments measuring boundary-layer disturbances in laminar flow and correlation with stability analysis

NASA Technical Reports Server (NTRS)

Lee, Cynthia C.; Obara, Clifford J.; Vijgen, Paul M.; Wusk, Michael S.

1991-01-01

Flight test results are reported from an experiment designed to study the detailed growth of disturbances in the laminar boundary layer. A gloved wing section incorporating closely-spaced flush-mounted streamwise-located instrumentation for measuring instability frequencies and amplitude growths as well as pressure distributions was used. The growth of Tollmien-Schlichting (T-S) and crossflow instabilities is predicted by the linear e exp n method and compared to the measured boundary-layer disturbance frequencies. The predictions showed good agreement with the measured data. The results exhibited fair agreement with previous n(T-S) and n(CF) flight correlations for several of the conditions analyzed. It is inferred from the high n(T-S) values for these data that moderately swept wings at compressible speeds can withstand higher combinations of n(T-S) and n(CF) values and still remain laminar than previously thought.

US Department of Energy Nevada Operations Office annual site environmental report: 1993. Volume 2: Appendices

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

Black, S.C.; Glines, W.M.; Townsend, Y.E.

1994-09-01

This report is comprised of appendices which support monitoring and surveillance on and around the Nevada Test Site (NTS) during 1993. Appendix A contains onsite Pu-238, gross beta, and gamma-emitting radionuclides in air. Appendix B contains onsite tritium in air. Appendix C contains onsite Pu-238, Sr-90, gross alpha and beta, gamma-emitting radionuclides, Ra-226, Ra-228 and tritium in water. A summary of 1993 results of offsite radiological monitoring is included in Appendix D. Appendix E contains radioactive noble gases in air onsite. Appendix F contains onsite thermoluminescent dosimeter data. Historical trends in onsite thermoluminescent dosimeter data are contained in Appendix G.more » Appendix H summarizes 1993 compliance at the DOE/NV NTS and non-NTS facilities. Appendix I summarizes the 1993 results of non radiological monitoring.« less

Enhanced photoelectrocatalytic performance of heterostructured TiO2-based nanoparticles decorated nanotubes

NASA Astrophysics Data System (ADS)

Wu, Liangpeng; Yang, Xu; Huang, Yanqin; Li, Xinjun

2017-06-01

Titanium oxide nanotubes were prepared by hydrothermal treatment of TiO2 powder in NaOH aqueous solution and subsequently calcined. Titanium oxide nanotubes were further decorated by TiO2 nanoparticles through in situ hydrolysis of titanium isopropoxide containing alcohol and ammonia in an aqueous medium to form the composite catalyst (TNP/TiO2NTs). The morphology and structure of TNP/TiO2NTs were characterized by scanning and transmission electron microscopy, X-ray diffraction, UV-Vis, and Raman spectra. The separation efficiency of photo-excited carriers was investigated by photoluminescence technique and photoelectrochemical behavior. The photocatalytic activity was evaluated by the photocatalytic degradation of methyl orange. Due to the synergy effect caused by the interaction of titanium oxide nanotubes and TiO2 nanoparticles, the TNP/TiO2NTs composite shows efficient photogenerated carriers' separation and the increased light absorption. The photocatalytic activity was enhanced.

Molten salt medium synthesis of wormlike platinum silver nanotubes without any organic surfactant or solvent for methanol and formic acid oxidation.

PubMed

Zhao, Haidong; Liu, Rui; Guo, Yong; Yang, Shengchun

2015-12-14

In the current research, the PtxAgy (x/y = 86/14, 79/21, 52/48, 21/79, 11/89) nanoparticles (NPs) are synthesized in the KNO3-LiNO3 molten salts without using any organic surfactant or solvent. The SEM results suggest that when the content of Ag is higher than 48%, the wormlike PtxAgy nanotubes (NTs) can be synthesized. The diameter of the PtxAgyNTs shows a slow decrease with the increase of Ag content. The TEM and HRTEM results indicate that the growth of hollow PtxAgy NTs undergoes an oriented attachment process and a Kirkendall effect approach. The results of cyclic voltammetry (CV) measurement indicate that the Pt52Ag48 catalyst presents a remarkable enhancement for methanol electrooxidation, while the Pt86Ag14 catalyst prefers electrochemically oxidizing formic acid compared with that of the commercially available Pt black.

Substrate-based inhibitors exhibiting excellent protective and therapeutic effects against Botulinum Neurotoxin A intoxication.

PubMed

Guo, Jiubiao; Wang, Jinglin; Gao, Shan; Ji, Bin; Waichi Chan, Edward; Chen, Sheng

2015-11-20

Potent inhibitors to reverse Botulinum neurotoxins (BoNTs) activity in neuronal cells are currently not available. A better understanding of the substrate recognition mechanism of BoNTs enabled us to design a novel class of peptide inhibitors which were derivatives of the BoNT/A substrate, SNAP25. Through a combination of in vitro, cellular based, and in vivo mouse assays, several potent inhibitors of approximately one nanomolar inhibitory strength both in vitro and in vivo have been identified. These compounds represent the first set of inhibitors that exhibited full protection against BoNT/A intoxication in mice model with undetectable toxicity. Our findings validated the hypothesis that a peptide inhibitor targeting the two BoNT structural regions which were responsible for substrate recognition and cleavage respectively could exhibit excellent inhibitory effect, thereby providing insight on future development of more potent inhibitors against BoNTs.

Chemosensitive Phox2b-expressing neurons are crucial for hypercapnic ventilatory response in the nucleus tractus solitarius.

PubMed

Fu, Congrui; Xue, Jinyu; Wang, Ri; Chen, Jinting; Ma, Lan; Liu, Yixian; Wang, Xuejiao; Guo, Fang; Zhang, Yi; Zhang, Xiangjian; Wang, Sheng

2017-07-15

Central hypercapnic hypoventilation is highly prevalent in children suffering from congenital central hypoventilation syndrome (CCHS). Mutations of the gene for paired-like homeobox 2b (Phox2b) are aetiologically associated with CCHS and Phox2b is present in central components of respiratory chemoreflex, such as the nucleus tractus solitarius (NTS). Injection of the neurotoxin substance P-saporin into NTS destroys Phox2b-expressing neurons. Impaired hypercapnic ventilatory response caused by this neurotoxin is attributable to a loss of CO 2 -sensitive Phox2b-expressing NTS neurons. A subgroup of Phox2b-expressing neurons exhibits intrinsic chemosensitivity. A background K + channel-like current is partially responsible for such chemosensitivity in Phox2b-expressing neurons. The present study helps us better understand the mechanism of respiratory deficits in CCHS and potentially locates a brainstem site for development of precise clinical intervention. The nucleus tractus solitarius (NTS) neurons have been considered to function as central respiratory chemoreceptors. However, the common molecular marker defined for these neurons remains unknown. The present study investigated whether paired-like homeobox 2b (Phox2b)-expressing NTS neurons are recruited in hypercapnic ventilatory response (HCVR) and whether these neurons exhibit intrinsic chemosensitivity. HCVR was assessed using whole body plethysmography and neuronal chemosensitivity was examined by patch clamp recordings in brainstem slices or dissociated neurons from Phox2b-EGFP transgenic mice. Injection of the neurotoxin substance P-saporin (SSP-SAP) into NTS destroyed Phox2b-expressing neurons. Minute ventilation and tidal volume were both reduced by 13% during exposure to 8% CO 2 in inspired air when ∼13% of the Phox2b-expressing neurons were eliminated. However, a loss of ∼18% of these neurons was associated with considerable decreases in minute ventilation by ≥18% and in tidal volume by≥22% when challenged by ≥4% CO 2 . In both cases, breathing frequency was unaffected. Most CO 2 -activated neurons were immunoreactive to Phox2b. In brainstem slices, ∼43% of Phox2b-expressing neurons from Phox2b-EGFP mice displayed a sustained or transient increase in firing rate during physiological acidification (pH 7.0 or 8% CO 2 ). Such a response was also present in dissociated neurons in favour of an intrinsic property. In voltage clamp recordings, a background K + channel-like current was found in a subgroup of Phox2b-expressing neurons. Thus, the respiratory deficits caused by injection of SSP-SAP into the NTS are attributable to proportional lesions of CO 2 /H + -sensitive Phox2b-expressing neurons. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Community radiation monitoring program. Annual report, October 1, 1992--September 30, 1993

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

Cooper, E.N.

1994-08-01

The Community Radiation Monitoring Program (CRMP) is a cooperative effort between the US Department of Energy (DOE), the US Environmental Protection Agency (EPA), the Desert Research Institute (DRI), a division of the University and Community College System of Nevada, and the Nuclear Engineering Laboratory of the University of Utah (UUNEL). The thirteenth year of this program began in the fall of 1992, and the work continues as an integral part of the DOE--sponsored long-term offsite radiological monitoring effort that has been conducted by EPA and its predecessors since the inception of nuclear testing at the Nevada Test Site (NTS). Themore » CRMP began by enhancing and centralizing environmental monitoring and sampling equipment at 15 communities in the then-existing EPA monitoring network around the NTS, and has since expanded to 19 locations in Nevada, Utah, and California. The primary objectives of this program are still to increase the understanding by the people who live in the area surrounding the NTS of the activities for which DOE is responsible, to enhance the performance of radiological sampling and monitoring, and to inform all concerned of the results of these efforts. One of the primary methods used to improve the communication link with the people in the potentially impacted area has been the hiring and training of local citizens as Station Managers and program representatives in those selected communities in the offsite area. These mangers, active science teachers wherever possible, have succeeded through their training, experience, community standing, and effort in becoming a very visible, able, and valuable asset in this link.« less

Indocyanine green fluorescence-navigated thoracoscopic anatomical segmentectomy

PubMed Central

Okumura, Sakae; Nakao, Masayuki; Matsuura, Yosuke; Nakagawa, Ken

2017-01-01

Background To evaluate the feasibility and efficacy of thoracoscopic anatomical segmentectomy (TS-S) using three-dimensional computed tomography (3D-CT) reconstruction and indocyanine green-fluorescence (ICGF) navigation. Methods Twenty TS-S procedures were performed for 15 primary lung cancers and 5 metastatic lung tumors. Preoperatively we evaluated the target segmental pulmonary artery and created a virtual intersegmental plane using 3D-CT reconstruction. Intraoperatively, the target segmental artery and bronchus were divided, and after intravenous systemic injection of indocyanine green (ICG, 0.25 mg/kg), ICGF of the non-target segments (NTS) was observed using infrared thoracoscopy (KARL STORZ Endoskope Japan K.K., Tokyo, Japan). We marked the border between target and NTS with electrocautery and divided the lung parenchyma along this border using electrocautery or staples. Strength of contrast between target and NTS was quantified as contrast index (CI) and compared over time. Results ICGF provided demarcation of sufficient clarity and duration to mark the lung surface in 19 patients (95%). TS-S was successfully performed in all patients. Mean operative duration was 186 min (90–310 min) and mean blood loss was 30 mL (0–107 mL). Demarcation appeared 20 s (10–100 s) after injection of ICG, and ICGF lasted 180 s (90–300 s). CI peaked 30 s after the appearance of ICGF and decreased over time. Effective contrast continued for 70 s (30–116 s), which was sufficient to mark the line of demarcation. There were no complications attributable to this method. Conclusions ICGF navigation is a safe and effective technique for TS-S. PMID:29078643

Native Plant Uptake Model for Radioactive Waste Disposal Areas at the Nevada Test Site

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

BROWN,THERESA J.; WIRTH,SHARON

1999-09-01

This report defines and defends the basic framework, methodology, and associated input parameters for modeling plant uptake of radionuclides for use in Performance Assessment (PA) activities of Radioactive Waste Management Sites (RWMS) at the Nevada Test Site (NTS). PAs are used to help determine whether waste disposal configurations meet applicable regulatory standards for the protection of human health, the environment, or both. Plants adapted to the arid climate of the NTS are able to rapidly capture infiltrating moisture. In addition to capturing soil moisture, plant roots absorb nutrients, minerals, and heavy metals, transporting them within the plant to the above-groundmore » biomass. In this fashion, plant uptake affects the movement of radionuclides. The plant uptake model presented reflects rooting characteristics important to plant uptake, biomass turnover rates, and the ability of plants to uptake radionuclides from the soil. Parameters are provided for modeling plant uptake and estimating surface contaminant flux due to plant uptake under both current and potential future climate conditions with increased effective soil moisture. The term ''effective moisture'' is used throughout this report to indicate the soil moisture that is available to plants and is intended to be inclusive of all the variables that control soil moisture at a site (e.g., precipitation, temperature, soil texture, and soil chemistry). Effective moisture is a concept used to simplify a number of complex, interrelated soil processes for which there are too little data to model actual plant available moisture. The PA simulates both the flux of radionuclides across the land surface and the potential dose to humans from that flux. Surface flux is modeled here as the amount of soil contamination that is transferred from the soil by roots and incorporated into aboveground biomass. Movement of contaminants to the surface is the only transport mechanism evaluated with the model presented here. Parameters necessary for estimating surface contaminant flux due to native plants expected to inhabit the NTS RWMSS are developed in this report. The model is specific to the plant communities found at the NTS and is designed for both short-term (<1,000 years) and long-term (>1,000 years) modeling efforts. While the model has been crafted for general applicability to any NTS PA, the key radionuclides considered are limited to the transuranic (TRU) wastes disposed of at the NTS.« less

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

David C. Anderson

The Environment, Safety and Health Division of the U.S. Department of Energy, Nevada Operations Office implements the Ecological Monitoring and Compliance Program on the Nevada Test Site (NTS). This program ensures compliance with applicable environmental laws and regulations, delineates and describes NTS ecosystems, and provides ecological information for predicting and evaluating potential impacts of proposed projects on those ecosystems. Over the last several decades, has taken an active role in providing information on the tatus of plant species proposed for protection under the Endangered Species Act(ESA). One such species is Clokey's eggvetch (Astragalus oophorus var. clokeyanus), which is a candidatemore » species under the listing guidelines of the ESA. Surveys for this species were conducted on the NTS in 1996, 1997, and 1998. Field surveys focused on potential habitat for this species in the southern Belted range and expanded to other areas with similar habitat. Over 30 survey day s were completed; five survey days in 1996, 25 survey days in 1997, and three survey days in 1998. Clokey's eggvetch was located at several sites in the southern Belted Range. It was found through much of the northern section of Kawich Canyon, one site at the head of Gritty Gulch, and a rather extensive location in Lambs Canyon. It was also located further south at Captain Jack Springs in the Eleana Range, in much of Falcon Canyon and around Echo Peak on Pahute Mesa, and was also found in the Timber and Shoshone Mountains. Overall, the locations of Clokey's eggvetch on the NTS appears to form a distinct bridge between populations of the species located further north in the Belted and Kawich Ranges and the population located in the Spring Mountains. Clokey's eggvetch was commonly found along washes and small draws, and typically in sandy loam soils with a covering of light tuffaceous rock. It occurs primarily above 1830 meters (6000 feet) in association with single-leaf pinyon (Pinus monophylla), Utah juniper (Juniperus osteosperma), and big sagebrush (Artemisia tridentata ssp. tridentata). Overall, the populations of Clokey's eggvetch on the NTS appear to be vigorous and do not appear threatened. It is estimated that there are approximately 2300 plants on the NTS. It should be considered as a species of concern because of its localized distribution, but it does not appear to warrant protection under the ESA.« less

Microbiological, clinical and molecular findings of non-typhoidal Salmonella bloodstream infections associated with malaria, Oriental Province, Democratic Republic of the Congo.

PubMed

Falay, Dadi; Kuijpers, Laura Maria Francisca; Phoba, Marie-France; De Boeck, Hilde; Lunguya, Octavie; Vakaniaki, Emmanuel; Bertrand, Sophie; Mattheus, Wesley; Ceyssens, Pieter-Jan; Vanhoof, Raymond; Devlieger, Hugo; Van Geet, Chris; Verheyen, Erik; Ngbonda, Dauly; Jacobs, Jan

2016-06-10

In sub-Saharan Africa, non-typhoidal Salmonella (NTS) can cause bloodstream infections, referred to as invasive non-typhoidal Salmonella disease (iNTS disease); it can occur in outbreaks and is often preceded by malaria. Data from Central Africa is limited. Clinical, microbiological and molecular findings of NTS recovered in a blood culture surveillance project (2009-2014) were analyzed. In March-July 2012 there was an epidemic increase in malaria infections in the Oriental Province of the Democratic Republic of the Congo (DRC). In one referral hospital, overall hospital admissions in June 2012 were 2.6 times higher as compared to the same period in the years before and after (336 versus an average of 128 respectively); numbers of malaria cases and blood transfusions were nearly three- and five-fold higher respectively (317 versus 112 and 250 versus 55). Case fatality rates (in-hospital deaths versus all admissions) peaked at 14.6 %. Salmonella Typhimurium and Salmonella Enteritidis together accounted for 88.9 % of pathogens isolated from blood cultures collected during an outreach visit to the affected districts in June 2012. Children infected with Salmonella Enteritidis (33 patient files available) tended to be co-infected with Plasmodium falciparum more often than children infected with Salmonella Typhimurium (40 patients files available) (81.8 % versus 62.5 %). Through the microbiological surveillance project (May 2009-May 2014) 113 unique NTS isolates were collected (28.5 % (113/396) of pathogens); most (95.3 %) were recovered from children < 15 years. Salmonella Typhimurium (n = 54) and Salmonella Enteritidis (n = 56) accounted for 47.8 % and of 49.6 % NTS isolates respectively. Multilocus variable-number tandem-repeat analysis (MLVA) revealed more heterogeneity for Salmonella Typhimurium than for Salmonella Enteritidis. Most (82/96, 85.4 %) NTS isolates that were available for antibiotic susceptibility testing were multidrug resistant. All isolates were susceptible to ceftriaxone and azithromycin. During the peak of an epidemic increase in malaria in the DRC in 2012, a high proportion of multidrug resistant Salmonella Typhimurium and Salmonella Enteritidis were isolated from blood cultures. Overall, the two serovars showed subtle differences in clinical presentation and genetic diversity.

Current Status and Future Directions of Botulinum Neurotoxins for Targeting Pain Processing

PubMed Central

Pellett, Sabine; Yaksh, Tony L.; Ramachandran, Roshni

2015-01-01

Current evidence suggests that botulinum neurotoxins (BoNTs) A1 and B1, given locally into peripheral tissues such as skin, muscles, and joints, alter nociceptive processing otherwise initiated by inflammation or nerve injury in animal models and humans. Recent data indicate that such locally delivered BoNTs exert not only local action on sensory afferent terminals but undergo transport to central afferent cell bodies (dorsal root ganglia) and spinal dorsal horn terminals, where they cleave SNAREs and block transmitter release. Increasing evidence supports the possibility of a trans-synaptic movement to alter postsynaptic function in neuronal and possibly non-neuronal (glial) cells. The vast majority of these studies have been conducted on BoNT/A1 and BoNT/B1, the only two pharmaceutically developed variants. However, now over 40 different subtypes of botulinum neurotoxins (BoNTs) have been identified. By combining our existing and rapidly growing understanding of BoNT/A1 and /B1 in altering nociceptive processing with explorations of the specific characteristics of the various toxins from this family, we may be able to discover or design novel, effective, and long-lasting pain therapeutics. This review will focus on our current understanding of the molecular mechanisms whereby BoNTs alter pain processing, and future directions in the development of these agents as pain therapeutics. PMID:26556371

Peribronchial innervation of the rat lung.

PubMed

Artico, Marco; Bosco, Sandro; Bronzetti, Elena; Felici, Laura M; Pelusi, Giuseppe; Lo Vasco, Vincenza Rita; Vitale, Marco

2004-10-01

Mammalian peribronchial tissue is supplied by several peptide-containing nerve fibers. Although it is well established that different neuropeptides exert significant effects on bronchial and vascular tone in the lungs, the role played by some neuromediators on the general regulation, differentiation and release of locally active substances is still controversial. We studied the innervation of rat peribronchial tissue by immunohistochemical techniques. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. A slight immunoreactivity for NT receptors is observed in lung bronchial epithelium. There is increasing evidence that NTs may act with a paracrine mechanism regulating functional activity of neuronal and non-neuronal structures. A specific immunoreactivity for NTs and NT receptors was also demonstrated within different layers of large, medium and small sized intrapulmonary arteries and veins, according to a recent study of our group. Moreover our data describe the expression of NTs and NT receptors in lymphoid aggregates of the lung (BALT) in which both lymphocytes and macrophages express TrkA receptor and synthesize NTs. Our results show the presence of an extensive network of innervation in the rat peribronchial tissue, confirming a morphological basis for a possible neural modulation of the respiratory mucosa and the physiological/pathophysiological mechanisms of the lung.

Thawing frozen shoulder by steroid injection.

PubMed

Pushpasekaran, Narendran; Kumar, Narender; Chopra, R K; Borah, Diganta; Arora, Sumit

2017-01-01

Frozen shoulder is not an uncommon disorder, and steroid injection into the glenohumeral (GH) joint is one of the most well-known approaches for the frozen shoulder. However, their results have been varied with beneficial effects or no additional advantage. With the understanding about the pathological changes taking place in frozen shoulder and the biomechanics involved, we wanted to evaluate the short- and long-term efficacy of steroid injection by a novel three-site (NTS) injection technique and compare it with the single-site injection (SSI). This was a prospective study with 85 patients including all stages and randomized into two groups. SSI group received steroid injection through posterior approach. NTS group received the same dose of steroid in diluted doses at three sites (posterior capsule, subacromial and subcoracoid). Second sitting was repeated after 3 weeks. Both groups had received the same physiotherapy. The patients were evaluated by CONSTANT score at initial, 3 week, 6 week and 6 month. NTS group patients had significant pain relief and early improvement in activities of daily living ( p < 0.005). Both groups had improvement in shoulder movements but with NTS group, early near-normal scores were attained and sustained after 6 months. About 43% in SSI group could not attain near-normal levels and had relapses. The three-site approach to steroid instillation in frozen shoulder is a safe method and provides early recovery and better improvement in shoulder function with less relapses.

Length and sequence heterogeneity in 5S rDNA of Populus deltoides.

PubMed

Negi, Madan S; Rajagopal, Jyothi; Chauhan, Neeti; Cronn, Richard; Lakshmikumaran, Malathi

2002-12-01

The 5S rRNA genes and their associated non-transcribed spacer (NTS) regions are present as repeat units arranged in tandem arrays in plant genomes. Length heterogeneity in 5S rDNA repeats was previously identified in Populus deltoides and was also observed in the present study. Primers were designed to amplify the 5S rDNA NTS variants from the P. deltoides genome. The PCR-amplified products from the two accessions of P. deltoides (G3 and G48) suggested the presence of length heterogeneity of 5S rDNA units within and among accessions, and the size of the spacers ranged from 385 to 434 bp. Sequence analysis of the non-transcribed spacer (NTS) revealed two distinct classes of 5S rDNA within both accessions: class 1, which contained GAA trinucleotide microsatellite repeats, and class 2, which lacked the repeats. The class 1 spacer shows length variation owing to the microsatellite, with two clones exhibiting 10 GAA repeat units and one clone exhibiting 16 such repeat units. However, distance analysis shows that class 1 spacer sequences are highly similar inter se, yielding nucleotide diversity (pi) estimates that are less than 0.15% of those obtained for class 2 spacers (pi = 0.0183 vs. 0.1433, respectively). The presence of microsatellite in the NTS region leading to variation in spacer length is reported and discussed for the first time in P. deltoides.

Nuclear transit studies of patients with intractable chronic constipation reveal a subgroup with rapid proximal colonic transit.

PubMed

Yik, Yee Ian; Cain, Timothy M; Tudball, Coral F; Cook, David J; Southwell, Bridget R; Hutson, John M

2011-07-01

Nuclear transit studies (NTS) allow us to follow transit through the stomach and the small and large intestines. We identified children with chronic constipation with rapid proximal colonic transit and characterized their clinical features. We reviewed NTS from 1998 to 2009 to identify patients with chronic constipation and rapid proximal colonic transit, defined as greater than 25% of tracer beyond hepatic flexure at 6 hour and/or greater than 25% of tracer beyond end of descending colon at 24 hour. This was correlated with clinical symptoms and outcome from patient records. Five hundred twenty children with chronic constipation underwent investigation by NTS, and 64 (12%) were identified with rapid proximal colonic transit. The clinical history, symptoms, and outcome in 55 of 64 available for analysis frequently showed family history of allergy (10.9%) and symptoms associated with food allergy/intolerance: abdominal pain (80%), anal fissure (27.3%), and other allergic symptoms (43.6%). Eighteen children were treated with dietary exclusion, with resolution of symptoms in 9 (50%). Some children with intractable chronic constipation have rapid proximal colonic transit, have symptoms consistent with possible food allergy/intolerance, and may respond to dietary exclusion. The NTS can identify these patients with rapid proximal transit that may be secondary to food intolerance. Copyright © 2011 Elsevier Inc. All rights reserved.

Sampling gaseous compounds from essential oils evaporation by solid phase microextraction devices

NASA Astrophysics Data System (ADS)

Cheng, Wen-Hsi; Lai, Chin-Hsing

2014-12-01

Needle trap samplers (NTS) are packed with 80-100 mesh divinylbenzene (DVB) particles to extract indoor volatile organic compounds (VOCs). This study compared extraction efficiency between an NTS and a commercially available 100 μm polydimethylsiloxane-solid phase microextration (PDMS-SPME) fiber sampler used to sample gaseous products in heated tea tree essential oil in different evaporation modes, which were evaporated respectively by free convection inside a glass evaporation dish at 27 °C, by evaporation diffuser at 60 °C, and by thermal ceramic wicks at 100 °C. The experimental results indicated that the NTS performed better than the SPME fiber samplers and that the NTS primarily adsorbed 5.7 ng ethylbenzene, 5.8 ng m/p-xylenes, 11.1 ng 1,2,3-trimethylbenzene, 12.4 ng 1,2,4-trimethylbenzene and 9.99 ng 1,4-diethylbenzene when thermal ceramic wicks were used to evaporate the tea tree essential oil during a 1-hr evaporation period. The experiment also indicated that the temperature used to heat the essential oils should be as low as possible to minimize irritant VOC by-products. If the evaporation temperature does not exceed 100 °C, the concentrations of main by-products trimethylbenzene and diethylbenzene are much lower than the threshold limit values recommended by the National Institute for Occupational Safety and Health (NIOSH).

Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex.

PubMed

Grabauskas, Gintautas; Zhou, Shi-Yi; Das, Sudipto; Lu, Yuanxu; Owyang, Chung; Moises, Hylan C

2004-12-15

Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the caudal portion of the nucleus tractus solitarius (NTS), an area which together with the dorsal motor nucleus of the vagus (DMV) comprises an integrated structure, the dorsal vagal complex (DVC) that processes visceral afferent signals from and provides parasympathetic motor innervation to the gastrointestinal tract. In this study, microinjection experiments were conducted in vivo in combination with whole-cell recording from neurones in rat medullary slices to test the hypothesis that PrRP plays a role in the central control of gastric motor function, acting within the DVC to modulate the activity of preganglionic vagal motor neurones that supply the stomach. Microinjection of PrRP (0.2 pmol (20 nl)(-1)) into the DMV at the level of the area postrema (+0.2 to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric contractions and increased intragastric pressure (IGP). Conversely, administration of peptide into the DMV at sites caudal to the obex (0.0 to -0.3 mm from the CS) decreased IGP and reduced phasic contractions. These effects occurred without change in mean arterial pressure and were abolished by ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s). The pattern of gastric motor responses evoked by PrRP mimicked that produced by administration of L-glutamate at the same sites, and both the effects of L-glutamate and PrRP were abolished following local administration of NMDA and non-NMDA-type glutamate receptor antagonists. On the other hand, microinjection of PrRP into the medial or comissural nucleus of the solitary tract (mNTS and comNTS, respectively) resulted in less robust changes in IGP in a smaller percentage of animals, accompanied by marked alterations in arterial pressure. Superfusion of brain slices with PrRP (100-300 nm) produced a small depolarization and increased spontaneous firing in 10 of 30 retrogradely labelled gastric-projecting DMV neurones. The excitatory effects were blocked by administration of TTX (2 mum) or specific glutamate receptor antagonists, indicating that they resulted from interactions of PrRP at a presynaptic site. Congruent with this, PrRP increased the amplitude of excitatory postsynaptic currents (EPSCs, 154 +/- 33%, 12 of 25 neurones) evoked by electrical stimulation in mNTS or comNTS. In addition, administration of PrRP decreased the paired-pulse ratio of EPSCs evoked by two identical stimuli delivered 100 ms apart (from 0.95 +/- 0.08 to 0.71 +/- 0.11, P < 0.05), whereas it did not affect the amplitude of inward currents evoked by exogenous application of L-glutamate to the slice. The frequency, but not amplitude of spontaneous EPSCs and action potential-independent miniature EPSCs was also increased by administration of PrRP, suggesting that the peptide was acting at least in part at receptors on presynaptic nerve terminals to enhance glutamatergic transmission. In recordings obtained from a separate group of slices, we did not observe any direct effects of PrRP on spontaneous discharge or postsynaptic excitability in either mNTS or comNTS neurones (n = 31). These data indicate that PrRP may act within the DVC to regulate gastric motor function by modulating the efficacy of conventional excitatory synaptic inputs from the NTS onto gastric-projecting vagal motor neurones.

Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex

PubMed Central

Grabauskas, Gintautas; Zhou, Shi-Yi; Das, Sudipto; Lu, Yuanxu; Owyang, Chung; Moises, Hylan C

2004-01-01

Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the caudal portion of the nucleus tractus solitarius (NTS), an area which together with the dorsal motor nucleus of the vagus (DMV) comprises an integrated structure, the dorsal vagal complex (DVC) that processes visceral afferent signals from and provides parasympathetic motor innervation to the gastrointestinal tract. In this study, microinjection experiments were conducted in vivo in combination with whole-cell recording from neurones in rat medullary slices to test the hypothesis that PrRP plays a role in the central control of gastric motor function, acting within the DVC to modulate the activity of preganglionic vagal motor neurones that supply the stomach. Microinjection of PrRP (0.2 pmol (20 nl)−1) into the DMV at the level of the area postrema (+0.2 to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric contractions and increased intragastric pressure (IGP). Conversely, administration of peptide into the DMV at sites caudal to the obex (0.0 to −0.3 mm from the CS) decreased IGP and reduced phasic contractions. These effects occurred without change in mean arterial pressure and were abolished by ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s). The pattern of gastric motor responses evoked by PrRP mimicked that produced by administration of l-glutamate at the same sites, and both the effects of l-glutamate and PrRP were abolished following local administration of NMDA and non-NMDA-type glutamate receptor antagonists. On the other hand, microinjection of PrRP into the medial or comissural nucleus of the solitary tract (mNTS and comNTS, respectively) resulted in less robust changes in IGP in a smaller percentage of animals, accompanied by marked alterations in arterial pressure. Superfusion of brain slices with PrRP (100–300 nm) produced a small depolarization and increased spontaneous firing in 10 of 30 retrogradely labelled gastric-projecting DMV neurones. The excitatory effects were blocked by administration of TTX (2 μm) or specific glutamate receptor antagonists, indicating that they resulted from interactions of PrRP at a presynaptic site. Congruent with this, PrRP increased the amplitude of excitatory postsynaptic currents (EPSCs, 154 ± 33%, 12 of 25 neurones) evoked by electrical stimulation in mNTS or comNTS. In addition, administration of PrRP decreased the paired-pulse ratio of EPSCs evoked by two identical stimuli delivered 100 ms apart (from 0.95 ± 0.08 to 0.71 ± 0.11, P < 0.05), whereas it did not affect the amplitude of inward currents evoked by exogenous application of l-glutamate to the slice. The frequency, but not amplitude of spontaneous EPSCs and action potential-independent miniature EPSCs was also increased by administration of PrRP, suggesting that the peptide was acting at least in part at receptors on presynaptic nerve terminals to enhance glutamatergic transmission. In recordings obtained from a separate group of slices, we did not observe any direct effects of PrRP on spontaneous discharge or postsynaptic excitability in either mNTS or comNTS neurones (n = 31). These data indicate that PrRP may act within the DVC to regulate gastric motor function by modulating the efficacy of conventional excitatory synaptic inputs from the NTS onto gastric-projecting vagal motor neurones. PMID:15486017

Bibliography of reports on studies of the geology, hydrogeology and hydrology at the Nevada Test Site, Nye County, Nevada, from 1951--1996

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

Seaber, P.R.; Stowers, E.D.; Pearl, R.H.

1997-04-01

The Nevada Test Site (NTS) was established in 1951 as a proving ground for nuclear weapons. The site had formerly been part of an Air Force bombing and gunnery range during World War II. Sponsor-directed studies of the geology, hydrogeology, and hydrology of the NTS began about 1956 and were broad based in nature, but were related mainly to the effects of the detonation of nuclear weapons. These effects included recommending acceptable media and areas for underground tests, the possibility of off-site contamination of groundwater, air blast and surface contamination in the event of venting, ground-shock damage that could resultmore » from underground blasts, and studies in support of drilling and emplacement. The studies were both of a pure scientific nature and of a practical applied nature. The NTS was the site of 828 underground nuclear tests and 100 above-ground tests conducted between 1951 and 1992 (U.S. Department of Energy, 1994a). After July 1962, all nuclear tests conducted in the United States were underground, most of them at the NTS. The first contained underground nuclear explosion was detonated on September 19, 1957, following extensive study of the underground effect of chemical explosives. The tests were performed by U.S. Department of Energy (DOE) and its predecessors, the U.S. Atomic Energy Commission and the Energy Research and Development Administration. As part of a nationwide complex for nuclear weapons design, testing and manufacturing, the NTS was the location for continental testing of new and stockpiled nuclear devices. Other tests, including Project {open_quotes}Plowshare{close_quotes} experiments to test the peaceful application of nuclear explosives, were conducted on several parts of the site. In addition, the Defense Nuclear Agency tested the effect of nuclear detonations on military hardware.« less

Development of a glycoconjugate vaccine to prevent invasive Salmonella Typhimurium infections in sub-Saharan Africa

PubMed Central

Baliban, Scott M.; Yang, Mingjun; Ramachandran, Girish; Curtis, Brittany; Shridhar, Surekha; Laufer, Rachel S.; Wang, Jin Y.; Van Druff, John; Higginson, Ellen E.; Hegerle, Nicolas; Varney, Kristen M.; Galen, James E.; Tennant, Sharon M.; Lees, Andrew; MacKerell, Alexander D.; Levine, Myron M.; Simon, Raphael

2017-01-01

Invasive infections associated with non-typhoidal Salmonella (NTS) serovars Enteritidis (SE), Typhimurium (STm) and monophasic variant 1,4,[5],12:i:- are a major health problem in infants and young children in sub-Saharan Africa, and currently, there are no approved human NTS vaccines. NTS O-polysaccharides and flagellin proteins are protective antigens in animal models of invasive NTS infection. Conjugates of SE core and O-polysaccharide (COPS) chemically linked to SE flagellin have enhanced the anti-COPS immune response and protected mice against fatal challenge with a Malian SE blood isolate. We report herein the development of a STm glycoconjugate vaccine comprised of STm COPS conjugated to the homologous serovar phase 1 flagellin protein (FliC) with assessment of the role of COPS O-acetyls for functional immunity. Sun-type COPS conjugates linked through the polysaccharide reducing end to FliC were more immunogenic and protective in mice challenged with a Malian STm blood isolate than multipoint lattice conjugates (>95% vaccine efficacy [VE] versus 30–43% VE). Immunization with de-O-acetylated STm-COPS conjugated to CRM197 provided significant but reduced protection against STm challenge compared to mice immunized with native STm-COPS:CRM197 (63–74% VE versus 100% VE). Although OPS O-acetyls were highly immunogenic, post-vaccination sera that contained various O-acetyl epitope-specific antibody profiles displayed similar in vitro bactericidal activity when equivalent titers of anti-COPS IgG were assayed. In-silico molecular modeling further indicated that STm OPS forms a single dominant conformation, irrespective of O-acetylation, in which O-acetyls extend outward and are highly solvent exposed. These preclinical results establish important quality attributes for an STm vaccine that could be co-formulated with an SE-COPS:FliC glycoconjugate as a bivalent NTS vaccine for use in sub-Saharan Africa. PMID:28388624

Effects of Technological Advances in Surgical Education on Quantitative Outcomes From Residency Programs.

PubMed

Dietl, Charles A; Russell, John C

2016-01-01

The purpose of this article is to review the literature on current technology for surgical education and to evaluate the effect of technological advances on the Accreditation Council of Graduate Medical Education (ACGME) Core Competencies, American Board of Surgery In-Training Examination (ABSITE) scores, and American Board of Surgery (ABS) certification. A literature search was obtained from MEDLINE via PubMed.gov, ScienceDirect.com, and Google Scholar on all peer-reviewed studies published since 2003 using the following search queries: technology for surgical education, simulation-based surgical training, simulation-based nontechnical skills (NTS) training, ACGME Core Competencies, ABSITE scores, and ABS pass rate. Our initial search list included the following: 648 on technology for surgical education, 413 on simulation-based surgical training, 51 on simulation-based NTS training, 78 on ABSITE scores, and 33 on ABS pass rate. Further, 42 articles on technological advances for surgical education met inclusion criteria based on their effect on ACGME Core Competencies, ABSITE scores, and ABS certification. Systematic review showed that 33 of 42 and 26 of 42 publications on technological advances for surgical education showed objective improvements regarding patient care and medical knowledge, respectively, whereas only 2 of 42 publications showed improved ABSITE scores, but none showed improved ABS pass rates. Improvements in the other ACGME core competencies were documented in 14 studies, 9 of which were on simulation-based NTS training. Most of the studies on technological advances for surgical education have shown a positive effect on patient care and medical knowledge. However, the effect of simulation-based surgical training and simulation-based NTS training on ABSITE scores and ABS certification has not been assessed. Studies on technological advances in surgical education and simulation-based NTS training showing quantitative evidence that surgery residency program objectives are achieved are still needed. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Meteorological modeling of arrival and deposition of fallout at intermediate distances downwind of the Nevada Test Site.

PubMed

Cederwall, R T; Peterson, K R

1990-11-01

A three-dimensional atmospheric transport and diffusion model is used to calculate the arrival and deposition of fallout from 13 selected nuclear tests at the Nevada Test Site (NTS) in the 1950s. Results are used to extend NTS fallout patterns to intermediate downwind distances (300 to 1200 km). The radioactive cloud is represented in the model by a population of Lagrangian marker particles, with concentrations calculated on an Eulerian grid. Use of marker particles, with fall velocities dependent on particle size, provides a realistic simulation of fallout as the debris cloud travels downwind. The three-dimensional wind field is derived from observed data, adjusted for mass consistency. Terrain is represented in the grid, which extends up to 1200 km downwind of NTS and has 32-km horizontal resolution and 1-km vertical resolution. Ground deposition is calculated by a deposition-velocity approach. Source terms and relationships between deposition and exposure rate are based on work by Hicks. Uncertainty in particle size and vertical distributions within the debris cloud (and stem) allow for some model "tuning" to better match measured ground-deposition values. Particle trajectories representing different sizes and starting heights above ground zero are used to guide source specification. An hourly time history of the modeled fallout pattern as the debris cloud moves downwind provides estimates of fallout arrival times. Results for event HARRY illustrate the methodology. The composite deposition pattern for all 13 tests is characterized by two lobes extending out to the north-northeast and east-northeast, respectively, at intermediate distances from NTS. Arrival estimates, along with modeled deposition values, augment measured deposition data in the development of data bases at the county level; these data bases are used for estimating radiation exposure at intermediate distances downwind of NTS. Results from a study of event TRINITY are also presented.

Structural Basis for the ABO Blood-Group Dependence of Plasmodium falciparum Rosetting

PubMed Central

Hessel, Audrey; Raynal, Bertrand; England, Patrick; Cohen, Jacques H.; Bertrand, Olivier; Peyrard, Thierry; Bentley, Graham A.; Lewit-Bentley, Anita; Mercereau-Puijalon, Odile

2012-01-01

The ABO blood group influences susceptibility to severe Plasmodium falciparum malaria. Recent evidence indicates that the protective effect of group O operates by virtue of reduced rosetting of infected red blood cells (iRBCs) with uninfected RBCs. Rosetting is mediated by a subgroup of PfEMP1 adhesins, with RBC binding being assigned to the N-terminal DBL1α1 domain. Here, we identify the ABO blood group as the main receptor for VarO rosetting, with a marked preference for group A over group B, which in turn is preferred to group O RBCs. We show that recombinant NTS-DBL1α1 and NTS-DBL1α1-CIDR1γ reproduce the VarO-iRBC blood group preference and document direct binding to blood group trisaccharides by surface plasmon resonance. More detailed RBC subgroup analysis showed preferred binding to group A1, weaker binding to groups A2 and B, and least binding to groups Ax and O. The 2.8 Å resolution crystal structure of the PfEMP1-VarO Head region, NTS-DBL1α1-CIDR1γ, reveals extensive contacts between the DBL1α1 and CIDR1γ and shows that the NTS-DBL1α1 hinge region is essential for RBC binding. Computer docking of the blood group trisaccharides and subsequent site-directed mutagenesis localized the RBC-binding site to the face opposite to the heparin-binding site of NTS-DBLα1. RBC binding involves residues that are conserved between rosette-forming PfEMP1 adhesins, opening novel opportunities for intervention against severe malaria. By deciphering the structural basis of blood group preferences in rosetting, we provide a link between ABO blood grouppolymorphisms and rosette-forming adhesins, consistent with the selective role of falciparum malaria on human genetic makeup. PMID:22807674

Enhanced light trapping and high charge transmission capacities of novel structures for efficient photoelectrochemical water splitting.

PubMed

Mu, Jianglong; Miao, Hui; Liu, Enzhou; Feng, Juan; Teng, Feng; Zhang, Dekai; Kou, Yumeng; Jin, Yanping; Fan, Jun; Hu, Xiaoyun

2018-06-13

Excellent PEC efficiency, good reusability and the super stability of trap-like SnS2/TiO2 nanotube arrays (NTs)-based photoanodes are reported. Specifically, the SnS2/TiO2-180 °C (ST-180) photoanode exhibited the highest photocurrent density (1.05 mA cm-2) and an optimal η (0.73%) at 0.5 V (vs. SCE) under simulated light irradiation (AM 1.5G), which are 4.6 and 3.8 times higher than those of pure TiO2 NTs (0.23 mA cm-2 and 0.19%). The IPCE values of ST-180 can reach 21.5% (365 nm) and 13.8% (420 nm), which are much higher than those of pure TiO2 NTs (10.6% at 365 nm and 0.8% at 420 nm). The APCE values of the pure TiO2 NTs photoelectrode are 12.8% (365 nm) and 1.1% (420 nm), while the ST-180 values are 22.3% and 14.2%, respectively. Furthermore, the generation rates of H2 and O2 for the ST-180 photoanode are 47.2 and 23.1 μmol cm-2 h-1 at 0.5 V under AM 1.5G, corresponding to faradaic efficiencies of around 80.1% and 78.3%, respectively. In short, the high-efficiency PEC water splitting performance of this SnS2/TiO2 photoanode results from the enhanced light harvesting ability of the trap-like SnS2 structure, accelerated carrier transportation properties of TiO2 NTs, and effective carrier separation of the type-II heterojunction structure. This work may offer a combinatorial strategy for the preparation of heterojunction structures with high PEC performance and can be a model structure for similar photoanode materials.

Localization and function of the Kv3.1b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarii

PubMed Central

Dallas, Mark L; Atkinson, Lucy; Milligan, Carol J; Morris, Neil P; Lewis, David I; Deuchars, Susan A; Deuchars, Jim

2005-01-01

The voltage-gated potassium channel subunit Kv3.1 confers fast firing characteristics to neurones. Kv3.1b subunit immunoreactivity (Kv3.1b-IR) was widespread throughout the medulla oblongata, with labelled neurones in the gracile, cuneate and spinal trigeminal nuclei. In the nucleus of the solitary tract (NTS), Kv3.1b-IR neurones were predominantly located close to the tractus solitarius (TS) and could be GABAergic or glutamatergic. Ultrastructurally, Kv3.1b-IR was detected in NTS terminals, some of which were vagal afferents. Whole-cell current-clamp recordings from neurones near the TS revealed electrophysiological characteristics consistent with the presence of Kv3.1b subunits: short duration action potentials (4.2 ± 1.4 ms) and high firing frequencies (68.9 ± 5.3 Hz), both sensitive to application of TEA (0.5 mm) and 4-aminopyridine (4-AP; 30 μm). Intracellular dialysis of an anti-Kv3.1b antibody mimicked and occluded the effects of TEA and 4-AP in NTS and dorsal column nuclei neurones, but not in dorsal vagal nucleus or cerebellar Purkinje cells (which express other Kv3 subunits, but not Kv3.1b). Voltage-clamp recordings from outside-out patches from NTS neurones revealed an outward K+ current with the basic characteristics of that carried by Kv3 channels. In NTS neurones, electrical stimulation of the TS evoked EPSPs and IPSPs, and TEA and 4-AP increased the average amplitude and decreased the paired pulse ratio, consistent with a presynaptic site of action. Synaptic inputs evoked by stimulation of a region lacking Kv3.1b-IR neurones were not affected, correlating the presence of Kv3.1b in the TS with the pharmacological effects. PMID:15528247

Development of a glycoconjugate vaccine to prevent invasive Salmonella Typhimurium infections in sub-Saharan Africa.

PubMed

Baliban, Scott M; Yang, Mingjun; Ramachandran, Girish; Curtis, Brittany; Shridhar, Surekha; Laufer, Rachel S; Wang, Jin Y; Van Druff, John; Higginson, Ellen E; Hegerle, Nicolas; Varney, Kristen M; Galen, James E; Tennant, Sharon M; Lees, Andrew; MacKerell, Alexander D; Levine, Myron M; Simon, Raphael

2017-04-01

Invasive infections associated with non-typhoidal Salmonella (NTS) serovars Enteritidis (SE), Typhimurium (STm) and monophasic variant 1,4,[5],12:i:- are a major health problem in infants and young children in sub-Saharan Africa, and currently, there are no approved human NTS vaccines. NTS O-polysaccharides and flagellin proteins are protective antigens in animal models of invasive NTS infection. Conjugates of SE core and O-polysaccharide (COPS) chemically linked to SE flagellin have enhanced the anti-COPS immune response and protected mice against fatal challenge with a Malian SE blood isolate. We report herein the development of a STm glycoconjugate vaccine comprised of STm COPS conjugated to the homologous serovar phase 1 flagellin protein (FliC) with assessment of the role of COPS O-acetyls for functional immunity. Sun-type COPS conjugates linked through the polysaccharide reducing end to FliC were more immunogenic and protective in mice challenged with a Malian STm blood isolate than multipoint lattice conjugates (>95% vaccine efficacy [VE] versus 30-43% VE). Immunization with de-O-acetylated STm-COPS conjugated to CRM197 provided significant but reduced protection against STm challenge compared to mice immunized with native STm-COPS:CRM197 (63-74% VE versus 100% VE). Although OPS O-acetyls were highly immunogenic, post-vaccination sera that contained various O-acetyl epitope-specific antibody profiles displayed similar in vitro bactericidal activity when equivalent titers of anti-COPS IgG were assayed. In-silico molecular modeling further indicated that STm OPS forms a single dominant conformation, irrespective of O-acetylation, in which O-acetyls extend outward and are highly solvent exposed. These preclinical results establish important quality attributes for an STm vaccine that could be co-formulated with an SE-COPS:FliC glycoconjugate as a bivalent NTS vaccine for use in sub-Saharan Africa.

Fabrication of Cu2O/TiO2 Nanotubes Heterojunction Arrays and Investigation of Their Photoelectrochemical Behaviour

DTIC Science & Technology

2012-11-05

investigate phase transformations in TiO2 NTs after annealing and as a consequence of the functionalization. Electrodeposition was performed in a...deposition Cu2O electrodeposition was performed by polarizing the Ti/TiO2 NTs electrodes at UE = - 0.4 V in the CuSO4 containing bath described in...polarization (UE = - 0.4 V) in the electrodeposition solution (see experimental section). As shown in Fig. 6, in spite of the constant polarizing voltage (i.e

Gaseous hydrogen embrittlement of PH 13-8 Mo steel

NASA Astrophysics Data System (ADS)

Ding, Y. S.; Tsay, L. W.; Chiang, M. F.; Chen, C.

2009-04-01

In this study, notched tensile and fatigue crack growth tests in gaseous hydrogen were performed on PH 13-8 Mo stainless steel specimens at room temperature. These specimens were susceptible to hydrogen embrittlement (HE), but at different degrees, depending on the aging conditions or the microstructures of the alloys. In hydrogen, the accelerated fatigue crack growth rate (FCGR) usually accompanied a reduced notched tensile strength (NTS) of the specimens, i.e., the faster the FCGR the lower the NTS. It was proposed that the same fracture mechanism could be applied to these two different types of specimens, regardless of the loading conditions. Rapid fatigue crack growth and high NTS loss were found in the H800 (426 °C under-aged) and H900 (482 °C peak-aged) specimens. The HE susceptibility of the steel was reduced by increasing the aging temperature above 593 °C, which was attributed to the increased amount of austenite in the structure. Extensive quasi-cleavage fracture was observed for the specimens that were deteriorated severely by HE.

Bandstructure modulation for Si-h and Si-g nanotubes in a transverse electric field: Tight binding approach

NASA Astrophysics Data System (ADS)

Chegel, Raad; Behzad, Somayeh

2013-11-01

We have investigated the electronic properties of SiNTs, under the external electric field, using Tight Binding (TB) approximation. It was found that the energy levels, energy gaps, and density of states (DOS) strongly depend on the electric field strength. The large electric strength leads to coupling the neighbor subbands and induce destruction of subband degeneracy, increase of low-energy states, and strong modulation of energy gap which these effects reflect in the DOS spectrum. It has been shown that, the band gap reduction of Si g-NTs is linearly proportional to the electric field strength. The band gap variation for Si h-NTs increases first and later decreases (Metallic) or first remains constant and then decreases (semiconductor). Also we show that the larger diameter tubes are more sensitive to the field strength than smaller ones. The semiconducting metallic transition or vice versa can be achieved through an increasing of applied fields. Number and position of peaks in DOS spectrum are dependent on electric field strength.

Structural, electronic properties and stability of metatitanic acid (H 2TiO 3) nanotubes

NASA Astrophysics Data System (ADS)

Enyashin, A. N.; Denisova, T. A.; Ivanovskii, A. L.

2009-12-01

Quite recently, metatitanic acid (H 2TiO 3) has been successfully prepared, which extended the family of known titanic acids H 2Ti nO 2n+1 ( n = 2, 3 and 4). Here the atomic models for nanotubes (NTs) of metatitanic acid are designed and their cohesive and electronic properties are considered depending on their chirality and radii by means of density-functional theory-tight-binding (DFTB) method. Our main findings are that the proposed H 2TiO 3 tubes are stable and that all these NTs will be the insulators (independently from their chirality and the diameters) with forbidden gaps at about ˜4.6 eV. We have found also that aforementioned properties of predicted H 2TiO 3 NTs are very similar with those of recently prepared fabricated nanotubes of polytitanic acids; thus, it is possible to expect that the proposed H 2TiO 3 tubular materials may be fabricated.

Fast growth with crystal splitting of morphology-controllable Bi2S3 flowers on TiO2 nanotube arrays

NASA Astrophysics Data System (ADS)

Yang, L. X.; Ding, Y. B.; Luo, S. L.; Luo, Y.; Deng, F.; Li, Y.

2013-03-01

Bi2S3 crystals with flower-like morphologies are deposited on TiO2 nanotube arrays (NTs) by applying the cathodic pulse electrodeposition (PED) technique at 120 °C in 20 s. The highly oriented TiO2 NTs/Ti serving as substrate has high surface energy which is favorable for Gibbs free energy decreasing in nucleation process. Numerous boundaries between NTs are nucleation sites for atomic clusters, resulting in a fast nucleation velocity. Effective and fast heterogeneous nucleation initiates a thermodynamic control growth model and finally leads to the fast formation of highly crystallized Bi2S3 with a typical splitting property. Ethylene glycol (EG) was introduced into the electrolytes to inhibit the typical growth along the c axis ([0 0 1] plane) and facilitate the growth along the ab plane, producing Bi2S3 crystals with variable morphologies from sheaves to flowers by increasing EG contents.

Ranges of Applicability for the Continuum-beam Model in the Constitutive Analysis of Carbon Nanotubes: Nanotubes or Nano-beams?

NASA Technical Reports Server (NTRS)

Harik, Vasyl Michael; Bushnell, Dennis M. (Technical Monitor)

2001-01-01

Ranges of validity for the continuum-beam model, the length-scale effects and continuum assumptions are analyzed in the framework of scaling analysis of NT structure. Two coupled criteria for the applicability of the continuum model are presented. Scaling analysis of NT buckling and geometric parameters (e.g., diameter and length) is carried out to determine the key non-dimensional parameters that control the buckling strains and modes of NT buckling. A model applicability map, which represents two classes of NTs, is constructed in the space of non-dimensional parameters. In an analogy with continuum mechanics, a mechanical law of geometric similitude is presented for two classes of beam-like NTs having different geometries. Expressions for the critical buckling loads and strains are tailored for the distinct groups of NTs and compared with the data provided by the molecular dynamics simulations. Implications for molecular dynamics simulations and the NT-based scanning probes are discussed.

Incorporation of hydrogel as a sensing medium for recycle of sensing material in chemical sensors

NASA Astrophysics Data System (ADS)

Hwang, Yunjung; Park, Jeong Yong; Kwon, Oh Seok; Joo, Seokwon; Lee, Chang-Soo; Bae, Joonwon

2018-01-01

A hydrogel, produced with agarose extracted from seaweed, was introduced as a reusable medium in ultrasensitive sensors employing conducting polymer nanomaterials and aptamers. A basic dopamine (DA) sensor was constructed by placing a hydrogel, containing a sensing material composed of aptamer-linked carboxylated polypyrrole nanotubes (PPy-COOH NTs), onto a micropatterned gold electrode. The hydrogel provided a benign electrochemical environment, facilitated specific interactions between DA and the PPy-COOH NT sensing material, and simplified the retrieval of PPy-COOH NTs after detection. It was demonstrated that the agarose hydrogel was successfully employed as a sensing medium for detection of DA, providing a benign environment for the electrode type sensor. PPy-COOH NTs were recovered by simply heating the hydrogel in water. The hydrogel also afforded stable signal intensity after repeated use with a limit of detection of 1 nmol and a clear, stable signal up to 100 nmol DA. This work provides relevant information for future research on reusable or recyclable sensors.

Modeling the Spatial and Temporal Variation of Monthly and Seasonal Precipitation on the Nevada Test Site and Vicinity, 1960-2006

USGS Publications Warehouse

Blainey, Joan B.; Webb, Robert H.; Magirl, Christopher S.

2007-01-01

The Nevada Test Site (NTS), located in the climatic transition zone between the Mojave and Great Basin Deserts, has a network of precipitation gages that is unusually dense for this region. This network measures monthly and seasonal variation in a landscape with diverse topography. Precipitation data from 125 climate stations on or near the NTS were used to spatially interpolate precipitation for each month during the period of 1960 through 2006 at high spatial resolution (30 m). The data were collected at climate stations using manual and/or automated techniques. The spatial interpolation method, applied to monthly accumulations of precipitation, is based on a distance-weighted multivariate regression between the amount of precipitation and the station location and elevation. This report summarizes the temporal and spatial characteristics of the available precipitation records for the period 1960 to 2006, examines the temporal and spatial variability of precipitation during the period of record, and discusses some extremes in seasonal precipitation on the NTS.

Brain stem NOS and ROS in neural mechanisms of hypertension.

PubMed

Chan, Samuel H H; Chan, Julie Y H

2014-01-01

There is now compelling evidence to substantiate the notion that by depressing baroreflex regulation of blood pressure and augmenting central sympathetic outflow through their actions on the nucleus tractus solitarii (NTS) and rostral ventrolateral medulla (RVLM), brain stem nitric oxide synthase (NOS) and reactive oxygen species (ROS) are important contributing factors to neural mechanisms of hypertension. This review summarizes our contemporary views on the impact of NOS and ROS in the NTS and RVLM on neurogenic hypertension, and presents potential antihypertensive strategies that target brain stem NOS/ROS signaling. NO signaling in the brain stem may be pro- or antihypertensive depending on the NOS isoform that generates this gaseous moiety and the site of action. Elevation of the ROS level when its production overbalances its degradation in the NTS and RVLM underlies neurogenic hypertension. Interventional strategies with emphases on alleviating the adverse actions of these molecules on blood pressure regulation have been investigated. The pathological roles of NOS in the RVLM and NTS in neural mechanisms of hypertension are highly complex. Likewise, multiple signaling pathways underlie the deleterious roles of brain-stem ROS in neurogenic hypertension. There are recent indications that interactions between brain stem ROS and NOS may play a contributory role. Given the complicity of action mechanisms of brain-stem NOS and ROS in neural mechanisms of hypertension, additional studies are needed to identify the most crucial therapeutic target that is applicable not only in animal models but also in patients suffering from neurogenic hypertension.

Linear Optical Response of Silicon Nanotubes Under Axial Magnetic Field

NASA Astrophysics Data System (ADS)

Chegel, Raad; Behzad, Somayeh

2013-01-01

We investigated the optical properties of silicon nanotubes (SiNTs) in the low energy region, E < 0.5 eV, and middle energy region, 1.8 eV < E < 2 eV. The dependence of optical matrix elements and linear susceptibility on radius and magnetic field, in terms of one-dimensional (1-d) wavevector and subband index, is calculated using the tight-binding approximation. It is found that, on increasing the nanotube diameter, the low-energy peaks show red-shift and their intensities are decreased. Also, we found that in the middle energy region all tubes have two distinct peaks, where the energy position of the second peak is approximately constant and independent of the nanotube diameter. Comparing the band structure of these tubes in different magnetic fields, several differences are clearly seen, such as splitting of degenerate bands, creation of additional band-edge states, and bandgap modification. It is found that applying the magnetic field leads to a phase transition in zigzag silicon hexagonal nanotubes (Si h-NTs), unlike in zigzag silicon gear-like nanotubes (Si g-NTs), which remain semiconducting in any magnetic field. We found that the axial magnetic field has two effects on the linear susceptibility spectrum, namely broadening and splitting. The axial magnetic field leads to the creation of a peak with energy less than 0.2 eV in metallic Si h-NTs, whereas in the absence of a magnetic field such a transition is not allowed.

Which non-technical skills do junior doctors require to prescribe safely? A systematic review.

PubMed

Dearden, Effie; Mellanby, Edward; Cameron, Helen; Harden, Jeni

2015-12-01

Prescribing errors are a major source of avoidable morbidity and mortality. Junior doctors write most in-hospital prescriptions and are the least experienced members of the healthcare team. This puts them at high risk of error and makes them attractive targets for interventions to improve prescription safety. Error analysis has shown a background of complex environments with multiple contributory conditions. Similar conditions in other high risk industries, such as aviation, have led to an increased understanding of so-called human factors and the use of non-technical skills (NTS) training to try to reduce error. To date no research has examined the NTS required for safe prescribing. The aim of this review was to develop a prototype NTS taxonomy for safe prescribing, by junior doctors, in hospital settings. A systematic search identified 14 studies analyzing prescribing behaviours and errors by junior doctors. Framework analysis was used to extract data from the studies and identify behaviours related to categories of NTS that might be relevant to safe and effective prescribing performance by junior doctors. Categories were derived from existing literature and inductively from the data. A prototype taxonomy of relevant categories (situational awareness, decision making, communication and team working, and task management) and elements was constructed. This prototype will form the basis of future work to create a tool that can be used for training and assessment of medical students and junior doctors to reduce prescribing error in the future. © 2015 The British Pharmacological Society.

A West Valley Demonstration Project Milestone - Achieving Certification to Ship Waste to the Nevada Test Site

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

Jackson, J. P.; Pastor, R. S.

2002-02-28

The West Valley Demonstration Project (WVDP) has successfully pretreated and vitrified nearly all of the 600,000 gallons of liquid high-level radioactive waste that was generated at the site of the only commercial nuclear fuel reprocessing plant to have operated in the United States. Low-level waste (LLW) generated during the course of the cleanup effort now requires disposal. Currently the WVDP only ships Class A LLW for off-site disposal. It has been shipping Class A wastes to Envirocare of Utah, Inc. since 1997. However, the WVDP may also have a future need to ship Class B and Class C waste, whichmore » Envirocare is not currently authorized to accept. The Nevada Test Site (NTS), a U.S. Department of Energy (DOE) facility, can accept all three waste classifications. The WVDP set a goal to receive certification to begin shipping Class A wastes to NTS by 2001. Formal certification/approval was granted by the DOE Nevada Operations Office on July 12, 2001. This paper discusses how the WVDP contractor, West Valley Nuclear Services Company (WVNSCO), completed the activities required to achieve NTS certification in 2001 to ship waste to its facility. The information and lessons learned provided are significant because the WVDP is the only new generator receiving certification based on an NTS audit in January 2001 that resulted in no findings and only two observations--a rating that is unparalleled in the DOE Complex.« less

Incidence, Antimicrobial Resistance, and Molecular Characteristics of Nontyphoidal Salmonella Including Extended-Spectrum β-Lactamase Producers in Retail Chicken Meat.

PubMed

Choi, Dasom; Chon, Jung-Whan; Kim, Hong-Seok; Kim, Dong-Hyeon; Lim, Jong-Soo; Yim, Jin-Hyeok; Seo, Kun-Ho

2015-11-01

The present study was undertaken to determine the prevalence of Salmonella in 100 chicken carcass samples from five integrated broiler operation brands in Korea. Serotypes, antibiotic resistance patterns, extended-spectrum β-lactamase (ESBL) genotype, and clonal divergence using multilocus sequence typing of the isolated strains were analyzed. A total of 42 chicken samples were contaminated with nontyphoidal Salmonella (NTS) isolates: 16 isolates (38%) were Salmonella Virchow, 9 (21%) were Salmonella Bareilly, and 8 (19%) were Salmonella Infantis. A multidrug resistance (MDR; resistant to more than three classes of antibiotics) phenotype was observed in 29% of the isolates, which were resistant to five or more classes of antibiotics. The dominant MDR type was resistance to classes of penicillin, cephalosporins, aminoglycosides, quinolones, and tetracyclines. All the MDR isolates were positive for ESBL producers, and all but one (with the CTX-M-1 genotype) had the CTX-M-15 genotype. Multilocus sequence typing of the isolates revealed ST16 as the dominant sequence type; Salmonella Virchow, Salmonella Infantis, and Salmonella Richmond were all ST16, indicating a close genetic relationship between these serovars. This is the first study in Korea showing the CTX-M-1 type of NTS and the prevalence of ESBL-producing strains among NTS isolated from retail chicken meat. Our findings suggest that MDR Salmonella contamination is widely prevalent in retail chicken meat, and consumption of inadequately cooked products could lead to dissemination of NTS, which is hazardous to human health.

Therapeutic use of botulinum toxin in migraine: mechanisms of action

PubMed Central

Ramachandran, Roshni; Yaksh, Tony L

2014-01-01

Migraine pain represents sensations arising from the activation of trigeminal afferents, which innervate the meningeal vasculature and project to the trigeminal nucleus caudalis (TNC). Pain secondary to meningeal input is referred to extracranial regions innervated by somatic afferents that project to homologous regions in the TNC. Such viscerosomatic convergence accounts for referral of migraine pain arising from meningeal afferents to particular extracranial dermatomes. Botulinum toxins (BoNTs) delivered into extracranial dermatomes are effective in and approved for treating chronic migraine pain. Aside from their well-described effect upon motor endplates, BoNTs are also taken up in local afferent nerve terminals where they cleave soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, and prevent local terminal release. However, a local extracranial effect of BoNT cannot account for allthe effects of BoNT upon migraine. We now know that peripherally delivered BoNTs are taken up in sensory afferents and transported to cleave SNARE proteins in the ganglion and TNC, prevent evoked afferent release and downstream activation. Such effects upon somatic input (as from the face) likewise would not alone account for block of input from converging meningeal afferents. This current work suggests that BoNTs may undergo transcytosis to cleave SNAREs in second-order neurons or in adjacent afferent terminals. Finally, while SNAREs mediate exocytotic release, they are also involved in transport of channels and receptors involved in facilitated pain states. The role of such post-synaptic effects of BoNT action in migraine remains to be determined. PMID:24819339

Domain Organization in Clostridium botulinum Neurotoxin Type E is Unique: Its Implication in Faster Translocation

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

Kumaran, D.; Eswaramoorthy, S; Furey, W

2009-01-01

Clostridium botulinum produces seven antigenically distinct neurotoxins [C. botulinum neurotoxins (BoNTs) A-G] sharing a significant sequence homology. Based on sequence and functional similarity, it was believed that their three-dimensional structures will also be similar. Indeed, the crystal structures of BoNTs A and B exhibit similar fold and domain association where the translocation domain is flanked on either side by binding and catalytic domains. Here, we report the crystal structure of BoNT E holotoxin and show that the domain association is different and unique, although the individual domains are similar to those of BoNTs A and B. In BoNT E, bothmore » the binding domain and the catalytic domain are on the same side of the translocation domain, and all three have mutual interfaces. This unique association may have an effect on the rate of translocation, with the molecule strategically positioned in the vesicle for quick entry into cytosol. Botulism, the disease caused by BoNT E, sets in faster than any other serotype because of its speedy internalization and translocation, and the present structure offers a credible explanation. We propose that the translocation domain in other BoNTs follows a two-step process to attain translocation-competent conformation as in BoNT E. We also suggest that this translocation-competent conformation in BoNT E is a probable reason for its faster toxic rate compared to BoNT A. However, this needs further experimental elucidation.« less

Molecular mechanisms of substrate recognition and specificity of botulinum neurotoxin serotype F.

PubMed

Chen, Sheng; Wan, Hoi Ying

2011-01-15

BoNTs (botulinum neurotoxins) are both deadly neurotoxins and natural toxins that are widely used in protein therapies to treat numerous neurological disorders of dystonia and spinal spasticity. Understanding the mechanism of action and substrate specificity of BoNTs is a prerequisite to develop antitoxin and novel BoNT-derived protein therapy. To date, there is a lack of detailed information with regard to how BoNTs recognize and hydrolyse the substrate VAMP-2 (vesicle-associated membrane protein 2), even though it is known to be cleaved by four of the seven BoNT serotypes, B, D, F, G and TeNT (tetanus neurotoxin). In the present study we dissected the molecular mechanisms of VAMP-2 recognition by BoNT serotype F for the first time. The initial substrate recognition was mediated through sequential binding of VAMP-2 to the B1, B2 and B3 pockets in LC/F (light chain of BoNT serotype F), which directed VAMP-2 to the active site of LC/F and stabilized the active site substrate recognition, where the P2, P1' and P2' sites of VAMP-2 were specifically recognized by the S2, S1' and S2' pockets of LC/F to promote substrate hydrolysis. The understanding of the molecular mechanisms of LC/F substrate recognition provides insights into the development of antitoxins and engineering novel BoNTs to optimize current therapy and extend therapeutic interventions.

New Elements To Consider When Modeling the Hazards Associated with Botulinum Neurotoxin in Food.

PubMed

Ihekwaba, Adaoha E C; Mura, Ivan; Malakar, Pradeep K; Walshaw, John; Peck, Michael W; Barker, G C

2016-01-15

Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the most potent biological substances known to mankind. BoNTs are the agents responsible for botulism, a rare condition affecting the neuromuscular junction and causing a spectrum of diseases ranging from mild cranial nerve palsies to acute respiratory failure and death. BoNTs are a potential biowarfare threat and a public health hazard, since outbreaks of foodborne botulism are caused by the ingestion of preformed BoNTs in food. Currently, mathematical models relating to the hazards associated with C. botulinum, which are largely empirical, make major contributions to botulinum risk assessment. Evaluated using statistical techniques, these models simulate the response of the bacterium to environmental conditions. Though empirical models have been successfully incorporated into risk assessments to support food safety decision making, this process includes significant uncertainties so that relevant decision making is frequently conservative and inflexible. Progression involves encoding into the models cellular processes at a molecular level, especially the details of the genetic and molecular machinery. This addition drives the connection between biological mechanisms and botulism risk assessment and hazard management strategies. This review brings together elements currently described in the literature that will be useful in building quantitative models of C. botulinum neurotoxin production. Subsequently, it outlines how the established form of modeling could be extended to include these new elements. Ultimately, this can offer further contributions to risk assessments to support food safety decision making. Copyright © 2015 Ihekwaba et al.

Cough reflex hypersensitivity: A role for neurotrophins.

PubMed

El-Hashim, Ahmed Z; Jaffal, Sahar M

2017-03-01

Cough is one of the most common complaints for which sufferers seek medical assistance. However, currently available drugs are not very effective in treating cough, particularly that which follows an upper respiratory tract infection. Nonetheless, there has been a significant increase in our understanding of the mechanisms and pathways of the defensive cough as well as the hypersensitive/pathophysiological cough, both at airway and central nervous system (CNS) levels. Numerous molecules and signaling pathways have been identified as potential targets for antitussive drugs, including neurotrophins (NTs). NTs belong to a family of trophic factors and are critical for the development and maintenance of neurons in the central and peripheral nervous system including sympathetic efferents, sensory neuron afferents, and immune cells. Nerve growth factor (NGF) was the first member of the NT family to be discovered, with wide ranging actions associated with synapse formation, survival, proliferation, apoptosis, axonal and dendritic outgrowth, expression and activity of functionally important proteins such as ion channels, receptors, and neurotransmitters. In addition, NGF has been implicated in several disease states particularly neuropathic pain and most recently in the sensitization of the cough reflex. This review will briefly address the peripheral and central sensitization mechanisms of airway neurons and will then focus on NGF signaling and its role in cough hypersensitivity.

Comparative study of large scale simulation of underground explosions inalluvium and in fractured granite using stochastic characterization

NASA Astrophysics Data System (ADS)

Vorobiev, O.; Ezzedine, S. M.; Antoun, T.; Glenn, L.

2014-12-01

This work describes a methodology used for large scale modeling of wave propagation fromunderground explosions conducted at the Nevada Test Site (NTS) in two different geological settings:fractured granitic rock mass and in alluvium deposition. We show that the discrete nature of rockmasses as well as the spatial variability of the fabric of alluvium is very important to understand groundmotions induced by underground explosions. In order to build a credible conceptual model of thesubsurface we integrated the geological, geomechanical and geophysical characterizations conductedduring recent test at the NTS as well as historical data from the characterization during the undergroundnuclear test conducted at the NTS. Because detailed site characterization is limited, expensive and, insome instances, impossible we have numerically investigated the effects of the characterization gaps onthe overall response of the system. We performed several computational studies to identify the keyimportant geologic features specific to fractured media mainly the joints; and those specific foralluvium porous media mainly the spatial variability of geological alluvium facies characterized bytheir variances and their integral scales. We have also explored common key features to both geologicalenvironments such as saturation and topography and assess which characteristics affect the most theground motion in the near-field and in the far-field. Stochastic representation of these features based onthe field characterizations have been implemented in Geodyn and GeodynL hydrocodes. Both codeswere used to guide site characterization efforts in order to provide the essential data to the modelingcommunity. We validate our computational results by comparing the measured and computed groundmotion at various ranges. This work performed under the auspices of the U.S. Department of Energy by Lawrence LivermoreNational Laboratory under Contract DE-AC52-07NA27344.

Area postrema projects to FoxP2 neurons of the pre-locus coeruleus and parabrachial nuclei: brainstem sites implicated in sodium appetite regulation.

PubMed

Stein, Matthew K; Loewy, Arthur D

2010-11-04

The area postrema (AP) is a circumventricular organ located in the dorsal midline of the medulla. It functions as a chemosensor for blood-borne peptides and solutes, and converts this information into neural signals that are transmitted to the nucleus tractus solitarius (NTS) and parabrachial nucleus (PB). One of its NTS targets in the rat is the aldosterone-sensitive neurons which contain the enzyme 11 β-hydroxysteroid dehydrogenase type 2 (HSD2). The HSD2 neurons are part of a central network involved in sodium appetite regulation, and they innervate numerous brain sites including the pre-locus coeruleus (pre-LC) and PB external lateral-inner (PBel-inner) cell groups of the dorsolateral pons. Both pontine cell groups express the transcription factor FoxP2 and become c-Fos activated following sodium depletion. Because the AP is a component in this network, we wanted to determine whether it also projects to the same sites as the HSD2 neurons. By using a combination of anterograde axonal and retrograde cell body tract-tracing techniques in individual rats, we show that the AP projects to FoxP2 immunoreactive neurons in the pre-LC and PBel-inner. Thus, the AP sends a direct projection to both the first-order medullary (HSD2 neurons of the NTS) and the second-order dorsolateral pontine neurons (pre-LC and PB-el inner neurons). All three sites transmit information related to systemic sodium depletion to forebrain sites and are part of the central neural circuitry that regulates the complex behavior of sodium appetite. Copyright © 2010 Elsevier B.V. All rights reserved.

Activation of TRKA receptor elicits mastocytosis in mice and is involved in the development of resistance to KIT-targeted therapy.

PubMed

Yang, Min; Pan, Zengkai; Huang, Kezhi; Büsche, Guntram; Feuerhake, Friedrich; Chaturvedi, Anuhar; Nie, Danian; Heuser, Michael; Thol, Felicitas; von Neuhoff, Nils; Ganser, Arnold; Li, Zhixiong

2017-09-26

The neurotrophins (NTs) play a key role in neuronal survival and maintenance. The TRK (tropomyosin-related kinase) tyrosine kinase receptors (TRKA, TRKB, TRKC) are high affinity receptors for NTs. There is increasing data demonstrating an important role of the TRK family in cancer initiation and progression. NTs have been known for many years to promote chemotaxis, maturation, and survival of mast cells. However, the role of NT signaling in the pathogenesis of mastocytosis is not well understood. In this study, we demonstrate that activation of TRKA by its ligand nerve growth factor (NGF) is potent to trigger a disease in mice with striking similarities to human systemic mastocytosis (SM). Moreover, activation of TRKA by NGF strongly rescues KIT inhibition-induced cell death of mast cell lines and primary mast cells from patients with SM, and this rescue effect can be efficiently blocked by entrectinib (a new pan TRK specific inhibitor). HMC-1 mast cell leukemia cells that are resistant to KIT inhibition induced by TRKA activation show reactivation of MAPK/ERK (extracellular signal-regulated kinase) and strong upregulation of early growth response 3 (EGR3), suggesting an important role of MAPK-EGR3 axis in the development of resistance to KIT inhibition. Targeting both TRK and KIT significantly prolongs survival of mice xenotransplanted with HMC-1 cells compared with targeting KIT alone. Thus, these data strongly suggest that TRKA signaling can improve neoplastic mast cell fitness. This might explain at least in part why treatment with KIT inhibitors alone so far has been disappointing in most published clinical trials for mastocytosis. Our data suggest that targeting both KIT and TRKs might improve efficacy of molecular therapy in SM with KIT mutations.

Functional Activity of Antibodies Directed towards Flagellin Proteins of Non-Typhoidal Salmonella

PubMed Central

Boyd, Mary A.; Wang, Jin Y.; Tulapurkar, Mohan E.; Pasetti, Marcela F.; Levine, Myron M.; Simon, Raphael

2016-01-01

Non-typhoidal Salmonella (NTS) serovars Typhimurium and Enteritidis are major causes of invasive bacterial infections in children under 5 years old in sub-Saharan Africa, with case fatality rates of ~20%. There are no licensed NTS vaccines for humans. Vaccines that induce antibodies against a Salmonella Typhi surface antigen, Vi polysaccharide, significantly protect humans against typhoid fever, establishing that immune responses to Salmonella surface antigens can be protective. Flagella proteins, abundant surface antigens in Salmonella serovars that cause human disease, are also powerful immunogens, but the functional capacity of elicited anti-flagellar antibodies and their role in facilitating bacterial clearance has been unclear. We examined the ability of anti-flagellar antibodies to mediate microbial killing by immune system components in-vitro and assessed their role in protecting mice against invasive Salmonella infection. Polyclonal (hyperimmune sera) and monoclonal antibodies raised against phase 1 flagellin proteins of S. Enteritidis and S. Typhimurium facilitated bacterial uptake and killing of the homologous serovar pathogen by phagocytes. Polyclonal anti-flagellar antibodies accompanied by complement also achieved direct bacterial killing. Serum bactericidal activity was restricted to Salmonella serovars expressing the same flagellin used as immunogen. Notably, individual anti-flagellin monoclonal antibodies with complement were not bactericidal, but this biological activity was restored when different monoclonal anti-flagellin antibodies were combined. Passive transfer immunization with a monoclonal IgG antibody specific for phase 1 flagellin from S. Typhimurium protected mice against lethal challenge with a representative African invasive S. Typhimurium strain. These findings have relevance for the use of flagellin proteins in NTS vaccines, and confirm the role of anti-flagellin antibodies as mediators of protective immunity. PMID:26998925

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

Jeremy Gwin and Douglas Frenette

This document contains process knowledge and radiological data and analysis to support approval for release of the 25-ton locomotive, Serial Number 21547, at the Area 25 Engine Maintenance, Assembly, and Disassembly (EMAD) Facility, located on the Nevada Test Site (NTS). The 25-ton locomotive is a small, one-of-a-kind locomotive used to move railcars in support of the Nuclear Engine for Rocket Vehicle Application project. This locomotive was identified as having significant historical value by the Nevada State Railroad Museum in Boulder City, Nevada, where it will be used as a display piece. A substantial effort to characterize the radiological conditions ofmore » the locomotive was undertaken by the NTS Management and Operations Contractor, National Security Technologies, LLC (NSTec). During this characterization process, seven small areas on the locomotive had contamination levels that exceeded the NTS release criteria (limits consistent with U.S. Department of Energy [DOE] Order DOE O 5400.5, “Radiation Protection of the Public and the Environment”). The decision was made to perform radiological decontamination of these known accessible impacted areas to further the release process. On February 9, 2010, NSTec personnel completed decontamination of these seven areas to within the NTS release criteria. Although all accessible areas of the locomotive had been successfully decontaminated to within NTS release criteria, it was plausible that inaccessible areas of the locomotive (i.e., those areas on the locomotive where it was not possible to perform radiological surveys) could potentially have contamination above unrestricted release limits. To access the majority of these inaccessible areas, the locomotive would have to be disassembled. A complete disassembly for a full radiological survey could have permanently destroyed parts and would have ruined the historical value of the locomotive. Complete disassembly would also add an unreasonable financial burden for the contractor. A decision was reached between the NTS regulator and NSTec, opting for alternative authorized limits from DOE Headquarters. In doing so, NSTec personnel performed a dose model using the DOE-approved modeling code RESRAD-BUILD v3.5 to evaluate scenarios. The parameters used in the dose model were conservative. NSTec’s Radiological Engineering Calculation, REC-2010-001, “Public Dose Estimate from the EMAD 25 Ton Locomotive,” concluded that the four scenarios evaluated were below the 25-millirem per year limit, the “likely” dose scenarios met the “few millirem in a year” criteria, and that the EMAD 25-ton locomotive met the radiological requirements to be released with residual radioactivity to the public.« less

Blood pressure long term regulation: A neural network model of the set point development

PubMed Central

2011-01-01

Background The notion of the nucleus tractus solitarius (NTS) as a comparator evaluating the error signal between its rostral neural structures (RNS) and the cardiovascular receptor afferents into it has been recently presented. From this perspective, stress can cause hypertension via set point changes, so offering an answer to an old question. Even though the local blood flow to tissues is influenced by circulating vasoactive hormones and also by local factors, there is yet significant sympathetic control. It is well established that the state of maturation of sympathetic innervation of blood vessels at birth varies across animal species and it takes place mostly during the postnatal period. During ontogeny, chemoreceptors are functional; they discharge when the partial pressures of oxygen and carbon dioxide in the arterial blood are not normal. Methods The model is a simple biological plausible adaptative neural network to simulate the development of the sympathetic nervous control. It is hypothesized that during ontogeny, from the RNS afferents to the NTS, the optimal level of each sympathetic efferent discharge is learned through the chemoreceptors' feedback. Its mean discharge leads to normal oxygen and carbon dioxide levels in each tissue. Thus, the sympathetic efferent discharge sets at the optimal level if, despite maximal drift, the local blood flow is compensated for by autoregulation. Such optimal level produces minimum chemoreceptor output, which must be maintained by the nervous system. Since blood flow is controlled by arterial blood pressure, the long-term mean level is stabilized to regulate oxygen and carbon dioxide levels. After development, the cardiopulmonary reflexes play an important role in controlling efferent sympathetic nerve activity to the kidneys and modulating sodium and water excretion. Results Starting from fixed RNS afferents to the NTS and random synaptic weight values, the sympathetic efferents converged to the optimal values. When learning was completed, the output from the chemoreceptors became zero because the sympathetic efferents led to normal partial pressures of oxygen and carbon dioxide. Conclusions We introduce here a simple simulating computational theory to study, from a neurophysiologic point of view, the sympathetic development of cardiovascular regulation due to feedback signals sent off by cardiovascular receptors. The model simulates, too, how the NTS, as emergent property, acts as a comparator and how its rostral afferents behave as set point. PMID:21693057

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

Hong, Seungwoo; Lu, Xiaoyan; Lee, Yong -Min

Here, a mononuclear nonheme iron(V)-imido complex bearing a tetraamido macrocyclic ligand (TAML), [Fe V(NTs)(TAML)] – (1), was oxidized by one-electron oxidants, affording formation of an iron(V)-imido TAML cation radical species, [Fe V(NTs)(TAML +•)] (2); 2 is a diamagnetic (S = 0) complex, resulting from the antiferromagnetic coupling of the low-spin iron(V) ion (S = 1/2) with the one-electron oxidized ligand (TAML +•). 2 is a competent oxidant in C–H bond functionalization and nitrene transfer reaction, showing that the reactivity of 2 is greater than that of 1.

Source amplitudes of NTS explosions inferred from Rayleigh waves at Albuquerque and Tucson. Topical report

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

Bache, T.C.; Rodi, W.L.; Mason, B.F.

1978-06-01

Comparing observed and synthetic seismograms, source amplitudes of NTS explosions are inferred from Rayleigh wave recordings from the WWSSN stations at Albuquerque, New Mexico (ALQ) and Tucson, Arizona (TUC). The potential influence of source complexities, particularly surface spallation and related phenomena, is studied in detail. As described in earlier work by Bache, Rodi and Harkrider, the earth model for the synthetic were converted from observations at ALQ and TUC. The agreement of observed and synthetic seismograms is quite good and is sensitive to important features of the source.

NEVADA TEST SITE WASTE ACCEPTANCE CRITERIA, JUNE 2006

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

U.S. DEPARTMENT OF ENERGY, NATIONAL NUCLEAR SECURITY ADMINISTRATION NEVADA SITE OFFICE

This document establishes the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO) waste acceptance criteria (WAC). The WAC provides the requirements, terms, and conditions under which the Nevada Test Site (NTS) will accept low-level radioactive (LLW) and mixed waste (MW) for disposal. It includes requirements for the generator waste certification program, characterization, traceability, waste form, packaging, and transfer. The criteria apply to radioactive waste received at the NTS Area 3 and Area 5 Radioactive Waste Management Complex (RWMC) for storage or disposal.

Nevada Test Site Waste Acceptance Criteria

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

U. S. Department of Energy, National Nuclear Security Administration Nevada Site Office

This document establishes the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO) waste acceptance criteria (WAC). The WAC provides the requirements, terms, and conditions under which the Nevada Test Site (NTS) will accept low-level radioactive (LLW) and mixed waste (MW) for disposal. It includes requirements for the generator waste certification program, characterization, traceability, waste form, packaging, and transfer. The criteria apply to radioactive waste received at the NTS Area 3 and Area 5 Radioactive Waste Management Complex (RWMC) for storage or disposal.

Design of titania nanotube structures by focused laser beam direct writing

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

Enachi, Mihai; Stevens-Kalceff, Marion A.; Sarua, Andrei

In this work, we report on electrochemical fabrication of titania films consisting of nanotubes (NTs) and their treatment by focused laser beam. The results of sample characterization by optical and scanning electron microscopy, cathodoluminescence imaging, and Raman scattering scanning spectroscopy are compared to those inherent to specimens subjected to thermal treatment in a furnace. The obtained data demonstrate possibilities for controlling crystallographic structure of TiO{sub 2} NTs by focused laser beam direct writing. These findings open new prospects for the design and fabrication of spatial architectures based on titania nanotubes.

Three year performance of the NTS-2 solar cell experiment

NASA Technical Reports Server (NTRS)

Statler, R. L.; Walker, D. H.

1980-01-01

Twelve different solar cell modules from the NTS 2 experiment are functioning after more than three years in a severe trapped radiation orbit of 20,367 km (10,990 nm) circular, 63 deg inclination. The rate of maximum power degradation may be fit to a predicted rate which is based on twice the value of 1 MeV electron equivalent damage fluence calculated from the space electron model AEI 7. The photovoltaic parameters of the cells are compared to their original values to demonstrate rank order of performance.

Humoral Activity of Cord Blood-Derived Stem/Progenitor Cells: Implications for Stem Cell-Based Adjuvant Therapy of Neurodegenerative Disorders

PubMed Central

Paczkowska, Edyta; Kaczyńska, Katarzyna; Pius-Sadowska, Ewa; Rogińska, Dorota; Kawa, Miłosz; Ustianowski, Przemysław; Safranow, Krzysztof; Celewicz, Zbigniew; Machaliński, Bogusław

2013-01-01

Background Stem/progenitor cells (SPCs) demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs) and their receptors in specific umbilical cord blood (UCB) SPC populations, including lineage-negative, CD34+, and CD133+ cells, with that in unsorted, nucleated cells (NCs). Methods and Results The expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34+, and CD133+ cells). To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3) was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34+, and CD133+ cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34+ or CD133+ cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM) from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation. Conclusions Collectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and that CM from SPCs favorable influence neural cell proliferation and survival. Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders. PMID:24391835

Ghrelin agonists impact on Fos protein expression in brain areas related to food intake regulation in male C57BL/6 mice.

PubMed

Pirnik, Z; Bundziková, J; Holubová, M; Pýchová, M; Fehrentz, J A; Martinez, J; Zelezná, B; Maletínská, L; Kiss, A

2011-11-01

Many peripheral substances, including ghrelin, induce neuronal activation in the brain. In the present study, we compared the effect of subcutaneously administered ghrelin and its three stable agonists: Dpr(3)ghr ([Dpr(N-octanoyl)(3)] ghrelin) (Dpr - diaminopropionic acid), YA GHRP-6 (H-Tyr-Ala-His-DTrp-Ala-Trp-DPhe-Lys-NH(2)), and JMV1843 (H-Aib-DTrp-D-gTrp-CHO) on the Fos expression in food intake-responsive brain areas such as the hypothalamic paraventricular (PVN) and arcuate (ARC) nuclei, the nucleus of the solitary tract (NTS), and area postrema (AP) in male C57BL/6 mice. Immunohistochemical analysis showed that acute subcutaneous dose of each substance (5mg/kg b.w.), which induced a significant food intake increase, elevated Fos protein expression in all brain areas studied. Likewise ghrelin, each agonist tested induced distinct Fos expression overall the PVN. In the ARC, ghrelin and its agonists specifically activated similarly distributed neurons. Fos occurrence extended from the anterior (aARC) to middle (mARC) ARC region. In the latter part of the ARC, the Fos profiles were localized bilaterally, especially in the ventromedial portions of the nucleus. In the NTS, all substances tested also significantly increased the number of Fos profiles in neurons, which also revealed specific location, i.e., in the NTS dorsomedial subnucleus (dmNTS) and the area subpostrema (AsP). In addition, cells located nearby the NTS, in the AP, also revealed a significant increase in number of Fos-activated cells. These results demonstrate for the first time that ghrelin agonists, regardless of their different chemical nature, have a significant and similar activating impact on specific groups of neurons that can be a part of the circuits involved in the food intake regulation. Therefore there is a real potency for ghrelin agonists to treat cachexia and food intake disorders. Thus, likewise JMV1843, the other ghrelin agonists represent substances that might be involved in trials for clinical purposes. Copyright © 2011 Elsevier B.V. All rights reserved.

Nevada Test Site-Directed Research and Development, FY 2007 Report

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

Wil Lewis, editor

2008-02-20

The Nevada Test Site-Directed Research and Development (SDRD) program completed a very successful year of research and development activities in FY 2007. Twenty-nine new projects were selected for funding this year, and eight projects started in FY 2006 were brought to conclusion. The total funds expended by the SDRD program were $5.67 million, for an average per-project cost of $153 thousand. An external audit conducted in September 2007 verified that appropriate accounting practices were applied to the SDRD program. Highlights for the year included: programmatic adoption of 8 SDRD-developed technologies; the filing of 9 invention disclosures for innovation evolving frommore » SDRD projects; participation in the tri-Lab Laboratory Directed Research and Development (LDRD) and SDRD Symposium that was broadly attended by Nevada Test Site (NTS), National Nuclear Security Administration (NNSA), LDRD, U.S. Department of Homeland Security (DHS), and U.S. Department of Defense (DoD) representatives; peer reviews of all FY 2007 projects; and the successful completion of 37 R&D projects, as presented in this report. In response to a company-wide call, authors throughout the NTS complex submitted 182 proposals for FY 2007 SDRD projects. The SDRD program has seen a dramatic increase in the yearly total of submitted proposals--from 69 in FY 2002 to 182 this year--while the number of projects funded has actually decreased from a program high of 57 in FY 2004. The overall effect of this trend has helped ensure an increasingly competitive program that benefited from a broader set of innovative ideas, making project selection both challenging and rewarding. Proposals were evaluated for technical merit, including such factors as innovation, probability of success, potential benefit, and mission applicability. Authors and reviewers benefited from the use of a shortfalls list entitled the 'NTS Technology Needs Assessment' that was compiled from NTS, National Weapons Laboratory (NWL), and NNSA sources. This tool continues to be of considerable value in aligning the SDRD program with mission priorities, and was expanded in FY 2007 to include technology development needs from the DHS and other agencies with missions closely aligned to that of the NTS.« less

Distribution of AMPA receptor subunits GluR1-4 in the dorsal vagal complex of the rat: a light and electron microscope immunocytochemical study.

PubMed

Kessler, J P; Baude, A

1999-10-01

The dorsal vagal complex, localized in the dorsomedial medulla, includes the nucleus tractus solitarii (NTS), the dorsal motor nucleus of the vagus nerve (DMN) and the area postrema (AP). The distribution of AMPA-preferring glutamate receptors (AMPA receptors) within this region was investigated using immunohistochemistry and antibodies recognizing either one (GluR1 or GluR4) or two (GluR2 and GluR3) AMPA receptors subunits. The distribution of GluR1 immunoreactivity showed high contrast of staining between strongly and lightly labeled areas. Labeling was intense in the AP and weak in the NTS, except for its medial and dorsalmost parts which exhibited moderate staining. Almost no GluR1 immunoreactivity was found in the DMN. GluR2/3 immunolabeling was present in the entire dorsal vagal complex. This labeling was strong in the AP, the DMN and the medial half of the NTS and moderate in the lateral half of the NTS, except for the interstitial subdivision which exhibited intense staining. Labeling induced by the GluR4 antibody was very weak throughout the dorsal vagal complex. Ultrastructural examination showed that GluR1 and GluR2/3 immunoreactivity was localized in neuronal cell bodies and dendrites. No labeled axon terminal or glial cell body was found. Immunoperoxidase staining in labeled cell bodies and dendrites was associated with intracellular organelles (microtubules, mitochondria, cisternae of the endoplasmic reticulum,.) and/or parts of the plasma membrane. Plasma membrane labeling was often associated with asymmetrical synaptic differentiations. No labeled symmetrical synapse was found using either GluR1 or GluR2/3 antibody. The present results show that AMPA receptors have a widespread distribution in neuronal perikarya and dendrites of the rat dorsal vagal complex. They suggest differences in subunit composition between AMPA receptors localized in the NTS, the DMN and the AP. Ultrastructural data are consistent with the fact that AMPA receptors associated with the plasma membrane are mostly synaptic receptors. However, they also suggest the existence of a large intracellular pool of receptor subunits in neuronal soma and dendrites. Copyright 1999 Wiley-Liss, Inc.

Humoral activity of cord blood-derived stem/progenitor cells: implications for stem cell-based adjuvant therapy of neurodegenerative disorders.

PubMed

Paczkowska, Edyta; Kaczyńska, Katarzyna; Pius-Sadowska, Ewa; Rogińska, Dorota; Kawa, Miłosz; Ustianowski, Przemysław; Safranow, Krzysztof; Celewicz, Zbigniew; Machaliński, Bogusław

2013-01-01

Stem/progenitor cells (SPCs) demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs) and their receptors in specific umbilical cord blood (UCB) SPC populations, including lineage-negative, CD34(+), and CD133(+) cells, with that in unsorted, nucleated cells (NCs). The expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34(+), and CD133(+) cells). To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3) was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34(+), and CD133(+) cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34(+) or CD133(+) cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM) from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation. Collectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and that CM from SPCs favorable influence neural cell proliferation and survival. Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders.

Arms Control and Nonproliferation Technologies, First Quarter 1994

DTIC Science & Technology

1994-01-01

earthquake show detectable signals PATWINGSPAC, U.S. Navy, (3) an array of the U.S. for magnitude 3 events at 320-360 kilometers. Initial Navy SOSUS system...30 explosions shots, in generating seismic signals at regional or greater than 50 tons, including one shot greater than teleseismic distances). These... general Rainier Mesa earthquakes from Rock Valley at NTS appear to be events (Area 12) of roughly the same yield had signif- intermediate between the

Improving the apo-state detergent stability of NTS1 with CHESS for pharmacological and structural studies.

PubMed

Scott, Daniel J; Kummer, Lutz; Egloff, Pascal; Bathgate, Ross A D; Plückthun, Andreas

2014-11-01

The largest single class of drug targets is the G protein-coupled receptor (GPCR) family. Modern high-throughput methods for drug discovery require working with pure protein, but this has been a challenge for GPCRs, and thus the success of screening campaigns targeting soluble, catalytic protein domains has not yet been realized for GPCRs. Therefore, most GPCR drug screening has been cell-based, whereas the strategy of choice for drug discovery against soluble proteins is HTS using purified proteins coupled to structure-based drug design. While recent developments are increasing the chances of obtaining GPCR crystal structures, the feasibility of screening directly against purified GPCRs in the unbound state (apo-state) remains low. GPCRs exhibit low stability in detergent micelles, especially in the apo-state, over the time periods required for performing large screens. Recent methods for generating detergent-stable GPCRs, however, offer the potential for researchers to manipulate GPCRs almost like soluble enzymes, opening up new avenues for drug discovery. Here we apply cellular high-throughput encapsulation, solubilization and screening (CHESS) to the neurotensin receptor 1 (NTS1) to generate a variant that is stable in the apo-state when solubilized in detergents. This high stability facilitated the crystal structure determination of this receptor and also allowed us to probe the pharmacology of detergent-solubilized, apo-state NTS1 using robotic ligand binding assays. NTS1 is a target for the development of novel antipsychotics, and thus CHESS-stabilized receptors represent exciting tools for drug discovery. Copyright © 2014 Elsevier B.V. All rights reserved.

Salmonella Serogroup C: Current Status of Vaccines and Why They Are Needed

PubMed Central

Fuche, Fabien J.; Sow, Ousmane; Simon, Raphael

2016-01-01

Nontyphoidal Salmonella (NTS; i.e., Salmonella enterica organisms that do not cause typhoid or paratyphoid) are responsible for 94 million infections and 155,000 deaths worldwide annually, 86% of which are estimated to be foodborne. Although more than 50 serogroups and 2,600 serovars have been described, not all Salmonella serovars cause disease in humans and animals. Efforts are being made to develop NTS vaccines, with most approaches eliciting protection against serovars Typhimurium and Enteritidis (serogroups B [O:4] and D [O:9], respectively), as they are widely considered the most prevalent. Here, we show that serogroup C (O:6,7, O:6,8, or O:8 epitopes) is the most common serogroup in the United States, and the prevalence of serovars from this serogroup has been increasing in Europe and the United States over the last decade. They are also the most commonly isolated serovars from healthy cattle and poultry, indicating the underlying importance of surveillance in animals. Four out of the 10 most lethal serovars in the United States are serogroup C, and reports from African countries suggest that strains within this serogroup are highly antibiotic resistant. Serogroup C consists of highly diverse organisms among which 37 serovars account for the majority of human cases, compared to 17 and 11 serovars for serogroups B and D, respectively. Despite these concerning data, no human vaccines targeting serogroup C NTS are available, and animal vaccines are in limited use. Here, we describe the underestimated burden represented by serogroup C NTS, as well as a discussion of vaccines that target these pathogens. PMID:27413069

A novel subunit structure of Clostridium botulinum serotype D toxin complex with three extended arms.

PubMed

Hasegawa, Kimiko; Watanabe, Toshihiro; Suzuki, Tomonori; Yamano, Akihito; Oikawa, Tetsuo; Sato, Yasuhiko; Kouguchi, Hirokazu; Yoneyama, Tohru; Niwa, Koichi; Ikeda, Toshihiko; Ohyama, Tohru

2007-08-24

The botulinum neurotoxins (BoNTs) are the most potent toxins known in nature, causing the lethal disease known as botulism in humans and animals. The BoNTs act by inhibiting neurotransmitter release from cholinergic synapses. Clostridium botulinum strains produce large BoNTs toxin complexes, which include auxiliary non-toxic proteins that appear not only to protect BoNTs from the hostile environment of the digestive tract but also to assist BoNT translocation across the intestinal mucosal layer. In this study, we visualize for the first time a series of botulinum serotype D toxin complexes using negative stain transmission electron microscopy (TEM). The complexes consist of the 150-kDa BoNT, 130-kDa non-toxic non-hemagglutinin (NTNHA), and three kinds of hemagglutinin (HA) subcomponents: 70-kDa HA-70, 33-kDa HA-33, and 17-kDa HA-17. These components assemble sequentially to form the complex. A novel TEM image of the mature L-TC revealed an ellipsoidal-shaped structure with "three arms" attached. The "body" section was comprised of a single BoNT, a single NTNHA and three HA-70 molecules. The arm section consisted of a complex of HA-33 and HA-17 molecules. We determined the x-ray crystal structure of the complex formed by two HA-33 plus one HA-17. On the basis of the TEM image and biochemical results, we propose a novel 14-mer subunit model for the botulinum toxin complex. This unique model suggests how non-toxic components make up a "delivery vehicle" for BoNT.

Vagal innervation of the aldosterone-sensitive HSD2 neurons in the NTS

PubMed Central

Shin, Jung-Won; Geerling, Joel C.; Loewy, Arthur D.

2009-01-01

The nucleus of the solitary tract (NTS) contains a unique subpopulation of aldosterone-sensitive neurons. These neurons express the enzyme 11-β-hydroxysteroid dehydrogenase type 2 (HSD2) and are activated by sodium deprivation. They are located in the caudal NTS, a region which is densely innervated by the vagus nerve, suggesting that they could receive direct viscerosensory input from the periphery. To test this possibility, we injected the highly sensitive axonal tracer biotinylated dextran amine (BDA) into the left nodose ganglion in rats. Using confocal microscopy, we observed a sparse input from the vagus to most HSD2 neurons. Roughly 80% of the ipsilateral HSD2 neurons exhibited at least one close contact with a BDA-labeled vagal bouton, although most of these cells received only a few total contacts. Most of these contacts were axo-dendritic (~80%), while ~20% were axo-somatic. In contrast, the synaptic vesicular transporters VGLUT2 or GAD7 labeled much larger populations of boutons contacting HSD2-labeled dendrites and somata, suggesting that direct input from the vagus may only account for a minority of the information integrated by these neurons. In summary, the aldosterone-sensitive HSD2 neurons in the NTS appear to receive a small amount of direct viscerosensory input from the vagus nerve. The peripheral sites of origin and functional significance of this projection remain unknown. Combined with previously-identified central sources of input to these cells, the present finding indicates that the HSD2 neurons integrate humoral information with input from a variety of neural afferents. PMID:19010311

Urocortin1-induced anorexia is regulated by activation of the serotonin 2C receptor in the brain.

PubMed

Harada, Yumi; Takayama, Kiyoshige; Ro, Shoki; Ochiai, Mitsuko; Noguchi, Masamichi; Iizuka, Seiichi; Hattori, Tomohisa; Yakabi, Koji

2014-01-01

This study was conducted to determine the mechanisms by which serotonin (5-hydroxytryptamine, 5-HT) receptors are involved in the suppression of food intake in a rat stress model and to observe the degree of activation in the areas of the brain involved in feeding. In the stress model, male Sprague-Dawley rats (8 weeks old) were given intracerebroventricular injections of urocortin (UCN) 1. To determine the role of the 5-HT2c receptor (5-HT2cR) in the decreased food intake in UCN1-treated rats, specific 5-HT2cR or 5-HT2b receptor (5-HT2bR) antagonists were administered. Food intake was markedly reduced in UCN1-injected rats compared with phosphate buffered saline treated control rats. Intraperitoneal administration of a 5-HT2cR antagonist, but not a 5-HT2bR antagonist, significantly inhibited the decreased food intake. To assess the involvement of neural activation, we tracked the expression of c-fos mRNA as a neuronal activation marker. Expression of the c-fos mRNA in the arcuate nucleus, ventromedial hypothalamic nucleus (VMH) and rostral ventrolateral medulla (RVLM) in UNC1-injected rats showed significantly higher expression than in the PBS-injected rats. Increased c-fos mRNA was also observed in the paraventricular nucleus (PVN), the nucleus of the solitary tract (NTS), and the amygdala (AMG) after injection of UCN1. Increased 5-HT2cR protein expression was also observed in several areas. However, increased coexpression of 5-HT2cR and c-fos was observed in the PVN, VMH, NTS, RVLM and AMG. Whereas, pro-opiomelanocortin mRNA expression was not changed. In an UNC1-induced stress model, 5-HT2cR expression and activation was found in brain areas involved in feeding control. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of temperature, strain rate, and vacancies on tensile and fatigue behaviors of silicon-based nanotubes

NASA Astrophysics Data System (ADS)

Jeng, Yeau-Ren; Tsai, Ping-Chi; Fang, Te-Hua

2005-02-01

This paper adopts the Tersoff-Brenner many-body potential function to perform molecular dynamics simulations of the tensile and fatigue behaviors of hypothetical silicon-based tubular nanostructures at various temperatures, strain rates, and vacancy percentages. The tensile test results indicate that with a predicted Young’s modulus of approximately 60GPa , silicon nanotubes (SiNTs) are significantly less stiff than conventional carbon nanotubes. It is observed that the presence of hydrogen has a significant influence on the tensile strength of SiNTs . Additionally, the present results indicate that the tensile strength clearly decreases with increasing temperature and with decreasing strain rate. Moreover, it is shown that the majority of the mechanical properties considered in the present study decrease with an increasing vacancy percentage. Regarding the fatigue tests, this study uses a standard theoretical model to derive curves of amplitude stress versus number of cycles for the current nanotubes. The results demonstrate that the fatigue limit of SiNTs increases with a decreasing vacancy percentage and with increasing temperature.

The Epidemiology of Childhood Salmonella Infections in Alberta, Canada.

PubMed

Faulder, Kate E; Simmonds, Kimberley; Robinson, Joan L

2017-06-01

The objectives were to describe the incidence, demographics, laboratory findings, and suspected sources of childhood Salmonella infections in Alberta, Canada, with a focus on preventable cases. Data from Notifiable Disease Reports for children with nontyphoidal salmonellosis (NTS) or typhoid/paratyphoid fever from 2007 through 2015 were analyzed. NTS was detected from 2285 children. Bacteremia was documented in 55 cases (2.4%), whereas a single infant had NTS meningitis. The suspected source was food (N = 577; 25.3%) followed by animal or animal manure contact (N = 426; 18.6%), of which a reptile was the suspected source in 264 cases (11.5%). There were 44 outbreaks with none sharing the same food source. Ninety-five children were diagnosed with typhoid/paratyphoid fever, of which 48 cases (51%) were typhoid cases in unimmunized children 2 years or older. There are still ∼275 pediatric cases of Salmonella infection in Alberta annually, the bulk of which are preventable. Public education about reptile exposure, food safety, and pretravel immunizations could potentially prevent many cases of Salmonella infection.

Monosynaptic convergence of chorda tympani and glossopharyngeal afferents onto ascending relay neurons in the nucleus of the solitary tract: A high-resolution confocal and correlative electron microscopy approach

PubMed Central

Corson, James A.; Erisir, Alev

2014-01-01

While physiological studies suggested convergence of chorda tympani and glossopharyngeal afferent axons onto single neurons of the rostral nucleus of the solitary tract (rNTS), anatomical evidence has been elusive. The current study uses high-magnification confocal microscopy to identify putative synaptic contacts from afferent fibers of the two nerves onto individual projection neurons. Imaged tissue is re-visualized with electron microscopy, confirming that overlapping fluorescent signals in confocal z-stacks accurately identify appositions between labeled terminal and dendrite pairs. Monte Carlo modeling reveals that the probability of overlapping fluorophores is stochastically unrelated to the density of afferent label suggesting that convergent innervation in the rNTS is selective rather than opportunistic. Putative synaptic contacts from each nerve are often compartmentalized onto dendrite segments of convergently innervated neurons. These results have important implications for orosensory processing in the rNTS, and the techniques presented here have applications in investigations of neural microcircuitry with an emphasis on innervation patterning. PMID:23640852

Vaccination of cattle with a recombinant bivalent toxoid against botulism serotypes C and D.

PubMed

Cunha, Carlos E P; Moreira, Gustavo M S G; Salvarani, Felipe M; Neves, Monique S; Lobato, Francisco C F; Dellagostin, Odir A; Conceição, Fabricio R

2014-01-03

Cattle botulism is a fatal intoxication caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum serotypes C and D resulting in economic losses. Vaccination is the most effective way to control botulism. However, the commercially available vaccines are difficult and hazardous to produce. Neutralizing antibodies against the C-terminal fragment of the BoNT heavy chain (HC) are known to protect against lethal doses of BoNTs. We report the vaccination of cattle with a previously tested recombinant chimera consisting of Escherichia coli heat-labile enterotoxin B subunit and the HC of BoNTs C and D. Vaccinated animals produced neutralizing antibodies against serotypes C and D averaging 5±0 and 6.14±1.06IU/mL, respectively. For BoNT D, the titers were greater than those measured for the commercial vaccine, which induced titers of 5±0 and 2.85±1.35 against the respective serotypes, suggesting that this chimera is effective against cattle botulism. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mode of VAMP Substrate Recognition and Inhibition of Clostridium botulinum Neurotoxin F

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

Agarwal, R.; Schmidt, J; Stafford, R

2009-01-01

Clostridium botulinum neurotoxins (BoNTs) cleave neuronal proteins responsible for neurotransmitter release, causing the neuroparalytic disease botulism. BoNT serotypes B, D, F and G cleave and inactivate vesicle-associated membrane protein (VAMP), each at a unique peptide bond. The specificity of BoNTs depends on the mode of substrate recognition. We have investigated the mechanism of substrate recognition of BoNT F by determining the crystal structures of its complex with two substrate-based inhibitors, VAMP 22-58/Gln58D-cysteine and 27-58/Gln58D-cysteine. The inhibitors bind to BoNT F in the canonical direction (as seen for BoNTs A and E substrates) but are positioned specifically via three major exositesmore » away from the active site. The cysteine sulfur of the inhibitors interacts with the zinc and exists as sulfinic acid in the inhibitor VAMP 27-58/Gln58D-cysteine. Arg133 and Arg171, which form part of two separate exosites, are crucial for substrate binding and catalysis.« less

Corrective action plan for corrective action Unit 342: Area 23 Mercury Fire Training Pit, Nevada Test Site, Nevada

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

Nacht, S.

1999-08-01

The Mercury Fire Training Pit is a former fire training area located in Area 23 of the Nevada Test Site (NTS). The Mercury Fire Training Pit was used from approximately 1965 to the early 1990s to train fire-fighting personnel at the NTS, and encompasses an area approximately 107 meters (m) (350 feet [ft]) by 137 m (450 ft). The Mercury Fire Training Pit formerly included a bermed burn pit with four small burn tanks, four large above ground storage tanks an overturned bus, a telephone pole storage area, and areas for burning sheds, pallets, and cables. Closure activities will includemore » excavation of the impacted soil in the aboveground storage tank and burn pit areas to a depth of 1.5 m (5 ft), and excavation of the impacted surface soil downgradient of the former ASTs and burnpit areas to a depth of 0.3 m (1 ft). Excavated soil will be disposed in the Area 6 Hydrocarbon Landfill at the NTS.« less

Survival of biofilm-forming Salmonella on stainless steel bolt threads under dry conditions.

PubMed

Morita, Yukio; Komoda, Emiko; Ono, Kazuaki; Kumagai, Susumu

2011-01-01

We examined the survival of two biofilm-forming strains and two biofilm-deficient strains of non typhoid Salmonella (NTS) on stainless steel bolt threads under dry conditions. Five µL of tryptone soya broth or egg yolke mulsion containing NTS strains at a concentration of 9 log cfu/mL was dropped onto the thread surfaces of hexagonal bolts. After inoculation, the bolts were screwed into the nuts, and then removed (Separate type) or not removed (Unit type). The two types of samples were kept in a dry environment (20.0-25.0°C, 2-15% humidity) and bacteria on the surfaces were periodically counted. Biofilm-forming strains were recovered from all samples after 336 days of incubation, but biofilm-deficient strains were isolated from only two of 8 samples after 336 days. This finding demonstrates that NTS can survive for approximately one year on bolt threads, providing direct evidence of the potential risk of constructions having crevices or uneven surfaces as possible contamination sources. The risk of cross-contamination may be higher for biofilm-forming strains than for biofilm-deficient strains.

Brainstem mechanisms underlying the cough reflex and its regulation.

PubMed

Mutolo, Donatella

2017-09-01

Cough is a very important airway protective reflex. Cough-related inputs are conveyed to the caudal nucleus tractus solitarii (cNTS) that projects to the brainstem respiratory network. The latter is reconfigured to generate the cough motor pattern. A high degree of modulation is exerted on second-order neurons and the brainstem respiratory network by sensory inputs and higher brain areas. Two medullary structures proved to have key functions in cough production and to be strategic sites of action for centrally active drugs: the cNTS and the caudal ventral respiratory group (cVRG). Drugs microinjected into these medullary structures caused downregulation or upregulation of the cough reflex. The results suggest that inhibition and disinhibition are prominent regulatory mechanisms of this reflex and that both the cNTS and the cVRG are essential in the generation of the entire cough motor pattern. Studies on the basic neural mechanisms subserving the cough reflex may provide hints for novel therapeutic approaches. Different proposals for further investigations are advanced. Copyright © 2017 Elsevier B.V. All rights reserved.

Kavalactones and dihydrokavain modulate GABAergic activity in a rat gastric-brainstem preparation.

PubMed

Yuan, Chun-Su; Dey, Lucy; Wang, Anbao; Mehendale, Sangeeta; Xie, Jing-Tian; Aung, Han H; Ang-Lee, Michael K

2002-12-01

Using an in vitro neonatal rat gastric-brainstem preparation, the activity of majority neurons recorded in the nucleus tractus solitarius (NTS) of the brainstem were significantly inhibited by GABA A receptor agonist, muscimol (30 microM), and this inhibition was reversed by selective GABA A receptor antagonist, bicuculline (10 microM). Application of kavalactones (300 microg/ml) and dihydrokavain (300 microM) into the brainstem compartment of the preparation also significantly reduced the discharge rate of these NTS neurons (39 % and 32 %, respectively, compared to the control level), and this reduction was partially reversed by bicuculline (10 microM). Kavalactones or dihydrokavain induced inhibitory effects were not reduced after co-application of saclofen (10 microM; a selective GABA B receptor antagonist) or naloxone (100 nM; an opioid receptor antagonist). Pretreatment with kavalactones (300 microg/ml) or dihydrokavain (300 microM) significantly decreased the NTS inhibitory effects induced by muscimol (30 microM), approximately from 51 % to 36 %. Our results demonstrated modulation of brainstem GABAergic mechanism by kavalactones and dihydrokavain, and suggested that these compounds may play an important role in regulation of GABAergic neurotransmission.

Curtailed respiration by repeated vs. isolated hypoxia in maturing piglets is unrelated to NTS ME or SP levels.

PubMed

Waters, K A; Laferrière, A; Paquette, J; Goodyer, C; Moss, I R

1997-08-01

In early development, respiratory disorders can produce recurring hypoxic episodes during sleep. To examine possible effects of daily repeated vs. isolated hypoxic hypoxia, cardiorespiratory functions and central, respiratory-related neuromodulator levels in 21- to 32-day-old, chronically instrumented, unsedated piglets were compared between a fifth sequential daily hypoxia and an isolated hypoxia (10% O2-90% N2 for 30 min). Diaphragmatic electromyographic activity, heart rate and arterial pressure, and pH and gas tensions were measured. In vivo microdialysis, via chronically implanted guides, served to sample interstitial substance P (SP) and methionine-enkephalin (ME) at the level of the respiratory-related nucleus tractus solitarii (NTS). Compared with an isolated hypoxia, repeated hypoxia resulted in 1) lower respiratory frequency (f), ventilation equivalent, and arterial pH, higher arterial PO2 during hypoxia, and lower f in recovery from hypoxia; and 2) increased SP concentrations but no change in ME concentrations. We conclude that, in these maturing swine, repeated vs. isolated hypoxic exposure curtails respiratory responses to hypoxia by a mechanism(s) unrelated to SP or ME levels at the NTS.

High level expression and immunochemical characterization of botulinum neurotoxin type F light chain.

PubMed

Chauhan, Ritika; Chauhan, Vinita; Rao, Mula Kameshwar; Chaudhary, Dilip; Bhagyawant, Sameer; Dhaked, Ram Kumar

2018-06-01

Botulinum neurotoxins (BoNTs) are the most toxic biological substances known. Their potential use as biological warfare agent results in their classification as category A biowarfare agent by Centers for Disease Control and Prevention (CDC), USA. Presently, there are no approved detection system and pharmacological treatments for BoNT intoxication. Although a toxoid vaccine is available for immuno-prophylaxis, vaccines cannot reverse the effect of pre-translocated toxin. Direct handling of the live BoNTs for developing detection and therapeutics may pose fatal danger. This concern was addressed by purifying the recombinant catalytically active light chain of BoNT/F. BoNT/F-LC gene was amplified from the genomic DNA using specifically designed primers and expressed in Escherichia coli. Expression and purification profile were optimized under different conditions for biologically active light chain production. Specific polyclonal antibodies generated against type F illustrates in vivo neutralization in mice and rabbit. These antibodies play key role in conceiving the development of high throughput SPR based detection system which is a highly precise label free technique for protein interaction analysis. The presented work is first of its kind, signifying the production of highly stable and active rBoNT/F-LC and its immunochemical characterization. The study aids in paving the path towards developing a persistent detection system as well as in presenting comprehended scheme for in vitro small molecule therapeutics analysis. Copyright © 2018 Elsevier Inc. All rights reserved.

Improving non-technical skills (teamwork) in post-partum haemorrhage: A grouped randomised trial.

PubMed

Letchworth, Pippa M; Duffy, Shane P; Phillips, Dan

2017-10-01

To determine the effect of a decision support technology on teamwork and associated non-technical (NTS) and technical skills when teams manage post-partum haemorrhage (PPH) in the simulated environment. Multidisciplinary (MDT) maternity teams were taught how to manage post partum haemorrhage. They were randomised to the intervention: using a decision support mobile digital platform or a control group. Each team managed a post-partum simulation, which was recorded and reviewed by assessors. Primary outcome measures to assess teams NTS were the validated Global Assessment of Obstetric Team Performance (GAOTP) and Clinical Teamwork Scale (CTS). Secondary outcome measures were the 'friends and family test', technical skills, and the System Usability Scale (SUS). Sample size estimation was calculated by using 80% power 5% significance two tailed test (p1=85% p2=40%) n=34. 38 teams from August 2014-February 2016, were recruited, technical issues with failure of recording equipment meant 4 teams were excluded from teamwork analysis (1 intervention 3 control). Teamwork improved across all domains with the intervention (using a decision support mobile digital platform) p <0.01. CTS improved between 6.7-16.8% (average 14.2%) and GAOTP between 8.6-17.1% (average 13.5%) for all domains. Using the control group as baseline, the intervention improved teamwork by 25% using CTS and 22% using GAOTP. Fewer technical skills were missed with the intervention (p<0.01). There was no statistical difference in the time technical skills were achieved. Assessors were more likely to recommend intervention teams 87.5% (77/88) than control teams 63.6% (56/88) p<0.01 to their friends or family. The SUS was 'Good' (69) becoming excellently 'Usable' (81.6) over the study period. We report a decision support system, which improved NTS when managing PPH. Lack of teamwork is often cited as the cause of failures in care and we report a usable technology that assists with and improves teamwork during an emergency. Copyright © 2017 Elsevier B.V. All rights reserved.

Corrective Action Investigation Plan for Corrective Action Unit 516: Septic Systems and Discharge Points, Nevada Test Site, Nevada, Rev. 0, Including Record of Technical Change No. 1

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

None

This Corrective Action Investigation Plan (CAIP) contains the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Sites Office's (NNSA/NSO's) approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 516, Septic Systems and Discharge Points, Nevada Test Site (NTS), Nevada, under the Federal Facility Agreement and Consent Order. CAU 516 consists of six Corrective Action Sites: 03-59-01, Building 3C-36 Septic System; 03-59-02, Building 3C-45 Septic System; 06-51-01, Sump Piping, 06-51-02, Clay Pipe and Debris; 06-51-03, Clean Out Box and Piping; and 22-19-04, Vehicle Decontamination Area. Located in Areasmore » 3, 6, and 22 of the NTS, CAU 516 is being investigated because disposed waste may be present without appropriate controls, and hazardous and/or radioactive constituents may be present or migrating at concentrations and locations that could potentially pose a threat to human health and the environment. Existing information and process knowledge on the expected nature and extent of contamination of CAU 516 are insufficient to select preferred corrective action alternatives; therefore, additional information will be obtained by conducting a corrective action investigation. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document. Record of Technical Change No. 1 is dated 3/2004.« less

An interim report on the NTS-2 solar cell experiment

NASA Technical Reports Server (NTRS)

Statler, R. L.; Walker, D. H.

1979-01-01

Data obtained from the fourteen solar cell modules on the NTS-2 satellite are presented together with a record of panel temperature and sun inclination. The following flight data are discussed: (1) state of the art solar cell configurations which embody improvements in solar cell efficiency through new silicon surface and bulk technology, (2) improved coverslip materials and coverslip bonding techniques, (3) short and long term effects of ultraviolet rejection filters vs. no filters on the cells, (4) degradation on a developmental type of liquid epitaxy gallium-aluminum-arsenide solar cell, and (5) space radiation effects.

Achieving One-Electron Oxidation of a Mononuclear Nonheme Iron(V)-Imido Complex

DOE PAGES

Hong, Seungwoo; Lu, Xiaoyan; Lee, Yong -Min; ...

2017-09-29

Here, a mononuclear nonheme iron(V)-imido complex bearing a tetraamido macrocyclic ligand (TAML), [Fe V(NTs)(TAML)] – (1), was oxidized by one-electron oxidants, affording formation of an iron(V)-imido TAML cation radical species, [Fe V(NTs)(TAML +•)] (2); 2 is a diamagnetic (S = 0) complex, resulting from the antiferromagnetic coupling of the low-spin iron(V) ion (S = 1/2) with the one-electron oxidized ligand (TAML +•). 2 is a competent oxidant in C–H bond functionalization and nitrene transfer reaction, showing that the reactivity of 2 is greater than that of 1.

Sensing the deadliest toxin: technologies for botulinum neurotoxin detection.

PubMed

Capek, Petr; Dickerson, Tobin J

2010-01-01

Sensitive and rapid detection of botulinum neurotoxins (BoNTs), the most poisonous substances known to date, is essential for studies of medical applications of BoNTs and detection of poisoned food, as well as for response to potential bioterrorist threats. Currently, the most common method of BoNT detection is the mouse bioassay. While this assay is sensitive, it is slow, quite expensive, has limited throughput and requires sacrificing animals. Herein, we discuss and compare recently developed alternative in vitro detection methods and assess their ability to supplement or replace the mouse bioassay in the analysis of complex matrix samples.

Ecological Monitoring and Compliance Program Fiscal Year 2002 Report

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

C. A. Wills

2002-12-01

The Ecological Monitoring and Compliance program, funded through the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office, monitors the ecosystem of the Nevada Test Site (NTS) and ensures compliance with laws and regulations pertaining to NTS biota. This report summarizes the program's activities conducted by Bechtel Nevada (BN) during fiscal year 2002. Program activities included: (1) biological surveys at proposed construction sites, (2) desert tortoise compliance, (3) ecosystem mapping and data management, (4) sensitive species and unique habitat monitoring, and (5) biological monitoring at the HAZMAT Spill Center. Biological surveys for the presence of sensitive species andmore » important biological resources were conducted for 26 NTS projects. These projects have the potential to disturb a total of 374 acres. Thirteen of the projects were in desert tortoise habitat, and 13.38 acres of desert tortoise habitat were disturbed. No tortoises were found in or displaced from project areas, and no tortoises were accidentally injured or killed at project areas or along paved roads. Compilation of historical wildlife data continued this year in efforts to develop faunal distribution maps for the NTS. Photographs associated with the NTS ecological landform units sampled to create the NTS vegetation maps were cataloged for future retrieval and analysis. The list of sensitive plant species for which long-term population monitoring is scheduled was revised. Six vascular plants and five mosses were added to the list. Plant density estimates from ten populations of Astragalus beatleyae were collected, and eight known populations of Eriogonum concinnum were visited to assess plant and habitat status. Minimal field monitoring of western burrowing owl burrows occurred. A report relating to the ecology of the western burrowing owl on the Nevada Test Site was prepared which summarizes four years of data collected on this species' distribution, burrow use, reproduction, activity patterns, and food habits. Bat roost sites within seven buildings slated for demolition were identified, and a BN biologist was a contributing author of the Nevada Bat Conservation Plan published by the Nevada Bat Working Group. Thirty-three adult horses and five foals were counted this year. Six active raptor nests (two American kestrel, two Red-tailed hawk, and two Great-horned owl nests) were found and monitored this year. Selected wetlands and man-made water sources were monitored for physical parameters and wildlife use. No dead animals were observed this year in any plastic-lined sump. The chemical release test plan for one experiment at the HAZMAT Spill Center on Frenchman Lake playa was reviewed. Seasonal sampling of downwind and upwind transects near the spill center was conducted to document baseline conditions of biota.« less

Ecological Monitoring and Compliance Program Fiscal Year 2002 Report (Part Two of Two)

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

C. A. Wills

2002-12-01

The Ecological Monitoring and Compliance program, funded through the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office, monitors the ecosystem of the Nevada Test Site (NTS) and ensures compliance with laws and regulations pertaining to NTS biota. This report summarizes the program's activities conducted by Bechtel Nevada (BN) during fiscal year 2002. Program activities included: (1) biological surveys at proposed construction sites, (2) desert tortoise compliance, (3) ecosystem mapping and data management, (4) sensitive species and unique habitat monitoring, and (5) biological monitoring at the HAZMAT Spill Center. Biological surveys for the presence of sensitive species andmore » important biological resources were conducted for 26 NTS projects. These projects have the potential to disturb a total of 374 acres. Thirteen of the projects were in desert tortoise habitat, and 13.38 acres of desert tortoise habitat were disturbed. No tortoises were found in or displaced from project areas, and no tortoises were accidentally injured or killed at project areas or along paved roads. Compilation of historical wildlife data continued this year in efforts to develop faunal distribution maps for the NTS. Photographs associated with the NTS ecological landform units sampled to create the NTS vegetation maps were cataloged for future retrieval and analysis. The list of sensitive plant species for which long-term population monitoring is scheduled was revised. Six vascular plants and five mosses were added to the list. Plant density estimates from ten populations of Astragalus beatleyae were collected, and eight known populations of Eriogonum concinnum were visited to assess plant and habitat status. Minimal field monitoring of western burrowing owl burrows occurred. A report relating to the ecology of the western burrowing owl on the Nevada Test Site was prepared which summarizes four years of data collected on this species' distribution, burrow use, reproduction, activity patterns, and food habits. Bat roost sites within seven buildings slated for demolition were identified, and a BN biologist was a contributing author of the Nevada Bat Conservation Plan published by the Nevada Bat Working Group. Thirty-three adult horses and five foals were counted this year. Six active raptor nests (two American kestrel, two Red-tailed hawk, and two Great-horned owl nests) were found and monitored this year. Selected wetlands and man-made water sources were monitored for physical parameters and wildlife use. No dead animals were observed this year in any plastic-lined sump. The chemical release test plan for one experiment at the HAZMAT Spill Center on Frenchman Lake playa was reviewed. Seasonal sampling of downwind and upwind transects near the spill center was conducted to document baseline conditions of biota.« less

Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.

PubMed

De Jonghe, Bart C; Holland, Ruby A; Olivos, Diana R; Rupprecht, Laura E; Kanoski, Scott E; Hayes, Matthew R

2016-01-01

While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (<24 h) phase following treatment, the anorexia, nausea, fatigue, and other illness-type behaviors during the delayed phase (>24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

Application for a Permit to Operate a Class III Solid Waste Disposal Site at the Nevada Test Site Area 5 Asbestiform Low-Level Solid Waste Disposal Site

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

NSTec Environmental Programs

The NTS solid waste disposal sites must be permitted by the state of Nevada Solid Waste Management Authority (SWMA). The SWMA for the NTS is the Nevada Division of Environmental Protection, Bureau of Federal Facilities (NDEP/BFF). The U.S. Department of Energy's National Nuclear Security Administration Nevada Site Office (NNSA/NSO) as land manager (owner), and National Security Technologies (NSTec), as operator, will store, collect, process, and dispose all solid waste by means that do not create a health hazard, a public nuisance, or cause impairment of the environment. NTS disposal sites will not be included in the Nye County Solid Wastemore » Management Plan. The NTS is located approximately 105 kilometers (km) (65 miles [mi]) northwest of Las Vegas, Nevada (Figure 1). The U.S. Department of Energy (DOE) is the federal lands management authority for the NTS, and NSTec is the Management and Operations contractor. Access on and off the NTS is tightly controlled, restricted, and guarded on a 24-hour basis. The NTS has signs posted along its entire perimeter. NSTec is the operator of all solid waste disposal sites on the NTS. The Area 5 RWMS is the location of the permitted facility for the Solid Waste Disposal Site (SWDS). The Area 5 RWMS is located near the eastern edge of the NTS (Figure 2), approximately 26 km (16 mi) north of Mercury, Nevada. The Area 5 RWMS is used for the disposal of low-level waste (LLW) and mixed low-level waste. Many areas surrounding the RWMS have been used in conducting nuclear tests. A Notice of Intent to operate the disposal site as a Class III site was submitted to the state of Nevada on January 28, 1994, and was acknowledged as being received in a letter to the NNSA/NSO on August 30, 1994. Interim approval to operate a Class III SWDS for regulated asbestiform low-level waste (ALLW) was authorized on August 12, 1996 (in letter from Paul Liebendorfer to Runore Wycoff), with operations to be conducted in accordance with the ''Management Plan for the Disposal of Low-Level Waste with Regulated Asbestos Waste.'' A requirement of the authorization was that on or before October 9, 1999, a permit was required to be issued. Because of NDEP and NNSA/NSO review cycles, the final permit was issued on April 5, 2000, for the operation of the Area 5 Low-Level Waste Disposal Site, utilizing Pit 7 (P07) as the designated disposal cell. The original permit applied only to Pit 7, with a total design capacity of 5,831 cubic yards (yd{sup 3}) (157,437 cubic feet [ft{sup 3}]). NNSA/NSO is expanding the SWDS to include the adjacent Upper Cell of Pit 6 (P06), with an additional capacity of 28,037 yd{sup 3} (756,999 ft{sup 3}) (Figure 3). The proposed total capacity of ALLW in Pit 7 and P06 will be approximately 33,870 yd{sup 3} (0.9 million ft{sup 3}). The site will be used for the disposal of regulated ALLW, small quantities of low-level radioactive hydrocarbon-burdened (LLHB) media and debris, LLW, LLW that contains PCB Bulk Product Waste greater than 50 ppm that leaches at a rate of less than 10 micrograms of PCB per liter of water, and small quantities of LLHB demolition and construction waste (hereafter called permissible waste). Waste containing free liquids, or waste that is regulated as hazardous waste under the Resource Conservation and Recovery Act (RCRA) or state-of-generation hazardous waste regulations, will not be accepted for disposal at the site. The only waste regulated under the Toxic Substances Control Act (TSCA) that will be accepted at the disposal site is regulated asbestos-containing materials (RACM). The term asbestiform is used throughout this document to describe this waste. Other TSCA waste (i.e., polychlorinated biphenyls [PCBs]) will not be accepted for disposal at the SWDS. The disposal site will be used as a depository of permissible waste generated both on site and off site. All generators designated by NNSA/NSO will be eligible to dispose regulated ALLW at the Asbestiform Low-Level Waste Disposal Site in accordance with the U.S. Department of Energy, Nevada Operations Office (DOE/NV) 325, Nevada Test Site Waste Acceptance Criteria (NTSWAC, current revision). Approval will be given by NNSA/NSO to generators that have successfully demonstrated through process knowledge (PK) and/or sampling and analysis that the waste is low-level, contains asbestiform material, and does not contain prohibited waste materials. Each waste stream will be approved through the Radioactive Waste Acceptance Program (RWAP), which ensures that the waste meets acceptance requirements outlined in the NTS Class III Permit and the NTSWAC.« less

Antimicrobial resistance and management of invasive Salmonella disease.

PubMed

Kariuki, Samuel; Gordon, Melita A; Feasey, Nicholas; Parry, Christopher M

2015-06-19

Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20-30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50-75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries. Copyright © 2015. Published by Elsevier Ltd.

Effects of seed origin and irrigation on survival and growth of transplanted shrubs

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

Winkel, V.K.

1995-10-01

Revegetation is difficult in the Mojave Desert due to limited, erratic precipitation and extreme temperatures. Establishing plant cover by transplanting native shrubs is known to be a promising technique, but many questions still remain regarding its use on a large operational scale. A study was initiated on the US Department of Energy Nevada Test Site (NTS) to determine the effects of seed origin and irrigation on survival and growth of transplanted shrubs. Plants of three species (Larrea tridentata, Ambrosia dumosa, and Atriplex canescens) were grown in a greenhouse and hardened outdoors. Plants of all three species were produced from twomore » seed sources: (1) seed collected from the NTS (Mojave Desert), and (2) commercially available seed collected from outside the NTS. One-year-old containerized plants (180 of each species) were transplanted to a site on the NTS and irrigated with two liters of water at one of the following frequencies: (1) at time of planting only, (2) at time of planting and monthly during the first growing season, and (3) at time of planting and twice monthly during the first growing season. After 16 months, survival of all species was generally greater than 80% and was unaffected by irrigation treatments. Survival of fourwing saltbush was significantly greater from local versus non-local seed. Survival of bursage and creosotebush was generally unaffected by seed origin. Shrub volumes regardless of species or seed origin increased during the first growing season, and then decreased during the second growing season. Shrub volumes for fourwing saltbush were significantly greater for shrubs from local versus non-local seed.« less

Xenin Augments Duodenal Anion Secretion via Activation of Afferent Neural Pathways

PubMed Central

Kaji, Izumi; Akiba, Yasutada; Kato, Ikuo; Maruta, Koji; Kuwahara, Atsukazu

2017-01-01

Xenin-25, a neurotensin (NT)-related anorexigenic gut hormone generated mostly in the duodenal mucosa, is believed to increase the rate of duodenal ion secretion, because xenin-induced diarrhea is not present after Roux-en-Y gastric bypass surgery. Because the local effects of xenin on duodenal ion secretion have remained uninvestigated, we thus examined the neural pathways underlying xenin-induced duodenal anion secretion. Intravenous infusion of xenin-8, a bioactive C-terminal fragment of xenin-25, dose dependently increased the rate of duodenal HCO3− secretion in perfused duodenal loops of anesthetized rats. Xenin was immunolocalized to a subset of enteroendocrine cells in the rat duodenum. The mRNA of the xenin/NT receptor 1 (NTS1) was predominantly expressed in the enteric plexus, nodose and dorsal root ganglia, and in the lamina propria rather than in the epithelium. The serosal application of xenin-8 or xenin-25 rapidly and transiently increased short-circuit current in Ussing-chambered mucosa-submucosa preparations in a concentration-dependent manner in the duodenum and jejunum, but less so in the ileum and colon. The selective antagonist for NTS1, substance P (SP) receptor (NK1), or 5-hydroxytryptamine (5-HT)3, but not NTS2, inhibited the responses to xenin. Xenin-evoked Cl- secretion was reduced by tetrodotoxin (TTX) or capsaicin-pretreatment, and abolished by the inhibitor of TTX-resistant sodium channel Nav1.8 in combination with TTX, suggesting that peripheral xenin augments duodenal HCO3− and Cl− secretion through NTS1 activation on intrinsic and extrinsic afferent nerves, followed by release of SP and 5-HT. Afferent nerve activation by postprandial, peripherally released xenin may account for its secretory effects in the duodenum. PMID:28115552

Converting environmentally hazardous materials into clean energy using a novel nanostructured photoelectrochemical fuel cell

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

Gan, Yong X., E-mail: yong.gan@utoledo.edu; Gan, Bo J.; Clark, Evan

2012-09-15

Highlights: ► A photoelectrochemical fuel cell has been made from TiO{sub 2} nanotubes. ► The fuel cell decomposes environmentally hazardous materials to produce electricity. ► Doping the anode with a transition metal oxide increases the visible light sensitivity. ► Loading the anode with a conducting polymer enhances the visible light absorption. -- Abstract: In this work, a novel photoelectrochemical fuel cell consisting of a titanium dioxide nanotube array photosensitive anode and a platinum cathode was made for decomposing environmentally hazardous materials to produce electricity and clean fuel. Titanium dioxide nanotubes (TiO{sub 2} NTs) were prepared via electrochemical oxidation of puremore » Ti in an ammonium fluoride and glycerol-containing solution. Scanning electron microscopy was used to analyze the morphology of the nanotubes. The average diameter, wall thickness and length of the as-prepared TiO{sub 2} NTs were determined. The photosensitive anode made from the highly ordered TiO{sub 2} NTs has good photo-catalytic property, as proven by the decomposition tests on urea, ammonia, sodium sulfide and automobile engine coolant under ultraviolet (UV) radiation. To improve the efficiency of the fuel cell, doping the TiO{sub 2} NTs with a transition metal oxide, NiO, was performed and the photosensitivity of the doped anode was tested under visible light irradiation. It is found that the NiO-doped anode is sensitive to visible light. Also found is that polyaniline-doped photosensitive anode can harvest photon energy in the visible light spectrum range much more efficiently than the NiO-doped one. It is concluded that the nanostructured photoelectrochemical fuel cell can generate electricity and clean fuel by decomposing hazardous materials under sunlight.« less

Antimicrobial resistance and management of invasive Salmonella disease

PubMed Central

Kariuki, Samuel; Gordon, Melita A.; Feasey, Nicholas; Parry, Christopher M

2015-01-01

Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20–30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50–75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries. PMID:25912288

Non-technical skills of surgeons and anaesthetists in simulated operating theatre crises.

PubMed

Doumouras, A G; Hamidi, M; Lung, K; Tarola, C L; Tsao, M W; Scott, J W; Smink, D S; Yule, S

2017-07-01

Deficiencies in non-technical skills (NTS) have been increasingly implicated in avoidable operating theatre errors. Accordingly, this study sought to characterize the impact of surgeon and anaesthetist non-technical skills on time to crisis resolution in a simulated operating theatre. Non-technical skills were assessed during 26 simulated crises (haemorrhage and airway emergency) performed by surgical teams. Teams consisted of surgeons, anaesthetists and nurses. Behaviour was assessed by four trained raters using the Non-Technical Skills for Surgeons (NOTSS) and Anaesthetists' Non-Technical Skills (ANTS) rating scales before and during the crisis phase of each scenario. The primary endpoint was time to crisis resolution; secondary endpoints included NTS scores before and during the crisis. A cross-classified linear mixed-effects model was used for the final analysis. Thirteen different surgical teams were assessed. Higher NTS ratings resulted in significantly faster crisis resolution. For anaesthetists, every 1-point increase in ANTS score was associated with a decrease of 53·50 (95 per cent c.i. 31·13 to 75·87) s in time to crisis resolution (P < 0·001). Similarly, for surgeons, every 1-point increase in NOTSS score was associated with a decrease of 64·81 (26·01 to 103·60) s in time to crisis resolution in the haemorrhage scenario (P = 0·001); however, this did not apply to the difficult airway scenario. Non-technical skills scores were lower during the crisis phase of the scenarios than those measured before the crisis for both surgeons and anaesthetists. A higher level of NTS of surgeons and anaesthetists led to quicker crisis resolution in a simulated operating theatre environment. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Adaptive leadership curriculum for Indian paramedic trainees.

PubMed

Mantha, Aditya; Coggins, Nathaniel L; Mahadevan, Aditya; Strehlow, Rebecca N; Strehlow, Matthew C; Mahadevan, S V

2016-12-01

Paramedic trainees in developing countries face complex and chaotic clinical environments that demand effective leadership, communication, and teamwork. Providers must rely on non-technical skills (NTS) to manage bystanders and attendees, collaborate with other emergency professionals, and safely and appropriately treat patients. The authors designed a NTS curriculum for paramedic trainees focused on adaptive leadership, teamwork, and communication skills critical to the Indian prehospital environment. Forty paramedic trainees in the first academic year of the 2-year Advanced Post-Graduate Degree in Emergency Care (EMT-paramedic equivalent) program at the GVK-Emergency Management and Research Institute campus in Hyderabad, India, participated in the 6-day leadership course. Trainees completed self-assessments and delivered two brief video-recorded presentations before and after completion of the curriculum. Independent blinded observers scored the pre- and post-intervention presentations delivered by 10 randomly selected paramedic trainees. The third-party judges reported significant improvement in both confidence (25 %, p < 0.01) and body language of paramedic trainees (13 %, p < 0.04). Self-reported competency surveys indicated significant increases in leadership (2.6 vs. 4.6, p < 0.001, d = 1.8), public speaking (2.9 vs. 4.6, p < 0.001, d = 1.4), self-reflection (2.7 vs. 4.6, p < 0.001, d = 1.6), and self-confidence (3.0 vs. 4.8, p < 0.001, d = 1.5). Participants in a 1-week leadership curriculum for prehospital providers demonstrated significant improvement in self-reported NTS commonly required of paramedics in the field. The authors recommend integrating focused NTS development curriculum into Indian paramedic education and further evaluation of the long term impacts of this adaptive leadership training.

Elevated mu-opioid receptor expression in the nucleus of the solitary tract accompanies attenuated withdrawal signs after chronic low dose naltrexone in opiate-dependent rats.

PubMed

Van Bockstaele, E J; Rudoy, C; Mannelli, P; Oropeza, V; Qian, Y

2006-02-15

We previously described a decrease in withdrawal behaviors in opiate-dependent rats that were chronically treated with very low doses of naltrexone in their drinking water. Attenuated expression of withdrawal behaviors correlated with decreased c-Fos expression and intracellular signal transduction elements [protein kinase A regulatory subunit II (PKA) and phosphorylated cAMP response element binding protein (pCREB)] in brainstem noradrenergic nuclei. In this study, to determine whether similar cellular changes occurred in forebrain nuclei associated with drug reward, expressions of PKA and pCREB were analyzed in the ventral tegmental area, frontal cortex, striatum, and amygdala of opiate-treated rats that received low doses of naltrexone in their drinking water. No significant difference in PKA or pCREB was detected in these regions following drug treatment. To examine further the cellular mechanisms in noradrenergic nuclei that could underlie attenuated withdrawal behaviors following low dose naltrexone administration, the nucleus of the solitary tract (NTS) and locus coeruleus (LC) were examined for opioid receptor (OR) protein expression. Results showed a significant increase in muOR expression in the NTS of morphine-dependent rats that received low doses of naltrexone in their drinking water, and increases in muOR expression were also found to be dose dependent. Protein expression of muOR in the LC and deltaOR in either brain region remained unchanged. In conclusion, our previously reported decreases in c-Fos and PKA expression in the NTS following pretreatment with low doses of naltrexone may be partially explained by a greater inhibition of NTS neurons resulting from increased muOR expression in this region.

Does teaching non-technical skills to medical students improve those skills and simulated patient outcome?

PubMed

Hagemann, Vera; Herbstreit, Frank; Kehren, Clemens; Chittamadathil, Jilson; Wolfertz, Sandra; Dirkmann, Daniel; Kluge, Annette; Peters, Jürgen

2017-03-29

The purpose of this study is to evaluate the effects of a tailor-made, non-technical skills seminar on medical student's behaviour, attitudes, and performance during simulated patient treatment. Seventy-seven students were randomized to either a non-technical skills seminar (NTS group, n=43) or a medical seminar (control group, n=34). The human patient simulation was used as an evaluation tool. Before the seminars, all students performed the same simulated emergency scenario to provide baseline measurements. After the seminars, all students were exposed to a second scenario, and behavioural markers for evaluating their non-technical skills were rated. Furthermore, teamwork-relevant attitudes were measured before and after the scenarios, and perceived stress was measured following each simulation. All simulations were also evaluated for various medical endpoints. Non-technical skills concerning situation awareness (p<.01, r=0.5) and teamwork (p<.01, r=0.45) improved from simulation I to II in the NTS group. Decision making improved in both groups (NTS: p<.01, r=0.39; control: p<.01, r=0.46). The attitude 'handling errors' improved significantly in the NTS group (p<.05, r=0.34). Perceived stress decreased from simulation I to II in both groups. Medical endpoints and patients´ outcome did not differ significantly between the groups in simulation II. This study highlights the effectiveness of a single brief seminar on non-technical skills to improve student's non-technical skills. In a next step, to improve student's handling of emergencies and patient outcomes, non-technical skills seminars should be accompanied by exercises and more broadly embedded in the medical school curriculum.

Synaptology of the direct projections from the nucleus of the solitary tract to pharyngeal motoneurons in the nucleus ambiguus of the rat.

PubMed

Hayakawa, T; Zheng, J Q; Seki, M; Yajima, Y

1998-04-13

During the pharyngeal phase of the swallowing reflex, the nucleus of the solitary tract (NTS) receives peripheral inputs from the pharynx by means of the glossopharyngeal ganglion and is the location of premotor neurons for the pharyngeal (PH) motoneurons. The semicompact formation of the nucleus ambiguus (AmS) is composed of small and medium-sized neurons that do not project to the pharynx, and large PH motoneurons. We investigated whether the neurons in the NTS projected directly to the PH motoneurons or to the other kinds of neurons in the AmS by using the electron microscope. When wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the NTS after cholera toxin subunit B-conjugated HRP (CT-HRP) injections into the pharyngeal muscles of male Sprague-Dawley rats, many nerve terminals anterogradely labeled with WGA-HRP were found to contact PH motoneurons retrogradely labeled with CT-HRP. Most of the labeled axodendritic terminals (63%) contained pleomorphic vesicles with symmetric synaptic contacts (Gray's type II), and the remaining ones contained round vesicles with asymmetric synaptic contacts (Gray's type I). About 14% of the axosomatic terminals on PH motoneuron in a sectional plane were anterogradely labeled, and about 70% of the labeled axosomatic terminals were Gray's type II. Observations of serial ultrathin sections revealed that both the small and the medium-sized neurons received only a few labeled axosomatic terminals that were exclusively Gray's type I. These results indicate that the NTS neurons may send mainly inhibitory as well as a few excitatory inputs directly to the PH motoneurons in the AmS.

Invasive Salmonella Infections in Areas of High and Low Malaria Transmission Intensity in Tanzania

PubMed Central

Biggs, Holly M.; Lester, Rebecca; Nadjm, Behzad; Mtove, George; Todd, Jim E.; Kinabo, Grace D.; Philemon, Rune; Amos, Ben; Morrissey, Anne B.; Reyburn, Hugh; Crump, John A.

2014-01-01

Background. The epidemiology of Salmonella Typhi and invasive nontyphoidal Salmonella (NTS) differs, and prevalence of these pathogens among children in sub-Saharan Africa may vary in relation to malaria transmission intensity. Methods. We compared the prevalence of bacteremia among febrile pediatric inpatients aged 2 months to 13 years recruited at sites of high and low malaria endemicity in Tanzania. Enrollment at Teule Hospital, the high malaria transmission site, was from June 2006 through May 2007, and at Kilimanjaro Christian Medical Centre (KCMC), the low malaria transmission site, from September 2007 through August 2008. Automated blood culture, malaria microscopy with Giemsa-stained blood films, and human immunodeficiency virus testing were performed. Results. At Teule, 3639 children were enrolled compared to 467 at KCMC. Smear-positive malaria was detected in 2195 of 3639 (60.3%) children at Teule and 11 of 460 (2.4%) at KCMC (P < .001). Bacteremia was present in 336 of 3639 (9.2%) children at Teule and 20 of 463 (4.3%) at KCMC (P < .001). NTS was isolated in 162 of 3639 (4.5%) children at Teule and 1 of 463 (0.2%) at KCMC (P < .001). Salmonella Typhi was isolated from 11 (0.3%) children at Teule and 6 (1.3%) at KCMC (P = .008). With NTS excluded, the prevalence of bacteremia at Teule was 5.0% and at KCMC 4.1% (P = .391). Conclusions. Where malaria transmission was intense, invasive NTS was common and Salmonella Typhi was uncommon, whereas the inverse was observed at a low malaria transmission site. The relationship between these pathogens, the environment, and the host is a compelling area for further research. PMID:24336909

Central representation of postingestive chemosensory cues in mice that lack the ability to taste.

PubMed

Stratford, Jennifer M; Finger, Thomas E

2011-06-22

The gustatory nerves of mice lacking P2X2 and P2X3 purinergic receptor subunits (P2X-dblKO) are unresponsive to taste stimulation (Finger et al., 2005). Surprisingly, P2X-dblKO mice show residual behavioral responses to concentrated tastants, presumably via postingestive detection. Therefore, the current study tested whether postingestive signaling is functional in P2X-dblKO mice and if so, whether it activates the primary viscerosensory nucleus of the medulla, the nucleus of the solitary tract (nTS). Like WT animals, P2X-dblKO mice learned to prefer a flavor paired with 150 mm monosodium glutamate (MSG) over a flavor paired with water. This preference shows that, even in the absence of taste sensory input, postingestive cues are detected and associated with a flavor in P2X-dblKO mice. MSG-evoked neuronal activation in the nTS was measured by expression of the immediate early gene c-Fos [c-Fos-like immunoreactivity (Fos-LI)]. In rostral, gustatory nTS, P2X-dblKO animals, unlike WT animals, showed no taste quality-specific labeling of neurons. Furthermore, MSG-evoked Fos-LI was significantly less in P2X-dblKO mice compared with WT animals. In contrast, in more posterior, viscerosensory nTS, MSG-induced Fos-LI was similar in WT and P2X-dblKO mice. Together, these results suggest that P2X-dblKO mice can form preferences based on postingestive cues and that postingestive detection of MSG does not rely on the same purinergic signaling that is crucial for taste.

High Prevalence of Tuberculosis and Serious Bloodstream Infections in Ambulatory Individuals Presenting for Antiretroviral Therapy in Malawi

PubMed Central

Bedell, Richard A.; Anderson, Suzanne T. B.; van Lettow, Monique; Åkesson, Ann; Corbett, Elizabeth L.; Kumwenda, Moses; Chan, Adrienne K.; Heyderman, Robert S.; Zachariah, Rony; Harries, Anthony D.; Ramsay, Andrew R.

2012-01-01

Background Tuberculosis (TB) and serious bloodstream infections (BSI) may contribute to the high early mortality observed among patients qualifying for antiretroviral therapy (ART) with unexplained weight loss, chronic fever or chronic diarrhea. Methods and Findings A prospective cohort study determined the prevalence of undiagnosed TB or BSI among ambulatory HIV-infected adults with unexplained weight loss and/or chronic fever, or diarrhea in two routine program settings in Malawi. Subjects with positive expectorated sputum smears for AFB were excluded. Investigations Bacterial and mycobacterial blood cultures, cryptococcal antigen test (CrAg), induced sputum (IS) for TB microscopy and solid culture, full blood count and CD4 lymphocyte count. Among 469 subjects, 52 (11%) had microbiological evidence of TB; 50 (11%) had a positive (non-TB) blood culture and/or positive CrAg. Sixty-five additional TB cases were diagnosed on clinical and radiological grounds. Nontyphoidal Salmonellae (NTS) were the most common blood culture pathogens (29 cases; 6% of participants and 52% of bloodstream isolates). Multivariate analysis of baseline clinical and hematological characteristics found significant independent associations between oral candidiasis or lymphadenopathy and TB, marked CD4 lymphopenia and NTS infection, and severe anemia and either infection, but low positive likelihood ratios (<2 for all combinations). Conclusions We observed a high prevalence of TB and serious BSI, particularly NTS, in a program cohort of chronically ill HIV-infected outpatients. Baseline clinical and hematological characteristics were inadequate predictors of infection. HIV clinics need better rapid screening tools for TB and BSI. Clinical trials to evaluate empiric TB or NTS treatment are required in similar populations. PMID:22761767

A mixed methods evaluation of paediatric trainee preparedness to manage cardiopulmonary arrests.

PubMed

Walsh, Órla; Lydon, Sinéad; O'Connor, Paul

2017-12-01

Paediatric cardiopulmonary arrest (CPA) survival rates are strongly linked to the training of the doctors responding to the event. This study sought to characterise the level of experience in managing CPAs among paediatric trainees and to investigate the nontechnical (NTS) required to effectively lead a paediatric CPA team. A mixed-methods research design was used. For the quantitative phase, a questionnaire was developed to assess training, confidence, and experiences related to CPA management. During the qualitative phase, 17 paediatric trainees participated in a series of critical incident technique (CIT) interviews to explore the NTS used during the management of paediatric CPAs. A total of 56 of 131 (37.1% response rate) trainees responded to the preparedness questionnaire. A total of 48.2% of respondents expressed low confidence in their skill as a team leader during the management of a CPA. The CIT interviews highlighted deficiencies in specific NTS (identifying options, prioritising, and identifying and utilising resources). Our results indicate that there is a desire for more training in CPA management among paediatric trainees, in particular as a team leader, which includes a focus on key NTS. What is Known • Levels of preparedness to be a paediatric cardiopulmonary arrests team member/leader are generally lower than desirable. • The importance of nontechnical skills to the effective performance of adult cardiopulmonary arrests teams has been identified. What is New • Levels of preparedness to be a cardiopulmonary arrests team member were higher than reported in US studies. • There is a need for greater training in cardiopulmonary arrest management which includes a focus on key nontechnical skills to include identifying options, prioritising, identifying and utilising resources.

Neurotensin effects on N-type calcium currents among rat pallidal neurons: an electrophysiological and immunohistochemical study.

PubMed

Martorana, Alessandro; Martella, Giuseppina; D'Angelo, Vincenza; Fusco, Francesca Romana; Spadoni, Francesca; Bernardi, Giorgio; Stefani, Alessandro

2006-10-01

The tridecapeptide neurotensin (NT) is involved in the modulation of dopamine (DA)-mediated functions in the nigrostriatal and mesocorticolimbic pathways. Its relevance in mammalian globus pallidus (GP) is questioned. A recent electrophysiological study on GP slices described NT-mediated robust membrane depolarization, depending upon the suppression of potassium conductance and/or the activation of cation current. Here, we have studied whether NT also affected high-voltage-activated calcium (Ca(2+)) currents, by means of whole-cell recordings on isolated GP neurons. In our hands, the full peptide and the segment NT8-13 reversibly inhibited N-like Ca(2+) current in about 60% of the recorded dissociated neurons, irrespective of their capacitance. The NT-mediated modulation showed no desensitization and was antagonized by the NT1 antagonists SR48692 and SR142948. These results imply an abundant expression of NTS(1) on GP cell somata. Then, we performed a light and immunofluorescence-confocal microscopy study of NTS(1) localization among GP neurons. We found that NTS(1) is localized in about 56% of GP neurons in both subpopulations of neurons, namely parvalbumin positive and negative. We conclude that NT, likely released from the striatal terminals in GP, acts through the postsynaptic NTS(1) preferentially localized in the lateral aspects of the GP. These data suggest a new implication (neither merely presynaptic nor simply "excitatory") for NT in the modulation of GP firing pattern. In addition, NT might have a role in affecting the interplay among the endogenous release of GABA/glutamate and DA. This hypothesis might have implications on both sensori-motor and associative functions of the GP and should be tested in DA-denervated disease models.

Changes in oestrogen receptor alpha expression in the nucleus of the solitary tract of the rat over the oestrous cycle and following ovariectomy.

PubMed

Spary, E J; Maqbool, A; Batten, T F C

2010-06-01

Oestrogen is capable of modulating autonomic outflow and baroreflex function via actions on groups of neurones in the brainstem. We investigated the presence of oestrogen receptor (ER) alpha in a part of the nucleus of the solitary tract (NTS) associated with central cardiovascular control, aiming to determine whether ERalpha mRNA and protein expression is correlated with levels of circulating oestrogen during the oestrous cycle. Polymerase chain reaction (PCR) detected ERalpha mRNA in the NTS at each stage of the oestrous cycle, from ovariectomised, sham-operated and male rats. Real-time PCR showed variations in ERalpha mRNA expression during the oestrous cycle, with the highest levels seen in oestrus, and lowest levels in metoestrus (P < 0.05 versus oestrus) and proestrus (P < 0.05 versus oestrus). Expression in males was lower than in dioestrus and oestrus females (P < 0.05). After ovariectomy, ERalpha mRNA levels were decreased compared to sham-operated animals (P < 0.01). Confocal fluorescence immunohistochemistry with stereological analysis showed that numbers of ERalpha immunoreactive cell nuclei per mm(3) of tissue in the caudal NTS were significantly greater in proestrus than in other groups of rats (P < 0.05). There were also differences among the groups in the extent of colocalisation of ERalpha in neurones immunoreactive for tyrosine hydroxylase and nitric oxide synthase. These results imply a complex pattern of region-specific oestrogen signalling in the NTS and suggest that ERalpha expression in this important autonomic nucleus may be related to circulating oestrogen levels. This may have consequences for the regulation of autonomic tone and baroreflex sensitivity when oestrogen levels decline, for example following menopause.

Improved Osteoblast and Chondrocyte Adhesion and Viability by Surface-Modified Ti6Al4V Alloy with Anodized TiO2 Nanotubes Using a Super-Oxidative Solution

PubMed Central

Beltrán-Partida, Ernesto; Moreno-Ulloa, Aldo; Valdez-Salas, Benjamín; Velasquillo, Cristina; Carrillo, Monica; Escamilla, Alan; Valdez, Ernesto; Villarreal, Francisco

2015-01-01

Titanium (Ti) and its alloys are amongst the most commonly-used biomaterials in orthopedic and dental applications. The Ti-aluminum-vanadium alloy (Ti6Al4V) is widely used as a biomaterial for these applications by virtue of its favorable properties, such as high tensile strength, good biocompatibility and excellent corrosion resistance. TiO2 nanotube (NTs) layers formed by anodization on Ti6Al4V alloy have been shown to improve osteoblast adhesion and function when compared to non-anodized material. In his study, NTs were grown on a Ti6Al4V alloy by anodic oxidation for 5 min using a super-oxidative aqueous solution, and their in vitro biocompatibility was investigated in pig periosteal osteoblasts and cartilage chondrocytes. Scanning electron microscopy (SEM), energy dispersion X-ray analysis (EDX) and atomic force microscopy (AFM) were used to characterize the materials. Cell morphology was analyzed by SEM and AFM. Cell viability was examined by fluorescence microscopy. Cell adhesion was evaluated by nuclei staining and cell number quantification by fluorescence microscopy. The average diameter of the NTs was 80 nm. The results demonstrate improved cell adhesion and viability at Day 1 and Day 3 of cell growth on the nanostructured material as compared to the non-anodized alloy. In conclusion, this study evidences the suitability of NTs grown on Ti6Al4V alloy using a super-oxidative water and a short anodization process to enhance the adhesion and viability of osteoblasts and chondrocytes. The results warrant further investigation for its use as medical implant materials. PMID:28787976

Cannabinoids suppress synaptic input to neurones of the rat dorsal motor nucleus of the vagus nerve

PubMed Central

Derbenev, Andrei V; Stuart, Thomas C; Smith, Bret N

2004-01-01

Cannabinoids bind central type 1 receptors (CB1R) and modify autonomic functions, including feeding and anti-emetic behaviours, when administered peripherally or into the dorsal vagal complex. Western blots and immunohistochemistry indicated the expression of CB1R in the rat dorsal vagal complex, and tissue polymerase chain reaction confirmed that CB1R message was made within the region. To identify a cellular substrate for the central autonomic effects of cannabinoids, whole-cell patch-clamp recordings were made in brainstem slices to determine the effects of CB1R activation on synaptic transmission to neurones of the dorsal motor nucleus of the vagus (DMV). A subset of these neurones was identified as gastric related after being labelled retrogradely from the stomach. The CB1R agonists WIN55,212-2 and anandamide decreased the frequency of spontaneous excitatory or inhibitory postsynaptic currents in a concentration-related fashion, an effect that persisted in the presence of tetrodotoxin. Paired pulse ratios of electrically evoked postsynaptic currents were also increased by WIN55,212-2. The effects of WIN55,212-2 were sensitive to the selective CB1R antagonist AM251. Cannabinoid agonist effects on synaptic input originating from neurones in the nucleus tractus solitarius (NTS) were determined by evoking activity in the NTS with local glutamate application. Excitatory and inhibitory synaptic inputs arising from the NTS were attenuated by WIN55,212-2. Our results indicate that cannabinoids inhibit transfer of synaptic information to the DMV, including that arising from the NTS, in part by acting at receptors located on presynaptic terminals contacting DMV neurones. Inhibition of synaptic input to DMV neurones is likely to contribute to the suppression of visceral motor responses by cannabinoids. PMID:15272041

Ecological studies of small vertebrates in Pu-contaminated study areas of NTS and TTR

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

Bradley, W.G.; Moor, K.S.; White, M.G.

Ecological studies of vertebrates in plutonium-contaminated areas of the Nevada Test Site (NTS) were initiated in March 1972, and have continued to date. In September 1973, standard census methods were also employed to derive a qualitative and quantitative inventory of vertebrate biota of four Nevada Applied Ecology Group (NAEG) study areas of the Tonopah Test Range (TTR). A checklist of vertebrates of NAEG study areas of NTS and TTR is presented. Data are presented on vertebrate composition, relative abundance, and seasonal status in the study areas. Concentrations of $sup 239$Pu and $sup 241$Am were determined in pelt or skin, GImore » tract, and carcass of 13 lizards and 16 mammals resident on Clean Slate 2, TTR, and Area 11, NTS. A total of 71 animals were collected for radioanalysis. However, the data were not available at the time this report was written. Pu tissue burdens were highest in lizards from Area 11 GZ. Maximum values obtained in nCi/g ash were 30.9, 42.2, and 0.43 for the pelt, GI tract, and carcass, respectively. Maximum $sup 239$Pu values in tissues of small rodents from Area 11 (not from GZ) were 11.4, 6.49, and 0.20 nCi/g ash for pelt, GI tract, and carcass, respectively. Pu/Am ratios were relatively consistent in tissue samples of lizards and small mammals from Area 11 (approximately 6:1, Pu/Am). Pu/Am ratios were not consistent in vertebrates of Clean Slate 2, TTR, and appeared to be lower in carcass (28:1, Pu/Am in mammals) than GI tract (9:1, Pu/Am in mammals). Although this trend was more conspicuous in mammals, it was also evident in reptiles. (auth)« less

Improved Osteoblast and Chondrocyte Adhesion and Viability by Surface-Modified Ti6Al4V Alloy with Anodized TiO₂ Nanotubes Using a Super-Oxidative Solution.

PubMed

Beltrán-Partida, Ernesto; Moreno-Ulloa, Aldo; Valdez-Salas, Benjamín; Velasquillo, Cristina; Carrillo, Monica; Escamilla, Alan; Valdez, Ernesto; Villarreal, Francisco

2015-03-02

Titanium (Ti) and its alloys are amongst the most commonly-used biomaterials in orthopedic and dental applications. The Ti-aluminum-vanadium alloy (Ti6Al4V) is widely used as a biomaterial for these applications by virtue of its favorable properties, such as high tensile strength, good biocompatibility and excellent corrosion resistance. TiO₂ nanotube (NTs) layers formed by anodization on Ti6Al4V alloy have been shown to improve osteoblast adhesion and function when compared to non-anodized material. In his study, NTs were grown on a Ti6Al4V alloy by anodic oxidation for 5 min using a super-oxidative aqueous solution, and their in vitro biocompatibility was investigated in pig periosteal osteoblasts and cartilage chondrocytes. Scanning electron microscopy (SEM), energy dispersion X-ray analysis (EDX) and atomic force microscopy (AFM) were used to characterize the materials. Cell morphology was analyzed by SEM and AFM. Cell viability was examined by fluorescence microscopy. Cell adhesion was evaluated by nuclei staining and cell number quantification by fluorescence microscopy. The average diameter of the NTs was 80 nm. The results demonstrate improved cell adhesion and viability at Day 1 and Day 3 of cell growth on the nanostructured material as compared to the non-anodized alloy. In conclusion, this study evidences the suitability of NTs grown on Ti6Al4V alloy using a super-oxidative water and a short anodization process to enhance the adhesion and viability of osteoblasts and chondrocytes. The results warrant further investigation for its use as medical implant materials.

Immunocytochemical localization of glutamic acid decarboxylase (GAD) and substance P in neural areas mediating motion-induced emesis: Effects of vagal stimulation on GAD immunoreactivity

NASA Technical Reports Server (NTRS)

Damelio, F.; Gibbs, M. A.; Mehler, W. R.; Daunton, Nancy G.; Fox, Robert A.

1991-01-01

Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid (GABA) by means of its biosynthetic enzyme glutamic acid decarboxylase (GAD) and the neuropeptide substance P in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), and gelatinous nucleus (GEL). In addition, electrical stimulation was applied to the night vagus nerve at the cervical level to assess the effects on GAD-immunoreactivity (GAR-IR). GAD-IR terminals and fibers were observed in the AP, ASP, NTS, and GEL. They showed pronounced density at the level of the ASP and gradual decrease towards the solitary complex. Nerve cells were not labelled in our preparations. Ultrastructural studies showed symmetric or asymmetric synaptic contracts between labelled terminals and non-immunoreactive dendrites, axons, or neurons. Some of the labelled terminals contained both clear- and dense-core vesicles. Our preliminary findings, after electrical stimulation of the vagus nerve, revealed a bilateral decrease of GAD-IR that was particularly evident at the level of the ASP. SP-immunoreactive (SP-IR) terminals and fibers showed varying densities in the AP, ASP, NTS, and GEL. In our preparations, the lateral sub-division of the NTS showed the greatest accumulation. The ASP showed medium density of immunoreactive varicosities and terminals and the AP and GEL displayed scattered varicose axon terminals. The electron microscopy revealed that all immunoreactive terminals contained clear-core vesicles which make symmetric or asymmetric synaptic contact with unlabelled dendrites. It is suggested that the GABAergic terminals might correspond to vagal afferent projections and that GAD/GABA and substance P might be co-localized in the same terminal allowing the possibility of a regulated release of the transmitters in relation to demands.

Substance P presynaptically depresses the transmission of sensory input to bronchopulmonary neurons in the guinea pig nucleus tractus solitarii

PubMed Central

Sekizawa, Shin-ichi; Joad, Jesse P; Bonham, Ann C

2003-01-01

Substance P modulates the reflex regulation of respiratory function by its actions both peripherally and in the CNS, particularly in the nucleus tractus solitarii (NTS), the first central site for synaptic contact of the lung and airway afferent fibres. There is considerable evidence that the actions of substance P in the NTS augment respiratory reflex output, but the precise effects on synaptic transmission have not yet been determined. Therefore, we determined the effects of substance P on synaptic transmission at the first central synapses by using whole-cell voltage clamping in an NTS slice preparation. Studies were performed on second-order neurons in the slice anatomically identified as receiving monosynaptic input from sensory nerves in the lungs and airways. This was done by the fluorescent labelling of terminal boutons after 1,1′-dioctadecyl-3,3,3′,3′-tetra-methylindocarbo-cyanine perchlorate (DiI) was applied via tracheal instillation. Substance P (1.0, 0.3 and 0.1 μM) significantly decreased the amplitude of excitatory postsynaptic currents (eEPSCs) evoked by stimulation of the tractus solitarius, in a concentration-dependent manner. The decrease was accompanied by an increase in the paired-pulse ratio of two consecutive eEPSCs, and a decrease in the frequency, but not the amplitude, of spontaneous EPSCs and miniature EPSCs, findings consistent with a presynaptic site of action. The effects were consistently and significantly attenuated by a neurokinin-1 (NK1) receptor antagonist (SR140333, 3 μM). The data suggest a new site of action for substance P in the NTS (NK1 receptors on the central terminals of sensory fibres) and a new mechanism (depression of synaptic transmission) for regulating respiratory reflex function. PMID:14561836

Ground-water discharge determined from estimates of evapotranspiration, Death Valley regional flow system, Nevada and California

USGS Publications Warehouse

Laczniak, Randell J.; Smith, J. LaRue; Elliott, Peggy E.; DeMeo, Guy A.; Chatigny, Melissa A.; Roemer, Gaius J.

2001-01-01

The Death Valley regional flow system (DVRFS) is one of the larger ground-water flow systems in the southwestern United States and includes much of southern Nevada and the Death Valley region of eastern California. Centrally located within the ground-water flow system is the Nevada Test Site (NTS). The NTS, a large tract covering about 1,375 square miles, historically has been used for testing nuclear devices and currently is being studied as a potential repository for the long-term storage of high-level nuclear waste generated in the United States. The U.S. Department of Energy, as mandated by Federal and State regulators, is evaluating the risk associated with contaminants that have been or may be introduced into the subsurface as a consequence of any past or future activities at the NTS. Because subsurface contaminants can be transported away from the NTS by ground water, components of the ground-water budget are of great interest. One such component is regional ground-water discharge. Most of the ground water leaving the DVRFS is limited to local areas where geologic and hydrologic conditions force ground water upward toward the surface to discharge at springs and seeps. Available estimates of ground-water discharge are based primarily on early work done as part of regional reconnaissance studies. These early efforts covered large, geologically complex areas and often applied substantially different techniques to estimate ground-water discharge. This report describes the results of a study that provides more consistent, accurate, and scientifically defensible measures of regional ground-water losses from each of the major discharge areas of the DVRFS. Estimates of ground-water discharge presented in this report are based on a rigorous quantification of local evapotranspiration (ET). The study identifies areas of ongoing ground-water ET, delineates different ET areas based on similarities in vegetation and soil-moisture conditions, and determines an ET rate for each delineated area. Each area, referred to as an ET unit, generally consists of one or more assemblages of local phreatophytes or a unique moist soil environment. Ten ET units are identified throughout the DVRFS based on differences in spectral-reflectance characteristics. Spectral differences are determined from satellite imagery acquired June 21, 1989, and June 13, 1992. The units identified include areas of open playa, moist bare soils, sparse to dense vegetation, and open water. ET rates estimated for each ET unit range from a few tenths of a foot per year for open playa to nearly 9 feet per year for open water. Mean annual ET estimates are computed for each discharge area by summing estimates of annual ET from each ET unit within a discharge area. The estimate of annual ET from each ET unit is computed as the product of an ET unit's acreage and estimated ET rate. Estimates of mean annual ET range from 450 acre-feet in the Franklin Well area to 30,000 acre-feet in Sarcobatus Flat. Ground-water discharge is estimated as annual ET minus that part of ET attributed to local precipitation. Mean annual ground-water discharge estimates range from 350 acre-feet in the Franklin Well area to 18,000 acre-feet in Ash Meadows. Generally, these estimates are greater for the northern discharge areas (Sarcobatus Flat and Oasis Valley) and less for the southern discharge areas (Franklin Lake, Shoshone area, and Tecopa/ California Valley area) than those previously reported.

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

BECHTEL NEVADA ECOLOGICAL SERVICES

The Ecological Monitoring and Compliance program (EMAC), funded through the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO), monitors the ecosystem of the Nevada Test Site (NTS) and ensures compliance with laws and regulations pertaining to NTS biota. This report summarizes the program’s activities conducted by Bechtel Nevada (BN) during the Calendar Year 2005. Program activities included: (1) biological surveys at proposed construction sites, (2) desert tortoise compliance, (3) ecosystem mapping and data management, (4) sensitive and protected/regulated species and unique habitat monitoring, (5) habitat restoration monitoring, and (6) biological monitoring at the Non-Proliferation Test andmore » Evaluation Complex (NPTEC).« less

Status of the flora and fauna on the Nevada Test Site, 1988. Results of continuing basic environmental monitoring, January--December 1988

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

Hunter, R.B.

1992-06-01

In 1987 the US Department of Energy (DOE) initiated a program to monitor the health of the Nevada Test Site (NTS) plants and animals in support of the National Environmental Protection Act. The program, part of DOE`s Basic Environmental Compliance and Monitoring Program (BECAMP), monitors perennial and ephemeral plants, the more common species of rodents and lizards, and the horses, deer, raptors and other large animals on the NTS. This is a report of data collected on these flora and fauna for the year 1988, the second year of monitoring.

Carbon nanotubes: physics and applications

NASA Astrophysics Data System (ADS)

Bellucci, S.

2005-01-01

We overview definitions, properties and applications of Carbon nanotubes (CNTs). We describe the CNTs lifecycle: starting with phases and requirements, going through the different synthesis methods, describing then the various purification techniques. The fundamentals of functionalization and the use of defects in CNTs are reviewed, in connection also to ion irradiation techniques. Metal oxides and other semiconducting 1D nanostructures are then considered, before entering the description of the main features of the present status of INFN-LNF research in nanoscience, focusing on CNTs, as well as on aluminium nitride NTs (AlN NTs). We conclude our review by illustrating device application criteria for many applications in different areas of the field of nanotechnology.

Performance of preproduction model cesium beam frequency standards for spacecraft applications

NASA Technical Reports Server (NTRS)

Levine, M. W.

1978-01-01

A cesium beam frequency standards for spaceflight application on Navigation Development Satellites was designed and fabricated and preliminary testing was completed. The cesium standard evolved from an earlier prototype model launched aboard NTS-2 and the engineering development model to be launched aboard NTS satellites during 1979. A number of design innovations, including a hybrid analog/digital integrator and the replacement of analog filters and phase detectors by clocked digital sampling techniques are discussed. Thermal and thermal-vacuum testing was concluded and test data are presented. Stability data for 10 to 10,000 seconds averaging interval, measured under laboratory conditions, are shown.

Facile electrochemical synthesis of antimicrobial TiO2 nanotube arrays

PubMed Central

Zhao, Yu; Xing, Qi; Janjanam, Jagadeesh; He, Kun; Long, Fei; Low, Ke-Bin; Tiwari, Ashutosh; Zhao, Feng; Shahbazian-Yassar, Reza; Friedrich, Craig; Shokuhfar, Tolou

2014-01-01

Infection-related complications have been a critical issue for the application of titanium orthopedic implants. The use of Ag nanoparticles offers a potential approach to incorporate antimicrobial properties into the titanium implants. In this work, a novel and simple method was developed for synthesis of Ag (II) oxide deposited TiO2 nanotubes (TiNTs) using electrochemical anodization followed by Ag electroplating processes in the same electrolyte. The quantities of AgO nanoparticles deposited in TiNT were controlled by selecting different electroplating times and voltages. It was shown that AgO nanoparticles were crystalline and distributed throughout the length of the nanotubes. Inductively coupled plasma mass spectrometry tests showed that the quantities of released Ag were less than 7 mg/L after 30 days at 37°C. Antimicrobial assay results show that the AgO-deposited TiNTs can effectively kill the Escherichia coli bacteria. Although the AgO-deposited TiNTs showed some cytotoxicity, it should be controllable by optimization of the electroplating parameters and incorporation of cell growth factor. The results of this study indicated that antimicrobial properties could be added to nanotextured medical implants through a simple and cost effective method. PMID:25429214

Geophysical interpretations west of and within the northwestern part of the Nevada Test Site

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

Grauch, V.J.; Sawyer, D.A.; Fridrich, C.J.

1997-12-31

This report focuses on interpretation of gravity and new magnetic data west of the Nevada Test Site (NTS) and within the northwestern part of NTS. The interpretations integrate the gravity and magnetic data with other geophysical, geological, and rock property data to put constraints on tectonic and magmatic features not exposed at the surface. West of NTS, where drill hole information is absent, these geophysical data provide the best available information on the subsurface. Interpreted subsurface features include calderas, intrusions, basalt flows and volcanoes, Tertiary basins, structurally high pre-Tertiary rocks, and fault zones. New features revealed by this study includemore » (1) a north-south buried tectonic fault east of Oasis Mountain, which the authors call the Hogback fault; (2) an east striking fault or accommodation zone along the south side of Oasis Valley basin, which they call the Hot Springs fault; (3) a NNE striking structural zone coinciding with the western margins of the caldera complexes; (4) regional magnetic highs that probably represent a thick sequence of Tertiary volcanic rocks; and (5) two probable buried calderas that may be related to the tuffs of Tolicha Peak and of Sleeping Butte, respectively.« less

Preparation, characterization, and application of Ti/TiO2-NTs/Sb-SnO2 electrode in photo-electrochemical treatment of industrial effluents under mild conditions.

PubMed

Subba Rao, Anantha N; Venkatarangaiah, Venkatesha T

2018-04-01

Ti/TiO 2 -NTs/Sb-SnO 2 electrode was prepared by gradient pulsed electrodeposition, and its electrochemical properties were evaluated. The catalytic activity and reusability of the electrode were tested by electrochemical oxidation (EO) and photoelectrochemical oxidation (PEO) of organics present in textile industry wastewater (TWW) and coffee bean processing industry wastewater (CWW). COD removal of ~ 41% was achieved after 5-h electrolysis under a constant applied current density of 30 mA cm -2 for TWW and 50 mA cm -2 for CWW. Nearly 14 and 18% increment in COD removal was observed under PEO for TWW and CWW, respectively. The turbidity of TWW reduced from 15 to ~ 3 NTU and the turbidity of CWW reduced from 27 to ~ 3 NTU by both EO and PEO. The % COD removal observed after 5-h electrolysis remained consistent for 7 repeated cycles; however, the catalytic activity of the electrode reduced gradually. These results suggested that the Ti/TiO 2 -NTs/Sb-SnO 2 can be a potential electrode for the treatment of industrial wastewater.

Platinum-ruthenium nanotubes and platinum-ruthenium coated copper nanowires as efficient catalysts for electro-oxidation of methanol

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

Zheng, Jie; Cullen, David A.; Forest, Robert V.

2015-01-15

The sluggish kinetics of methanol oxidation reaction (MOR) is a major barrier to the commercialization of direct methanol fuel cells (DMFCs). In this study, we report a facile synthesis of platinum–ruthenium nanotubes (PtRuNTs) and platinum–ruthenium-coated copper nanowires (PtRu/CuNWs) by galvanic displacement reaction using copper nanowires as a template. The PtRu compositional effect on MOR is investigated; the optimum Pt/Ru bulk atomic ratio is about 4 and surface atomic ratio about 1 for both PtRuNTs and PtRu/CuNWs. Enhanced specific MOR activities are observed on both PtRuNTs and PtRu/CuNWs compared with the benchmark commercial carbon-supported PtRu catalyst (PtRu/C, Hispec 12100). Finally, x-raymore » photoelectron spectroscopy (XPS) reveals a larger extent of electron transfer from Ru to Pt on PtRu/CuNWs, which may lead to a modification of the d-band center of Pt and consequently a weaker bonding of CO (the poisoning intermediate) on Pt and a higher MOR activity on PtRu/CuNWs.« less

Reactor-pumped laser facility at DOE's Nevada Test Site

NASA Astrophysics Data System (ADS)

Lipinski, Ronald J.

1994-05-01

The Nevada Test Site (NTS) is one excellent possibility for a laser power beaming site. It is in the low latitudes of the U.S., is in an exceptionally cloud-free area of the southwest, is already an area of restricted access (which enhances safety considerations), and possesses a highly skilled technical team with extensive engineering and research capabilities from underground testing of our nation's nuclear deterrence. The average availability of cloud-free clear line of site to a given point in space is about 84%. With a beaming angle of +/- 60 degree(s) from the zenith, about 52 geostationary-orbit (GEO) satellites could be accessed continuously from NTS. In addition, the site would provide an average view factor of about 10% for orbital transfer from low earth orbit to GEO. One of the major candidates for a long-duration, high- power laser is a reactor-pumped laser being developed by DOE. The extensive nuclear expertise at NTS makes this site a prime candidate for utilizing the capabilities of a rector pumped laser for power beaming. The site then could be used for many dual-use roles such as industrial material processing research, defense testing, and removing space debris.

Magnetic interactions and reversal mechanisms in Co nanowire and nanotube arrays

NASA Astrophysics Data System (ADS)

Proenca, M. P.; Sousa, C. T.; Escrig, J.; Ventura, J.; Vazquez, M.; Araujo, J. P.

2013-03-01

Ordered hexagonal arrays of Co nanowires (NWs) and nanotubes (NTs), with diameters between 40 and 65 nm, were prepared by potentiostatic electrodeposition into suitably modified nanoporous alumina templates. The geometrical parameters of the NW/NT arrays were tuned by the pore etching process and deposition conditions. The magnetic interactions between NWs/NTs with different diameters were studied using first-order reversal curves (FORCs). From a quantitative analysis of the FORC measurements, we are able to obtain the profiles of the magnetic interactions and the coercive field distributions. In both NW and NT arrays, the magnetic interactions were found to increase with the diameter of the NWs/NTs, exhibiting higher values for NW arrays. A comparative study of the magnetization reversal processes was also performed by analyzing the angular dependence of the coercivity and correlating the experimental data with theoretical calculations based on a simple analytical model. The magnetization in the NW arrays is found to reverse by the nucleation and propagation of a transverse-like domain wall; on the other hand, for the NT arrays a non-monotonic behavior occurs above a diameter of ˜50 nm, revealing a transition between the vortex and transverse reversal modes.

Modular structural elements in the replication origin region of Tetrahymena rDNA.

PubMed Central

Du, C; Sanzgiri, R P; Shaiu, W L; Choi, J K; Hou, Z; Benbow, R M; Dobbs, D L

1995-01-01

Computer analyses of the DNA replication origin region in the amplified rRNA genes of Tetrahymena thermophila identified a potential initiation zone in the 5'NTS [Dobbs, Shaiu and Benbow (1994), Nucleic Acids Res. 22, 2479-2489]. This region consists of a putative DNA unwinding element (DUE) aligned with predicted bent DNA segments, nuclear matrix or scaffold associated region (MAR/SAR) consensus sequences, and other common modular sequence elements previously shown to be clustered in eukaryotic chromosomal origin regions. In this study, two mung bean nuclease-hypersensitive sites in super-coiled plasmid DNA were localized within the major DUE-like element predicted by thermodynamic analyses. Three restriction fragments of the 5'NTS region predicted to contain bent DNA segments exhibited anomalous migration characteristic of bent DNA during electrophoresis on polyacrylamide gels. Restriction fragments containing the 5'NTS region bound Tetrahymena nuclear matrices in an in vitro binding assay, consistent with an association of the replication origin region with the nuclear matrix in vivo. The direct demonstration in a protozoan origin region of elements previously identified in Drosophila, chick and mammalian origin regions suggests that clusters of modular structural elements may be a conserved feature of eukaryotic chromosomal origins of replication. Images PMID:7784181

Response to palatability after area postrema lesions: a result of learned aversions.

PubMed

Tomoyasu, N; Kenney, N J

1989-11-01

The role of palatability, novelty, and food aversion in determining changes of food choice after ablation of the area postrema and caudal-medial aspect of the nucleus of the solitary tract (AP/cmNTS) is examined through a series of studies utilizing 24-h, two-food choice tests. On test days, the food that the animal has ingested since the time of lesioning or sham surgery is presented along with a novel food that varies in palatability. The results indicate that postlesion diet history is the major determinant of food choice by lesioned rats. Lesioned rats consistently take less of their familiar postlesion food than diet-matched controls, suggesting that the lesioned rats have developed an aversion to that food. Over-ingestion of the novel food may occur, but this outcome is not reliable. No indication that the animals' response to food palatability is affected by AP/cmNTS ablation was found. Learned aversion to a food ingested after AP/cmNTS ablation may account not only for changes of food preference after the lesion but also may be involved in the hypophagia and weight loss resulting from the ablation.

The psychometric testing of the Nursing Teamwork Survey in Iceland.

PubMed

Bragadóttir, Helga; Kalisch, Beatrice J; Smáradóttir, Sigríður Bríet; Jónsdóttir, Heiður Hrund

2016-06-01

The purpose of this study was to test the psychometric properties of the Nursing Teamwork Survey-Icelandic (NTS-Icelandic), which was translated from US English to Icelandic. The Nursing Teamwork Survey, with 33 items, measures overall teamwork and five factors of teamwork: trust, team orientation, backup, shared mental models, and team leadership. The psychometric testing of the NTS-Icelandic was carried out on data from a pilot study and a national study. The sample for a pilot study included 123 nursing staff from five units, and the sample for a national study included 925 nursing staff from 27 inpatient units. The overall test-retest intraclass correlation coefficient in the pilot study was 0.693 (lower bound = 0.498, upper bound = 0.821) (p < 0.001). The Cronbach's alpha reliability for the total scale and subscales ranged from 0.737 to 0.911. A confirmatory factor analysis indicated a good fit of the data from the national study with the five-factor model for nursing teamwork. The NTS-Icelandic tested valid and reliable in this study. Study findings support further use of the Nursing Teamwork Survey internationally. © 2016 John Wiley & Sons Australia, Ltd.

Porous platinum nanotubes labeled with hemin/G-quadruplex based electrochemical aptasensor for sensitive thrombin analysis via the cascade signal amplification.

PubMed

Sun, Aili; Qi, Qingan; Wang, Xuannian; Bie, Ping

2014-07-15

For the first time, a sensitive electrochemical aptasensor for thrombin (TB) was developed by using porous platinum nanotubes (PtNTs) labeled with hemin/G-quadruplex and glucose dehydrogenase (GDH) as labels. Porous PtNTs with large surface area exhibited the peroxidase-like activity. Coupling with GDH and hemin/G-quadruplex as NADH oxidase and HRP-mimicking DNAzyme, the cascade signal amplification was achieved by the following ways: in the presence of glucose and NAD(+) in the working buffer, GDH electrocatalyzed the oxidation of glucose with the production of NADH. Then, hemin/G-quadruplex as NADH oxidase catalyzed the oxidation of NADH to in situ generate H2O2. Based on the corporate electrocatalysis of PtNTs and hemin/G-quadruplex toward H2O2, the electrochemical signal was significantly amplified, allowing the detection limit of TB down to 0.15 pM level. Moreover, the proposed strategy was simple because the intercalated hemin offered the readout signal, avoiding the adding of additional redox mediator as signal donator. Such an electrochemical aptasensor is highly promising for sensitive detection of other proteins in clinical diagnostics. Copyright © 2014 Elsevier B.V. All rights reserved.

Enhanced Charge Collection in MOF‐525–PEDOT Nanotube Composites Enable Highly Sensitive Biosensing

PubMed Central

Huang, Tzu‐Yen; Kung, Chung‐Wei; Liao, Yu‐Te; Kao, Sheng‐Yuan; Cheng, Mingshan; Chang, Ting‐Hsiang; Henzie, Joel; Alamri, Hatem R.; Alothman, Zeid A.

2017-01-01

Abstract With the aim of a reliable biosensing exhibiting enhanced sensitivity and selectivity, this study demonstrates a dopamine (DA) sensor composed of conductive poly(3,4‐ethylenedioxythiophene) nanotubes (PEDOT NTs) conformally coated with porphyrin‐based metal–organic framework nanocrystals (MOF‐525). The MOF‐525 serves as an electrocatalytic surface, while the PEDOT NTs act as a charge collector to rapidly transport the electron from MOF nanocrystals. Bundles of these particles form a conductive interpenetrating network film that together: (i) improves charge transport pathways between the MOF‐525 regions and (ii) increases the electrochemical active sites of the film. The electrocatalytic response is measured by cyclic voltammetry and differential pulse voltammetry techniques, where the linear concentration range of DA detection is estimated to be 2 × 10−6–270 × 10−6 m and the detection limit is estimated to be 0.04 × 10−6 m with high selectivity toward DA. Additionally, a real‐time determination of DA released from living rat pheochromocytoma cells is realized. The combination of MOF5‐25 and PEDOT NTs creates a new generation of porous electrodes for highly efficient electrochemical biosensing. PMID:29201623

Status of the flora and fauna on the Nevada Test Site, 1989--1991

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

Hunter, R.B.

1994-03-01

This volume includes six reports of monitoring work to determine the status of and trends in flora and fauna populations on the Nevada Test Site (NTS) from 1989 through 1991. The Nevada Operations Office of the US Department of Energy supported monitoring under its Basic Environmental Compliance and Monitoring Program (BECAMP) since 1987. Under this program several undisturbed baseline plots, and numerous plots in disturbed areas, are sampled on annual or three-year cycles. Perennial plant populations, ephemeral plants, small mammals, reptiles, birds, and large mammals were monitored. Monitoring results are reported for five baseline sites, one from each major landformmore » on the NTS (Jackass Flats, Frenchman Flat, Yucca Flat, Pahute Mesa, and Rainier Mesa), and for areas cleared of vegetation by fires, atmospheric nuclear weapons tests, construction, and gophers. Roadside flora and fauna were studied at two locations, and several historical study plots around the NTS were recensused to determine vegetation changes over long time spans. Three subsidence craters resulting from below-ground nuclear weapons tests were also studied. A major influence on plants and animals during the report period was a severe drought during 1989 and 1990, followed by more moderate drought in 1991.« less