Stress Ratio Effects on Crack Opening Loads and Crack Growth Rates in Aluminum Alloy 2024

NASA Technical Reports Server (NTRS)

Riddell, William T.; Piascik, Robert S.

1998-01-01

The effects of stress ratio (R) and crack opening behavior on fatigue crack growth rates (da/dN) for aluminum alloy (AA) 2024-T3 were investigated using constant-delta K testing, closure measurements, and fractography. Fatigue crack growth rates were obtained for a range of delta K and stress ratios. Results show that constant delta K fatigue crack growth for R ranging from near 0 to 1 is divided into three regions. In Region 1, at low R, da/dN increases with increasing R. In Region 2, at intermediate R, fatigue crack growth rates are relatively independent of R. In Region 3, at high R, further increases in da/dN are observed with increasing R.

Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Torres, Gonzalo E; Wagner, Amy K

2015-03-02

Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can assess real-time in vivo dopamine (DA) concentration changes to study the kinetics of DA neurotransmission. Electrical stimulation of dopaminergic (DAergic) pathways can elicit FSCV DA responses that largely reflect a balance of DA release and reuptake. Interpretation of these evoked DA responses requires a framework to discern the contribution of DA release and reuptake. The current, widely implemented interpretive framework for doing so is the Michaelis-Menten (M-M) model, which is grounded on two assumptions- (1) DA release rate is constant during stimulation, and (2) DA reuptake occurs through dopamine transporters (DAT) in a manner consistent with M-M enzyme kinetics. Though the M-M model can simulate evoked DA responses that rise convexly, response types that predominate in the ventral striatum, the M-M model cannot simulate dorsal striatal responses that rise concavely. Based on current neurotransmission principles and experimental FSCV data, we developed a novel, quantitative, neurobiological framework to interpret DA responses that assumes DA release decreases exponentially during stimulation and continues post-stimulation at a diminishing rate. Our model also incorporates dynamic M-M kinetics to describe DA reuptake as a process of decreasing reuptake efficiency. We demonstrate that this quantitative, neurobiological model is an extension of the traditional M-M model that can simulate heterogeneous regional DA responses following manipulation of stimulation duration, frequency, and DA pharmacology. The proposed model can advance our interpretive framework for future in vivo FSCV studies examining regional DA kinetics and their alteration by disease and DA pharmacology. Copyright © 2015 Elsevier B.V. All rights reserved.

Amyloid beta precursor protein and ubiquitin epitopes in human and experimental dystrophic axons. Ultrastructural localization.

PubMed Central

Bacci, B.; Cochran, E.; Nunzi, M. G.; Izeki, E.; Mizutani, T.; Patton, A.; Hite, S.; Sayre, L. M.; Autilio-Gambetti, L.; Gambetti, P.

1994-01-01

Dystrophic axons (DA) represent a major pathological feature of several neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD) and Alzheimer disease. We have previously presented evidence that amyloid beta precursor protein (BPP) and ubiquitin (Ub) are present in DA of different origin. We have now characterized the immunoreactivity of DA experimentally induced in rat by the administration of parabromophenylacetylurea (BPAU) and examined the subcellular localization of Ub and BPP in BPAU-induced DA and in DA present in subjects affected by INAD. BPAU-induced DA strongly immunoreacted with antisera to Ub and to COOH- and NH2-terminal regions of BPP. Immunoblots of DA-enriched brain regions were consistent with an increase in the amount of Ub and BPP in DA. Moreover, BPAU-induced DA immunoreacted with antibodies to PGP 9.5, a neuronal-specific Ub COOH-terminal hydrolase, and to the inducible heat shock protein 70. Antigenic characterization also indicated that the tubulovesicular membranes within DA derived largely from the smooth endoplasmic reticulum rather than from the Golgi system or the synaptic vesicles. Subcellular immunolocalization of Ub and BPP in both INAD- and BPAU-induced DA revealed that Ub and BPP colocalize in granulovesicular material in both conditions. In INAD DA intense Ub immunoreactivity was also detected in nonmembranous electron dense structures that were present only in these DA, probably because of the chronic course of INAD. Although BPP immunostaining may be related to accumulation of BPP-containing membranes in DA, Ub immunostaining is likely to result from activation of the Ub system by the neuron in the attempt to remove excessive and possibly abnormal proteins. A similar pathogenesis can be postulated for DA of Alzheimer disease. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7512790

Dopamine response to psychosocial stress in humans and its relationship to individual differences in personality traits.

PubMed

Suridjan, Ivonne; Boileau, Isabelle; Bagby, Michael; Rusjan, Pablo M; Wilson, Alan A; Houle, Sylvain; Mizrahi, Romina

2012-07-01

Previous studies have reported inter-individual variability in the dopamine (DA) response to stress. This variability might be related to individual differences in the vulnerability to experience the negative effect of stress. To investigate whether personality traits as measured by the revised NEO personality inventory explain variability in DA response to a psychosocial stress task. Eleven healthy adults, mean age of 26 ± 3.87 underwent two positron emission tomography (PET) scans using the dopamine D(2/3) agonist, [11C]-(+)-PHNO under a control and stress condition. The simplified reference tissue model (SRTM) was used to obtain [11C]-(+)-PHNO binding potential (BP(ND)). Stress-induced DA response was indexed as a percent change in [11C]-(+)-PHNO BP(ND) between control and stress conditions. The regions of interest were defined into D2-rich regions, which included the Associative and Sensorimotor Striatum (AST and SMST); D(2/3) mixed regions, which included the limbic striatum (LST) and globus pallidus (GP); and D3-rich region, which included the Substantia Nigra (SN). Several personality traits within the Neuroticism and Openness to Experience domain were significantly correlated with blunted DA response to stress. Specifically, the Angry-Hostility, Vulnerability, and Depression trait were associated with blunted DA stress response in the AST (r = -0.645, p = 0.032), LST (r = -0.677, p = 0.022) and GP (r = -0.736, p = 0.010), respectively. The Openness to Values was correlated with a decreased DA release in the SN (r = -0.706, p = 0.015). Variability in DA stress response might be related to individual differences in personality. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

32 CFR 635.22 - Reserve component, U.S. Army Reserve, and Army National Guard personnel.

Code of Federal Regulations, 2010 CFR

2010-07-01

... civilians. (b) The DA Form 3975 and DA Form 4833 will be forwarded directly to the appropriate Regional Readiness Command or the Soldier's division commander. A copy of the DA Form 3975 will also be forwarded to...

Locomotor stimulation produced by 3,4-methylenedioxymethamphetamine (MDMA) is correlated with dialysate levels of serotonin and dopamine in rat brain

PubMed Central

Baumann, Michael H.; Clark, Robert D.; Rothman, Richard B.

2008-01-01

(±)-3,4-Methylenedioxymethamphetmine (MDMA, or Ecstasy) is an illicit drug that evokes transporter-mediated release of monoamines, including serotonin (5-HT) and dopamine (DA). Here we monitored the effects of MDMA on neurochemistry and motor activity in rats, as a means to evaluate relationships between 5-HT, DA, and behavior. Male rats undergoing in vivo microdialysis were housed in chambers equipped with photobeams for measurement of ambulation (i.e., forward locomotion) and stereotypy (i.e., head weaving and forepaw treading). Microdialysis probes were placed into the n. accumbens, striatum or prefrontal cortex in separate groups of rats. Dialysate samples were assayed for 5-HT and DA by microbore HPLC-ECD. Rats received two i.v. injections of MDMA, 1 mg/kg followed by 3 mg/kg 60 min later; neurochemical and locomotor parameters were measured concurrently. MDMA produced dose-related elevations in extracellular 5-HT and DA in all regions, with the magnitude of 5-HT release always exceeding that of DA release. MDMA-induced ambulation was positively correlated with dialysate DA levels in all regions (P<0.05-0.0001) and with dialysate 5-HT in striatum and cortex (P<0.001-0.0001). Stereotypy was strongly correlated with dialysate 5-HT in all areas (P<0.001-0.0001) and with dialysate DA in accumbens and striatum (P<0.001-0.0001). These data support previous work and suggest the complex spectrum of behaviors produced by MDMA involves 5-HT and DA in a region- and modality-specific manner. PMID:18403002

Intraspecific Variation of Centruroides Edwardsii Venom from Two Regions of Colombia

PubMed Central

Estrada-Gómez, Sebastián; Cupitra, Nelson Ivan; Arango, Walter Murillo; Vargas Muñoz, Leidy Johana

2014-01-01

We report the first description studies, partial characterization, and intraspecific difference of Centruroides edwardsii, Gervais 1843, venom. C. edwardsii from two Colombian regions (Antioquia and Tolima) were evaluated. Both venoms showed hemolytic activity, possibly dependent of enzymatic active phospholipases, and neither coagulant nor proteolytic activities were observed. Venom electrophoretic profile showed significant differences between C. edwardsii venom from both regions. A high concentration of proteins with molecular masses between 31 kDa and 97.4 kDa, and an important concentration close or below 14.4 kDa were detected. RP-HPLC retention times between 38.2 min and 42.1 min, showed bands close to 14.4 kDa, which may correspond to phospholipases. RP-HPLC venom profile showed a well conserved region in both venoms between 7 and 17 min, after this, significant differences were detected. From Tolima region venom, 50 well-defined peaks were detected, while in the Antioquia region venom, 55 well-defined peaks were detected. Larvicidal activity was only detected in the C. edwardsii venom from Antioquia. No antimicrobial activity was observed using complete venom or RP-HPLC collected fractions of both venoms. Lethally activity (carried out on female albino swiss mice) was detected at doses over 19.2 mg/kg of crude venom. Toxic effects included distress, excitability, eye irritation and secretions, hyperventilation, ataxia, paralysis, and salivation. PMID:25025710

The role of transparency in da Vinci stereopsis.

PubMed

Zannoli, Marina; Mamassian, Pascal

2011-10-15

The majority of natural scenes contains zones that are visible to one eye only. Past studies have shown that these monocular regions can be seen at a precise depth even though there are no binocular disparities that uniquely constrain their locations in depth. In the so-called da Vinci stereopsis configuration, the monocular region is a vertical line placed next to a binocular rectangular occluder. The opacity of the occluder has been mentioned to be a necessary condition to obtain da Vinci stereopsis. However, this opacity constraint has never been empirically tested. In the present study, we tested whether da Vinci stereopsis and perceptual transparency can interact using a classical da Vinci configuration in which the opacity of the occluder varied. We used two different monocular objects: a line and a disk. We found no effect of the opacity of the occluder on the perceived depth of the monocular object. A careful analysis of the distribution of perceived depth revealed that the monocular object was perceived at a depth that increased with the distance between the object and the occluder. The analysis of the skewness of the distributions was not consistent with a double fusion explanation, favoring an implication of occlusion geometry in da Vinci stereopsis. A simple model that includes the geometry of the scene could account for the results. In summary, the mechanism responsible to locate monocular regions in depth is not sensitive to the material properties of objects, suggesting that da Vinci stereopsis is solved at relatively early stages of disparity processing. Copyright © 2011 Elsevier Ltd. All rights reserved.

JCoDA: a tool for detecting evolutionary selection.

PubMed

Steinway, Steven N; Dannenfelser, Ruth; Laucius, Christopher D; Hayes, James E; Nayak, Sudhir

2010-05-27

The incorporation of annotated sequence information from multiple related species in commonly used databases (Ensembl, Flybase, Saccharomyces Genome Database, Wormbase, etc.) has increased dramatically over the last few years. This influx of information has provided a considerable amount of raw material for evaluation of evolutionary relationships. To aid in the process, we have developed JCoDA (Java Codon Delimited Alignment) as a simple-to-use visualization tool for the detection of site specific and regional positive/negative evolutionary selection amongst homologous coding sequences. JCoDA accepts user-inputted unaligned or pre-aligned coding sequences, performs a codon-delimited alignment using ClustalW, and determines the dN/dS calculations using PAML (Phylogenetic Analysis Using Maximum Likelihood, yn00 and codeml) in order to identify regions and sites under evolutionary selection. The JCoDA package includes a graphical interface for Phylip (Phylogeny Inference Package) to generate phylogenetic trees, manages formatting of all required file types, and streamlines passage of information between underlying programs. The raw data are output to user configurable graphs with sliding window options for straightforward visualization of pairwise or gene family comparisons. Additionally, codon-delimited alignments are output in a variety of common formats and all dN/dS calculations can be output in comma-separated value (CSV) format for downstream analysis. To illustrate the types of analyses that are facilitated by JCoDA, we have taken advantage of the well studied sex determination pathway in nematodes as well as the extensive sequence information available to identify genes under positive selection, examples of regional positive selection, and differences in selection based on the role of genes in the sex determination pathway. JCoDA is a configurable, open source, user-friendly visualization tool for performing evolutionary analysis on homologous coding sequences. JCoDA can be used to rapidly screen for genes and regions of genes under selection using PAML. It can be freely downloaded at http://www.tcnj.edu/~nayaklab/jcoda.

JCoDA: a tool for detecting evolutionary selection

PubMed Central

2010-01-01

Background The incorporation of annotated sequence information from multiple related species in commonly used databases (Ensembl, Flybase, Saccharomyces Genome Database, Wormbase, etc.) has increased dramatically over the last few years. This influx of information has provided a considerable amount of raw material for evaluation of evolutionary relationships. To aid in the process, we have developed JCoDA (Java Codon Delimited Alignment) as a simple-to-use visualization tool for the detection of site specific and regional positive/negative evolutionary selection amongst homologous coding sequences. Results JCoDA accepts user-inputted unaligned or pre-aligned coding sequences, performs a codon-delimited alignment using ClustalW, and determines the dN/dS calculations using PAML (Phylogenetic Analysis Using Maximum Likelihood, yn00 and codeml) in order to identify regions and sites under evolutionary selection. The JCoDA package includes a graphical interface for Phylip (Phylogeny Inference Package) to generate phylogenetic trees, manages formatting of all required file types, and streamlines passage of information between underlying programs. The raw data are output to user configurable graphs with sliding window options for straightforward visualization of pairwise or gene family comparisons. Additionally, codon-delimited alignments are output in a variety of common formats and all dN/dS calculations can be output in comma-separated value (CSV) format for downstream analysis. To illustrate the types of analyses that are facilitated by JCoDA, we have taken advantage of the well studied sex determination pathway in nematodes as well as the extensive sequence information available to identify genes under positive selection, examples of regional positive selection, and differences in selection based on the role of genes in the sex determination pathway. Conclusions JCoDA is a configurable, open source, user-friendly visualization tool for performing evolutionary analysis on homologous coding sequences. JCoDA can be used to rapidly screen for genes and regions of genes under selection using PAML. It can be freely downloaded at http://www.tcnj.edu/~nayaklab/jcoda. PMID:20507581

Selecting global climate models for regional climate change studies

PubMed Central

Pierce, David W.; Barnett, Tim P.; Santer, Benjamin D.; Gleckler, Peter J.

2009-01-01

Regional or local climate change modeling studies currently require starting with a global climate model, then downscaling to the region of interest. How should global models be chosen for such studies, and what effect do such choices have? This question is addressed in the context of a regional climate detection and attribution (D&A) study of January-February-March (JFM) temperature over the western U.S. Models are often selected for a regional D&A analysis based on the quality of the simulated regional climate. Accordingly, 42 performance metrics based on seasonal temperature and precipitation, the El Nino/Southern Oscillation (ENSO), and the Pacific Decadal Oscillation are constructed and applied to 21 global models. However, no strong relationship is found between the score of the models on the metrics and results of the D&A analysis. Instead, the importance of having ensembles of runs with enough realizations to reduce the effects of natural internal climate variability is emphasized. Also, the superiority of the multimodel ensemble average (MM) to any 1 individual model, already found in global studies examining the mean climate, is true in this regional study that includes measures of variability as well. Evidence is shown that this superiority is largely caused by the cancellation of offsetting errors in the individual global models. Results with both the MM and models picked randomly confirm the original D&A results of anthropogenically forced JFM temperature changes in the western U.S. Future projections of temperature do not depend on model performance until the 2080s, after which the better performing models show warmer temperatures. PMID:19439652

Differences in the time course of dopaminergic supersensitivity following chronic administration of haloperidol, molindone, or sulpiride.

PubMed

Prosser, E S; Pruthi, R; Csernansky, J G

1989-01-01

The onset and persistence of changes in 3H-spiroperidol binding to dopamine (DA) D2 receptors were examined in rat mesolimbic and striatal brain regions following daily administration of haloperidol, molindone, or sulpiride for 3, 7, 14, or 28 days. Neuroleptic dose equivalencies were determined by inhibition of 3H-spiroperidol in vivo binding in several rat brain regions. Changes in locomotor and stereotyped responses to the specific DA D2 agonist quinpirole were examined 3 days after the last treatment dose. Haloperidol or molindone administration increased mean stereotypy scores and striatal DA D2 receptor densities throughout the 28-day treatment period. In contrast, mesolimbic DA D2 receptor densities were transiently increased and returned to control values, after 28 days of haloperidol or molindone treatment. Sulpiride treatment increased mean stereotypy scores and striatal Bmax values, but had no effect on locomotion or mesolimbic dopamine receptor density. Additionally, the magnitude of change in the various measures of brain DA function varied among the three neuroleptic treatment groups. Results from this study suggest that mesolimbic and striatal brain regions differ in their response to long-term neuroleptic administration and that drug choice may influence the magnitude of neuroleptic-induced dopaminergic supersensitivity.

Reversal of dopamine system dysfunction in response to high-fat diet.

PubMed

Carlin, Jesselea; Hill-Smith, Tiffany E; Lucki, Irwin; Reyes, Teresa M

2013-12-01

To test whether high-fat diet (HFD) decreases dopaminergic tone in reward regions of the brain and evaluate whether these changes reverse after removal of the HFD. Male and female mice were fed a 60% HFD for 12 weeks. An additional group was evaluated 4 weeks after removal of the HFD. These groups were compared with control fed, age-matched controls. Sucrose and saccharin preference was measured along with mRNA expression of dopamine (DA)-related genes by Real Time-quantitative PCR (RT-qPCR). DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography. DNA methylation of the dopamine transporter (DAT) promoter was measured by methylated DNA immunoprecipitation and RT-qPCR. After chronic HFD, sucrose preference was reduced, and then normalized after removal of the HFD. Decreased expression of DA genes, decreased DA content and alterations in DAT promoter methylation, was observed. Importantly, response to HFD and the persistence of changes depended on sex and brain region. These data identify diminished DA tone after early-life chronic HFD with a complex pattern of reversal and persistence that varies by both sex and brain region. Central nervous system changes that did not reverse after HFD withdrawal may contribute to the difficulty in maintaining weight-loss after diet intervention. Copyright © 2013 The Obesity Society.

Education

DTIC Science & Technology

2003-01-01

Frank Sosa, Dept. of the Air Force Col Juan Urbano , Peruvian Army Dr. Francis A’Hearn, Faculty Prof. William Mayall, Faculty COL Mark McGuire...insufficient time to meet job requirements such as planning lessons to grading papers, to participating in mandatory training to phoning parents to...

Mass transit : review of the Tren Urbano finance plan

DOT National Transportation Integrated Search

2000-03-31

In summary, we found that the Authority has sufficient funding to meet the expected cost of the project without seeking additional New Starts funds or adversely affecting other parts of the transportation system in Puerto Rico. To finance the project...

The location of a disease-associated polymorphism and genomic structure of the human 52-kDa Ro/SSA locus (SSA1)

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

Tsugu, H.; Horowitz, R.; Gibson, N.

1994-12-01

Sera from approximately 30% of patients with systemic lupus erythematosus (SLE) contain high titers of autoantibodies that bind to the 52-kDa Ro/SSA protein. We previously detected polymorphisms in the 52-kDa Ro/SSA gene (SSA1) with restriction enzymes, one of which is strongly associated with the presence of SLE (P < 0.0005) in African Americans. A higher disease frequency and more severe forms of the disease are commonly noted among these female patients. To determine the location and nature of this polymorphism, we obtained two clones that span 8.5 kb of the 52-kDa Ro/SSA locus including its upstream regulatory region. Six exonsmore » were identified, and their nucleotide sequences plus adjacent noncoding regions were determined. No differences were found between these exons and the coding region of one of the reported cDNAs. The disease-associated polymorphic site suggested by a restriction enzyme map and confirmed by DNA amplification and nucleotide sequencing was present upstream of exon 1. This polymorphism may be a genetic marker for a disease-related variation in the coding region for the protein or in the upstream regulatory region of this gene. Although this RFLP is present in Japanese, it is not associated with lupus in this race. 41 refs., 4 figs., 2 tabs.« less

Positron emission tomography (PET) imaging of nicotine-induced dopamine release in squirrel monkeys using [18F]Fallypride.

PubMed

Naylor, Jennifer E; Hiranita, Takato; Matazel, Katelin S; Zhang, Xuan; Paule, Merle G; Goodwin, Amy K

2017-10-01

Nicotine, the principal psychoactive tobacco constituent, is thought to produce its reinforcing effects via actions within the mesolimbic dopamine (DA) system. The objective of the current study was to examine the effect of nicotine on DA D 2 /D 3 receptor availability in the nonhuman primate brain with the use of the radioligand [ 18 F]fallypride and positron emission tomography (PET). Ten adult male squirrel monkeys were used in the current study. Each subject underwent two PET scans, one with an injection (IV) of saline and subsequently one with an injection of nicotine (0.032mg/kg). The DA D 2 /D 3 antagonist, [ 18 F]fallypride, was delivered IV at the beginning of each scan, and nicotine or saline was delivered at 45min into the scan. Regions of interest (ROI) were drawn on specific brain regions and these were used to quantify standard uptake values (SUVs). The SUV is defined as the average concentration of radioactivity in the ROI x body weight/injected dose. Using the cerebellum as a reference region, SUV ratios (SUV ROI /SUV cerebellum ) were calculated to compare saline and nicotine effects in each ROI. Two-way repeated ANOVA revealed a significant decrease of SUV ratios in both striatal and extrastriatal regions following an injection of nicotine during the PET scans. Like other drugs of abuse, these results indicate that nicotine administration may produce DA release, as suggested by the decrease in [ 18 F]fallypride signal in striatal regions. These findings from a nonhuman primate model provide further evidence that the mesolimbic DA system is affected by the use of products that contain nicotine. Published by Elsevier B.V.

Assimilating AOD retrievals from GOCI and VIIRS to forecast surface PM2.5 episodes over Eastern China

NASA Astrophysics Data System (ADS)

Pang, Jiongming; Liu, Zhiquan; Wang, Xuemei; Bresch, Jamie; Ban, Junmei; Chen, Dan; Kim, Jhoon

2018-04-01

In this study, Geostationary Ocean Color Imager (GOCI) AOD and Visible Infrared Imaging Radiometer Suite (VIIRS) AOD data were assimilated to forecast surface PM2.5 concentrations over Eastern China, by using the three-dimensional variational (3DAVR) data assimilation (DA) system, to compare DA impacts by assimilating AOD retrievals from these two types of satellites. Three experiments were conducted, including a CONTROL without the AOD assimilation, and GOCIDA and VIIRSDA with the assimilation of AOD retrievals from GOCI and VIIRS, respectively. By utilizing the Weather Research and Forecasting with Chemistry (WRF/Chem) model, 48-h forecasts were initialized at each 06 UTC from 19 November to 06 December 2013. These forecasts were evaluated with 248 ground-based measurements from the air quality monitoring network across 67 China cities. The results show that overall the CONTROL underestimated surface PM2.5 concentrations, especially over Jing-Jin-Ji (JJJ) region and Yangtze River Delta (YRD) region. Both the GOCIDA and VIIRSDA produced higher surface PM2.5 concentrations mainly over Eastern China, which fits well with the PM2.5 measurements at these eastern sites, with more than 8% error reductions (ER). Moreover, compared to CONTROL, GOCIDA reduced 14.0% and 6.4% error on JJJ region and YRD region, respectively, while VIIRSDA reduced respectively 2.0% and 13.4% error over the corresponding areas. During the heavy polluted period, VIIRSDA improved all sites within YRD region, and GOCIDA enhanced 84% sites. Meanwhile, GOCIDA improved 84% sites on JJJ region, while VIIRSDA did not affect that region. These geographic distinctions might result from spatial dissimilarity between GOCI AOD and VIIRS AOD at time intervals. Moreover, the larger increment produced by AOD DA under stable meteorological conditions could lead to a longer duration (e.g., 1-2 days, > 2 days) of AOD DA impacts. Even though with AOD DA, surface PM2.5 concentrations were still underestimated clearly over heavy polluted periods. And 3% sites performed worse, where low PM2.5 values were observed and CONTROL performed well. With this study, the results indicate that AOD DA can partially improve the accuracy of PM2.5 forecasts. And the obvious geographic differences on forecasts emphasize the potential and importance of combining AOD retrievals from GOCI and VIIRS into data assimilation.

Ecological Carrying Capacity of Land Use Changes in Da'an City

NASA Astrophysics Data System (ADS)

Wang, H.; Zhang, J.; Li, B.

2018-04-01

Based on GIS and RS technology, this paper analyzed the land use change in Da'an city from 1995 to 2010. land-use ecological evaluation index was constructed to evaluate the land-use ecological risk of Da 'an city dynamically, and the land-use ecological risk level map was made, and then the distribution and change of the land-use ecological carrying capacity pattern of Da'an city were analyzed qualitatively. According to the evaluation results of ecological carrying capacity, the ecological environment of Da'an city has deteriorated in fifteen years. in 1995, the poor ecological environment area is mainly distributed in the northeast area of Da'an city, and the area is small, while the area of the central and southern areas is large; In 2010, the western region also appeared environmental degradation, the northeast environment deterioration is serious, the dominant area is reduced, and a small amount of deterioration in the central and southern regions. According to the study of this paper, in the future, we should strengthen the comprehensive management of this part of the area, strengthen vegetation coverage, reduce soil erosion, ensure the effective improvement of ecological environment.

Tryptic digestion of human GPIIIa. Isolation and biochemical characterization of the 23 kDa N-terminal glycopeptide carrying the antigenic determinant for a monoclonal antibody (P37) which inhibits platelet aggregation.

PubMed Central

Calvete, J J; Rivas, G; Maruri, M; Alvarez, M V; McGregor, J L; Hew, C L; Gonzalez-Rodriguez, J

1988-01-01

Early digestion of pure human platelet glycoprotein IIIa (GPIIIa) leads to a single cleavage of the molecule at 23 kDa far from one of the terminal amino acids. Automated Edman degradation demonstrates that GPIIIa and the smaller (23 kDa) tryptic fragment share the same N-terminal amino acid sequence. A further cleavage occurs in the larger fragment (80 kDa), reducing its apparent molecular mass by 10 kDa. The 23 kDa fragment remains attached to the larger ones in unreduced samples. Stepwise reduction of early digested GPIIIa with dithioerythritol selectively reduces the single disulphide bond joining the smaller (23 kDa) to the larger (80/70 kDa) fragments. Two fractions were obtained by size-exclusion chromatography of early digested GPIIIa after partial or full reduction and alkylation. The larger-size fraction contains the 80/70 kDa fragments, while the 23 kDa fragment is isolated in the smaller. The amino acid compositions of these fractions do not differ very significantly from the composition of GPIIIa; however the 23 kDa fragment contains only 10.2% by weight of sugars and is richer in neuraminic acid. Disulphide bonds are distributed four in the 23 kDa glycopeptide and 20-21 in the 80/70 kDa glycopeptide. The epitope for P37, a monoclonal antibody which inhibits platelet aggregation [Melero & González-Rodríguez (1984) Eur. J. Biochem. 141, 421-427] is situated within the first 17 kDa of the N-terminal region of GPIIIa, which gives a special functional interest to this extracellular region of GPIIIa. On the other hand, the epitopes for GPIIIa-specific monoclonal antibodies, P6, P35, P40 and P97, which do not interfere with platelet aggregation, are located within the larger tryptic fragment (80/70 kDa). Thus, the antigenic areas available in the extracellular surface of GPIIIa for these five monoclonal antibodies are now more precisely delineated. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2455507

Application of fast-scan cyclic voltammetry for the in vivo characterization of optically evoked dopamine in the olfactory tubercle of the rat brain.

PubMed

Wakabayashi, Ken T; Bruno, Michael J; Bass, Caroline E; Park, Jinwoo

2016-06-21

The olfactory tubercle (OT), as a component of the ventral striatum, serves as an important multisensory integration center for reward-related processes in the brain. Recent studies show that dense dopaminergic innervation from the ventral tegmental area (VTA) into the OT may play an outsized role in disorders such as psychostimulant addiction and disorders of motivation, increasing recent scientific interest in this brain region. However, due to its anatomical inaccessibility, relative small size, and proximity to other dopamine-rich structures, neurochemical assessments using conventional methods cannot be readily employed. Here, we investigated dopamine (DA) regulation in the OT of urethane-anesthetized rats using in vivo fast-scan voltammetry (FSCV) coupled with carbon-fiber microelectrodes, following optogenetic stimulation of the VTA. The results were compared with DA regulation in the nucleus accumbens (NAc), a structure located adjacent to the OT and which also receives dense DA innervation from the VTA. FSCV coupled with optically evoked release allowed us to investigate the spatial distribution of DA in the OT and characterize OT DA dynamics (release and clearance) with subsecond temporal and micrometer spatial resolution for the first time. In this study, we demonstrated that DA transporters play an important role in regulating DA in the OT. However, the control of extracellular DA by uptake in the OT was less than in the NAc. The difference in DA transmission in the terminal fields of the OT and NAc may be involved in region-specific responses to drugs of abuse and contrasting roles in mediating reward-related behavior.

Fast-scan cyclic voltammetry reveals that L-Dopa produces regionally selective, bimodal influences on striatal dopamine kinetics in vivo

PubMed Central

Harun, R; Munoz, M; Grassi, C; Hare, K; Brough, E; Torres, GE; Grace, AA; Wagner, AK

2016-01-01

Parkinson’s disease (PD) is a debilitating condition that is caused by a relatively specific degeneration of dopaminergic (DAergic) neurons of the substantia nigra pars compacta. Levodopa (L-Dopa) was introduced as a viable treatment option for PD over 40 years ago and still remains the most common and effective therapy for PD. Though the effects of L-Dopa to augment striatal DA production are well known, little is actually known about how L-Dopa alters the kinetics of DA neurotransmission that contribute to its beneficial and adverse effects. In this study, we examined the effects of L-Dopa administration (100mg/kg carbidopa/250mg/kg L-Dopa) on regional electrically stimulated DA response kinetics using fast-scan cyclic voltammetry (FSCV) in anesthetized rats. We demonstrate that L-Dopa enhances DA release in both the dorsal striatum (D-STR) and nucleus accumbens (NAc), but surprisingly causes a delayed inhibition of release in the D-STR, a finding that may be related to high-dose L-Dopa effects. In both regions, L-Dopa progressively attenuated reuptake kinetics through a decrease in Vmax and an increase in Km. This finding is consistent with recent clinical studies suggesting that L-Dopa chronically down-regulates the DA transporter (DAT), which may relate to the common development of L-Dopa induced dyskinesias (LID) in PD subjects. PMID:26611352

The activation of metabotropic glutamate 5 receptors in the rat ventral tegmental area increases dopamine extracellular levels.

PubMed

Ferrada, Carla; Sotomayor-Zárate, Ramón; Abarca, Jorge; Gysling, Katia

2017-01-01

The mesocorticolimbic circuit projects to the prefrontal cortex, hippocampus, amygdala, and nucleus accumbens, among others, and it originates in the dopaminergic neurons of the ventral tegmental area (VTA). The VTA receives glutamatergic inputs from the prefrontal cortex and several subcortical regions. The glutamate released activates dopaminergic neurons and its action depends on the activation of ionotropic and metabotropic glutamate receptors. VTA dopaminergic neurons release dopamine (DA) from axon terminals in the innervated regions and somatodendritically in the VTA itself. DA release in the VTA is directly correlated with the activity of dopaminergic neurons. We hypothesized that metabotropic glutamate 5 receptors (mGlu5) directly regulate the activity of VTA dopaminergic neurons. To test this hypothesis, the extracellular levels of VTA DA and glutamate were studied by in-vivo microdialysis after an intra-VTA perfusion of (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG), selective mGlu5 agonist. We observed that CHPG induced a significant increase in VTA DA and glutamate extracellular levels. To determine whether the effect of CHPG on DA levels is because of the increase in glutamate release, we perfused kynurenic acid, an ionotropic glutamate receptor antagonist, through the probe. Our results showed that kynurenic acid did not block the ability of CHPG to cause DA release. Thus, our results suggest that CHPG acts directly on mGlu5 in dopaminergic neurons to induce the release of DA.

Estimated bankfull discharge for selected Michigan rivers and regional hydraulic geometry curves for estimating bankfull characteristics in southern Michigan rivers

USGS Publications Warehouse

Rachol, Cynthia M.; Boley-Morse, Kristine

2009-01-01

Regional hydraulic geometry curves are power-function equations that relate riffle dimensions and bankfull discharge to drainage-basin size. They are defined by data collected through surveys conducted at stable stream reaches and can be used to aid watershed managers, design engineers, and others involved in determination of the best course of action for an unstable stream. Hydraulic geometry curves provide a mechanism through which comparisons can be made between riffle dimensions collected at an unstable stream to those collected at stable streams within the same region. In 2005, a study was initiated to delineate regional hydraulic geometry curves for Michigan. After in-office review of 343 U.S. Geological Survey streamgaging stations and an extensive field reconnaissance effort, 44 stable reaches were selected for this study. Detailed surveys that included cross-sectional and longitudinal profiles and pebble counts were conducted at selected streamgages, which were distributed throughout Michigan. By use of survey data from riffle cross sections and water-surface slope, bankfull discharge was estimated and compared to flood-recurrence intervals using regional flood equations. This comparison shows that bankfull discharges in Michigan recur more frequently than every 2 years. Regional hydraulic geometry curves were developed rather than statewide curves owing to large differences in factors that control channel geometry across the State. However, after the data were subdivided according to ecoregions, it was determined that there were enough data to delineate regional hydraulic geometry curves only for the Southern Lower Michigan Ecoregion. For this ecoregion, geometry curve equations and their coefficients of determination are: Width = 8.19 x DA0.44; R2 = 0.69, Depth = 0.67 x DA0.27; R2 = 0.28, Area = 4.38 x DA0.74; R2 = 0.59, where DA is the drainage area and R2 is the coefficient of determination. By use of discharge estimates for the Southern Lower Michigan Ecoregion, a bankfull discharge curve was delineated. The corresponding equation and its coefficient of determination are: Discharge = 4.05 x DA0.95; R2 = 0.60

Primary Health Care: care coordinator in regionalized networks?

PubMed

Almeida, Patty Fidelis de; Santos, Adriano Maia Dos

2016-12-22

To analyze the breadth of care coordination by Primary Health Care in three health regions. This is a quantitative and qualitative case study. Thirty-one semi-structured interviews with municipal, regional and state managers were carried out, besides a cross-sectional survey with the administration of questionnaires to physicians (74), nurses (127), and a representative sample of users (1,590) of Estratégia Saúde da Família (Family Health Strategy) in three municipal centers of health regions in the state of Bahia. Primary Health Care as first contact of preference faced strong competition from hospital outpatient and emergency services outside the network. Issues related to access to and provision of specialized care were aggravated by dependence on the private sector in the regions, despite progress observed in institutionalizing flows starting out from Primary Health Care. The counter-referral system was deficient and interprofessional communication was scarce, especially concerning services provided by the contracted network. Coordination capacity is affected both by the fragmentation of the regional network and intrinsic problems in Primary Health Care, which poorly supported in its essential attributes. Although the health regions have common problems, Primary Health Care remains a subject confined to municipal boundaries. Analisar o alcance da coordenação do cuidado pela Atenção Primária à Saúde em três regiões de saúde. Trata-se de estudo de caso, com abordagem quantitativa e qualitativa. Foram realizadas 31 entrevistas semiestruturadas com gestores municipais, regionais e estaduais e estudo transversal com aplicação de questionários para médicos (74), enfermeiros (127) e amostra representativa de usuários (1.590) da Estratégia Saúde da Família em três municípios-sede de regiões de saúde do estado da Bahia. A função de porta de entrada preferencial pela Atenção Primária à Saúde deparava-se com forte concorrência de serviços ambulatoriais hospitalares e de pronto-atendimento, desarticulados da rede. Problemas de acesso e oferta de atenção especializada eram agravados pela dependência do setor privado nas regiões, ainda que tenham sido observados avanços na institucionalização de fluxos desde a Atenção Primária à Saúde. A contrarreferência era deficiente e a comunicação interprofissional escassa, principalmente quando o usuário era atendido na rede contratada ou conveniada. A capacidade de coordenação mostra-se afetada tanto pela fragmentação da rede regional, quanto por problemas intrínsecos à Atenção Primária à Saúde, pouco fortalecida em seus atributos essenciais. Apesar de as regiões de saúde apresentarem problemas em comum, a Atenção Primária à Saúde continua sendo um tema circunscrito aos limites municipais.

Widespread Increases in Malondialdehyde Immunoreactivity in Dopamine-Rich and Dopamine-Poor Regions of Rat Brain Following Multiple, High Doses of Methamphetamine

PubMed Central

Horner, Kristen A.; Gilbert, Yamiece E.; Cline, Susan D.

2011-01-01

Treatment with multiple high doses of methamphetamine (METH) can induce oxidative damage, including dopamine (DA)-mediated reactive oxygen species (ROS) formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu) and substantia nigra pars compacta (SNpc). Malondialdehyde (MDA), a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg) every 2 h for 6 h, sacrificed 1 week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir) in the CPu, SNpc, cortex, and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area and nucleus accumbens. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system. PMID:21602916

Concurrent Exposure of Bottlenose Dolphins (Tursiops truncatus) to Multiple Algal Toxins in Sarasota Bay, Florida, USA

PubMed Central

Twiner, Michael J.; Fire, Spencer; Schwacke, Lori; Davidson, Leigh; Wang, Zhihong; Morton, Steve; Roth, Stephen; Balmer, Brian; Rowles, Teresa K.; Wells, Randall S.

2011-01-01

Sentinel species such as bottlenose dolphins (Tursiops truncatus) can be impacted by large-scale mortality events due to exposure to marine algal toxins. In the Sarasota Bay region (Gulf of Mexico, Florida, USA), the bottlenose dolphin population is frequently exposed to harmful algal blooms (HABs) of Karenia brevis and the neurotoxic brevetoxins (PbTx; BTX) produced by this dinoflagellate. Live dolphins sampled during capture-release health assessments performed in this region tested positive for two HAB toxins; brevetoxin and domoic acid (DA). Over a ten-year study period (2000–2009) we have determined that bottlenose dolphins are exposed to brevetoxin and/or DA on a nearly annual basis (i.e., DA: 2004, 2005, 2006, 2008, 2009; brevetoxin: 2000, 2004, 2005, 2008, 2009) with 36% of all animals testing positive for brevetoxin (n = 118) and 53% positive for DA (n = 83) with several individuals (14%) testing positive for both neurotoxins in at least one tissue/fluid. To date there have been no previously published reports of DA in southwestern Florida marine mammals, however the May 2008 health assessment coincided with a Pseudo-nitzschia pseudodelicatissima bloom that was the likely source of DA observed in seawater and live dolphin samples. Concurrently, both DA and brevetoxin were observed in common prey fish. Although no Pseudo-nitzschia bloom was identified the following year, DA was identified in seawater, fish, sediment, snails, and dolphins. DA concentrations in feces were positively correlated with hematologic parameters including an increase in total white blood cell (p = 0.001) and eosinophil (p<0.001) counts. Our findings demonstrate that dolphins within Sarasota Bay are commonly exposed to two algal toxins, and provide the impetus to further explore the potential long-term impacts on bottlenose dolphin health. PMID:21423740

Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson’s patients with medication-induced pathological gambling: A [11C] FLB-457 and PET study

PubMed Central

Ray, Nicola J.; Miyasaki, Janis M.; Zurowski, Mateusz; Ko, Ji Hyun; Cho, Sang Soo; Pellecchia, Giovanna; Antonelli, Francesca; Houle, Sylvain; Lang, Anthony E.; Strafella, Antonio P.

2012-01-01

Impulse control disorders such as pathological gambling (PG) are a serious and common adverse effect of dopamine (DA) replacement medication in Parkinson’s disease (PD). Patients with PG have increased impulsivity and abnormalities in striatal DA, in common with behavioural and substance addictions in the non-PD population. To date, no studies have investigated the role of extrastriatal dopaminergic abnormalities in PD patients with PG. We used the PET radiotracer, [11C] FLB-457, with high-affinity for extrastriatal DA D2/3 receptors. 14 PD patients on DA agonists were imaged while they performed a gambling task involving real monetary reward and a control task. Trait impulsivity was measured with the Barratt Impulsivity Scale (BIS). Seven of the patients had a history of PG that developed subsequent to DA agonist medication. Change in [11C] FLB-457 binding potential (BP) during gambling was reduced in PD with PG patients in the midbrain, where D2/D3 receptors are dominated by autoreceptors. The degree of change in [11C] FLB-457 binding in this region correlated with impulsivity. In the cortex, [11C] FLB-457 BP was significantly greater in the anterior cingulate cortex (ACC) in PD patients with PG during the control task, and binding in this region was also correlated with impulsivity. Our findings provide the first evidence that PD patients with PG have dysfunctional activation of DA autoreceptors in the midbrain and low DA tone in the ACC. Thus, altered striatal and cortical DA homeostasis may incur vulnerability for the development of PG in PD, linked with the impulsive personality trait. PMID:22766031

Molecules of various pharmacologically-relevant sizes can cross the ultrasound-induced blood-brain barrier opening in vivo

PubMed Central

Choi, James J.; Wang, Shougang; Tung, Yao-Sheng; Morrison, Barclay; Konofagou, Elisa E.

2009-01-01

Focused ultrasound (FUS) is hereby shown to noninvasively and selectively deliver compounds at pharmacologically relevant molecular weights through the opened blood-brain barrier (BBB). A complete examination on the size of the FUS-induced BBB opening, the spatial distribution of the delivered agents and its dependence on the agent's molecular weight were imaged and quantified using fluorescence microscopy. BBB opening in mice (n=13) was achieved in vivo after systemic administration of microbubbles and subsequent application of pulsed FUS (frequency: 1.525 MHz, peak-rarefactional pressure in situ: 569 kPa) to the left murine hippocampus through the intact skin and skull. BBB-impermeant, fluorescent-tagged dextrans at three distinct molecular weights spanning over several orders of magnitude were systemically administered and acted as model therapeutic compounds. First, dextrans of 3 and 70 kDa were delivered trans-BBB while 2000 kDa dextran was not. Second, compared to 70 kDa dextran, a higher concentration of 3 kDa dextran was delivered through the opened BBB. Third, the 3 and 70 kDa dextrans were both diffusely distributed throughout the targeted brain region. However, high concentrations of 70 kDa dextran appeared more punctated throughout the targeted region. In conclusion, FUS combined with microbubbles opened the BBB sufficiently to allow passage of compounds of at least 70 kDa, but not greater than 2000 kDa, into the brain parenchyma. This noninvasive and localized BBB opening technique could thus provide a unique means for the delivery of compounds of several magnitudes of kDa that include agents with shown therapeutic promise in vitro, but whose in vivo translation has been hampered by their associated BBB impermeability. PMID:19900750

Papain cleavage of the 38,000-dalton fragment inhibits the binding of 4, 4'-diisothiocyanostilbene-2, 2'-disulfonate to lys-539 on the 60,000-dalton fragment in human band 3.

PubMed

Yamaguchi, Takeo; Kojima, Hideaki; Kawaguchi, Shiori; Shimada, Maiko; Aso, Haruka

2017-08-01

Human band 3 is a 98-kDa transmembrane (TM) protein comprising 14 TM segments. Papain cleavages band 3 into 38- and 60-kDa fragments. Under vigorous conditions, the cleavage of the loop region between the TM 7 of gate domain and the TM 8 of core domain in the 38-kDa fragment produces 7- and 31-kDa fragments. Conformational changes of the TM 5 segment containing Lys-539 by cleavage of the 38-kDa fragment remain unclear. Pressure-induced haemolysis of erythrocytes was suppressed by binding of 4, 4'-diisothiocyanostilbene-2, 2'-disulfonate (DIDS) to Lys-539. Such effect of DIDS was not observed upon cleavage of the 38-kDa fragment, because of inhibition of DIDS binding to Lys-539. Using fluorescence of DIDS labelled to Lys-539, conformational changes of band 3 were examined. Fluorescence spectra demonstrated that the molecular motion of DIDS is more restricted upon digestion of the 38-kDa fragment. Interestingly, the quenching of DIDS fluorescence showed that Hg2+ is less accessible to DIDS upon digestion of the 38-kDa fragment. Taken together, we propose that the conformational changes of the TM 5 segment characterized by the sequestration and restricted motion of Lys-539 are induced by the cleavage of the loop region between the TM 7 and the TM 8. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Age-related changes in glial cells of dopamine midbrain subregions in rhesus monkeys.

PubMed

Kanaan, Nicholas M; Kordower, Jeffrey H; Collier, Timothy J

2010-06-01

Aging remains the strongest risk factor for developing Parkinson's disease (PD), and there is selective vulnerability in midbrain dopamine (DA) neuron degeneration in PD. By tracking normal aging-related changes with an emphasis on regional specificity, factors involved in selective vulnerability and resistance to degeneration can be studied. Towards this end, we sought to determine whether age-related changes in microglia and astrocytes in rhesus monkeys are region-specific, suggestive of involvement in regional differences in vulnerability to degeneration that may be relevant to PD pathogenesis. Gliosis in midbrain DA subregions was measured by estimating glia number using unbiased stereology, assessing fluorescence intensity for proteins upregulated during activation, and rating morphology. With normal aging, microglia exhibited increased staining intensity and a shift to more activated morphologies preferentially in the vulnerable substantia nigra-ventral tier (vtSN). Astrocytes did not exhibit age-related changes consistent with an involvement in regional vulnerability in any measure. Our results suggest advancing age is associated with chronic mild inflammation in the vtSN, which may render these DA neurons more vulnerable to degeneration. Copyright 2008 Elsevier Inc. All rights reserved.

Effects of hot-iron disbudding, using regional anaesthesia with and without carprofen, on cortisol and behaviour of calves.

PubMed

Stilwell, G; Lima, M S; Carvalho, R C; Broom, D M

2012-04-01

The objective of this study was to assess cortisol and behaviour changes in calves hot-iron disbudded after different analgesic protocols. We assessed the response of 27 calves at 1, 3, 6 and 24 h after disbudding with regional anaesthesia (DA), regional anaesthesia plus carprofen (DAC), disbudded only (D) or sham-disbudded (ND). At 1h cortisol was higher in D compared with all other groups. At 3h DA showed higher cortisol than ND but did not differ from baseline. At 15 min and 1h pain-related behaviours were more frequent in the D group than in all other groups. Group D (3 h) and DA (3 and 6 h) showed more ear flicks and head rubs compared with DAC and ND. We concluded that head rubbing, head shaking and ear flicking are useful behaviours for evaluating pain after hot-iron disbudding. Disbudding causes severe pain in calves and only the association of regional anaesthesia with carprofen assures good welfare for 24 h. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rapid detection of trichodysplasia spinulosa-associated polyomavirus in skin biopsy specimen.

PubMed

Urbano, Paulo Roberto P; Pannuti, Cláudio Sérgio; Pierrotti, Ligia C; David-Neto, Elias; Romano, Camila Malta

2014-07-24

Trichodysplasia spinulosa-associated polyomavirus (TSV) is responsible for a rare skin cancer. Using metagenomic approaches, we determined the complete genome sequence of a TSV first detected in Brazil in spicules of an immunocompromised patient suspected to have trichodysplasia spinulosa. Copyright © 2014 Urbano et al.

Changes of brain monoamine levels and physiological indexes during heat acclimation in rats.

PubMed

Nakagawa, Hikaru; Matsumura, Takeru; Suzuki, Kota; Ninomiya, Chisa; Ishiwata, Takayuki

2016-05-01

Brain monoamines, such as noradrenaline (NA), dopamine (DA), and serotonin (5-HT), regulate many important physiological functions including thermoregulation. The purpose of this study was to clarify changes in NA, DA, and 5-HT levels in several brain regions in response to heat acclimation while also recording body temperature (Tb), heart rate (HR), and locomotor activity (Act). Rats were exposed to a heated environment (32°C) for 3h (3H), 1 day (1D), 7 days, 14 days (14D), 21 days, or 28 days (28D). After heat exposure, each of the following brain regions were immediately extracted and homogenized: the caudate putamen (CPu), preoptic area (PO), dorsomedial hypothalamus (DMH), frontal cortex (FC), and hippocampus (Hip). NA, DA, and 5-HT levels in the extract were measured by high performance liquid chromatography. Although Tb increased immediately after heat exposure, it decreased about 14D later. HR was maintained at a low level throughout heat exposure, and Act tended to increase near the end of heat exposure. After 3H, we observed a marked increase in NA level in the CPu. Although this response vanished after 1D, the level increased again after 28D. DA level in the CPu decreased significantly from 1D to 28D. 5-HT level in the PO and DMH decreased from 1D to 14D. It returned to control levels after 28D with increment of DA level. 5-HT level in the FC decreased at the start of heat exposure, but recovered after 28D; a time point at which DA level also increased. Monoamine levels in the Hip were unchanged after early heat exposure, but both 5-HT and DA levels increased after 28D. These results provide definitive evidence of changes in monoamines in individual brain regions involved in thermoregulation and behavioral, cognitive, and memory function during both acute and chronic heat exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

MK-801-induced behavioural sensitisation alters dopamine release and turnover in rat prefrontal cortex.

PubMed

Cui, Xiaoying; Lefevre, Emilia; Turner, Karly M; Coelho, Carlos M; Alexander, Suzy; Burne, Thomas H J; Eyles, Darryl W

2015-02-01

Repeated exposure to psychostimulants that either increase dopamine (DA) release or target N-methyl-D-aspartate (NMDA) receptors can induce behavioural sensitisation, a phenomenon that may be important for the processes of addiction and even psychosis. A critical component of behavioural sensitisation is an increase in DA release within mesocorticolimbic circuits. In particular, sensitisation to amphetamine leads to increased DA release within well-known sub-cortical brain regions and also regulatory regions such as prefrontal cortex (PFC). However, it is unknown how DA release within the PFC of animals is altered by sensitisation to NMDA receptor antagonists. The aims of the present study were twofold, firstly to examine whether a single dose of dizocilpine maleate (MK-801) could induce long-term behavioural sensitisation and secondly to examine DA release in the PFC of sensitised rats. Behavioural sensitisation was assessed by measuring locomotion after drug exposure. DA release in the PFC was measured using freely moving microdialysis. We show that a single dose of MK-801 can induce sensitisation to subsequent MK-801 exposure in a high percentage of rats (66 %). Furthermore, rats sensitised to MK-801 have altered DA release and turnover in the PFC compared with non-sensitised rats. Schizophrenia patients have been postulated to have 'endogenous sensitisation' to psychostimulants. MK-801-induced sensitised rats, in particular when compared with non-sensitised rats, provide a useful model for studying PFC dysfunction in schizophrenia.

Definition of IgG- and albumin-binding regions of streptococcal protein G.

PubMed

Akerström, B; Nielsen, E; Björck, L

1987-10-05

Protein G, the immunoglobin G-binding surface protein of group C and G streptococci, also binds serum albumin. The albumin-binding site on protein G is distinct from the immunoglobulin G-binding site. By mild acid hydrolysis of the papain-liberated protein G fragment (35 kDa), a 28-kDa fragment was produced which retained full immunoglobulin G-binding activity (determined by Scatchard plotting) but had lost all albumin-binding capacity. A protein G (65 kDa), isolated after cloning and expression of the protein G gene in Escherichia coli, had comparable affinity to immunoglobulin G (5-10 X 10(10)M-1), but much higher affinity to albumin than the 35- and 28-kDa protein G fragments (31, 2.6, and 0 X 10(9)M-1, respectively). The amino-terminal amino acid sequences of the 65-, 35-, and 28-kDa fragments allowed us to exactly locate the three fragments in an overall sequence map of protein G, based on the partial gene sequences published by Guss et al. (Guss, B., Eliasson, M., Olsson, A., Uhlen, M., Frej, A.-K., Jörnvall, H., Flock, J.-I., and Lindberg, M. (1986) EMBO J. 5, 1567-1575) and Fahnestock et al. (Fahnestock, S. R., Alexander, P., Nagle, J., and Filpula, D. (1986) J. Bacteriol. 167, 870-880). In this map could then be deduced the location of three homologous albumin-binding regions and three homologous immunoglobulin G-binding regions.

Hunting for the Tristan mantle plume - An upper mantle tomography around the volcanic island of Tristan da Cunha

NASA Astrophysics Data System (ADS)

Schlömer, Antje; Geissler, Wolfram H.; Jokat, Wilfried; Jegen, Marion

2017-03-01

The active volcanic island Tristan da Cunha, located at the southwestern and youngest end of the Walvis Ridge - Tristan/Gough hotspot track, is believed to be the surface expression of a huge thermal mantle anomaly. While several criteria for the diagnosis of a classical hotspot track are met, the Tristan region also shows some peculiarities. Consequently, it is vigorously debated if the active volcanism in this region is the expression of a deep mantle plume, or if it is caused by shallow plate tectonics and the interaction with the nearby Mid-Atlantic Ridge. Because of a lack of geophysical data in the study area, no model or assumption has been completely confirmed. We present the first amphibian P-wave finite-frequency travel time tomography of the Tristan da Cunha region, based on cross-correlated travel time residuals of teleseismic earthquakes recorded by 24 ocean-bottom seismometers. The data can be used to image a low velocity structure southwest of the island. The feature is cylindrical with a radius of ∼100 km down to a depth of 250 km. We relate this structure to the origin of Tristan da Cunha and name it the Tristan conduit. Below 250 km the low velocity structure ramifies into narrow veins, each with a radius of ∼50 km. Furthermore, we imaged a linkage between young seamounts southeast of Tristan da Cunha and the Tristan conduit.

Optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens reveals local modulation of presynaptic release

PubMed Central

Melchior, James R.; Ferris, Mark J.; Stuber, Garret D.; Riddle, David R.; Jones, Sara R.

2015-01-01

The nucleus accumbens is highly heterogeneous, integrating regionally distinct afferent projections and accumbal interneurons, resulting in diverse local microenvironments. Dopamine (DA) neuron terminals similarly express a heterogeneous collection of terminal receptors that modulate DA signaling. Cyclic voltammetry is often used to probe DA terminal dynamics in brain slice preparations; however, this method traditionally requires electrical stimulation to induce DA release. Electrical stimulation excites all of the neuronal processes in the stimulation field, potentially introducing simultaneous, multi-synaptic modulation of DA terminal release. We used optogenetics to selectively stimulate DA terminals and used voltammetry to compare DA responses from electrical and optical stimulation of the same area of tissue around a recording electrode. We found that with multiple pulse stimulation trains, optically stimulated DA release increasingly exceeded that of electrical stimulation. Furthermore, electrical stimulation produced inhibition of DA release across longer duration stimulations. The GABAB antagonist, CGP 55845, increased electrically stimulated DA release significantly more than light stimulated release. The nicotinic acetylcholine receptor antagonist, dihydro-β-erythroidine hydrobromide, inhibited single pulse electrically stimulated DA release while having no effect on optically stimulated DA release. Our results demonstrate that electrical stimulation introduces local multi-synaptic modulation of DA release that is absent with optogenetically targeted stimulation. PMID:26011081

40 CFR 60.48Da - Compliance provisions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 60.48Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... extensions shall be granted by the relevant air division or office director of the appropriate Regional... Protection Agency (U.S. EPA); Office of Air Quality Planning and Standards; Sector Policies and Programs...

40 CFR 60.48Da - Compliance provisions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 60.48Da Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... extensions shall be granted by the relevant air division or office director of the appropriate Regional... Protection Agency (U.S. EPA); Office of Air Quality Planning and Standards; Sector Policies and Programs...

Domain organization of p130, PLC-related catalytically inactive protein, and structural basis for the lack of enzyme activity.

PubMed

Kanematsu, T; Yoshimura, K; Hidaka, K; Takeuchi, H; Katan, M; Hirata, M

2000-05-01

The 130-kDa protein (p130) was isolated as a novel inositol 1,4, 5-trisphosphate [Ins(1,4,5)P3]-binding protein similar to phospholipase C-delta1 (PLC-delta1), but lacking catalytic activity [Kanematsu, T., Takeya, H., Watanabe, Y., Ozaki, S., Yoshida, M., Koga, T., Iwanaga, S. & Hirata, M. (1992) J. Biol. Chem. 267, 6518-6525; Kanematsu, T., Misumi, Y., Watanabe, Y., Ozaki, S., Koga, T., Iwanaga, S., Ikehara, Y. & Hirata, M. (1996) Biochem. J. 313, 319-325]. To test experimentally the domain organization of p130 and structural basis for lack of PLC activity, we subjected p130 to limited proteolysis and also constructed a number of chimeras with PLC-delta1. Trypsin treatment of p130 produced four major polypeptides with molecular masses of 86 kDa, 55 kDa, 33 kDa and 25 kDa. Two polypeptides of 86 kDa and 55 kDa started at Lys93 and were calculated to end at Arg851 and Arg568, respectively. Using the same approach, it has been found that the polypeptides of 33 kDa and 25 kDa are likely to correspond to regions between Val569 and Arg851 and Lys869 and Leu1096, respectively. All the proteolytic sites were in interconnecting regions between the predicted domains, therefore supporting domain organization based on sequence similarity to PLC-delta1 and demonstrating that all domains of p130, including the unique region at the C-terminus, are stable, tightly folded structures. p130 truncated at either or both the N-terminus (94 amino acids) and C-terminus (851-1096 amino acids) expressed in COS-1 cells showed no catalytic activity, indicating that p130 has intrinsically no PLC activity. A number of chimeric molecules between p130 and PLC-delta1 were constructed and assayed for PLC activity. It was shown that structural differences in interdomain interactions exist between the two proteins, as only some domains of p130 could replace the corresponding structures in PLC-delta1 to form a functional enzyme. These results suggest that p130 and the related proteins could represent a new protein family that may play some distinct role in cells due to the capability of binding Ins(1,4,5)P3 but the lack of catalytic activity.

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

El-Labany, S. K., E-mail: skellabany@hotmail.com; Zedan, N. A., E-mail: nesreenplasma@yahoo.com; El-Taibany, W. F., E-mail: eltaibany@hotmail.com, E-mail: eltaibany@du.edu.eg

The nonplanar amplitude modulation of dust acoustic (DA) envelope solitary waves in a strongly coupled dusty plasma (SCDP) has been investigated. By using a reductive perturbation technique, a modified nonlinear Schrödinger equation (NLSE) including the effects of geometry, polarization, and ion superthermality is derived. The modulational instability (MI) of the nonlinear DA wave envelopes is investigated in both planar and nonplanar geometries. There are two stable regions for the DA wave propagation strongly affected by polarization and ion superthermality. Moreover, it is found that the nonlinear DA waves in spherical geometry are the more structurally stable. The larger growth ratemore » of the nonlinear DA MI is observed in the cylindrical geometry. The salient characteristics of the MI in the nonplanar geometries cannot be found in the planar one. The DA wave propagation and the NLSE solutions are investigated both analytically and numerically.« less

Dopamine modulation of emotional processing in cortical and subcortical neural circuits: evidence for a final common pathway in schizophrenia?

PubMed

Laviolette, Steven R

2007-07-01

The neural regulation of emotional perception, learning, and memory is essential for normal behavioral and cognitive functioning. Many of the symptoms displayed by individuals with schizophrenia may arise from fundamental disturbances in the ability to accurately process emotionally salient sensory information. The neurotransmitter dopamine (DA) and its ability to modulate neural regions involved in emotional learning, perception, and memory formation has received considerable research attention as a potential final common pathway to account for the aberrant emotional regulation and psychosis present in the schizophrenic syndrome. Evidence from both human neuroimaging studies and animal-based research using neurodevelopmental, behavioral, and electrophysiological techniques have implicated the mesocorticolimbic DA circuit as a crucial system for the encoding and expression of emotionally salient learning and memory formation. While many theories have examined the cortical-subcortical interactions between prefrontal cortical regions and subcortical DA substrates, many questions remain as to how DA may control emotional perception and learning and how disturbances linked to DA abnormalities may underlie the disturbed emotional processing in schizophrenia. Beyond the mesolimbic DA system, increasing evidence points to the amygdala-prefrontal cortical circuit as an important processor of emotionally salient information and how neurodevelopmental perturbances within this circuitry may lead to dysregulation of DAergic modulation of emotional processing and learning along this cortical-subcortical emotional processing circuit.

Dopaminergic Neurons Controlling Anterior Pituitary Functions: Anatomy and Ontogenesis in Zebrafish.

PubMed

Fontaine, Romain; Affaticati, Pierre; Bureau, Charlotte; Colin, Ingrid; Demarque, Michaël; Dufour, Sylvie; Vernier, Philippe; Yamamoto, Kei; Pasqualini, Catherine

2015-08-01

Dopaminergic (DA) neurons located in the preoptico-hypothalamic region of the brain exert a major neuroendocrine control on reproduction, growth, and homeostasis by regulating the secretion of anterior pituitary (or adenohypophysis) hormones. Here, using a retrograde tract tracing experiment, we identified the neurons playing this role in the zebrafish. The DA cells projecting directly to the anterior pituitary are localized in the most anteroventral part of the preoptic area, and we named them preoptico-hypophyseal DA (POHDA) neurons. During development, these neurons do not appear before 72 hours postfertilization (hpf) and are the last dopaminergic cell group to differentiate. We found that the number of neurons in this cell population continues to increase throughout life proportionally to the growth of the fish. 5-Bromo-2'-deoxyuridine incorporation analysis suggested that this increase is due to continuous neurogenesis and not due to a phenotypic change in already-existing neurons. Finally, expression profiles of several genes (foxg1a, dlx2a, and nr4a2a/b) were different in the POHDA compared with the adjacent suprachiasmatic DA neurons, suggesting that POHDA neurons develop as a distinct DA cell population in the preoptic area. This study offers some insights into the regional identity of the preoptic area and provides the first bases for future functional genetic studies on the development of DA neurons controlling anterior pituitary functions.

Deterministic Role of Collision Cascade Density in Radiation Defect Dynamics in Si

NASA Astrophysics Data System (ADS)

Wallace, J. B.; Aji, L. B. Bayu; Shao, L.; Kucheyev, S. O.

2018-05-01

The formation of stable radiation damage in solids often proceeds via complex dynamic annealing (DA) processes, involving point defect migration and interaction. The dependence of DA on irradiation conditions remains poorly understood even for Si. Here, we use a pulsed ion beam method to study defect interaction dynamics in Si bombarded in the temperature range from ˜-30 ° C to 210 °C with ions in a wide range of masses, from Ne to Xe, creating collision cascades with different densities. We demonstrate that the complexity of the influence of irradiation conditions on defect dynamics can be reduced to a deterministic effect of a single parameter, the average cascade density, calculated by taking into account the fractal nature of collision cascades. For each ion species, the DA rate exhibits two well-defined Arrhenius regions where different DA mechanisms dominate. These two regions intersect at a critical temperature, which depends linearly on the cascade density. The low-temperature DA regime is characterized by an activation energy of ˜0.1 eV , independent of the cascade density. The high-temperature regime, however, exhibits a change in the dominant DA process for cascade densities above ˜0.04 at.%, evidenced by an increase in the activation energy. These results clearly demonstrate a crucial role of the collision cascade density and can be used to predict radiation defect dynamics in Si.

Deterministic Role of Collision Cascade Density in Radiation Defect Dynamics in Si.

PubMed

Wallace, J B; Aji, L B Bayu; Shao, L; Kucheyev, S O

2018-05-25

The formation of stable radiation damage in solids often proceeds via complex dynamic annealing (DA) processes, involving point defect migration and interaction. The dependence of DA on irradiation conditions remains poorly understood even for Si. Here, we use a pulsed ion beam method to study defect interaction dynamics in Si bombarded in the temperature range from ∼-30 °C to 210 °C with ions in a wide range of masses, from Ne to Xe, creating collision cascades with different densities. We demonstrate that the complexity of the influence of irradiation conditions on defect dynamics can be reduced to a deterministic effect of a single parameter, the average cascade density, calculated by taking into account the fractal nature of collision cascades. For each ion species, the DA rate exhibits two well-defined Arrhenius regions where different DA mechanisms dominate. These two regions intersect at a critical temperature, which depends linearly on the cascade density. The low-temperature DA regime is characterized by an activation energy of ∼0.1  eV, independent of the cascade density. The high-temperature regime, however, exhibits a change in the dominant DA process for cascade densities above ∼0.04 at.%, evidenced by an increase in the activation energy. These results clearly demonstrate a crucial role of the collision cascade density and can be used to predict radiation defect dynamics in Si.

[Applicability of the da Vinci robotic system in the skull base surgical approach. Preclinical investigation].

PubMed

Fernandez-Nogueras Jimenez, Francisco J; Segura Fernandez-Nogueras, Miguel; Jouma Katati, Majed; Arraez Sanchez, Miguel Ángel; Roda Murillo, Olga; Sánchez Montesinos, Indalecio

2015-01-01

The role of robotic surgery is well established in various specialties such as urology and general surgery, but not in others such as neurosurgery and otolaryngology. In the case of surgery of the skull base, it has just emerged from an experimental phase. To investigate possible applications of the da Vinci surgical robot in transoral skull base surgery, comparing it with the authors' experience using conventional endoscopic transnasal surgery in the same region. A transoral transpalatal approach to the nasopharynx and medial skull base was performed on 4 cryopreserved cadaver heads. We used the da Vinci robot, a 30° standard endoscope 12mm thick, dual camera and dual illumination, Maryland forceps on the left terminal and curved scissors on the right, both 8mm thick. Bone drilling was performed manually. For the anatomical study of this region, we used 0.5cm axial slices from a plastinated cadaver head. Various skull base structures at different depths were reached with relative ease with the robot terminals Transoral robotic surgery with the da Vinci system provides potential advantages over conventional endoscopic transnasal surgery in the surgical approach to this region. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

[Linee guida italiane per il trattamento dell'alcolismo].

PubMed

Ceccanti, Mauro; Iannitelli, Angela; Fiore, Marco

2018-01-01

RIASSUNTO. L'Europa è la regione con il più forte consumo di alcol al mondo, con la più elevata percentuale di malattie totali e morti premature alcol-correlate. In Italia, questo fenomeno coinvolge circa il 13% della popolazione oltre i 18 anni e oltre il 25% dei pazienti ospedalizzati. Sfortunatamente, solo il 5% di questi pazienti vengono riconosciuti come persone affette da disturbo da uso di alcol (DUA). Una scarsa conoscenza della malattia, la mancanza di accesso alle cure e le poche risorse messe a disposizione nella gestione del problema sono tra le principali cause di ritardo nella diagnosi, alla fine con conseguenze cliniche molto più importanti e costose da gestire. Alla luce di ciò, abbiamo deciso di dedicare questo numero speciale della Rivista di psichiatria a una serie di articoli riguardanti le linee guida italiane per il trattamento della dipendenza da alcol. Realizzate in collaborazione con numerosi esperti e importanti società scientifiche italiane come il Centro di Riferimento Alcologico della Regione Lazio (CRARL), la Società Italiana Tossicodipendenze (SITD), la Società italiana per il Trattamento dell'Alcolismo e le sue Complicanze (SITAC), la Società Italiana Psichiatria delle Dipendenze (SIPDip), la Società Italiana Patologie da Dipendenza (SIPaD) e l'Istituto di Biologia Cellulare e Neurobiologia (IBCN-CNR), queste linee guida forniscono agli operatori una serie di raccomandazioni basate su prove di efficacia volte ad aumentare la conoscenza e un uso appropriato dei farmaci per le persone affette da DUA. Con la possibilità di un continuo aggiornamento, l'obiettivo principale di queste linee guida sarà quello di garantire l'omogeneità dei trattamenti e un incremento qualitativo nell'assistenza dei pazienti affetti da DUA, così da ridurre le conseguenze psicosociali e sulla salute pubblica di questa importante malattia psichiatrica.

Analisis espacial de las areas protegidas terrestres de Puerto Rico

Treesearch

M. Quinones; W.A. Gould; J. Castro-Prieto; S. Martinuzzi

2013-01-01

En este mapa de investigacion describimos las areas protegidas terrestres de Puerto Rico basado en elementos naturales y antropogenicos del paisaje. Utilizamos datos geoespaciales para calcular la extension y representatividad de elementos del paisaje dentro de las areas protegidas de Puerto Rico, i.e., cobertura del terreno (Gould et al. 2007), asentamientos urbanos...

Collaborative Disaster Preparedness: Vietnam, the United States, and Regional Experiences (Proceedings from Da Nang, Vietnam, August 1820, 2015)

DTIC Science & Technology

2016-05-19

August 18 –20, 2015) Sarah Weilant Limited Print and Electronic Distribution Rights This document and trademark(s) contained herein are protected by...from Da Nang, Vietnam, August 18 –20, 2015) Operation Damayan... 18 Operation Sahayogi Haat

Multi-Model Validation in the Chesapeake Bay Region During Frontier Sentinel 2010

DTIC Science & Technology

2012-09-28

which a 72-hr forecast took approximately 1 hr. Identical runs were performed on the DoD Supercomputing Resources Center (DSRC) host “ DaVinci ” at the...performance Navy DSRC host DaVinci . Products of water level and horizontal current maps as well as station time series, identical to those produced by the...forecast meteorological fields. The NCOM simulations were run daily on 128 CPUs at the Navy DSRC host DaVinci and required approximately 5 hrs of wall

Multi-Model Validation of Currents in the Chesapeake Bay Region in June 2010

DTIC Science & Technology

2012-01-01

host “ DaVinci ” at the Naval Oceanographic Office (NAVOCEANO). The same model configuration also took approximately 1 hr of wall clock time for a 72-hr...comparable to the performance Navy DSRC host DaVinci . Products of water level and horizontal current maps as well as station time series, identical to...DSRC host DaVinci and required approximately 5 hrs of wall-clock time for 72-hr forecasts, including data Figure 10. The Chesapeake Bay Delft3D

T227. THE METABOTROPIC GLUTAMATE RECEPTOR SUBTYPE 1 REGULATES STRIATAL DOPAMINE RELEASE VIA AN ENDOCANNABINOID-DEPENDENT MECHANISM: IMPLICATIONS FOR THE TREATMENT OF SCHIZOPHRENIA

PubMed Central

Yohn, Samantha; Covey, Daniel; Foster, Daniel; Moehle, Mark; Galbraith, Jordan; Cheer, Joseph; Lindsley, Craig; Jeffrey Conn, P

2018-01-01

Abstract Background Clinical and preclinical studies suggest that selective activators of the muscarinic M4 receptor have exciting potential as a novel approach for treatment of schizophrenia. M4 reduces striatal dopamine (DA) though release of endocannabinoids (eCB), providing a mechanism for local effects on DA signaling in the striatum. M4 signals through Gαi/o and does not couple to Gαq/11 or induce calcium (Ca++) mobilization. This raises the possibility that M4-induced eCB release and inhibition of DA release may require co-activation of another receptor that activates Gαq/11. If so, this receptor could provide a novel target that may be more proximal to inhibition of DA release. Interestingly, the group 1 metabotropic glutamate (mGlu) receptors (mGlu1 and Glu5), couple to Gαq/11 and activate eCB signaling in multiple brain regions. Methods We tested the hypothesis that M4-induced reductions in DA release and subsequent antipsychotic-effect requires co-activation of group 1 mGlu receptors. The effect of M4 activation on electrically-evoked DA release in striatal slices was assessed using fast-scan cyclic voltammetry (FSCV) in the absence or presence of selective negative allosteric modulators (NAMs) of group 1 mGlu receptor subtypes. To evaluate the potential role of mGlu1, we determined the effects of a selective mGlu1 positive allosteric modulators (PAMs) on striatal DA release and antipsychotic-like activity in rodent models that are dependent on increased DA transmission. Since reductions in DA signaling, including D1 signaling have been implicated in reduced motivation, we also determined the effects of an mGlu1 PAM, M4 PAM, and the typical antipsychotic haloperidol on motivational responding in a progressive ratio (PR) schedule. Results We now present exciting new data in which we found that activation of mGlu1 through application of exogenous agonists or selective stimulation of thalamostriatal afferents induces a reduction of striatal DA release and that selective mGlu1 PAMs have robust antipsychotic-like effects in rodent models. Interestingly, our studies also suggest that mGlu1 activation is required for M4 PAM-induced inhibition of DA release and antipsychotic-like effects. However, in contrast to available antipsychotic agents, the present results and previous studies suggest that mGlu1 and M4 PAMs reduce DA signaling through local release of an eCB from striatal SPNs and activation of CB2 receptors on neighboring DA terminals to reduce DA release. While these studies suggest that the effects of M4 PAMs on DA release require activation of mGlu1, we have also found that these targets have important differences. Most notably, M4 PAMs also directly inhibits D1 signaling in D1-SPN terminals in the substatnia nigra pars reticulata (SNr). Unlike M4, mGlu1 does not directly inhibit DA D1 receptor signaling and does not induce behavioral changes that could be associated with negative symptoms. Discussion Our findings are especially interesting in light of recent findings that multiple loss of function single nucleotide polymorphisms (SNPs) in the human gene encoding mGlu1 (GRM1) are associated with schizophrenia, and points to GRM1/mGlu1 as a gene within the “druggable genome” that could be targeted for treatment of schizophrenia. Recent clinical imaging studies suggesting that symptoms in schizophrenia patients are associated with selective increases in striatal DA signaling and while extrastriatal regions display hypo-dopaminergic function; thus, mGlu1 and M4 PAMs may provide a mechanism for selective inhibition of DA release in striatal regions that are important for antipsychotic efficacy, without further disruptions in extrastriatal DA signaling.

Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection.

PubMed

Chung, Chee Yeun; Seo, Hyemyung; Sonntag, Kai Christian; Brooks, Andrew; Lin, Ling; Isacson, Ole

2005-07-01

Molecular differences between dopamine (DA) neurons may explain why the mesostriatal DA neurons in the A9 region preferentially degenerate in Parkinson's disease (PD) and toxic models, whereas the adjacent A10 region mesolimbic and mesocortical DA neurons are relatively spared. To characterize innate physiological differences between A9 and A10 DA neurons, we determined gene expression profiles in these neurons in the adult mouse by laser capture microdissection, microarray analysis and real-time PCR. We found 42 genes relatively elevated in A9 DA neurons, whereas 61 genes were elevated in A10 DA neurons [> 2-fold; false discovery rate (FDR) < 1%]. Genes of interest for further functional analysis were selected by criteria of (i) fold differences in gene expression, (ii) real-time PCR validation and (iii) potential roles in neurotoxic or protective biochemical pathways. Three A9-elevated molecules [G-protein coupled inwardly rectifying K channel 2 (GIRK2), adenine nucleotide translocator 2 (ANT-2) and the growth factor IGF-1] and three A10-elevated peptides (GRP, CGRP and PACAP) were further examined in both alpha-synuclein overexpressing PC12 (PC12-alphaSyn) cells and rat primary ventral mesencephalic (VM) cultures exposed to MPP+ neurotoxicity. GIRK2-positive DA neurons were more vulnerable to MPP+ toxicity and overexpression of GIRK2 increased the vulnerability of PC12-alphaSyn cells to the toxin. Blocking of ANT decreased vulnerability to MPP+ in both cell culture systems. Exposing cells to IGF-1, GRP and PACAP decreased vulnerability of both cell types to MPP+, whereas CGRP protected PC12-alphaSyn cells but not primary VM DA neurons. These results indicate that certain differentially expressed molecules in A9 and A10 DA neurons may play key roles in their relative vulnerability to toxins and PD.

Neuroprotective Effect of a New Synthetic Aspirin-decursinol Adduct in Experimental Animal Models of Ischemic Stroke

PubMed Central

Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

2013-01-01

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants. PMID:24073226

Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental animal models of ischemic stroke.

PubMed

Yan, Bing Chun; Park, Joon Ha; Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

2013-01-01

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.

Socioeconomic and regional differences in active transportation in Brazil.

PubMed

Sá, Thiago Hérick de; Pereira, Rafael Henrique Moraes; Duran, Ana Clara; Monteiro, Carlos Augusto

2016-06-27

To present national estimates regarding walking or cycling for commuting in Brazil and in 10 metropolitan regions. By using data from the Health section of 2008's Pesquisa Nacional por Amostra de Domicílio (Brazil's National Household Sample Survey), we estimated how often employed people walk or cycle to work, disaggregating our results by sex, age range, education level, household monthly income per capita, urban or rural address, metropolitan regions, and macro-regions in Brazil. Furthermore, we estimated the distribution of this same frequency according to quintiles of household monthly income per capita in each metropolitan region of the country. A third of the employed men and women walk or cycle from home to work in Brazil. For both sexes, this share decreases as income and education levels rise, and it is higher among younger individuals, especially among those living in rural areas and in the Northeast region of the country. Depending on the metropolitan region, the practice of active transportation is two to five times more frequent among low-income individuals than among high-income individuals. Walking or cycling to work in Brazil is most frequent among low-income individuals and the ones living in less economically developed areas. Active transportation evaluation in Brazil provides important information for public health and urban mobility policy-making. Apresentar estimativas nacionais sobre o deslocamento a pé ou de bicicleta no trajeto casa-trabalho no Brasil e em 10 de suas regiões metropolitanas. Utilizando dados do Suplemento sobre Saúde da Pesquisa Nacional por Amostra de Domicílios de 2008, estimamos a frequência de pessoas empregadas que se deslocam a pé ou de bicicleta no trajeto casa-trabalho estratificada por sexo, e segundo faixa etária, escolaridade, renda domiciliar per capita, residência em área urbana ou rural, regiões metropolitanas e macrorregiões do país. Adicionalmente, estimamos a distribuição da mesma frequência segundo quintos da distribuição da renda domiciliar per capita em cada região metropolitana. Um terço dos homens e mulheres empregados desloca-se a pé ou de bicicleta de casa para o trabalho no Brasil. Em ambos os sexos, esta proporção diminui com o aumento da renda e da escolaridade e é maior entre os mais jovens, entre os que residem em área rural e naqueles residentes na região Nordeste. A depender da região metropolitana, a prática de deslocamento ativo entre os mais pobres é de duas a cinco vezes maior do que entre os mais ricos. O deslocamento a pé ou de bicicleta para o trabalho no Brasil é mais frequente entre os mais pobres e entre pessoas que vivem em áreas e regiões economicamente menos desenvolvidas. A avaliação do deslocamento ativo no País traz informações importantes para a discussão de políticas públicas de mobilidade.

Mixing and overshooting in surface convection zones of DA white dwarfs: first results from ANTARES

NASA Astrophysics Data System (ADS)

Kupka, F.; Zaussinger, F.; Montgomery, M. H.

2018-03-01

We present results of a large, high-resolution 3D hydrodynamical simulation of the surface layers of a DA white dwarf (WD) with Teff = 11 800 K and log (g) = 8 using the ANTARES code, the widest and deepest such simulation to date. Our simulations are in good agreement with previous calculations in the Schwarzschild-unstable region and in the overshooting region immediately beneath it. Farther below, in the wave-dominated region, we find that the rms horizontal velocities decay with depth more rapidly than the vertical ones. Since mixing requires both vertical and horizontal displacements, this could have consequences for the size of the region that is well mixed by convection, if this trend is found to hold for deeper layers. We discuss how the size of the mixed region affects the calculated settling times and inferred steady-state accretion rates for WDs with metals observed in their atmospheres.

A procedure for the sensory evaluation of Salama da sugo, a typical fermented sausage produced in the Emilia Romagna Region, Italy.

PubMed

Coloretti, Fabio; Grazia, Luigi; Gardini, Fausto; Lanciotti, Rosalba; Montanari, Chiara; Tabanelli, Giulia; Chiavari, Cristiana

2015-03-30

Salama da sugo is a fermented sausage from the Ferrara tradition (Italy, Emilia-Romagna region), subjected to a long ripening period (4-6 months) and characterised by a high content of wine and spices in the mixture. It can be consumed after cooking and it is served with its sugo, i.e. the liquid extracted by cooking process. The aim of this work was to set up a method for the sensory profile of Salama da sugo as a request for Protected Geographical Indication (PGI) has been made to the European Commission. A system of sample preparation that provides for the precooking in an autoclave and cooking in boiling water was set up. A specific sheet for sensory evaluation of Salama da sugo has been created and reports 23 descriptors identified during the lexicon development. The differences in sensory profile of four samples were evaluated and principal component analysis highlighted the more discriminant parameters, i.e. odour intensity, wine odour, spicy aroma, fat/lean connection, sweet, bitter, juiciness, chewiness and pricking. The proposed method allows the standardisation of sensory profiling of Salama da sugo, and is also to verify compliance with the specification PGI. © 2014 Society of Chemical Industry.

Epigenetic dysregulation of the dopamine system in diet-induced obesity.

PubMed

Vucetic, Zivjena; Carlin, Jesse Lea; Totoki, Kathy; Reyes, Teresa M

2012-03-01

Chronic intake of high-fat (HF) diet is known to alter brain neurotransmitter systems that participate in the central regulation of food intake. Dopamine (DA) system changes in response to HF diet have been observed in the hypothalamus, important in the homeostatic control of food intake, as well as within the central reward circuitry [ventral tegmental area (VTA), nucleus accumbens (NAc), and pre-frontal cortex (PFC)], critical for coding the rewarding properties of palatable food and important in hedonically driven feeding behavior. Using a mouse model of diet-induced obesity (DIO), significant alterations in the expression of DA-related genes were documented in adult animals, and the general pattern of gene expression changes was opposite within the hypothalamus versus the reward circuitry (increased vs. decreased, respectively). Differential DNA methylation was identified within the promoter regions of tyrosine hydroxylase (TH) and dopamine transporter (DAT), and the pattern of this response was consistent with the pattern of gene expression. Behaviors consistent with increased hypothalamic DA and decreased reward circuitry DA were observed. These data identify differential DNA methylation as an epigenetic mechanism linking the chronic intake of HF diet with altered DA-related gene expression, and this response varies by brain region and DNA sequence. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Self-perception of oral health in older adults from an urban population in Lisbon, Portugal.

PubMed

Carvalho, Catarina; Manso, Ana Cristina; Escoval, Ana; Salvado, Francisco; Nunes, Carla

2016-08-22

To analyze if the self-perception of oral health in the urban context is associated with sociodemographic factors that interfere in the life quality of oral health. Cross-sectional study with convenience sample of older individuals (65 years old or more) enrolled in the Agrupamento de Centros de Saúde de Lisboa Norte (ACES Lisboa Norte - Health Centers Groupings North Lisbon). The self-perception of oral health and associated life quality was evaluated by the Geriatric Oral Health Assessment Index and the individuals were classified according to sociodemographic characteristics. The internal consistency of the questionnaire was evaluated by Cronbach's alpha (α). Later, we used binary logistic regression models to characterize the factors associated with the self-perception of oral health, considering the sociodemographic variables and the older adults' clinical conditions of oral health and establishing the crude and adjusted (to age) odds ratios and their 90% confidence intervals. A total of 369 older adults participated in this study, with an average age of 74.2 years (SD = 6.75); 62.9% were female. On average, the index was moderated, with tendency to be high: 32.9 (SD = 3.6; 12-36 interval). The Cronbach's alpha was high: 0.805. Age, marital status, and the last dental appointment were the factors significantly associated with self-perception of oral health. The study shows that these individuals have a moderate, with tendency to high, self-perception of oral health. The self-perception of oral health assessment allowed us to identify the main associated sociodemographic factors. This instrument can help guiding planning strategies and oral health promotion directed toward a better life quality for this population group. Analisar se a autopercepção de saúde bucal em contexto urbano está associada aos factores sociodemográficos que interferem na qualidade de vida da saúde bucal. Estudo transversal com amostra de conveniência de indivíduos idosos (65 anos ou mais) inscritos no Agrupamento de Centros de Saúde de Lisboa Norte. A autopercepção da saúde bucal e qualidade de vida associada foi avaliada pelo índice de avaliação da saúde bucal em idosos (Geriatric Oral Health Assessment Index) e os indivíduos foram classificados de acordo com as características sociodemográficas. A consistência interna do questionário foi avaliada por meio do alfa (α) de Cronbach. Posteriormente, foram utilizados modelos de regressão logística binária para caracterizar os factores associados com a autopercepção de saúde bucal considerando as variáveis sociodemográficas e de condições clínicas de saúde bucal dos idosos e determinados os odds ratios bruto e ajustado (à idade) e respectivos intervalos de confiança a 90%. Participaram 369 idosos, com média de idade de 74,2 anos (DP = 6,75); 62,9% eram do sexo feminino. Em média, o índice foi moderado com tendência a elevado: 32,9 (DP = 3,6; intervalo 12-36). O alfa de Cronbach foi elevado: 0,805. A idade, o estado civil e a última consulta de Medicina Dentária foram os factores significativamente associados a autopercepção da saúde bucal. O estudo mostra que esses indivíduos apresentam uma autopercepção de saúde bucal moderada, com tendência a elevada. A avaliação da autopercepção da saúde bucal permitiu identificar os principais factores sociodemográficos associados. Este instrumento pode contribuir para orientar as estratégias de planejamento e promoção da saúde bucal direcionadas para uma melhor qualidade de vida deste grupo populacional.

Comparative neurobiological effects of ibogaine and MK-801 in rats.

PubMed

Baumann, M H; Rothman, R B; Ali, S F

2000-05-01

Ibogaine is a plant-derived alkaloid with putative 'anti-addictive' properties. Although ibogaine binds to multiple targets in the brain, recent evidence suggests the drug acts as an N-methyl-D-aspartate (NMDA) antagonist similar to MK-801. The purpose of the present study was to compare neurochemical and neuroendocrine effects of ibogaine and MK-801 in vivo. Male rats received either i.p. saline, ibogaine (10 and 100 mg/kg), or MK-801 (0.1 and 1 mg/kg). Groups of rats (N=6-8/group) were decapitated 30 or 60 min after injection. Brains were harvested for analysis of dopamine (DA) and its metabolites, while trunk blood was collected for analysis of plasma corticosterone and prolactin. Ibogaine produced marked dose-dependent reductions in tissue DA with concurrent increases in the metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This profile of ibogaine-induced effects on DA metabolism was consistently observed in the cortex, striatum, olfactory tubercle, and hypothalamus. MK-801, on the other hand, did not reduce DA levels in any brain region but did cause modest region-specific elevations in DA metabolites. Ibogaine and MK-801 caused comparable elevations in circulating corticosterone, but only ibogaine increased prolactin. The present findings show that the effects of ibogaine on DA neurotransmission and neuroendocrine secretion are not fully mimicked by MK-801. Thus, the wide spectrum of in vivo actions of ibogaine can probably not be explained simply on the basis of antagonism at NMDA receptors.

Fast-scan cyclic voltammetry demonstrates that L-DOPA produces dose-dependent regionally selective, bimodal effects on striatal dopamine kinetics in vivo.

PubMed

Harun, R; Hare, K M; Brough, M E; Munoz, M J; Grassi, C M; Torres, G E; Grace, A A; Wagner, A K

2015-11-27

Parkinson's disease (PD) is a debilitating condition that is caused by a relatively specific degeneration of dopaminergic (DAergic) neurons of the substantia nigra pars compacta. Levodopa (L-DOPA) was introduced as a viable treatment option for PD over 40 years ago and still remains the most common and effective therapy for PD. Though the effects of L-DOPA to augment striatal DA production are well known, little is actually known about how L-DOPA alters the kinetics of DA neurotransmission that contribute to its beneficial and adverse effects. In this study, we examined the effects of L-DOPA administration (50mg/kg carbidopa + 0, 100, and 250mg/kg L-DOPA) on regional electrically stimulated DA response kinetics using fast-scan cyclic voltammetry (FSCV) in anesthetized rats. We demonstrate that L-DOPA enhances DA release in both the dorsal striatum (D-STR) and nucleus accumbens (NAc), but surprisingly causes a delayed inhibition of release in the D-STR. In both regions, L-DOPA progressively attenuated reuptake kinetics, predominantly through a decrease in Vmax. These findings have important implications on understanding the pharmacodynamics of L-DOPA, which can be informative for understand its therapeutic effects and also common side effects like L-DOPA induced dyskinesias (LID). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses.

PubMed

Scott, David J; Stohler, Christian S; Egnatuk, Christine M; Wang, Heng; Koeppe, Robert A; Zubieta, Jon-Kar

2008-02-01

Placebo and nocebo effects, the therapeutic and adverse effects, respectively, of inert substances or sham procedures, represent serious confounds in the evaluation of therapeutic interventions. They are also an example of cognitive processes, particularly expectations, capable of influencing physiology. To examine the contribution of 2 different neurotransmitters, the endogenous opioid and the dopaminergic (DA) systems, to the development of placebo and nocebo effects. Using a within-subject design, subjects twice underwent a 20-minute standardized pain challenge, in the absence and presence of a placebo with expected analgesic properties. Studies were conducted in a university hospital setting. Twenty healthy men and women aged 20 to 30 years recruited by advertisement. Activation of DA and opioid neurotransmission by a pain stressor with and without placebo (changes in the binding potential of carbon 11 [11C]-labeled raclopride and [11C] carfentanil with positron emission tomography) and ratings of pain, affective state, and anticipation and perception of analgesia. Placebo-induced activation of opioid neurotransmission was detected in the anterior cingulate, orbitofrontal and insular cortices, nucleus accumbens, amygdala, and periaqueductal gray matter. Dopaminergic activation was observed in the ventral basal ganglia, including the nucleus accumbens. Regional DA and opioid activity were associated with the anticipated and subjectively perceived effectiveness of the placebo and reductions in continuous pain ratings. High placebo responses were associated with greater DA and opioid activity in the nucleus accumbens. Nocebo responses were associated with a deactivation of DA and opioid release. Nucleus accumbens DA release accounted for 25% of the variance in placebo analgesic effects. Placebo and nocebo effects are associated with opposite responses of DA and endogenous opioid neurotransmission in a distributed network of regions. The brain areas involved in these phenomena form part of the circuit typically implicated in reward responses and motivated behavior.

Effect of long-term actual spaceflight on the expression of key genes encoding serotonin and dopamine system

NASA Astrophysics Data System (ADS)

Popova, Nina; Shenkman, Boris; Naumenko, Vladimir; Kulikov, Alexander; Kondaurova, Elena; Tsybko, Anton; Kulikova, Elisabeth; Krasnov, I. B.; Bazhenova, Ekaterina; Sinyakova, Nadezhda

The effect of long-term spaceflight on the central nervous system represents important but yet undeveloped problem. The aim of our work was to study the effect of 30-days spaceflight of mice on Russian biosatellite BION-M1 on the expression in the brain regions of key genes of a) serotonin (5-HT) system (main enzymes in 5-HT metabolism - tryptophan hydroxylase-2 (TPH-2), monoamine oxydase A (MAO A), 5-HT1A, 5-HT2A and 5-HT3 receptors); b) pivotal enzymes in DA metabolism (tyrosine hydroxylase, COMT, MAO A, MAO B) and D1, D2 receptors. Decreased expression of genes encoding the 5-HT catabolism (MAO A) and 5-HT2A receptor in some brain regions was shown. There were no differences between “spaceflight” and control mice in the expression of TPH-2 and 5-HT1A, 5-HT3 receptor genes. Significant changes were found in genetic control of DA system. Long-term spaceflight decreased the expression of genes encoding the enzyme in DA synthesis (tyrosine hydroxylase in s.nigra), DA metabolism (MAO B in the midbrain and COMT in the striatum), and D1 receptor in hypothalamus. These data suggested that 1) microgravity affected genetic control of 5-HT and especially the nigrostriatal DA system implicated in the central regulation of muscular tonus and movement, 2) the decrease in the expression of genes encoding key enzyme in DA synthesis, DA degradation and D1 receptor contributes to the movement impairment and dyskinesia produced by the spaceflight. The study was supported by Russian Foundation for Basic Research grant No. 14-04-00173.

Ezrin is a cyclic AMP-dependent protein kinase anchoring protein.

PubMed Central

Dransfield, D T; Bradford, A J; Smith, J; Martin, M; Roy, C; Mangeat, P H; Goldenring, J R

1997-01-01

cAMP-dependent protein kinase (A-kinase) anchoring proteins (AKAPs) are responsible for the subcellular sequestration of the type II A-kinase. Previously, we identified a 78 kDa AKAP which was enriched in gastric parietal cells. We have now purified the 78 kDa AKAP to homogeneity from gastric fundic mucosal supernates using type II A-kinase regulatory subunit (RII) affinity chromatography. The purified 78 kDa AKAP was recognized by monoclonal antibodies against ezrin, the canalicular actin-associated protein. Recombinant ezrin produced in either Sf9 cells or bacteria also bound RII. Recombinant radixin and moesin, ezrin-related proteins, also bound RII in blot overlay. Analysis of recombinant truncations of ezrin mapped the RII binding site to a region between amino acids 373 and 439. This region contained a 14-amino-acid amphipathic alpha-helical putative RII binding region. A synthetic peptide containing the amphipathic helical region (ezrin409-438) blocked RII binding to ezrin, but a peptide with a leucine to proline substitution at amino acid 421 failed to inhibit RII binding. In mouse fundic mucosa, RII immunoreactivity redistributed from a predominantly cytosolic location in resting parietal cells, to a canalicular pattern in mucosa from animals stimulated with gastrin. These results demonstrate that ezrin is a major AKAP in gastric parietal cells and may function to tether type II A-kinase to a region near the secretory canaliculus. PMID:9009265

Dopamine D2 Receptor Levels in Striatum, Thalamus, Substantia Nigra, Limbic Regions, and Cortex in Schizophrenic Subjects

PubMed Central

Kessler, Robert M; Woodward, Neil D; Riccardi, Patrizia; Li, Rui; Ansari, M Sib; Anderson, Sharlett; Dawant, Benoit; Zald, David; Meltzer, Herbert Y

2009-01-01

Background Studies in schizophrenics have reported dopaminergic abnormalities in striatum, substantia nigra, thalamus, anterior cingulate, hippocampus and cortex which have been related to positive symptoms and cognitive impairments. Methods [18F]fallypride PET studies were performed in off medication or never medicated schizophrenic subjects [N = 11, 6 M, 5 F; mean age of 30.5 ± 8.0 (S.D.); 4 drug naive] and age matched healthy subjects [N = 11, 5M, 6F, mean age of 31.6 ± 9.2 (S.D.)] to examine dopamine D2 receptor (DA D2r) levels in the caudate, putamen, ventral striatum, medial thalamus, posterior thalamus, substantia nigra, amygdala, temporal cortex, anterior cingulate, and hippocampus. Results In schizophrenic subjects increased DA D2r levels were seen in the substantia nigra bilaterally; decreased levels were seen in the left medial thalamus. Correlations of symptoms with region of interest data demonstrated a significant correlation of disorganized thinking/nonparanoid delusions with the right temporal cortex region of interest (r = 0.94, P = 0.0001) which remained significant after correction for multiple comparisons (P<0.03). Correlations of symptoms with parametric images of DA D2r levels revealed no significant clusters of correlations with negative symptoms, but significant clusters of positive correlations of total positive symptoms, delusions and bizarre behavior with the lateral and anterior temporal cortex, and hallucinations with the left ventral striatum. Conclusions The results of this study demonstrate abnormal DA D2r mediated neurotransmission in the substantia nigra consistent with nigral dysfunction in schizophrenia and suggest that both temporal cortical and ventral striatal DA D2r mediate positive symptoms. PMID:19251247

Dopamine in the nucleus accumbens core, but not shell, increases during signaled food reward and decreases during delayed extinction.

PubMed

Biesdorf, C; Wang, A-L; Topic, B; Petri, D; Milani, H; Huston, J P; de Souza Silva, M A

2015-09-01

Microdialysis studies in rat have generally shown that appetitive stimuli release dopamine (DA) in the nucleus accumbens (NAc) shell and core. Here we examined the release of DA in the NAc during delivery of reward (food) and during extinction of food reward in the freely moving animal by use of in vivo microdialysis and HPLC. Fifty-two male Wistar rats were trained to receive food reward associated with appearance of cue-lights in a Skinner-box during in vivo microdialysis. Different behavioral protocols were used to assess the effects of extinction on DA and its metabolites. Results Exp. 1: (a) During a 20-min period of cued reward delivery, DA increased significantly in the NAc core, but not shell subregion; (b) for the next 60min period half of the rats underwent immediate extinction (with the CS light presented during non-reward) and the other half did not undergo extinction to the cue lights (CS was not presented during non-reward). DA remained significantly increased in both groups, providing no evidence for a decrease in DA during extinction in either NAc core or shell regions. (c) In half of the animals of the group that was not subjected to extinction, the cue lights were turned on for 30min, thus, initiating extinction to cue CS at a 1h delay from the period of reward. In this group DA in the NAc core, but not shell, significantly decreased. Behavioral analysis showed that while grooming is an indicator of extinction-induced behavior, glances toward the cue-lights (sign tracking) are an index of resistance to extinction. Results Exp. 2: (a) As in Exp. 1, during a 30-min period of cued reward delivery, DA levels again increased significantly in the NAc core but not in the NAc shell. (b) When extinction (the absence of reward with the cue lights presented) was administered 24h after the last reward session, DA again significantly decreased in the NAc core, but not in the NAc shell. (a) These results confirm the importance of DA release in the NAc for reward-related states, with DA increasing in the core, but not shell subregion. (b) They provide first evidence that during the withholding of expected reward, DA decreases in the NAc core, but not shell region. (c) This decrease in DA appears only after a delay between delivery of reward and extinction likely due to it being masked by persisting DA release. We hypothesize the decrease in extinction-induced release of DA in the NAc core to be a marker for the despair/depression that is known to accompany the failure to obtain expected rewards/reinforcers. Copyright © 2015 Elsevier Inc. All rights reserved.

Trends in the application of dynamic allocation methods in multi-arm cancer clinical trials.

PubMed

Pond, Gregory R; Tang, Patricia A; Welch, Stephen A; Chen, Eric X

2010-06-01

Dynamic allocation (DA) methods which attempt to balance baseline prognostic factors between treatment arms, can be used in multi-arm clinical trials to sequentially allocate patients to treatment. Although some experts express concern regarding the validity of inference from trials using DA, others believe DA methods produce more credible results. A review of published multi-arm cancer clinical trials was conducted to explore the frequency of DA use in oncology. Multi-arm phase III clinical trials of at least 100 patients per arm, published in 13 major oncology journals from 1995-2005 were manually reviewed. Information about reported use of DA methods, or randomization via random permuted blocks (PB), was extracted along with trial characteristics. Of 476 published clinical trials, 112 (23.5%) reported using some form of DA method, while 103 (21.6%) reported using PB methods. Most trials (403 or 84.7%) reported stratifying on at least one baseline factor. The mean number of stratification factors was 2.70 per trial, and 78.6% of DA trials reported 3 or more stratification factors compared with 30.2% of non-DA trials (p < 0.001). The frequency of DA use increased over time, with 20.2%, 21.3%, 25.8%, 28.8% and 38.9% of trials reported use in 1995-2001, 2002, 2003, 2004, and 2005, respectively. Use of DA methods was more frequently reported in trials involving an academic co-operative group (28.4% vs. 13.8%), however, no difference was observed between industry-funded and other-funded trials (24.0% vs. 23.2%) or geographical region (19.7% of North American trials, 26.2% of European trials and 21.7% of multinational/other trials). As a retrospective analysis, the true frequency of DA use is likely underreported. Few trials gave complete details of the allocation method used, thus it is possible some manuscripts reported incorrect allocation methods. Journals were selected which were assumed to publish most large, multi-arm clinical trials in cancer from 1995-2005, however, some trials were likely reported in journals other than what was reviewed. DA methods are frequently used in multi-arm cancer clinical trials. The use of DA appears to becoming more common over time and are used more frequently when an academic cooperative group is involved. No relationship between industry funded trials or geographic region and allocation method was observed. Clinical Trials 2010; 7: 227-234. http://ctj.sagepub.com.

76 FR 46295 - The Regional Sports Network Marketplace

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-02

... FEDERAL COMMUNICATIONS COMMISSION [MB Docket No. 11-128; DA 11-1238] The Regional Sports Network... network (RSN) access and carriage issues and committed to examine these matters before the expiration of... this Public Notice, the Media Bureau seeks comment on issues related to regional sports network (RSN...

Metaproteomics of Microbiota in Naturally Fermented Soybean Paste, Da-jiang.

PubMed

Zhang, Ping; Zhang, Pengfei; Xie, Mengxi; An, Feiyu; Qiu, Boshu; Wu, Rina

2018-05-01

Da-jiang is a typical traditional fermented soybean product in China. At present, the proteins in da-jiang are needed to be explored. The composition and species of microbial proteins in traditional fermented da-jiang were analyzed by metaproteomics based on sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The results showed that the number and variety of microbial proteins in the traditional fermented da-jiang from different regions were different. The production site influences the fermentation in da-jiang. Then we analyzed the functions of the microbial proteins identified in da-jiang, and found that they were mainly involved in the process of protein synthesis, glycometabolism and nucleic acid synthesis. In addtion, we compared the proteins composition in different da-jiang. There are 51 common proteins of naturally fermented da-jiang, and 25 common microbial sources. The main commonly microbial sources of fungal proteins are Saccharomyces cerevisiae and Schizosaccharomyces; the main commonly microbial sources of bacterial proteins are Enterococcus faecalis, Leuconostoc mesenteroides, Acinetobacter baumannii, and Bacillus subtilis. These common microbes play the predominant role in da-jiang fermentation. The present results help us to understand the fermentation of da-jiang and improve the quality and safety of final products in the future. The study illustrated metaproteome of microbiota in traditional fermented soybean paste, da-jiang, by sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). A method of extracting metaproteome from microbiota in da-jiang was attempted. The findings help to understand the fermentation of da-jiang and improve the quality and safety of da-jiang in fermented industry. © 2018 Institute of Food Technologists®.

Ebf2 is required for development of dopamine neurons in the midbrain periaqueductal gray matter of mouse.

PubMed

Yang, Qiaoqiao; Liu, Shuxi; Yin, Min; Yin, Yanqing; Zhou, Guomin; Zhou, Jiawei

2015-11-01

Dopaminergic (DA) neurons in the midbrain ventral periaqueductal gray matter (PAG) play critical roles in various physiological and pathophysiological processes including sleep-wake rhyme, antinociception, and drug addiction. However, the molecular mechanisms underlying their development are poorly understood. Here, we showed that PAG DA neurons arose as early as E15.5 in mouse embryos. During the prenatal period, the majority of PAG DA neurons was distributed in the intermediate and caudal regions of the PAG. In the postnatal brain, ∼50% of PAG DA neurons were preferentially located in the caudal portion of the PAG. Moreover, transcription factor early B-cell factor 2 (Ebf2) was transiently expressed in a subset of DA neurons in embryonic ventral mesencephalon. Functional analysis revealed that loss of Ebf2 in vivo caused a marked reduction in the number of DA neurons in the midbrain PAG but not in the substantia nigra and ventral tegmental area. Thus, Ebf2 is identified as a novel and important regulator selectively required for midbrain PAG DA neuron development. © 2015 Wiley Periodicals, Inc.

Explaining the disease phenotype of intergenic SNP through predicted long range regulation

PubMed Central

Chen, Jingqi; Tian, Weidong

2016-01-01

Thousands of disease-associated SNPs (daSNPs) are located in intergenic regions (IGR), making it difficult to understand their association with disease phenotypes. Recent analysis found that non-coding daSNPs were frequently located in or approximate to regulatory elements, inspiring us to try to explain the disease phenotypes of IGR daSNPs through nearby regulatory sequences. Hence, after locating the nearest distal regulatory element (DRE) to a given IGR daSNP, we applied a computational method named INTREPID to predict the target genes regulated by the DRE, and then investigated their functional relevance to the IGR daSNP's disease phenotypes. 36.8% of all IGR daSNP-disease phenotype associations investigated were possibly explainable through the predicted target genes, which were enriched with, were functionally relevant to, or consisted of the corresponding disease genes. This proportion could be further increased to 60.5% if the LD SNPs of daSNPs were also considered. Furthermore, the predicted SNP-target gene pairs were enriched with known eQTL/mQTL SNP-gene relationships. Overall, it's likely that IGR daSNPs may contribute to disease phenotypes by interfering with the regulatory function of their nearby DREs and causing abnormal expression of disease genes. PMID:27280978

Standardization and Prevalence of the Booster Phenomenon: Evaluation Using a Two-Step Skin Test with 43 kDa Glycoprotein in Individuals from an Endemic Region of Paracoccidioidomycosis.

PubMed

Marques, Ana Paula C; Oliveira, Sandra Maria V L; Rezende, Grazielli R; Melo, Dayane A; Fernandes-Fitts, Sonia M; Pontes, Elenir Rose J C; Bonecini-Almeida, Maria da Glória; Camargo, Zoilo P; Mendes, Rinaldo P; Paniago, Anamaria M M

2017-10-01

We estimated the occurrence rate of the booster phenomenon by using an intradermal test with 43 kDa glycoprotein in an endemic area of paracoccidioidomycosis in the central-west region of Brazil. Individuals who had a negative result on a survey performed by using an intradermal test with 43 kDa glycoprotein in an endemic area of paracoccidioidomycosis underwent a second intradermal test after 10-15 days to determine the presence or absence of the booster phenomenon. Statistical analyses were performed using the Chi-square test, Chi-square for linear trend test, Student's t test, and binomial test; p < 0.05 was considered significant. For the first time, we reported the occurrence of the booster phenomenon to an intradermal reaction caused by 43 kDa glycoprotein at a rate of 5.8-8.4%, depending on the test's cutoff point. This suggests that a cutoff point should be considered for the booster phenomenon in intradermal tests with 43 kDa glycoprotein: a difference of 6-7 mm between readings according to the first and second tests, depending on the purpose of the evaluation. The results indicate that the prevalence of paracoccidioidal infection in endemic areas is underestimated, as the booster phenomenon has not been considered in epidemiological surveys for this infection.

Solving da Vinci stereopsis with depth-edge-selective V2 cells

PubMed Central

Assee, Andrew; Qian, Ning

2007-01-01

We propose a new model for da Vinci stereopsis based on a coarse-to-fine disparity-energy computation in V1 and disparity-boundary-selective units in V2. Unlike previous work, our model contains only binocular cells, relies on distributed representations of disparity, and has a simple V1-to-V2 feedforward structure. We demonstrate with random dot stereograms that the V2 stage of our model is able to determine the location and the eye-of-origin of monocularly occluded regions and improve disparity map computation. We also examine a few related issues. First, we argue that since monocular regions are binocularly defined, they cannot generally be detected by monocular cells. Second, we show that our coarse-to-fine V1 model for conventional stereopsis explains double matching in Panum’s limiting case. This provides computational support to the notion that the perceived depth of a monocular bar next to a binocular rectangle may not be da Vinci stereopsis per se (Gillam et al., 2003). Third, we demonstrate that some stimuli previously deemed invalid have simple, valid geometric interpretations. Our work suggests that studies of da Vinci stereopsis should focus on stimuli more general than the bar-and-rectangle type and that disparity-boundary-selective V2 cells may provide a simple physiological mechanism for da Vinci stereopsis. PMID:17698163

Pre-clinical and Clinical Development of Low Dose Methamphetamine for the Treatment of Traumatic Brain Injury

DTIC Science & Technology

2014-12-01

Aim 3: Secure FDA approval of a phase I/II clinical trial plan and obtain an amended IND in preparation for initiating human clinical testing in TBI...Neurology 6:193–201. Raineri M, Gonzalez B, Goitia B, Garcia-Rill E, Krasnova IN, Cadet JL, Urbano FJ, Bisagno V. 2012. Modafinil abrogates

A More Realistic Approach to the Measurement of Occupational Interests in a Service Setting. Part 1. Form EZ.

DTIC Science & Technology

1979-12-01

their engagement who use a specific outside job opportunity in support could have the reality of their plans evaluated by either previously recorded...programme. Factored data on this are now to hand 3 at the suggestion of P. J. Oswnld Nita Cherry, Linda Gatiss, John Urbano and will be discussed in

Composición y estructura de un bosque tropical urbano en el karso norteno de Puerto Rico

Treesearch

E. López Machado; K. Soto Hidalgo; T. Heartsill-Scalley

2012-01-01

Tropical secondary forests provide many products, environmental services, and recreation. These forests have a set of biological features, such as their high productivity and a uniform composition of dominant tree species. To understand the composition and structure of a secondary forest in the northern karst zone, we selected the Santa Ana Environmental Center (CASA...

Subset of Kappa and Lambda Germline Sequences Result in Light Chains with a Higher Molecular Mass Phenotype.

PubMed

Barnidge, David R; Lundström, Susanna L; Zhang, Bo; Dasari, Surendra; Murray, David L; Zubarev, Roman A

2015-12-04

In our previous work, we showed that electrospray ionization of intact polyclonal kappa and lambda light chains isolated from normal serum generates two distinct, Gaussian-shaped, molecular mass distributions representing the light-chain repertoire. During the analysis of a large (>100) patient sample set, we noticed a low-intensity molecular mass distribution with a mean of approximately 24 250 Da, roughly 800 Da higher than the mean of the typical kappa molecular-mass distribution mean of 23 450 Da. We also observed distinct clones in this region that did not appear to contain any typical post-translational modifications that would account for such a large mass shift. To determine the origin of the high molecular mass clones, we performed de novo bottom-up mass spectrometry on a purified IgM monoclonal light chain that had a calculated molecular mass of 24 275.03 Da. The entire sequence of the monoclonal light chain was determined using multienzyme digestion and de novo sequence-alignment software and was found to belong to the germline allele IGKV2-30. The alignment of kappa germline sequences revealed ten IGKV2 and one IGKV4 sequences that contained additional amino acids in their CDR1 region, creating the high-molecular-mass phenotype. We also performed an alignment of lambda germline sequences, which showed additional amino acids in the CDR2 region, and the FR3 region of functional germline sequences that result in a high-molecular-mass phenotype. The work presented here illustrates the ability of mass spectrometry to provide information on the diversity of light-chain molecular mass phenotypes in circulation, which reflects the germline sequences selected by the immunoglobulin-secreting B-cell population.

Comparison of extracellular protein profiles of seven serotypes of mutans streptococci grown under controlled conditions.

PubMed

Hardy, L N; Knox, K W; Brown, R A; Wicken, A J; Fitzgerald, R J

1986-05-01

Extracellular proteins produced by the four human commensal species of mutans streptococci were analysed. The organisms used were Streptococcus mutans, serotypes c, e and f, Streptococcus cricetus, serotype a, Streptococcus rattus, serotype b, and Streptococcus sobrinus, serotypes d and g. They were grown in continuous culture at different generation times and pH values in media containing either glucose or fructose to determine the extent of variation in extracellular protein production that could occur for an individual strain. The results for different organisms grown under the same conditions were then compared. The total amount of protein of molecular mass greater than or equal to 60 kDa varied considerably with the growth conditions and with the strain. Generally more protein was present at a higher pH, conditions under which the organisms also form more lipoteichoic acid. With respect to individual protein components SDS-PAGE proved better than isoelectric focusing for detecting phenotypic responses by a particular strain to environmental changes and differences between the different strains. Differences in the molecular masses of protein components were particularly pronounced in the regions designated P1 (185-200 kDa), P2 (130-155 kDa) and P3 (60-95 kDa). Every strain produced at least one component in the P1 region that cross-reacted with antiserum to the purified protein from S. mutans serotype c, a protein which is indistinguishable from antigens B and I/II. Two components in the P2 region were dominant in the case of S. cricetus and S. sobrinus strains and showed glucosyltransferase (GTF) activity. GTF activity was also detected in the P3 region, particularly with S. mutans strains.

Requirement of Dopamine Signaling in the Amygdala and Striatum for Learning and Maintenance of a Conditioned Avoidance Response

ERIC Educational Resources Information Center

Darvas, Martin; Fadok, Jonathan P.; Palmiter, Richard D.

2011-01-01

Two-way active avoidance (2WAA) involves learning Pavlovian (association of a sound cue with a foot shock) and instrumental (shock avoidance) contingencies. To identify regions where dopamine (DA) is involved in mediating 2WAA, we restored DA signaling in specific brain areas of dopamine-deficient (DD) mice by local reactivation of conditionally…

Mortality of sea lions along the central California coast linked to a toxic diatom bloom.

PubMed

Scholin, C A; Gulland, F; Doucette, G J; Benson, S; Busman, M; Chavez, F P; Cordaro, J; DeLong, R; De Vogelaere, A; Harvey, J; Haulena, M; Lefebvre, K; Lipscomb, T; Loscutoff, S; Lowenstine, L J; Marin, R; Miller, P E; McLellan, W A; Moeller, P D; Powell, C L; Rowles, T; Silvagni, P; Silver, M; Spraker, T; Trainer, V; Van Dolah, F M

2000-01-06

Over 400 California sea lions (Zalophus californianus) died and many others displayed signs of neurological dysfunction along the central California coast during May and June 1998. A bloom of Pseudo-nitzschia australis (diatom) was observed in the Monterey Bay region during the same period. This bloom was associated with production of domoic acid (DA), a neurotoxin that was also detected in planktivorous fish, including the northern anchovy (Engraulis mordax), and in sea lion body fluids. These and other concurrent observations demonstrate the trophic transfer of DA resulting in marine mammal mortality. In contrast to fish, blue mussels (Mytilus edulus) collected during the DA outbreak contained no DA or only trace amounts. Such findings reveal that monitoring of mussel toxicity alone does not necessarily provide adequate warning of DA entering the food web at levels sufficient to harm marine wildlife and perhaps humans.

Human influence on sub-regional surface air temperature change over India.

PubMed

Dileepkumar, R; AchutaRao, Krishna; Arulalan, T

2018-06-12

Human activities have been implicated in the observed increase in Global Mean Surface Temperature. Over regional scales where climatic changes determine societal impacts and drive adaptation related decisions, detection and attribution (D&A) of climate change can be challenging due to the greater contribution of internal variability, greater uncertainty in regionally important forcings, greater errors in climate models, and larger observational uncertainty in many regions of the world. We examine the causes of annual and seasonal surface air temperature (TAS) changes over sub-regions (based on a demarcation of homogeneous temperature zones) of India using two observational datasets together with results from a multimodel archive of forced and unforced simulations. Our D&A analysis examines sensitivity of the results to a variety of optimal fingerprint methods and temporal-averaging choices. We can robustly attribute TAS changes over India between 1956-2005 to anthropogenic forcing mostly by greenhouse gases and partially offset by other anthropogenic forcings including aerosols and land use land cover change.

Development of a benthic multimetric index for the Serra da Bocaina bioregion in Southeast Brazil.

PubMed

Baptista, D F; Henriques-Oliveira, A L; Oliveira, R B S; Mugnai, R; Nessimian, J L; Buss, D F

2013-08-01

Brazil faces a challenge to develop biomonitoring tools to be used in water quality assessment programs, but few multimetric indices were developed so far. This study is part of an effort to test and implement programs using benthic macroinvertebrates as bioindicators in Rio de Janeiro State. Our aim was first to test the Multimetric Index for Serra dos Órgãos (SOMI) for a different area--Serra da Bocaina (SB)--in the same ecoregion. We sampled 27 streams of different sizes and altitudes in the SB region. Despite the environmental similarities, results indicated biological differences between reference sites of the two regions. Considering these differences, we decided to develop an index specific for the SB region, the Serra da Bocaina Multimetric Index (MISB). We tested twenty-two metrics for sensitivity to impairment and redundancy, and six metrics were considered valid to integrate the MISB: Family Richness, Trichoptera Richness, % Coleoptera, % Diptera, IBE-IOC index, EPT / Chironomidae ratio. A test of the MISB in eleven sites indicated it was more related to land-use and water physico-chemical parameters than with altitude or stream width, being a useful tool for the monitoring and assessment of streams in the bioregion.

A novel Amoeba proteus 120 kDa actin-binding protein with only 1 filamin repeat and a coiled-coil region.

PubMed

Sobczak, Magdalena; Kocik, Elzbieta; Redowicz, Maria Jolanta

2007-02-01

A novel 120 kDa actin-binding protein (ApABP-F1) was found in Amoeba proteus. It was distributed throughout the cytoplasm, mainly in the subplasma membrane and perinuclear-nuclear areas, enriched in actin. The full-length cDNA of ApABP consisted of 2672 nucleotides with an open reading frame of 878 amino acids, giving a ~95 kDa protein with a theoretical pI value of 5.11. It had a novel domain organization pattern: the N terminus (residues 1-104) contained 1 calponin-homology (CH) domain, followed by only 1 region that was homologous to the filamin repeat (FR, residues 209-324), and a central region (residues 344-577) exhibiting a very high probability of coiled-coil formation, probably engaged in the observed protein dimerization. A phylogenetic tree constructed for CH domains from 25 various proteins revealed that the CH domain of ApABP was most related to that of the hypothetical mouse KIAA0903-like protein, whereas not much relationship to either filamins or the gelation factor (ABP-120) of Dictyostelium discoideum and Entamoeba histolytica was found.

Evaluation in health: participatory methodology and involvement of municipal managers.

PubMed

Almeida, Cristiane Andrea Locatelli de; Tanaka, Oswaldo Yoshimi

2016-08-04

To analyze scopes and limits of the use of participatory methodology of evaluation with municipal health managers and administrators. Qualitative research with health policymakers and managers of the Comissão Intergestores Regional (CIR - Regional Interagency Commission) of a health region of the state of Sao Paulo in Brazil. Representatives from seven member cities participated in seven workshops facilitated by the researchers, with the aim of assessing a specific problem of the care line, which would be used as a tracer of the system integrality. The analysis of the collected empirical material was based on the hermeneutic-dialectic methodology and aimed at the evaluation of the applied participatory methodology, according to its capacity of promoting a process of assessment capable to be used as a support for municipal management. With the participatory approach of evaluation, we were able to promote in-depth discussions with the group, especially related to the construction of integral care and to the inclusion of the user's perspective in decision-making, linked to the search for solution to concrete problems of managers. By joint exploration, the possibility of using data from electronic information systems was opened, as well as information coming directly from the users of the services, to enhance discussions and negotiations between partners. The participants were disbelievers of the replication potential of this type of evaluation without the direct monitoring of the academy, given the difficulty of organizing the process in everyday life, already taken by emergency and political issues. Evaluations of programs and services carried out within the Regional Interagency Commission, starting from the local interest and facilitating the involvement of its members by the use of participatory methodologies, can contribute to the construction of integral care. To the extent that the act of evaluating stay invested with greater significance to the local actors, its involvement with the evaluations at the federal level can also be stimulated. Analisar alcances e limites do uso de metodologia participativa de avaliação junto a gestores e gerentes municipais de saúde. Pesquisa qualitativa com gestores e gerentes de saúde da Comissão Intergestores Regional de uma região de saúde do estado de São Paulo. Representantes de sete municípios membros participaram de sete oficinas facilitadas pelos pesquisadores, com o objetivo de avaliar um problema específico da linha de cuidados sob a perspectiva da integralidade. A análise do material empírico coletado baseou-se na metodologia hermenêutica-dialética e visou a avaliação da metodologia participativa aplicada, segundo sua capacidade de promover um processo de avaliação passível de ser utilizado como suporte à gestão municipal. Com a abordagem participativa de avaliação, foi possível promover debates em profundidade com o grupo, principalmente relacionados à construção da integralidade da atenção e à inclusão da perspectiva do usuário na tomada de decisão, de forma vinculada à busca de solução para problemas concretos dos gestores. Mediante a exploração conjunta, foi aberta a possibilidade de utilização de dados advindos dos sistemas eletrônicos de informação, bem como de informações advindas diretamente dos usuários dos serviços, para enriquecer debates e negociações entre parceiros. Os participantes se mostraram descrentes do potencial de replicação deste tipo de avaliação sem o acompanhamento direto da academia, dada a dificuldade de organização do processo no cotidiano, já tomado por questões emergenciais e políticas. Avaliações de programas e serviços realizadas no âmbito da Comissão Intergestores Regional, partindo do interesse local e facilitando o envolvimento de seus membros pelo uso de metodologias participativas, podem contribuir para a construção da integralidade do cuidado. Na medida em que o ato de avaliar fique investido de maior significado para os atores locais, seu envolvimento com as avaliações em nível federal poderá ser também estimulado.

Explaining the disease phenotype of intergenic SNP through predicted long range regulation.

PubMed

Chen, Jingqi; Tian, Weidong

2016-10-14

Thousands of disease-associated SNPs (daSNPs) are located in intergenic regions (IGR), making it difficult to understand their association with disease phenotypes. Recent analysis found that non-coding daSNPs were frequently located in or approximate to regulatory elements, inspiring us to try to explain the disease phenotypes of IGR daSNPs through nearby regulatory sequences. Hence, after locating the nearest distal regulatory element (DRE) to a given IGR daSNP, we applied a computational method named INTREPID to predict the target genes regulated by the DRE, and then investigated their functional relevance to the IGR daSNP's disease phenotypes. 36.8% of all IGR daSNP-disease phenotype associations investigated were possibly explainable through the predicted target genes, which were enriched with, were functionally relevant to, or consisted of the corresponding disease genes. This proportion could be further increased to 60.5% if the LD SNPs of daSNPs were also considered. Furthermore, the predicted SNP-target gene pairs were enriched with known eQTL/mQTL SNP-gene relationships. Overall, it's likely that IGR daSNPs may contribute to disease phenotypes by interfering with the regulatory function of their nearby DREs and causing abnormal expression of disease genes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Behavioural and biochemical responses following activation of midbrain dopamine pathways by receptor selective neurokinin agonists.

PubMed

Elliott, P J; Mason, G S; Stephens-Smith, M; Hagan, R M

1991-06-01

Preferential activation of mesolimbic and nigro-striatal dopamine (DA) pathways by receptor-selective and peptidase-resistant neurokinin (NK) agonists is reported. The DA cell body region of the mesolimbic pathway appears to be activated by NK agonists selective for NK-1 and NK-3 receptors whereas the DA cell bodies in the substantia nigra are under an excitatory NK-2 receptor-mediated influence. Stimulation of the mesolimbic DA pathway by NK-1 (Ava[L-Pro9,N-Me-Leu10]SP (7-11) [GR73632]) or NK-3 (Senktide) agonists increase locomotor activity. Additional studies showed that this elevated motor response observed after intra-VTA infusion of GR73632 was accompanied by a corresponding increase in DA turnover in the terminal fields of this pathway. Similarly, unilateral activation of the nigro-striatal DA pathway by NK-2 selective agonists (Ava (D-Pro9) SP (7-11) [GR51667] or [Lys3,Gly8,R-Lac-Leu9]NKA (3-10) [GR64349]) elicit contralateral rotational activity and an increase in DA turnover in the ipsilateral striatum. The rotational response was attenuated by prior administration of an NK-2 antagonist (cyclo (Gln, Trp, Phe, Gly, Leu, Met)] L-659877]) into the nigra. Peripheral injection of haloperidol, a DA antagonist, also blocked the NK-2 agonist induced rotations.

Industry Studies 2002: Construction

DTIC Science & Technology

2002-01-01

Jacksonville, FL Rotary Club of San Juan, San Juan, PR Tren Urbano Subway Project, San Juan, PR U.S. Army South, San Juan, PR U.S. Coast Guard Housing Project...Bechtel Corporation (IBM Plant Construction Site), Shanghai American Chamber of Commerce, Shanghai Urban Planning Exhibit, Shanghai 3 INTRODUCTION The...of states have or are working on a statewide or agency-wide privatization plan , including California, Maryland, Massachusetts, Michigan and

Translations on Narcotics and Dangerous Drugs No. 270.

DTIC Science & Technology

1976-11-04

persons arrested were: Hugo Norberto Ammirante,30; Urbano Vicente Toledo, 31; Carlos Roberto Cejas, 28; Leandro Alberto Herrera, 27; and... Carlos Alberto Ignatier, 33. The ring brought cocaine from Bolivia and processed it in Salt a, selling it mainly to someone known as El Chuco who...Garcia. Some escaped to Brownsville, among them Inspector Carlos Morales who walked across the bridge and Supervisor Joaquin Cardenas who abandoned

Urban Ecosystems. Environment Booklet 4. Teacher's Edition =Ecosist urbanos. Libro del medio ambiente 4. Manual para El Maestro.

ERIC Educational Resources Information Center

California State Univ., Los Angeles. National Dissemination and Assessment Center.

The booklet is part of a grade 10-12 social studies series produced for bilingual education. The series consists of six major thematic modules, with four to five booklets in each. The interdisciplinary modules are based on major ideas and are designed to help students understand some major human problems and make sound, responsive decisions to…

Modulating dopamine release by optogenetics in transgenic mice reveals terminal dopaminergic dynamics

PubMed Central

Lu, Yao; Driscoll, Nicolette; Ozden, Ilker; Yu, Zeyang; Nurmikko, Arto V.

2015-01-01

Abstract. Dopamine (DA) release and uptake dynamics in the nucleus accumbens (NAc) have important implications for neurological diseases and mammalian animal behaviors. We demonstrate here the use of cell-type-specific optogenetic targeting in conjunction with fast-scan cyclic voltammetry applied to brain slices prepared from specifically tailored transgenic mice, which conditionally express channelrhodopsin-2 (ChR2) through dopamine transporter (DAT)-Cre. Terminal dopaminergic dynamics and the direct manipulation of induced DA release level by controlling light intensity, pulse width, and the shape of stimulation waveforms were studied. Effective cell terminal-targeting optogenetic induction of DA release at physiological levels in NAc is demonstrated and discussed. It was found that delivering more light energy by increasing stimulation intensity and length is not the only way to control DA release; the temporal shape of the stimulus waveform at light onset is also critically related to induced DA concentrations. In addition, DA uptake dynamics as well as the recovery of the presynaptic releasable DA pool are studied and modeled. More broadly, our experimental findings provide important further evidence for effectively applying optogenetics to induce neurotransmitter release in the behaviorally relevant region of the brain in a highly cell-type selective context. PMID:26171413

Characteristics of Dynamic Magnetic Resonance Image Enhancement in Prolactinomas Resistant to Dopamine Agonist Therapy

PubMed Central

Guo, Qinghua; Erickson, Bradley J.; Chang, Alice Y.; Erickson, Dana

2015-01-01

Objective To determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. Methods We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, Minnesota). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naïve groups, and between the first and follow-up dMRIs. Results We identified 49 patients with prolactinomas, with 6 (12.2%) that showed DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group vs the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P=.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P=.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% CI, 1.07-3.27; P=.02). Conclusions dMRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas. PMID:25551412

Characteristics of dynamic magnetic resonance image enhancement in prolactinomas resistant to dopamine agonist therapy.

PubMed

Guo, Qinghua; Erickson, Bradley J; Chang, Alice Y; Erickson, Dana

2015-03-01

The objective of this study was to determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, MN). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naive groups, and between the first and follow-up dMRIs. We identified 49 patients with prolactinomas, with 6 (12.2%) showing DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group versus the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P = 0.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P = 0.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% confidence interval, 1.07-3.27; P = 0.02). Dynamic MRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas.

Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice.

PubMed

Hirata, H; Ladenheim, B; Carlson, E; Epstein, C; Cadet, J L

1996-04-01

Methamphetamine (METH) has long-lasting neurotoxic effects on the nigrostriatal dopamine (DA) system of rodents. METH-induced neurotoxicity is thought to involve release of DA in presynaptic DA terminals, which is associated with increased formation of oxygen-based free radicals. We have recently shown that METH-induced striatal DA depletion is attenuated in transgenic (Tg) mice that express the human CuZn-superoxide dismutase (SOD) enzyme. That study did not specifically address the issue of loss of DA terminals. In the present study, we have used receptor autoradiographic studies of [(125)I]RTI-121-labeled DA uptake sites to evaluate the effects of several doses of METH on striatal DA terminals of Non-Tg as well as of heterozygous and homozygous SOD-Tg mice. In Non-Tg mice, METH caused decreases in striatal DA uptake sites in a dose-dependent fashion. The loss of DA terminals was more prominent in the lateral region than in the medial subdivisions of the striatum. In SOD-Tg mice, the loss of DA terminals caused by METH was attenuated in a gene dosage-dependent fashion, with the homozygous mice showing the greatest protection. Female mice were somewhat more resistant than male mice against these deleterious effects of METH. These results provide further evidence for a role of superoxide radicals in the long-term effects of METH. They also suggest the notion of a gender-specific handling of oxidative stress.

Preconditioning of the background error covariance matrix in data assimilation for the Caspian Sea

NASA Astrophysics Data System (ADS)

Arcucci, Rossella; D'Amore, Luisa; Toumi, Ralf

2017-06-01

Data Assimilation (DA) is an uncertainty quantification technique used for improving numerical forecasted results by incorporating observed data into prediction models. As a crucial point into DA models is the ill conditioning of the covariance matrices involved, it is mandatory to introduce, in a DA software, preconditioning methods. Here we present first studies concerning the introduction of two different preconditioning methods in a DA software we are developing (we named S3DVAR) which implements a Scalable Three Dimensional Variational Data Assimilation model for assimilating sea surface temperature (SST) values collected into the Caspian Sea by using the Regional Ocean Modeling System (ROMS) with observations provided by the Group of High resolution sea surface temperature (GHRSST). We also present the algorithmic strategies we employ.

Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida).

PubMed

Linck, Viviane M; Ganzella, Marcelo; Herrmann, Ana P; Okunji, Christopher O; Souza, Diogo O; Antonelli, Marta C; Elisabetsky, Elaine

2015-01-15

Alstonine is the major component of plant based remedies that traditional psychiatrists use in Nigeria. Alstonine is an indole alkaloid that has an antipsychotic experimental profile comparable with that of clozapine and is compatible with the alleged effects in mental patients. Representing a desirable innovation in the pharmacodynamics of antipsychotic medications, the evidence indicates that alstonine does not bind to D2 dopamine receptors (D2R) and differentially regulates dopamine in the cortical and limbic areas. The purpose of this study was to further investigate the effects of alstonine on D2R binding in specific brain regions using quantitative autoradiography (QAR) and its effects on dopamine (DA) uptake in mouse striatal synaptosomes. The effects of alstonine on D2R binding were determined in the nucleus accumbens and caudate-putamen using QAR in mice treated with alstonine doses that have antipsychotic effects. The effects of alstonine [3H]DA uptake were assessed in synaptosomes prepared from striatal tissue obtained from mice treated acutely or for 7 days with alstonine. Alstonine did not change the D2R binding densities in the studied regions. DA uptake was increased after acute (but not after 7 days) treatment with alstonine. Consistent with the alstonine behavioral profile, these results indicate that alstonine indirectly modulates DA receptors, specifically by modulating DA uptake. This unique mechanism for DA transmission modulation contributes to the antipsychotic-like effects of alstonine and is compatible with its behavioral profile in mice and alleged effects in patients. These results may represent an innovation in the antipsychotic development field. Copyright © 2014 Elsevier GmbH. All rights reserved.

The amino-terminal matrix assembly domain of fibronectin stabilizes cell shape and prevents cell cycle progression.

PubMed

Christopher, R A; Judge, S R; Vincent, P A; Higgins, P J; McKeown-Longo, P J

1999-10-01

Adhesion to the extracellular matrix modulates the cellular response to growth factors and is critical for cell cycle progression. The present study was designed to address the relationship between fibronectin matrix assembly and cell shape or shape dependent cellular processes. The binding of fibronectin's amino-terminal matrix assembly domain to adherent cells represents the initial step in the assembly of exogenous fibronectin into the extracellular matrix. When added to monolayers of pulmonary artery endothelial cells, the 70 kDa fragment of fibronectin (which contains the matrix assembly domain) stabilized both the extracellular fibronectin matrix as well as the actin cytoskeleton against cytochalasin D-mediated structural reorganization. This activity appeared to require specific fibronectin sequences as fibronectin fragments containing the cell adhesion domain as well as purified vitronectin were ineffective inhibitors of cytochalasin D-induced cytoarchitectural restructuring. Such pronounced morphologic consequences associated with exposure to the 70 kDa fragment suggested that this region of the fibronectin molecule may affect specific growth traits known to be influenced by cell shape. To assess this possibility, the 70 kDa fragment was added to scrape-wounded monolayers of bovine microvessel endothelium and the effects on two shape-dependent processes (i.e. migration and proliferation) were measured as a function of time after injury and location from the wound. The addition of amino-terminal fragments of fibronectin to the monolayer significantly inhibited (by >50%) wound closure. Staining of wounded monolayers with BrdU, moreover, indicated that either the 70 kDa or 25 kDa amino-terminal fragments of fibronectin, but not the 40 kDa collagen binding fragment, also inhibited cell cycle progression. These results suggest that the binding of fibronectin's amino-terminal region to endothelial cell layers inhibits cell cycle progression by stabilizing cell shape.

Scene construction in developmental amnesia: An fMRI study☆

PubMed Central

Mullally, Sinéad L.; Vargha-Khadem, Faraneh; Maguire, Eleanor A.

2014-01-01

Amnesic patients with bilateral hippocampal damage sustained in adulthood are generally unable to construct scenes in their imagination. By contrast, patients with developmental amnesia (DA), where hippocampal damage was acquired early in life, have preserved performance on this task, although the reason for this sparing is unclear. One possibility is that residual function in remnant hippocampal tissue is sufficient to support basic scene construction in DA. Such a situation was found in the one amnesic patient with adult-acquired hippocampal damage (P01) who could also construct scenes. Alternatively, DA patients’ scene construction might not depend on the hippocampus, perhaps being instead reliant on non-hippocampal regions and mediated by semantic knowledge. To adjudicate between these two possibilities, we examined scene construction during functional MRI (fMRI) in Jon, a well-characterised patient with DA who has previously been shown to have preserved scene construction. We found that when Jon constructed scenes he activated many of the regions known to be associated with imagining scenes in control participants including ventromedial prefrontal cortex, posterior cingulate, retrosplenial and posterior parietal cortices. Critically, however, activity was not increased in Jon's remnant hippocampal tissue. Direct comparisons with a group of control participants and patient P01, confirmed that they activated their right hippocampus more than Jon. Our results show that a type of non-hippocampal dependent scene construction is possible and occurs in DA, perhaps mediated by semantic memory, which does not appear to involve the vivid visualisation of imagined scenes. PMID:24231038

Scene construction in developmental amnesia: an fMRI study.

PubMed

Mullally, Sinéad L; Vargha-Khadem, Faraneh; Maguire, Eleanor A

2014-01-01

Amnesic patients with bilateral hippocampal damage sustained in adulthood are generally unable to construct scenes in their imagination. By contrast, patients with developmental amnesia (DA), where hippocampal damage was acquired early in life, have preserved performance on this task, although the reason for this sparing is unclear. One possibility is that residual function in remnant hippocampal tissue is sufficient to support basic scene construction in DA. Such a situation was found in the one amnesic patient with adult-acquired hippocampal damage (P01) who could also construct scenes. Alternatively, DA patients' scene construction might not depend on the hippocampus, perhaps being instead reliant on non-hippocampal regions and mediated by semantic knowledge. To adjudicate between these two possibilities, we examined scene construction during functional MRI (fMRI) in Jon, a well-characterised patient with DA who has previously been shown to have preserved scene construction. We found that when Jon constructed scenes he activated many of the regions known to be associated with imagining scenes in control participants including ventromedial prefrontal cortex, posterior cingulate, retrosplenial and posterior parietal cortices. Critically, however, activity was not increased in Jon's remnant hippocampal tissue. Direct comparisons with a group of control participants and patient P01, confirmed that they activated their right hippocampus more than Jon. Our results show that a type of non-hippocampal dependent scene construction is possible and occurs in DA, perhaps mediated by semantic memory, which does not appear to involve the vivid visualisation of imagined scenes. © 2013 Published by Elsevier Ltd.

Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping.

PubMed

Beier, Kevin T; Steinberg, Elizabeth E; DeLoach, Katherine E; Xie, Stanley; Miyamichi, Kazunari; Schwarz, Lindsay; Gao, Xiaojing J; Kremer, Eric J; Malenka, Robert C; Luo, Liqun

2015-07-30

Dopamine (DA) neurons in the midbrain ventral tegmental area (VTA) integrate complex inputs to encode multiple signals that influence motivated behaviors via diverse projections. Here, we combine axon-initiated viral transduction with rabies-mediated trans-synaptic tracing and Cre-based cell-type-specific targeting to systematically map input-output relationships of VTA-DA neurons. We found that VTA-DA (and VTA-GABA) neurons receive excitatory, inhibitory, and modulatory input from diverse sources. VTA-DA neurons projecting to different forebrain regions exhibit specific biases in their input selection. VTA-DA neurons projecting to lateral and medial nucleus accumbens innervate largely non-overlapping striatal targets, with the latter also sending extensive extra-striatal axon collaterals. Using electrophysiology and behavior, we validated new circuits identified in our tracing studies, including a previously unappreciated top-down reinforcing circuit from anterior cortex to lateral nucleus accumbens via VTA-DA neurons. This study highlights the utility of our viral-genetic tracing strategies to elucidate the complex neural substrates that underlie motivated behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

Isolation, purification and characterization of collagenase from hepatopancreas of the land snail Achatina fulica.

PubMed

Indra, D; Ramalingam, K; Babu, Mary

2005-09-01

Collagenase (matrix metalloproteinase-1, EC:3.4.24.7) was isolated from the hepatopancreas of Achatina fulica and characterized for its enzymatic activity and immunological properties. Procollagenase was isolated using ammonium sulphate precipitation and gel filtration, followed by purification by reverse-phase high performance liquid chromatography in the presence of trifluoroacetic acid and by dialysis in neutral buffer. In the presence of SDS and beta-mercaptoethanol, the procollagenase resolved into two subunits with molecular masses of 63 and 28 kDa, respectively. The 63 kDa fragment retained its ability to bind and degrade gelatin, but the 28 kDa was inactive. Analysis by 2D gel electrophoresis revealed that the 63 kDa fragment was basic (pIs 7.6, 7.8 and 8.15), while the 28 kDa fragment was acidic (pI 4.7 and 5.1). Western blot analysis confirmed the identity of collagenase, as only matrix metalloproteinase-1 rabbit antibodies against human matrix metalloproteinase-1 (N-terminal region) recognized both the isolated procollagenase and the 63 kDa fragment.

Absence of Ret Signaling in Mice Causes Progressive and Late Degeneration of the Nigrostriatal System

PubMed Central

Kramer, Edgar R; Aron, Liviu; Ramakers, Geert M. J; Seitz, Sabine; Zhuang, Xiaoxi; Beyer, Klaus; Smidt, Marten P; Klein, Rüdiger

2007-01-01

Support of ageing neurons by endogenous neurotrophic factors such as glial cell line–derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) may determine whether the neurons resist or succumb to neurodegeneration. GDNF has been tested in clinical trials for the treatment of Parkinson disease (PD), a common neurodegenerative disorder characterized by the loss of midbrain dopaminergic (DA) neurons. BDNF modulates nigrostriatal functions and rescues DA neurons in PD animal models. The physiological roles of GDNF and BDNF signaling in the adult nigrostriatal DA system are unknown. We generated mice with regionally selective ablations of the genes encoding the receptors for GDNF (Ret) and BDNF (TrkB). We find that Ret, but not TrkB, ablation causes progressive and adult-onset loss of DA neurons specifically in the substantia nigra pars compacta, degeneration of DA nerve terminals in striatum, and pronounced glial activation. These findings establish Ret as a critical regulator of long-term maintenance of the nigrostriatal DA system and suggest conditional Ret mutants as useful tools for gaining insights into the molecular mechanisms involved in the development of PD. PMID:17298183

Use of generic medicines by the Brazilian population: an evaluation of PNAUM 2014.

PubMed

Bertoldi, Andréa Dâmaso; Arrais, Paulo Sergio Dourado; Tavares, Noemia Urruth Leão; Ramos, Luiz Roberto; Luiza, Vera Lucia; Mengue, Sotero Serrate; Dal-Pizzol, Tatiane da Silva; Farias, Mareni Rocha; Oliveira, Maria Auxiliadora

2016-12-01

To analyze the existence of differences in the use of generic medicines in Brazil according to demographic and socioeconomic variables and acquisition sources of the medicines. Population-based cross-sectional study, conducted with data from the Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines). Data collection took place between September, 2013 and February, 2014 in homes of Brazilian cities (urban area). The use of medicines has been investigated in relation to the treatment of chronic diseases and, in the case of acute events, regarding use over the previous 15 days. Generics were identified by visualization of packaging presented by the users of the medicines. The independent variables used were sex, age, education level, economic class, and region of the Country. The statistical significance of differences between the groups was evaluated by Pearson's Chi-squared test, considering a 5% significance level. The prevalence of generic medicines use was 45.5% (95%CI 43.7-47.3). There was no difference considering education level. The prevalence was higher in females (47.0%; 95%CI 44.9-49.0) than in males (43.1%; 95%CI 40.5-45.8), and were higher with increasing age. Generic medicines were more used in the economic class C (47.0%; 95%CI 44.9-49.1) and in the South (50.6%; 95%CI 46.6-54.6) and Southeast (49.9%; 95%CI 46.8-53.0) regions. Generics accounted for 37.3% of the medicines provided by the Brazilian Unified Health System. Currently, there is a choice of purchase or free provision by the Brazilian Unified Health System, characterized by quality assurance and reduced price regarding branded medicines considered as reference. In the private market, a considerable part of the population is choosing generic medicines thanks to the availability of this option for virtually all medicines most used by the population. Analisar se há diferença no uso de medicamentos genéricos no Brasil segundo variáveis demográficas, socioeconômicas e fontes de obtenção dos medicamentos. Estudo transversal de base populacional, conduzido com dados da Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM), com coleta de dados entre setembro de 2013 e fevereiro de 2014 em residências de municípios brasileiros urbanos. O uso dos medicamentos foi investigado em relação ao tratamento de doenças crônicas e, no caso de eventos agudos, quanto ao uso nos últimos 15 dias. Os genéricos foram identificados por visualização das embalagens apresentadas pelos usuários dos medicamentos. As variáveis independentes utilizadas foram sexo, idade, escolaridade, classe econômica e região do País. A avaliação da significância estatística das diferenças entre os grupos foi analisada pelo teste Qui-quadrado de Pearson, considerando nível de significância de 5%. A prevalência de uso de genéricos foi de 45,5% (IC95% 43,7-47,3). Não houve diferença por escolaridade, as prevalências foram maiores no sexo feminino (47,0%; IC95% 44,9-49,0) em relação ao masculino (43,1%; IC95% 40,5-45,8) e foram crescentes com o aumento da idade. Maiores usos de genéricos foram encontrados na classe econômica C (47,0%; IC95% 44,9-49,1) e nas regiões Sul (50,6%; IC95% 46,6-54,6) e Sudeste (49,9%; IC95% 46,8-53,0). Observou-se ainda que os genéricos representaram 37,3% dos medicamentos disponibilizados pelo Sistema Único de Saúde . Pode-se concluir que hoje existe uma alternativa de compra ou fornecimento gratuito pelo Sistema Único de Saúde, caracterizada por garantia de qualidade e preço reduzido em relação aos medicamentos de marca comercial considerados como referência. No mercado privado, boa parte da população está optando pelo uso de medicamentos genéricos, graças à disponibilidade dessa opção para praticamente todos os medicamentos mais utilizados pela população.

Mass and Charge Measurements on Heavy Ions

PubMed Central

Sugai, Toshiki

2017-01-01

The relationship between mass and charge has been a crucial topic in mass spectrometry (MS) because the mass itself is typically evaluated based on the m/z ratio. Despite the fact that this measurement is indirect, a precise mass can be obtained from the m/z value with a high m/z resolution up to 105 for samples in the low mass and low charge region under 10,000 Da and 20 e, respectively. However, the target of MS has recently been expanded to the very heavy region of Mega or Giga Da, which includes large particles and biocomplexes, with very large and widely distributed charge from kilo to Mega range. In this region, it is necessary to evaluate charge and mass simultaneously. Recent studies for simultaneous mass and charge observation and related phenomena are discussed in this review. PMID:29302406

Dynamic fluctuations in dopamine efflux in the prefrontal cortex and nucleus accumbens during risk-based decision making.

PubMed

St Onge, Jennifer R; Ahn, Soyon; Phillips, Anthony G; Floresco, Stan B

2012-11-21

Mesocorticolimbic dopamine (DA) has been implicated in cost/benefit decision making about risks and rewards. The prefrontal cortex (PFC) and nucleus accumbens (NAc) are two DA terminal regions that contribute to decision making in distinct manners. However, how fluctuations of tonic DA levels may relate to different aspects of decision making remains to be determined. The present study measured DA efflux in the PFC and NAc with microdialysis in well trained rats performing a probabilistic discounting task. Selection of a small/certain option always delivered one pellet, whereas another, large/risky option yielded four pellets, with probabilities that decreased (100-12.5%) or increased (12.5-100%) across four blocks of trials. Yoked-reward groups were also included to control for reward delivery. PFC DA efflux during decision making decreased or increased over a session, corresponding to changes in large/risky reward probabilities. Similar profiles were observed from yoked-rewarded rats, suggesting that fluctuations in PFC DA reflect changes in the relative rate of reward received. NAc DA efflux also showed decreasing/increasing trends over the session during both tasks. However, DA efflux was higher during decision making on free- versus forced-choice trials and during periods of greater reward uncertainty. Moreover, changes in NAc DA closely tracked shifts in choice biases. These data reveal dynamic and dissociable fluctuations in PFC and NAc DA transmission associated with different aspects of risk-based decision making. PFC DA may signal changes in reward availability that facilitates modification of choice biases, whereas NAc DA encodes integrated signals about reward rates, uncertainty, and choice, reflecting implementation of decision policies.

Sex differences in the relationship of regional dopamine release to affect and cognitive function in striatal and extrastriatal regions using positron emission tomography and [¹⁸F]fallypride.

PubMed

Riccardi, Patrizia; Park, Sohee; Anderson, Sharlet; Doop, Mikisha; Ansari, M Sib; Schmidt, Dennis; Baldwin, Ronald

2011-02-01

The purpose of this study was to examine sex differences in the correlations of d-amphetamine (d-AMPH) induced displacements of [¹⁸F]fallypride in striatal and extrastriatal regions in relation to affect and cognition. Seven male and six female healthy subjects, whose mean age was 25.9 years, underwent positron emission tomography (PET) with [¹⁸F]fallypride at baseline and 3 h after a 0.43 mg/kg oral dose of d-AMPH. Percent displacements in striatal and extrastriatal regions were calculated using regions of interest (ROI) analysis and on a pixel-by-pixel basis. Subjects underwent neuropsychological testing prior to the baseline PET study and one hour after d-AMPH administration for the second PET. In order to examine the subjective effect of d-AMPH, subjects rated PANAS at baseline and after administration of amphetamine. Correlations of changes in cognition and affect with regional dopamine (DA) release revealed several significant sex related differences. The results of this study demonstrate in vivo sex related differences in the relationship of regional DA release to affect and cognitive function. Copyright © 2010 Wiley-Liss, Inc.

Sex differences in corticolimbic dopamine and serotonin systems in the rat and the effect of postnatal handling.

PubMed

Duchesne, Annie; Dufresne, Marc M; Sullivan, Ron M

2009-03-17

Stress-related psychopathology is particularly prevalent in women, although the neurobiological reason(s) for this are unclear. Dopamine (DA) and serotonin (5-HT) systems however, are known to play important adaptive roles in stress and emotion regulation. The aims of the present study included examination of sex differences in stress-related behaviour and neuroendocrine function as well as post mortem neurochemistry, with the main hypothesis that corticolimbic DA and 5-HT systems would show greater functional activity in males than females. Long-Evans rats of both sexes were employed. Additional factors incorporated included differential postnatal experience (handled vs. nonhandled) and adult mild stress experience (acute vs. repeated (5) restraint). Regional neurochemistry measures were conducted separately for left and right hemispheres. Behaviourally, females showed more exploratory behaviour than males in the elevated plus maze and an openfield/holeboard apparatus. Females also exhibited significantly higher levels of adrenocorticotrophic hormone and corticosterone at all time points in response to restraint stress than males across treatment conditions, although both sexes showed similar habituation in stress-induced ACTH activation with repeated mild stress. Neurochemically, females had significantly higher levels of DA (in ventromedial prefrontal cortex (vmPFC), insular cortex and n. accumbens) and 5-HT (in vmPFC, amygdala, dorsal hippocampus and insula) than males. In contrast, males had higher levels of the DA metabolite DOPAC or DOPAC/DA ratios than females in all five regions and higher levels of the 5-HT metabolite 5-HIAA or 5-HIAA/5-HT ratios in vmPFC, amygdala and insula, suggesting greater neurotransmitter utilization in males. Moreover, handling treatment induced a significant male-specific upregulation of 5-HT metabolism in all regions except n. accumbens. Given the adaptive role of 5-HT and DAergic neurotransmission in stress and emotion regulation, the intrinsic sex differences we report in the functional status of these systems across conditions, may be highly relevant to the differential vulnerability to disorders of stress and emotion regulation.

Conflict in the Middle East: Egyptian Policy and Strategy to Create an Egyptian Proposal to Achieve Stability in the Region.

DTIC Science & Technology

1986-05-14

trainina ca:res. There are nartv schools at the provincial level and a senior one in Da- ascus . O’nozition: the Challence fro::. without The !:usli...Da: ascus zja.. :rinci1 fac’.cr, and fou~ht on difrnts1. ~ h itro coriZlict d-evactatin<- tha t counitrv.2 7 Syria’s involve:. ,ent in the Le"b.anCSQ...ro_,A~ to Lhn: runs tnrouz:;i Da:.. ascus . Conversely, it has mia_ th’e Palest ina lje_)anese realize thlat the roa.Z to thie outsiue worl,’ lea ’s

Brain imaging studies of the cocaine addict: Implications for reinforcement and addiction

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

Volkow, N.D.; Fowler, J.S.

1995-07-01

These studies document dopaminergic abnormalities in cocaine abusers. They also suggest a regulatory role of Dopamine (DA) in frontal metabolism. The correlation of striatal D{sub 2} receptor availability with metabolism was strongest for orbital frontal cortex (OFC) cingulate and prefrontal cortices. In cocaine abusers tested during early withdrawal (<1 week) the OFC was found to be hypermetabolic and metabolism in OFC and prefrontal cortices were found to be significantly associated with cocaine craving . Thus, we postulate that repeated and intermittent DA stimulation, as seen during a cocaine binge, activates the prefrontal and OFC cortices increasing the drive to compulsivelymore » self-administer cocaine. During cocaine discontinuation and protracted withdrawal and with decreased DA stimulation, these frontal cortical regions become hyponietabolic. Dopaminergic stimulation by a DA-enhancing drug and/or environmental conditioning will reactivate these frontal regions resetting the compulsion to self-administer cocaine and the inability to terminate this behavior. The pharmacokionetic studies with [11C]cocaine are consistent with behavioral and pharmacological studies in animals as well as in vitro studies which have revealed that while the mechanisms for cocaine`s reinforcing properties are complex, they partly involve the brain`s dopamine system and also highlight the importance of cocaine`s pharmacokinetic on its unique reinforcing properties.« less

Modeling Parkinson's disease falls associated with brainstem cholinergic systems decline.

PubMed

Kucinski, Aaron; Sarter, Martin

2015-04-01

In addition to the primary disease-defining symptoms, approximately half of patients with Parkinson's disease (PD) suffer from postural instability, impairments in gait control and a propensity for falls. Consistent with evidence from patients, we previously demonstrated that combined striatal dopamine (DA) and basal forebrain (BF) cholinergic cell loss causes falls in rats traversing dynamic surfaces. Because evidence suggests that degeneration of brainstem cholinergic neurons arising from the pedunculopontine nucleus (PPN) also contributes to impaired gait and falls, here we assessed the effects of selective cholinergic PPN lesions in combination with striatal DA loss or BF cholinergic cells loss as well as losses in all 3 regions. Results indicate that all combination losses that included the BF cholinergic system slowed traversal and increased slips and falls. However, the performance of rats with losses in all 3 regions (PPN, BF, and DA) was not more severely impaired than following combined BF cholinergic and striatal DA lesions. These results confirm the hypothesis that BF cholinergic-striatal disruption of attentional-motor interactions is a primary source of falls. Additional losses of PPN cholinergic neurons may worsen posture and gait control in situations not captured by the current testing conditions. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Cloning and expression of 130-kd mosquito-larvicidal delta-endotoxin gene of Bacillus thuringiensis var. Israelensis in Escherichia coli.

PubMed

Angsuthanasombat, C; Chungjatupornchai, W; Kertbundit, S; Luxananil, P; Settasatian, C; Wilairat, P; Panyim, S

1987-07-01

Five recombinant E. coli clones exhibiting toxicity to Aedes aegypti larvae were obtained from a library of 800 clones containing XbaI DNA fragments of 110 kb plasmid from B. thuringiensis var. israelensis. All the five clones (pMU 14/258/303/388/679) had the same 3.8-kb insert and encoded a major protein of 130 kDa which was highly toxic to A. aegypti larvae. Three clones (pMU 258/303/388) transcribed the 130 kD a gene in the same direction as that of lac Z promoter of pUC12 vector whereas the transcription of the other two (pMU 14/679) was in the opposite direction. A 1.9-kb fragment of the 3.8 kb insert coded for a protein of 65 kDa. Partial DNA sequence of the 3.8 kb insert, corresponding to the 5'-terminal of the 130 kDa gene, revealed a continuous reading frame, a Shine-Dalgarno sequence and a tentative 5'-regulatory region. These results demonstrated that the 3.8 kb insert is a minimal DNA fragment containing a regulatory region plus the coding sequence of the 130 kDa protein that is highly toxic to mosquito larvae.

A multivariate prediction model for Rho-dependent termination of transcription.

PubMed

Nadiras, Cédric; Eveno, Eric; Schwartz, Annie; Figueroa-Bossi, Nara; Boudvillain, Marc

2018-06-21

Bacterial transcription termination proceeds via two main mechanisms triggered either by simple, well-conserved (intrinsic) nucleic acid motifs or by the motor protein Rho. Although bacterial genomes can harbor hundreds of termination signals of either type, only intrinsic terminators are reliably predicted. Computational tools to detect the more complex and diversiform Rho-dependent terminators are lacking. To tackle this issue, we devised a prediction method based on Orthogonal Projections to Latent Structures Discriminant Analysis [OPLS-DA] of a large set of in vitro termination data. Using previously uncharacterized genomic sequences for biochemical evaluation and OPLS-DA, we identified new Rho-dependent signals and quantitative sequence descriptors with significant predictive value. Most relevant descriptors specify features of transcript C>G skewness, secondary structure, and richness in regularly-spaced 5'CC/UC dinucleotides that are consistent with known principles for Rho-RNA interaction. Descriptors collectively warrant OPLS-DA predictions of Rho-dependent termination with a ∼85% success rate. Scanning of the Escherichia coli genome with the OPLS-DA model identifies significantly more termination-competent regions than anticipated from transcriptomics and predicts that regions intrinsically refractory to Rho are primarily located in open reading frames. Altogether, this work delineates features important for Rho activity and describes the first method able to predict Rho-dependent terminators in bacterial genomes.

Hepatitis Delta virus genotype 8 infection in Northeast Brazil: inheritance from African slaves?

PubMed

Barros, L M F; Gomes-Gouvêa, M S; Pinho, J R R; Alvarado-Mora, M V; Dos Santos, A; Mendes-Corrêa, M C J; Caldas, A J M; Sousa, M T; Santos, M D C; Ferreira, A S P

2011-09-01

Hepatitis Delta virus (HDV) is endemic worldwide, but its prevalence varies in different geographical areas. While in the Brazilian Amazon, HDV is known to be endemic and to represent a significant public health problem, few studies have assessed its prevalence in other regions in the country. This study evaluated the seroprevalence of HDV among HBsAg chronic carriers from Maranhão state, a region located in the Northeast of Brazil. Among 133 patients, 5 had anti-HD, of whom 3 had HDV RNA. HDV genotypes were characterized by Bayesian phylogenetic analysis of nucleotide sequences from the HDAg coding region. HDV-3 was identified in one patient who lives in Maranhão, but was born in Amazonas state (Western Amazon basin). Phylogenetic analysis shows that this HDV-3 sequence grouped with other HDV-3 sequences isolated in this state, which suggests that the patient probably contracted HDV infection there. Surprisingly, the other two patients were infected with HDV-8, an African genotype. These patients were born and have always lived in Urbano Santos, a rural county of Maranhão state, moreover they had never been to Africa and denied any contact with people from that continent. This is the first description of the HDV-8 in non-native African populations. This genotype may have been introduced to Brazil through the slaves brought to the country from the West Africa regions during the 16-18th centuries. Our results indicate that the need of clinical and epidemiological studies to investigate the presence of this infection in other areas in Brazil. Copyright © 2011 Elsevier B.V. All rights reserved.

Natives in Blue: The Employment of Armed Auxiliaries in the Philippines, 1899-1913

DTIC Science & Technology

2012-12-06

responsibility of administering its accidental empire without any civil official on hand, without a plan to govern its new colonial possessions, and...moved well past normal lawlessness and approached open rebellion. Proper understanding of why operations were planned and executed as they were, and...lieutenants, Brigadier General Urbano Lacuna. On 23 March 1901, Aguinaldo, the self-proclaimed President of the Philippine Revolutionary Government

Construction. A Report on the Industry

DTIC Science & Technology

2004-06-01

Transportation and Tres Urbano Subway Project, San Juan, Puerto Rico U.S. Corps of Engineers, San Juan, Puerto Rico U.S. Corps of Engineers, Mobile...recently approved a plan to privatize construction of over 6,000 miles of expressways through the use of a build, transfer, and operate options.xl...security standards in Federal facilities, including an aggressive plan to build and renovate embassies and consular offices worldwide.xlv The

Role of Dopamine Signaling in Drug Addiction.

PubMed

Chen, Wan; Nong, Zhihuan; Li, Yaoxuan; Huang, Jianping; Chen, Chunxia; Huang, Luying

2017-01-01

Addiction is a chronic, relapsing disease of the brain that includes drug-induced compulsive seeking behavior and consumption of drugs. Dopamine (DA) is considered to be critical in drug addiction due to reward mechanisms in the midbrain. In this article, we review the major animal models in addictive drug experiments in vivo and in vitro. We discuss the relevance of the structure and pharmacological function of DA receptors. To improve the understanding of the role of DA receptors in reward pathways, specific brain regions, including the Ventral tegmental area, Nucleus accumbens, Prefrontal cortex, and Habenula, are highlighted. These factors contribute to the development of novel therapeutic targets that act at DA receptors. In addiction, the development of neuroimaging method will increase our understanding of the mechanisms underlying drug addiction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Norepinephrine Activates Dopamine D4 Receptors in the Rat Lateral Habenula

PubMed Central

Root, David H.; Hoffman, Alexander F.; Good, Cameron H.; Zhang, Shiliang; Gigante, Eduardo

2015-01-01

The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that >90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2 (VMAT2) mRNA, and there is little coexpression of TH and VMAT2 protein in this mesohabenular pathway. Consistent with this, electrical stimulation of LHb did not evoke DA-like signals, assessed with fast-scan cyclic voltammetry. However, electrophysiological currents that were inhibited by L741,742, a DA-D4-receptor antagonist, were observed in LHb neurons when DA uptake or degradation was blocked. To prevent DA activation of D4 receptors, we repeated this experiment in LHb slices from DA-depleted rats. However, this did not disrupt D4 receptor activation initiated by the dopamine transporter inhibitor, GBR12935. As the LHb is also targeted by noradrenergic afferents, we examined whether GBR12935 activation of DA-D4 receptors occurred in slices depleted of norepinephrine (NE). Unlike DA, NE depletion prevented the activation of DA-D4 receptors. Moreover, direct application of NE elicited currents in LHb neurons that were blocked by L741,742, and GBR12935 was found to be a more effective blocker of NE uptake than the NE-selective transport inhibitor nisoxetine. These findings demonstrate that NE is released in the rat LHb under basal conditions and that it activates DA-D4 receptors. Therefore, NE may be an important regulator of LHb function. PMID:25716845

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate

PubMed Central

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-01-01

The central extended amygdala (CEA) has been conceptualized as a ‘macrosystem’ that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the ‘limbic-associative’ striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning. PMID:28220796

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

PubMed

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

Molecular modeling and molecular dynamics simulations based structural analysis of the SG2NA protein variants.

PubMed

Soni, Sangeeta; Tyagi, Chetna; Grover, Abhinav; Goswami, Shyamal K

2014-07-11

SG2NA is a member of the striatin sub-family of WD-40 repeat proteins. Striatin family members have been associated with diverse physiological functions. SG2NA has also been shown to have roles in cell cycle progression, signal transduction etc. They have been known to interact with a number of proteins including Caveolin and Calmodulin and also propagate the formation of a multimeric protein unit called striatin-interacting phosphatase and kinase. As a pre-requisite for such interaction ability, these proteins are known to be unstable and primarily disordered in their arrangement. Earlier we had identified that it has multiple isoforms (namely 35, 78, 87 kDa based on its molecular weight) which are generated by alternative splicing. However, detailed structural information of SG2NA is still eluding the researchers. This study was aimed towards three-dimensional molecular modeling and characterization of SG2NA protein and its isoforms. One structure out of five was selected for each variant having the least value for C score. Out of these, m35 kDa with a C score value of -3.21 was the most poorly determined structure in comparison to m78 kDa and m87 kDa variants with C scores of -1.16 and -1.97 respectively. Further evaluation resulted in about 61.6% residues of m35 kDa, 76.6% residues of m78 kDa and 72.1% residues of m87 kDa falling in the favorable regions of Ramchandran Plot. Molecular dynamics simulations were also carried out to obtain biologically relevant structural models and compared with previous atomic coordinates. N-terminal region of all variants was found to be highly disordered. This study provides first-hand detailed information to understand the structural conformation of SG2NA protein variants (m35 kDa, m78 kDa and m87 kDa). The WD-40 repeat domain was found to constitute antiparallel strands of β-sheets arranged circularly. This study elucidates the crucial structural features of SG2NA proteins which are involved in various protein-protein interactions and also reveals the extent of disorder present in the SG2NA structure crucial for excessive interaction and multimeric protein complexes. The study also potentiates the role of computational approaches for preliminary examination of unknown proteins in the absence of experimental information.

The genome sequence of Agrotis segetum granulovirus, isolate AgseGV-DA, reveals a new Betabaculovirus species of a slow killing granulovirus.

PubMed

Gueli Alletti, Gianpiero; Eigenbrod, Marina; Carstens, Eric B; Kleespies, Regina G; Jehle, Johannes A

2017-06-01

The European isolate Agrotis segetum granulovirus DA (AgseGV-DA) is a slow killing, type I granulovirus due to low dose-mortality responses within seven days post infection and a tissue tropism of infection restricted solely to the fat body of infected Agrotis segetum host larvae. The genome of AgseGV-DA was completely sequenced and compared to the whole genome sequences of the Chinese isolates AgseGV-XJ and AgseGV-L1. All three isolates share highly conserved genomes. The AgseGV-DA genome is 131,557bp in length and encodes for 149 putative open reading frames, including 37 baculovirus core genes and the per os infectivity factor ac110. Comprehensive investigations of repeat regions identified one putative non-hr like origin of replication in AgseGV-DA. Phylogenetic analysis based on concatenated amino acid alignments of 37 baculovirus core genes as well as pairwise distances based on the nucleotide alignments of partial granulin, lef-8 and lef-9 sequences with deposited betabaculoviruses confirmed AgseGV-DA, AgseGV-XJ and AgseGV-L1 as representative isolates of the same Betabaculovirus species. AgseGV encodes for a distinct putative enhancin, distantly related to enhancins from other granuloviruses. Copyright © 2017. Published by Elsevier Inc.

Standardized metrics for accessibility : establishing a federal policy-relevant knowledge base : USDOT Region V Regional University Transportation Center final report.

DOT National Transportation Integrated Search

2016-12-01

This report seeks opportunities for standardization of these data and explains findings on three principal tasks. First, it assesses the current state of standardized transportation data. By studying documentation of other programs of standardized da...

Cortical ionotropic glutamate receptor antagonism protects against methamphetamine-induced striatal neurotoxicity.

PubMed

Gross, N B; Duncker, P C; Marshall, J F

2011-12-29

Binge administration of the psychostimulant drug, methamphetamine (mAMPH), produces long-lasting structural and functional abnormalities in the striatum. mAMPH binges produce nonexocytotic release of dopamine (DA), and mAMPH-induced activation of excitatory afferent inputs to cortex and striatum is evidenced by elevated extracellular glutamate (GLU) in both regions. The mAMPH-induced increases in DA and GLU neurotransmission are thought to combine to injure striatal DA nerve terminals of mAMPH-exposed brains. Systemic pretreatment with either competitive or noncompetitive N-methyl-D-aspartic acid (NMDA) antagonists protects against mAMPH-induced striatal DA terminal damage, but the locus of these antagonists' effects has not been determined. Here, we applied either the NMDA receptor antagonist, (dl)-amino-5-phosphonovaleric acid (AP5), or the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, dinitroquinoxaline-2,3-dione (DNQX), directly to the dura mater over frontoparietal cortex to assess their effects on mAMPH-induced cortical and striatal immediate-early gene (c-fos) expression. In a separate experiment we applied AP5 or DNQX epidurally in the same cortical location of rats during a binge regimen of mAMPH and assessed mAMPH-induced striatal dopamine transporter (DAT) depletions 1 week later. Our results indicate that both ionotropic glutamate receptor antagonists reduced the mAMPH-induced Fos expression in cerebral cortex regions near the site of epidural application and reduced Fos immunoreactivity in striatal regions innervated by the affected cortical regions. Also, epidural application of the same concentration of either antagonist during a binge mAMPH regimen blunted the mAMPH-induced striatal DAT depletions with a topography similar to its effects on Fos expression. These findings demonstrate that mAMPH-induced dopaminergic injury depends upon cortical NMDA and AMPA receptor activation and suggest the involvement of the corticostriatal projections in mAMPH neurotoxicity. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Detection of prosecretory mitogen lacritin in nonprimate tears primarily as a C-terminal-like fragment.

PubMed

Laurie, Diane E; Splan, Rebecca K; Green, Kari; Still, Katherine M; McKown, Robert L; Laurie, Gordon W

2012-09-12

Lacritin is a human tear glycoprotein that promotes basal tear protein secretion in cultured rat lacrimal acinar cells and proliferation of subconfluent human corneal epithelial cells. When topically added to rabbit eyes, lacritin promotes basal tearing. Despite these activities on several species, lacritin's presence in nonprimate tears or other tissues has not been explored. Here we probed for lacritin in normal horse tears. Sequences were collected from the Ensembl genomic alignment of human LACRT gene with high-quality draft horse genome (EquCab2.0) and analyzed. Normal horse tears were collected and assayed by Western blotting, ELISA, and mass spectrometry. Newly generated rabbit antibodies, respectively, against N- and C-terminal regions of human lacritin were employed. Identity was 75% and 45%, respectively, at nucleotide and protein levels. Structural features were conserved, including a C-terminal amphipathic α-helix. Anti-C-terminal antibodies strongly detected a ∼13 kDa band in horse tears that was validated by mass spectrometry. In human tears, the same antibody detected uncleaved lacritin (∼24 kDa) strongly and C-terminal fragments of ∼13 and ∼11 kDa weakly. Anti-N-terminal antibodies were slightly reactive with a ∼24 kDa horse antigen and showed no reaction with the anti-C-terminal-reactive ∼13 kDa species. Similar respective levels of horse C-terminal versus N-terminal immunoreactivity were apparent by ELISA. Lacritin is present in horse tears, largely as a C-terminal fragment homologous to the mitogenic and bactericidal region in human lacritin, suggesting potential benefit in corneal wound repair.

Polypharmacy and Polymorbidity in Older Adults in Brazil: a public health challenge.

PubMed

Ramos, Luiz Roberto; Tavares, Noemia Urruth Leão; Bertoldi, Andréa Dâmaso; Farias, Mareni Rocha; Oliveira, Maria Auxiliadora; Luiza, Vera Lucia; Pizzol, Tatiane da Silva Dal; Arrais, Paulo Sérgio Dourado; Mengue, Sotero Serrate

2016-12-01

To analyze variations in the prevalence of chronic use of medicines by older adults in Brazil according to its possible association with the most prevalent chronic diseases and demographic and health factors, and to identify risk factors for polypharmacy. A study based on data from the National Survey on Access, Use and Promotion of Rational Use of Medicines (PNAUM), a cross-sectional, population-based survey with probability sampling in Brazilian urban areas. The independent variable was the number of chronic-use medicines taken by older adults, linked to eight chronic diseases investigated. The intervening variables were gender, age group, marital status, level of education, socioeconomic status, Brazilian region, body mass index, smoking, self-perceived health, hospitalization in the previous year and having health insurance, besides the investigated chronic diseases. A multivariable analysis identified risk factors for polypharmacy. Prevalence of at least one chronic-use medicines among older adults was 93.0%. Of the total number of older adults, 18.0% used at least five medications (polypharmacy). Polypharmacy was higher among the oldest individuals (20.0%), in the South region (25.0%), in those with poor self-perceived health (35.0%), in obese individuals (26.0%), in those with reported health insurance (23.0%) or hospitalization in the previous year (31.0%), and among those who reported any of the investigated diseases, particularly diabetes (36.0%) and heart diseases (43.0%). The variables remaining in the final risk model for polypharmacy were age, region, perceived health, health insurance, hospitalization in the previous year and all investigated diseases except stroke. Older adults with specific diseases have risk factors for polypharmacy modifiable by actions aimed at the rational use of medicines. With the current population aging and successful drug access policy, the trend is an increase in drug use by older adults, which should feature as a priority in the planning agenda of the Brazilian Unified Health System (SUS). Analisar as variações da prevalência do uso crônico de medicamentos por idosos no Brasil segundo sua possível associação com as doenças crônicas mais prevalentes, fatores sociodemográficos e de saúde, e identificar fatores de risco para polifarmácia. Estudo com dados da Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos, de caráter transversal e amostra probabilística populacional em municípios brasileiros urbanos. A variável independente foi o número de medicamentos de uso crônico por idosos, vinculados às oito doenças crônicas investigadas. As variáveis intervenientes foram sexo, faixa etária, situação conjugal, escolaridade, nível socioeconômico, região do País, índice de massa corporal, hábito de fumar, percepção da própria saúde, internação no último ano e posse de plano de saúde privado, além das doenças crônicas referidas. Uma análise multivariável identificou os fatores de risco para polifarmácia. A prevalência de pelo menos um medicamento de uso crônico entre idosos foi de 93,0%. Do total de idosos, 18,0% utilizavam pelo menos cinco medicamentos (polifarmácia). A polifarmácia foi maior entre os mais idosos (20,0%), na região Sul (25,0%), nos que avaliaram a própria saúde como ruim (35,0%), nos obesos (26,0%), nos que referiram ter plano de saúde (23,0%) ou internação no último ano (31,0%) e entre os que referiram qualquer uma das doenças investigadas, particularmente diabetes (36,0%) e doenças cardíacas (43,0%). No modelo final de risco para polifarmácia permaneceram idade, região, percepção de saúde, posse de plano de saúde, internação no último ano e todas as doenças investigadas exceto acidente vascular cerebral. Idosos com doenças específicas têm fatores de risco para polifarmácia modificáveis por ações que visem o uso racional de medicamentos. Com o envelhecimento populacional em curso e a política exitosa de acesso a medicamentos, a tendência é aumentar a utilização de medicamentos por idosos, que deve ser prioridade na agenda de planejamento do Sistema Único de Saúde.

Measurement in vivo of dopamine receptor density II: Effect of d-amphetamine on spiroperidol binding

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

Friedman, A.M.; De Jesus, O.T.; Woolverton, W.

1984-01-01

In the authors continuing studies to measure dopamine (DA) receptors in vivo using the DA antagonist bromospiroperidol (BrSP) and positron emission tomography (PET). The authors have examined the effect of d-amphetamine (d-AMP) on BrSP distribution in primate brain. Using the University of Chicago PETT VI scanner, /sup 76/Br-BrSP was found to localize in the caudate and putamen of anesthetized rhesus monkeys. The maximum level of this drug in these regions was reached at 100 minutes post-injection and remained constant for the next 200 minutes. Levels in the cerebellum, on the other hand, decline steadily after an hour post-injection. This ismore » consistent with the presence of high level of DA receptors in the basal ganglia and low levels in the cerebellum. Preliminary studies showed that the administration of d-AMP (0.5 mg/kg i.v.) resulted in a small but statistically significant decrease in caudate /sup 76/Br-BrSP levels. Since d-AMP is known to release DA in the caudate, these findings are consistent with the competition of released DA for BrSP binding at caudate DA binding sites.« less

Cloning and sequencing of a gene encoding the 69-kDa extracellular chitinase of Janthinobacterium lividum.

PubMed

Gleave, A P; Taylor, R K; Morris, B A; Greenwood, D R

1995-09-15

Janthinobacterium lividum secretes a major 56-kDa chitinase and a minor 69-kDa chitinase. A chitinase gene was defined on a 3-kb fragment of clone pRKT10, by virtue of fluorescent colonies in the presence of 4-methylumbelliferyl-beta-D-N,N',N"-chitotrioside. Nucleotide sequencing revealed an 1998-bp open reading frame with the potential to encode a 69,716-Da protein with amino acid sequences similar to those in other chitinases, suggesting it encodes the minor chitinase (Chi69). Chitinase activity of Escherichia coli (pRKT10) lysates was detected mainly in the periplasmic fraction and immunoblotting detected a 70-kDa protein in this fraction. Chi69 has an N-terminal secretory leader peptide preceding two probable chitin-binding domains and a catalytic domain. These functional domains are separated by linker regions of proline-threonine repeats. Amino acid sequencing of cyanogen bromide cleavage-derived peptides from the major 56-kDa chitinase suggested that Chi69 may be a precursor of Chi56. In addition, an N-terminally truncated version of Chi69 retained chitinase activity as expected if in vivo processing of Chi69 generates Chi56.

DAT Genotype Modulates Brain and Behavioral Responses Elicited by Cigarette Cues

PubMed Central

Franklin, Teresa R; Lohoff, Falk W; Wang, Ze; Sciortino, Nathan; Harper, Derek; Li, Yin; Jens, Will; Cruz, Jeffrey; Kampman, Kyle; Ehrman, Ron; Berrettini, Wade; Detre, John A; O'Brien, Charles P; Childress, Anna Rose

2011-01-01

We previously demonstrated differential activation of the mesocorticolimbic reward circuitry in response to cigarette cues independent of withdrawal. Despite robust effects, we noted considerable individual variability in brain and subjective responses. As dopamine (DA) is critical for reward and its predictive signals, genetically driven variation in DA transmission may account for the observed differences. Evidence suggests that a variable number of tandem repeats (VNTRs) polymorphism in the DA transporter (DAT) SLC6A3 gene may influence DA transport. Brain and behavioral responses may be enhanced in probands carrying the 9-repeat allele. To test this hypothesis, perfusion fMR images were acquired during cue exposure in 19 smokers genotyped for the 40 bp VNTR polymorphism in the SLC6A3 gene. Contrasts between groups revealed that 9-repeat (9-repeats) had a greater response to smoking (vs nonsmoking) cues than smokers homozygous for the 10-repeat allele (10/10-repeats) bilaterally in the interconnected ventral striatal/pallidal/orbitofrontal cortex regions (VS/VP/OFC). Activity was increased in 9-repeats and decreased in 10/10-repeats in the VS/VP/OFC (p<0.001 for all analyses). Brain activity and craving was strongly correlated in 10/10-repeats in these regions and others (anterior cingulate, parahippocampal gyrus, and insula; r2 = 0.79–0.86, p<0.001 in all regions). Alternatively, there were no significant correlations between brain and behavior in 9-repeats. There were no differences in cigarette dependence, demographics, or resting baseline neural activity between groups. These results provide evidence that genetic variation in the DAT gene contributes to the neural and behavioral responses elicited by smoking cues. PMID:18704100

Constraints for the thawing and freezing potentials

NASA Astrophysics Data System (ADS)

Hara, Tetsuya; Suzuki, Anna; Saka, Shogo; Tanigawa, Takuma

2018-01-01

We study the accelerating present universe in terms of the time evolution of the equation of state w(z) (redshift z) due to thawing and freezing scalar potentials in the quintessence model. The values of dw/da and d^2w/da^2 at a scale factor of a = 1 are associated with two parameters of each potential. For five types of scalar potentials, the scalar fields Q and w as functions of time t and/or z are numerically calculated under the fixed boundary condition of w(z=0)=-1+Δ. The observational constraint w_obs (Planck Collaboration, arXiv:1502.01590) is imposed to test whether the numerical w(z) is in w_obs. Some solutions show thawing features in the freezing potentials. Mutually exclusive allowed regions in the dw/da vs. d^2w/da^2 diagram are obtained in order to identify the likely scalar potential and even the potential parameters for future observational tests.

Translations on Environmental Quality, No. 152

DTIC Science & Technology

1977-11-01

information was released during a press conference called by Manuel Diaz Dorado, under-secretary for Environmental Planning , Luis Urbano Juagueri, technical...seriousness of this threat, as well as what is being done and what plans have been made to eliminate the hazard. It is not superfluous to reiterate...the floating solids in the harbor; the use of a floating in- cinerator to collect and burn the garbage from ships anchored in the port; the planning

Breast Cancer Research Training Grant

DTIC Science & Technology

1997-10-01

students and answer questions and plan each student’s curriculum. Trainees are encouraged to consult any of the participating faculty for general advice...ROOM L301, REFRESHMENTS AT 1:00 September 20 Alexander Urbano Identification of novel endonucleases in drug- Department of Pathology & Laboratory...highly relevant. Plan to attend if you can. AER/cs Special Seminar 11/7/96 Dr. Harold Varmus •i• i .*: i •i •• • .iiil Boston University School of

Densidad de desarrollo alta y baja en Puerto Rico

Treesearch

William A. Gould; Sebastian Martinuzzi; Olga M. Ramos Gonzalez

2008-01-01

Este mapa demuestra la distribución de terrenos de alta y baja densidad de desarrollo urbano en Puerto Rico (Martinuzzi et al. 2007). El mapa fue creado mediante el analisis de un mosaico de imagenes de satelite Landsat ETM+ de los años 2000 – 2003. La clasificacion no supervisada ISODATA (“Iterative Self-Organizing Data Analysis Technique”) (ERDAS 2003) fue utilizada...

Translations on Narcotics and Dangerous Drugs, Number 291

DTIC Science & Technology

1977-03-23

EL SOL DE MEXICO, 19 Feb 77) 53 Traffickers, Drugs, Weapons Seized in Tijuana (EXCELSIOR, 18 Feb 77) 55 Briefs Heroin Seizure in...women are Elena Urbano Hurtado, Celia Marina [last name indistinct] and Luz Angela Hoyos. The cocaine seized, which is 95 percent pure, has been...pesos. 8743 CSO: 5300 52 MEXICO TRAFFICKERS ARRESTED, WEAPONS AID DRUGS SEIZED Mexico City EL SOL DE MEXICO in Spanish 19 Feb 77 p 10-A

Amygdala response to faces parallels social behavior in Williams syndrome

PubMed Central

Snyder, Abraham Z.; Haist, Frank; Raichle, Marcus E.; Bellugi, Ursula; Stiles, Joan

2009-01-01

Individuals with Williams syndrome (WS), a genetically determined disorder, show relatively strong face-processing abilities despite poor visuospatial skills and depressed intellectual function. Interestingly, beginning early in childhood they also show an unusually high level of interest in face-to-face social interaction. We employed functional magnetic resonance imaging (fMRI) to investigate physiological responses in face-sensitive brain regions, including ventral occipito-temporal cortex and the amygdala, in this unique genetic disorder. Participants included 17 individuals with WS, 17 age- and gender-matched healthy adults (chronological age-matched controls, CA) and 17 typically developing 8- to 9-year-old children (developmental age controls, DA). While engaged in a face discrimination task, WS participants failed to recruit the amygdala, unlike both CA and DA controls. WS fMRI responses in ventral occipito-temporal cortex, however, were comparable to those of DA controls. Given the integral role of the amygdala in social behavior, the failure of WS participants to recruit this region during face processing may be a neural correlate of the abnormally high sociability that characterizes this disorder. PMID:19633063

Altered neuronal activity in the primary motor cortex and globus pallidus after dopamine depletion in rats.

PubMed

Wang, Min; Li, Min; Geng, Xiwen; Song, Zhimin; Albers, H Elliott; Yang, Maoquan; Zhang, Xiao; Xie, Jinlu; Qu, Qingyang; He, Tingting

2015-01-15

The involvement of dopamine (DA) neuron loss in the etiology of Parkinson's disease has been well documented. The neural mechanisms underlying the effects of DA loss and the resultant motor dysfunction remain unknown. To gain insights into how loss of DA disrupts the electrical processes in the cortico-subcortical network, the present study explores the effects of DA neuron depletion on electrical activity in the primary motor cortex (M1), on the external and the internal segment of the globus pallidus (GPe and GPi respectively), and on their temporal relationships. Comparison of local field potentials (LFPs) in these brain regions from unilateral hemispheric DA neuron depleted rats and neurologically intact rats revealed that the spectrum power of LFPs in 12-70Hz (for M1, and GPe) and in 25-40Hz (for GPi) was significantly greater in the DA depleted rats than that in the control group. These changes were associated with a shortening of latency in LFP activities between M1 and GPe, from several hundred milliseconds in the intact animals to close to zero in the DA depleted animals. LFP oscillations in M1 were significantly more synchronized with those in GPe in the DA depleted rats compared with those in the control rats. By contrast, the synchronization of oscillation in LFP activities between M1 and GPi did not differ between the DA depleted and intact rats. Not surprisingly, rats that had DA neuron depletion spent more time along the ladder compared with the control rats. These data suggest that enhanced oscillatory activity and increased synchronization of LFPs may contribute to movement impairment in the rat model of Parkinson's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Exploring the Neither in João Pedro Rodrigues and João Rui Guerra Da Mata's "A ultima vez que vi Macau"

ERIC Educational Resources Information Center

ten Haaf, Rachel

2017-01-01

Torn between two colonial powers, Macau has long existed as a peripheral region in Lusophone studies. This current study explores João Pedro Rodrigues and João Rui Guerra da Mata's 2012 film "A ultima vez que vi Macau". With a focus on a contemporary Macau that seeks to resolve its fundamental duality through investigation of gender,…

Brazil-U.S. Relations

DTIC Science & Technology

2007-02-28

Relations Summary On January 1, 2007, Luis Inácio “Lula” da Silva, of the leftist Workers’ Party (PT), was inaugurated for a second four-year term as...United Nations (U.N.) and the Organization of American States ( OAS ), and act at times as a countervailing force to U.S. political and economic influence...in Latin America. In addition to its active engagement in regional and multilateral trade talks, Brazil under President Luis Inácio “Lula” da Silva

Molecular characterization of a 40 kDa OmpC-like porin from Serratia marcescens.

PubMed

Hutsul, J A; Worobec, E

1994-02-01

An oligonucleotide that encodes the N-terminal portion of a 41 kDa porin of Serratia marcescens was used to probe S. marcescens UOC-51 genomic DNA. An 11 kb EcoRI fragment which hybridized with the oligonucleotide was subcloned into Escherichia coli, examined for expression, and sequenced. The product expressed by the cloned gene was 40 kDa. The nucleotide sequence has an ORF of 1.13 kb. When the deduced amino acid sequence was aligned and compared to other enterobacterial porins the cloned S. marcescens porin most closely resembled E. coli OmpC. Although we did not detect osmoregulation or thermoregulation of any porins in S. marcescens UOC-51, sequences analogous to the E. coli osmoregulator OmpR-binding regions are seen upstream to the cloned gene. We examined the regulation of the S. marcescens porin in E. coli and found that its expression increased in a high salt environment. A micF gene, whose transcriptional product functions to inhibit synthesis of OmpF by hybridizing with the ompF transcript, was also seen upstream of the S. marcescens ompC. An alignment with the E. coli micF gene revealed that the functional region of the S. marcescens micF gene is conserved. Based on the results obtained we have determined that S. marcescens UOC-51 produces a 40 kDa porin similar to the E. coli OmpC porin.

Structure, function and tissue forms of the C-terminal globular domain of collagen XVIII containing the angiogenesis inhibitor endostatin.

PubMed Central

Sasaki, T; Fukai, N; Mann, K; Göhring, W; Olsen, B R; Timpl, R

1998-01-01

The C-terminal domain NC1 of mouse collagen XVIII (38 kDa) and the shorter mouse and human endostatins (22 kDa) were prepared in recombinant form from transfected mammalian cells. The NC1 domain aggregated non-covalently into a globular trimer which was partially cleaved by endogenous proteolysis into several monomers (25-32 kDa) related to endostatin. Endostatins were obtained in a highly soluble, monomeric form and showed a single N-terminal sequence which, together with other data, indicated a compact folding. Endostatins and NC1 showed a comparable binding activity for the microfibrillar fibulin-1 and fibulin-2, and for heparin. Domain NC1, however, was a distinctly stronger ligand than endostatin for sulfatides and the basement membrane proteins laminin-1 and perlecan. Immunological assays demonstrated endostatin epitopes on several tissue components (22-38 kDa) and in serum (120-300 ng/ml), the latter representing the smaller variants. The data indicated that the NC1 domain consists of an N-terminal association region (approximately 50 residues), a central protease-sensitive hinge region (approximately 70 residues) and a C-terminal stable endostatin domain (approximately 180 residues). They also demonstrated that proteolytic release of endostatin can occur through several pathways, which may lead to a switch from a matrix-associated to a more soluble endocrine form. PMID:9687493

Effect of atomoxetine on hyperactivity in an animal model of attention-deficit/hyperactivity disorder (ADHD).

PubMed

Moon, Su Jin; Kim, Chang Ju; Lee, Yeon Jung; Hong, Minha; Han, Juhee; Bahn, Geon Ho

2014-01-01

Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD). To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus. Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined. The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner. Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway.

Effect of Atomoxetine on Hyperactivity in an Animal Model of Attention-Deficit/Hyperactivity Disorder (ADHD)

PubMed Central

Moon, Su Jin; Kim, Chang Ju; Lee, Yeon Jung; Hong, Minha; Han, Juhee; Bahn, Geon Ho

2014-01-01

Background Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD). Purpose To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus. Methods Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined. Results The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner. Conclusion Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway. PMID:25271814

A new anisotropy index on trabecular bone radiographic images using the fast Fourier transform

PubMed Central

Brunet-Imbault, Barbara; Lemineur, Gerald; Chappard, Christine; Harba, Rachid; Benhamou, Claude-Laurent

2005-01-01

Background The degree of anisotropy (DA) on radiographs is related to bone structure, we present a new index to assess DA. Methods In a region of interest from calcaneus radiographs, we applied a Fast Fourier Transform (FFT). All the FFT spectra involve the horizontal and vertical components corresponding respectively to longitudinal and transversal trabeculae. By visual inspection, we measured the spreading angles: Dispersion Longitudinal Index (DLI) and Dispersion Transverse Index (DTI) and calculated DA = 180/(DLI+DTI). To test the reliability of DA assessment, we synthesized images simulating radiological projections of periodic structures with elements more or less disoriented. Results Firstly, we tested synthetic images which comprised a large variety of structures from highly anisotropic structure to the almost isotropic, DA was ranging from 1.3 to 3.8 respectively. The analysis of the FFT spectra was performed by two observers, the Coefficients of Variation were 1.5% and 3.1 % for intra-and inter-observer reproducibility, respectively. In 22 post-menopausal women with osteoporotic fracture cases and 44 age-matched controls, DA values were respectively 1.87 ± 0.15 versus 1.72 ± 0.18 (p = 0.001). From the ROC analysis, the Area Under Curve (AUC) were respectively 0.65, 0.62, 0.64, 0.77 for lumbar spine, femoral neck, total femoral BMD and DA. Conclusion The highest DA values in fracture cases suggest that the structure is more anisotropic in osteoporosis due to preferential deletion of trabeculae in some directions. PMID:15927072

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

PubMed Central

Volkow, Nora D.; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S.; Alexoff, David; Logan, Jean; Jayne, Millard; Wong, Christopher; Tomasi, Dardo

2014-01-01

Moves to legalize marijuana highlight the urgency to investigate effects of chronic marijuana in the human brain. Here, we challenged 48 participants (24 controls and 24 marijuana abusers) with methylphenidate (MP), a drug that elevates extracellular dopamine (DA) as a surrogate for probing the reactivity of the brain to DA stimulation. We compared the subjective, cardiovascular, and brain DA responses (measured with PET and [11C]raclopride) to MP between controls and marijuana abusers. Although baseline (placebo) measures of striatal DA D2 receptor availability did not differ between groups, the marijuana abusers showed markedly blunted responses when challenged with MP. Specifically, compared with controls, marijuana abusers had significantly attenuated behavioral (“self-reports” for high, drug effects, anxiety, and restlessness), cardiovascular (pulse rate and diastolic blood pressure), and brain DA [reduced decreases in distribution volumes (DVs) of [11C]raclopride, although normal reductions in striatal nondisplaceable binding potential (BPND)] responses to MP. In ventral striatum (key brain reward region), MP-induced reductions in DVs and BPND (reflecting DA increases) were inversely correlated with scores of negative emotionality, which were significantly higher for marijuana abusers than controls. In marijuana abusers, DA responses in ventral striatum were also inversely correlated with addiction severity and craving. The attenuated responses to MP, including reduced decreases in striatal DVs, are consistent with decreased brain reactivity to the DA stimulation in marijuana abusers that might contribute to their negative emotionality (increased stress reactivity and irritability) and addictive behaviors. PMID:25024177

Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints.

PubMed

Mwangi, Timothy K; Berke, Ian M; Nieves, Eduardo H; Bell, Richard D; Adams, Samuel B; Setton, Lori A

2018-05-26

Determine the effects of arthritis on the trans-synovial clearance of small and large model compounds following local delivery to the knee joint in a rat model. Intra-articular delivery was studied in rat knee joints in an osteoarthritis model of joint instability (medial collateral ligament and meniscus transection model or MMT). Fluorescently-labeled 10 kDa or 500 kDa dextran was injected in the arthritic or unoperated control (naive) joints 3 weeks after surgical destabilization, and the temporal clearance pattern was evaluated via in vivo regional fluorescence imaging, dextran concentrations in plasma and draining lymph nodes, and by quantification of fluorescence in histological synovium sections. Together these data were used to evaluate the effect of osteoarthritis and solute size on the rate of drug clearance from the joint. Clearance of 10 kDa dextran from the joint space quantified using in vivo fluorescence imaging of the knee joint region was not significantly different between naive and MMT joints. In contrast, clearance of 500 kDa dextran was significantly reduced for MMT joints when compared to naive joints by fluorescence in vivo imaging. Drug accumulation in lymph nodes and plasma were lower for the 500 kDa dextran as compared to 10 kDa dextran, and lymph node levels were further reduced with the presence of osteoarthritis. Furthermore, synovium was significantly thicker in MMT joints than in naive joints and image analysis of joint tissue sections revealed different trans-synovial distributions of 10 and 500 kDa dextran. Large macromolecules were retained in the arthritic joint longer than in the healthy joint, while smaller molecules were cleared similarly in healthy and arthritic joints. In vivo fluorescence imaging, plasma and lymph node concentrations, and spatial distributions of drug fluorescence identified differences in higher molecular weight clearance between naive and arthritic disease states. Findings may relate to a thickening of synovium for joints with induced arthritis, and support the concept that intra-articular drug delivery effectiveness may vary with the state of joint pathology. Copyright © 2018 Elsevier B.V. All rights reserved.

Complete genomic sequence of a Tobacco rattle virus isolate from Michigan-grown potatoes.

PubMed

Crosslin, James M; Hamm, Philip B; Kirk, William W; Hammond, Rosemarie W

2010-04-01

Tobacco rattle virus (TRV) causes stem mottle on potato leaves and necrotic arcs and rings in potato tubers, known as corky ringspot disease. Recently, TRV was reported in Michigan potato tubers cv. FL1879 exhibiting corky ringspot disease. Sequence analysis of the RNA-1-encoded 16-kDa gene of the Michigan isolate, designated MI-1, revealed homology to TRV isolates from Florida and Washington. Here, we report the complete genomic sequence of RNA-1 (6,791 nt) and RNA-2 (3,685 nt) of TRV MI-1. RNA-1 is predicted to contain four open reading frames, and the genome structure and phylogenetic analyses of the RNA-1 nucleotide sequence revealed significant homologies to the known sequences of other TRV-1 isolates. The relationships based on the full-length nucleotide sequence were different from than those based on the 16-kDa gene encoded on genomic RNA-1 and reflect sequence variation within a 20-25-aa residue region of the 16-kDa protein. MI-1 RNA-2 is predicted to contain three ORFs, encoding the coat protein (CP), a 37.6-kDa protein (ORF 2b), and a 33.6-kDa protein (ORF 2c). In addition, it contains a region of similarity to the 3' terminus of RNA-1, including a truncated portion of the 16-kDa cistron. Phylogenetic analysis of RNA-2, based on a comparison of nucleotide sequences with other members of the genus Tobravirus, indicates that TRV MI-1 and other North American isolates cluster as a distinct group. TRV M1-1 is only the second North American isolate for which there is a complete sequence of the genome, and it is distinct from the North American isolate TRV ORY. The relationship of the TRV MI-1 isolate to other tobravirus isolates is discussed.

Proteolytic cleavage and activation of PAK2 during UV irradiation-induced apoptosis in A431 cells.

PubMed

Tang, T K; Chang, W C; Chan, W H; Yang, S D; Ni, M H; Yu, J S

1998-09-15

Exposure of mammalian cells to ultraviolet (UV) light elicits a cellular response and can also lead to apoptotic cell death. In this report, we show that a 36-kDa myelin basic protein (MBP) kinase detected by an in-gel kinase assay can be dramatically activated during the early stages of UV irradiation-triggered apoptosis of A431 cells. Immunoblot analysis revealed that this 36-kDa MBP kinase could be recognized by an antibody against the C-terminal regions of a family of p21Cdc42/Rac-activated kinases (PAKs). By using this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 as studying tools, we further demonstrated that UV irradiation caused cleavage of PAK2 to generate a 36-kDa C-terminal catalytic fragment and a 30-kDa N-terminal fragment in A431 cells. The appearance of the 36-kDa C-terminal catalytic fragment of PAK2 matched exactly with the activation of the 36-kDa MBP kinase in A431 cells upon UV irradiation. In addition, UV irradiation also led to activation of CPP32/caspase-3, but not ICH-1L/caspase-2 and ICE/caspase-1, in A431 cells and the kinetics of activation of CPP32/caspase-3 appeared to correlate well with that of DNA fragmentation and of cleavage/activation of PAK2, respectively. Moreover, blockage of activation of CPP32/caspase-3 by pretreating the cells with two specific tetrapeptidic inhibitors for caspases (Ac-DEVD-cho and Ac-YVAD-cmk) could significantly attenuate the extent of cleavage/activation of PAK2 induced by UV irradiation. Collectively, the results demonstrate that cleavage and activation of PAK2 can be induced during the early stages of UV irradiation-triggered apoptosis and indicate the involvement of CPP32/caspase-3 in this process.

Neurotoxic Effects of 5-MeO-DIPT: A Psychoactive Tryptamine Derivative in Rats.

PubMed

Noworyta-Sokołowska, Karolina; Kamińska, Katarzyna; Kreiner, Grzegorz; Rogóż, Zofia; Gołembiowska, Krystyna

2016-11-01

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT, 'foxy') is one of the most popular tryptamine hallucinogens in the illicit drug market. It produces serious adverse effects, but its pharmacological profile is not well recognized. In vitro data have shown that 5-MeO-DIPT acts as a potent serotonin transporter (SERT) inhibitor and displays high affinity at serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors. In this study, using microdialysis in freely moving rats, we examined the effect of 5-MeO-DIPT on dopamine (DA), serotonin (5-HT), and glutamate release in the rat striatum, nucleus accumbens, and frontal cortex. In search of a possible neurotoxic effect of 5-MeO-DIPT, we measured DA and 5-HT tissue content in the above rat brain regions and also determined the oxidative DNA damage with the comet assay. Moreover, we tested drug-elicited head-twitch response and a forepaw treading induced by 8-OH-DPAT. 5-MeO-DIPT at doses of 5, 10, and 20 mg/kg increased extracellular DA, 5-HT, and glutamate level but the differences in the potency were found between brain regions. 5-MeO-DIPT increased 5-HT and decreased 5-HIAA tissue content which seems to result from SERT inhibition. On the other hand, a decrease in DA, DOPAC, and HVA tissue contents suggests possible adaptive changes in DA turnover or damage of DA terminals by 5-MeO-DIPT. DNA single and double-strand breaks persisted up to 60 days after the treatment, indicating marked neurotoxicity of 5-MeO-DIPT. The induction of head-twitch response and potentiation of forepaw treading induced by 8-OH-DPAT indicate that hallucinogenic activity seems to be mediated through the stimulation of 5-HT2A and 5-HT1A receptors by 5-MeO-DIPT.

Pancreatic Islets and Insulinoma Cells Express a Novel Isoform of Group VIA Phospholipase A2 (iPLA2β) that Participates in Glucose-Stimulated Insulin Secretion and Is Not Produced by Alternate Splicing of the iPLA2β Transcript†

PubMed Central

Ramanadham, Sasanka; Song, Haowei; Hsu, Fong-Fu; Zhang, Sheng; Crankshaw, Mark; Grant, Gregory A.; Newgard, Christopher B.; Bao, Shunzhong; Ma, Zhongmin; Turk, John

2013-01-01

Many cells express a group VIA 84 kDa phospholipase A2 (iPLA2β) that is sensitive to inhibition by a bromoenol lactone (BEL) suicide substrate. Inhibition of iPLA2β in pancreatic islets and insulinoma cells suppresses, and overexpression of iPLA2β in INS-1 insulinoma cells amplifies, glucose-stimulated insulin secretion, suggesting that iPLA2β participates in secretion. Western blotting analyses reveal that glucose-responsive 832/13 INS-1 cells express essentially no 84 kDa iPLA2β-immunoreactive protein but predominantly express a previously unrecognized immunoreactive iPLA2β protein in the 70 kDa region that is not generated by a mechanism of alternate splicing of the iPLA2β transcript. To determine if the 70 kDa-immunoreactive protein is a short isoform of iPLA2β, protein from the 70 kDa region was digested with trypsin and analyzed by mass spectrometry. Such analyses reveal several peptides with masses and amino acid sequences that exactly match iPLA2β tryptic peptides. Peptide sequences identified in the 70 kDa tryptic digest include iPLA2β residues 7–53, suggesting that the N-terminus is preserved. We also report here that the 832/13 INS-1 cells express iPLA2β catalytic activity and that BEL inhibits secretagogue-stimulated insulin secretion from these cells but not the incorporation of arachidonic acid into membrane PC pools of these cells. These observations suggest that the catalytic iPLA2β activity expressed in 832/13 INS-1 cells is attributable to a short isoform of iPLA2β and that this isoform participates in insulin secretory but not in membrane phospholipid remodeling pathways. Further, the finding that pancreatic islets also express predominantly a 70 kDa iPLA2β-immunoreactive protein suggests that a signal transduction role of iPLA2β in the native β-cell might be attributable to a 70 kDa isoform of iPLA2β. PMID:14636061

Pancreatic islets and insulinoma cells express a novel isoform of group VIA phospholipase A2 (iPLA2 beta) that participates in glucose-stimulated insulin secretion and is not produced by alternate splicing of the iPLA2 beta transcript.

PubMed

Ramanadham, Sasanka; Song, Haowei; Hsu, Fong-Fu; Zhang, Sheng; Crankshaw, Mark; Grant, Gregory A; Newgard, Christopher B; Bao, Shunzhong; Ma, Zhongmin; Turk, John

2003-12-02

Many cells express a group VIA 84 kDa phospholipase A(2) (iPLA(2)beta) that is sensitive to inhibition by a bromoenol lactone (BEL) suicide substrate. Inhibition of iPLA(2)beta in pancreatic islets and insulinoma cells suppresses, and overexpression of iPLA(2)beta in INS-1 insulinoma cells amplifies, glucose-stimulated insulin secretion, suggesting that iPLA(2)beta participates in secretion. Western blotting analyses reveal that glucose-responsive 832/13 INS-1 cells express essentially no 84 kDa iPLA(2)beta-immunoreactive protein but predominantly express a previously unrecognized immunoreactive iPLA(2)beta protein in the 70 kDa region that is not generated by a mechanism of alternate splicing of the iPLA(2)beta transcript. To determine if the 70 kDa-immunoreactive protein is a short isoform of iPLA(2)beta, protein from the 70 kDa region was digested with trypsin and analyzed by mass spectrometry. Such analyses reveal several peptides with masses and amino acid sequences that exactly match iPLA(2)beta tryptic peptides. Peptide sequences identified in the 70 kDa tryptic digest include iPLA(2)beta residues 7-53, suggesting that the N-terminus is preserved. We also report here that the 832/13 INS-1 cells express iPLA(2)beta catalytic activity and that BEL inhibits secretagogue-stimulated insulin secretion from these cells but not the incorporation of arachidonic acid into membrane PC pools of these cells. These observations suggest that the catalytic iPLA(2)beta activity expressed in 832/13 INS-1 cells is attributable to a short isoform of iPLA(2)beta and that this isoform participates in insulin secretory but not in membrane phospholipid remodeling pathways. Further, the finding that pancreatic islets also express predominantly a 70 kDa iPLA(2)beta-immunoreactive protein suggests that a signal transduction role of iPLA(2)beta in the native beta-cell might be attributable to a 70 kDa isoform of iPLA(2)beta.

Calcium binding to an elastic portion of connectin/titin filaments.

PubMed

Tatsumi, R; Maeda, K; Hattori, A; Takahashi, K

2001-01-01

Alpha-connectin/titin-1 exists as an elastic filament that links a thick filament with the Z-disk, keeping thick filaments centered within the sarcomere during force generation. We have shown that the connectin filament has an affinity for calcium ions and its binding site(s) is restricted to the beta-connectin/titin-2 portion. We now report the localization and the characterization of calcium-binding sites on beta-connectin. Purified beta-connectin was digested by trypsin into 1700- and 400-kDa fragments. which were then subjected to fluorescence calcium-binding assays. The 400-kDa fragment possesses calcium-binding activity; the binding constant was 1.0 x 10(7) M(-1) and the molar ratio of bound calcium ions to the 400-kDa fragment reached a maximum of 12 at a free calcium ion concentration of approximately 1.0 microM. Antibodies against the 400-kDa fragment formed a sharp dense stripe at the boundary of the A and the I bands, indicating that the calcium-binding domain constitutes the N-terminal region of beta-connectin, that is, the elastic portion of connectin filaments. Furthermore, we estimated the N-terminal location of beta-connectin of various origins (n = 26). Myofibrils were treated with a solution containing 0.1 mM CaCl2 and 70 microM leupeptin to split connectin filaments into beta-connectin and a subfragment, and chain weights of these polypeptides were estimated according to their mobility in 2% polyacrylamide slab gels. The subfragment exhibited a similar chain weight of 1200+/-33 kDa (mean+/-SD), while alpha- and beta-connectins were variable in size according to their origin. These results suggest that the apparent length of the 1200-kDa subfragment portion is almost constant in all instances, about 0.34 microm at the slack condition, therefore that the C-terminus of the 1200-kDa subfragment, that is, the N-terminus of the calcium-binding domain, is at the N2 line region of parent filaments in situ. Because the secondary structure of the 400-kDa fragment was changed by the binding of calcium ions, connectin filaments could be expected to alter their elasticity during the contraction-relaxation cycle of skeletal muscle.

Competitive adsorption of dopamine and rhodamine 6G on the surface of graphene oxide.

PubMed

Ren, Hui; Kulkarni, Dhaval D; Kodiyath, Rajesh; Xu, Weinan; Choi, Ikjun; Tsukruk, Vladimir V

2014-02-26

Competitive adsorption-desorption behavior of popular fluorescent labeling and bioanalyte molecules, Rhodamine 6G (R6G) and dopamine (DA), on a chemically heterogeneous graphene oxide (GO) surface is discussed in this study. Individually, R6G and DA compounds were found to adsorb rapidly on the surface of graphene oxide as they followed the traditional Langmuir adsorption behavior. FTIR analysis suggested that both R6G and DA molecules predominantly adsorb on the hydrophilic oxidized regions of the GO surface. Thus, when R6G and DA compounds were adsorbed from mixed solution, competitive adsorption was observed around the oxygen-containing groups of GO sheets, which resulted in partial desorption of R6G molecules from the surface of GO into the solution. The desorbed R6G molecules can be monitored by fluorescence change in solution and was dependent on the DA concentration. We suggest that the efficient competitive adsorption of different strongly bound bioanalytes onto GO-dye complex can be used for the development of sensitive and selective colorimetric biosensors.

ESR dating of Smilodon populator from Toca de Cima dos Pilão, Piauí, Brazil.

PubMed

Kinoshita, Angela; Mollemberg, Michelle; Santana, William; G Figueiredo, Ana Maria; Guidon, Niede; Fátima da Luz, Maria de; Guérin, Claude; Baffa, Oswaldo

2017-02-01

Smilodon is a genus of big cats that lived from the early to the late Pleistocene in regions extending from North to South America. The fossil records of the "saber-toothed cats" are uneven, with some taxa being quite abundant in certain regions. In Brazil, Smilodon populator is a well-known species whose remains, although scarce in comparison to other large mammals, are found all across the country. In particular, there are multiple records of this species in the region of the Serra da Capivara National Park. This area was home to a rich Pleistocene-Holocene fauna, including many mammals. Here, we report on the Electron Spin Resonance dating of a Smilodon populator tooth found in "Toca de Cima dos Pilão", located in the surroundings of the Serra da Capivara National Park. The equivalent dose found after exponential fitting of dose-response curve was (2.7±0.3)x10 2 Gy. Neutron Activation Analysis was used to determine the concentration of radioisotopes present in the sample and in the sediment to calculate the internal and external dose rates. The result of age found is 93±9ka, which confirmed the presence of this species in Serra da Capivara National Park in the late Pleistocene. Copyright © 2016 Elsevier Ltd. All rights reserved.

Expression and function of dopamine receptors in the developing medial frontal cortex and striatum of the rat

PubMed Central

Sillivan, Stephanie E.; Konradi, Christine

2011-01-01

The timeline of dopamine (DA) system maturation and the signaling properties of dopamine receptors (DRs) during rat brain development are not fully characterized. We used in situ hybridization and quantitative PCR to map DR mRNA transcripts in the medial frontal cortex (mFC) and striatum (STR) of the rat from embryonic day (E) 15 to E21. The developmental trajectory of DR mRNAs revealed distinct patterns of DA receptors 1 and 2 (DRD1, DRD2) in these brain regions. Whereas the mFC had a steeper increase in DRD1 mRNA, the STR had a steeper increase in DRD2 mRNA. Both DR mRNAs were expressed at a higher level in the STR compared to the mFC. To identify the functional properties of DRs during embryonic development, the phosphorylation states of cyclic AMP response element binding protein (CREB), extracellular signal-regulated kinase 1/2 (ERK1/2), and glycogen synthase kinase 3 beta (GSK3β) were examined after DR stimulation in primary neuronal cultures obtained from E15 and E18 embryos and cultured for 3 days to ensure a stable baseline level. DR-mediated signaling cascades were functional in E15 cultures in both brain regions. Because DA fibers do not reach the mFC by E15, and DA was not present in cultures, these data indicate that DRs can become functional in the absence of DA innervation. Since activation of DR signal transduction pathways can affect network organization of the developing brain, maternal exposure to drugs that affect DR activity may be liable to interfere with fetal brain development. PMID:22015925

Reactive transport under stress: Permeability evolution by chemo-mechanical deformation

NASA Astrophysics Data System (ADS)

Roded, R.; Holtzman, R.

2017-12-01

The transport of reactive fluids in porous media is important in many natural and engineering processes. Reaction with the solid matrix—e.g. dissolution—changes the transport properties, which in turn affect the rate of reagent transport and hence the reaction. The importance of this highly nonlinear problem has motivated intensive research. Specifically, there have been numerous studies concerning the permeability evolution, especially the process of "wormholing", where preferential dissolution of the most conductive regions leads to a runaway permeability increase. Much less attention, however, has been given to the effect of geomechanics; that is, how the fact that the medium is under stress changes the permeability evolution. Here, we present a novel, mechanistic pore-scale model, simulating the interplay between pore opening by matrix dissolution and pore closure by mechanical compaction, facilitated by weakening caused by the very same process of dissolution. We combine a pore network model of reactive transport with a block-spring model that captures the effect of geomechanics through the update of the network properties. Our simulations show that permeability enhancement is inhibited by stress concentration downstream, in the less dissolved (hence stiffer) regions. Higher stresses lead to stronger inhibition, in agreement with experiments. The effect of stress also depends on the Damkohler number (Da)—the ratio between the flow and the reaction rate. At rapid injection (small Da), where dissolution is relatively uniform, stress has a significant effect on permeability. At slower flow rates (high Da, wormholing regime), stress affects the permeability evolution mostly in early stages, with a much smaller effect on the injected volume required for a significant permeability increase (breakthrough) than at low Da. Interestingly, at higher Da, stress concentration downstream induced by the more heterogeneous dissolution leads to a more homogeneous reagent transport, promoting wormhole competition.

High-frequency stimulation of the subthalamic nucleus restores neural and behavioral functions during reaction time task in a rat model of Parkinson's disease.

PubMed

Li, Xiang-Hong; Wang, Jin-Yan; Gao, Ge; Chang, Jing-Yu; Woodward, Donald J; Luo, Fei

2010-05-15

Deep brain stimulation (DBS) has been used in the clinic to treat Parkinson's disease (PD) and other neuropsychiatric disorders. Our previous work has shown that DBS in the subthalamic nucleus (STN) can improve major motor deficits, and induce a variety of neural responses in rats with unilateral dopamine (DA) lesions. In the present study, we examined the effect of STN DBS on reaction time (RT) performance and parallel changes in neural activity in the cortico-basal ganglia regions of partially bilateral DA- lesioned rats. We recorded neural activity with a multiple-channel single-unit electrode system in the primary motor cortex (MI), the STN, and the substantia nigra pars reticulata (SNr) during RT test. RT performance was severely impaired following bilateral injection of 6-OHDA into the dorsolateral part of the striatum. In parallel with such behavioral impairments, the number of responsive neurons to different behavioral events was remarkably decreased after DA lesion. Bilateral STN DBS improved RT performance in 6-OHDA lesioned rats, and restored operational behavior-related neural responses in cortico-basal ganglia regions. These behavioral and electrophysiological effects of DBS lasted nearly an hour after DBS termination. These results demonstrate that a partial DA lesion-induced impairment of RT performance is associated with changes in neural activity in the cortico-basal ganglia circuit. Furthermore, STN DBS can reverse changes in behavior and neural activity caused by partial DA depletion. The observed long-lasting beneficial effect of STN DBS suggests the involvement of the mechanism of neural plasticity in modulating cortico-basal ganglia circuits. (c) 2009 Wiley-Liss, Inc.

Detection of Prosecretory Mitogen Lacritin in Nonprimate Tears Primarily as a C-Terminal-Like Fragment

PubMed Central

Laurie, Diane E.; Splan, Rebecca K.; Green, Kari; Still, Katherine M.; McKown, Robert L.; Laurie, Gordon W.

2012-01-01

Purpose. Lacritin is a human tear glycoprotein that promotes basal tear protein secretion in cultured rat lacrimal acinar cells and proliferation of subconfluent human corneal epithelial cells. When topically added to rabbit eyes, lacritin promotes basal tearing. Despite these activities on several species, lacritin's presence in nonprimate tears or other tissues has not been explored. Here we probed for lacritin in normal horse tears. Methods. Sequences were collected from the Ensembl genomic alignment of human LACRT gene with high-quality draft horse genome (EquCab2.0) and analyzed. Normal horse tears were collected and assayed by Western blotting, ELISA, and mass spectrometry. Newly generated rabbit antibodies, respectively, against N- and C-terminal regions of human lacritin were employed. Results. Identity was 75% and 45%, respectively, at nucleotide and protein levels. Structural features were conserved, including a C-terminal amphipathic α-helix. Anti-C-terminal antibodies strongly detected a ∼13 kDa band in horse tears that was validated by mass spectrometry. In human tears, the same antibody detected uncleaved lacritin (∼24 kDa) strongly and C-terminal fragments of ∼13 and ∼11 kDa weakly. Anti-N-terminal antibodies were slightly reactive with a ∼24 kDa horse antigen and showed no reaction with the anti-C-terminal–reactive ∼13 kDa species. Similar respective levels of horse C-terminal versus N-terminal immunoreactivity were apparent by ELISA. Conclusions. Lacritin is present in horse tears, largely as a C-terminal fragment homologous to the mitogenic and bactericidal region in human lacritin, suggesting potential benefit in corneal wound repair. PMID:22871838

Cholinergic modulation of mesolimbic dopamine function and reward.

PubMed

Mark, Gregory P; Shabani, Shkelzen; Dobbs, Lauren K; Hansen, Stephen T

2011-07-25

The substantial health risk posed by obesity and compulsive drug use has compelled a serious research effort to identify the neurobiological substrates that underlie the development these pathological conditions. Despite substantial progress, an understanding of the neurochemical systems that mediate the motivational aspects of drug-seeking and craving remains incomplete. Important work from the laboratory of Bart Hoebel has provided key information on neurochemical systems that interact with dopamine (DA) as potentially important components in both the development of addiction and the expression of compulsive behaviors such as binge eating. One such modulatory system appears to be cholinergic pathways that interact with DA systems at all levels of the reward circuit. Cholinergic cells in the pons project to DA-rich cell body regions in the ventral tegmental area (VTA) and substantial nigra (SN) where they modulate the activity of dopaminergic neurons and reward processing. The DA terminal region of the nucleus accumbens (NAc) contains a small but particularly important group of cholinergic interneurons, which have extensive dendritic arbors that make synapses with a vast majority of NAc neurons and afferents. Together with acetylcholine (ACh) input onto DA cell bodies, cholinergic systems could serve a vital role in gating information flow concerning the motivational value of stimuli through the mesolimbic system. In this report we highlight evidence that CNS cholinergic systems play a pivotal role in behaviors that are motivated by both natural and drug rewards. We argue that the search for underlying neurochemical substrates of compulsive behaviors, as well as attempts to identify potential pharmacotherapeutic targets to combat them, must include a consideration of central cholinergic systems. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluating a Local Ensemble Transform Kalman Filter snow cover data assimilation method to estimate SWE within a high-resolution hydrologic modeling framework across Western US mountainous regions

NASA Astrophysics Data System (ADS)

Oaida, C. M.; Andreadis, K.; Reager, J. T., II; Famiglietti, J. S.; Levoe, S.

2017-12-01

Accurately estimating how much snow water equivalent (SWE) is stored in mountainous regions characterized by complex terrain and snowmelt-driven hydrologic cycles is not only greatly desirable, but also a big challenge. Mountain snowpack exhibits high spatial variability across a broad range of spatial and temporal scales due to a multitude of physical and climatic factors, making it difficult to observe or estimate in its entirety. Combing remotely sensed data and high resolution hydrologic modeling through data assimilation (DA) has the potential to provide a spatially and temporally continuous SWE dataset at horizontal scales that capture sub-grid snow spatial variability and are also relevant to stakeholders such as water resource managers. Here, we present the evaluation of a new snow DA approach that uses a Local Ensemble Transform Kalman Filter (LETKF) in tandem with the Variable Infiltration Capacity macro-scale hydrologic model across the Western United States, at a daily temporal resolution, and a horizontal resolution of 1.75 km x 1.75 km. The LETKF is chosen for its relative simplicity, ease of implementation, and computational efficiency and scalability. The modeling/DA system assimilates daily MODIS Snow Covered Area and Grain Size (MODSCAG) fractional snow cover over, and has been developed to efficiently calculate SWE estimates over extended periods of time and covering large regional-scale areas at relatively high spatial resolution, ultimately producing a snow reanalysis-type dataset. Here we focus on the assessment of SWE produced by the DA scheme over several basins in California's Sierra Nevada Mountain range where Airborne Snow Observatory data is available, during the last five water years (2013-2017), which include both one of the driest and one of the wettest years. Comparison against such a spatially distributed SWE observational product provides a greater understanding of the model's ability to estimate SWE and SWE spatial variability, and highlights under which conditions snow cover DA can add value in estimating SWE.

Constitutive expression of DaCBF7, an Antarctic vascular plant Deschampsia antarctica CBF homolog, resulted in improved cold tolerance in transgenic rice plants.

PubMed

Byun, Mi Young; Lee, Jungeun; Cui, Li Hua; Kang, Yoonjee; Oh, Tae Kyung; Park, Hyun; Lee, Hyoungseok; Kim, Woo Taek

2015-07-01

Deschampsia antarctica is an Antarctic hairgrass that grows on the west coast of the Antarctic peninsula. In this report, we have identified and characterized a transcription factor, D. antarctica C-repeat binding factor 7 (DaCBF7), that is a member of the monocot group V CBF homologs. The protein contains a single AP2 domain, a putative nuclear localization signal, and the typical CBF signature. DaCBF7, like other monocot group V homologs, contains a distinct polypeptide stretch composed of 43 amino acids in front of the AP2 motif. DaCBF7 was predominantly localized to nuclei and interacted with the C-repeat/dehydration responsive element (CRT/DRE) core sequence (ACCGAC) in vitro. DaCBF7 was induced by abiotic stresses, including drought, cold, and salinity. To investigate its possible cellular role in cold tolerance, a transgenic rice system was employed. DaCBF7-overexpressing transgenic rice plants (Ubi:DaCBF7) exhibited markedly increased tolerance to cold stress compared to wild-type plants without growth defects; however, overexpression of DaCBF7 exerted little effect on tolerance to drought or salt stress. Transcriptome analysis of a Ubi:DaCBF7 transgenic line revealed 13 genes that were up-regulated in DaCBF7-overexpressing plants compared to wild-type plants in the absence of cold stress and in short- or long-term cold stress. Five of these genes, dehydrin, remorin, Os03g63870, Os11g34790, and Os10g22630, contained putative CRT/DRE or low-temperature responsive elements in their promoter regions. These results suggest that overexpression of DaCBF7 directly and indirectly induces diverse genes in transgenic rice plants and confers enhanced tolerance to cold stress. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

User satisfaction with primary health care by region in Brazil: 1st cycle of external evaluation from PMAQ-AB.

PubMed

Protasio, Ane Polline Lacerda; Gomes, Luciano Bezerra; Machado, Liliane Dos Santos; Valença, Ana Maria Gondim

2017-06-01

The National Program for Access and Quality Improvement in Primary Care (Programa Nacional de Melhoria do Acesso e da Qualidade da Atenção Básica, PMAQ-AB) aimed to improve healthcare public service quality and satisfaction of health service users. This study's objective was to identify the main factors influencing user satisfaction with primary care (PC) services by region in Brazil. Using secondary data from the 1st Cycle of PMAQ-AB, logistic regression models were developed by region, with user satisfaction as the dependent variable, as defined by cluster analysis. Based on the obtained models, the health unit's ability to solve users' problems and feeling respected by the health providers were the most important factors for user satisfaction in all regions in Brazil. However, other important factors by region included the following: the health unit's hours of operation meeting the user's needs (Northeast); providers asking about family members (North); providers asking about other health needs (Midwest); users being seen without an appointment (South); and users asking questions after the appointment (Southeast). In conclusion, the factors influencing user satisfaction with PC vary according to region and are mainly associated with access quality, meeting users' needs, and work process organization.

Three new species of mealybug (Hemiptera, Coccomorpha, Pseudococcidae) on persimmon fruit trees (Diospyros kaki) in southern Brazil.

PubMed

Pacheco da Silva, Vitor C; Kaydan, Mehmet Bora; Germain, Jean-François; Malausa, Thibaut; Botton, Marcos

2016-01-01

Brazil has the greatest insect diversity in the world; however, little is known about its scale insect species (Hemiptera: Coccomorpha). Mealybugs (Pseudococcidae) have been found in at least 50% of persimmon orchards Diospyros kaki L. in the southern part of the country. In this study three new mealybug species on persimmon trees located in the Serra Gaúcha Region, RS, Brazil, namely, Anisococcus granarae Pacheco da Silva & Kaydan, sp. n., Ferrisia kaki Kaydan & Pacheco da Silva, sp. n. and Pseudococcus rosangelae Pacheco da Silva & Kaydan, sp. n. are described. In addition, an identification key for the genera occurring on fruit orchards and vineyards in Brazil is provided, together with illustrations and molecular data for the new species.

The Assessment of Military Multitasking Performance: Validation of a Dual-Task and Multitask Protocol

DTIC Science & Technology

2014-08-01

Revisions based on IRR findings and rater comments Charge of Quarters (CQ) Duty Requires the subject to organize and implement a plan in order to...to evaluate test burden) and malingering are planned . Where feasible, test-retest reliability for several of the tasks is being assessed during...in either a shopping mall or hospital lobby setting (Alderman, Burgess,Knight,&Henman, 2003;Cuberos- Urbano et al., 2013; Dawson et al., 2009

Evaluating the potential of marine Bacteriovorax sp. DA5 as a biocontrol agent against vibriosis in Litopenaeus vannamei larvae.

PubMed

Wen, Chongqing; Xue, Ming; Liang, Huafang; Zhou, Shining

2014-09-17

The potential application of Bdellovibrio-and-like organisms (BALOs) for the biocontrol of bacterial diseases has been widely recognized. However, no marine BALOs have been reported for Vibrio-related infections in penaeid shrimp. In the present study, the bacteriolytic ability of the marine Bacteriovorax strain DA5 against Vibrio alginolyticus zouA was examined by cocultivation and electron microscopy, and optimal lysis was observed at 30-35°C and 20-30‰ salinity along with a high multiplicity of infection. Then, we showed that experimentally infected Litopenaeus vannamei larvae exhibited significantly higher survival with incremental DA5 levels. Finally, variation in the bacterial counts and the bacterial community in larval rearing water was investigated after prophylactic application of DA5. The elimination effect of DA5 on vibrios was visible at early time points, whereas only a few non-dominant bacteria, rather than the predominant populations, were affected through analysis of denaturing gradient gel electrophoresis of the 16S rDNA V3 region. Accordingly, the prophylactic and therapeutic efficacies of DA5 on vibriosis associated with L. vannamei could markedly enhance larval survivability, and these results will facilitate the application of marine Bacteriovorax to control vibriosis in shrimp larviculture. Copyright © 2014 Elsevier B.V. All rights reserved.

Striatal dopaminergic modulation of reinforcement learning predicts reward-oriented behavior in daily life.

PubMed

Kasanova, Zuzana; Ceccarini, Jenny; Frank, Michael J; Amelsvoort, Thérèse van; Booij, Jan; Heinzel, Alexander; Mottaghy, Felix; Myin-Germeys, Inez

2017-07-01

Much human behavior is driven by rewards. Preclinical neurophysiological and clinical positron emission tomography (PET) studies have implicated striatal phasic dopamine (DA) release as a primary modulator of reward processing. However, the relationship between experimental reward-induced striatal DA release and responsiveness to naturalistic rewards, and therefore functional relevance of these findings, has been elusive. We therefore combined, for the first time, a DA D 2/3 receptor [ 18 F]fallypride PET during a probabilistic reinforcement learning (RL) task with a six day ecological momentary assessments (EMA) of reward-related behavior in the everyday life of 16 healthy volunteers. We detected significant reward-induced DA release in the bilateral putamen, caudate nucleus and ventral striatum, the extent of which was associated with better behavioral performance on the RL task across all regions. Furthermore, individual variability in the extent of reward-induced DA release in the right caudate nucleus and ventral striatum modulated the tendency to be actively engaged in a behavior if the active engagement was previously deemed enjoyable. This study suggests a link between striatal reward-related DA release and ecologically relevant reward-oriented behavior, suggesting an avenue for the inquiry into the DAergic basis of optimal and impaired motivational drive. Copyright © 2017 Elsevier B.V. All rights reserved.

The N-Terminal Residues 43 to 60 Form the Interface for Dopamine Mediated α-Synuclein Dimerisation

PubMed Central

Leong, Su Ling; Hinds, Mark G.; Connor, Andrea R.; Smith, David P.; Illes-Toth, Eva; Pham, Chi L. L.; Barnham, Kevin J.; Cappai, Roberto

2015-01-01

α-synuclein (α-syn) is a major component of the intracellular inclusions called Lewy bodies, which are a key pathological feature in the brains of Parkinson’s disease patients. The neurotransmitter dopamine (DA) inhibits the fibrillisation of α-syn into amyloid, and promotes α-syn aggregation into SDS-stable soluble oligomers. While this inhibition of amyloid formation requires the oxidation of both DA and the methionines in α-syn, the molecular basis for these processes is still unclear. This study sought to define the protein sequences required for the generation of oligomers. We tested N- (α-syn residues 43–140) and C-terminally (1–95) truncated α-syn, and found that similar to full-length protein both truncated species formed soluble DA:α-syn oligomers, albeit 1–95 had a different profile. Using nuclear magnetic resonance (NMR), and the N-terminally truncated α-syn 43–140 protein, we analysed the structural characteristics of the DA:α-syn 43–140 dimer and α-syn 43–140 monomer and found the dimerisation interface encompassed residues 43 to 60. Narrowing the interface to this small region will help define the mechanism by which DA mediates the formation of SDS-stable soluble DA:α-syn oligomers. PMID:25679387

The DA antagonist tiapride impairs context-related extinction learning in a novel context without affecting renewal

PubMed Central

Lissek, Silke; Glaubitz, Benjamin; Wolf, Oliver T.; Tegenthoff, Martin

2015-01-01

Renewal describes the recovery of an extinguished response if recall is tested in a context different from the extinction context. Behavioral studies demonstrated that attention to relevant context strengthens renewal. Neurotransmitters mediating attention and learning such as the dopaminergic (DA) system presumably modulate extinction learning and renewal. However, the role of DA for non-fear-based extinction learning and renewal in humans has not yet been investigated. This fMRI study investigated effects of DA-antagonism upon context-related extinction in a predictive learning task in which extinction occurred either in a novel (ABA) or an unchanged (AAA) context. The tiapride-treated group (TIA) showed significantly impaired ABA extinction learning and a significant within-group difference between ABA and AAA extinction, compared to placebo (PLAC). Groups did not differ in their level of ABA renewal. In ABA extinction, TIA showed reduced activation in dlPFC and OFC, hippocampus, and temporal regions. Across groups, activation in PFC and hippocampus correlated negatively with ABA extinction errors. Results suggest that in context-related extinction learning DA in PFC and hippocampus is involved in readjusting the cue-outcome relationship in the presence of a novel context. However, relating context to the appropriate association during recall does not appear to rely exclusively on DA signaling. PMID:26388752

Organization of GABAergic synaptic circuits in the rat ventral tegmental area.

PubMed

Ciccarelli, Alessandro; Calza, Arianna; Panzanelli, Patrizia; Concas, Alessandra; Giustetto, Maurizio; Sassoè-Pognetto, Marco

2012-01-01

The ventral tegmental area (VTA) is widely implicated in drug addiction and other psychiatric disorders. This brain region is densely populated by dopaminergic (DA) neurons and also contains a sparse population of γ-aminobutyric acid (GABA)ergic cells that regulate the activity of the principal neurons. Therefore, an in-depth knowledge of the organization of VTA GABAergic circuits and of the plasticity induced by drug consumption is essential for understanding the mechanisms by which drugs induce stable changes in brain reward circuits. Using immunohistochemistry, we provide a detailed description of the localization of major GABA(A) and GABA(B) receptor subunits in the rat VTA. We show that DA and GABAergic cells express both GABA(A) and GABA(B) receptors. However VTA neurons differ considerably in the expression of GABA(A) receptor subunits, as the α1 subunit is associated predominantly with non-DA cells, whereas the α3 subunit is present at low levels in both types of VTA neurons. Using an unbiased stereological method, we then demonstrate that α1-positive elements represent only a fraction of non-DA neurons and that the ratio of DA and non-DA cells is quite variable throughout the rostro-caudal extent of the VTA. Interestingly, DA and non-DA cells receive a similar density of perisomatic synapses, whereas axo-dendritic synapses are significantly more abundant in non-DA cells, indicating that local interneurons receive prominent GABAergic inhibition. These findings reveal a differential expression of GABA receptor subtypes in the two major categories of VTA neurons and provide an anatomical basis for interpreting the plasticity of inhibitory circuits induced by drug exposure.

Light and scanning electron microscopy of the ecdysis of Haemonchus contortus infective larvae.

PubMed

Gamble, H R; Lichtenfels, J R; Purcell, J P

1989-04-01

During the second ecdysis of ruminant trichostrongyles, a region of the second molt cuticle is digested by a 44-kDa Zn-metalloprotease. We have examined this digestion process by light and scanning electron microscopy (SEM). The substrate region of the cuticle appeared, during the ecdysis process, as an indented ring at the 20th cuticular annulus coincident with the anterior terminus of the lateral alae. Continued digestion of the cuticle resulted in holes in the ring region that expanded until they became continuous and separation occurred between the anterior and posterior portions of the cuticle. Mechanical movements of the L3 forced aside the cuticle cap that generally remained attached on one side to the posterior portion as the larva escaped from the sheath. The site of secretion of the 44-kDa ecdysing enzyme causing cuticle digestion was not clear from morphological observations; however, existing evidence strongly points to the release of enzyme from the esophageal (pharyngeal) glands through the mouth.

Normal-phase liquid chromatography retention behavior of polycyclic aromatic hydrocarbon and their methyl-substituted derivatives on an aminopropyl stationary phase.

PubMed

Wilson, Walter B; Hayes, Hugh V; Sander, Lane C; Campiglia, Andres D; Wise, Stephen A

2017-09-01

Retention indices for 124 polycyclic aromatic hydrocarbons (PAHs) and 62 methyl-substituted (Me-) PAHs were determined using normal-phase liquid chromatography (NPLC) on a aminopropyl (NH 2 ) stationary phase. PAH retention behavior on the NH 2 phase is correlated to the total number of aromatic carbons in the PAH structure. Within an isomer group, non-planar isomers generally elute earlier than planar isomers. MePAHs generally elute slightly later but in the same region as the parent PAHs. Correlations between PAH retention behavior on the NH 2 phase and PAH thickness (T) values were investigated to determine the influence of non-planarity for isomeric PAHs with four to seven aromatic rings. Correlation coefficients ranged from r = 0.19 (five-ring peri-condensed molecular mass (MM) 252 Da) to r = -0.99 (five-ring cata-condensed MM 278 Da). In the case of the smaller PAHs (MM ≤ 252 Da), most of the PAHs had a planar structure and provided a low correlation. In the case of larger PAHs (MM ≥ 278 Da), nonplanarity had a significant influence on the retention behavior and good correlation between retention and T was obtained for the MM 278 Da, MM 302 Da, MM 328 Da, and MM 378 Da isomer sets. Graphical abstract NPLC separation of the three-, four-, five-, and six-ring PAH isomers with different number of aromatic carbon atoms and degrees of non-planarity (Thickness, T). The inserted figure plots the number of aromatic carbon atoms vs. the log I value for the 124 parent PAHs.

Striatal dopamine transmission in healthy humans during a passive monetary reward task.

PubMed

Hakyemez, Hélène S; Dagher, Alain; Smith, Stephen D; Zald, David H

2008-02-15

Research on dopamine (DA) transmission has emphasized the importance of increased phasic DA cell firing in the presence of unpredictable rewards. Using [(11)C]raclopride PET, we previously reported that DA transmission was both suppressed and enhanced in different regions of the striatum during an unpredictable reward task [Zald, D.H., Boileau, I., El Dearedy, W., Gunn, R., McGlone, F., Dichter, G.S. et al. (2004). Dopamine transmission in the human striatum during monetary reward tasks. J. Neurosci. 24, 4105-4112]. However, it was unclear if reductions in DA release during this task reflected a response to the high proportion of nonrewarding trials, and whether the behavioral demands of the task influenced the observed response. To test these issues, we presented 10 healthy subjects with an automated (passive) roulette wheel game in which the amount of reward and its timing were unpredictable and the rewarding trials greatly outnumbered the nonrewarding ones. As in the previous study, DA transmission in the putamen was significantly suppressed relative to a predictable control condition. A similar suppression occurred when subjects were presented with temporally unpredictable novel pictures and sounds. At present, models of DA functioning during reward do not account for this suppression, but given that it has been observed in two different studies using different reward paradigms, this phenomenon warrants attention. Neither the unpredictable reward nor the novelty conditions produced consistent increases in striatal DA transmission. These data suggest that active behavioral engagement may be necessary to observe robust statewise increases in DA release in the striatum.

Proteolytic processing of connective tissue growth factor in normal ocular tissues and during corneal wound healing.

PubMed

Robinson, Paulette M; Smith, Tyler S; Patel, Dilan; Dave, Meera; Lewin, Alfred S; Pi, Liya; Scott, Edward W; Tuli, Sonal S; Schultz, Gregory S

2012-12-13

Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is up-regulated by TGF-β and mediates most key fibrotic actions of TGF-β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. This study addresses the role of proteolytic processing of CTGF in human corneal fibroblasts (HCF) stimulated with TGF-β, normal ocular tissues and wounded corneas. Proteolytic processing of CTGF in HCF cultures, normal animal eyes, and excimer laser wounded rat corneas were examined by Western blot. The identity of a 21-kDa band was determined by tandem mass spectrometry, and possible alternative splice variants of CTGF were assessed by 5' Rapid Amplification of cDNA Ends (RACE). HCF stimulated by TGF-β contained full length 38-kDa CTGF and fragments of 25, 21, 18, and 13 kDa, while conditioned medium contained full length 38- and a 21-kDa fragment of CTGF that contained the middle "hinge" region of CTGF. Fragmentation of recombinant CTGF incubated in HCF extracts was blocked by the aspartate protease inhibitor, pepstatin. Normal mouse, rat, and rabbit whole eyes and rabbit ocular tissues contained abundant amounts of C-terminal 25- and 21-kDa fragments and trace amounts of 38-kDa CTGF, although no alternative transcripts were detected. All forms of CTGF (38, 25, and 21 kDa) were detected during healing of excimer ablated rat corneas, peaking on day 11. Proteolytic processing of 38-kDa CTGF occurs during corneal wound healing, which may have important implications in regulation of corneal scar formation.

[Determination of wine original regions using information fusion of NIR and MIR spectroscopy].

PubMed

Xiang, Ling-Li; Li, Meng-Hua; Li, Jing-Mingz; Li, Jun-Hui; Zhang, Lu-Da; Zhao, Long-Lian

2014-10-01

Geographical origins of wine grapes are significant factors affecting wine quality and wine prices. Tasters' evaluation is a good method but has some limitations. It is important to discriminate different wine original regions quickly and accurately. The present paper proposed a method to determine wine original regions based on Bayesian information fusion that fused near-infrared (NIR) transmission spectra information and mid-infrared (MIR) ATR spectra information of wines. This method improved the determination results by expanding the sources of analysis information. NIR spectra and MIR spectra of 153 wine samples from four different regions of grape growing were collected by near-infrared and mid-infrared Fourier transform spe trometer separately. These four different regions are Huailai, Yantai, Gansu and Changli, which areall typical geographical originals for Chinese wines. NIR and MIR discriminant models for wine regions were established using partial least squares discriminant analysis (PLS-DA) based on NIR spectra and MIR spectra separately. In PLS-DA, the regions of wine samples are presented in group of binary code. There are four wine regions in this paper, thereby using four nodes standing for categorical variables. The output nodes values for each sample in NIR and MIR models were normalized first. These values stand for the probabilities of each sample belonging to each category. They seemed as the input to the Bayesian discriminant formula as a priori probability value. The probabilities were substituteed into the Bayesian formula to get posterior probabilities, by which we can judge the new class characteristics of these samples. Considering the stability of PLS-DA models, all the wine samples were divided into calibration sets and validation sets randomly for ten times. The results of NIR and MIR discriminant models of four wine regions were as follows: the average accuracy rates of calibration sets were 78.21% (NIR) and 82.57% (MIR), and the average accuracy rates of validation sets were 82.50% (NIR) and 81.98% (MIR). After using the method proposed in this paper, the accuracy rates of calibration and validation changed to 87.11% and 90.87% separately, which all achieved better results of determination than individual spectroscopy. These results suggest that Bayesian information fusion of NIR and MIR spectra is feasible for fast identification of wine original regions.

CURRENT SITUATION OF MEDICINE III AND CHALLENGES.

PubMed

Ferreira, Lydia Masako

2015-01-01

Describe the current situation of the area Medicine III of CAPES and detect challenges for the next four years of evaluation. The area's documents and reports of meetings were read from 2004 to 2013 Medicine III Capes as well as reports and evaluation form of each Postgraduate Program (PPG) of the area and the sub-page of the area from the Capes website. The data relating to the evaluation process, the assessment form and faculty, student and scientific production data of all of Post-Graduate Programs of Medicine III were computed and analyzed. From these data were detected the challenges of the area for the next four years (2013-2016). Among the 3,806 PPG, Medicine III had 41 PPG during last triennial evaluation and progressed from 18% to 43% of PPG very good or more concept (triennium 2001-2003 and 2010-2012). Most PPG were located in the South-East region (32), three in the South and two in the North-East. There was no PPG in North or Central-West regions. In 2013 and 2014 there were four approved Professional Master Degree Programs and one Master (M) and Doctorate (PhD). The average of permanent professors was 558 teachers with about three students/professor. The number of PhD graduates has increased as well as the reason PhD/MD. The proportion of in high impact periodicals (A1, A2, B1 and B2) jumped from 30% to 50% demonstrating positive community response to the policy area. The challenges identified were: decrease regional asymmetry, increase the number of masters and doctors of excellence, reassessment of Brazilian journals, stimulate and set internationalization indicators, including post-doctors and definition of its indicators, the PPG nucleation analysis, PPG 3x3, include primary and secondary education, professional master and indicators of technological scientific production and solidarity. Medicine III has been scientifically consolidated and their scientific researchers demonstrated maturity reaching a high level and matched to areas of greatest tradition and history. For the maintenance and advancement of the area some challenges and goals were established to be developed in the period from 2013 to 2016. Descrever a situação atual da área Medicina III da Capes e detectar os desafios para o próximo quadriênio de avaliação. Os documentos e relatórios de reuniões de área a partir de 2004 até 2013 da Medicina III da Capes foram lidos assim como os relatórios e as fichas de avaliação de cada Programa de Pós Graduação (PPG) da área e a subpágina da área no site da Capes. Os dados referentes ao Processo de Avaliação, à Ficha de Avaliação e aos dados do Corpo Docente, Discente e Produção científica de todos os PPG da Medicina III foram computados e analisados. A partir desses dados foram detectados os desafios da área para o próximo quadriênio (2013-2016). Dentre os 3.806 PPG, a Medicina III apresentava 41 PPG durante última avaliação trienal e evoluiu de 18% para 43% de PPG > conceito muito bom (Triênios 2001-2003 e 2010-2012). A maioria dos PPG se localizavam na Região Sudeste (32), três no Sul e dois no Nordeste. Não havia nenhum PPG no Norte ou Centro-Oeste. Em 2013 e 2014 foram aprovadas quatro mestrados profissionais e um mestrado e doutorado acadêmico. A média de docente permanente no triênio foi de 558 docentes com cerca de três alunos titulados/docente. O número de doutores titulados tem aumentado assim como a razão Doutorado/Mestrado. A proporção de publicações em periódicos de maior impacto (A1, A2, B1 e B2) saltou de 30% para 50% demonstrando resposta positiva da comunidade à política da área. Os desafios detectados foram: diminuir assimetria regional, elevar o número de mestres e doutores de excelência, reavaliação das revistas nacionais, estimular e definir indicadores de internacionalização, inclusão de pós-doutores e definição de seus indicadores, análise da nucleação do PPG, PPG 3x3, inclusão ensino médio e fundamental, mestrado profissional e indicadores da produção científico-tecnológica e solidariedade. A Medicina III tem se consolidado cientificamente e seus pesquisadores demonstraram maturidade científica chegando a um patamar elevado e igualado às áreas de maior tradição e história. Para a manutenção e avanço da área alguns desafios e metas foram traçadas para serem desenvolvidas no quadriênio 2013-2016.

Modulation of Memory Consolidation by the Basolateral Amygdala or Nucleus Accumbens Shell Requires Concurrent Dopamine Receptor Activation in Both Brain Regions

ERIC Educational Resources Information Center

LaLumiere, Ryan T.; Nawar, Erene M.; McGaugh, James L.

2005-01-01

Previous findings indicate that the basolateral amygdala (BLA) and the nucleus accumbens (NAc) interact in influencing memory consolidation. The current study investigated whether this interaction requires concurrent dopamine (DA) receptor activation in both brain regions. Unilateral, right-side cannulae were implanted into the BLA and the…

Depth of Monocular Elements in a Binocular Scene: The Conditions for da Vinci Stereopsis

ERIC Educational Resources Information Center

Cook, Michael; Gillam, Barbara

2004-01-01

Quantitative depth based on binocular resolution of visibility constraints is demonstrated in a novel stereogram representing an object, visible to 1 eye only, and seen through an aperture or camouflaged against a background. The monocular region in the display is attached to the binocular region, so that the stereogram represents an object which…

Application of graphene oxide/lanthanum-modified carbon paste electrode for the selective determination of dopamine

NASA Astrophysics Data System (ADS)

Ye, Fengying; Feng, Chenqi; Fu, Ning; Wu, Huihui; Jiang, Jibo; Han, Sheng

2015-12-01

A home-made carbon paste electrode (CPE) was reformed by graphene oxide (GO)/lanthanum (La) complexes, and a modified electrode, called GO-La/CPE, was fabricated for the selective determination of dopamine (DA) by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Several factors affecting the electrocatalytic performance of the modified sensor were investigated. Owning to the combination of GO and La ions, the GO-La/CPE sensor exhibited large surface area, well selectivity, good repeatability and stability in the oxidation reaction of DA. At optimal conditions, the response of the GO-La/CPE electrode for determining DA was linear in the region of 0.01-0.1 μM and 0.1-400.0 μM. The limit of detection was down to 0.32 nM (S/N = 3). In addition, this modified electrode was successfully applied to the detection of DA in real urine and serum samples by using standard adding method, showing its promising application in the electroanalysis of real samples.

The Value of Information from a GRACE-Enhanced Drought Severity Index

NASA Astrophysics Data System (ADS)

Kuwayama, Y.; Bernknopf, R.; Brookshire, D.; Macauley, M.; Zaitchik, B. F.; Rodell, M.; Vail, P.; Thompson, A.

2015-12-01

In this project, we develop a framework to estimate the economic value of information from the Gravity and Climate Experiment (GRACE) for drought monitoring and to understand how the GRACE Data Assimilation (GRACE-DA) system can inform decision making to improve regional economic outcomes. Specifically, we consider the potential societal value of further incorporating GRACE-DA information into the U.S. Drought Monitor mapmaking process. Research activities include (a) a literature review, (b) a series of listening sessions with experts and stakeholders, (c) the development of a conceptual economic framework based on a Bayesian updating procedure, and (d) an econometric analysis and retrospective case study to understand the GRACE-DA contribution to agricultural policy and production decisions. Taken together, the results from these research activities support our conclusion that GRACE-DA has the potential to lower the variance associated with our understanding of drought and that this improved understanding has the potential to change policy decisions that lead to tangible societal benefits.

AlN/GaN Digital Alloy for Mid- and Deep-Ultraviolet Optoelectronics.

PubMed

Sun, Wei; Tan, Chee-Keong; Tansu, Nelson

2017-09-19

The AlN/GaN digital alloy (DA) is a superlattice-like nanostructure formed by stacking ultra-thin ( ≤ 4 monolayers) AlN barriers and GaN wells periodically. Here we performed a comprehensive study on the electronics and optoelectronics properties of the AlN/GaN DA for mid- and deep-ultraviolet (UV) applications. Our numerical analysis indicates significant miniband engineering in the AlN/GaN DA by tuning the thicknesses of AlN barriers and GaN wells, so that the effective energy gap can be engineered from ~3.97 eV to ~5.24 eV. The band structure calculation also shows that the valence subbands of the AlN/GaN DA is properly rearranged leading to the heavy-hole (HH) miniband being the top valence subband, which results in the desired transverse-electric polarized emission. Furthermore, our study reveals that the electron-hole wavefunction overlaps in the AlN/GaN DA structure can be remarkably enhanced up to 97% showing the great potential of improving the internal quantum efficiency for mid- and deep-UV device application. In addition, the optical absorption properties of the AlN/GaN DA are analyzed with wide spectral coverage and spectral tunability in mid- and deep-UV regime. Our findings suggest the potential of implementing the AlN/GaN DA as a promising active region design for high efficiency mid- and deep-UV device applications.

Infusions of ascorbic acid into the medial preoptic area facilitate appetitive sexual behavior in the female rat.

PubMed

Graham, M Dean; Pfaus, James G

2013-10-02

Ascorbic acid (AA), also known as Vitamin C, enhances dopamine (DA) transmission in mesolimbic and nigrostriatal terminals and augments DA-mediated behaviors. It is not yet known whether AA has a similar influence in other DA terminals, in particular terminals of the incertohypothalamic system that modulate the function of the medial preoptic area (mPOA). In female rats, DA in the mPOA plays a critical role in the generation of appetitive sexual responses, notably solicitations, hops, and darts, and we have shown previously that the role of DA in this region on female sexual behavior changes depending on the hormonal profile of the female. Since AA has often been used as a vehicle control in the examination of rat sexual behavior, the present study examined the effect of infusions of AA to the mPOA of sexual experienced ovariectomized rats under two hormonal conditions: partially-primed with estradiol benzoate (EB) alone or fully-primed with EB and progesterone. Relative to saline baselines, females under both hormonal conditions displayed a significant increase in appetitive sexual behaviors following infusions of AA. No difference in lordosis behavior was observed following AA infusions relative to saline baselines. We suggest that the mechanism by which AA infusions to the mPOA increase appetitive sexual behaviors in female rats may be through dose-dependent DA receptor interactions, possibly through both presynaptic release mechanisms and postsynaptic DA D1-related messenger systems. © 2013.

Seizures, cysticercosis and rural-to-urban migration: the PERU MIGRANT study

PubMed Central

Gonzales, Isidro; Miranda, J Jaime; Rodriguez, Silvia; Vargas, Victor; Cjuno, Alfredo; Smeeth, Liam; Gonzalez, Armando E; Tsang, Victor C W; Gilman, Robert H; Garcia, Hector H

2015-01-01

Objectives To examine the prevalence of seizures, epilepsy and seropositivity to cysticercosis in rural villagers (cysticercosis-endemic setting), rural-to-urban migrants into a non-endemic urban shanty town and urban inhabitants of the same non-endemic shanty town. Methods Three Peruvian populations (n = 985) originally recruited into a study about chronic diseases and migration were studied. These groups included rural inhabitants from an endemic region (n = 200), long-term rural-to-urban migrants (n = 589) and individuals living in the same urban setting (n = 196). Seizure disorders were detected by a survey, and a neurologist examined positive respondents. Serum samples from 981/985 individuals were processed for cysticercosis antibodies on immunoblot. Results Epilepsy prevalence (per 1000 people) was 15.3 in the urban group, 35.6 in migrants and 25 in rural inhabitants. A gradient in cysticercosis antibody seroprevalence was observed: urban 2%, migrant 13.5% and rural group 18% (P < 0.05). A similarly increasing pattern of higher seroprevalence was observed among migrants by age at migration. In rural villagers, there was strong evidence of an association between positive serology and having seizures (P = 0.011) but such an association was not observed in long-term migrants or in urban residents. In the entire study population, compared with seronegative participants, those with strong antibody reactions (≥ 4 antibody bands) were more likely to have epilepsy (P < 0.001). Conclusions It is not only international migration that affects cysticercosis endemicity; internal migration can also affect patterns of endemicity within an endemic country. The neurological consequences of cysticercosis infection likely outlast the antibody response for years after rural-to-urban migration. Objectifs Examiner la prévalence des crises d’épilepsie, de l’épilepsie et de la séropositivité à la cysticercose chez les villageois des zones rurales (cadre endémique pour la cysticercose), chez les migrants des zones ruraux vers les zones urbaines dans un bidonville urbain non endémique et chez les habitants urbains du même bidonville non endémique. Méthodes Trois populations péruviennes (n = 985) recrutées initialement dans une étude sur les maladies chroniques et la migration, ont été étudiées. Ces groupes comprenaient des habitants de zones rurales d'une région d'endémie (n = 200), des migrants de long terme de zones ruraux vers les villes (n = 589) et les personnes vivant dans le même milieu urbain (n = 196). Les troubles épileptiques ont été détectés par un sondage et un neurologue a examiné les répondants positifs. Des échantillons de sérum de 981/985 individus ont été testés pour les anticorps de cysticercose par Immunoblot. Résultats La prévalence de l’épilepsie (pour 1000 personnes) était de 15,3 dans le groupe urbain; 35,6 chez les migrants et 25 dans la population rurale. Un gradient dans la séroprévalence des anticorps de la cysticercose a été observé: dans le groupe urbain 2%, le groupe de migrants 13,5% et le groupe rural 18% (p <0,05). Une tendance croissante similaire de séroprévalence plus élevée a été observée chez les migrants selon l’âge à la migration. Chez les villageois ruraux, il y avait des preuves solides d'une association entre une sérologie positive et le fait d'avoir des crises (p = 0,011), mais une telle association n'a pas été observée chez les migrants de long terme ou chez les résidents urbains. Dans l'ensemble de la population de l’étude, ceux avec de fortes réactions d'anticorps (≥ 4 bandes d'anticorps) étaient plus susceptibles d'avoir l’épilepsie (p <0,001) comparé aux participants séronégatifs. Conclusions La migration internationale n'est pas la seule qui affecte l'endémicité de la cysticercose; la migration interne peut aussi modifier les profils d'endémicité au sein d'un même pays d'endémie. Les conséquences neurologiques de l'infection par la cysticercose sont susceptibles de survivre à la réponse d'anticorps durant des années après la migration des zones rurales vers les zones urbaines. Objetivos Examinar la prevalencia de convulsiones, epilepsia, y seropositividad para cisticercosis entre población rural (de zonas endémicas para cisticercosis), inmigrantes provenientes de zonas rurales a tugurios urbanos no endémicos, y habitantes urbanos de los mismo tugurios urbanos no endémicos. Métodos Se estudiaron tres poblaciones peruanas (n=985) originalmente reclutadas en un estudio de enfermedades crónicas y migración. Estos grupos incluían habitantes rurales de una región endémica (n=200), inmigrantes de larga duración de zonas rurales a urbanas (n=589), e individuos que vivían en la misma zona urbana (n=196). Las convulsiones se detectaron mediante una encuesta y un neurólogo examinó a quienes habían respondido positivamente. Se procesaron muestras de suero de 981/985 individuos en busca de anticuerpos para cisticercosis mediante inmunoblot. Resultados La prevalencia de epilepsia (por 1,000 personas) era de 15.3 en el grupo urbano, 35.6 en inmigrantes y 25 en habitantes rurales. Se observó un gradiente en la seroprevalencia de los anticuerpos para cisticercosis: grupos urbano 2%, inmigrante 13.5% y rural 18% (p<0.05). Se observó un patrón de aumento similar de mayor seroprevalencia entre inmigrantes según la edad que tenían en el momento de emigrar. En pobladores rurales, había una evidencia importante de asociación entre tener una serología positiva y sufrir convulsiones (p=0.011), pero esta asociación no se observaba en inmigrantes de larga duración o residentes urbanos. En la población al completo, comparada con los participantes seronegativos, aquellos con una fuerte reactividad de anticuerpos (≥4 bandas de anticuerpos) tenían una mayor probabilidad de sufrir epilepsia (p<0.001). Conclusiones No solo la migración internacional afecta la endemicidad de cisticercosis; la migración interna también puede afectar los patrones de endemicidad dentro de un país endémico. Las consecuencias neurológicas de la infección por cisticercos podrían durar más que la respuesta a anticuerpos años después de la migración de zonas rurales a zonas urbanas. PMID:25581851

Spatiotemporal Distribution and Population Structure of Monokalliapseudes schubarti (Tanaidacea: Kalliapseudidae) in an Estuary in Southern Brazil

PubMed Central

Freitas-Júnior, Felipe; Christoffersen, Martin Lindsey; de Araújo, Joafrâncio Pereira; Branco, Joaquim Olinto

2013-01-01

Monokalliapseudes schubarti is an endemic tanaidacean microcrustacean from southeastern Brazil to Uruguay inhabiting low energy estuaries. Saco da Fazenda is located in the estuary of the Itajaí-Açú River, state of Santa Catarina, Brazil. It is exposed to strong anthropic impact and receives intensive flows of domestic wastewater, solid residues, and drainage activities. Specimens of M. schubarti were collected monthly, in the intertidal and subtidal regions of Saco da Fazenda, in four stations defined as a function of the physiography of the environment during the period of July 2003 to June 2004. Fecundity values were high, with continuous reproductive activity during the whole period of study. The greatest population densities were observed in the intertidal region, where they are nevertheless intensely consumed by birds, swimming crabs, and fish. This species represents a fundamental link in the food chain of Saco da Fazenda, transferring energy from the detritus level to higher trophic levels. Habitat disturbance and high organic matter may represent factors controlling the distribution of populations of M. schubarti. For this reason, the species may be used to monitor anthropic effects in estuarine areas. PMID:24298211

Analytic Evolution of Singular Distribution Amplitudes in QCD

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

Tandogan Kunkel, Asli

2014-08-01

Distribution amplitudes (DAs) are the basic functions that contain information about the quark momentum. DAs are necessary to describe hard exclusive processes in quantum chromodynamics. We describe a method of analytic evolution of DAs that have singularities such as nonzero values at the end points of the support region, jumps at some points inside the support region and cusps. We illustrate the method by applying it to the evolution of a at (constant) DA, antisymmetric at DA, and then use the method for evolution of the two-photon generalized distribution amplitude. Our approach to DA evolution has advantages over the standardmore » method of expansion in Gegenbauer polynomials [1, 2] and over a straightforward iteration of an initial distribution with evolution kernel. Expansion in Gegenbauer polynomials requires an infinite number of terms in order to accurately reproduce functions in the vicinity of singular points. Straightforward iteration of an initial distribution produces logarithmically divergent terms at each iteration. In our method the logarithmic singularities are summed from the start, which immediately produces a continuous curve. Afterwards, in order to get precise results, only one or two iterations are needed.« less

Dopamine-induced changes in neural network patterns supporting aversive conditioning.

PubMed

Diaconescu, Andreea Oliviana; Menon, Mahesh; Jensen, Jimmy; Kapur, Shitij; McIntosh, Anthony Randal

2010-02-08

The aim of the present paper is to assess the effects of altered dopamine (DA) transmission on the functional connectivity among brain regions mediating aversive conditioning in humans. To this aim, we analyzed a previous published data set from a double-blind design combined with functional magnetic resonance imaging (fMRI) recordings in which healthy volunteers were randomly assigned to one of three drug groups: amphetamine (an indirect DA agonist), haloperidol (DA D2 receptor antagonist), and placebo. Participants were exposed to an aversive classical conditioning paradigm using cutaneous electrical stimulation as the unconditioned stimulus (US), and visual cues as the conditioned stimuli (CS) where one colour (CS+) was followed by the US in 33% of the trials and another colour (CS-) had no consequences. All participants reported awareness of stimulus contingencies. Group analysis of fMRI data revealed that the left ventral striatum (VS) and amygdala activated in response to the CS+ in all the three groups. Because of their activation patterns and documented involvement in aversive conditioning, both regions were used as seeds in the functional connectivity analysis. To constrain the functional networks obtained to relate to the conditioned response, we also correlated seed activity with the Galvanic Skin Response (GSR). In the placebo group, the right ventral tegmental area/substantia nigra (VTA/SN), bilateral caudate, right parahippocampal gyrus, left inferior parietal lobule (IPL), bilateral postcentral gyrus, bilateral middle frontal (BA 46), orbitofrontal, and ventromedial prefrontal cortices (PFC, BA 10/11) correlated with the VS and amygdala seeds in response to the CS+ compared to the CS-. Enhancing dopamine transmission via amphetamine was associated with reduced task differences and significant functional connectivity for both CS+ and CS- conditions between the left VS seed and regions modulated by DA, such as the left VTA/SN, right caudate, left amygdala, left middle frontal gyrus (BA 46), and bilateral ventromedial PFC (BA 10). Blocking dopamine transmission via haloperidol was associated with significant functional connectivity across an alternate network of regions including the left amygdala seed and the right insula, the left ACC (BA 24/32), bilateral IPL (BA 40), precuneus (BA 7), post-central gyrus, middle frontal gyrus (BA 46), and supplementary motor area (SMA, BA 6) to the CS+ versus the CS-. These data provide insight into the distinct effects of DA agents on the functional connectivity between striatal, limbic, and prefrontal areas. Copyright 2009 Elsevier B.V. All rights reserved.

Distinctive Modulation of Dopamine Release in the Nucleus Accumbens Shell Mediated by Dopamine and Acetylcholine Receptors.

PubMed

Shin, Jung Hoon; Adrover, Martin F; Alvarez, Veronica A

2017-11-15

Nucleus accumbens (NAc) shell shows unique dopamine (DA) signals in vivo and plays a unique role in DA-dependent behaviors such as reward-motivated learning and the response to drugs of abuse. A disynaptic mechanism for DA release was reported and shown to require synchronized firing of cholinergic interneurons (CINs) and activation of nicotinic acetylcholine (ACh) receptors (nAChRs) in DA neuron (DAN) axons. The properties of this disynaptic mechanism of DA transmission are not well understood in the NAc shell. In this study, in vitro fast-scan cyclic voltammetry was used to examine the modulation of DA transmission evoked by CINs firing in the shell of mice and compared with other striatal regions. We found that DA signals in the shell displayed significant degree of summation in response to train stimulation of CINs, contrary to core and dorsal striatum. The summation was amplified by a D2-like receptor antagonist and experiments with mice with targeted deletion of D2 receptors to DANs or CINs revealed that D2 receptors in CINs mediate a fast inhibition observed within 100 ms of the first pulse, whereas D2 autoreceptors in DAN terminals are engaged in a slower inhibition that peaks at ∼500 ms. ACh also contributes to the use-dependent inhibition of DA release through muscarinic receptors only in the shell, where higher activity of acetylcholinesterase minimizes nAChR desensitization and promotes summation. These findings show that DA signals are modulated differentially by endogenous DA and ACh in the shell, which may underlie the unique features of shell DA signals in vivo SIGNIFICANCE STATEMENT The present study reports that dopamine (DA) release evoked by activation of cholinergic interneurons displays a high degree of summation in the shell and shows unique modulation by endogenous DA and acetylcholine. Desensitization of nicotinic receptors, which is a prevailing mechanism for use-dependent inhibition in the nucleus accumbens core and dorsal striatum, is also minimal in the shell in part due to elevated acetylcholinesterase activity. This distinctive modulation of DA transmission in the shell may have functional implications in the acquisition of reward-motivated behaviors and reward seeking. Copyright © 2017 the authors 0270-6474/17/3711166-15$15.00/0.

Evidence of new species for malaria vector Anopheles nuneztovari sensu lato in the Brazilian Amazon region.

PubMed

Scarpassa, Vera Margarete; Cunha-Machado, Antonio Saulo; Saraiva, José Ferreira

2016-04-12

Anopheles nuneztovari sensu lato comprises cryptic species in northern South America, and the Brazilian populations encompass distinct genetic lineages within the Brazilian Amazon region. This study investigated, based on two molecular markers, whether these lineages might actually deserve species status. Specimens were collected in five localities of the Brazilian Amazon, including Manaus, Careiro Castanho and Autazes, in the State of Amazonas; Tucuruí, in the State of Pará; and Abacate da Pedreira, in the State of Amapá, and analysed for the COI gene (Barcode region) and 12 microsatellite loci. Phylogenetic analyses were performed using the maximum likelihood (ML) approach. Intra and inter samples genetic diversity were estimated using population genetics analyses, and the genetic groups were identified by means of the ML, Bayesian and factorial correspondence analyses and the Bayesian analysis of population structure. The Barcode region dataset (N = 103) generated 27 haplotypes. The haplotype network suggested three lineages. The ML tree retrieved five monophyletic groups. Group I clustered all specimens from Manaus and Careiro Castanho, the majority of Autazes and a few from Abacate da Pedreira. Group II clustered most of the specimens from Abacate da Pedreira and a few from Autazes and Tucuruí. Group III clustered only specimens from Tucuruí (lineage III), strongly supported (97 %). Groups IV and V clustered specimens of A. nuneztovari s.s. and A. dunhami, strongly (98 %) and weakly (70 %) supported, respectively. In the second phylogenetic analysis, the sequences from GenBank, identified as A. goeldii, clustered to groups I and II, but not to group III. Genetic distances (Kimura-2 parameters) among the groups ranged from 1.60 % (between I and II) to 2.32 % (between I and III). Microsatellite data revealed very high intra-population genetic variability. Genetic distances showed the highest and significant values (P = 0.005) between Tucuruí and all the other samples, and between Abacate da Pedreira and all the other samples. Genetic distances, Bayesian (Structure and BAPS) analyses and FCA suggested three distinct biological groups, supporting the barcode region results. The two markers revealed three genetic lineages for A. nuneztovari s.l. in the Brazilian Amazon region. Lineages I and II may represent genetically distinct groups or species within A. goeldii. Lineage III may represent a new species, distinct from the A. goeldii group, and may be the most ancestral in the Brazilian Amazon. They may have differences in Plasmodium susceptibility and should therefore be investigated further.

High resolution structure of cleaved Serpin 42 Da from Drosophila melanogaster.

PubMed

Ellisdon, Andrew M; Zhang, Qingwei; Henstridge, Michelle A; Johnson, Travis K; Warr, Coral G; Law, Ruby Hp; Whisstock, James C

2014-04-24

The Drosophila melanogaster Serpin 42 Da gene (previously Serpin 4) encodes a serine protease inhibitor that is capable of remarkable functional diversity through the alternative splicing of four different reactive centre loop exons. Eight protein isoforms of Serpin 42 Da have been identified to date, targeting the protease inhibitor to both different proteases and cellular locations. Biochemical and genetic studies suggest that Serpin 42 Da inhibits target proteases through the classical serpin 'suicide' inhibition mechanism, however the crystal structure of a representative Serpin 42 Da isoform remains to be determined. We report two high-resolution crystal structures of Serpin 42 Da representing the A/B isoforms in the cleaved conformation, belonging to two different space-groups and diffracting to 1.7 Å and 1.8 Å. Structural analysis reveals the archetypal serpin fold, with the major elements of secondary structure displaying significant homology to the vertebrate serpin, neuroserpin. Key residues known to have central roles in the serpin inhibitory mechanism are conserved in both the hinge and shutter regions of Serpin 42 Da. Furthermore, these structures identify important conserved interactions that appear to be of crucial importance in allowing the Serpin 42 Da fold to act as a versatile template for multiple reactive centre loops that have different sequences and protease specificities. In combination with previous biochemical and genetic studies, these structures confirm for the first time that the Serpin 42 Da isoforms are typical inhibitory serpin family members with the conserved serpin fold and inhibitory mechanism. Additionally, these data reveal the remarkable structural plasticity of serpins, whereby the basic fold is harnessed as a template for inhibition of a large spectrum of proteases by reactive centre loop exon 'switching'. This is the first structure of a Drosophila serpin reported to date, and will provide a platform for future mutational studies in Drosophila to ascertain the functional role of each of the Serpin 42 Da isoforms.

Towards guided data assimilation for operational hydrologic forecasting in the US Tennessee River basin

NASA Astrophysics Data System (ADS)

Weerts, A.; Wood, A. W.; Clark, M. P.; Carney, S.; Day, G. N.; Lemans, M.; Sumihar, J.; Newman, A. J.

2014-12-01

In the US, the forecasting approach used by the NWS River Forecast Centers and other regional organizations such as the Bonneville Power Administration (BPA) or Tennessee Valley Authority (TVA) has traditionally involved manual model input and state modifications made by forecasters in real-time. This process is time consuming and requires expert knowledge and experience. The benefits of automated data assimilation (DA) as a strategy for avoiding manual modification approaches have been demonstrated in research studies (eg. Seo et al., 2009). This study explores the usage of various ensemble DA algorithms within the operational platform used by TVA. The final goal is to identify a DA algorithm that will guide the manual modification process used by TVA forecasters and realize considerable time gains (without loss of quality or even enhance the quality) within the forecast process. We evaluate the usability of various popular algorithms for DA that have been applied on a limited basis for operational hydrology. To this end, Delft-FEWS was wrapped (via piwebservice) in OpenDA to enable execution of FEWS workflows (and the chained models within these workflows, including SACSMA, UNITHG and LAGK) in a DA framework. Within OpenDA, several filter methods are available. We considered 4 algorithms: particle filter (RRF), Ensemble Kalman Filter and Asynchronous Ensemble Kalman and Particle filter. Retrospective simulation results for one location and algorithm (AEnKF) are illustrated in Figure 1. The initial results are promising. We will present verification results for these methods (and possible more) for a variety of sub basins in the Tennessee River basin. Finally, we will offer recommendations for guided DA based on our results. References Seo, D.-J., L. Cajina, R. Corby and T. Howieson, 2009: Automatic State Updating for Operational Streamflow Forecasting via Variational Data Assimilation, 367, Journal of Hydrology, 255-275. Figure 1. Retrospectively simulated streamflow for the headwater basin above Powell River at Jonesville (red is observed flow, blue is simulated flow without DA, black is simulated flow with DA)

A 32 kDa viral attachment protein of lymphocystis disease virus (LCDV) specifically interacts with a 27.8 kDa cellular receptor from flounder (Paralichthys olivaceus).

PubMed

Zhong, Ying; Fei, Chenjie; Tang, Xiaoqian; Zhan, Wenbin; Sheng, Xiuzhen

2017-06-01

The 27.8 kDa protein in flounder gill (FG) cells was previously proved to be a receptor specific for lymphocystis disease virus (LCDV) entry and infection. In this paper, a 32 kDa viral attachment protein (VAP) of LCDV specifically binding to the 27.8 kDa receptor (27.8R) was found by far-Western blotting coupled with monoclonal antibodies (MAbs) against 27.8R. The 32 kDa protein was confirmed to be encoded by the open reading frame (ORF) 038 gene in LCDV-C, and predicted to contain a putative transmembrane region, multiple N-myristoylation and glycosylation sites and phosphorylation motifs. The expression plasmid of pET-32a-ORF038 was constructed and the recombinant VAP (rVAP) was obtained. Rabbit polyclonal antibodies against the rVAP were prepared and could recognize the rVAP and 32 kDa protein in LCDV. Immunogold electron microscopy showed that the 32 kDa protein was located on the surface of LCDV particles. Immunofluorescence assay demonstrated that the rVAP could bind to the 27.8R on the cell membrane of the FG monolayer and the anti-27.8R MAbs could block the rVAP binding. Pre-incubation of the rVAP with FG cells before LCDV infection, or pre-incubation of LCDV with the antibodies against the rVAP, could significantly decrease the LCDV copy numbers (P<0.05) and delay the emergence of cytopathic effects in FG cells in a dose-dependent manner. These results indicated for the first time that the 32 kDa protein functioned as an attachment protein for the initial attachment and entry of LCDV, and the interaction of the 32 kDa VAP with the 27.8R-initiated LCDV infection.

Emissions and prevention/control techniques for automobile body shops in Ciudad Juarez, Mexico

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

Jeffery, J.D.; Sager, M.

1999-08-01

Emissions of Volatile Organic Compounds (VOC) from automobile body repair shops are believed to be significant and to contribute to ozone nonattainment in El Paso, Texas and to violations of ozone air quality standards in Ciudad Juarez, Mexico. The Direccion de Desarrollo Urbano Y Ecologia (DDUE), (the local agency in Ciudad Juarez, Mexico) requested CICA's assistance in determining emissions from and identifying appropriate pollution prevention and control techniques for automobile body repair shops in Ciudad Juarez.

Normal-phase liquid chromatography retention behavior of polycyclic aromatic sulfur heterocycles and alkyl-substituted polycyclic aromatic sulfur heterocycle isomers on an aminopropyl stationary phase.

PubMed

Wilson, Walter B; Hayes, Hugh V; Sander, Lane C; Campiglia, Andres D; Wise, Stephen A

2018-02-01

Retention indices for 67 polycyclic aromatic sulfur heterocycles (PASHs) and 80 alkyl-substituted PASHs were determined using normal-phase liquid chromatography (NPLC) on an aminopropyl (NH 2 ) stationary phase. The retention behavior of PASH on the NH 2 phase is correlated with the number of aromatic carbon atoms and two structural characteristics have a significant influence on their retention: non-planarity (thickness, T) and the position of the sulfur atom in the bay-region of the structure. Correlations between solute retention on the NH 2 phase and T of PASHs were investigated for three cata-condensed (cata-) PASH isomer groups: (a) 13 four-ring molecular mass (MM) 234 Da cata-PASHs, (b) 20 five-ring MM 284 Da cata-PASHs, and (c) 12 six-ring MM 334 Da cata-PASHs. Correlation coefficients ranged from r = -0.49 (MM 234 Da) to r = -0.65 (MM 334 Da), which were significantly lower than structurally similar PAH isomer groups (r = -0.70 to r = -0.99). The NPLC retention behavior of the PASHs are compared to similar results for PAHs.

A tobacco extract containing alkaloids induces distinct effects compared to pure nicotine on dopamine release in the rat.

PubMed

Khalki, Hanane; Navailles, Sylvia; Piron, Camille L; De Deurwaerdère, Philippe

2013-06-07

It has been suggested that minor alkaloids in plants play a role in the biological and neuronal actions of nicotine. We hypothesized that these molecules modulate the effect of nicotine on the activity of central dopamine (DA) neurons, one of the main cellular targets in addiction to drugs. In this study the effect of a single intraperitoneal injection of either nicotine or an alkaloid extract of the tobacco plant (0.5 mg/kg) on the efflux of DA were investigated. DA was measured in vivo by intracerebral microdialysis in the nucleus accumbens and the striatum of freely-moving rats. Results show that nicotine enhanced accumbal and striatal DA extracellular levels (+47 and 20% above baseline, respectively). The extract also evoked a significant increase in DA extracellular levels in both regions (+33 and +38% above baseline). However, this effect was significantly higher compared to nicotine in the striatum only. In conclusion, the tobacco extract enhanced the neurochemical effect of nicotine alone in the striatum, a response that could underlie the higher propensity of developing addictive-like behavior using nicotine with tobacco alkaloids. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Allergenic Characterization of 27-kDa Glycoprotein, a Novel Heat Stable Allergen, from the Pupa of Silkworm, Bombyx mori.

PubMed

Jeong, Kyoung Yong; Son, Mina; Lee, June Yong; Park, Kyung Hee; Lee, Jae-Hyun; Park, Jung-Won

2016-01-01

Boiled silkworm pupa is a traditional food in Asia, and patients with silkworm pupa food allergy are common in these regions. Still now only one allergen from silkworm, arginine kinase, has been identified. The purpose of this study was to identify novel food allergens in silkworm pupa by analyzing a protein extract after heat treatment. Heat treated extracts were examined by proteomic analysis. A 27-kDa glycoprotein was identified, expressed in Escherichia coli, and purified. IgE reactivity of the recombinant protein was investigated by ELISA. High molecular weight proteins (above 100 kDa) elicited increased IgE binding after heat treatment compared to that before heat treatment. The molecular identities of these proteins, however, could not be determined. IgE reactivity toward a 27-kDa glycoprotein was also increased after heating the protein extract. The recombinant protein was recognized by IgE antibodies from allergic subjects (33.3%). Glycation or aggregation of protein by heating may create new IgE binding epitopes. Heat stable allergens are shown to be important in silkworm allergy. Sensitization to the 27-kDa glycoprotein from silkworm may contribute to elevation of IgE to silkworm.

Allergenic Characterization of 27-kDa Glycoprotein, a Novel Heat Stable Allergen, from the Pupa of Silkworm, Bombyx mori

PubMed Central

Son, Mina; Lee, June Yong

2016-01-01

Boiled silkworm pupa is a traditional food in Asia, and patients with silkworm pupa food allergy are common in these regions. Still now only one allergen from silkworm, arginine kinase, has been identified. The purpose of this study was to identify novel food allergens in silkworm pupa by analyzing a protein extract after heat treatment. Heat treated extracts were examined by proteomic analysis. A 27-kDa glycoprotein was identified, expressed in Escherichia coli, and purified. IgE reactivity of the recombinant protein was investigated by ELISA. High molecular weight proteins (above 100 kDa) elicited increased IgE binding after heat treatment compared to that before heat treatment. The molecular identities of these proteins, however, could not be determined. IgE reactivity toward a 27-kDa glycoprotein was also increased after heating the protein extract. The recombinant protein was recognized by IgE antibodies from allergic subjects (33.3%). Glycation or aggregation of protein by heating may create new IgE binding epitopes. Heat stable allergens are shown to be important in silkworm allergy. Sensitization to the 27-kDa glycoprotein from silkworm may contribute to elevation of IgE to silkworm. PMID:26770033

Experience-Dependent Effects of Cocaine Self-Administration/Conditioning on Prefrontal and Accumbens Dopamine Responses

PubMed Central

Ikegami, Aiko; Olsen, Christopher M.; D’Souza, Manoranjan S.; Duvauchelle, Christine L.

2008-01-01

Experiments were performed to examine the effects of cocaine self-administration and conditioning experience on operant behavior, locomotor activity, and nucleus accumbens (NAcc) and prefrontal cortex (PFC) dopamine (DA) responses. Sensory cues were paired with alternating cocaine and nonreinforcement during 12 (limited training) or 40 (long-term training) daily operant sessions. After limited training, NAcc DA responses to cocaine were significantly enhanced in the presence of cocaine-associated cues compared with nonreward cues and significantly depressed after cocaine-paired cues accompanied a nonreinforced lever response. PFC DA levels were generally nonresponsive to cues after the same training duration. However, after long-term training, cocaine-associated cues increased the magnitude of cocaine-stimulated PFC DA levels significantly over levels observed with nonreinforcement cues. Conversely, conditioned cues no longer influenced NAcc DA levels after long-term training. In addition, cocaine-stimulated locomotor activity was enhanced by cocaine-paired cues after long-term, but not after limited, training. Findings demonstrate that cue-induced cocaine expectation exerts a significant impact on dopaminergic and behavioral systems, progressing from mesolimbic to mesocortical regions and from latent to patent behaviors as cocaine and associative experiences escalate. PMID:17469929

Translocation of an 89-kDa periplasmic protein is associated with Holospora infection

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

Iwatani, Koichi; Dohra, Hideo; Lang, B. Franz

2005-12-02

The symbiotic bacterium Holospora obtusa infects the macronucleus of the ciliate Paramecium caudatum. After ingestion by its host, an infectious form of Holospora with an electron-translucent tip passes through the host digestive vacuole and penetrates the macronuclear envelope with this tip. To investigate the underlying molecular mechanism of this process, we raised a monoclonal antibody against the tip-specific 89-kDa protein, sequenced this partially, and identified the corresponding complete gene. The deduced protein sequence carries two actin-binding motifs. Indirect immunofluorescence microscopy shows that during escape from the host digestive vacuole, the 89-kDa proteins translocates from the inside to the outside ofmore » the tip. When the bacterium invades the macronucleus, the 89-kDa protein is left behind at the entry point of the nuclear envelope. Transmission electron microscopy shows the formation of fine fibrous structures that co-localize with the antibody-labeled regions of the bacterium. Our findings suggest that the 89-kDa protein plays a role in Holospora's escape from the host digestive vacuole, the migration through the host cytoplasm, and the invasion into the macronucleus.« less

Region and Domain Dependent Action of Nomifensine

PubMed Central

Shu, Zhan; Taylor, I. Mitch; Walters, Seth H.; Michael, Adrian C.

2014-01-01

The dopamine (DA) terminal fields in the rat dorsal striatum (DS) and nucleus accumbens core (NAcc) are organized as patchworks of domains that exhibit distinct kinetics of DA release and clearance. The present study used fast-scan cyclic voltammetry recordings of electrically evoked DA overflow to test the hypothesis that nomifensine might exhibit domain-dependent actions within the NAcc, as we previously found to be the case within the DS. Within the NAcc, nomifensine preferentially enhanced evoked dopamine overflow in the slow compared to the fast domains. To seek a kinetic explanation for nomifensine’s selective actions, we quantified the apparent KM of DA clearance by numerically evaluating the derivative of the descending phase of the DA signal after the end of the stimulus. For comparison, we likewise quantified apparent KM in the domains of the DS. As expected because it is a competitive inhibitor, nomifensine significantly increased the apparent KM in both the fast and slow domains of both the NAcc and DS. However, our analysis also leads to the novel finding that nomifensine preferentially increases the apparent KM in the NAcc compared to the DS: apparent KM increased by ~500% in the NAcc and ~200% in the DS. PMID:24766210

Three new species of mealybug (Hemiptera, Coccomorpha, Pseudococcidae) on persimmon fruit trees (Diospyros kaki) in southern Brazil

PubMed Central

Pacheco da Silva, Vitor C.; Kaydan, Mehmet Bora; Germain, Jean-François; Malausa, Thibaut; Botton, Marcos

2016-01-01

Abstract Brazil has the greatest insect diversity in the world; however, little is known about its scale insect species (Hemiptera: Coccomorpha). Mealybugs (Pseudococcidae) have been found in at least 50% of persimmon orchards Diospyros kaki L. in the southern part of the country. In this study three new mealybug species on persimmon trees located in the Serra Gaúcha Region, RS, Brazil, namely, Anisococcus granarae Pacheco da Silva & Kaydan, sp. n., Ferrisia kaki Kaydan & Pacheco da Silva, sp. n. and Pseudococcus rosangelae Pacheco da Silva & Kaydan, sp. n. are described. In addition, an identification key for the genera occurring on fruit orchards and vineyards in Brazil is provided, together with illustrations and molecular data for the new species. PMID:27199595

Expression of Somatostatin, cortistatin, and their receptors, as well as dopamine receptors, but not of neprilysin, are reduced in the temporal lobe of Alzheimer's disease patients.

PubMed

Gahete, Manuel D; Rubio, Alicia; Durán-Prado, Mario; Avila, Jesús; Luque, Raúl M; Castaño, Justo P

2010-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive deficit, wherein the impairment of episodic memory is the major hallmark. AD patients exhibit augmented accumulation of amyloid-beta (Abeta) and hyperphosphorylated tau protein in specific brain regions. In addition, several neuropeptides/neurotransmitter axes clearly associated with cognitive processes, Abeta turnover, and tau phosphorylation have also been found to be impaired in AD, such as somatostatin (SST)/cortistatin (CST) and dopamine (DA) systems. However, to date there is no precise quantitative data on the expression of these systems in the human brain of AD and normal patients. Here we measured by quantitative real-time PCR the mRNA levels of SST/CST, their receptors (sst1-5 and DA receptors (drd1-5) in addition to neprilysin (a SST-regulated enzyme involved in Abeta degradation) in three regions of the temporal lobe, one of the cortical regions most severely affected by AD. Our results reveal that some components of SST/CST- and DA-axes are divergently altered in the three areas of AD patients. Despite this region-specific regulation, an overall, common reduction of these systems was observed in the temporal lobe of AD patients. Conversely, neprilysin expression was not altered in AD, suggesting that Abeta accumulation observed in AD is due to a lack of neprilysin activation by SST rather than to a reduction of its expression. Collectively, our results define a comprehensive scenario wherein reduction of ssts, drds, and sst ligands SST and CST, could be involved, at least in part, in some of the more important defects observed in AD.

Site-specific activation of dopamine and serotonin transmission by aniracetam in the mesocorticolimbic pathway of rats.

PubMed

Nakamura, K; Shirane, M; Koshikawa, N

2001-04-06

The effects of aniracetam on extracellular levels of dopamine (DA), serotonin (5-HT) and their metabolites were examined in five brain regions in freely moving stroke-prone spontaneously hypertensive rats (SHRSP) using in vivo microdialysis. Basal DA release in SHRSP was uniformly lower in all regions tested than that in age-matched control Wistar Kyoto rats. 3,4-Dihydroxyphenylacetic acid and homovanillic acid levels were altered in the basolateral amygdala, dorsal hippocampus and prefrontal cortex of SHRSP. While basal 5-HT release decreased in the striatum and increased in the basolateral amygdala, there was no associated change in 5-hydroxyindoleacetic acid levels. Systemic administration of aniracetam to SHRSP enhanced both DA and 5-HT release with partly associated change in their metabolite levels in the prefrontal cortex, basolateral amygdala and dorsal hippocampus, but not in the striatum and nucleus accumbens shell, in a dose-dependent manner (30 and/or 100 mg/kg p.o.). Microinjection (1 and 10 ng) of aniracetam or its metabolites (N-anisoyl-GABA and 2-pyrrolidinone) into the nucleus accumbens shell produced no turning behavior. These findings indicate that SHRSP have a dopaminergic hypofunction throughout the brain and that aniracetam elicits a site-specific activation in mesocorticolimbic dopaminergic and serotonergic pathways in SHRSP, possibly via nicotinic acetylcholine receptors in the ventral tegmental area and raphe nuclei. The physiological roles in the aniracetam-sensitive brain regions may closely link with their clinical efficacy towards emotional disturbances appearing after cerebral infarction.

Genetic analysis of the agrocinopine catabolic region of Agrobacterium tumefaciens Ti plasmid pTiC58, which encodes genes required for opine and agrocin 84 transport.

PubMed Central

Hayman, G T; Beck von Bodman, S; Kim, H; Jiang, P; Farrand, S K

1993-01-01

The acc region, subcloned from pTiC58 of classical nopaline and agrocinopine A and B Agrobacterium tumefaciens C58, allowed agrobacteria to grow using agrocinopine B as the sole source of carbon and energy. acc is approximately 6 kb in size. It consists of at least five genes, accA through accE, as defined by complementation analysis using subcloned fragments and transposon insertion mutations of acc carried on different plasmids within the same cell. All five regions are required for agrocin 84 sensitivity, and at least four are required for agrocinopine and agrocin 84 uptake. The complementation results are consistent with the hypothesis that each of the five regions is separately transcribed. Maxicell experiments showed that the first of these genes, accA, encodes a 60-kDa protein. Analysis of osmotic shock fractions showed this protein to be located in the periplasm. The DNA sequence of the accA region revealed an open reading frame encoding a predicted polypeptide of 59,147 Da. The amino acid sequence encoded by this open reading frame is similar to the periplasmic binding proteins OppA and DppA of Escherichia coli and Salmonella typhimurium and OppA of Bacillus subtilis. Images PMID:8366042

Separable Roles for Attentional Control Sub-Systems in Reading Tasks: A Combined Behavioral and fMRI Study

PubMed Central

Ihnen, S.K.Z.; Petersen, Steven E.; Schlaggar, Bradley L.

2015-01-01

Attentional control is important both for learning to read and for performing difficult reading tasks. A previous study invoked 2 mechanisms to explain reaction time (RT) differences between reading tasks with variable attentional demands. The present study combined behavioral and neuroimaging measures to test the hypotheses that there are 2 mechanisms of interaction between attentional control and reading; that these mechanisms are dissociable both behaviorally and neuro-anatomically; and that the 2 mechanisms involve functionally separable control systems. First, RT evidence was found in support of the 2-mechanism model, corroborating the previous study. Next, 2 sets of brain regions were identified as showing functional magnetic resonance imaging blood oxygen level-dependent activity that maps onto the 2-mechanism distinction. One set included bilateral Cingulo-opercular regions and mostly right-lateralized Dorsal Attention regions (CO/DA+). This CO/DA+ region set showed response properties consistent with a role in reporting which processing pathway (phonological or lexical) was biased for a particular trial. A second set was composed primarily of left-lateralized Frontal-parietal (FP) regions. Its signal properties were consistent with a role in response checking. These results demonstrate how the subcomponents of attentional control interact with subcomponents of reading processes in healthy young adults. PMID:24275830

DYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson's disease.

PubMed

Barallobre, M J; Perier, C; Bové, J; Laguna, A; Delabar, J M; Vila, M; Arbonés, M L

2014-06-12

In the brain, programmed cell death (PCD) serves to adjust the numbers of the different types of neurons during development, and its pathological reactivation in the adult leads to neurodegeneration. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) is a pleiotropic kinase involved in neural proliferation and cell death, and its role during brain growth is evolutionarily conserved. Human DYRK1A lies in the Down syndrome critical region on chromosome 21, and heterozygous mutations in the gene cause microcephaly and neurological dysfunction. The mouse model for DYRK1A haploinsufficiency (the Dyrk1a(+/-) mouse) presents neuronal deficits in specific regions of the adult brain, including the substantia nigra (SN), although the mechanisms underlying these pathogenic effects remain unclear. Here we study the effect of DYRK1A copy number variation on dopaminergic cell homeostasis. We show that mesencephalic DA (mDA) neurons are generated in the embryo at normal rates in the Dyrk1a haploinsufficient model and in a model (the mBACtgDyrk1a mouse) that carries three copies of Dyrk1a. We also show that the number of mDA cells diminishes in postnatal Dyrk1a(+/-) mice and increases in mBACtgDyrk1a mice due to an abnormal activity of the mitochondrial caspase9 (Casp9)-dependent apoptotic pathway during the main wave of PCD that affects these neurons. In addition, we show that the cell death induced by 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), a toxin that activates Casp9-dependent apoptosis in mDA neurons, is attenuated in adult mBACtgDyrk1a mice, leading to an increased survival of SN DA neurons 21 days after MPTP intoxication. Finally, we present data indicating that Dyrk1a phosphorylation of Casp9 at the Thr125 residue is the mechanism by which this kinase hinders both physiological and pathological PCD in mDA neurons. These data provide new insight into the mechanisms that control cell death in brain DA neurons and they show that deregulation of developmental apoptosis may contribute to the phenotype of patients with imbalanced DYRK1A gene dosage.

Differential glutamatergic modulation of monoamine release in the limbic lobe by selective anticonvulsant ionotropic and metabotropic glutamate receptor ligands.

PubMed

Smolders, I

2005-01-01

Several researchers are currently trying to unravel neurobiological relationships between epilepsy and depression. After all, these disorders often develop in the same vulnerable brain regions and the importance of comorbid depression and epilepsy is still underscored. Facilitation of central serotonin (5-HT), dopamine (DA) and noradrenaline (NAD) release seems to be associated with both anticonvulsant and antidepressant effects. We show that selective ionotropic and metabotropic glutamate receptor ligands with anticonvulsant properties differentially modulate NAD, DA and 5-HT in rat limbic lobe structures.

Dopamine D2 Receptors Act Upstream of AVP in the Latero-Anterior Hypothalamus to Modulate Adolescent Anabolic/Androgenic Steroid-Induced Aggression in Syrian Hamsters

PubMed Central

Morrison, Thomas R.; Ricci, Lesley A.; Melloni, Richard H.

2015-01-01

In pubertal male Syrian hamsters, exposure to anabolic/androgenic steroids (AAS) during adolescence facilitates a high level of offensive aggression modulated by the enhanced development and activity of the vasopressin (AVP) and dopamine (DA) neural systems within the latero-anterior hypothalamus (LAH), i.e., a brain region implicated in the control of aggression. The present studies provide a detailed report of the pharmacologic interactions between AVP and DA D2 receptor signaling within the LAH in the control of adolescent AAS-induced offensive aggression. Male Syrian hamsters were treated with AAS throughout adolescence and tested for aggression after local infusion of the DA D2 receptor antagonist eticlopride (ETIC) alone, or in combination with AVP in the LAH in an effort to determine the influence of DA D2 receptors relative to AVP-receptor mediated aggression mechanisms. As previously shown, ETIC infusion into the LAH suppressed adolescent AAS-induced aggressive responding; however, the AAS-induced aggressive phenotype was rescued by the co-infusion of AVP into the LAH. These behavioral data indicate that interactions between AVP and DA neural systems within the LAH modulate the control of aggression following adolescent exposure to AAS and that DA D2 receptor signaling functions upstream of AVP in the LAH to control this behavioral response. PMID:25798632

Dynamic changes in dopamine neuron function after DNSP-11 treatment: effects in vivo and increased ERK 1/2 phosphorylation in vitro.

PubMed

Fuqua, Joshua L; Littrell, Ofelia M; Lundblad, Martin; Turchan-Cholewo, Jadwiga; Abdelmoti, Lina G; Galperin, Emilia; Bradley, Luke H; Cass, Wayne A; Gash, Don M; Gerhardt, Greg A

2014-04-01

Glial cell-line derived neurotrophic factor (GDNF) has demonstrated robust effects on dopamine (DA) neuron function and survival. A post-translational processing model of the human GDNF proprotein theorizes the formation of smaller, amidated peptide(s) from the proregion that exhibit neurobiological function, including an 11-amino-acid peptide named dopamine neuron stimulating peptide-11 (DNSP-11). A single treatment of DNSP-11 was delivered to the substantia nigra in the rat to investigate effects on DA-neuron function. Four weeks after treatment, potassium (K+) and D-amphetamine evoked DA release were studied in the striatum using microdialysis. There were no significant changes in DA-release after DNSP-11 treatment determined by microdialysis. Dopamine release was further examined in discrete regions of the striatum using high-speed chronoamperometry at 1-, 2-, and 4-weeks after DNSP-11 treatment. Two weeks after DNSP-11 treatment, potassium-evoked DA release was increased in specific subregions of the striatum. However, spontaneous locomotor activity was unchanged by DNSP-11 treatment. In addition, we show that a single treatment of DNSP-11 in the MN9D dopaminergic neuronal cell line results in phosphorylation of ERK1/2, which suggests a novel cellular mechanism responsible for increases in DA function. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantitation of Hydrogen Peroxide Fluctuations and Their Modulation of Dopamine Dynamics in the Rat Dorsal Striatum Using Fast-Scan Cyclic Voltammetry

PubMed Central

2013-01-01

The dopaminergic neurons of the nigrostriatal dopamine (DA) projection from the substantia nigra to the dorsal striatum become dysfunctional and slowly degenerate in Parkinson’s disease, a neurodegenerative disorder that afflicts more than one million Americans. There is no specific known cause for idiopathic Parkinson’s disease; however, multiple lines of evidence implicate oxidative stress as an underlying factor in both the initiation and progression of the disease. This involves the enhanced generation of reactive oxygen species, including hydrogen peroxide (H2O2), whose role in complex biological processes is not well understood. Using fast-scan cyclic voltammetry at bare carbon-fiber microelectrodes, we have simultaneously monitored and quantified H2O2 and DA fluctuations in intact striatal tissue under basal conditions and in response to the initiation of oxidative stress. Furthermore, we have assessed the effect of acute increases in local H2O2 concentration on both electrically evoked DA release and basal DA levels. Increases in endogenous H2O2 in the dorsal striatum attenuated electrically evoked DA release, and also decreased basal DA levels in this brain region. These novel results will help to disambiguate the chemical mechanisms underlying the progression of neurodegenerative disease states, such as Parkinson’s disease, that involve oxidative stress. PMID:23556461

Agarose and Polyacrylamide Gel Electrophoresis Methods for Molecular Mass Analysis of 5–500 kDa Hyaluronan

PubMed Central

Bhilocha, Shardul; Amin, Ripal; Pandya, Monika; Yuan, Han; Tank, Mihir; LoBello, Jaclyn; Shytuhina, Anastasia; Wang, Wenlan; Wisniewski, Hans-Georg; de la Motte, Carol; Cowman, Mary K.

2011-01-01

Agarose and polyacrylamide gel electrophoresis systems for the molecular mass-dependent separation of hyaluronan (HA) in the size range of approximately 5–500 kDa have been investigated. For agarose-based systems, the suitability of different agarose types, agarose concentrations, and buffers systems were determined. Using chemoenzymatically synthesized HA standards of low polydispersity, the molecular mass range was determined for each gel composition, over which the relationship between HA mobility and logarithm of the molecular mass was linear. Excellent linear calibration was obtained for HA molecular mass as low as approximately 9 kDa in agarose gels. For higher resolution separation, and for extension to molecular masses as low as approximately 5 kDa, gradient polyacrylamide gels were superior. Densitometric scanning of stained gels allowed analysis of the range of molecular masses present in a sample, and calculation of weight-average and number-average values. The methods were validated for polydisperse HA samples with viscosity-average molecular masses of 112, 59, 37, and 22 kDa, at sample loads of 0.5 µg (for polyacrylamide) to 2.5 µg (for agarose). Use of the methods for electrophoretic mobility shift assays was demonstrated for binding of the HA-binding region of aggrecan (recombinant human aggrecan G1-IGD-G2 domains) to a 150 kDa HA standard. PMID:21684248

Wnt/B-Catenin Signaling is Required to Rescue Midbrain Dopaminergic Progenitors and Promote Neurorepair in Ageing Mouse Model of Parkinson’s Disease

PubMed Central

L’Episcopo, Francesca; Tirolo, Cataldo; Testa, Nunzio; Caniglia, Salvatore; Morale, Maria Concetta; Serapide, Maria Francesca; Pluchino, Stefano; Marchetti, Bianca

2014-01-01

SUMMARY Wnt/β-catenin signaling is required for specification and neurogenesis of midbrain dopaminergic (mDA) neurons, the pivotal neuronal population that degenerates in Parkinson’s disease (PD) and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Wnt/β-catenin signaling plays a vital role in adult neurogenesis but whether it might engage DA neurogenesis/neurorepair in the affected PD brain is yet unresolved. Recently, the adult midbrain aqueduct periventricular regions (Aq-PVRs) were shown to harbor neural stem/progenitor cells (mNPCs) with DA potential in vitro, but restrictive mechanisms in vivo are believed to limit their DA regenerative capacity. Using in vitro mNPC culture systems we herein demonstrate that aging is one most critical factor restricting mNPC neurogenic potential via dysregulation of Wnt/β-catenin signaling. Cococulture paradigms between young/aged (Y/A) mNPCs and Y/A astrocytes identified glial age and a decline of glial-derived factors including Wnts as key determinants of impaired neurogenic potential, whereas Wnt activation regimens efficiently reversed the diminished proliferative, neuronal and DA differentiation potential of A-mNPCs. Next, in vivo studies in wild (Wt) and transgenic β-catenin reporter mice uncovered Wnt/β-catenin signaling activation and remarkable astrocyte remodeling of Aq-PVR in response to MPTP-induced DA neuron death. Spatio-temporal analyses unveiled β-catenin signaling in predopaminergic (Nurr1+/TH−) and imperiled or rescuing DAT+ neurons during MPTP-induced DA neuron injury and self-repair. Aging inhibited Wnt signaling, whereas β-catenin activation in situ with a specific GSK-3β antagonist promoted a significant degree of DA neurorestoration associated with reversal of motor deficit, with implications for neurorestorative approaches in PD. PMID:24648001

Study protocol for promoting respectful maternity care initiative to assess, measure and design interventions to reduce disrespect and abuse during childbirth in Kenya

PubMed Central

2013-01-01

Background Increases in the proportion of facility-based deliveries have been marginal in many low-income countries in the African region. Preliminary clinical and anthropological evidence suggests that one major factor inhibiting pregnant women from delivering at facility is disrespectful and abusive treatment by health care providers in maternity units. Despite acknowledgement of this behavior by policy makers, program staff, civil society groups and community members, the problem appears to be widespread but prevalence is not well documented. Formative research will be undertaken to test the reliability and validity of a disrespect and abuse (D&A) construct and to then measure the prevalence of disrespect and abuse suffered by clinic clients and the general population. Methods/design A quasi-experimental design will be followed with surveys at twelve health facilities in four districts and one large maternity hospital in Nairobi and areas before and after the introduction of disrespect and abuse (D&A) interventions. The design is aimed to control for potential time dependent confounding on observed factors. Discussion This study seeks to conduct implementation research aimed at designing, testing, and evaluating an approach to significantly reduce disrespectful and abusive (D&A) care of women during labor and delivery in facilities. Specifically the proposed study aims to: (i) determine the manifestations, types and prevalence of D&A in childbirth (ii) develop and validate tools for assessing D&A (iii) identify and explore the potential drivers of D&A (iv) design, implement, monitor and evaluate the impact of one or more interventions to reduce D&A and (v) document and assess the dynamics of implementing interventions to reduce D&A and generate lessons for replication at scale. PMID:23347548

L-MPZ, a Novel Isoform of Myelin P0, Is Produced by Stop Codon Readthrough*

PubMed Central

Yamaguchi, Yoshihide; Hayashi, Akiko; Campagnoni, Celia W.; Kimura, Akio; Inuzuka, Takashi; Baba, Hiroko

2012-01-01

Myelin protein zero (P0 or MPZ) is a major myelin protein (∼30 kDa) expressed in the peripheral nervous system (PNS) in terrestrial vertebrates. Several groups have detected a P0-related 36-kDa (or 35-kDa) protein that is expressed in the PNS as an antigen for the serum IgG of patients with neuropathy. The molecular structure and function of this 36-kDa protein are, however, still unknown. We hypothesized that the 36-kDa protein may be derived from P0 mRNA by stop codon readthrough. We found a highly conserved region after the regular stop codon in predicted sequences from the 3′-UTR of P0 in higher animals. MS of the 36-kDa protein revealed that both P0 peptides and peptides deduced from the P0 3′-UTR sequence were found among the tryptic fragments. In transfected cells and in an in vitro transcription/translation system, the 36-kDa molecule was also produced from the identical mRNA that produced P0. We designated this 36-kDa molecule as large myelin protein zero (L-MPZ), a novel isoform of P0 that contains an additional domain at the C terminus. In the PNS, L-MPZ was localized in compact myelin. In transfected cells, just like P0, L-MPZ was localized at cell-cell adhesion sites in the plasma membrane. These results suggest that L-MPZ produced by the stop codon readthrough mechanism is potentially involved in myelination. Since this is the first finding of stop codon readthrough in a common mammalian protein, detailed analysis of L-MPZ expression will help to understand the mechanism of stop codon readthrough in mammals. PMID:22457349

Diffusion of macromolecules through sclera.

PubMed

Miao, Heng; Wu, Bi-Dong; Tao, Yong; Li, Xiao-Xin

2013-02-01

To quantify the in vitro permeability coefficient over different topographical locations of porcine sclera to macromolecules with different molecular weight. Fresh equatorial and posterior superotemporal porcine sclera was mounted in a two-chamber diffusion apparatus, and its permeability to fluorescein isothiocyanate (FITC)-conjugated dextrans ranging in molecular weight from 40 kDa to 150 kDa was determined by fluorescence spectrophotometry. The sclera was processed as frozen sections and viewed with a fluorescence microscope. The thickness of the area and the thickness that macromolecules enriched in the surface of sclera were measured. The permeability coefficient (Pc) of porcine sclera to macromolecules was significantly higher (40 kDa, p = 0.028; 70 kDa, p = 0.033; 150 kDa, p = 0.007) in equatorial region than posterior, which could be attributed to the significant difference of thickness (p < 0.001, Kruskal-Wallis) between them. Moreover, linear regression indicated a significant negative relationship (40 kDa, p < 0.001; 70 kDa, p = 0.015; 150 kDa, p < 0.001) between scleral permeability coefficient and thickness. Also, Pc declined significantly with increasing molecular weight (MW, p < 0.001, Kruskal-Wallis). The area that the macromolecules enriched in the scleral surface was thicker for those with larger MW (p < 0.001, Kruskal-Wallis). The maximum MW and size for equatorial and posterior superotemporal scleral tissue were 185.01 KDa and 180.42 KDa, 9.92 nm and 9.67 nm, respectively. The permeability coefficient of porcine sclera has a significant negative relationship with scleral thickness and MW of macromolecules. Larger macromolecules are more likely to accumulate in scleral surface. The difference between topographical locations may have pharmacokinetic implications when considering transscleral diffusion of macromolecules. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

A Global Solar Irradiance Climatology of an Intermountain Region.

DTIC Science & Technology

1986-01-01

D-A!171 97 A GLOBAL SOLAIR IRRRDIANCE CLIMATOLOGY OF AN INTERMOUNTAIN REGION(U) AIR FORCE INST OF TECH MRIGHT-PATTERSON APR ON E W DOBRY 1986...DD~ I JAN 73 1473 EDITION OF I NOV 65 IS OBSOLETE SECURITY CLASSIFICATION OF THIS PAGE Denfata E1ilered) %.ir.. , t . ~. ~ ~ ~ $~:V ( e vis ABSTRACT...Professor: Dr. G. E . Bingham De artment: Soil Science and Biometeorology A global solar irradiance climatology of an intermountain region is developed using

Mature parasite-infected erythrocyte surface antigen (MESA) of Plasmodium falciparum binds to the 30-kDa domain of protein 4.1 in malaria-infected red blood cells.

PubMed

Waller, Karena L; Nunomura, Wataru; An, Xiuli; Cooke, Brian M; Mohandas, Narla; Coppel, Ross L

2003-09-01

The Plasmodium falciparum mature parasite-infected erythrocyte surface antigen (MESA) is exported from the parasite to the infected red blood cell (IRBC) membrane skeleton, where it binds to protein 4.1 (4.1R) via a 19-residue MESA sequence. Using purified RBC 4.1R and recombinant 4.1R fragments, we show MESA binds the 30-kDa region of RBC 4.1R, specifically to a 51-residue region encoded by exon 10 of the 4.1R gene. The 3D structure of this region reveals that the MESA binding site overlaps the region of 4.1R involved in the p55, glycophorin C, and 4.1R ternary complex. Further binding studies using p55, 4.1R, and MESA showed competition between p55 and MESA for 4.1R, implying that MESA bound at the IRBC membrane skeleton may modulate normal 4.1R and p55 interactions in vivo. Definition of minimal binding domains involved in critical protein interactions in IRBCs may aid the development of novel therapies for falciparum malaria.

Evaluation of metabolites extraction strategies for identifying different brain regions and their relationship with alcohol preference and gender difference using NMR metabolomics.

PubMed

Wang, Jie; Zeng, Hao-Long; Du, Hongying; Liu, Zeyuan; Cheng, Ji; Liu, Taotao; Hu, Ting; Kamal, Ghulam Mustafa; Li, Xihai; Liu, Huili; Xu, Fuqiang

2018-03-01

Metabolomics generate a profile of small molecules from cellular/tissue metabolism, which could directly reflect the mechanisms of complex networks of biochemical reactions. Traditional metabolomics methods, such as OPLS-DA, PLS-DA are mainly used for binary class discrimination. Multiple groups are always involved in the biological system, especially for brain research. Multiple brain regions are involved in the neuronal study of brain metabolic dysfunctions such as alcoholism, Alzheimer's disease, etc. In the current study, 10 different brain regions were utilized for comparative studies between alcohol preferring and non-preferring rats, male and female rats respectively. As many classes are involved (ten different regions and four types of animals), traditional metabolomics methods are no longer efficient for showing differentiation. Here, a novel strategy based on the decision tree algorithm was employed for successfully constructing different classification models to screen out the major characteristics of ten brain regions at the same time. Subsequently, this method was also utilized to select the major effective brain regions related to alcohol preference and gender difference. Compared with the traditional multivariate statistical methods, the decision tree could construct acceptable and understandable classification models for multi-class data analysis. Therefore, the current technology could also be applied to other general metabolomics studies involving multi class data. Copyright © 2017 Elsevier B.V. All rights reserved.

A Preliminary Investigation of the Effect of Acute Alcohol on Dopamine Transmission as Assessed by [11 C]-(+)-PHNO.

PubMed

Thiruchselvam, Thulasi; Wilson, Alan A; Boileau, Isabelle; Le Foll, Bernard

2017-06-01

Previous positron emission tomography (PET) studies exploring the effect of acute alcohol on dopamine (DA) levels have yielded inconsistent results, with only some studies suggesting increased synaptic DA levels after an alcohol challenge. The D 2 /D 3 agonist radiotracer, [ 11 C]-(+)-propyl-hexahydro-naphtho-oxazin ([ 11 C]-(+)-PHNO), has greater sensitivity to synaptic DA fluctuation than previously used antagonist radiotracers and is in principle more suitable for imaging alcohol-induced changes in DA. Its high affinity for the D 3 receptor also enables measuring changes in D 3 -rich brain areas which have previously been unexplored. The aim of this study was to investigate whether alcohol reduces [ 11 C]-(+)-PHNO binding in the striatum and in D 3 -rich extra-striatal areas. Eight healthy drinkers underwent 2 [ 11 C]-(+)-PHNO PET scans following alcohol and placebo in a randomized, single-blind, crossover design. [ 11 C]-(+)-PHNO binding in the striatum and in the extra-striatal regions were compared between the 2 scans. Acute alcohol administration did not significantly reduce [ 11 C]-(+)-PHNO binding in either the limbic striatum (d = 0.64), associative striatum (d < 0.20), or the sensorimotor striatum (d < 0.15). Similarly, there were no changes in binding in the D 3 -rich areas of the ventral pallidum (d = 0.53), substantia nigra (d < 0.15), or globus pallidus (d < 0.15). However, greater percent change in [ 11 C]-(+)-PHNO binding (ΔBP ND ) between scans was related to lower blood alcohol levels. Using the agonist radiotracer, [ 11 C]-(+)-PHNO, our preliminary findings suggest that alcohol is not associated with robust changes in tracer binding in striatal or extra-striatal regions. However, we found that changes in [ 11 C]-(+)-PHNO binding following alcohol are dependent on blood alcohol levels suggesting that increases in DA may occur at lower stimulating doses. The effect of lower doses of alcohol on DA warrants further investigation in a larger study. Copyright © 2017 by the Research Society on Alcoholism.

[Identification of cyst and trophozoite antigens from Colombian Giardia duodenalis isolates recognized by IgA].

PubMed

Olmos, Rosana Natalia; Duque, Sofía; López, Myriam Consuelo; Arévalo, Adriana; Guerrero, Rafael; Velandia, Martha Patricia; Nicholls, Ruben Santiago

2003-09-01

Little is known about the role of IgA in the immune response against Giardia duodenalis infection. The current study identified the antigens of Colombian G. duodenalis isolates which stimulate the production of IgA anti-G. dudoenalis. Cyst and trophozoite stage proteins were separated by SDS-PAGE and their antigenicity was determined by Western blot. Without 2-mercapto ethanol (2-ME), the protein profile of the cyst stage showed 24 proteins within a molecular weight range of 23-270 kDa; with 2-ME, 35 polypeptides ranging from 22 to 241 kDa were distinguished. The trophozoite stage protein profile without 2-ME was formed by 16 proteins within the range of 24-270 kDa; with 2-ME, 45 proteins were present between 18 and 241 kDa. The identification of 20 and 29 antigens from the cyst and trophozoite stage, respectively, suggested that G. duodenalis stimulates a specific humoral immune response in the human host. The antigens of 31, 57, 110, 133, and 170 kDa recognized by anti-G duodenalis IgA in both cysts and trophozoites corresponded with G. duodenalis isolates from other geographic regions, whereas those of 35, 38, 43, 45, 49, 52, 60, 62, 65, 72, 82, 99, 145, 155, and 185 kDa seemed specific to Colombian isolates. This indicated that antigens of 57, 65, 145, and 170 kDa, recognized by anti-G. duodenalis IgA antibodies in cysts (with frequencies between 82% and 96%) and trophozoites (with frequencies between 86% and 97%) can be considered identification markers for G. duodenalis infections.

Assimilation of Gridded GRACE Terrestrial Water Storage Estimates in the North American Land Data Assimilation System

NASA Technical Reports Server (NTRS)

Kumar, Sujay V.; Zaitchik, Benjamin F.; Peters-Lidard, Christa D.; Rodell, Matthew; Reichle, Rolf; Li, Bailing; Jasinski, Michael; Mocko, David; Getirana, Augusto; De Lannoy, Gabrielle;

Cocaine cue-induced dopamine release in the human prefrontal cortex.

PubMed

Milella, Michele S; Fotros, Aryandokht; Gravel, Paul; Casey, Kevin F; Larcher, Kevin; Verhaeghe, Jeroen A J; Cox, Sylvia M L; Reader, Andrew J; Dagher, Alain; Benkelfat, Chawki; Leyton, Marco

2016-08-01

Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence. Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self-reported craving. Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release. In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms.

Contribution of dopamine to mitochondrial complex I inhibition and dopaminergic deficits caused by methylenedioxymethamphetamine in mice.

PubMed

Barros-Miñones, L; Goñi-Allo, B; Suquia, V; Beitia, G; Aguirre, N; Puerta, E

2015-06-01

Methylenedioxymethamphetamine (MDMA) causes a persistent loss of dopaminergic cell bodies in the substantia nigra of mice. Current evidence indicates that MDMA-induced neurotoxicity is mediated by oxidative stress probably due to the inhibition of mitochondrial complex I activity. In this study we investigated the contribution of dopamine (DA) to such effects. For this, we modulated the dopaminergic system of mice at the synthesis, uptake or metabolism levels. Striatal mitochondrial complex I activity was decreased 1 h after MDMA; an effect not observed in the striatum of DA depleted mice or in the hippocampus, a dopamine spare region. The DA precursor, L-dopa, caused a significant reduction of mitochondrial complex I activity by itself and exacerbated the dopaminergic deficits when combined with systemic MDMA. By contrast, no damage was observed when L-dopa was combined with intrastriatal injections of MDMA. On the other hand, dopamine uptake blockade using GBR 12909, inhibited both, the acute inhibition of complex I activity and the long-term dopaminergic toxicity caused by MDMA. Moreover, the inhibition of DA metabolism with the monoamine oxidase (MAO) inhibitor, pargyline, afforded a significant protection against MDMA-induced complex I inhibition and neurotoxicity. Taken together, these findings point to the formation of hydrogen peroxide subsequent to DA metabolism by MAO, rather than a direct DA-mediated mitochondrial complex I inhibition, and the contribution of a peripheral metabolite of MDMA, as the key steps in the chain of biochemical events leading to DA neurotoxicity caused by MDMA in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dopamine transport by the serotonin transporter: a mechanistically distinct mode of substrate translocation

PubMed Central

Larsen, Mads Breum; Sonders, Mark S.; Mortensen, Ole Valente; Larson, Gaynor A.; Zahniser, Nancy R.; Amara, Susan G.

2011-01-01

The serotonin transporter (SERT) is the principal mechanism for terminating serotonin (5HT) signals in the nervous system and is a site of action for a variety of psychoactive drugs including antidepressants, amphetamines, and cocaine. Here we show that human SERTs (hSERTs) and rat SERTs are capable of robust dopamine (DA) uptake through a process that differs mechanistically from 5HT transport in several unanticipated ways. DA transport by hSERT has a higher maximum velocity than 5HT transport, requires significantly higher Na+ and Cl− concentrations to sustain transport, is inhibited non-competitively by 5HT and is more sensitive to SERT inhibitors, including selective serotonin reuptake inhibitors (SSRIs). We use a thiol reactive methane thiosulfonate (MTS) reagent to modify a conformationally-sensitive cysteine residue to demonstrate that hSERT spends more time in an outward facing conformation when transporting DA than when transporting 5HT. Co-transfection of an inactive or an MTS-sensitive SERT with wild type SERT subunits reveals an absence of cooperative interactions between subunits during DA, but not 5HT transport. To establish the physiological relevance of this mechanism for DA clearance, we show using in vivo high-speed chronoamperometry that SERT has the capacity to clear extracellularly applied DA in the hippocampal CA3 region of anesthetized rats. Together, these observations suggest the possibility that SERT serves as a DA transporter in vivo and highlight the idea that there can be distinct modes of transport of alternative physiological substrates by SERT. PMID:21525301

The 32-Kilodalton Subunit of Replication Protein A Interacts with Menin, the Product of the MEN1 Tumor Suppressor Gene

PubMed Central

Sukhodolets, Karen E.; Hickman, Alison B.; Agarwal, Sunita K.; Sukhodolets, Maxim V.; Obungu, Victor H.; Novotny, Elizabeth A.; Crabtree, Judy S.; Chandrasekharappa, Settara C.; Collins, Francis S.; Spiegel, Allen M.; Burns, A. Lee; Marx, Stephen J.

2003-01-01

Menin is a 70-kDa protein encoded by MEN1, the tumor suppressor gene disrupted in multiple endocrine neoplasia type 1. In a yeast two-hybrid system based on reconstitution of Ras signaling, menin was found to interact with the 32-kDa subunit (RPA2) of replication protein A (RPA), a heterotrimeric protein required for DNA replication, recombination, and repair. The menin-RPA2 interaction was confirmed in a conventional yeast two-hybrid system and by direct interaction between purified proteins. Menin-RPA2 binding was inhibited by a number of menin missense mutations found in individuals with multiple endocrine neoplasia type 1, and the interacting regions were mapped to the N-terminal portion of menin and amino acids 43 to 171 of RPA2. This region of RPA2 contains a weak single-stranded DNA-binding domain, but menin had no detectable effect on RPA-DNA binding in vitro. Menin bound preferentially in vitro to free RPA2 rather than the RPA heterotrimer or a subcomplex consisting of RPA2 bound to the 14-kDa subunit (RPA3). However, the 70-kDa subunit (RPA1) was coprecipitated from HeLa cell extracts along with RPA2 by menin-specific antibodies, suggesting that menin binds to the RPA heterotrimer or a novel RPA1-RPA2-containing complex in vivo. This finding was consistent with the extensive overlap in the nuclear localization patterns of endogenous menin, RPA2, and RPA1 observed by immunofluorescence. PMID:12509449

Marek's disease virus protein kinase gene identified within the short unique region of the viral genome is not essential for viral replication in cell culture and vaccine-induced immunity in chickens.

PubMed

Sakaguchi, M; Urakawa, T; Hirayama, Y; Miki, N; Yamamoto, M; Zhu, G S; Hirai, K

1993-07-01

The open reading frame (ORF) of 1206 bp within the short unique region (Us) of Marek's disease virus type 1 (MDV1) shows significant homology with the herpes simplex virus type 1 US3 gene encoding protein kinase (PK). The lacZ gene of Escherichia coli was inserted within the ORF, designated MDV1-US3, of MDV1 K544 strain DNA by homologous recombination. The plaque-purified recombinant MDV1 stably expressed the beta-galactosidase encoded by the inserted lacZ gene in infected cells and replicated well as the parental K544 strain. Antibodies against both MDV1 antigen and beta-galactosidase were detected in the sera of chickens immunized with recombinant MDV1. Chickens vaccinated with the recombinant MDV1 were protected from challenge with virulent MDV1. The MDV1 US3 gene expressed by a baculovirus vector encoded a 44-kDa protein. Mouse antisera against the 44-kDa protein reacted with two proteins of 44 and 45 kDa in extracts of cells infected with MDV1 but not with MDV types 2 or 3. The PK activity was detected in immune complexes of the anti-44-kDa sera with extracts of cells infected with MDV1 but not with the recombinant MDV1. Thus, PK encoded from the MDV1-US3 is not essential for virus replication in cell culture and vaccine-induced immunity.

Embryogenesis-promoting factors in rat serum.

PubMed

Katoh, M; Kimura, R; Shoji, R

1998-06-15

Regarding whole rat embryo cultures in vitro, rat serum as a culture medium is known to support the normal growth of rat embryos in the organogenesis phase. The purpose of the present study was to isolate the embryogenesis-promoting factors from rat serum as a first step in the development of a defined serum-free medium for a whole embryo culture system. Pooled rat serum after heat inactivation was fractionated into three major peaks (frA, containing a region of void volume, frB, and frC) by gel filtration. The 9.5-day rat embryos that were cultivated for 48 hr in essential salt medium containing frB (with a molecular size range of 100-500 kDa) revealed normal growth. Three proteins (27 kDa, 76 kDa, and 190 kDa) that had the embryogenesis-promoting effects were isolated from 3-hr delayed centrifuged rat serum by the ion exchange chromatography. The 76-kDa protein was found to be rat transferrin by immunoblotting. The 27-kDa protein was identified as apo-AI (the major apoprotein of high-density lipoprotein) by immunoblotting. High-density lipoprotein obtained from pooled rat serum by a NaBr density gradient ultracentrifugation was found to have a positive effect on embryogenesis. The 10-kDa protein was also identified as alpha 1-inhibitor 3 by immunoblotting. In addition, the embryogenesis-promoting effect of the fraction containing 27-kDa and 190-kDa proteins declined within a short period of storage at -20 degrees C. This decrease was countered by supplementing its fraction (D-2) with albumin isolated from rat serum. These results in the present study suggest that transferrin, high-density lipoprotein, and alpha 1-inhibitor 3 in rat serum may be embryogenesis-promoting factors, and that albumin appeared to play a role in the embryogenesis of rat embryos in whole embryo cultures.

Selective activation of mesolimbic and mesocortical dopamine metabolism in rat brain by infusion of a stable substance P analogue into the ventral tegmental area.

PubMed

Elliott, P J; Alpert, J E; Bannon, M J; Iversen, S D

1986-01-15

Microinfusion of the metabolically stable substance P (SP) agonist, [pGlu5,MePhe8,Sar9]-SP5-11 (DiMe-C7), into the ventral tegmental area (VTA) of rat brain increased levels of the dopamine (DA) metabolite dihydroxyphenylacetic acid in the prefrontal cortex (+ 120%) and nucleus accumbens (+30%) but not in other regions of forebrain. In contrast, infusions of DiMe-C7 or SP into the lateral ventricles or microinfusions of SP into VTA failed to elicit increases in DOPAC levels in forebrain. DA levels were unaffected by SP or DiMe-C7 regardless of the route of administration. These data and previous studies suggest a role for endogenous SP in the modulation of mesocortical and mesolimbic DA neurones.

Epidemiological surveillance of tegumentary leishmaniasis: local territorial analysis.

PubMed

Soares, Valdenir Bandeira; Almeida, Andréa Sobral de; Sabroza, Paulo Chagastelles; Vargas, Waldemir Paixão

2017-06-26

To propose a new operational unit in the locality scale capable of subsidizing the construction of an information system to control the transmission of tegumentary leishmaniasis at this scale, in a region of high endemicity of the Atlantic Forest. We examined the adequacy of data and instruments in an area of high endemicity in the Atlantic Forest located in the South of the State of Rio de Janeiro from 1990 to 2012. The study proposed an operational unit called Local Surveillance Unit to make all used databases compatible by adjusting census sectors. This enabled the overlap and comparison of information in different periods. The spreading process of the transmission of tegumentary leishmaniasis in the Baía da Ilha Grande region does not depend on great population movements, and can occur in areas with population growth or decrease. The data information system allowed the adequate identification and characterization of the place of residence. We identified relevant characteristics of the place of transmission, such as self-limited in time and not associated with recent deforestation. The results also highlight the lack of synchronicity in the case production in territorial units involved in the endemic-epidemic process, noting that this process is in constant motion. The transmission process seems more connected to the presence and movement of rodents that move continuously in the region than to the local density of vectors or the permanence of infected dogs at home. New control strategies targeted at the foci of transmission must be considered. The construction of a new operational unit, called Local Surveillance Unit, was instrumental in the endemic-epidemic process analysis. Propor uma nova unidade operacional na escala de localidade capaz de subsidiar a construção de um sistema de informação orientado para o controle da transmissão da leishmaniose tegumentar nesse nível. Uma região de alta endemicidade da Mata Atlântica no sul do estado do Rio de Janeiro de 1990 a 2012 foi selecionada para analisar a adequação dos dados e instrumentos. Uma unidade operacional denominada Unidade de Vigilância Local foi proposta para compatibilizar todos os bancos de dados utilizados por meio de ajustes dos setores censitários. Isso possibilitou a sobreposição das informações e a sua comparação em diferentes períodos. O processo de deslocamento da transmissão da leishmaniose tegumentar na região da Baía da Ilha Grande não dependeu de movimentos populacionais importantes, podendo ocorrer tanto em áreas com crescimento como em áreas com decremento populacional. Os dados do sistema de informação permitiram a identificação e caracterização adequada do local de residência. Identificaram-se características relevantes do lugar de transmissão, como autolimitados no tempo e não associados a desmatamentos recentes. Os resultados evidenciam também a falta de sincronicidade na produção de casos nas unidades territoriais envolvidas no processo endêmico-epidêmico, mostrando que esse processo está em constante movimento. O processo de transmissão parece estar mais ligado à presença e circulação de roedores que se desloquem continuadamente na região do que da densidade local de vetores ou da permanência de cães infectados no domicílio. Novas estratégias de controle orientadas para os focos de transmissão devem ser consideradas. A construção de uma nova unidade operacional, denominada Unidade de Vigilância Local, foi fundamental na análise do processo endêmico-epidêmico.

Skipjack tuna as a bioindicator of contamination by perfluorinated compounds in the oceans.

PubMed

Hart, Kimberly; Kannan, Kurunthachalam; Tao, Lin; Takahashi, Shin; Tanabe, Shinsuke

2008-09-15

Perfluorinated chemicals (PFCs) have emerged as global environmental contaminants. Studies have reported the widespread occurrence of PFCs in biota from marine coastal waters and in remote polar regions. However, few studies have reported the distribution of PFCs in biota from offshore waters and open oceans. In this study, concentrations of nine PFCs were determined in the livers of 60 skipjack tuna (Katsuwonus pelamis) collected from offshore waters and the open ocean along the Pacific Rim, including the Sea of Japan, the East China Sea, the Indian Ocean, and the Western North Pacific Ocean, during 1997-1999. At least one of the nine PFCs was found in every tuna sample analyzed. Overall, perfluorooctanesulfonate (PFOS) and perfluoroundecanoic acid (PFUnDA) were the predominant compounds found in livers of tuna at concentrations of <1-58.9 and <1-31.6 ng/g, wet wt, respectively. Long-chain perfluorocarboxylates such as perfluorodecanoic acid (PFDA) and perfluorododecanoic acid (PFDoDA) were common in the tuna livers. In livers of tuna from several offshore and open-ocean locations, concentrations of PFUnDA were greater than the concentrations of PFOS. The profiles and concentrations of PFCs in tuna livers suggest that the sources in East Asia are dominated by long-chain perfluorocarboxylates, especially PFUnDA. High concentrations of PFUnDA in tuna may indicate a shift in sources of PFCs in East Asia. The spatial distribution of PFOS in skipjack tuna reflected the concentrations previously reported in seawater samples from the Pacific and Indian Oceans, suggesting that tuna are good bioindicators of pollution by PFOS. Despite its predominance in ocean waters, PFOA was rarely found in tuna livers, indicative of the low bioaccumulation potential of this compound. Our study establishes baseline concentrations of PFCs in skipjack tuna from the oceans of the Asia-Pacific region, enabling future temporal trend studies of PFCs in oceans.

Integrative overview of the herpetofauna from Serra da Mocidade, a granitic mountain range in northern Brazil.

PubMed

Moraes, Leandro J C L; de Almeida, Alexandre P; de Fraga, Rafael; Rojas, Rommel R; Pirani, Renata M; Silva, Ariane A A; de Carvalho, Vinícius T; Gordo, Marcelo; Werneck, Fernanda P

2017-01-01

The Brazilian mountain ranges from the Guiana Shield highlands are largely unexplored, with an understudied herpetofauna. Here the amphibian and reptile species diversity of the remote Serra da Mocidade mountain range, located in extreme northern Brazil, is reported upon, and biogeographical affinities and taxonomic highlights are discussed. A 22-days expedition to this mountain range was undertaken during which specimens were sampled at four distinct altitudinal levels (600, 960, 1,060 and 1,365 m above sea level) using six complementary methods. Specimens were identified through an integrated approach that considered morphological, bioacoustical, and molecular analyses. Fifty-one species (23 amphibians and 28 reptiles) were found, a comparable richness to other mountain ranges in the region. The recorded assemblage showed a mixed compositional influence from assemblages typical of other mountain ranges and lowland forest habitats in the region. Most of the taxa occupying the Serra da Mocidade mountain range are typical of the Guiana Shield or widely distributed in the Amazon. Extensions of known distribution ranges and candidate undescribed taxa are also recorded. This is the first herpetofaunal expedition that accessed the higher altitudinal levels of this mountain range, contributing to the basic knowledge of these groups in remote areas.

Latitudinal transects in the southeastern Pacific Ocean reveal a diverse but patchy distribution of phycotoxins.

PubMed

Trefault, N; Krock, B; Delherbe, N; Cembella, A; Vásquez, M

2011-10-01

Phycotoxin distribution and abundance was determined during an oceanographic expedition along a latitudinal transect of 27° extent in the southeastern Pacific Ocean, from the fjords of Tierra del Fuego Island to offshore Copiapó in the Atacama region along the Chilean coast. Plankton samples were harvested at regular intervals during the entire cruise and later analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for domoic acid (DA) and lipophilic toxins. Although no evident toxic algal bloom was encountered during this transect, several phycotoxin analogues from distinct toxin groups were detected. These phycotoxins included DA, the pectenotoxins PTX-2, PTX-2sa and PTX-11, dinophystoxin-1 (DTX-1) and gymnodimine (GYM), which is the first report of this latter toxin in the southeast Pacific. A region-specific and rather disjunct distribution of GYM, DA and DTX-1 was observed, whereas PTX-2, PTX-2sa and PTX-11 were more widely distributed over almost the entire transect. This work represents the first assessment of lipophilic toxins through a wide latitudinal transect of the southeastern Pacific, revealing a patchy distribution of several phycotoxins and pointing out the specific geographical distribution of the putative toxigenic organisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Integrative overview of the herpetofauna from Serra da Mocidade, a granitic mountain range in northern Brazil

PubMed Central

Moraes, Leandro J.C.L.; de Almeida, Alexandre P.; de Fraga, Rafael; Rojas, Rommel R.; Pirani, Renata M.; Silva, Ariane A.A.; de Carvalho, Vinícius T.; Gordo, Marcelo; Werneck, Fernanda P.

2017-01-01

Abstract The Brazilian mountain ranges from the Guiana Shield highlands are largely unexplored, with an understudied herpetofauna. Here the amphibian and reptile species diversity of the remote Serra da Mocidade mountain range, located in extreme northern Brazil, is reported upon, and biogeographical affinities and taxonomic highlights are discussed. A 22-days expedition to this mountain range was undertaken during which specimens were sampled at four distinct altitudinal levels (600, 960, 1,060 and 1,365 m above sea level) using six complementary methods. Specimens were identified through an integrated approach that considered morphological, bioacoustical, and molecular analyses. Fifty-one species (23 amphibians and 28 reptiles) were found, a comparable richness to other mountain ranges in the region. The recorded assemblage showed a mixed compositional influence from assemblages typical of other mountain ranges and lowland forest habitats in the region. Most of the taxa occupying the Serra da Mocidade mountain range are typical of the Guiana Shield or widely distributed in the Amazon. Extensions of known distribution ranges and candidate undescribed taxa are also recorded. This is the first herpetofaunal expedition that accessed the higher altitudinal levels of this mountain range, contributing to the basic knowledge of these groups in remote areas. PMID:29302235

Endemic and threatened tetrapods in the restingas of the biodiversity corridors of Serra do Mar and of the Central da Mata Atlântica in eastern Brazil.

PubMed

Rocha, C F D; Van Sluys, M; Bergallo, H G; Alves, M A S

2005-02-01

Biodiversity corridors comprise a mosaic of land uses connecting fragments of natural forest across a landscape. Two such corridors have been established along the eastern coast of Brazil: the Serra do Mar and the Central da Mata Atlântica corridors, along which most of the coastal plains are restinga areas. In this study, we analyze the present status of the endemic and endangered terrestrial vertebrates of both corridors. We sampled 10 restingas in both corridors, recording species of amphibians, reptiles, birds, and mammals. Some restingas harbor a relatively large number of endemic species,and two main regions of endemism can be identified along the restingas of both corridors: the coastal restingas from northern Espirito Santo State to southern Bahia State (between Linhares, ES, and Tarancoso, BA), and the coastal region between the restingas of Maricá and Jurubatiba, Rio de Janeiro State. Six species of terrestrial vertebrates considered threatened with extinction are found in the restingas of Serra do Mar and Central da Mata Atlântica biodiversity corridors (Liolaemus lutzae, Formicivora littoralis, Mimus gilvus, Schistochlamys melanopis, and Trinomys eliasi). The region located between the restinga of Maricá and that of Jurubatiba is of special relevance for the conservation of vertebrate species of the restingas of the corridors because a considerable number of threatened species of terrestrial vertebrates are found there. We strongly recommend efforts to develop checklists of threatened faunas for the States of Espirito Santo and Bahia.

Regional influence of cocaine on evoked dopamine release in the nucleus accumbens core: A role for the caudal brainstem.

PubMed

Gerth, Ashlynn I; Alhadeff, Amber L; Grill, Harvey J; Roitman, Mitchell F

2017-01-15

Cocaine increases dopamine concentration in the nucleus accumbens through competitive binding to the dopamine transporter (DAT). However, it also increases the frequency of dopamine release events, a finding that cannot be explained by action at the DAT alone. Rather, this effect may be mediated by cocaine-induced modulation of brain regions that project to dopamine neurons. To explore regional contributions of cocaine to dopamine signaling, we administered cocaine to the lateral or fourth ventricles and compared the effects on dopamine release in the nucleus accumbens evoked by electrical stimulation of the ventral tegmental area to that of systemically-delivered cocaine. Stimulation trains caused a sharp rise in dopamine followed by a slower return to baseline. The magnitude of dopamine release ([DA]max) as well as the latency to decay to fifty percent of the maximum (t(1/2); index of DAT activity) by each stimulation train were recorded. All routes of cocaine delivery caused an increase in [DA]max; only systemic cocaine caused an increase in t(1/2). Importantly, these data are the first to show that hindbrain (fourth ventricle)-delivered cocaine modulates phasic dopamine signaling. Fourth ventricular cocaine robustly increased cFos immunoreactivity in the nucleus of the solitary tract (NTS), suggesting a neural substrate for hindbrain cocaine-mediated effects on [DA]max. Together, the data demonstrate that cocaine-induced effects on phasic dopamine signaling are mediated via actions throughout the brain including the hindbrain. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Trends in corrected lung cancer mortality rates in Brazil and regions.

PubMed

Malta, Deborah Carvalho; Abreu, Daisy Maria Xavier de; Moura, Lenildo de; Lana, Gustavo C; Azevedo, Gulnar; França, Elisabeth

2016-06-27

To describe the trend in cancer mortality rates in Brazil and regions before and after correction for underreporting of deaths and redistribution of ill-defined and nonspecific causes. The study used data of deaths from lung cancer among the population aged from 30 to 69 years, notified to the Mortality Information System between 1996 and 2011, corrected for underreporting of deaths, non-registered sex and age , and causes with ill-defined or garbage codes according to sex, age, and region. Standardized rates were calculated by age for raw and corrected data. An analysis of time trend in lung cancer mortality was carried out using the regression model with autoregressive errors. Lung cancer in Brazil presented higher rates among men compared to women, and the South region showed the highest death risk in 1996 and 2011. Mortality showed a trend of reduction for males and increase for women. Lung cancer in Brazil presented different distribution patterns according to sex, with higher rates among men and a reduction in the mortality trend for men and increase for women. Descrever a tendência da mortalidade por câncer de pulmão no Brasil e regiões, antes e após as correções por sub-registro de óbitos, redistribuição de causas mal definidas e causas inespecíficas. Foram utilizados dados de óbitos por câncer de pulmão da população de 30 a 69 anos, notificados ao Sistema de Informação sobre Mortalidade, entre 1996 e 2011, corrigidos para sub-registro de óbitos, declaração de sexo e idade ignorados e causas com códigos mal definidos e inespecíficos segundo sexo, idade e região. Foram calculadas taxas padronizadas por idade para dados brutos e corrigidos. Realizou-se análise da tendência temporal da mortalidade por câncer de pulmão por meio do modelo de regressão com erros autorregressivos. O câncer de pulmão no Brasil apresentou taxas mais elevadas em homens que em mulheres e a região Sul foi a que apresentou maior risco de morte em 1996 e 2011. A mortalidade tendeu a reduzir para o sexo masculino e a aumentar para o sexo feminino. O câncer de pulmão no Brasil apresenta padrão de distribuição diferente segundo sexo, com taxas mais elevadas em homens e com redução da tendência de mortalidade para o sexo masculino e aumento das taxas para o sexo feminino.

Improving estimates of water resources in a semi-arid region by assimilating GRACE data into the PCR-GLOBWB hydrological model

NASA Astrophysics Data System (ADS)

Tangdamrongsub, Natthachet; Steele-Dunne, Susan C.; Gunter, Brian C.; Ditmar, Pavel G.; Sutanudjaja, Edwin H.; Sun, Yu; Xia, Ting; Wang, Zhongjing

2017-04-01

An accurate estimation of water resources dynamics is crucial for proper management of both agriculture and the local ecology, particularly in semi-arid regions. Imperfections in model physics, uncertainties in model land parameters and meteorological data, as well as the human impact on land changes often limit the accuracy of hydrological models in estimating water storages. To mitigate this problem, this study investigated the assimilation of terrestrial water storage variation (TWSV) estimates derived from the Gravity Recovery And Climate Experiment (GRACE) data using an ensemble Kalman filter (EnKF) approach. The region considered was the Hexi Corridor in northern China. The hydrological model used for the analysis was PCR-GLOBWB, driven by satellite-based forcing data from April 2002 to December 2010. The impact of the GRACE data assimilation (DA) scheme was evaluated in terms of the TWSV, as well as the variation of individual hydrological storage estimates. The capability of GRACE DA to adjust the storage level was apparent not only for the entire TWSV but also for the groundwater component. In this study, spatially correlated errors in GRACE data were taken into account, utilizing the full error variance-covariance matrices provided as a part of the GRACE data product. The benefits of this approach were demonstrated by comparing the EnKF results obtained with and without taking into account error correlations. The results were validated against in situ groundwater data from five well sites. On average, the experiments showed that GRACE DA improved the accuracy of groundwater storage estimates by as much as 25 %. The inclusion of error correlations provided an equal or greater improvement in the estimates. In contrast, a validation against in situ streamflow data from two river gauges showed no significant benefits of GRACE DA. This is likely due to the limited spatial and temporal resolution of GRACE observations. Finally, results of the GRACE DA study were used to assess the status of water resources over the Hexi Corridor over the considered 9-year time interval. Areally averaged values revealed that TWS, soil moisture, and groundwater storages over the region decreased with an average rate of approximately 0.2, 0.1, and 0.1 cm yr-1 in terms of equivalent water heights, respectively. A particularly rapid decline in TWS (approximately -0.4 cm yr-1) was seen over the Shiyang River basin located in the southeastern part of Hexi Corridor. The reduction mostly occurred in the groundwater layer. An investigation of the relationship between water resources and agricultural activities suggested that groundwater consumption required to maintain crop yield in the growing season for this specific basin was likely the cause of the groundwater depletion.

A top-down perspective on dopamine, motivation and memory.

PubMed

Phillips, Anthony G; Vacca, Giada; Ahn, Soyon

2008-08-01

Dopamine (DA) activity, in the form of increased neural firing or enhanced release of transmitter from nerve terminals and varicosities, is linked to a number of important psychological processes including: movement; hedonic reactions to positive reward; provision of an error detection signal during the acquisition of new learning; response to novel stimuli; provision of reinforcement signals essential for acquisition of new action patterns; and incentive motivation. This review focuses primarily on our research linking dynamic changes in DA efflux on the timescale of minutes, with incentive motivation, as revealed by brain dialysis experiments in behaving animals. Recent experiments on sensory-specific satiety and successive positive and negative contrast are discussed along with the distinction between preparatory behaviors that precede contact with biologically significant stimuli and subsequent consummatory behaviors. The relationship between DA efflux in the medial prefrontal cortex (mPFC) and foraging for food based on working memory is also discussed in support of the conjecture that DA may serve as a link between motivation and memory functions. Evidence in support of 'top-down' regulation of dopaminergic activity in the mesocorticolimbic DA pathways is reviewed briefly to introduce a mechanism by which activation of ascending DA projections in this manner might optimize dopaminergic modulation of executive function within regions such as the mPFC. Collectively, these processes could ensure coordination between cognitive processes that assess current opportunities and the motivational systems that select and engage patterns of approach behavior that bring organisms into contact with the essentials for survival.

Addiction: beyond dopamine reward circuitry.

PubMed

Volkow, Nora D; Wang, Gene-Jack; Fowler, Joanna S; Tomasi, Dardo; Telang, Frank

2011-09-13

Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

EFFECTS OF CHRONIC ANTIDEPRESSANT DRUG ADMINISTRATION AND ELECTROCONVULSIVE SHOCK ON ACTIVITY OF DOPAMINERGIC NEURONS IN THE VENTRAL TEGMENTUM

PubMed Central

West, Charles Hutchison Keesor; Weiss, Jay Michael

2010-01-01

Increasing attention is now focused on reduced dopaminergic neurotransmission in the forebrain as participating in depression. The present paper assessed whether effective antidepressant (AD) treatments might counteract, or compensate for, such a change by altering the neuronal activity of dopaminergic neurons in the ventral tegmental area (VTA-DA neurons), the cell bodies of the mesocorticolimbic dopaminergic system. Eight AD drugs or vehicle were administered to rats for 14 days via subcutaneously-implanted minipumps, at which time single-unit electrophysiological activity of VTA-DA neurons was recorded under anesthesia. Also, animals received a series of five electroconvulsive shocks (ECS) or control procedures, after which VTA-DA activity was measured either three or five days after the last ECS. Results showed that the chronic administration of all AD drugs tested except for the monoamine oxidase inhibitor increased the spontaneous firing rate of VTA-DA neurons, while effects on “burst” firing activity were found to be considerably less notable or consistent. ECS increased both spontaneous firing rate and burst firing of VTA-DA neurons. It is suggested that the effects observed are consistent with reports of increased dopamine release in regions to which VTA neurons project after effective AD treatment. However, it is further suggested that changes in VTA-DA neuronal activity in response to AD treatment should be most appropriately assessed under conditions associated with depression, such as stressful conditions. PMID:20482941

Aniracetam enhances cortical dopamine and serotonin release via cholinergic and glutamatergic mechanisms in SHRSP.

PubMed

Shirane, M; Nakamura, K

2001-10-19

Aniracetam, a cognition enhancer, has been recently found to preferentially increase extracellular levels of dopamine (DA) and serotonin (5-HT) in the prefrontal cortex (PFC), basolateral amygdala and dorsal hippocampus of the mesocorticolimbic system in stroke-prone spontaneously hypertensive rats. In the present study, we aimed to identify actually active substances among aniracetam and its major metabolites and to clarify the mode of action in DA and 5-HT release in the PFC. Local perfusion of mecamylamine, a nicotinic acetylcholine (nACh) and N-methyl-D-aspartate (NMDA) receptor antagonist, into the ventral tegmental area (VTA) and dorsal raphe nucleus (DRN) completely blocked DA and 5-HT release, respectively, in the PFC elicited by orally administered aniracetam. The effects of aniracetam were mimicked by local perfusion of N-anisoyl-gamma-aminobutyric acid [corrected] (N-anisoyl-GABA), one of the major metabolites of aniracetam, into the VTA and DRN. The cortical DA release induced by N-anisoyl-GABA applied to the VTA was also completely abolished by co-perfusion of mecamylamine. Additionally, when p-anisic acid, another metabolite of aniracetam, and N-anisoyl-GABA were locally perfused into the PFC, they induced DA and 5-HT release in the same region, respectively. These results indicate that aniracetam enhances DA and 5-HT release by mainly mediating the action of N-anisoyl-GABA that targets not only somatodendritic nACh and NMDA receptors but also presynaptic nACh receptors.

A plastic corticostriatal circuit model of adaptation in perceptual decision making

PubMed Central

Hsiao, Pao-Yueh; Lo, Chung-Chuan

2013-01-01

The ability to optimize decisions and adapt them to changing environments is a crucial brain function that increase survivability. Although much has been learned about the neuronal activity in various brain regions that are associated with decision making, and about how the nervous systems may learn to achieve optimization, the underlying neuronal mechanisms of how the nervous systems optimize decision strategies with preference given to speed or accuracy, and how the systems adapt to changes in the environment, remain unclear. Based on extensive empirical observations, we addressed the question by extending a previously described cortico-basal ganglia circuit model of perceptual decisions with the inclusion of a dynamic dopamine (DA) system that modulates spike-timing dependent plasticity (STDP). We found that, once an optimal model setting that maximized the reward rate was selected, the same setting automatically optimized decisions across different task environments through dynamic balancing between the facilitating and depressing components of the DA dynamics. Interestingly, other model parameters were also optimal if we considered the reward rate that was weighted by the subject's preferences for speed or accuracy. Specifically, the circuit model favored speed if we increased the phasic DA response to the reward prediction error, whereas the model favored accuracy if we reduced the tonic DA activity or the phasic DA responses to the estimated reward probability. The proposed model provides insight into the roles of different components of DA responses in decision adaptation and optimization in a changing environment. PMID:24339814

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

Volkow, N.D.; Wang, G.; Volkow, N.D.

Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditionedmore » cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.« less

Global and disease-associated genetic variation in the human Fanconi anemia gene family

PubMed Central

Rogers, Kai J.; Fu, Wenqing; Akey, Joshua M.; Monnat, Raymond J.

2014-01-01

Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57 240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. PMID:25104853

Grain boundary oxidation and fatigue crack growth at elevated temperatures

NASA Technical Reports Server (NTRS)

Liu, H. W.; Oshida, Y.

1986-01-01

Fatigue crack growth rate at elevated temperatures can be accelerated by grain boundary oxidation. Grain boundary oxidation kinetics and the statistical distribution of grain boundary oxide penetration depth were studied. At a constant delta K-level and at a constant test temperature, fatigue crack growth rate, da/dN, is a function of cyclic frequency, nu. A fatigue crack growth model of intermittent micro-ruptures of grain boundary oxide is constructed. The model is consistent with the experimental observations that, in the low frequency region, da/dN is inversely proportional to nu, and fatigue crack growth is intergranular.

USSR Report, International Affairs, The Working Class and the Contemporary World, Number 2, March-April 1986.

DTIC Science & Technology

1986-07-31

3. Ibid., p 36. 4. "Yearbook of Labor Statistics. 1984," Geneva, 1984, p 827; G. Farrel, "Mercado de trabajo urbano y el movimiento sindiecal...Frente de liberacion nacional y social," Buenos .Aires, 1984, p 51. 10. EL PERIODISTA DE BUENOS AIRES, Buenos Aires, 1985, No 61, p 6. 11. OPINION...documents of the 27th CPSU Congress correctly point out, has set difficult tasks "for the young and rapidly growing working class in Asia , Africa and

West European and East Asian Perspectives on Defense, Deterrence and Strategy. Volume 4. Portuguese Perspectives on Defense, Deterrence and Strategy.

DTIC Science & Technology

1984-05-16

in U.S. military planning , the West has to face growing threats in the peripheral zones, namely in those that are essential to the supply of raw...to a re-definition of U.S. strategic planning . In accordance with the ’Maritime strategy" of deployment from the U.S. territory of important military...Socialist Party, and the editor of the Communist daily, O’Diario, Miguel Urbano Rodriques. Neutralist doctrines are abundantly expressed in Liber 25

Metals in some lagoons of Mexico.

PubMed

Vazquez, F G; Sharma, V K; Alexander, V H; Frausto, C A

1995-02-01

The concentrations of metals, Cd, Cu, Fe, Mn, Ni, Pb, and Zn were determined in some lagoons to establish the level of metal pollution. The lagoons studied were Alvarado lagoon, Veracruz; San Andres lagoon, Tamaulipas; and Terminos lagoon, Campeche. The concentrations were determined in water, oyster (Crassostrea virginica), and sediments. Metals were accumulated in either oysters or sediments. Cu and Zn were higher in oysters and Fe and Mn were higher in sediments. The results in water samples were compared with the limit established by the Secretaria de Ecologia and Desarrollo Urbano Report and briefly discussed.

Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker responses in east Greenland polar bears (Ursus maritimus).

PubMed

Eggers Pedersen, Kathrine; Basu, Niladri; Letcher, Robert; Greaves, Alana K; Sonne, Christian; Dietz, Rune; Styrishave, Bjarne

2015-04-01

Perfluoroalkyl substances (PFASs) is a growing class of contaminants in the Arctic environment, and include the established perfluorinated sulfonates (PFSAs; especially perfluorooctane sulfonate (PFOS)) and carboxylic acids (PFCAs). PFSAs and PFCAs of varying chain length have been reported to bioaccumulate in lipid rich tissues of the brain among other tissues such as liver, and can reach high concentrations in top predators including the polar bear. PFCA and PFSA bioaccummulation in the brain has the potential to pose neurotoxic effects and therefore we conducted a study to investigate if variations in neurochemical transmitter systems i.e. the cholinergic, glutaminergic, dopaminergic and GABAergic, could be related to brain-specific bioaccumulation of PFASs in East Greenland polar bears. Nine brain regions from nine polar bears were analyzed for enzyme activity (monoamine oxidase (MAO), acetylcholinesterase (AChE) and glutamine synthetase (GS)) and receptor density (dopamine-2 (D2), muscarinic cholinergic (mAChR) and gamma-butyric acid type A (GABA-A)) along with PFSA and PFCA concentrations. Average brain ∑PFSA concentration was 25ng/g ww where PFOS accounted for 91%. Average ∑PFCA concentration was 88ng/g ww where PFUnDA, PFDoDA and PFTrDA combined accounted for 79%. The highest concentrations of PFASs were measured in brain stem, cerebellum and hippocampus. Correlative analyses were performed both across and within brain regions. Significant positive correlations were found between PFASs and MAO activity in occipital lobe (e.g. ∑PFCA; rp=0.83, p=0.041, n=6) and across brain regions (e.g. ∑PFCA; rp=0.47, p=0.001, ∑PFSA; rp=0.44, p>0.001; n=50). GABA-A receptor density was positively correlated with two PFASs across brain regions (PFOS; rp=0.33, p=0.02 and PFDoDA; rp=0.34, p=0.014; n=52). Significant negative correlations were found between mAChR density and PFASs in cerebellum (e.g. ∑PFCA; rp=-0.95, p=0.013, n=5) and across brain regions (e.g. ∑PFCA; rp=-0.40, p=0.003, ∑PFSA; rp=-0.37, p=0.007; n=52). AChE activity and D2 density were negatively correlated with single PFCAs in several brain regions, whereas GS activity was positively correlated with PFASs primarily in occipital lobe. Results from the present study support the hypothesis that PFAS concentrations in polar bears from East Greenland have exceeded the threshold limits for neurochemical alterations. It is not known whether the observed alterations in neurochemical signaling are currently having negative effects on neurochemistry in East Greenland polar bears. However given the importance of these systems in cognitive processes and motor function, the present results indicate an urgent need for a better understanding of neurochemical effects of PFAS exposure to wildlife. Copyright © 2015 Elsevier Inc. All rights reserved.

Toxic diatoms and domoic acid in natural and iron enriched waters of the oceanic Pacific

PubMed Central

Silver, Mary W.; Bargu, Sibel; Coale, Susan L.; Benitez-Nelson, Claudia R.; Garcia, Ana C.; Roberts, Kathryn J.; Sekula-Wood, Emily; Bruland, Kenneth W.; Coale, Kenneth H.

2010-01-01

Near-surface waters ranging from the Pacific subarctic (58°N) to the Southern Ocean (66°S) contain the neurotoxin domoic acid (DA), associated with the diatom Pseudo-nitzschia. Of the 35 stations sampled, including ones from historic iron fertilization experiments (SOFeX, IronEx II), we found Pseudo-nitzschia at 34 stations and DA measurable at 14 of the 26 stations analyzed for DA. Toxin ranged from 0.3 fg·cell−1 to 2 pg·cell−1, comparable with levels found in similar-sized cells from coastal waters. In the western subarctic, descent of intact Pseudo-nitzschia likely delivered significant amounts of toxin (up to 4 μg of DA·m−2·d−1) to underlying mesopelagic waters (150–500 m). By reexamining phytoplankton samples from SOFeX and IronEx II, we found substantial amounts of DA associated with Pseudo-nitzschia. Indeed, at SOFeX in the Antarctic Pacific, DA reached 220 ng·L−1, levels at which animal mortalities have occurred on continental shelves. Iron ocean fertilization also occurs naturally and may have promoted blooms of these ubiquitous algae over previous glacial cycles during deposition of iron-rich aerosols. Thus, the neurotoxin DA occurs both in coastal and oceanic waters, and its concentration, associated with changes in Pseudo-nitzschia abundance, likely varies naturally with climate cycles, as well as with artificial iron fertilization. Given that iron fertilization in iron-depleted regions of the sea has been proposed to enhance phytoplankton growth and, thereby, both reduce atmospheric CO2 and moderate ocean acidification in surface waters, consideration of the potentially serious ecosystem impacts associated with DA is prudent. PMID:21068374

Role of ventral pallidal D2 dopamine receptors in the consolidation of spatial memory.

PubMed

Péczely, László; Ollmann, Tamás; László, Kristóf; Kovács, Anita; Gálosi, Rita; Kertes, Erika; Zagorácz, Olga; Kállai, Veronika; Karádi, Zoltán; Lénárd, László

2016-10-15

The role of dopamine (DA) receptors in spatial memory consolidation has been demonstrated in numerous brain regions, among others in the nucleus accumbens which innervates the ventral pallidum (VP). The VP contains both D1 and D2 DA receptors. We have recently shown that the VP D1 DA receptor activation facilitates consolidation of spatial memory in Morris water maze test. In the present study, the role of VP D2 DA receptors was investigated in the same paradigm. In the first experiment, the D2 DA receptor agonist quinpirole was administered into the VP of male Wistar rats in three doses (0.1, 1.0 or 5.0μg, respectively in 0.4μl physiological saline). In the second experiment, the D2 DA receptor antagonist sulpiride was applied to elucidate whether it can antagonise the effects of quinpirole. The antagonist (4.0μg, dissolved in 0.4μl physiological saline) was microinjected into the VP either by itself or prior to 1.0μg agonist treatment. Control animals received saline in both experiments. The two higher doses (1.0 and 5.0μg) of the agonist accelerated memory consolidation relative to controls and increased the stability of the consolidated memory against extinction. Sulpiride pretreatment antagonised the effects of quinpirole. In addition, the antagonist microinjected into the VP immediately after the second conditioning trial impaired learning functions. The present data provide evidences for the important role of VP D2 DA receptors in the consolidation and stabilization of spatial memory. Copyright © 2016 Elsevier B.V. All rights reserved.

Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.

PubMed

Thibault, Dominic; Giguère, Nicolas; Loustalot, Fabien; Bourque, Marie-Josée; Ducrot, Charles; El Mestikawy, Salah; Trudeau, Louis-Éric

2016-05-01

Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit.

Striatal dopamine release and impaired reinforcement learning in adults with 22q11.2 deletion syndrome.

PubMed

van Duin, Esther D A; Kasanova, Zuzana; Hernaus, Dennis; Ceccarini, Jenny; Heinzel, Alexander; Mottaghy, Felix; Mohammadkhani-Shali, Siamak; Winz, Oliver; Frank, Michael; Beck, Merrit C H; Booij, Jan; Myin-Germeys, Inez; van Amelsvoort, Thérèse

2018-06-01

22q11.2 deletion syndrome (22q11DS) is a genetic disorder caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk for developing psychosis. The catechol-O-methyltransferase (COMT) gene is located in the deleted region and involved in dopamine (DA) breakdown. Impaired reinforcement learning (RL) is a recurrent feature in psychosis and thought to be related to abnormal striatal DA function. This study aims to examine RL and the potential association with striatal DA-ergic neuromodulation in 22q11DS. Twelve non-psychotic adults with 22q11DS and 16 healthy controls (HC) were included. A dopamine D 2/3 receptor [ 18 F]fallypride positron emission tomography (PET) scan was acquired while participants performed a modified version of the probabilistic stimulus selection task. RL-task performance was significantly worse in 22q11DS compared to HC. There were no group difference in striatal nondisplaceable binding potential (BP ND ) and task-induced DA release. In HC, striatal task-induced DA release was positively associated with task performance, but no such relation was found in 22q11DS subjects. Moreover, higher caudate nucleus task-induced DA release was found in COMT Met hemizygotes relative to Val hemizygotes. This study is the first to show impairments in RL in 22q11DS. It suggests that potentially motivational impairments are not only present in psychosis, but also in this genetic high risk group. These deficits may be underlain by abnormal striatal task-induced DA release, perhaps as a consequence of COMT haplo-insufficiency. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

Dopamine depresses excitatory synaptic transmission onto rat subicular neurons via presynaptic D1-like dopamine receptors.

PubMed

Behr, J; Gloveli, T; Schmitz, D; Heinemann, U

2000-07-01

Schizophrenia is considered to be associated with an abnormal functioning of the hippocampal output. The high clinical potency of antipsychotics that act as antagonists at dopamine (DA) receptors indicate a hyperfunction of the dopaminergic system. The subiculum obtains information from area CA1 and the entorhinal cortex and represents the major output region of the hippocampal complex. To clarify whether an enhanced dopaminergic activity alters the hippocampal output, the effect of DA on alveus- and perforant path-evoked excitatory postsynaptic currents (EPSCs) in subicular neurons was examined using conventional intracellular and whole cell voltage-clamp recordings. Dopamine (100 microM) depressed alveus-elicited (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated EPSCs to 56 +/- 8% of control while perforant path-evoked EPSCs were attenuated to only 76 +/- 7% of control. Dopamine had no effect on the EPSC kinetics. Dopamine reduced the frequency of spontaneous miniature EPSCs without affecting their amplitudes. The sensitivity of subicular neurons to the glutamate receptor agonist (S)-alpha-amino-3-hydoxy-5-methyl-4-isoxazolepropionic acid was unchanged by DA pretreatment, excluding a postsynaptic mechanism for the observed reduction of excitatory synaptic transmission. The effect of DA on evoked EPSCs was mimicked by the D1 receptor agonist SFK 38393 and partially antagonized by the D1 receptor antagonist SCH 23390. While the D2 receptor agonist quinelorane failed to reduce the EPSCs, the D2 receptor antagonist sulpiride did not block the action of DA. The results indicate that DA strongly depresses the hippocampal and the entorhinal excitatory input onto subicular neurons by decreasing the glutamate release following activation of presynaptic D1-like DA receptors.

Reduced levels of Cacna1c attenuate mesolimbic dopamine system function.

PubMed

Terrillion, C E; Dao, D T; Cachope, R; Lobo, M K; Puche, A C; Cheer, J F; Gould, T D

2017-06-01

Genetic variation in CACNA1C, which codes for the L-type calcium channel (LTCC) Ca v 1.2, is associated with clinical diagnoses of bipolar disorder, depression and schizophrenia. Dysregulation of the mesolimbic-dopamine (ML-DA) system is linked to these syndromes and LTCCs are required for normal DAergic neurotransmission between the ventral tegmental area (VTA) and nucleus accumbens (NAc). It is unclear, however, how variations in CACNA1C genotype, and potential subsequent changes in expression levels in these regions, modify risk. Using constitutive and conditional knockout mice, and treatment with the LTCC antagonist nimodipine, we examined the role of Cacna1c in DA-mediated behaviors elicited by psychomotor stimulants. Using fast-scan cyclic voltammetry, DA release and reuptake in the NAc were measured. We find that subsecond DA release in Cacna1c haploinsufficient mice lacks normal sensitivity to inhibition of the DA transporter (DAT). Constitutive haploinsufficiency of Cacna1c led to attenuation of hyperlocomotion following acute administration of stimulants specific to DAT, and locomotor sensitization of these mice to the DAT antagonist GBR12909 did not reach the same level as wild-type mice. The maintenance of sensitization to GBR12909 was attenuated by administration of nimodipine. Sensitization to GBR12909 was attenuated in mice with reduced Cacna1c selectively in the VTA but not in the NAc. Our findings show that Cacna1c is crucial for normal behavioral responses to DA stimulants and that its activity in the VTA is required for behavioral sensitization. Cacna1c likely exerts these effects through modifications to presynaptic ML-DA system function. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity.

PubMed

Dunn, Julia P; Kessler, Robert M; Feurer, Irene D; Volkow, Nora D; Patterson, Bruce W; Ansari, Mohammad S; Li, Rui; Marks-Shulman, Pamela; Abumrad, Naji N

2012-05-01

Midbrain dopamine (DA) neurons, which are involved with reward and motivation, are modulated by hormones that regulate food intake (insulin, leptin, and acyl ghrelin [AG]). We hypothesized that these hormones are associated with deficits in DA signaling in obesity. We assessed the relationships between fasting levels of insulin and leptin, and AG, BMI, and insulin sensitivity index (S(I)) with the availability of central DA type 2 receptor (D2R). We measured D2R availability using positron emission tomography and [(18)F]fallypride (radioligand that competes with endogenous DA) in lean (n = 8) and obese (n = 14) females. Fasting hormones were collected prior to scanning and S(I) was determined by modified oral glucose tolerance test. Parametric image analyses revealed associations between each metabolic measure and D2R. The most extensive findings were negative associations of AG with clusters involving the striatum and inferior temporal cortices. Regional regression analyses also found extensive negative relationships between AG and D2R in the caudate, putamen, ventral striatum (VS), amygdala, and temporal lobes. S(I) was negatively associated with D2R in the VS, while insulin was not. In the caudate, BMI and leptin were positively associated with D2R availability. The direction of associations of leptin and AG with D2R availability are consistent with their opposite effects on DA levels (decreasing and increasing, respectively). After adjusting for BMI, AG maintained a significant relationship in the VS. We hypothesize that the increased D2R availability in obese subjects reflects relatively reduced DA levels competing with the radioligand. Our findings provide evidence for an association between the neuroendocrine hormones and DA brain signaling in obese females.

Cocaine cue–induced dopamine release in the human prefrontal cortex

PubMed Central

Milella, Michele S.; Fotros, Aryandokht; Gravel, Paul; Casey, Kevin F.; Larcher, Kevin; Verhaeghe, Jeroen A.J.; Cox, Sylvia M.L.; Reader, Andrew J.; Dagher, Alain; Benkelfat, Chawki; Leyton, Marco

2016-01-01

Background Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. Methods We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence. Results Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self-reported craving. Limitations Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release. Conclusion In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms. PMID:26900792

BMP9 and BMP10 are necessary for proper closure of the ductus arteriosus

PubMed Central

Levet, Sandrine; Ouarné, Marie; Ciais, Delphine; Coutton, Charles; Subileau, Mariela; Mallet, Christine; Ricard, Nicolas; Bidart, Marie; Debillon, Thierry; Faravelli, Francesca; Rooryck, Caroline; Feige, Jean-Jacques; Tillet, Emmanuelle; Bailly, Sabine

2015-01-01

The transition to pulmonary respiration after birth requires rapid alterations in the structure of the mammalian cardiovascular system. One dramatic change that occurs is the closure of the ductus arteriosus (DA), an arterial connection in the fetus that directs blood flow away from the pulmonary circulation. Two members of the TGFβ family, bone morphogenetic protein 9 (BMP9) and BMP10, have been recently involved in postnatal angiogenesis, both being necessary for remodeling of newly formed microvascular beds. The aim of the present work was to study whether BMP9 and BMP10 could be involved in closure of the DA. We found that Bmp9 knockout in mice led to an imperfect closure of the DA. Further, addition of a neutralizing anti-BMP10 antibody at postnatal day 1 (P1) and P3 in these pups exacerbated the remodeling defect and led to a reopening of the DA at P4. Transmission electron microscopy images and immunofluorescence stainings suggested that this effect could be due to a defect in intimal cell differentiation from endothelial to mesenchymal cells, associated with a lack of extracellular matrix deposition within the center of the DA. This result was supported by the identification of the regulation by BMP9 and BMP10 of several genes known to be involved in this process. The involvement of these BMPs was further supported by human genomic data because we could define a critical region in chromosome 2 encoding eight genes including BMP10 that correlated with the presence of a patent DA. Together, these data establish roles for BMP9 and BMP10 in DA closure. PMID:26056270

Toxic diatoms and domoic acid in natural and iron enriched waters of the oceanic Pacific.

PubMed

Silver, Mary W; Bargu, Sibel; Coale, Susan L; Benitez-Nelson, Claudia R; Garcia, Ana C; Roberts, Kathryn J; Sekula-Wood, Emily; Bruland, Kenneth W; Coale, Kenneth H

2010-11-30

Near-surface waters ranging from the Pacific subarctic (58°N) to the Southern Ocean (66°S) contain the neurotoxin domoic acid (DA), associated with the diatom Pseudo-nitzschia. Of the 35 stations sampled, including ones from historic iron fertilization experiments (SOFeX, IronEx II), we found Pseudo-nitzschia at 34 stations and DA measurable at 14 of the 26 stations analyzed for DA. Toxin ranged from 0.3 fg·cell(-1) to 2 pg·cell(-1), comparable with levels found in similar-sized cells from coastal waters. In the western subarctic, descent of intact Pseudo-nitzschia likely delivered significant amounts of toxin (up to 4 μg of DA·m(-2)·d(-1)) to underlying mesopelagic waters (150-500 m). By reexamining phytoplankton samples from SOFeX and IronEx II, we found substantial amounts of DA associated with Pseudo-nitzschia. Indeed, at SOFeX in the Antarctic Pacific, DA reached 220 ng·L(-1), levels at which animal mortalities have occurred on continental shelves. Iron ocean fertilization also occurs naturally and may have promoted blooms of these ubiquitous algae over previous glacial cycles during deposition of iron-rich aerosols. Thus, the neurotoxin DA occurs both in coastal and oceanic waters, and its concentration, associated with changes in Pseudo-nitzschia abundance, likely varies naturally with climate cycles, as well as with artificial iron fertilization. Given that iron fertilization in iron-depleted regions of the sea has been proposed to enhance phytoplankton growth and, thereby, both reduce atmospheric CO(2) and moderate ocean acidification in surface waters, consideration of the potentially serious ecosystem impacts associated with DA is prudent.

Metabolic Profiling and Classification of Propolis Samples from Southern Brazil: An NMR-Based Platform Coupled with Machine Learning.

PubMed

Maraschin, Marcelo; Somensi-Zeggio, Amélia; Oliveira, Simone K; Kuhnen, Shirley; Tomazzoli, Maíra M; Raguzzoni, Josiane C; Zeri, Ana C M; Carreira, Rafael; Correia, Sara; Costa, Christopher; Rocha, Miguel

2016-01-22

The chemical composition of propolis is affected by environmental factors and harvest season, making it difficult to standardize its extracts for medicinal usage. By detecting a typical chemical profile associated with propolis from a specific production region or season, certain types of propolis may be used to obtain a specific pharmacological activity. In this study, propolis from three agroecological regions (plain, plateau, and highlands) from southern Brazil, collected over the four seasons of 2010, were investigated through a novel NMR-based metabolomics data analysis workflow. Chemometrics and machine learning algorithms (PLS-DA and RF), including methods to estimate variable importance in classification, were used in this study. The machine learning and feature selection methods permitted construction of models for propolis sample classification with high accuracy (>75%, reaching ∼90% in the best case), better discriminating samples regarding their collection seasons comparatively to the harvest regions. PLS-DA and RF allowed the identification of biomarkers for sample discrimination, expanding the set of discriminating features and adding relevant information for the identification of the class-determining metabolites. The NMR-based metabolomics analytical platform, coupled to bioinformatic tools, allowed characterization and classification of Brazilian propolis samples regarding the metabolite signature of important compounds, i.e., chemical fingerprint, harvest seasons, and production regions.

Leveraging 35 years of Pinus taeda research in the southeastern US to constrain forest carbon cycle predictions: regional data assimilation using ecosystem experiments

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

Thomas, R. Quinn; Brooks, Evan B.; Jersild, Annika L.

Predicting how forest carbon cycling will change in response to climate change and management depends on the collective knowledge from measurements across environmental gradients, ecosystem manipulations of global change factors, and mathematical models. Formally integrating these sources of knowledge through data assimilation, or model–data fusion, allows the use of past observations to constrain model parameters and estimate prediction uncertainty. Data assimilation (DA) focused on the regional scale has the opportunity to integrate data from both environmental gradients and experimental studies to constrain model parameters. Here, we introduce a hierarchical Bayesian DA approach (Data Assimilation to Predict Productivity for Ecosystems and Regions,more » DAPPER) that uses observations of carbon stocks, carbon fluxes, water fluxes, and vegetation dynamics from loblolly pine plantation ecosystems across the southeastern US to constrain parameters in a modified version of the Physiological Principles Predicting Growth (3-PG) forest growth model. The observations included major experiments that manipulated atmospheric carbon dioxide (CO 2) concentration, water, and nutrients, along with nonexperimental surveys that spanned environmental gradients across an 8.6 × 10 5 km 2 region. We optimized regionally representative posterior distributions for model parameters, which dependably predicted data from plots withheld from the data assimilation. While the mean bias in predictions of nutrient fertilization experiments, irrigation experiments, and CO 2 enrichment experiments was low, future work needs to focus modifications to model structures that decrease the bias in predictions of drought experiments. Predictions of how growth responded to elevated CO 2 strongly depended on whether ecosystem experiments were assimilated and whether the assimilated field plots in the CO 2 study were allowed to have different mortality parameters than the other field plots in the region. We present predictions of stem biomass productivity under elevated CO 2, decreased precipitation, and increased nutrient availability that include estimates of uncertainty for the southeastern US. Overall, we (1) demonstrated how three decades of research in southeastern US planted pine forests can be used to develop DA techniques that use multiple locations, multiple data streams, and multiple ecosystem experiment types to optimize parameters and (2) developed a tool for the development of future predictions of forest productivity for natural resource managers that leverage a rich dataset of integrated ecosystem observations across a region.« less

Leveraging 35 years of Pinus taeda research in the southeastern US to constrain forest carbon cycle predictions: regional data assimilation using ecosystem experiments

DOE PAGES

Thomas, R. Quinn; Brooks, Evan B.; Jersild, Annika L.; ...

2017-07-26

Predicting how forest carbon cycling will change in response to climate change and management depends on the collective knowledge from measurements across environmental gradients, ecosystem manipulations of global change factors, and mathematical models. Formally integrating these sources of knowledge through data assimilation, or model–data fusion, allows the use of past observations to constrain model parameters and estimate prediction uncertainty. Data assimilation (DA) focused on the regional scale has the opportunity to integrate data from both environmental gradients and experimental studies to constrain model parameters. Here, we introduce a hierarchical Bayesian DA approach (Data Assimilation to Predict Productivity for Ecosystems and Regions,more » DAPPER) that uses observations of carbon stocks, carbon fluxes, water fluxes, and vegetation dynamics from loblolly pine plantation ecosystems across the southeastern US to constrain parameters in a modified version of the Physiological Principles Predicting Growth (3-PG) forest growth model. The observations included major experiments that manipulated atmospheric carbon dioxide (CO 2) concentration, water, and nutrients, along with nonexperimental surveys that spanned environmental gradients across an 8.6 × 10 5 km 2 region. We optimized regionally representative posterior distributions for model parameters, which dependably predicted data from plots withheld from the data assimilation. While the mean bias in predictions of nutrient fertilization experiments, irrigation experiments, and CO 2 enrichment experiments was low, future work needs to focus modifications to model structures that decrease the bias in predictions of drought experiments. Predictions of how growth responded to elevated CO 2 strongly depended on whether ecosystem experiments were assimilated and whether the assimilated field plots in the CO 2 study were allowed to have different mortality parameters than the other field plots in the region. We present predictions of stem biomass productivity under elevated CO 2, decreased precipitation, and increased nutrient availability that include estimates of uncertainty for the southeastern US. Overall, we (1) demonstrated how three decades of research in southeastern US planted pine forests can be used to develop DA techniques that use multiple locations, multiple data streams, and multiple ecosystem experiment types to optimize parameters and (2) developed a tool for the development of future predictions of forest productivity for natural resource managers that leverage a rich dataset of integrated ecosystem observations across a region.« less

The Effects of Threonine Phosphorylation on the Stability and Dynamics of the Central Molecular Switch Region of 18.5-kDa Myelin Basic Protein

PubMed Central

De Avila, Miguel; Polverini, Eugenia; Harauz, George

2013-01-01

The classic isoforms of myelin basic protein (MBP) are essential for the formation and maintenance of myelin in the central nervous system of higher vertebrates. The protein is involved in all facets of the development, compaction, and stabilization of the multilamellar myelin sheath, and also interacts with cytoskeletal and signaling proteins. The predominant 18.5-kDa isoform of MBP is an intrinsically-disordered protein that is a candidate auto-antigen in the human demyelinating disease multiple sclerosis. A highly-conserved central segment within classic MBP consists of a proline-rich region (murine 18.5-kDa sequence –T92-P93-R94-T95-P96-P97-P98-S99–) containing a putative SH3-ligand, adjacent to a region that forms an amphipathic α-helix (P82-I90) upon interaction with membranes, or under membrane-mimetic conditions. The T92 and T95 residues within the proline-rich region can be post-translationally modified through phosphorylation by mitogen-activated protein (MAP) kinases. Here, we have investigated the structure of the α-helical and proline-rich regions in dilute aqueous buffer, and have evaluated the effects of phosphorylation at T92 and T95 on the stability and dynamics of the α-helical region, by utilizing four 36-residue peptides (S72–S107) with differing phosphorylation status. Nuclear magnetic resonance spectroscopy reveals that both the α-helical as well as the proline-rich regions are disordered in aqueous buffer, whereas they are both structured in a lipid environment (cf., Ahmed et al., Biochemistry 51, 7475-9487, 2012). Thermodynamic analysis of trifluoroethanol-titration curves monitored by circular dichroism spectroscopy reveals that phosphorylation, especially at residue T92, impedes formation of the amphipathic α-helix. This conclusion is supported by molecular dynamics simulations, which further illustrate that phosphorylation reduces the folding reversibility of the α-helix upon temperature perturbation and affect the global structure of the peptides through altered electrostatic interactions. The results support the hypothesis that the central conserved segment of MBP constitutes a molecular switch in which the conformation and/or intermolecular interactions are mediated by phosphorylation/dephosphorylation at T92 and T95. PMID:23861868

Leveraging 35 years of Pinus taeda research in the southeastern US to constrain forest carbon cycle predictions: regional data assimilation using ecosystem experiments

NASA Astrophysics Data System (ADS)

Quinn Thomas, R.; Brooks, Evan B.; Jersild, Annika L.; Ward, Eric J.; Wynne, Randolph H.; Albaugh, Timothy J.; Dinon-Aldridge, Heather; Burkhart, Harold E.; Domec, Jean-Christophe; Fox, Thomas R.; Gonzalez-Benecke, Carlos A.; Martin, Timothy A.; Noormets, Asko; Sampson, David A.; Teskey, Robert O.

2017-07-01

Predicting how forest carbon cycling will change in response to climate change and management depends on the collective knowledge from measurements across environmental gradients, ecosystem manipulations of global change factors, and mathematical models. Formally integrating these sources of knowledge through data assimilation, or model-data fusion, allows the use of past observations to constrain model parameters and estimate prediction uncertainty. Data assimilation (DA) focused on the regional scale has the opportunity to integrate data from both environmental gradients and experimental studies to constrain model parameters. Here, we introduce a hierarchical Bayesian DA approach (Data Assimilation to Predict Productivity for Ecosystems and Regions, DAPPER) that uses observations of carbon stocks, carbon fluxes, water fluxes, and vegetation dynamics from loblolly pine plantation ecosystems across the southeastern US to constrain parameters in a modified version of the Physiological Principles Predicting Growth (3-PG) forest growth model. The observations included major experiments that manipulated atmospheric carbon dioxide (CO2) concentration, water, and nutrients, along with nonexperimental surveys that spanned environmental gradients across an 8.6 × 105 km2 region. We optimized regionally representative posterior distributions for model parameters, which dependably predicted data from plots withheld from the data assimilation. While the mean bias in predictions of nutrient fertilization experiments, irrigation experiments, and CO2 enrichment experiments was low, future work needs to focus modifications to model structures that decrease the bias in predictions of drought experiments. Predictions of how growth responded to elevated CO2 strongly depended on whether ecosystem experiments were assimilated and whether the assimilated field plots in the CO2 study were allowed to have different mortality parameters than the other field plots in the region. We present predictions of stem biomass productivity under elevated CO2, decreased precipitation, and increased nutrient availability that include estimates of uncertainty for the southeastern US. Overall, we (1) demonstrated how three decades of research in southeastern US planted pine forests can be used to develop DA techniques that use multiple locations, multiple data streams, and multiple ecosystem experiment types to optimize parameters and (2) developed a tool for the development of future predictions of forest productivity for natural resource managers that leverage a rich dataset of integrated ecosystem observations across a region.

The effects of threonine phosphorylation on the stability and dynamics of the central molecular switch region of 18.5-kDa myelin basic protein.

PubMed

Vassall, Kenrick A; Bessonov, Kyrylo; De Avila, Miguel; Polverini, Eugenia; Harauz, George

2013-01-01

The classic isoforms of myelin basic protein (MBP) are essential for the formation and maintenance of myelin in the central nervous system of higher vertebrates. The protein is involved in all facets of the development, compaction, and stabilization of the multilamellar myelin sheath, and also interacts with cytoskeletal and signaling proteins. The predominant 18.5-kDa isoform of MBP is an intrinsically-disordered protein that is a candidate auto-antigen in the human demyelinating disease multiple sclerosis. A highly-conserved central segment within classic MBP consists of a proline-rich region (murine 18.5-kDa sequence -T92-P93-R94-T95-P96-P97-P98-S99-) containing a putative SH3-ligand, adjacent to a region that forms an amphipathic α-helix (P82-I90) upon interaction with membranes, or under membrane-mimetic conditions. The T92 and T95 residues within the proline-rich region can be post-translationally modified through phosphorylation by mitogen-activated protein (MAP) kinases. Here, we have investigated the structure of the α-helical and proline-rich regions in dilute aqueous buffer, and have evaluated the effects of phosphorylation at T92 and T95 on the stability and dynamics of the α-helical region, by utilizing four 36-residue peptides (S72-S107) with differing phosphorylation status. Nuclear magnetic resonance spectroscopy reveals that both the α-helical as well as the proline-rich regions are disordered in aqueous buffer, whereas they are both structured in a lipid environment (cf., Ahmed et al., Biochemistry 51, 7475-9487, 2012). Thermodynamic analysis of trifluoroethanol-titration curves monitored by circular dichroism spectroscopy reveals that phosphorylation, especially at residue T92, impedes formation of the amphipathic α-helix. This conclusion is supported by molecular dynamics simulations, which further illustrate that phosphorylation reduces the folding reversibility of the α-helix upon temperature perturbation and affect the global structure of the peptides through altered electrostatic interactions. The results support the hypothesis that the central conserved segment of MBP constitutes a molecular switch in which the conformation and/or intermolecular interactions are mediated by phosphorylation/dephosphorylation at T92 and T95.

Cloning, Expression, and Nucleotide Sequence of the Pseudomonas aeruginosa 142 ohb Genes Coding for Oxygenolytic ortho Dehalogenation of Halobenzoates

PubMed Central

Tsoi, Tamara V.; Plotnikova, Elena G.; Cole, James R.; Guerin, William F.; Bagdasarian, Michael; Tiedje, James M.

1999-01-01

We have cloned and characterized novel oxygenolytic ortho-dehalogenation (ohb) genes from 2-chlorobenzoate (2-CBA)- and 2,4-dichlorobenzoate (2,4-dCBA)-degrading Pseudomonas aeruginosa 142. Among 3,700 Escherichia coli recombinants, two clones, DH5αF′(pOD22) and DH5αF′(pOD33), converted 2-CBA to catechol and 2,4-dCBA and 2,5-dCBA to 4-chlorocatechol. A subclone of pOD33, plasmid pE43, containing the 3,687-bp minimized ohb DNA region conferred to P. putida PB2440 the ability to grow on 2-CBA as a sole carbon source. Strain PB2440(pE43) also oxidized but did not grow on 2,4-dCBA, 2,5-dCBA, or 2,6-dCBA. Terminal oxidoreductase ISPOHB structural genes ohbA and ohbB, which encode polypeptides with molecular masses of 20,253 Da (β-ISP) and 48,243 Da (α-ISP), respectively, were identified; these proteins are in accord with the 22- and 48-kDa (as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) polypeptides synthesized in E. coli and P. aeruginosa parental strain 142. The ortho-halobenzoate 1,2-dioxygenase activity was manifested in the absence of ferredoxin and reductase genes, suggesting that the ISPOHB utilized electron transfer components provided by the heterologous hosts. ISPOHB formed a new phylogenetic cluster that includes aromatic oxygenases featuring atypical structural-functional organization and is distant from the other members of the family of primary aromatic oxygenases. A putative IclR-type regulatory gene (ohbR) was located upstream of the ohbAB genes. An open reading frame (ohbC) of unknown function that overlaps lengthwise with ohbB but is transcribed in the opposite direction was found. The ohbC gene codes for a 48,969-Da polypeptide, in accord with the 49-kDa protein detected in E. coli. The ohb genes are flanked by an IS1396-like sequence containing a putative gene for a 39,715-Da transposase A (tnpA) at positions 4731 to 5747 and a putative gene for a 45,247-Da DNA topoisomerase I/III (top) at positions 346 to 1563. The ohb DNA region is bordered by 14-bp imperfect inverted repeats at positions 56 to 69 and 5984 to 5997. PMID:10224014

Effects of intrinsic aerobic capacity and ovariectomy on voluntary wheel running and nucleus accumbens dopamine receptor gene expression.

PubMed

Park, Young-Min; Kanaley, Jill A; Padilla, Jaume; Zidon, Terese; Welly, Rebecca J; Will, Matthew J; Britton, Steven L; Koch, Lauren G; Ruegsegger, Gregory N; Booth, Frank W; Thyfault, John P; Vieira-Potter, Victoria J

2016-10-01

Rats selectively bred for high (HCR) and low (LCR) aerobic capacity show a stark divergence in wheel running behavior, which may be associated with the dopamine (DA) system in the brain. HCR possess greater motivation for voluntary running along with greater brain DA activity compared to LCR. We recently demonstrated that HCR are not immune to ovariectomy (OVX)-associated reductions in spontaneous cage (i.e. locomotor) activity. Whether HCR and LCR rats differ in their OVX-mediated voluntary wheel running response is unknown. To determine whether HCR are protected from OVX-associated reduction in voluntary wheel running. Forty female HCR and LCR rats (age ~27weeks) had either SHM or OVX operations, and given access to a running wheel for 11weeks. Weekly wheel running distance was monitored throughout the intervention. Nucleus accumbens (NAc) was assessed for mRNA expression of DA receptors at sacrifice. Compared to LCR, HCR ran greater distance and had greater ratio of excitatory/inhibitory DA mRNA expression (both line main effects, P<0.05). Wheel running distance was significantly, positively correlated with the ratio of excitatory/inhibitory DA mRNA expression across animals. In both lines, OVX reduced wheel running (P<0.05). Unexpectedly, although HCR started with significantly greater voluntary wheel running, they had greater OVX-induced reduction in wheel running than LCR such that no differences were found 11weeks after OVX between HCROVX and LCROVX (interaction, P<0.05). This significant reduction in wheel running in HCR was associated with an OVX-mediated reduction in the ratio of excitatory/inhibitory DA mRNA expression. The DA system in the NAc region may play a significant role in motivation to run in female rats. Compared to LCR, HCR rats run significantly more, which associates with greater ratio of excitatory/inhibitory DA mRNA expression. However, despite greater inherent motivation to run and an associated brain DA mRNA expression profile, HCR rats are not protected against OVX-induced reduction in wheel running or OVX-mediated reduction in the ratio of excitatory/inhibitory DA receptor mRNA expression. OVX-mediated reduction in motivated physical activity may be partially explained by a reduced ratio of excitatory/inhibitory DA receptor mRNA expression for which intrinsic fitness does not confer protection. Copyright © 2016 Elsevier Inc. All rights reserved.

Reactive transport under stress: Permeability evolution in deformable porous media

NASA Astrophysics Data System (ADS)

Roded, R.; Paredes, X.; Holtzman, R.

2018-07-01

We study reactive transport in a stressed porous media, where dissolution of the solid matrix causes two simultaneous, competing effects: pore enlargement due to chemical deformation, and pore compaction due to mechanical weakening. We use a novel, mechanistic pore-scale model to simulate flooding of a sample under fixed confining stress. Our simulations show that increasing the stress inhibits the permeability enhancement, increasing the injected volume required to reach a certain permeability, in agreement with recent experiments. We explain this behavior by stress concentration downstream, in the less dissolved (hence stiffer) outlet region. As this region is also less conductive, even its small compaction has a strong bottleneck effect that curbs the permeability. Our results also elucidate that the impact of stress depends on the dissolution regime. Under wormholing conditions (slow injection, i.e. high Damkohler number, Da), the development of a sharp dissolution front and high porosity contrast accentuates the bottleneck effect. This reduces transport heterogeneity, promoting wormhole competition. Once the outlet starts eroding, the extreme focusing of transport and hence dissolution-characteristic of wormholing-becomes dominant, diminishing the bottleneck effect and hence the impact of stress at breakthrough. In contrast, at high flow rates (low Da), incomplete reaction upstream allows some of the reactant to traverse the sample, causing a more uniform dissolution. The continuous dissolution and its partial counteraction by compaction at the outlet provides a steady, gradual increase in the effect of stress. Consequently, the impact of stress is more pronounced at high Da during early stages (low permeability), and at low Da close breakthrough. Our work promotes understanding of the interplay between dissolution and compaction and its effect on the hydromechanical property evolution, with important implications for processes ranging from diagenesis and weathering of rocks, to well stimulation and carbon sequestration.

The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies.

PubMed

Volkow, Nora D; Fowler, Joanna S; Wang, Gene-Jack

2004-01-01

Imaging studies have provided evidence of how the human brain changes as an individual becomes addicted. Here, we integrate the findings from imaging studies to propose a model of drug addiction. The process of addiction is initiated in part by the fast and high increases in DA induced by drugs of abuse. We hypothesize that this supraphysiological effect of drugs trigger a series of adaptations in neuronal circuits involved in saliency/reward, motivation/drive, memory/conditioning, and control/disinhibition, resulting in an enhanced (and long lasting) saliency value for the drug and its associated cues at the expense of decreased sensitivity for salient events of everyday life (including natural reinforcers). Although acute drug intake increases DA neurotransmission, chronic drug consumption results in a marked decrease in DA activity, associated with, among others, dysregulation of the orbitofrontal cortex (region involved with salience attribution) and cingulate gyrus (region involved with inhibitory control). The ensuing increase in motivational drive for the drug, strengthened by conditioned responses and the decrease in inhibitory control favors emergence of compulsive drug taking. This view of how drugs of abuse affect the brain suggests strategies for intervention, which might include: (a) those that will decrease the reward value of the drug of choice; (b) interventions to increase the saliency value of non-drug reinforcers; (c) approaches to weaken conditioned drug behaviors; and (d) methods to strengthen frontal inhibitory and executive control. Though this model focuses mostly on findings from PET studies of the brain DA system it is evident that other neurotransmitters are involved and that a better understanding of their roles in addiction would expand the options for therapeutic targets.

DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding.

PubMed

Sambataro, Fabio; Fazio, Leonardo; Taurisano, Paolo; Gelao, Barbara; Porcelli, Annamaria; Mancini, Marina; Sinibaldi, Lorenzo; Ursini, Gianluca; Masellis, Rita; Caforio, Grazia; Di Giorgio, Annabella; Niccoli-Asabella, Artor; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

2013-01-01

The default mode network (DMN) comprises a set of brain regions with "increased" activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([(123)I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling.

DRD2 Genotype-Based Variation of Default Mode Network Activity and of Its Relationship With Striatal DAT Binding

PubMed Central

Sambataro, Fabio; Fazio, Leonardo; Taurisano, Paolo; Gelao, Barbara; Porcelli, Annamaria; Mancini, Marina; Sinibaldi, Lorenzo; Ursini, Gianluca; Masellis, Rita; Caforio, Grazia; Di Giorgio, Annabella; Niccoli-Asabella, Artor; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

2013-01-01

The default mode network (DMN) comprises a set of brain regions with “increased” activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([123I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling. PMID:21976709

Patterns of directional asymmetry in the pelvis and pelvic canal.

PubMed

Tobolsky, Victoria A; Kurki, Helen K; Stock, Jay T

2016-11-01

The human pelvis is unique among modern taxa for supporting both parturition of large brained young and obligate bipedalism. Though much work has focused on pelvic development and variation, little work has explored the presence or absence of asymmetry in the pelvis despite well-known patterns of asymmetry in other skeletal regions. This study investigated whether patterns of directional asymmetry (DA) could be observed in the pelvis or pelvic canal. Seventeen bilaterally paired osteometric measurements of the os coxae (34 measures in total) were taken from 128 skeletons (female n = 65, male n = 63) from recent human populations in five geographic regions. Paired sample t-tests and Mann-Whitney U-tests were used to investigate DA. Results from a pooled sample of all individuals showed that the pelvis exhibited a left-bias in DA. In contrast, the pelvic canal exhibited a pattern in which the anterior canal exhibited a right-bias and the posterior canal exhibited a left-bias. Neither sex nor populational differences in DA were observed in the pelvis or pelvic canal. The varying patterns of asymmetry uncovered here accord with prior work and may indicate that loading from the trunk and legs place differing stresses on the pelvis and canal, yielding these unequal asymmetries. However, this is speculative and the possible influence of genetics, biomechanics, and nutritional status on the development of pelvic and canal asymmetries presents a rich area for future study. Additionally, the potential influence of pelvic canal asymmetry on obstetric measures of pelvic capacity merits future research. Am. J. Hum. Biol. 28:804-810, 2016. © 2016Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Exposure to a high-fat high-sugar diet causes strong up-regulation of proopiomelanocortin and differentially affects dopamine D1 and D2 receptor gene expression in the brainstem of rats.

PubMed

Alsiö, Johan; Rask-Andersen, Mathias; Chavan, Rohit A; Olszewski, Pawel K; Levine, Allen S; Fredriksson, Robert; Schiöth, Helgi B

2014-01-24

A strong link between obesity and dopamine (DA) has been established by studies associating body weight status to variants of genes related to DA signalling. Human and animal studies investigating this relationship have so far focused mainly on the role of DA within the mesolimbic pathway. The aim of this study was to investigate potential DA receptor dysregulation in the brainstem, where these receptors play a potential role in meal termination, during high-fat high-sugar diet (HFHS) exposure. Expression of other key genes, including proopiomelanocortin (POMC), was also analyzed. We randomized rats into three groups; ad libitum access to HFHS (n=24), restricted HFHS access (n=10), or controls (chow-fed, n=10). After 5 weeks, brainstem gene expression was investigated by qRT-PCR. We observed an increase in POMC expression in ad libitum HFHS-fed rats compared to chow-fed controls (p<0.05). Further, expression of DA D2 receptor mRNA was down-regulated in the brainstem of the HFHS ad libitum-fed rats (p<0.05), whereas expression of the DA D1 receptor was upregulated (p<0.05) in these animals compared to chow-fed rats. In control experiments, we observed no effect relative to chow-fed controls on DA-receptor or POMC gene expression in the hypothalamus of HFHS diet-exposed rats, or in the brainstem of acutely food deprived rats. The present findings suggest brainstem POMC to be responsive to palatable foods, and that DA dysregulation after access to energy-dense diets occurs not only in striatal regions, but also in the brainstem, which could be relevant for overeating and for the development and maintenance of obesity. Copyright © 2013. Published by Elsevier Ireland Ltd.

Enhanced regional brain metabolic responses to benzodiazepines in cocaine abusers

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

Volkow, N.D.; Wang, G.J.; Fowler, J.S.

While dopamine (DA) appears to be crucial for cocaine reinforcement, its involvement in cocaine addiction is much less clear. Using PET we have shown persistent reductions in striatal DA D2 receptors (which arc predominantly located on GABA cells) in cocaine abusers. This finding coupled to GABA`s role as an effector for DA led us to investigate if there were GABAergic abnormalities in cocaine abusers. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission). Methods: The experimental subjects consisted of 12 active cocaine abusers and 32 age matched controls. Eachmore » subject underwent two PET FDG scans obtained within 1 week of each other. The first FDG scan was obtained after administration of placebo (3 cc of saline solution) given 40-50 minutes prior to FDG; and the second after administration of lorazepam (30 {mu}g/kg) given 40-50 minutes prior to FDG. The subjects were blind to the drugs received. Results: Lorazepam-induced sleepiness was significantly greater in abusers than in controls (p<0.001). Lorazepam-induced decreases in brain glucose metabolism were significantly larger in cocaine abusers than in controls. Whereas in controls whole brain metabolism decreased 13{+-}7 %, in cocaine abusers it decreased 21{+-}13 % (p < 0.05). Lorazepam-induced decrements in regional metabolism were significantly larger in striatum (p < 0.0 1), thalamus (p < 0.01) and cerebellum (p < 0.005) of cocaine abusers than of controls (ANOVA diagnosis by condition (placebo versus lorazepam) interaction effect). The only brain region for which the absolute metabolic changes-induced by lorazepam in cocaine abusers were equivalent to those in controls was the orbitofrontal cortex. These results document an accentuated sensitivity to benzodiazepines in cocaine abusers which is compatible with disrupted GABAergic function in these patients.« less

Coupling of microbial nitrogen transformations and climate in sclerophyll forest soils from the Mediterranean Region of central Chile.

PubMed

Pérez, Cecilia A; Armesto, Juan J

2018-06-01

The Mediterranean region of central Chile is experiencing extensive "mega-droughts" with detrimental effects for the environment and economy of the region. In the northern hemisphere, nitrogen (N) limitation of Mediterranean ecosystems has been explained by the decoupling between N inputs and plant uptake during the dormant season. In central Chile, soils have often been considered N-rich in comparison to other Mediterranean ecosystems of the world, yet the impacts of expected intensification of seasonal drought remain unknown. In this work, we seek to disentangle patterns of microbial N transformations and their seasonal coupling with climate in the Chilean sclerophyll forest-type. We aim to assess how water limitation affects microbial N transformations, thus addressing the impact of ongoing regional climate trends on soil N status. We studied four stands of the sclerophyll forest-type in Chile. Field measurements in surface soils showed a 67% decline of free-living diazotrophic activity (DA) and 59% decrease of net N mineralization rates during the summer rainless and dormant season, accompanied by a stimulation of in-situ denitrification rates to values 70% higher than in wetter winter. Higher rates of both free-living DA and net N mineralization found during spring, provided evidence for strong coupling of these two processes during the growing season. Overall, the experimental addition of water in the field to litter samples almost doubled DA but had no effect on denitrification rates. We conclude that coupling of microbial mediated soil N transformations during the wetter growing season explains the N enrichment of sclerophyll forest soils. Expected increases in the length and intensity of the dry period, according to climate change models, reflected in the current mega-droughts may drastically reduce biological N fixation and net N mineralization, increasing at the same time denitrification rates, thereby potentially reducing long-term soil N capital. Copyright © 2017 Elsevier B.V. All rights reserved.

Sex-Specific Genetic Loci for Femoral Neck Bone Mass and Strength Identified in Inbred COP and DA Rats

PubMed Central

Alam, Imranul; Sun, Qiwei; Liu, Lixiang; Koller, Daniel L; Carr, Lucinda G; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

Introduction Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans identified chromosomal regions linked to hip size and bone mass. Animal models, particularly the inbred rat, serve as complementary approaches for studying the genetic influence on hip fragility. The purpose of this study is to identify sex-independent and sex-specific quantitative trait loci (QTLs) for femoral neck density, structure, and strength in inbred Copenhagen 2331 (COP) and Dark Agouti (DA) rats. Materials and Methods A total of 828 (405 males and 423 females) F2 progeny derived from the inbred COP and DA strains of rats were phenotyped for femoral neck volumetric BMD (vBMD), cross-sectional area, polar moment of inertia (Ip), neck width, ultimate force, and energy to break. A whole genome screen was performed using 93 microsatellite markers with an average intermarker distance of 20 cM. Recombination-based marker maps were generated using MAPMAKER/EXP from the COP × DA F2 data and compared with published Rat Genome Database (RGD) maps. These maps were used for genome-wide linkage analyses to detect sex-independent and sex-specific QTLs. Results Significant evidence of linkage (p < 0.01) for sex-independent QTLs were detected for (1) femoral neck vBMD on chromosomes (Chrs) 1, 6, 10, and 12, (2) femoral neck structure on Chrs 5, 7, 10, and 18, and (3) biomechanical properties on Chrs 1 and 4. Male-specific QTLs were discovered on Chrs 2, 9, and 18 for total vBMD, on Chr 17 for trabecular vBMD, on Chr 9 for total bone area, and on Chr 15 for ultimate force. A female-specific QTL was discovered on Chr 2 for ultimate force. The effect size of the individual QTL varied between 1% and 4%. Conclusions We detected evidence that sex-independent and sex-specific QTLs contribute to hip fragility in the inbred rat. Several QTLs regions identified in this study are homologous to human chromosomal regions previously linked to QTLs contributing to femoral neck and related phenotypes. PMID:18282130

Diversity and toxicity of the diatom Pseudo-nitzschia Peragallo in the Gulf of Maine, Northwestern Atlantic Ocean

PubMed Central

Fernandes, Luciano F.; Hubbard, Katherine A.; Richlen, Mindy L.; Smith, Juliette; Bates, Stephen S.; Ehrman, James; Léger, Claude; Mafra, Luiz L.; Kulis, David; Quilliam, Michael; Libera, Katie; McCauley, Linda; Anderson, Donald M.

2014-01-01

Multiple species in the toxic marine diatom genus Pseudo-nitzschia have been identified in the Northwestern Atlantic region encompassing the Gulf of Maine (GOM), including the Bay of Fundy (BOF). To gain further knowledge of the taxonomic composition and toxicity of species in this region, Pseudo-nitzschia isolates (n=146) were isolated from samples collected during research cruises that provided broad spatial coverage across the GOM and the southern New England shelf, herein referred to as the GOM region, during 2007-2008. Isolates, and cells in field material collected at 38 stations, were identified using electron microscopy (EM). Eight species (P. americana, P. fraudulenta, P. subpacifica, P. heimii, P. pungens, P. seriata, P. delicatissima and P. turgidula), and a novel form, Pseudo-nitzschia sp. GOM, were identified. Species identity was confirmed by sequencing the large subunit of the ribosomal rDNA (28S) and the internal transcribed spacer 2 (ITS2) for six species (36 isolates). Phylogenetic analyses (including neighbor joining, maximum parsimony, and maximum likelihood estimates and ITS2 secondary structure analysis) and morphometric data supported the placement of P. sp. GOM in a novel clade that includes morphologically and genetically similar isolates from Australia and Spain and is genetically most similar to P. pseudodelicatissima and P. cuspidata. Seven species (46 isolates) were grown in nutrient-replete batch culture and aliquots consisting of cells and growth medium were screened by Biosense ASP ELISA to measure total domoic acid (DA) produced (intracellular + extracellular); P. americana and P. heimii were excluded from all toxin analyses as they did not persist in culture long enough for testing. All 46 isolates screened produced DA in culture and total DA varied among species (e.g., 0.04 to 320 ng ml-1 for P. pungens and P. sp. GOM isolates, respectively) and among isolates of the same species (e.g., 0.24 – 320 ng ml-1 for P. sp. GOM). The 15 most toxic isolates corresponded to P. seriata, P. sp. GOM and P. pungens, and fg DA cell-1 was determined for whole cultures (cells and medium) using ELISA and liquid chromatography (LC) with fluorescence detection (FLD); for seven isolates, toxin levels were also estimated using LC - with mass spectrometry and ultraviolet absorbance detection. Pseudo-nitzschia seriata was the most toxic species (up to 3,500 fg cell-1) and was observed in the GOM region during all cruises (i.e., during the months of April, May, June and October). Pseudo-nitzschia sp. GOM, observed only during September and October 2007, was less toxic (19 – 380 fg cell-1) than P. seriata but more toxic than P. pungens var. pungens (0. 4 fg cell-1). Quantitation of DA indicated that concentrations measured by LC and ELISA were positively and significantly correlated; the lower detection limit of the ELISA permitted quantification of toxicity in isolates that were found to be nontoxic with LC methods. The confirmation of at least seven toxic species and the broad spatial and temporal distribution of toxic Pseudo-nitzschia spp. have significant implications for the regional management of nearshore and offshore shellfisheries resources. PMID:25143669

Electrochemical Investigation of DA and UA on Carboxylated Graphene Oxide/lanthanum Electrodes with Sundry Content of Ctab

NASA Astrophysics Data System (ADS)

Jiang, J.; Zhu, L.; Qian, W.; Chen, H.; Feng, C.; Han, S.; Lin, H.; Ye, F. Y.

Glassy carbon electrodes (GCE) were modified by carboxylated graphene oxide/lanthanum with various concentrations of hexadecyl trimethyl ammonium bromide (CTAB), and the treated electrodes, called CTAB/GO-COOLa/GCE, were prepared for the detection of uric acid (UA) and dopamine (DA) by using the differential pulse voltammetry (DPV) and the cyclic voltammetry (CV). The results show that the modified electrode’s electrocatalytic activity could be affected by several factors in the examination, they are the pH value of the system, the main content of CTAB, various concentrations and rates of scan. With a combination of carboxylated graphene oxide/lanthanum and CTAB, the resulted CTAB/GO-COOLa/GCE sensors showed preeminent selectivity and obvious catalytic property toward the electro-oxidation of UA and DA. In optimized conditions, the response of the CTAB/GO-COOLa/GCE electrode for DA was linear in the region of 0.03-500.0μM with detection limits of 0.036μM (S/N=3). Two linear response ranges for the determination UA were obtained from ranges of 1 to 200μM and 200 to 1300μM with a detection limit of 0.42μM (S/N=3). Moreover, the refined electrode was used in the inspection of DA and UA in real samples of serum and urine successfully, displaying its potential application of real samples involved in electroanalysis.

Ethanol drinking reduces extracellular dopamine levels in the posterior ventral tegmental area of nondependent alcohol-preferring rats.

PubMed

Engleman, Eric A; Keen, Elizabeth J; Tilford, Sydney S; Thielen, Richard J; Morzorati, Sandra L

2011-09-01

Moderate ethanol exposure produces neuroadaptive changes in the mesocorticolimbic dopamine (DA) system in nondependent rats and increases measures of DA neuronal activity in vitro and in vivo. Moreover, moderate ethanol drinking and moderate systemic exposure elevates extracellular DA levels in mesocorticolimbic projection regions. However, the neuroadaptive changes subsequent to moderate ethanol drinking on basal DA levels have not been investigated in the ventral tegmental area (VTA). In the present study, adult female alcohol-preferring (P) rats were divided into alcohol-naive, alcohol-drinking, and alcohol-deprived groups. The alcohol-drinking group had continuous access to water and ethanol (15%, vol/vol) for 8 weeks. The alcohol-deprived group had 6 weeks of access followed by 2 weeks of ethanol deprivation, 2 weeks of ethanol re-exposure, followed again by 2 weeks of deprivation. The deprived rats demonstrated a robust alcohol deprivation effect (ADE) on ethanol reinstatement. The alcohol-naïve group had continuous access to water only. In the last week of the drinking protocol, all rats were implanted with unilateral microdialysis probes aimed at the posterior VTA and no-net-flux microdialysis was conducted to quantify extracellular DA levels and DA clearance. Results yielded significantly lower basal extracellular DA concentrations in the posterior VTA of the alcohol-drinking group compared with the alcohol-naive and alcohol-deprived groups (3.8±0.3nM vs. 5.0±0.5nM [P<.02] and 4.8±0.4nM, [P<.05], respectively). Extraction fractions were significantly (P<.0002) different between the alcohol-drinking and alcohol-naive groups (72±2% vs. 46±4%, respectively) and not significantly different (P=.051) between alcohol-deprived and alcohol-naive groups (61±6% for the alcohol-deprived group). The data indicate that reductions in basal DA levels within the posterior VTA occur after moderate chronic ethanol intake in nondependent P rats. This reduction may result, in part, from increased DA uptake and may be important for the maintenance of ethanol drinking. These adaptations normalize with ethanol deprivation and may not contribute to the ADE. Copyright © 2011 Elsevier Inc. All rights reserved.

Recognition unit-free and self-cleaning photoelectrochemical sensing platform on TiO2 nanotube photonic crystals for sensitive and selective detection of dopamine release from mouse brain.

PubMed

Xin, Yanmei; Li, Zhenzhen; Wu, Wenlong; Fu, Baihe; Wu, Hongjun; Zhang, Zhonghai

2017-01-15

For implementing sensitive and selective detection of biological molecules, the biosensors are been designed more and more complicated. The exploration of detection platform in a simple way without loss their sensitivity and selectivity is always a big challenge. Herein, a prototype of recognition biomolecule unit-free photoelectrochemical (PEC) sensing platform with self-cleaning activity is proposed with TiO 2 nanotube photonic crystal (TiO 2 NTPCs) materials as photoelectrode, and dopamine (DA) molecule as both sensitizer and target analyte. The unique adsorption between DA and TiO 2 NTPCs induces the formation of charge transfer complex, which not only expends the optical absorption of TiO 2 into visible light region, thus significantly boosts the PEC performance under illumination of visible light, but also implements the selective detection of DA on TiO 2 photoelectrode. This simple but efficient PEC analysis platform presents a low detection limit of 0.15nm for detection of DA, which allows to realize the sensitive and selective determination of DA release from the mouse brain for its practical application after coupled with a microdialysis probe. The DA functionalized TiO 2 NTPCs PEC sensing platform opens up a new PEC detection model, without using extra-biomolecule auxiliary, just with target molecule naturally adsorbed on the electrode for sensitive and selective detection, and paves a new avenue for biosensors design with minimalism idea. Copyright © 2016 Elsevier B.V. All rights reserved.

Adulthood Exposure to Lipopolysaccharide Exacerbates the Neurotoxic and Inflammatory Effects of Rotenone in the Substantia Nigra

PubMed Central

Huang, Chun; Zhu, Li; Li, Huan; Shi, Fu-Guo; Wang, Guo-Qing; Wei, Yi-Zheng; Liu, Jie; Zhang, Feng

2017-01-01

Parkinson’s disease (PD) is the second most neurodegenerative disorder with a regional decrease of dopamine (DA) neurons in the substantia nigra (SN). Despite intense exploration, the etiology of PD progressive process remains unclear. This study was to investigate the synergistic effects of systemic inflammation of lipopolysaccharide (LPS) and neurotoxicity of rotenone (ROT) on exacerbating DA neuron lesion. Male SD adulthood rats received a single intraperitoneal injection of LPS. Seven months later, rats were subcutaneously given ROT five times a week for consecutive 4 weeks. Rat behavior changes were assessed via rotarod and open-field tests. Brain SN was immunostained to evaluate DA neuronal loss and microglia activation. Striatum DA and its metabolites levels were determined by high performance liquid chromatography (HPLC) coupled with electrochemistry. The protein levels of α-synuclein (α-Syn), inflammatory factors and mitogen-activated protein kinase (MAPK) pathway activation were detected by western blotting analysis. Results indicated that no significant difference between the control and LPS alone groups was shown. Compared with ROT alone group, LPS combined with ROT significantly reduced motor activity and induced SN DA neurons loss accompanied by the decreased contents of striatum DA and its metabolites. Furthermore, LPS together with ROT enhanced microglia activation and the increased expressions of α-Syn and inflammatory factors and also MAPK signaling pathway activation. However, LPS alone had no significant effects on the above parameters. These findings suggest that adulthood exposure to LPS exacerbates the neurotoxic and inflammatory effects of ROT in the SN. PMID:28533741

Global and disease-associated genetic variation in the human Fanconi anemia gene family.

PubMed

Rogers, Kai J; Fu, Wenqing; Akey, Joshua M; Monnat, Raymond J

2014-12-20

Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57,240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Presence of Lutzomyia longipalpis (Diptera: Psychodidae) in the Parque Estadual da Serra da Tiririca, State of Rio de Janeiro, Southeastern Brazil.

PubMed

Fuzari, Andressa Alencastre; Delmondes, Aline Ferreira Dos Santos; Barbosa, Vanessa De Araújo; Marra, Francisco de Assis; Brazil, Reginaldo Peçanha

2016-01-01

The sand fly, Lutzomyia longipalpis, is the main vector of Leishmania infantum in the Americas, primarily occurring in areas of apparent anthropomorphic modifications in several regions of Brazil. Sand flies were captured using light traps. Out of all captured species, Lu. longipalpis numbers had increased within the park. We report the occurrence of Lu. longipalpis in an area of Atlantic Forest, possibly representing the first sylvatic population of Lu. longipalpis in an area absent of peridomestic captures, but with the risk of L. infantum transmission in the areas of Niterói and Maricá.

[Science and nation: romanticism and natural history in the works of E. J. da Silva Maia].

PubMed

Kury, L

1998-01-01

The works of physician and naturalist Emílio Joaquim da Silva Maia (1808-59) can be viewed as a scientific project that discovers Brazil and its inhabitants. Maia's nationalism and his romantic view of nature formed the underpinnings of his scientific theories, especially his studies on zoological geography. He subordinated the issue of the biological specificity of different regions of the world to his era's debates on the construction of Brazil as an independent nation. In his interpretations of European natural history, Maia endeavored to understand Brazilian nature as a specific achievement of the Cosmos, in keeping with Alexander von Humboldt's approach.

Cocaine. Selective regional effects on central monoamines.

PubMed

Hadfield, M G

1995-01-01

Cocaine HCl (0, 10, or 50 mg/kg) was injected into adult male ICR mice ip. Thirty minutes later, the brains were removed, and nine regions were isolated: olfactory bulbs, olfactory tubercles, prefrontal cortex, septum, striatum, amygdala, hypothalamus, hippocampus, and thalamus. Using high-performance liquid chromatography, concentrations of norepinephrine, dopamine, serotonin, and their major metabolites and the metabolite/neurotransmitter ratios were determined as an indicator of utilization. Serotonergic systems responded most dramatically. 5HIAA/5-HT decreases were seen in all the brain regions, except the septum, hippocampus, and olfactory bulbs. In most instances, the alterations were dose-dependent. The most profound changes were seen in the amygdala, prefrontal cortex, hypothalamus, and thalamus. For noradrenergic systems, significant responses were seen only in the amygdala, prefrontal cortex, and hypothalamus, but then only at the lower dose. The dopaminergic responses were more complex and not always dose-dependent. The DOPAC/DA ratio was decreased only in the amygdala and striatum at the lower dose, and the olfactory tubercles at the higher dose. It was increased in the septum. The HVA/DA ratios were decreased in the amygdala, prefrontal cortex, and hypothalamus, but only at the lower dose (like MHPG/NE). The 3MT/DA ratio was decreased in the thalamus at the lower dose and in the olfactory tubercles at the higher dose, whereas it was increased in the prefrontal cortex at the lower dose. The HVA and DOPAC routes of degradation were both utilized only by the amygdala. Thus, cocaine produced its most comprehensive effects in this nucleus, as well as the greatest absolute percentage changes for all three of the monoamine systems studied.

[Epidemiologic aspects of the dialysis treatment in Grande São Paulo. Comissão Regional de Nefrologia da Secretaria da Saúde de São Paulo and Centro de Informática da Escola Paulista de Medicina].

PubMed

Sesso, R; Anção, M S; Madeira, S A

1994-01-01

Epidemiological data about the treatment of patients with end-stage renal disease in the Great Sao Paulo, Brazil, are presented. Patients on dialysis in the city of Sao Paulo and surroundings, distributed in 15 Regional Offices of Health (ERSAs), during 1991, were studied. Data were collected by the Secretary of Health of the State of Sao Paulo. There was an increase of 18.6% in the number of alive patients on dialysis from January 1 to December 31 (n = 2,425 to 2,875). Patients were treated in 40 dialysis centers, of which 24 were located in the ERSAs 1, 2 and 3. Depending on the ERSA, a percentage of patients varying from 37% to 88% did not live in the same region where they received treatment. At the end of the year, 79% of the patients were on hemodialysis, 15% on continuous ambulatory peritoneal dialysis and 6% on intermittent peritoneal dialysis. The diagnoses more frequently reported of primary disease were non-determined, glomerulonephritis, hypertension and diabetes (36%, 27%, 17% and 8%, respectively). New cases (1,483) initiated dialysis during the year, corresponding to an incidence rate of 83 patients per million population (pmp). The prevalence of patients on dialysis was 148 pmp. The annual fatality rate was 17.2% (range in the ERSAs: 12.0-3.5). The actuarial one year survival for the patients who started treatment in 1991 was 80.2%. 246 patients received transplantation, corresponding to 14 patients pmp. Dialysis treatment provided in the Great Sao Paulo is satisfactory.(ABSTRACT TRUNCATED AT 250 WORDS)

Spinocerebellar ataxia 36 (SCA36): «Costa da Morte ataxia».

PubMed

Arias, M; García-Murias, M; Sobrido, M J

To describe the history of the discovery of SCA36 and review knowledge of this entity, which is currently the most prevalent hereditary ataxia in Galicia (Spain) owing to a founder effect. SCA36 is an autosomal dominant hereditary ataxia with late onset and slow progression. It presents with cerebellar ataxia, sensorineural hearing loss, and discrete motor neuron impairment (tongue atrophy with denervation, discrete pyramidal signs). SCA36 was first described in Japan (Asida River ataxia) and in Galicia(Costa da Morte ataxia). The condition is caused by a genetic mutation (intronic hexanucleotide repeat expansion) in the NOP56 gene on the short arm of chromosome 20 (20p13). Magnetic resonance image study initially shows cerebellar vermian atrophy that subsequently extends to the rest of the cerebellum and finally to the pontomedullary region of the brainstem without producing white matter lesions. Peripheral nerve conduction velocities are normal, and sensorimotor evoked potential studies show delayed conduction of stimuli to lower limbs. In patients with hearing loss, audiometric studies show a drop of >40dB in frequencies exceeding 2,500Hz. Auditory evoked potential studies may also show lack of waves I and II. Costa da Morte ataxia or SCA36 is the most prevalent SCA in the Spanish region of Galicia. Given the region's history of high rates of emigration, new cases may be diagnosed in numerous countries, especially in Latin America. Genetic studies are now available to patients and asymptomatic carriers. Since many people are at risk for this disease, we will continue our investigations aimed at elucidating the underlying pathogenic molecular mechanisms and discovering effective treatment. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Advanced control of liquid water region in diffusion media of polymer electrolyte fuel cells through a dimensionless number

NASA Astrophysics Data System (ADS)

Wang, Yun; Chen, Ken S.

2016-05-01

In the present work, a three-dimension (3-D) model of polymer electrolyte fuel cells (PEFCs) is employed to investigate the complex, non-isothermal, two-phase flow in the gas diffusion layer (GDL). Phase change in gas flow channels is explained, and a simplified approach accounting for phase change is incorporated into the fuel cell model. It is found that the liquid water contours in the GDL are similar along flow channels when the channels are subject to two-phase flow. Analysis is performed on a dimensionless parameter Da0 introduced in our previous paper [Y. Wang and K. S. Chen, Chemical Engineering Science 66 (2011) 3557-3567] and the parameter is further evaluated in a realistic fuel cell. We found that the GDL's liquid water (or liquid-free) region is determined by the Da0 number which lumps several parameters, including the thermal conductivity and operating temperature. By adjusting these factors, a liquid-free GDL zone can be created even though the channel stream is two-phase flow. Such a liquid-free zone is adjacent to the two-phase region, benefiting local water management, namely avoiding both severe flooding and dryness.

Impact of experimental hypothyroidism on monoamines level in discrete brain regions and other peripheral tissues of young and adult male rats.

PubMed

Hassan, Wafaa A; Aly, Mona S; Rahman, Taghride Abdel; Shahat, Asmaa S

2013-06-01

The levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats were measured following experimentally induced hypothyroidism. Hypothyroidism induced by daily oral administration of propylthiouracil (PTU, 5mg/kg body wt) caused a significant reduction in DA levels in most of the tissues examined of both young and adult rats after 21 and 28 days, in NE levels after all the time intervals studied in young rats, and after 21 and 28 days in adult rats. 5-HT exhibited a significant reduction in the selected brain regions and blood plasma after 21 and 28 days and in cardiac muscle after all the time intervals in the two age groups of animals. It may be suggested that the changes in monoamine levels induced by hypothyroidism may be due to disturbance in the synthesis and release of these amines through the neurons impairment or may be due to an alteration pattern of their synthesizing and/or degradative enzymes. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Advanced control of liquid water region in diffusion media of polymer electrolyte fuel cells through a dimensionless number

DOE PAGES

Wang, Yun; Chen, Ken S.

2016-03-21

In the present study, a three-dimension (3-D) model of polymer electrolyte fuel cells (PEFCs) is employed to investigate the complex, non-isothermal, two-phase flow in the gas diffusion layer (GDL). Phase change in gas flow channels is explained, and a simplified approach accounting for phase change is incorporated into the fuel cell model. It is found that the liquid water contours in the GDL are similar along flow channels when the channels are subject to two-phase flow. Here, analysis is performed on a dimensionless parameter Da 0 introduced in our previous paper and the parameter is further evaluated in a realisticmore » fuel cell. We found that the GDL's liquid water (or liquid-free) region is determined by the Da 0 number which lumps several parameters, including the thermal conductivity and operating temperature. By adjusting these factors, a liquid-free GDL zone can be created even though the channel stream is two-phase flow. Such a liquid-free zone is adjacent to the two-phase region, benefiting local water management, namely avoiding both severe flooding and dryness.« less

Microbiological characterization of Serra da Estrela cheese throughout its Appellation d'Origine Protégée region.

PubMed

Tavaria, F K; Malcata, F X

1998-05-01

The purpose of this study was to assess the typical microbiological quality of the most famous Portuguese traditional cheese, Serra da Estrela, and to assess its ripening time and geographical dependence. Ninety-six experimental cheeses manufactured from sixteen batches of milk on eight dairy farms scattered over the Appellation d' Origine Protégée (AOP) region were qualitatively and quantitatively evaluated microbiologically at various ripening times. Viable counts were performed after inoculation on appropriate selective media for aerobic mesophiles and proteolytic and lipolytic microflora, as well as lactococci, lactobacilli, species of Enterobacteriaceae, lactic streptococci, staphylococci, and yeasts. Members of the Enterobacteriaceae and lactic acid bacteria were the predominant microbial groups on all dairy farms throughout maturation; the latter are probably the microbial group responsible for most proteolytic and lipolytic breakdown in Serra da Estrela cheese. The microbial groups whose numbers were most affected by dairy-to-dairy variation were species of Enterobacteriaceae staphylococci, and enterococci, which are the most critical groups in terms of health hazards. It is therefore suggested that tighter control should be implemented at the level of choice of raw materials, in milk-handling practices, and in general throughout the manufacturing process in attempts to standardize production and consistently reduce microbiological risks (even though the distinctiveness of a few final organoleptic characteristics may somehow be reduced.

Elevation of D4 dopamine receptor mRNA in postmortem schizophrenic brain.

PubMed

Stefanis, N C; Bresnick, J N; Kerwin, R W; Schofield, W N; McAllister, G

1998-01-01

The D4 dopamine (DA) receptor has been proposed to be a target for the development of a novel antipsychotic drug based on its pharmacological and distribution profile. There is much interest in whether D4 DA receptor levels are altered in schizophrenia, but the lack of an available receptor subtype-specific radioligand made this difficult to quantitate. In this study, we examined whether D4 mRNA levels are altered in different brain regions of schizophrenics compared to controls. Ribonuclease protection assays were carried out on total RNA samples isolated postmortem from frontal cortex and caudate brain regions of schizophrenics and matched controls. 32P-labelled RNA probes to the D4 DA receptor and to the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (G3PDH), were hybridised with the RNA samples, digested with ribonucleases to remove unhybridised probe, and separated on 6% sequencing gels. Densitometer analysis on the subsequent autoradiogams was used to calculate the relative optical density of D4 mRNA compared to G3PDH mRNA. Statistical analysis of the data revealed a 3-fold higher level (P<0.011) of D4 mRNA in the frontal cortex of schizophrenics compared to controls. No increase was seen in caudate. D4 receptors could play a role in mediating dopaminergic activity in frontal cortex, an activity which may be malfunctioning in schizophrenia.

Relationship between genetic polymorphisms in the DRD5 gene and paranoid schizophrenia in northern Han Chinese.

PubMed

Zhao, Y; Ding, M; Pang, H; Xu, X M; Wang, B J

2014-03-12

Dopamine (DA) has been implicated in the pathophysiol-ogy of several psychiatric disorders, including schizophrenia. Thus, genes related to the dopaminergic (DAergic) system are good candidate genes for schizophrenia. One of receptors of the DA receptor system is dopa-mine receptor 5 (DRD5). Single nucleotide polymorphisms (SNPs) in the regulatory regions of DRD5 gene may affect gene expression, influence biosynthesis of DA and underlie various neuropsychiatric disorders re-lated to DA dysfunction. The present study explored the association of SNPs within the DRD5 gene with paranoid schizophrenia in Han Chinese. A total of 176 patients with schizophrenia and 206 healthy controls were genotyped for four DRD5 SNPs (rs77434921, rs2076907, rs6283, and rs1800762). Significant group differences were observed in the allele and genotype frequencies of rs77434921 and rs1800762 and in the frequen-cies of GC haplotypes corresponding to rs77434921-rs1800762. Our find-ings suggest that common genetic variations of DRD5 are likely to con-tribute to genetic susceptibility to paranoid schizophrenia in Han Chinese. Further studies in larger samples are needed to replicate this association.

Transoral robotic surgery of craniocervical junction and atlantoaxial spine: a cadaveric study.

PubMed

Lee, John Y K; O'Malley, Bert W; Newman, Jason G; Weinstein, Gregory S; Lega, Bradley; Diaz, Jason; Grady, M Sean

2010-01-01

The goal of this study was to determine the potential role and current limitations of the da Vinci surgical robot in transoral decompression of craniocervical junction (CCJ). The da Vinci Surgical System was used in 2 cadaver heads with neck and clavicles intact. Both neurosurgeons and otolaryngologists familiar with the open microscopic procedure, as well as the transoral robotic surgical procedure, undertook dissection and decompression of the CCJ. The robotic system provided superb illumination and 3D depth perception even several centimeters deep to the posterior oropharyngeal mucosa. The 30 degrees endoscope improved cephalad visualization, eliminating the need to split the soft palate for exposure of the lower clivus. The "intuitive" nature of the da Vinci surgical robot arms provided an advantage in allowing the ability to suture the dura mater in a deep, dark corridor. Because visualization was excellent, tremor-free closure was possible. The authors' findings suggest that transoral robotic surgery, with the da Vinci robot system, holds great potential for decompression of the CCJ as well as resection of both extra- and intradural tumors of this region. Further instrument development is necessary and continued investigation is warranted.

A murC gene in Porphyromonas gingivalis 381.

PubMed

Ansai, T; Yamashita, Y; Awano, S; Shibata, Y; Wachi, M; Nagai, K; Takehara, T

1995-09-01

The gene encoding a 51 kDa polypeptide of Porphyromonas gingivalis 381 was isolated by immunoblotting using an antiserum raised against P. gingivalis alkaline phosphatase. DNA sequence analysis of a 2.5 kb DNA fragment containing a gene encoding the 51 kDa protein revealed one complete and two incomplete ORFs. Database searches using the FASTA program revealed significant homology between the P. gingivalis 51 kDa protein and the MurC protein of Escherichia coli, which functions in peptidoglycan synthesis. The cloned 51 kDa protein encoded a functional product that complemented an E. coli murC mutant. Moreover, the ORF just upstream of murC coded for a protein that was 31% homologous with the E. coli MurG protein. The ORF just downstream of murC coded for a protein that was 17% homologous with the Streptococcus pneumoniae penicillin-binding protein 2B (PBP2B), which functions in peptidoglycan synthesis and is responsible for antibiotic resistance. These results suggest that P. gingivalis contains a homologue of the E. coli peptidoglycan synthesis gene murC and indicate the possibility of a cluster of genes responsible for cell division and cell growth, as in the E. coli mra region.

Timing of Moderate Level Prenatal Alcohol Exposure Influences Gene Expression of Sensory Processing Behavior in Rhesus Monkeys

PubMed Central

Schneider, Mary L.; Moore, Colleen F.; Larson, Julie A.; Barr, Christina S.; DeJesus, Onofre T.; Roberts, Andrew D.

2009-01-01

Sensory processing disorder, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and striatal dopamine (DA) function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s) rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l) allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. Moreover, prenatal timing of alcohol exposure altered the relationship between sensory scores and DA D2R availability. In early-exposed monkeys, a positive relationship was shown between sensory scores and DA D2R availability, with low or blunted DA function associated with under-responsive sensory function. The opposite pattern was found for the middle-to-late gestation alcohol-exposed group. These findings raise questions about how the timing of prenatal perturbation and genotype contributes to effects on neural processing and possibly alters neural connections. PMID:19936317

Induction of HSP70 promotes DeltaF508 CFTR trafficking.

PubMed

Choo-Kang, L R; Zeitlin, P L

2001-07-01

The DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) is a temperature-sensitive trafficking mutant that is detected as an immature 160-kDa form (band B) in gel electrophoresis. The goal of this study was to test the hypothesis that HSP70, a member of the 70-kDa heat shock protein family, promotes DeltaF508 CFTR processing to the mature 180-kDa form (band C). Both pharmacological and genetic techniques were used to induce HSP70. IB3-1 cells were treated with sodium 4-phenylbutyrate (4PBA) to promote maturation of DeltaF508 CFTR to band C. A dose-dependent increase in band C and total cellular HSP70 was observed. Under these conditions, HSP70-CFTR complexes were increased and 70-kDa heat shock cognate protein-CFTR complexes were decreased. Increased DeltaF508 CFTR maturation was also seen after transfection with an HSP70 expression plasmid and exposure to glutamine, an inducer of HSP70. With immunofluorescence techniques, the increased appearance of CFTR band C correlated with CFTR distribution beyond the perinuclear regions. These data suggest that induction of HSP70 promotes DeltaF508 CFTR maturation and trafficking.

Leptin Increases Striatal Dopamine D2 Receptor Binding in Leptin-Deficient Obese (ob/ob) Mice

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

Pfaffly, J.; Michaelides, M.; Wang, G-J.

2010-06-01

Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R-binding differences contribute to the phenotypic behaviors of leptin-deficient ob/ob mice, and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Basal striatal D2Rmore » binding (measured with autoradiography [{sup 3}H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice, leptin decreased striatal D2R binding, whereas, in ob/ob mice, leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2R expression in striatum and that these effects are genotype/phenotype dependent.« less

Purification and cDNA cloning of ferritin from the hepatopancreas of the freshwater crayfish Pacifastacus leniusculus.

PubMed

Huang, T S; Law, J H; Söderhäll, K

1996-03-01

Ferritin was purified from the hepatopancreas of the freshwater crayfish Pacifastacus leniusculus after injection of iron. It has the same size as horse spleen ferritin (440 kDa) and migrates as two bands, 19 kDa and 20 kDa, respectively, in SDS/PAGE under reducing conditions. Crayfish ferritin (20 kDa) was cloned from a hepatopancreas cDNA library. The deduced amino acid sequence of the crayfish ferritin shows a closer relationship to vertebrate ferritin heavy chains than to insect ferritin and contains the conserved H-specific residues for the ferroxidase centre found in vertebrate ferritin heavy chain. An IRE(iron-responsive element)-like sequence with a predicted stem-loop structure was present in the 5' untranslated region of the crayfish ferritin mRNA. Crayfish ferritin does not share the atypical properties of insect ferritins, such as high molecular mass of intact protein, abundance in hemolymph, and export into vacuoles. We suggest that there are two different types of ferritins distributed in different species: insect-type or secretory ferritins which are predominant in the snail oocyte and insects, and vertebrate (crustacean)-type or cytosolic ferritins which are predominant in vertebrates and crustacea.

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

Impaired inference in a case of developmental amnesia.

PubMed

D'Angelo, Maria C; Rosenbaum, R Shayna; Ryan, Jennifer D

2016-10-01

Amnesia is associated with impairments in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm, we previously showed that age-related impairments in inference were mitigated when judgments could be predicated on known pairwise relations, however, such advantages were not observed in the adult-onset amnesic case D.A. Here, we replicate and extend this finding in a developmental amnesic case (N.C.), who also shows impaired relational learning and transitive expression. Unlike D.A., N.C.'s damage affected the extended hippocampal system and diencephalic structures, and does not extend to neocortical areas that are affected in D.A. Critically, despite their differences in etiology and affected structures, N.C. and D.A. perform similarly on the task. N.C. showed intact pairwise knowledge, suggesting that he is able to use existing semantic information, but this semantic knowledge was insufficient to support transitive expression. The present results suggest a critical role for regions connected to the hippocampus and/or medial prefrontal cortex in inference beyond learning of pairwise relations. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. © 2016 The Authors. Wiley Periodicals, Inc.

Soil Moisture Data Assimilation in the NASA Land Information System for Local Modeling Applications and Improved Situational Awareness

NASA Technical Reports Server (NTRS)

Case, Jonathan L.; Blakenship, Clay B.; Zavodsky, Bradley T.

2014-01-01

As part of the NASA Soil Moisture Active Passive (SMAP) Early Adopter (EA) program, the NASA Shortterm Prediction Research and Transition (SPoRT) Center has implemented a data assimilation (DA) routine into the NASA Land Information System (LIS) for soil moisture retrievals from the European Space Agency's Soil Moisture Ocean Salinity (SMOS) satellite. The SMAP EA program promotes application-driven research to provide a fundamental understanding of how SMAP data products will be used to improve decision-making at operational agencies. SPoRT has partnered with select NOAA/NWS Weather Forecast Offices (WFOs) that use output from a real-time regional configuration of LIS, without soil moisture DA, to initialize local numerical weather prediction (NWP) models and enhance situational awareness. Improvements to local NWP with the current LIS have been demonstrated; however, a better representation of the land surface through assimilation of SMOS (and eventually SMAP) retrievals is expected to lead to further model improvement, particularly during warm-season months. SPoRT will collaborate with select WFOs to assess the impact of soil moisture DA on operational forecast situations. Assimilation of the legacy SMOS instrument data provides an opportunity to develop expertise in preparation for using SMAP data products shortly after the scheduled launch on 5 November 2014. SMOS contains a passive L-band radiometer that is used to retrieve surface soil moisture at 35-km resolution with an accuracy of 0.04 cu cm cm (exp -3). SMAP will feature a comparable passive L-band instrument in conjunction with a 3-km resolution active radar component of slightly degraded accuracy. A combined radar-radiometer product will offer unprecedented global coverage of soil moisture at high spatial resolution (9 km) for hydrometeorological applications, balancing the resolution and accuracy of the active and passive instruments, respectively. The LIS software framework manages land surface model (LSM) simulations and includes an Ensemble Kalman Filter for conducting land surface DA. SPoRT has added a module to read, quality-control and bias-correct swaths of Level II SMOS soil moisture retrievals prior to assimilation within LIS. The impact of SMOS DA is being tested using the Noah LSM. Experiments are being conducted to examine the impacts of SMOS soil moisture DA on the resulting LISNoah fields and subsequent NWP simulations using the Weather Research and Forecasting (WRF) model initialized with LIS-Noah output. LIS-Noah soil moisture will be validated against in situ observations from Texas A&M's North American Soil Moisture Database to reveal the impact and possible improvement in soil moisture trends through DA. WRF model NWP case studies will test the impacts of DA on the simulated near-surface and boundary-layer environments, and precipitation during both quiescent and disturbed weather scenarios. Emphasis will be placed on cases with large analysis increments, especially due to contributions from regional irrigation patterns that are not represented by precipitation input in the baseline LIS-Noah run. This poster presentation will describe the soil moisture DA methodology and highlight LIS-Noah and WRF simulation results with and without assimilation.

Effects of intrinsic aerobic capacity and ovariectomy on voluntary wheel running and nucleus accumbens dopamine receptor gene expression

PubMed Central

Park, Young-Min; Kanaley, Jill A.; Padilla, Jaume; Zidon, Terese; Welly, Rebecca J.; Will, Matthew J.; Britton, Steven L.; Koch, Lauren G.; Ruegsegger, Gregory N.; Booth, Frank W.; Thyfault, John P.; Vieira-Potter, Victoria J.

2016-01-01

Rats selectively bred for high (HCR) and low (LCR) aerobic capacity show a stark divergence in wheel running behavior, which may be associated with dopamine (DA) system in the brain. HCR possess greater motivation for voluntary running along with greater brain DA activity compared to LCR. We recently demonstrated that HCR are not immune to ovariectomy (OVX)-associated reductions in spontaneous cage (i.e. locomotor) activity. Whether HCR and LCR rats differ in their OVX-mediated voluntary wheel running response is unknown. PURPOSE To determine whether HCR are protected from OVX-associated reduction in voluntary wheel running. METHODS Forty female HCR and LCR rats (age ~27 weeks) had either SHM or OVX operations, and given access to a running wheel for 11 weeks. Weekly wheel running distance was monitored throughout the intervention. Nucleus accumbens (NAc) was assessed for mRNA expression of DA receptors at sacrifice. RESULTS Compared to LCR, HCR ran greater distance and had greater ratio of excitatory/inhibitory DA mRNA expression (both line main effects, P<0.05). Wheel running distance was significantly, positively correlated with the ratio of excitatory/inhibitory DA mRNA expression across animals. In both lines, OVX reduced wheel running (P<0.05). Unexpectedly, although HCR started with significantly greater voluntary wheel running, they had greater OVX-induced reduction in wheel running than LCR such that no differences were found 11 weeks after OVX between HCROVX and LCROVX (interaction, P<0.05). This significant reduction in wheel running in HCR was associated with an OVX-mediated reduction in the ratio of excitatory/inhibitory DA mRNA expression. CONCLUSION DA system in the NAc region may play a significant role in motivation to run in female rats. Compared to LCR, HCR rats run significantly more, which associates with greater ratio of excitatory/inhibitory DA mRNA expression. However, despite greater inherent motivation to run and an associated brain DA mRNA expression profile, these HCR rats are not protected against OVX-induced reduction in wheel running. The impairment in wheel running in HCR rats may be partially explained by their reduced ratio of excitatory/inhibitory DA receptor mRNA expression. PMID:27297873

A murC gene from coryneform bacteria.

PubMed

Wachi, M; Wijayarathna, C D; Teraoka, H; Nagai, K

1999-02-01

The upstream flanking region of the ftsQ and ftsZ genes of Brevibacterium flavum MJ233, which belongs to the coryneform bacteria, was amplified by the inverse polymerase chain reaction method and cloned in Escherichia coli. Complementation analysis of E. coli mutant with a defective cell-wall synthesis mechanism with the cloned fragment and its DNA sequencing indicated the presence of the murC gene, encoding UDP-N-acetylmuramate:L-alanine ligase involved in peptidoglycan synthesis, just upstream from the ftsQ gene. The B. flavum murC gene could encode a protein of 486 amino acid residues with a calculated molecular mass of 51 198 Da. A 50-kDa protein was synthesized by the B. flavum murC gene in an in vitro transcription/translation system using E. coli S30 lysate. These results indicate that the genes responsible for cell-wall synthesis and cell division are located as a cluster in B. flavum similar to the E. coli mra region.

Molecular cloning and sequence analysis of the gene coding for the 57kDa soluble antigen of the salmonid fish pathogen Renibacterium salmoninarum

USGS Publications Warehouse

Chien, Maw-Sheng; Gilbert , Teresa L.; Huang, Chienjin; Landolt, Marsha L.; O'Hara, Patrick J.; Winton, James R.

1992-01-01

The complete sequence coding for the 57-kDa major soluble antigen of the salmonid fish pathogen, Renibacterium salmoninarum, was determined. The gene contained an opening reading frame of 1671 nucleotides coding for a protein of 557 amino acids with a calculated Mr value of 57190. The first 26 amino acids constituted a signal peptide. The deduced sequence for amino acid residues 27–61 was in agreement with the 35 N-terminal amino acid residues determined by microsequencing, suggesting the protein in synthesized as a 557-amino acid precursor and processed to produce a mature protein of Mr 54505. Two regions of the protein contained imperfect direct repeats. The first region contained two copies of an 81-residue repeat, the second contained five copies of an unrelated 25-residue repeat. Also, a perfect inverted repeat (including three in-frame UAA stop codons) was observed at the carboxyl-terminus of the gene.

Influence of neonatal vitamin A or vitamin D treatment on the concentration of biogenic amines and their metabolites in the adult rat brain.

PubMed

Tekes, K; Gyenge, M; Folyovich, A; Csaba, G

2009-04-01

Newborn male rats were treated with a single dose of 3 mg vitamin A (retinol) or 0.05 mg vita-min D (cholecalciferol), and three months later five brain regions (frontopolar cortex, hypothalamus, hippocampus, striatum, and brainstem) were studied for tissue levels of dopamine (DA), serotonin (5HT), and metabolites such as homovanillic acid (HVA), as well as 5-hydroxyindole-3-acetic acid (5HIAA). Vitamin A treatment as hormonal imprinting significantly decreased 5HIAA levels in each brain region. Vitamin D imprinting significantly elevated DA only in the brainstem and HVA levels in striatum and hypothalamus. Present and earlier brain-imprinting results (with brain-produced substances), show that the profound and life-long effect of neonatal hormonal imprinting on neurotransmitter production of the adult brain seems to be well established. As prophylactic treatment with these vitamins is frequent in the perinatal period, the imprinting effect of vitamin A and vitamin D must be taken into consideration.

Vegetation stability in the Southeastern Brazilian coastal area from 5500 to 1400 14C yr BP deduced from charcoal analysis.

PubMed

Scheel-Ybert

2000-06-01

Charcoal analysis of six shell mounds showed that no major changes of the mainland vegetation ecosystem have taken place along the southeastern Brazilian coast (22 degrees 53'-22 degrees 57'S, 42 degrees 03'-42 degrees 33'W) from 5500 to 1400 14C yr BP. These shell mounds have been occupied by sedentary fisher-gatherer-hunters. Charcoal fragments retrieved from vertical profiles in the archaeological sites were examined; taxonomic determinations were based on a reference collection of charred woods and a program for computer-aided identification. Charcoal assemblages of all the studied sites present taxa from various restinga vegetation types, mangroves, xeromorphic coastal forest, and inland Atlantic Forest. The restinga ecosystem, characteristic of the Brazilian coast, is associated with sandy beach ridges; the restinga forest was much more abundant during the studied period than nowadays. The charcoal assemblages represent mainly the local vegetation; a regional reconstruction depends on the study of numerous sites. In the Cabo Frio region, open restinga taxa are more abundant in the Sambaqui do Forte, while forest elements are more important in the Sambaquis Salinas Peroano and Boca da Barra. The sites studied in the Arraial do Cabo (Sambaqui da Ponta da Cabeça) and in the Saquarema regions (Sambaquis da Pontinha and da Beirada) show that open restinga formations were locally predominant. A comparison of multivariate analysis applied to both charcoal assemblages and to phytosociological data of the extant vegetation showed a good correspondence between the charcoal spectra and the present vegetation. The high taxonomic diversity of archaeological charcoal samples and numerous fragments showing traces of decay before charring suggests that aleatory gathering of dead wood constituted the main source of firewood for fisher-gatherer-hunters populations. Condalia sp. was probably selected for cultural reasons.The only significant fluctuations on the charcoal spectra relate to the mangrove vegetation. Two relatively humid episodes (recorded from ca. 5500 to 4900/4500 and from ca. 2300 to 2000 14C yr BP), intercalated by two episodes of increased dryness with increased lagoon salinity (from ca. 4900/4500 to 2300 and from ca. 2000 to 1400 14C yr BP) were recorded in the Cabo Frio region. The changes in mangrove vegetation cannot be attributed to sea-level variations, for the three regressive and the two transgressive episodes identified for the Brazilian coast during this period are not in phase with the development of mangroves. The stability of the mainland vegetation ecosystem is probably due to the edaphic character of the coastal environments, which makes coastal formations much more resistant to climatic variations and less sensitive to climatic change. We propose that this environmental stability was a decisive factor in the maintenance of the fisher-gatherer-hunter sociocultural system.

[A comparative study of Da Vinci robot system with video-assisted thoracoscopy in the surgical treatment of mediastinal lesions].

PubMed

Ding, Renquan; Tong, Xiangdong; Xu, Shiguang; Zhang, Dakun; Gao, Xin; Teng, Hong; Qu, Jiaqi; Wang, Shumin

2014-07-20

In recent years, Da Vinci robot system applied in the treatment of intrathoracic surgery mediastinal diseases become more mature. The aim of this study is to summarize the clinical data about mediastinal lesions of General Hospital of Shenyang Military Region in the past 4 years, then to analyze the treatment effect and promising applications of da Vinci robot system in the surgical treatment of mediastinal lesions. 203 cases of mediastinal lesions were collected from General Hospital of Shenyang Military Region between 2010 and 2013. These patients were divided into two groups da Vinci and video-assisted thoracoscopic surgery (VATS) according to the selection of the treatments. The time in surgery, intraoperative blood loss, postoperative drainage amount within three days after surgery, the period of bearing drainage tubes, hospital stays and hospitalization expense were then compared. All patients were successfully operated, the postoperative recovery is good and there is no perioperative death. The different of the time in surgery between two groups is Robots group 82 (20-320) min and thoracoscopic group 89 (35-360) min (P>0.05). The intraoperative blood loss between two groups is robot group 10 (1-100) mL and thoracoscopic group 50 (3-1,500) mL. The postoperative drainage amount within three days after surgery between two groups is robot group 215 (0-2,220) mL and thoracoscopic group 350 (50-1,810) mL. The period of bearing drainage tubes after surgery between two groups is robot group 3 (0-10) d and thoracoscopic group: 5 (1-18) d. The difference of hospital stays between two groups is robot group 7 (2-15) d and thoracoscopic group 9 (2-50) d. The hospitalization expense between two groups is robot group (18,983.6±4,461.2) RMB and thoracoscopic group (9,351.9±2,076.3) RMB (All P<0.001). The da Vinci robot system is safe and efficient in the treatment of mediastinal lesions compared with video-assisted thoracoscopic approach, even though its expense is higher.

EXPRESSION AND CHARACTERIZATION OF FULL-LENGTH HUMAN HEME OXYGENASE-1: PRESENCE OF INTACT MEMBRANE-BINDING REGION LEADS TO INCREASED BINDING AFFINITY FOR NADPH-CYTOCHROME P450 REDUCTASE

PubMed Central

Huber, Warren J.; Backes, Wayne L.

2009-01-01

Heme oxygenase (HO) is the chief regulatory enzyme in the oxidative degradation of heme to biliverdin. In the process of heme degradation, this NADPH and cytochrome P450 reductase (CPR)-dependent oxidation of heme also releases free iron and carbon monoxide. Much of the recent research involving heme oxygenase is done using a 30-kDa soluble form of the enzyme, which lacks the membrane binding region (C-terminal 23 amino acids). The goal of this study was to express and purify a full-length human HO-1 (hHO-1) protein; however, due to the lability of the full-length form, a rapid purification procedure was required. This was accomplished by use of a GST-tagged hHO-1 construct. Although the procedure permitted the generation of a full-length HO-1, this form was contaminated with a 30-kDa degradation product that could not be eliminated. Therefore, we attempted to remove a putative secondary thrombin cleavage site by a conservative mutation of amino acid 254, which replaces lysine with arginine. This mutation allowed the expression and purification of a full length hHO-1 protein. Unlike wild-type HO-1, the K254R mutant could be purified to a single 32-kDa protein capable of degrading heme at the same rate as the wild-type enzyme. The K254R full-length form had a specific activity of ~200–225 nmol bilirubin hr−1nmol−1 HO-1 as compared to ~140–150 nmol bilirubin hr−1nmol−1 for the WT form, which contains the 30-kDa contaminant. This is a 2–3-fold increase from the previously reported soluble 30-kDa HO-1, suggesting that the C-terminal 23 amino acids are essential for maximal catalytic activity. Because the membrane spanning domain is present, the full-length hHO-1 has the potential to incorporate into phospholipid membranes, which can be reconstituted at known concentrations, in combination with other ER-resident enzymes. PMID:17915953

Expression and characterization of full-length human heme oxygenase-1: the presence of intact membrane-binding region leads to increased binding affinity for NADPH cytochrome P450 reductase.

PubMed

Huber, Warren J; Backes, Wayne L

2007-10-30

Heme oxygenase-1 (HO-1) is the chief regulatory enzyme in the oxidative degradation of heme to biliverdin. In the process of heme degradation, HO-1 receives the electrons necessary for catalysis from the flavoprotein NADPH cytochrome P450 reductase (CPR), releasing free iron and carbon monoxide. Much of the recent research involving heme oxygenase has been done using a 30 kDa soluble form of the enzyme, which lacks the membrane binding region (C-terminal 23 amino acids). The goal of this study was to express and purify a full-length human HO-1 (hHO-1) protein; however, due to the lability of the full-length form, a rapid purification procedure was required. This was accomplished by use of a glutathione-s-transferase (GST)-tagged hHO-1 construct. Although the procedure permitted the generation of a full-length HO-1, this form was contaminated with a 30 kDa degradation product that could not be eliminated. Therefore, attempts were made to remove a putative secondary thrombin cleavage site by a conservative mutation of amino acid 254, which replaces arginine with lysine. This mutation allowed the expression and purification of a full-length hHO-1 protein. Unlike wild type (WT) HO-1, the R254K mutant could be purified to a single 32 kDa protein capable of degrading heme at the same rate as the WT enzyme. The R254K full-length form had a specific activity of approximately 200-225 nmol of bilirubin h-1 nmol-1 HO-1 as compared to approximately 140-150 nmol of bilirubin h-1 nmol-1 for the WT form, which contains the 30 kDa contaminant. This is a 2-3-fold increase from the previously reported soluble 30 kDa HO-1, suggesting that the C-terminal 23 amino acids are essential for maximal catalytic activity. Because the membrane-spanning domain is present, the full-length hHO-1 has the potential to incorporate into phospholipid membranes, which can be reconstituted at known concentrations, in combination with other endoplasmic reticulum resident enzymes.

Metals in some lagoons of Mexico.

PubMed Central

Vazquez, F G; Sharma, V K; Alexander, V H; Frausto, C A

1995-01-01

The concentrations of metals, Cd, Cu, Fe, Mn, Ni, Pb, and Zn were determined in some lagoons to establish the level of metal pollution. The lagoons studied were Alvarado lagoon, Veracruz; San Andres lagoon, Tamaulipas; and Terminos lagoon, Campeche. The concentrations were determined in water, oyster (Crassostrea virginica), and sediments. Metals were accumulated in either oysters or sediments. Cu and Zn were higher in oysters and Fe and Mn were higher in sediments. The results in water samples were compared with the limit established by the Secretaria de Ecologia and Desarrollo Urbano Report and briefly discussed. PMID:7621796

Docking and molecular dynamics simulations of the Fyn-SH3 domain with free and phospholipid bilayer-associated 18.5-kDa myelin basic protein (MBP)-Insights into a noncanonical and fuzzy interaction.

PubMed

Bessonov, Kyrylo; Vassall, Kenrick A; Harauz, George

2017-07-01

The molecular details of the association between the human Fyn-SH3 domain, and the fragment of 18.5-kDa myelin basic protein (MBP) spanning residues S38-S107 (denoted as xα2-peptide, murine sequence numbering), were studied in silico via docking and molecular dynamics over 50-ns trajectories. The results show that interaction between the two proteins is energetically favorable and heavily dependent on the MBP proline-rich region (P93-P98) in both aqueous and membrane environments. In aqueous conditions, the xα2-peptide/Fyn-SH3 complex adopts a "sandwich"-like structure. In the membrane context, the xα2-peptide interacts with the Fyn-SH3 domain via the proline-rich region and the β-sheets of Fyn-SH3, with the latter wrapping around the proline-rich region in a form of a clip. Moreover, the simulations corroborate prior experimental evidence of the importance of upstream segments beyond the canonical SH3-ligand. This study thus provides a more-detailed glimpse into the context-dependent interaction dynamics and importance of the β-sheets in Fyn-SH3 and proline-rich region of MBP. Proteins 2017; 85:1336-1350. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Plant genotype effects on a host specific thrips and the impact on biological control

USDA-ARS?s Scientific Manuscript database

A promising thrips, Pseudophilothrips ichini (Phlaeothripidae) has been considered for biological control of the invasive weed Brazilian pepper Schinus terebinthifolius. This thrips was originally collected from a southern region of Brazil where it was frequently found associated with significant da...

Neighborhood linking social capital as a predictor of drug abuse: A Swedish national cohort study

PubMed Central

Sundquist, Jan; Sjöstedt, Cecilia; Winkleby, Marilyn; Li, Xinjun; Kendler, Kenneth S.; Sundquist, Kristina

2016-01-01

Aims This study examines the association between the incidence of drug abuse (DA) and linking (communal) social capital, a theoretical concept describing the amount of trust between individuals and societal institutions. Methods We present results from an 8-year population-based cohort study that followed all residents in Sweden, aged 15–44, from 2003 through 2010, for a total of 1,700,896 men and 1,642,798 women. Linking social capital was conceptualized as the proportion of people in a geographically defined neighborhood who voted in local government elections. Multilevel logistic regression was used to estimate odds ratios (ORs) and between-neighborhood variance. Results We found robust associations between linking social capital and DA in men and women. For men, the OR for DA in the crude model was 2.11 [95% confidence interval (CI) 2.02–2.21] for those living in neighborhoods with the lowest vs. highest level of social capital. After accounting for neighborhood level deprivation, the OR fell to 1.59 (1.51–1-68). The ORs remained significant after accounting for age, family income, marital status, country of birth, education level, and region of residence, and after further accounting for comorbidities and family history of comorbidities and family history of DA. For women, the OR decreased from 2.15 (2.03–2.27) in the crude model to 1.31 (1.22–1.40) in the final model, adjusted for multiple neighborhood-level, individual-level variables, and family history for DA. Conclusions Our study suggests that low linking social capital may have significant independent effects on DA. PMID:27416013

Sensitivity analysis of a data assimilation technique for hindcasting and forecasting hydrodynamics of a complex coastal water body

NASA Astrophysics Data System (ADS)

Ren, Lei; Hartnett, Michael

2017-02-01

Accurate forecasting of coastal surface currents is of great economic importance due to marine activities such as marine renewable energy and fish farms in coastal regions in recent twenty years. Advanced oceanographic observation systems such as satellites and radars can provide many parameters of interest, such as surface currents and waves, with fine spatial resolution in near real time. To enhance modelling capability, data assimilation (DA) techniques which combine the available measurements with the hydrodynamic models have been used since the 1990s in oceanography. Assimilating measurements into hydrodynamic models makes the original model background states follow the observation trajectory, then uses it to provide more accurate forecasting information. Galway Bay is an open, wind dominated water body on which two coastal radars are deployed. An efficient and easy to implement sequential DA algorithm named Optimal Interpolation (OI) was used to blend radar surface current data into a three-dimensional Environmental Fluid Dynamics Code (EFDC) model. Two empirical parameters, horizontal correlation length and DA cycle length (CL), are inherent within OI. No guidance has previously been published regarding selection of appropriate values of these parameters or how sensitive OI DA is to variations in their values. Detailed sensitivity analysis has been performed on both of these parameters and results presented. Appropriate value of DA CL was examined and determined on producing the minimum Root-Mean-Square-Error (RMSE) between radar data and model background states. Analysis was performed to evaluate assimilation index (AI) of using an OI DA algorithm in the model. AI of the half-day forecasting mean vectors' directions was over 50% in the best assimilation model. The ability of using OI to improve model forecasts was also assessed and is reported upon.

Neighborhood linking social capital as a predictor of drug abuse: A Swedish national cohort study.

PubMed

Sundquist, Jan; Sjöstedt, Cecilia; Winkleby, Marilyn; Li, Xinjun; Kendler, Kenneth S; Sundquist, Kristina

2016-12-01

This study examines the association between the incidence of drug abuse (DA) and linking (communal) social capital, a theoretical concept describing the amount of trust between individuals and societal institutions. We present results from an 8-year population-based cohort study that followed all residents in Sweden, aged 15-44, from 2003 through 2010, for a total of 1,700,896 men and 1,642,798 women. Linking social capital was conceptualized as the proportion of people in a geographically defined neighborhood who voted in local government elections. Multilevel logistic regression was used to estimate odds ratios (ORs) and between-neighborhood variance. We found robust associations between linking social capital and DA in men and women. For men, the OR for DA in the crude model was 2.11 [95% confidence interval (CI) 2.02-2.21] for those living in neighborhoods with the lowest vs. highest level of social capital. After accounting for neighborhood level deprivation, the OR fell to 1.59 (1.51-1-68). The ORs remained significant after accounting for age, family income, marital status, country of birth, education level, and region of residence, and after further accounting for comorbidities and family history of comorbidities and family history of DA. For women, the OR decreased from 2.15 (2.03-2.27) in the crude model to 1.31 (1.22-1.40) in the final model, adjusted for multiple neighborhood-level, individual-level variables, and family history for DA. Our study suggests that low linking social capital may have significant independent effects on DA. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decision Modeling Framework to Minimize Arrival Delays from Ground Delay Programs

NASA Astrophysics Data System (ADS)

Mohleji, Nandita

Convective weather and other constraints create uncertainty in air transportation, leading to costly delays. A Ground Delay Program (GDP) is a strategy to mitigate these effects. Systematic decision support can increase GDP efficacy, reduce delays, and minimize direct operating costs. In this study, a decision analysis (DA) model is constructed by combining a decision tree and Bayesian belief network. Through a study of three New York region airports, the DA model demonstrates that larger GDP scopes that include more flights in the program, along with longer lead times that provide stakeholders greater notice of a pending program, trigger the fewest average arrival delays. These findings are demonstrated to result in a savings of up to $1,850 per flight. Furthermore, when convective weather is predicted, forecast weather confidences remain the same level or greater at least 70% of the time, supporting more strategic decision making. The DA model thus enables quantification of uncertainties and insights on causal relationships, providing support for future GDP decisions.

Isolation and initial structural characterization of a 27 kDa protein from Zingiber officinale

NASA Astrophysics Data System (ADS)

Rasheed, Saima; Malik, Shoaib Ahmad; Falke, Sven; Arslan, Ali; Fazel, Ramin; Schlüter, Hartmut; Betzel, Christian; Choudhary, M. Iqbal

2018-03-01

Zingiber officinale Roscoe (Ginger) is a widely used traditional medicinal plant (for different ailments such as arthritis, constipation, and hypertension). This article describes the isolation and characterization of a so far unknown protein from ginger rhizomes applying ion exchange, affinity, size-exclusion chromatography, small angle X-ray scattering (SAXS), and mass spectrometry techniques. One-dimensional Coomassie-stained SDS-PAGE was performed under non-reducing conditions, showing one band corresponding to approx. 27 kDa. Dynamic light scattering (DLS) analysis of the protein solution revealed monodispersity and a monomeric state of the purified protein. Circular dichroism (CD) spectroscopy strongly indicated a β-sheet-rich protein, and disordered regions. MALDI-TOF-MS, and LC-MS/MS analysis resulted in the identification of 27.29 kDa protein, having 32.13% and 25.34% sequence coverage with Zingipain-1 and 2, respectively. The monomeric state and molecular weight were verified by small angle X-ray scattering (SAXS) studies. An elongated ab-initio model was calculated based on the scattering intensity distribution.

Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons.

PubMed

Jo, Junghyun; Xiao, Yixin; Sun, Alfred Xuyang; Cukuroglu, Engin; Tran, Hoang-Dai; Göke, Jonathan; Tan, Zi Ying; Saw, Tzuen Yih; Tan, Cheng-Peow; Lokman, Hidayat; Lee, Younghwan; Kim, Donghoon; Ko, Han Seok; Kim, Seong-Oh; Park, Jae Hyeon; Cho, Nam-Joon; Hyde, Thomas M; Kleinman, Joel E; Shin, Joo Heon; Weinberger, Daniel R; Tan, Eng King; Je, Hyunsoo Shawn; Ng, Huck-Hui

2016-08-04

Recent advances in 3D culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. Importantly, we detected electrically active and functionally mature mDA neurons and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using 2D methods or MLOs generated from mouse embryonic stem cells, our human MLOs produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a tractable in vitro system to study the human midbrain and its related diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of afferent input in load-dependent plasticity of rat muscle

NASA Astrophysics Data System (ADS)

Kawano, F.; Umemoto, S.; Higo, Y.; Kawabe, N.; Wang, X. D.; Lan, Y. B.; Ohira, Y.

We have been studying the role of afferent input in the plasticity of skeletal muscles. The present study was performed to investigate the mechanisms responsible for the deafferentation-related inhibition of the compensatory hypertrophy in rat soleus muscle. Adult male Wistar rats were randomly separated into the control, functionally overloaded (FO), and functionally overloaded + deafferentation (FO+DA) group. The tendons of plantaris and gastrocnemius muscles were transected in the FO rats. The dorsal roots of the spinal cord at the L4-5 segmental levels were additionally transected in the FO+DA rats. The sampling of the soleus was performed 2 weeks after the surgery and ambulation recovery. The single muscle fibers were isolated in low-calcium relaxing solution. Further, the myonuclei or argyrophilic nucleolar organizer regions (AgNORs) were stained. Significant increase of the fiber cross-sectional area (CSA) was seen in the FO, but not in the FO+DA, rats. The myonuclear number in fiber was significantly decreased by FO. Addition of DA to FO further promoted the reduction of myonuclear number. The mean nucleus size and DNA content in single nucleus in all groups were identical. Although a single or double AgNORs were seen in ~90% of myonuclei in the control rats, their distributions were 72 and 76% in the FO and FO+DA rats, respectively (p<0.05). More myonuclei containing 3-5 AgNORs were noted in the FO and FO+DA rats. The mean number of the AgNORs per myonucleus was 1.7 in the control, 2.1 in both FO and FO+DA rats (p<0.05). It was suggested that the FO-related increase of the number of AgNORs may be responsible for the induction of compensatory hypertrophy. It was also indicated that intact afferent input plays an essential role in these phenomena.

Donkey Orchid Symptomless Virus: A Viral ‘Platypus’ from Australian Terrestrial Orchids

PubMed Central

Wylie, Stephen J.; Li, Hua; Jones, Michael G. K.

2013-01-01

Complete and partial genome sequences of two isolates of an unusual new plant virus, designated Donkey orchid symptomless virus (DOSV) were identified using a high-throughput sequencing approach. The virus was identified from asymptomatic plants of Australian terrestrial orchid Diuris longifolia (Common donkey orchid) growing in a remnant forest patch near Perth, western Australia. DOSV was identified from two D. longifolia plants of 264 tested, and from at least one plant of 129 Caladenia latifolia (pink fairy orchid) plants tested. Phylogenetic analysis of the genome revealed open reading frames (ORF) encoding seven putative proteins of apparently disparate origins. A 69-kDa protein (ORF1) that overlapped the replicase shared low identity with MPs of plant tymoviruses (Tymoviridae). A 157-kDa replicase (ORF2) and 22-kDa coat protein (ORF4) shared 32% and 40% amino acid identity, respectively, with homologous proteins encoded by members of the plant virus family Alphaflexiviridae. A 44-kDa protein (ORF3) shared low identity with myosin and an autophagy protein from Squirrelpox virus. A 27-kDa protein (ORF5) shared no identity with described proteins. A 14-kDa protein (ORF6) shared limited sequence identity (26%) over a limited region of the envelope glycoprotein precursor of mammal-infecting Crimea-Congo hemorrhagic fever virus (Bunyaviridae). The putative 25-kDa movement protein (MP) (ORF7) shared limited (27%) identity with 3A-like MPs of members of the plant-infecting Tombusviridae and Virgaviridae. Transmissibility was shown when DOSV systemically infected Nicotiana benthamiana plants. Structure and organization of the domains within the putative replicase of DOSV suggests a common evolutionary origin with ‘potexvirus-like’ replicases of viruses within the Alphaflexiviridae and Tymoviridae, and the CP appears to be ancestral to CPs of allexiviruses (Alphaflexiviridae). The MP shares an evolutionary history with MPs of dianthoviruses, but the other putative proteins are distant from plant viruses. DOSV is not readily classified in current lower order virus taxa. PMID:24223974

Ghrelin promotes and protects nigrostriatal dopamine function via an UCP2-dependent mitochondrial mechanism

PubMed Central

Andrews, Zane B.; Erion, Derek; Beiler, Rudolph; Liu, Zhong-Wu; Abizaid, Alfonso; Zigman, Jeffrey; Elsworth, John D.; Savitt, Joseph M.; DiMarchi, Richard; Tschoep, Matthias; Roth, Robert H.; Gao, Xiao-Bing; Horvath, Tamas L.

2010-01-01

Ghrelin targets the hypothalamus to regulate food intake and adiposity. Endogenous ghrelin receptors (growth hormone secretagogue receptor, GHSR) are also present in extrahypothalamic sites where they promote circuit activity associated with learning and memory, and reward seeking behavior. Here, we show that the substantia nigra pars compacta (SNpc), a brain region where dopamine (DA) cell degeneration leads to Parkinson’s disease (PD), expresses GHSR. Ghrelin binds to SNpc cells, electrically activates SNpc DA neurons, increases tyrosine hydroxylase mRNA and increases DA concentration in the dorsal striatum. Exogenous ghrelin administration decreased SNpc DA cell loss and restricted striatal dopamine loss after 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine (MPTP) treatment. Genetic ablation of ghrelin or the ghrelin receptor (GHSR) increased SNpc DA cell loss and lowered striatal dopamine levels after MPTP treatment, an effect that was reversed by selective reactivation of GHSR in catecholaminergic neurons. Ghrelin-induced neuroprotection was dependent on the mitochondrial redox state via uncoupling protein 2 (UCP2)-dependent alterations in mitochondrial respiration, ROS production and biogenesis. Taken together, our data reveals that peripheral ghrelin plays an important role in the maintenance and protection of normal nigrostriatal dopamine function by activating UCP2-dependent mitochondrial mechanisms. These studies support ghrelin as a novel therapeutic strategy to combat neurodegeneration, loss of appetite and body weight associated with PD. Finally, we discuss the potential implications of these studies on the link between obesity and neurodegeneration. PMID:19906954

A Tyrosine-Hydroxylase Characterization of Dopaminergic Neurons in the Honey Bee Brain

PubMed Central

Tedjakumala, Stevanus R.; Rouquette, Jacques; Boizeau, Marie-Laure; Mesce, Karen A.; Hotier, Lucie; Massou, Isabelle; Giurfa, Martin

2017-01-01

Dopamine (DA) plays a fundamental role in insect behavior as it acts both as a general modulator of behavior and as a value system in associative learning where it mediates the reinforcing properties of unconditioned stimuli (US). Here we aimed at characterizing the dopaminergic neurons in the central nervous system of the honey bee, an insect that serves as an established model for the study of learning and memory. We used tyrosine hydroxylase (TH) immunoreactivity (ir) to ensure that the neurons detected synthesize DA endogenously. We found three main dopaminergic clusters, C1–C3, which had been previously described; the C1 cluster is located in a small region adjacent to the esophagus (ES) and the antennal lobe (AL); the C2 cluster is situated above the C1 cluster, between the AL and the vertical lobe (VL) of the mushroom body (MB); the C3 cluster is located below the calyces (CA) of the MB. In addition, we found a novel dopaminergic cluster, C4, located above the dorsomedial border of the lobula, which innervates the visual neuropils of the bee brain. Additional smaller processes and clusters were found and are described. The profuse dopaminergic innervation of the entire bee brain and the specific connectivity of DA neurons, with visual, olfactory and gustatory circuits, provide a foundation for a deeper understanding of how these sensory modules are modulated by DA, and the DA-dependent value-based associations that occur during associative learning. PMID:28740466

Inter-individual differences in the impulsive/compulsive dimension: deciphering related dopaminergic and serotonergic metabolisms at rest.

PubMed

Dellu-Hagedorn, Françoise; Rivalan, Marion; Fitoussi, Aurélie; De Deurwaerdère, Philippe

2018-04-19

Several impulse control disorders such as ADHD, mania, personality disorders or substance abuse share common behavioural traits, like impulsiveness, risk-taking or inflexible behaviour. These disorders are treated with drugs targeting dopamine (DA) and/or serotonin (5-HT). However, the patient's monoamine imbalance that these neurotransmitters compensate is unclear. This study aims to investigate the patterns of DA and 5-HT metabolisms at rest within selected brain regions related to inter-individual variability in six main components of impulsivity/compulsivity (anticipatory hyperactivity, premature responses, delay discounting, risk-taking, perseveration, flexibility). Rats with adaptive and highly inadaptive behaviours were identified in each task and a sensitive biochemical approach allowed mapping of post-mortem endogenous monoamine tissue content in 20 brain areas. Distinct patterns of 5-HT and DA metabolisms were revealed according to the behavioural traits. Except for hyperactive responses, lower control of actions was mainly associated with a lower DA or 5-HT metabolism in prefrontal and/or subcortical areas (i.e. in orbitofrontal cortex (DA), amygdala and anterior cingulate cortex (5-HT) for inflexible and risk-prone rats). Our results reveal the complex nature of behavioural traits related to impulse control disorders through their associated monoaminergic networks at rest, paving the way for understanding the link between mental disorders and drug therapeutic actions.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'. © 2018 The Author(s).

Evaluating the Impact of AIRS Observations on Regional Forecasts at the SPoRT Center

NASA Technical Reports Server (NTRS)

Zavodsky, Bradley

2011-01-01

NASA Short-term Prediction Research and Transition (SPoRT) Center collaborates with operational partners of different sizes and operational goals to improve forecasts using targeted projects and data sets. Modeling and DA activities focus on demonstrating utility of NASA data sets and capabilities within operational systems. SPoRT has successfully assimilated the Atmospheric Infrared Sounder (AIRS) radiance and profile data. A collaborative project is underway with the Joint Center for Satellite Data Assimilation (JCSDA) to use AIRS profiles to better understand the impact of AIRS radiances assimilated within Gridpoint Statistical Interpolation (GSI) in hopes of engaging the operational DA community in a reassessment of assimilation methodologies to more effectively assimilate hyperspectral radiances.

PRIMARY STRUCTURE OF THE P450 LANOSTEROL DEMETHYLASE GENE FROM SACCHAROMYCES CEREVISIAE

EPA Science Inventory

We have sequenced the structural gene and flanking regions for lanosterol 14 alpha-demethylase (14DM) from Saccharomyces cerevisiae. An open reading frame of 530 codons encodes a 60.7-kDa protein. When this gene is disrupted by integrative transformation, the resulting strain req...

Review of Thermal Properties of Snow, Ice and Sea Ice,

DTIC Science & Technology

1981-06-01

AD-AL03 734 COLD RE61ONS RESEARCH AND ENGINEERING LAS HANOVER NH F/G 8/12AI3 3REVIEW OF THERMAL PROPERTIES OF SNOW. ICE AND SEA ICE,(U)UNCLASSIFIlED...Distribution/ Availability Codes Avail and/or D~ Dis~t Special D 1 7 C- T > L) UNITED STATES ARMY CORPS OF ENGINEERS COLD REGIONS RESEARCH AND ENGINEERING...PROGRAM ELEMENT, PROJECT. TASK AREA A WORK UNIT NUMBERS U.S. Army Cold Regions Research and Engineering Laboratory Hanover, New Hampshire 03755 DA Pr

Synoptic Meteorology during the SNOW-ONE-A Field Experiment.

DTIC Science & Technology

1983-05-01

AD ,34 888 SYNOPTIC METEOROLOGY DURING tHE SNOW-ONE A FIELD I EXPERIMENTIUP COLD REGIONS RESEARCH AND ENGINEERING LABHANOVER NN M A BILELLO MAY 83...PROGRAM ELEMENT. PROJECT. TASK U. S. Army Cold Regions Research and AREA & WORK UNIT NUMBERS Engineering Laboratory DA Project 4A762730AT42- Hanover, New...Hampshire 03755 B-El-5 It. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE Office of the Ch ief of Engineers May 1983 Washington, D.C. 20314 13

Access to and use of high blood pressure medications in Brazil.

PubMed

Mengue, Sotero Serrate; Bertoldi, Andréa Dâmaso; Ramos, Luiz Roberto; Farias, Mareni Rocha; Oliveira, Maria Auxiliadora; Tavares, Noemia Urruth Leão; Arrais, Paulo Sergio Dourado; Luiza, Vera Lucia; Pizzol, Tatiane da Silva Dal

2016-12-01

To analyze the access to and use of medicines for high blood pressure among the Brazilian population according to social and demographic conditions. Analysis of data from Pesquisa Nacional Sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines), a nationwide cross-sectional, population-based study, with probability sampling, carried out between September 2013 and February 2014 in urban households in the five Brazilian regions. The study evaluated the access and use of medicines to treat people with high blood pressure. The independent variables were gender, age, socioeconomic status and Brazilian region. The study also described the most commonly used drugs and the percentage of people treated with one, two, three or more drugs. Point estimations and confidence intervals were calculated considering the sample weights and sample complex plan. Prevalence of high blood pressure was 23.7% (95%CI 22.8-24.6). Regarding people with this condition, 93.8% (95%CI 92.8-94.8) had indication for drug therapy and, of those, 94.6% (95%CI 93.5-95.5) were using the medication at the time of interview. Full access to medicines was 97.9% (95%CI 97.3-98.4); partial access, 1.9% (95%CI 1.4-2.4); and no access, 0.2% (95%CI 0.1-0.4). The medication used to treat high blood pressure, 56.0% (95%CI 52.6-59.2) were obtained from SUS (Brazilian Unified Health System), 16.0% (95%CI 14.3-17.9) from Popular Pharmacy Program, 25.7% (95%CI 23.4-28.2) were paid for by the patients themselves and 2.3% (95%CI 1.8-2.9) were obtained from other locations. The five most commonly used drugs were, in descending order, hydrochlorothiazide, losartan, captopril, enalapril and atenolol. Of the total number of patients on treatment, 36.1% (95%CI 34.1-37.1) were using two medicines and 13.5% (95%CI 12.3-14.9) used three or more. Access to medicines for the treatment of high blood pressure may be considered high and many of them are available free of charge. The most commonly used drugs are among those recommended as first-line treatment for high blood pressure control. The percentage of people using more than one drug seems to follow the behavior observed in other countries. Analisar o acesso e a utilização de medicamentos para a hipertensão na população brasileira segundo condições sociais e demográficas. Análise dos dados da Pesquisa Nacional Sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos, estudo nacional de delineamento transversal de base populacional, com amostra probabilística, realizado entre setembro de 2013 e fevereiro de 2014 em domicílios urbanos nas cinco regiões do Brasil. Avaliou-se o uso e acesso aos medicamentos para os cuidados com pessoas que apresentam hipertensão arterial. As variáveis independentes utilizadas foram sexo, idade, nível socioeconômico e região do País. Também foram descritos os fármacos mais utilizados e a proporção de pessoas tratadas com um, dois, três ou mais fármacos. As estimativas de ponto e os intervalos de confiança foram calculados considerando os pesos amostrais e o plano complexo da amostra. A prevalência de hipertensão arterial foi de 23,7% (IC95% 22,8-24,6). Das pessoas com a condição, 93,8% (IC95% 92,8-94,8) tinham indicação de tratamento com medicamentos e, destes, 94,6% (IC95% 93,5-95,5) estavam usando os medicamentos no momento da entrevista. O acesso total aos medicamentos foi de 97,9% (IC95% 97,3-98,4); o acesso parcial, de 1,9% (IC95% 1,4-2,4); e o acesso nulo, de 0,2% (IC95% 0,1-0,4). Dos medicamentos utilizados para tratar a hipertensão, 56,0% (IC95% 52,6-59,2) foram obtidos no SUS, 16,0% (IC95% 14,3-17,9), no Programa Farmácia Popular, 25,7% (IC95% 23,4-28,2) pago do próprio bolso e 2,3% (IC95% 1,8-2,9) em outros locais. Os cinco fármacos mais utilizados foram, em ordem descrente, hidroclorotiazida, losartana, captopril, enalapril e atenolol. Do total de tratados, 36,1% (IC95% 34,1-37,1) estavam usando dois fármacos e 13,5% (IC95% 12,3-14,9) utilizavam três ou mais fármacos. : O acesso aos medicamentos para tratamento da hipertensão pode ser considerado elevado e grande parte desses medicamentos é obtida gratuitamente. Os fármacos mais utilizados estão entre os preconizados como de primeira linha para o controle de hipertensão arterial. A proporção de pessoas utilizando mais de um fármaco parece seguir o comportamento observado em outros países.

Sociodemographic profile of medicines users in Brazil: results from the 2014 PNAUM survey.

PubMed

Bertoldi, Andréa Dâmaso; Pizzol, Tatiane da Silva Dal; Ramos, Luiz Roberto; Mengue, Sotero Serrate; Luiza, Vera Lucia; Tavares, Noemia Urruth Leão; Farias, Mareni Rocha; Oliveira, Maria Auxiliadora; Arrais, Paulo Sergio Dourado

2016-12-01

To analyze the prevalence of medicine use by the Brazilian population and its distribution according to sociodemographic factors. Study using data from the Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines), a nationwide household survey of a representative sample of the Brazilian urban population. The data were collected between September 2013 and February 2014. The overall use of medicines, defined as the use of any medicine, use of medicines for treating chronic medical conditions and for acute health conditions, was evaluated. The independent variables included gender, age group, socioeconomic position, and region of Brazil. Analyzes included prevalence calculations, 95% confidence intervals (95%CI) and Pearson Chi-square tests to evaluate the differences between groups, considering a 5% level of significance. The prevalence of medicines use was 50.7% (95%CI 49.3-52.2), with 39.3% (95%CI 37.5-41.1) accounting for men and 61.0% (95%CI 59.3-62.6) for women. Medicines use was observed to increase with increasing age, except among children within the zero to four years age group. The lowest prevalence for medicines use was found among those with a low socioeconomic position and those who reside in the North region of Brazil. The prevalence of medicine use to treat chronic diseases was 24.3% (95%CI 23.3-25.4), whereas it was 33.7% (95%CI 32.1-35.4) for treating acute diseases. We found extensive variability in the prevalence of medicines use across regions of Brazil. The poorest regions (North, Northeast, and Midwest) have a lower prevalence of medicines use to treat chronic diseases, indicating the need to minimize inequalities in access to medicines within the country. Analisar a prevalência do uso de medicamentos pela população brasileira e sua distribuição segundo aspectos sociodemográficos. Estudo com dados da Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM), pesquisa nacional de base populacional, realizada entre setembro de 2013 e fevereiro de 2014 em residências de municípios urbanos. Avaliou-se o uso de todos os medicamentos (global), uso de medicamentos para doenças crônicas e uso de medicamentos para doenças agudas. As variáveis independentes utilizadas foram sexo, idade, classificação econômica e região do País. Foram calculados prevalências e intervalos de confiança de 95% (IC95%) e aplicado teste Qui-quadrado de Pearson para avaliação das diferenças entre os grupos, considerando o nível de significância de 5%. A prevalência global de uso de medicamentos foi de 50,7% (IC95% 49,3-52,2), sendo 39,3% (IC95% 37,5-41,1) no sexo masculino e 61,0% (IC95% 59,3-62,6) no sexo feminino. Observou-se aumento nas prevalências de uso com a idade (exceto de zero a quatro anos). As menores prevalências de uso ocorreram no grupo mais pobre e na região Norte do País. A prevalência de uso de medicamentos para doenças crônicas foi de 24,3% (IC95% 23,3-25,4) e para doenças agudas foi de 33,7% (IC95% 32,1-35,4). Existe grande variabilidade nas prevalências globais de uso de medicamentos por regiões brasileiras. As regiões consideradas mais pobres (Norte, Nordeste e Centro-Oeste) apresentam menores prevalências de uso de medicamentos para doenças crônicas, o que indica a necessidade de minimizar as desigualdades no acesso aos medicamentos dentro do País.

Chandra Grating Spectroscopy of Three Hot White Dwarfs

NASA Technical Reports Server (NTRS)

Adamczak, J.; Werner, K.; Rauch, T.; Schuh, S.; Drake, J. J.; Kruk, J. W.

2013-01-01

High-resolution soft X-ray spectroscopic observations of single hot white dwarfs are scarce. With the Chandra Low-Energy Transmission Grating, we have observed two white dwarfs, one is of spectral type DA (LB1919) and the other is a non-DA of spectral type PG1159 (PG1520+525). The spectra of both stars are analyzed, together with an archival Chandra spectrum of another DA white dwarf (GD246). Aims. The soft X-ray spectra of the two DA white dwarfs are investigated in order to study the effect of gravitational settling and radiative levitation of metals in their photospheres. LB1919 is of interest because it has a significantly lower metallicity than DAs with otherwise similar atmospheric parameters. GD246 is the only white dwarf known that shows identifiable individual iron lines in the soft X-ray range. For the PG1159 star, a precise effective temperature determination is performed in order to confine the position of the blue edge of the GW Vir instability region in the HRD. Methods. The Chandra spectra are analyzed with chemically homogeneous as well as stratified NLTE model atmospheres that assume equilibrium between gravitational settling and radiative acceleration of chemical elements. Archival EUV and UV spectra obtained with EUVE, FUSE, and HST are utilized to support the analysis. Results. No metals could be identified in LB1919. All observations are compatible with a pure hydrogen atmosphere. This is in stark contrast to the vast majority of hot DA white dwarfs that exhibit light and heavy metals and to the stratified models that predict significant metal abundances in the atmosphere. For GD246 we find that neither stratified nor homogeneous models can fit the Chandra spectrum. The Chandra spectrum of PG1520+525 constrains the effective temperature to T(sub eff) = 150 000 +/- 10 000 K. Therefore, this nonpulsating star together with the pulsating prototype of the GWVir class (PG1159-035) defines the location of the blue edge of the GWVir instability region. The result is in accordance with predictions from nonadiabatic stellar pulsation models. Such models are therefore reliable tools to investigate the interior structure of GW Vir variables. Conclusions. Our soft X-ray study reveals that the understanding of metal abundances in hot DA white dwarf atmospheres is still incomplete. On the other hand, model atmospheres of hydrogen-deficient PG1159-type stars are reliable and reproduce well the observed spectra from soft X-ray to optical wavelengths.

VPS35 in Dopamine Neurons Is Required for Endosome-to-Golgi Retrieval of Lamp2a, a Receptor of Chaperone-Mediated Autophagy That Is Critical for α-Synuclein Degradation and Prevention of Pathogenesis of Parkinson's Disease

PubMed Central

Tang, Fu-Lei; Erion, Joanna R.; Tian, Yun; Liu, Wei; Yin, Dong-Min; Ye, Jian; Tang, Baisha; Mei, Lin

2015-01-01

Vacuolar protein sorting-35 (VPS35) is essential for endosome-to-Golgi retrieval of membrane proteins. Mutations in the VPS35 gene have been identified in patients with autosomal dominant PD. However, it remains poorly understood if and how VPS35 deficiency or mutation contributes to PD pathogenesis. Here we provide evidence that links VPS35 deficiency to PD-like neuropathology. VPS35 was expressed in mouse dopamine (DA) neurons in substantia nigra pars compacta (SNpc) and STR (striatum)—regions that are PD vulnerable. VPS35-deficient mice exhibited PD-relevant deficits including accumulation of α-synuclein in SNpc-DA neurons, loss of DA transmitter and DA neurons in SNpc and STR, and impairment of locomotor behavior. Further mechanical studies showed that VPS35-deficient DA neurons or DA neurons expressing PD-linked VPS35 mutant (D620N) had impaired endosome-to-Golgi retrieval of lysosome-associated membrane glycoprotein 2a (Lamp2a) and accelerated Lamp2a degradation. Expression of Lamp2a in VPS35-deficient DA neurons reduced α-synuclein, supporting the view for Lamp2a as a receptor of chaperone-mediated autophagy to be critical for α-synuclein degradation. These results suggest that VPS35 deficiency or mutation promotes PD pathogenesis and reveals a crucial pathway, VPS35-Lamp2a-α-synuclein, to prevent PD pathogenesis. SIGNIFICANCE STATEMENT VPS35 is a key component of the retromer complex that is essential for endosome-to-Golgi retrieval of membrane proteins. Mutations in the VPS35 gene have been identified in patients with PD. However, if and how VPS35 deficiency or mutation contributes to PD pathogenesis remains unclear. We demonstrated that VPS35 deficiency or mutation (D620N) in mice leads to α-synuclein accumulation and aggregation in the substantia nigra, accompanied with DA neurodegeneration. VPS35-deficient DA neurons exhibit impaired endosome-to-Golgi retrieval of Lamp2a, which may contribute to the reduced α-synuclein degradation through chaperone-mediated autophagy. These results suggest that VPS35 deficiency or mutation promotes PD pathogenesis, and reveals a crucial pathway, VPS35-Lamp2a-α-synuclein, to prevent PD pathogenesis. PMID:26203154

The Spanish long-term care system in transition: Ten years since the 2006 Dependency Act.

PubMed

Peña-Longobardo, Luz María; Oliva-Moreno, Juan; García-Armesto, Sandra; Hernández-Quevedo, Cristina

2016-10-01

At the end of 2006, a new System for Promotion of Personal Autonomy and Assistance for Persons in a Situation of Dependency (SAAD) was established in Spain through the approval of the Act 39/2006 of 14th December (the Dependency Act, DA). The DA acknowledged the universal entitlement of Spanish citizens to social services. The recent economic crisis added degrees of uncertainty to several dimensions of the SAAD implementation process. Firstly, the political consensus on which its foundation rested upon has weakened. Secondly, implementation of the SAAD was hampered by several challenges that emerged in the context of the economic crisis. Thirdly, the so-called "dependency limbo" (i.e. the existence of a large number of people eligible for benefits but who do not receive them) has become a structural feature of the system. Finally, contrary to the spirit of the DA, monetary benefits have become the norm rather than a last resort. High heterogeneity across regions regarding the number of beneficiaries covered and services provided reveal the existence of regional inequity in access to long-term care services in the country. Broadly, the current evidence on the state of the SAAD suggests the need to improve the quality of governance, to enhance coordination between health and social systems, to increase the system's transparency, to foster citizens' participation in decision-making and to implement a systematic monitoring of the system. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

A metabolic fingerprinting approach based on selected ion flow tube mass spectrometry (SIFT-MS) and chemometrics: A reliable tool for Mediterranean origin-labeled olive oils authentication.

PubMed

Bajoub, Aadil; Medina-Rodríguez, Santiago; Ajal, El Amine; Cuadros-Rodríguez, Luis; Monasterio, Romina Paula; Vercammen, Joeri; Fernández-Gutiérrez, Alberto; Carrasco-Pancorbo, Alegría

2018-04-01

Selected Ion flow tube mass spectrometry (SIFT-MS) in combination with chemometrics was used to authenticate the geographical origin of Mediterranean virgin olive oils (VOOs) produced under geographical origin labels. In particular, 130 oil samples from six different Mediterranean regions (Kalamata (Greece); Toscana (Italy); Meknès and Tyout (Morocco); and Priego de Córdoba and Baena (Spain)) were considered. The headspace volatile fingerprints were measured by SIFT-MS in full scan with H 3 O + , NO + and O 2 + as precursor ions and the results were subjected to chemometric treatments. Principal Component Analysis (PCA) was used for preliminary multivariate data analysis and Partial Least Squares-Discriminant Analysis (PLS-DA) was applied to build different models (considering the three reagent ions) to classify samples according to the country of origin and regions (within the same country). The multi-class PLS-DA models showed very good performance in terms of fitting accuracy (98.90-100%) and prediction accuracy (96.70-100% accuracy for cross validation and 97.30-100% accuracy for external validation (test set)). Considering the two-class PLS-DA models, the one for the Spanish samples showed 100% sensitivity, specificity and accuracy in calibration, cross validation and external validation; the model for Moroccan oils also showed very satisfactory results (with perfect scores for almost every parameter in all the cases). Copyright © 2017 Elsevier Ltd. All rights reserved.

Advancing Data assimilation for Baltic Monitoring and Forecasting Center: implementation and evaluation of HBP-PDAF system

NASA Astrophysics Data System (ADS)

Korabel, Vasily; She, Jun; Huess, Vibeke; Woge Nielsen, Jacob; Murawsky, Jens; Nerger, Lars

2017-04-01

The potential of an efficient data assimilation (DA) scheme to improve model forecast skill was successfully demonstrated by many operational centres around the world. The Baltic-North Sea region is one of the most heavily monitored seas. Ferryboxes, buoys, ADCP moorings, shallow water Argo floats, and research vessels are providing more and more near-real time observations. Coastal altimetry has now providing increasing amount of high resolution sea level observations, which will be significantly expanded by the launch of SWOT satellite in next years. This will turn operational DA into a valuable tool for improving forecast quality in the region. This motivated us to focus on advancing DA for the Baltic Monitoring and Forecasting Centre (BAL MFC) in order to create a common framework for operational data assimilation in the Baltic Sea. We have implemented HBM-PDAF system based on the Parallel Data Assimilation Framework (PDAF), a highly versatile and optimised parallel suit with a choice of sequential schemes originally developed at AWI, and a hydrodynamic HIROMB-BOOS Model (HBM). At initial phase, only the satellite Sea Surface Temperature (SST) Level 3 data has been assimilated. Several related aspects are discussed, including improvements of the forecast quality for both surface and subsurface fields, the estimation of ensemble-based forecast error covariance, as well as possibilities of assimilating new types of observations, such as in-situ salinity and temperature profiles, coastal altimetry, and ice concentration.

Glycosylated chicken ZP2 accumulates in the egg coat of immature oocytes and remains localized to the germinal disc region of mature eggs.

PubMed

Nishio, Shunsuke; Kohno, Yoshinori; Iwata, Yuki; Arai, Mayumi; Okumura, Hiroki; Oshima, Kenzi; Nadano, Daita; Matsuda, Tsukasa

2014-11-01

Vertebrate eggs are surrounded by an egg coat, which is a specific extracellular egg matrix consisting of several glycoproteins with a conserved zona pellucida (ZP) domain. Two mammalian egg coat subunits, ZP2 and ZP3, have been suggested to act as sperm receptors. In bird eggs, however, ZP2 has never been identified in the egg coat of mature oocytes and ovulated eggs. Here we report that chicken ZP2 is expressed in immature small follicles and remains as an egg-coat component locally in the germinal disc region of mature eggs. RT-PCR analysis indicated marked expression of the ZP2 and ZP4 genes in the granulosa cells of immature white follicles, whereas the ZP3 and ZPD genes showed marked expression in the cells of maturing yellow follicles. ZP2 was identified in the egg coat isolated from immature follicles as a heavily N-glycosylated glycoprotein of ∼200 kDa, which was enzymatically converted to a 70-kDa deglycosylated form. Immunoblotting and immunohistological analyses showed that ZP2 was localized around the germinal disc region of mature follicles. ZP2 was accumulated in the egg coat of immature white follicles at the earlier stages of oocyte development and became a minor component in the egg coat of maturing yellow follicles, except for the germinal disc region. Localization of ZP2 in the germinal disc region of mature eggs, where sperm bind to the egg coat at high density, suggests some role for ZP2 in the preferential binding and penetration of sperm in the germinal disc region of bird eggs. © 2014 by the Society for the Study of Reproduction, Inc.

Distribution of atmospheric mercury in northern Southeast Asia and South China Sea during Dongsha Experiment

NASA Astrophysics Data System (ADS)

Sheu, Guey-Rong; Lin, Neng-Huei; Lee, Chung-Te; Wang, Jia-Lin; Chuang, Ming-Tung; Wang, Sheng-Hsiang; Chi, Kai Hsine; Ou-Yang, Chang-Feng

2013-10-01

Northern South China Sea (SCS) is adjacent to major atmospheric mercury (Hg) emission source regions; however, studies concerning regional atmospheric Hg distribution and cycling are very limited. Accordingly, measurements of atmospheric Hg were conducted in March and April during the 2010 Dongsha Experiment to study its spatial and temporal distribution. Atmospheric Hg was measured at Hengchun and Dongsha Island (Taiwan), Da Nang (Vietnam), Chiang Mai (Thailand) and over the northern SCS. Atmospheric Hg concentrations ranged between 1.54 and 6.83 ng m-3, mostly higher than the Northern Hemisphere background value. Regional wind fields and backward trajectories indicated that the atmospheric Hg concentrations over northern SCS should principally reflect the export of the East Asian Hg emissions by northeast monsoon. However, significantly elevated Hg concentrations were always observed at Da Nang, possibly due to the influence of local Hg emissions. Chiang Mai is located in the intense biomass burning region in northern Thailand. Therefore, atmospheric Hg concentrations at Chiang Mai reflected the influence of regional biomass burning Hg emissions. Two dust storms were encountered at Dongsha Island, one on March 16 and the other on March 21, with atmospheric Hg enhancements. Compared with the 2008 summer values, elevated Hg levels were observed at Dongsha Island in the spring of 2010. Summer air masses were mainly from the deep SCS, representing relatively clean marine air. On the other hand, air masses were from the north in spring, passing eastern China or Taiwan prior to reaching Dongsha Island. Results of this research thus demonstrated the transport of atmospheric Hg from the East Asian continent to northern SCS by regional monsoon activity in spring, but special events, such as biomass burning and dust storms, can also cause enhancements of ambient Hg levels.

Characterization of the antinociceptive and anti-inflammatory activities from Cocos nucifera L. (Palmae).

PubMed

Rinaldi, Sebastian; Silva, Davi O; Bello, Fabiana; Alviano, Celuta S; Alviano, Daniela S; Matheus, Maria Eline; Fernandes, Patricia D

2009-04-21

Cocos nucifera cultivated in Brazil is known as "coco-da-Bahia" or "coqueiro-da-India". The tea from the husk fiber is widely used to several inflammatory disorders. Crude extract and fractions obtained from Cocos nucifera "common variety" were evaluated to test the anti-inflammatory and antinociceptive activities. Crude extract (CE, 50, 100, and 150 mg/kg), fraction 1 (F1, molecular weight lesser than 1 kDa, 1, 10, and 50mg/kg), fraction 2 (F2, molecular weight higher than 1 kDa, 1, 10, and 50mg/kg), and the references drugs morphine (5mg/kg), acetilsalicilic acid (200mg/kg), prometazine (30 mg/kg), and metisergide (5mg/kg) were evaluated on models of analgesia and inflammation. CE, F1, and F2 significantly develop peripheral and central antinociceptive activity but with less effect on supra-spinal regions of the brain. Administration of the opioid antagonist, naloxone (5mg/kg) inhibited the antinociceptive effect indicating that Cocos nucifera crude extract and fractions may be acting in opioid receptors. CE and F1 also inhibited rat paw edema induced by histamine, and serotonin. results demonstrated that Cocos nucifera and its fractions have antinociceptive and anti-inflammatory activities which confirm the popular use of this plant in several inflammatory disorders.

The dopamine D2 receptor antagonist sulpiride modulates striatal BOLD signal during the manipulation of information in working memory.

PubMed

Dodds, Chris M; Clark, Luke; Dove, Anja; Regenthal, Ralf; Baumann, Frank; Bullmore, Ed; Robbins, Trevor W; Müller, Ulrich

2009-11-01

Dopamine (DA) plays an important role in working memory. However, the precise functions supported by different DA receptor subtypes in different neural regions remain unclear. The present study used pharmacological, event-related fMRI to test the hypothesis that striatal dopamine is important for the manipulation of information in working memory. Twenty healthy human subjects were scanned twice, once after placebo and once after sulpiride 400 mg, a selective DA D2 receptor antagonist, while performing a verbal working memory task requiring different levels of manipulation. Whilst there was no overall effect of sulpiride on task-dependent activation, individual variation in sulpiride plasma levels predicted the effect of working memory manipulation on activation in the putamen, suggesting a dose-dependent effect of DA antagonism on a striatally based manipulation process. These effects occurred in the context of a drug-induced improvement in performance on trials requiring the manipulation of information in working memory but not on simple retrieval trials. No significant drug effects were observed in the prefrontal cortex. These results support models of dopamine function that posit a 'gating' function for dopamine D2 receptors in the striatum, which enables the flexible updating and manipulation of information in working memory.

Proteomic analysis of carbon concentrating chemolithotrophic bacteria Serratia sp. for sequestration of carbon dioxide.

PubMed

Bharti, Randhir K; Srivastava, Shaili; Thakur, Indu Shekhar

2014-01-01

A chemolithotrophic bacterium enriched in the chemostat in presence of sodium bicarbonate as sole carbon source was identified as Serratia sp. by 16S rRNA sequencing. Carbon dioxide sequestering capacity of bacterium was detected by carbonic anhydrase enzyme and ribulose-1, 5- bisphosphate carboxylase/oxygenase (RuBisCO). The purified carbonic anhydrase showed molecular weight of 29 kDa. Molecular weight of RuBisCO was 550 kDa as determined by fast protein liquid chromatography (FPLC), however, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) showed presence of two subunits whose molecular weights were 56 and 14 kDa. The Western blot analysis of the crude protein and purified sample cross reacted with RuBisCO large-subunit polypeptides antibodies showed strong band pattern at molecular weight around 56 kDa regions. Whole cell soluble proteins of Serratia sp. grown under autotrophic and heterotrophic conditions were resolved by two-dimensional gel electrophoresis and MALDI-TOF/MS for differential expression of proteins. In proteomic analysis of 63 protein spots, 48 spots were significantly up-regulated in the autotrophically grown cells; seven enzymes showed its utilization in autotrophic carbon fixation pathways and other metabolic activities of bacterium including lipid metabolisms indicated sequestration potency of carbon dioxide and production of biomaterials.

Proteomic Analysis of Carbon Concentrating Chemolithotrophic Bacteria Serratia sp. for Sequestration of Carbon Dioxide

PubMed Central

Bharti, Randhir K.; Srivastava, Shaili; Thakur, Indu Shekhar

2014-01-01

A chemolithotrophic bacterium enriched in the chemostat in presence of sodium bicarbonate as sole carbon source was identified as Serratia sp. by 16S rRNA sequencing. Carbon dioxide sequestering capacity of bacterium was detected by carbonic anhydrase enzyme and ribulose-1, 5- bisphosphate carboxylase/oxygenase (RuBisCO). The purified carbonic anhydrase showed molecular weight of 29 kDa. Molecular weight of RuBisCO was 550 kDa as determined by fast protein liquid chromatography (FPLC), however, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) showed presence of two subunits whose molecular weights were 56 and 14 kDa. The Western blot analysis of the crude protein and purified sample cross reacted with RuBisCO large-subunit polypeptides antibodies showed strong band pattern at molecular weight around 56 kDa regions. Whole cell soluble proteins of Serratia sp. grown under autotrophic and heterotrophic conditions were resolved by two-dimensional gel electrophoresis and MALDI-TOF/MS for differential expression of proteins. In proteomic analysis of 63 protein spots, 48 spots were significantly up-regulated in the autotrophically grown cells; seven enzymes showed its utilization in autotrophic carbon fixation pathways and other metabolic activities of bacterium including lipid metabolisms indicated sequestration potency of carbon dioxide and production of biomaterials. PMID:24619032

A long-term perspective on biomass burning in the Serra da Estrela, Portugal

NASA Astrophysics Data System (ADS)

Connor, Simon E.; Araújo, João; van der Knaap, Willem O.; van Leeuwen, Jacqueline F. N.

2012-11-01

Fire is currently perceived as a major threat to ecosystems and biodiversity in the mountains of the Mediterranean region. Portugal's highest mountain range, the Serra da Estrela, is one of the country's most important protected areas and also the most fire-prone. We present a ˜14,000-year fire history based on microscopic charred particles in an infilled glacial lake to better understand the antiquity of biomass burning and its effects on Mediterranean vegetation at the Atlantic margin. Results indicate the continuous occurrence of fire in the Serra da Estrela over the period of the record. Two periods of increased fire activity - around 12,000-11,000 calendar years before the present (cal. a BP) and 3500-2500 cal. a BP - were accompanied by major vegetation changes and followed by long periods of vegetation stabilisation. Cross-correlation analyses reveal that post-fire succession consistently began with herbaceous vegetation, followed by forest and shrubland stages. Past successional trends were often markedly different to those observed at present. Holocene climatic changes, including shifts in the North Atlantic Oscillation, played a pivotal role in the vegetation development and fire history of the Serra da Estrela. In the late Holocene, human use of fire became a major agent of vegetation change, accelerating the Holocene decline of forests.

Cloning and characterization of mouse extracellular-signal-regulated protein kinase 3 as a unique gene product of 100 kDa.

PubMed

Turgeon, B; Saba-El-Leil, M K; Meloche, S

2000-02-15

MAP (mitogen-activated protein) kinases are a family of serine/threonine kinases that have a pivotal role in signal transduction. Here we report the cloning and characterization of a mouse homologue of extracellular-signal-regulated protein kinase (ERK)3. The mouse Erk3 cDNA encodes a predicted protein of 720 residues, which displays 94% identity with human ERK3. Transcription and translation of this cDNA in vitro generates a 100 kDa protein similar to the human gene product ERK3. Immunoblot analysis with an antibody raised against a unique sequence of ERK3 also recognizes a 100 kDa protein in mouse tissues. A single transcript of Erk3 was detected in every adult mouse tissue examined, with the highest expression being found in the brain. Interestingly, expression of Erk3 mRNA is acutely regulated during mouse development, with a peak of expression observed at embryonic day 11. The mouse Erk3 gene was mapped to a single locus on central mouse chromosome 9, adjacent to the dilute mutation locus and in a region syntenic to human chromosome 15q21. Finally, we provide several lines of evidence to support the existence of a unique Erk3 gene product of 100 kDa in mammalian cells.

Profiling of Human Acquired Immunity Against the Salivary Proteins of Phlebotomus papatasi Reveals Clusters of Differential Immunoreactivity

PubMed Central

Geraci, Nicholas S.; Mukbel, Rami M.; Kemp, Michael T.; Wadsworth, Mariha N.; Lesho, Emil; Stayback, Gwen M.; Champion, Matthew M.; Bernard, Megan A.; Abo-Shehada, Mahmoud; Coutinho-Abreu, Iliano V.; Ramalho-Ortigão, Marcelo; Hanafi, Hanafi A.; Fawaz, Emadeldin Y.; El-Hossary, Shabaan S.; Wortmann, Glenn; Hoel, David F.; McDowell, Mary Ann

2014-01-01

Phlebotomus papatasi sand flies are among the primary vectors of Leishmania major parasites from Morocco to the Indian subcontinent and from southern Europe to central and eastern Africa. Antibody-based immunity to sand fly salivary gland proteins in human populations remains a complex contextual problem that is not yet fully understood. We profiled the immunoreactivities of plasma antibodies to sand fly salivary gland sonicates (SGSs) from 229 human blood donors residing in different regions of sand fly endemicity throughout Jordan and Egypt as well as 69 US military personnel, who were differentially exposed to P. papatasi bites and L. major infections in Iraq. Compared with plasma from control region donors, antibodies were significantly immunoreactive to five salivary proteins (12, 26, 30, 38, and 44 kDa) among Jordanian and Egyptian donors, with immunoglobulin G4 being the dominant anti-SGS isotype. US personnel were significantly immunoreactive to only two salivary proteins (38 and 14 kDa). Using k-means clustering, donors were segregated into four clusters distinguished by unique immunoreactivity profiles to varying combinations of the significantly immunogenic salivary proteins. SGS-induced cellular proliferation was diminished among donors residing in sand fly-endemic regions. These data provide a clearer picture of human immune responses to sand fly vector salivary constituents. PMID:24615125

RG-I regions from elderflower pectins substituted on GalA are strong immunomodulators.

PubMed

Ho, Giang Thanh Thi; Zou, Yuan-Feng; Wangensteen, Helle; Barsett, Hilde

2016-11-01

Sambuci flos, also known as elderflower, has traditionally been used and is still in use for treatment of various types of illnesses related to the immune system such as cold, flu, fever and inflammation. Pectic polysaccharides from 50% EtOH, 50°C water and 100°C water extracts from elderflowers were treated with endo-α-d-(1-4)-polygalacturonase after previous de-esterification with the intention of isolating hairy regions and relate variation in structure to immunomodulating activity. High molecular weight sub-fractions (25-29kDa) and medium molecular weight sub-fractions (6-17kDa) were isolated after enzymatic treatment in addition to oligogalacturonides. Structural elucidation indicated that RG-I regions with AG-I and AG-II sidechains were the predominant structures in the high molecular weight sub-fractions, and two of three 1,4-linked GalA units in the rhamnogalacturonan backbone were branched in either position 2 or 3. The medium molecular weight sub-fractions had monomers and linkages typical for both RG-I and RG-II. The results showed that the high molecular RG-I containing polymers exhibit the highest dose-dependent complement fixing and macrophage stimulating activities. Copyright © 2016 Elsevier B.V. All rights reserved.

High resolution reconstruction of monthly autumn and winter precipitation of Iberian Peninsula for last 150 years.

NASA Astrophysics Data System (ADS)

Cortesi, N.; Trigo, R.; González-Hidalgo, J. C.; Ramos, A.

2012-04-01

Precipitation over Iberian Peninsula (IP) presents large values of interannual variability and large spatial contrasts between wet mountainous regions in the north and dry regions in the southern plains. Unlike other European regions, IP was poorly monitored for precipitation during 19th century. Here we present a new approach to fill this gap. A set of 26 atmospheric circulation weather types (Trigo R.M. and DaCamara C.C., 2000) derived from a recent SLP dataset, the EMULATE (European and North Atlantic daily to multidecadal climate variability) Project, was used to reconstruct Iberian monthly precipitation from October to March during 1851-1947. Principal Component Regression Analysis was chosen to develop monthly precipitation reconstruction back to 1851 and calibrated over 1948-2003 period for 3030 monthly precipitation series of high-density homogenized MOPREDAS (Monthly Precipitation Database for Spain and Portugal) database. Validation was conducted over 1920-1947 at 15 key site locations. Results show high model performance for selected months, with a mean coefficient of variation (CV) around 0.6 during validation period. Lower CV values were achieved in western area of IP. Trigo, R. M., and DaCamara, C.C., 2000: "Circulation weather types and their impact on the precipitation regime in Portugal". Int. J. Climatol., 20, 1559-1581.

Novel genes on rat chromosome 10 are linked to body fat mass, preadipocyte number and adipocyte size.

PubMed

Weingarten, A; Turchetti, L; Krohn, K; Klöting, I; Kern, M; Kovacs, P; Stumvoll, M; Blüher, M; Klöting, N

2016-12-01

The genetic architecture of obesity is multifactorial. We have previously identified a quantitative trait locus (QTL) on rat chromosome 10 in a F2 cross of Wistar Ottawa Karlsburg (WOKW) and Dark Agouti (DA) rats responsible for obesity-related traits. The QTL was confirmed in congenic DA.WOKW10 rats. To pinpoint the region carrying causal genes, we established two new subcongenic lines, L1 and L2, with smaller refined segments of chromosome 10 to identify novel candidate genes. All lines were extensively characterized under different diet conditions. We employed transcriptome analysis in visceral adipose tissue (VAT) by RNA-Seq technology to identify potential underlying genes in the segregating regions. Three candidate genes were measured in human paired samples of VAT and subcutaneous (SC) AT (SAT) (N=304) individuals with a wide range of body weight and glucose homeostasis parameters. DA.WOKW and L1 subcongenic lines were protected against body fat gain under high-fat diet (HFD), whereas L2 and DA had significantly more body fat after high-fat feeding. Interestingly, adipocyte size distribution in SAT and epigonadal AT of L1 subcongenic rats did not undergo typical ballooning under HFD and the number of preadipocytes in AT was significantly elevated in L2 compared with L1 and parental rats. Transcriptome analysis identified three candidate genes in VAT on rat chromosome 10. In humans, these candidate genes were differentially expressed between SAT and VAT. Moreover, HID1 mRNA significantly correlates with parameters of obesity and glucose metabolism. Our data suggest novel candidate genes for obesity that map on rat chromosome 10 in an interval 102.2-104.7 Mb and are strongly associated with body fat mass regulation, preadipocyte number and adipocyte size in rats. Among those genes, AT head involution defective (HID1) mRNA expression may be relevant for human fat distribution and glucose homeostasis.

MtDNA diversity among four Portuguese autochthonous dog breeds: a fine-scale characterisation

PubMed Central

van Asch, Barbara; Pereira, Luísa; Pereira, Filipe; Santa-Rita, Pedro; Lima, Manuela; Amorim, António

2005-01-01

Background The picture of dog mtDNA diversity, as obtained from geographically wide samplings but from a small number of individuals per region or breed, has revealed weak geographic correlation and high degree of haplotype sharing between very distant breeds. We aimed at a more detailed picture through extensive sampling (n = 143) of four Portuguese autochthonous breeds – Castro Laboreiro Dog, Serra da Estrela Mountain Dog, Portuguese Sheepdog and Azores Cattle Dog-and comparatively reanalysing published worldwide data. Results Fifteen haplotypes belonging to four major haplogroups were found in these breeds, of which five are newly reported. The Castro Laboreiro Dog presented a 95% frequency of a new A haplotype, while all other breeds contained a diverse pool of existing lineages. The Serra da Estrela Mountain Dog, the most heterogeneous of the four Portuguese breeds, shared haplotypes with the other mainland breeds, while Azores Cattle Dog shared no haplotypes with the other Portuguese breeds. A review of mtDNA haplotypes in dogs across the world revealed that: (a) breeds tend to display haplotypes belonging to different haplogroups; (b) haplogroup A is present in all breeds, and even uncommon haplogroups are highly dispersed among breeds and continental areas; (c) haplotype sharing between breeds of the same region is lower than between breeds of different regions and (d) genetic distances between breeds do not correlate with geography. Conclusion MtDNA haplotype sharing occurred between Serra da Estrela Mountain dogs (with putative origin in the centre of Portugal) and two breeds in the north and south of the country-with the Castro Laboreiro Dog (which behaves, at the mtDNA level, as a sub-sample of the Serra da Estrela Mountain Dog) and the southern Portuguese Sheepdog. In contrast, the Azores Cattle Dog did not share any haplotypes with the other Portuguese breeds, but with dogs sampled in Northern Europe. This suggested that the Azores Cattle Dog descended maternally from Northern European dogs rather than Portuguese mainland dogs. A review of published mtDNA haplotypes identified thirteen non-Portuguese breeds with sufficient data for comparison. Comparisons between these thirteen breeds, and the four Portuguese breeds, demonstrated widespread haplotype sharing, with the greatest diversity among Asian dogs, in accordance with the central role of Asia in canine domestication. PMID:15972107

The epidemiology of travel-related Salmonella Enteritidis in Ontario, Canada, 2010–2011

PubMed Central

2012-01-01

Background Increases in the number of salmonellosis cases due to Salmonella Enteritidis (SE) in 2010 and 2011 prompted a public health investigation in Ontario, Canada. In this report, we describe the current epidemiology of travel-related (TR) SE, compare demographics, symptoms and phage types (PTs) of TR and domestically-acquired (DA) cases, and estimate the odds of acquiring SE by region of the world visited. Methods All incident cases of culture confirmed SE in Ontario obtained from isolates and specimens submitted to public health laboratories were included in this study. Demographic and illness characteristics of TR and DA cases were compared. A national travel survey was used to provide estimates for the number of travellers to various destinations to approximate rates of SE in travellers. Multivariate logistic regression was used to estimate the odds of acquiring SE when travelling to various world regions. Results Overall, 51.9% of SE cases were TR during the study period. This ranged from 35.7% TR cases in the summer travel period to 65.1% TR cases in the winter travel period. Compared to DA cases, TR cases were older and were less likely to seek hospital care. For Ontario travellers, the adjusted odds of acquiring SE was the highest for the Caribbean (OR 37.29, 95% CI 17.87-77.82) when compared to Europe. Certain PTs were more commonly associated with travel (e.g., 1, 4, 5b, 7a, Atypical) than with domestic infection. Of the TR cases, 88.9% were associated with travel to the Caribbean and Mexico region, of whom 90.1% reported staying on a resort. Within this region, there were distinct associations between PTs and countries. Conclusions There is a large burden of TR illness from SE in Ontario. Accurate classification of cases by travel history is important to better understand the source of infections. The findings emphasize the need to make travellers, especially to the Caribbean, and health professionals who provide advice to travellers, aware of this risk. The findings may be generalized to other jurisdictions with travel behaviours in their residents similar to Ontario residents. PMID:22537320

Brazilian environmental legislation and scenarios for carbon balance in Areas of Permanent Preservation (APP) in dairy livestock regions

NASA Astrophysics Data System (ADS)

Hott, M. C.; Fonseca, L. D.; Andrade, R. G.

2011-12-01

The present study aimed at mapping some categories of Areas of Permanent Preservation (APP) for natural regeneration of semideciduous forests in the regions of Zona da Mata and Campo das Vertentes, Minas Gerais State (Figure 1), and from this to establish what impact the deployment of APP over area of pastures and subsequently milk production and carbon sequestration, considering areas of pasture as one of major factors for the dairy farming in the regions concerned. From the altimetric information from MDE, it was possible to extract morphological and morphometrical data to estimate the areas of APP. We used imagery of MODIS/Terra for extraction of the pastures areas from the vegetation index data NDVI to intersect with the estimated area of APP. In a linear or deterministic scenario of deployment of APPs over in the pasture areas considering that wich are proportionately responsible for sizing the herd, and thus for the milk production in extensive livestock, despite the existence of numerous other factors, there would be an impact 12% in the production of Campo das Vertentes region and 21.5% for the Zona da Mata. In this scenario, according to the carbon balance of forests and livestock, there would be a positive balance with the deployment of areas of permanent preservation and, subsequent promotion of natural regeneration. Considering the current grazing area of the Zona da Mata and Campo das Vertentes, 1.6 million hectares, with the carbon balance estimated at 1 ton/hectare/year, 300,000 hectares would have a balance of 5 ton/hectare/year in whole cycle of 40 years, totaling 200 tons carbon by hectare, or additional 48 million tons fixed, considering 4 tons more than pastures in the case of semideciduous forest. At the end of the cycle or forest climax, there would still be positive carbon balance, estimated as a balance of 2 ton/hectare/year. However, despite the higher carbon balance for the semideciduous forest, compared to livestock, it is important to maintain a balance between conservation of natural resources, land suitability and demand for food, especially for milk in these regions, which provide inputs for the dairy industry. The brazilian environmental legislation faces a turbulent period of change, but certainly it can contribute to increase carbon sequestration.

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

Ogami, Koichi; Cho, Rihe; Hoshino, Shin-ichi, E-mail: hoshino@phar.nagoya-cu.ac.jp

Highlights: ► So far, only an enzymatically inactive isoform of PAPD7 was reported. ► The novel isoform: PAPD7 l shows robust nucleotidyl transferase activity. ► The newly identified amino terminal region is required for the activity. ► PAPD7 l localizes to the nucleoplasm. ► The N terminal region identified is also required for the nuclear localization. - Abstract: Non-canonical poly(A) polymerases (ncPAPs) catalyze the addition of poly(A) tail to the 3′ end of RNA to play pivotal roles in the regulation of gene expression and also in quality control. Here we identified a novel isoform of the 7th member ofmore » ncPAPs: PAPD7 (PAPD7 l), which contains 230 extra amino acids at the amino terminus of the previously identified PAPD7 (PAPD7 s). In sharp contrast to the inactive PAPD7 s, PAPD7 l showed robust nucleotidyl transferase activity when tethered to an RNA. A region required for the activity was localized to 187–219 aa, and this region was also required for the nuclear retention of PAPD7 l. Western blot analysis revealed that 94 kDa band (corresponding to PAPD7 l) but not 62 kDa band (corresponding to PAPD7 s) detected by PAPD7 antibody was specifically depleted by treatment with PAPD7 siRNA in both HeLa and U2OS cells. These results suggest that PAPD7 l is the major and active isoform of PAPD7 expressed in cells.« less

Photoaffinity labeling of the Torpedo californica nicotinic acetylcholine receptor with an aryl azide derivative of phosphatidylserine

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

Blanton, M.P.; Wang, H.H.

1990-02-06

A photoactivatable analogue of phosphatidylserine, {sup 125}I-labeled 4-azidosalicylic acid-phosphatidylserine ({sup 125}I ASA-PS), was used to label both native acetylcholine receptor (AchR)-rich membranes from Torpedo californica and AchR membranes affinity purified from Torpedo reconstituted into asolectin vesicles. The radioiodinated arylazido group attaches directly to the phospholipid head group and thus probes for regions of the AchR structure in contact with the negatively charged head group of phosphatidylserine. All four subunits of the AchR incorporated the label, with the {alpha} subunit incorporating approximately twice as much as each of the other subunits on a per mole basis. The regions of the AchRmore » {alpha} subunit that incorporated {sup 125}I ASA-PS were mapped by Staphylococcus aureus V8 protease digestion. The majority of label incorporated into fragments representing a more complete digestion of the {alpha} subunit was localized to 11.7- and 10.1-kDa V8 cleavage fragments, both beginning at Asn-339 and of sufficient length to contain the hydrophobic region M4. An 18.7-kDa fragment beginning at Ser-173 and of sufficient length to contain the hydrophobic regions M1, M2, and M3 was also significantly labeled. In contrast, V8 cleavage fragments representing roughly a third of the amino-terminal portion of the {alpha} subunit incorporated little or no detectable amount of probe.« less

Associative learning and regional white matter deficits in mild cognitive impairment.

PubMed

Boespflug, Erin L; Eliassen, James; Welge, Jeffrey; Krikorian, Robert

2014-01-01

While diagnostic criteria for Alzheimer's disease (AD) include neuroimaging biomarkers, there remains no definitive biomarker of mild cognitive impairment (MCI). MCI is a risk factor for AD that may be amenable to early intervention. Early decline in white matter (WM) integrity identified by diffusion tensor imaging (DTI) is a predictor of future progression of neurodegeneration. Identify regionally specific WM differences between individuals with MCI and those with age-associated memory impairment (AAMI) and relationships with specific memory decrements. DTI and neuropsychological data were acquired from 38 participants (23 MCI and 15 AAMI). A region of interest approach was used to evaluate regional differences between groups and correlative relationships with performance on memory tasks. Fornix WM had higher mean (MD), radial (DR), and axial (DA) diffusivity in MCI participants relative to AAMI. Temporal stem (TS) WM had higher MD and DR in MCI than in AAMI. In MCI, TS MD and DR varied, while fornix MD and DR was uniformly high, and in AAMI, TS MD and DR were uniformly low and fornix MD and DR varied. In MCI, TS MD and DA were inversely associated with associative learning but not list learning. In addition to supporting prior evidence implicating the fornix in early AD pathology, these data implicate a profile of neurodegeneration associated with early MCI. Further, they suggest that associative learning tasks are more sensitive to early neurodegeneration and may be useful in identifying individuals at risk for AD.

32 CFR Appendix H to Part 623 - References

Code of Federal Regulations, 2014 CFR

2014-07-01

... MATERIEL Pt. 623, App. H Appendix H to Part 623—References AR 1-4Deployment of DA Resources in Support of... Administration (OP/GSA) Regional Field Boards in Crisis Management Operations. AR 28-19Department of the Army Domestic Action Program. AR 34-1United States Army Participation in International Military Rationalization...

32 CFR Appendix H to Part 623 - References

Code of Federal Regulations, 2013 CFR

2013-07-01

... MATERIEL Pt. 623, App. H Appendix H to Part 623—References AR 1-4Deployment of DA Resources in Support of... Administration (OP/GSA) Regional Field Boards in Crisis Management Operations. AR 28-19Department of the Army Domestic Action Program. AR 34-1United States Army Participation in International Military Rationalization...

32 CFR Appendix H to Part 623 - References

Code of Federal Regulations, 2012 CFR

2012-07-01

... MATERIEL Pt. 623, App. H Appendix H to Part 623—References AR 1-4Deployment of DA Resources in Support of... Administration (OP/GSA) Regional Field Boards in Crisis Management Operations. AR 28-19Department of the Army Domestic Action Program. AR 34-1United States Army Participation in International Military Rationalization...

Measuring short-crop reference evapotranspiration in a humid region using electronic atmometers

USDA-ARS?s Scientific Manuscript database

The Crop Water Use phone app is a weather-based program developed by the Missouri Extension Service to help farmers with irrigation scheduling. A limitation of the program is that it only works on Missouri fields. The app is linked to the state agricultural weather station network, which supplies da...

Detection of pit fragments in fresh cherries using near infrared spectroscopy

USDA-ARS?s Scientific Manuscript database

NIR spectroscopy in the wavelength region from 900nm to 2600nm was evaluated as the basis for a rapid, non-destructive method for the detection of pits and pit fragments in fresh cherries. Partial Least Squares discriminant analysis (PLS-DA) following various spectral pretreatments was applied to sp...

The NWRA Classification Infrastructure: description and extension to the Discriminant Analysis Flare Forecasting System (DAFFS)

NASA Astrophysics Data System (ADS)

Leka, K. D.; Barnes, Graham; Wagner, Eric

2018-04-01

A classification infrastructure built upon Discriminant Analysis (DA) has been developed at NorthWest Research Associates for examining the statistical differences between samples of two known populations. Originating to examine the physical differences between flare-quiet and flare-imminent solar active regions, we describe herein some details of the infrastructure including: parametrization of large datasets, schemes for handling "null" and "bad" data in multi-parameter analysis, application of non-parametric multi-dimensional DA, an extension through Bayes' theorem to probabilistic classification, and methods invoked for evaluating classifier success. The classifier infrastructure is applicable to a wide range of scientific questions in solar physics. We demonstrate its application to the question of distinguishing flare-imminent from flare-quiet solar active regions, updating results from the original publications that were based on different data and much smaller sample sizes. Finally, as a demonstration of "Research to Operations" efforts in the space-weather forecasting context, we present the Discriminant Analysis Flare Forecasting System (DAFFS), a near-real-time operationally-running solar flare forecasting tool that was developed from the research-directed infrastructure.

Pectic polysaccharides from Panax ginseng as the antirotavirus principals in ginseng.

PubMed

Baek, Seung-Hoon; Lee, Jin Gyun; Park, Seo Young; Bae, Ok Nam; Kim, Dong-Hyun; Park, Jeong Hill

2010-08-09

To evaluate the antidiarrheal effect of ginseng, the active principals of ginseng were studied in vitro model of rotavirus infection, the leading cause of severe diarrhea. Two pectic polysaccharides, named as GP50-dHR (56.0 kDa) and GP50-eHR (77.0 kDa), were purified from hot water extract of ginseng by bioassay-linked fractionation. Both polysaccharides rescued cell viability from rotavirus infection dose-dependently (IC50 are 15 and 10 microg/mL, respectively). Both polysaccharides had common structural features of homogalacturonan backbone with hairy regions of rhamnogalacturonan type I. Arabinose-rich side chains with abundant branch points were unique in GP50-eHR and may contribute to a greater antirotavirus effect of GP50-eHR than GP50-dHR. Because homogalacturonan itself did not show an antirotavirus effect, hairy regions might be functional sites. Of note, the antirotavirus effect of both polysaccharides resulted from inhibiting rotavirus attachment to cells. Together with a wide range of noncytotoxicity, these findings suggest that ginseng polysaccharides are viable therapeutic options for rotavirus diarrhea.

The 1-aminocyclopropane-1-carboxylate synthase of Cucurbita. Purification, properties, expression in Escherichia coli, and primary structure determination by DNA sequence analysis.

PubMed

Sato, T; Oeller, P W; Theologis, A

1991-02-25

The key regulatory enzyme in the biosynthetic pathway of the plant hormone ethylene is 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (EC 4.4.1.14). We have partially purified ACC synthase 6,000-fold from Cucurbita fruit tissue treated with indoleacetic acid + benzyladenine + aminooxyacetic acid + LiCl. The enzyme has a specific activity of 35,000 nmol/h/mg protein, a pH optimum of 9.5, an isoelectric point of 5.0, a Km of 17 microM with respect to S-adenosylmethionine, and is a dimer of two identical subunits of approximately 46,000 Da each. The subunit exists in vivo as a 55,000-Da species similar in size to the primary in vitro translation product. DNA sequence analysis of the cDNA clone pACC1 revealed that the coding region of the ACC synthase mRNA spans 493 amino acids corresponding to a 55,779-Da polypeptide; and expression of the coding sequence (pACC1) in Escherichia coli as a COOH terminus hybrid of beta-galactosidase or as a nonhybrid polypeptide catalyzed the conversion of S-adenosylmethionine to ACC (Sato, T., and Theologis, A. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6621-6625). Immunoblotting experiments herein show that the molecular mass of the beta-galactosidase hybrid polypeptide is 170,000 Da, and the size of the largest nonhybrid polypeptide is 53,000 Da. The data suggest that the enzyme is post-translationally processed during protein purification.

Selective detection of thiosulfate-containing peptides using tandem mass spectrometry.

PubMed

Raftery, Mark J

2005-01-01

Incubation of proteins or peptides containing disulfide bonds (S-S) with sodium sulfite (Na(2)SO(3)) cleaves S-S bonds producing approximately equimolar amounts of free thiols (-SH) and thiosulfates (-S-SO(3)H), a process known as sulfitolysis. Proteins and peptides containing thiosulfates were separated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by mass spectrometry (MS) and peptide mapping. The mass of the thiosulfate-containing peptide formed from oxidized insulin B chain was 3478.02 Da, 80 Da greater than the reduced peptide and corresponding precisely to addition of sulfur trioxide (SO(3)). Disulfide bond cleavage was also observed using RP-HPLC and MS after incubation of the intramolecular homodimer of mouse S100A8 (mass 20614 Da). The mass of HPLC-separated A8-SH was 10308 Da, and 10388 Da for A8-S-SO(3)H. Loss of SO(3) from multiply charged precursor ions was generally observed at elevated declustering potentials in the source region or within q(2) at relatively low collision energies (approximately 20 V). The characteristic loss of SO(3) at low collision energies preceded peptide backbone fragmentations at higher collision energies. Accurate mass measurement and charge-state discrimination, using a hybrid quadrupole time-of-flight mass spectrometer, allowed specific detection of thiosulfate-containing peptides. An information-dependent acquisition method, where the switch criterion was loss of m/z 79.9568, specifically identified 11 thiosulfate-containing peptides using nano-LC/MS from a tryptic digest of bovine serum albumin (BSA).

Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine.

PubMed

Ericson, Mia; Molander, Anna; Stomberg, Rosita; Söderpalm, Bo

2006-06-01

The mesolimbic dopamine (DA) system, projecting from the ventral tegmental area (VTA) to the nucleus accumbens (nAcc), is involved in reward-related behaviours and addictive processes, such as alcoholism and drug addiction. It was recently suggested that strychnine-sensitive glycine receptors (GlyR) in the nAcc regulate both basal and ethanol-induced mesolimbic DA activity via a neuronal loop involving endogenous activation of nicotinic acetylcholine receptors (nAChR) in the VTA. However, as the nAcc appears to contain few glycine-immunoreactive cell bodies or fibres, the question as to what may be the endogenous ligand for GlyRs in this brain region remains open. Here we have investigated whether the amino acid taurine could serve this purpose using in vivo microdialysis in awake, freely moving male Wistar rats. Local perfusion of taurine (1, 10 or 100 mm in the perfusate) increased DA levels in the nAcc. The taurine (10 mm)-induced DA increase was, similarly to that previously observed after ethanol, completely blocked by (i) perfusion of the competitive GlyR antagonist strychnine in the nAcc, (ii) perfusion of the nAChR antagonist mecamylamine (100 microm) in the VTA, and (iii) systemic administration of the acetylcholine-depleting drug vesamicol (0.4 mg/kg, i.p). The present results suggest that taurine may be an endogenous ligand for GlyRs in the nAcc and that the taurine-induced elevation of DA levels in this area, similarly to that observed after local ethanol, is mediated via a neuronal loop involving endogenous activation of nAChRs in the VTA.

Dopamine D2 receptor levels in striatum, thalamus, substantia nigra, limbic regions, and cortex in schizophrenic subjects.

PubMed

Kessler, Robert M; Woodward, Neil D; Riccardi, Patrizia; Li, Rui; Ansari, M Sib; Anderson, Sharlett; Dawant, Benoit; Zald, David; Meltzer, Herbert Y

2009-06-15

Studies in schizophrenic patients have reported dopaminergic abnormalities in striatum, substantia nigra, thalamus, anterior cingulate, hippocampus, and cortex that have been related to positive symptoms and cognitive impairments. [(18)F]fallypride positron emission tomography studies were performed in off-medication or never-medicated schizophrenic subjects (n = 11, 6 men, 5 women; mean age of 30.5 +/- 8.0 [SD] years; 4 drug-naive) and age-matched healthy subjects (n = 11, 5 men, 6 women, mean age of 31.6 +/- 9.2 [SD]) to examine dopamine D(2) receptor (DA D(2)r) levels in the caudate, putamen, ventral striatum, medial thalamus, posterior thalamus, substantia nigra, amygdala, temporal cortex, anterior cingulate, and hippocampus. In schizophrenic subjects, increased DA D(2)r levels were seen in the substantia nigra bilaterally; decreased levels were seen in the left medial thalamus. Correlations of symptoms with ROI data demonstrated a significant correlation of disorganized thinking/nonparanoid delusions with the right temporal cortex ROI (r = .94, p = .0001), which remained significant after correction for multiple comparisons (p < .03). Correlations of symptoms with parametric images of DA D(2)r levels revealed no significant clusters of correlations with negative symptoms but significant clusters of positive correlations of total positive symptoms, delusions and bizarre behavior with the lateral and anterior temporal cortex, and hallucinations with the left ventral striatum. The results of this study demonstrate abnormal DA D(2)r-mediated neurotransmission in the substantia nigra consistent with nigral dysfunction in schizophrenia and suggest that both temporal cortical and ventral striatal DA D(2)r mediate positive symptoms.

Five unique open reading frames of infectious laryngotracheitis virus are expressed during infection but are dispensable for virus replication in cell culture.

PubMed

Veits, Jutta; Mettenleiter, Thomas C; Fuchs, Walter

2003-06-01

The chicken alphaherpesvirus infectious laryngotracheitis virus (ILTV) exhibits several unique genetic features including an internal inversion of a conserved part of the unique long genome region. At one end, this inversion is preceded by a cluster of five open reading frames (ORFs) of 335-411 codons, designated ORF A to ORF E, that are not present in any other known herpesvirus genome. In this report we analysed expression of these genes and identified the corresponding viral RNA and protein products. Northern blot analyses showed 3'-coterminal transcripts of ORFs A and B, and monocistronic mRNAs of ORFs C and D. ORF E is part of a 3'-coterminal transcription unit that includes the conserved glycoprotein H and thymidine kinase genes. Monospecific antisera obtained after immunization of rabbits with bacterial fusion proteins allowed detection of the protein products of ORF A (40 kDa), ORF B (34 kDa), ORF C (38 and 30 kDa), ORF D (41 kDa) and ORF E (44 kDa) in ILTV-infected cells. For functional analyses, five virus recombinants possessing deletions within the individual ORFs and concomitant insertions of a reporter gene cassette encoding green fluorescent protein were generated. All virus mutants were replication competent in cell culture, but exhibited reduced virus titres or plaque sizes when compared to wild-type ILTV. These findings indicate that the ILTV-specific ORF A to ORF E genes might be important for virus replication in the natural host organism.

Commercial tree species discrimination using airborne AISA Eagle hyperspectral imagery and partial least squares discriminant analysis (PLS-DA) in KwaZulu-Natal, South Africa

NASA Astrophysics Data System (ADS)

Peerbhay, Kabir Yunus; Mutanga, Onisimo; Ismail, Riyad

2013-05-01

Discriminating commercial tree species using hyperspectral remote sensing techniques is critical in monitoring the spatial distributions and compositions of commercial forests. However, issues related to data dimensionality and multicollinearity limit the successful application of the technology. The aim of this study was to examine the utility of the partial least squares discriminant analysis (PLS-DA) technique in accurately classifying six exotic commercial forest species (Eucalyptus grandis, Eucalyptus nitens, Eucalyptus smithii, Pinus patula, Pinus elliotii and Acacia mearnsii) using airborne AISA Eagle hyperspectral imagery (393-900 nm). Additionally, the variable importance in the projection (VIP) method was used to identify subsets of bands that could successfully discriminate the forest species. Results indicated that the PLS-DA model that used all the AISA Eagle bands (n = 230) produced an overall accuracy of 80.61% and a kappa value of 0.77, with user's and producer's accuracies ranging from 50% to 100%. In comparison, incorporating the optimal subset of VIP selected wavebands (n = 78) in the PLS-DA model resulted in an improved overall accuracy of 88.78% and a kappa value of 0.87, with user's and producer's accuracies ranging from 70% to 100%. Bands located predominantly within the visible region of the electromagnetic spectrum (393-723 nm) showed the most capability in terms of discriminating between the six commercial forest species. Overall, the research has demonstrated the potential of using PLS-DA for reducing the dimensionality of hyperspectral datasets as well as determining the optimal subset of bands to produce the highest classification accuracies.

Preparing for the Future Nankai Trough Tsunami: A Data Assimilation and Inversion Analysis From Various Observational Systems

NASA Astrophysics Data System (ADS)

Mulia, Iyan E.; Inazu, Daisuke; Waseda, Takuji; Gusman, Aditya Riadi

2017-10-01

The future Nankai Trough tsunami is one of the imminent threats to the Japanese coastal communities that could potentially cause a catastrophic event. As a part of the countermeasure efforts for such an occurrence, this study analyzes the efficacy of combining tsunami data assimilation (DA) and waveform inversion (WI). The DA is used to continuously refine a wavefield model whereas the WI is used to estimate the tsunami source. We consider a future scenario of the Nankai Trough tsunami recorded at various observational systems, including ocean bottom pressure (OBP) gauges, global positioning system (GPS) buoys, and ship height positioning data. Since most of the OBP gauges are located inside the source region, the recorded tsunami signals exhibit significant offsets from surface measurements due to coseismic seafloor deformation effects. Such biased data are not applicable to the standard DA, but can be taken into account in the WI. On the other hand, the use of WI for the ship data may not be practical because a considerably large precomputed tsunami database is needed to cope with the spontaneous ship locations. The DA is more suitable for such an observational system as it can be executed sequentially in time and does not require precomputed scenarios. Therefore, the combined approach of DA and WI allows us to concurrently make use of all observational resources. Additionally, we introduce a bias correction scheme for the OBP data to improve the accuracy, and an adaptive thinning of observations to determine the efficient number of observations.

STRESS AND FAILURE ANALYSIS OF RAPIDLY ROTATING ASTEROID (29075) 1950 DA

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

Hirabayashi, Masatoshi; Scheeres, Daniel J., E-mail: masatoshi.hirabayashi@colorado.edu

Rozitis et al. recently reported that near-Earth asteroid (29075) 1950 DA, whose bulk density ranges from 1.0 g cm{sup –3} to 2.4 g cm{sup –3}, is a rubble pile and requires a cohesive strength of at least 44-76 Pa to keep from failing due to its fast spin period. Since their technique for giving failure conditions required the averaged stress over the whole volume, it discarded information about the asteroid's failure mode and internal stress condition. This paper develops a finite element model and revisits the stress and failure analysis of 1950 DA. For the modeling, we do not consider material hardening andmore » softening. Under the assumption of an associated flow rule and uniform material distribution, we identify the deformation process of 1950 DA when its constant cohesion reaches the lowest value that keeps its current shape. The results show that to avoid structural failure the internal core requires a cohesive strength of at least 75-85 Pa. It suggests that for the failure mode of this body, the internal core first fails structurally, followed by the surface region. This implies that if cohesion is constant over the whole volume, the equatorial ridge of 1950 DA results from a material flow going outward along the equatorial plane in the internal core, but not from a landslide as has been hypothesized. This has additional implications for the likely density of the interior of the body.« less

Macromolecules of extracellular matrix: determination of selective structures and their functional significance.

PubMed

Butler, William T

2008-01-01

In this brief review, I recount events and scientific endeavors in which I have been privileged to participate. The descriptive information includes discovery and characterization of hydroxylysine glycosides from collagen, isolation of dentin sialoprotein (DSP), investigations on dentin phosphoprotein (DPP), and the discovery of a single gene for both DSP and DPP that requires posttranslational proteolytic cleavage of the parent DSPP molecule to generate the two fragments. Finally, I address our unexpected finding of fragments of DMP1 in bone extracts. These fragments are from the NH2-terminal (37 kDa) and COOH-terminal (57 kDa) regions of DMP1. Our studies showed that, similar to DSPP, DMP1 is proteolytically processed by cleavages at X-Asp bonds.

[Deforestation in the state of Mato Grosso in the book Journey around Brazil 1875-1878, by the doctor João Severiano da Fonseca].

PubMed

Ferraro, Mário Roberto; Figueirôa, Silvia Fernanda de Mendonça

2017-01-01

This presents reflections on scientific production issued by the Commission for the Demarcation of the Empire's Border Limits with Bolivia, with a focus on the environmental destruction of Mato Grosso state, as reported in João Severiano da Fonseca's book, Journey around Brazil 1875-1878. Fonseca reported severe deforestation on the banks of the river Paraguay and advocated for protectionist measures from the state government. He set out a vision for Mato Grosso's development that involved better use of the state's natural resources, raw materials exports, and regional industrialization support. The methodology created an interface between environmental history and history of the sciences.

Identification of candidates for interacting partners of the tail domain of DcNMCP1, a major component of the Daucus carota nuclear lamina-like structure.

PubMed

Mochizuki, Ryota; Tsugama, Daisuke; Yamazaki, Michihiro; Fujino, Kaien; Masuda, Kiyoshi

2017-05-04

NMCP/CRWN (NUCLEAR MATRIX CONSTITUENT PROTEIN/CROWDED NUCLEI) is a major component of a protein fibrous meshwork (lamina-like structure) on the plant inner nuclear membrane. NMCP/CRWN contributes to regulating nuclear shape and nuclear functions. An NMCP/CRWN protein in Daucus carota (DcNMCP1) is localized to the nuclear periphery in interphase cells, and surrounds chromosomes in cells in metaphase and anaphase. The N-terminal region and the C-terminal region of DcNMCP1 are both necessary for localizing DcNMCP1 to the nuclear periphery. Here candidate interacting partners of the amino acid position 975-1053 of DcNMCP1 (T975-1053), which is present in the C-terminal region and contains a conserved sequence that plays a role in localizing DcNMCP1 to the nuclear periphery, are screened for. Arabidopsis thaliana nuclear proteins were subjected to far-Western blotting with GST-fused T975-1053 as a probe, and signals were detected at the positions corresponding to ∼70, ∼40, and ∼18 kDa. These ∼70, ∼40, and ∼18 kDa nuclear proteins were identified by mass spectrometry, and subjected to a yeast 2-hybrid (Y2H) analysis with T975-1053 as bait. In this analysis, the ∼40 kDa protein ARP7, which is a nuclear actin-related protein possibly involved in regulating chromatin structures, was confirmed to interact with T975-1053. Independently of the far-Western blotting, a Y2H screen was performed using T975-1053 as bait. Targeted Y2H assays confirmed that 3 proteins identified in the screen, MYB3, SINAT1, and BIM1, interact with T975-1053. These proteins might have roles in NMCP/CRWN protein-mediated biologic processes.

Inhibition of 5a-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation

PubMed Central

Devoto, Paola; Frau, Roberto; Bini, Valentina; Pillolla, Giuliano; Saba, Pierluigi; Flore, Giovanna; Corona, Marta; Marrosu, Francesco; Bortolato, Marco

2012-01-01

Summary Cogent evidence highlights a key role of neurosteroids and androgens in schizophrenia. We recently reported that inhibition of steroid 5α-reductase (5αR), the rate-limiting enzyme in neurosteroid synthesis and androgen metabolism, elicits antipsychotic-like effects in humans and animal models, without inducing extrapyramidal side effects. To elucidate the anatomical substrates mediating these effects, we investigated the contribution of peripheral and neural structures to the behavioral effects of the 5αR inhibitor finasteride (FIN) on the prepulse inhibition (PPI) of the acoustic startle reflex (ASR), a rat paradigm that dependably simulates the sensorimotor gating impairments observed in schizophrenia and other neuropsychiatric disorders. The potential effect of drug-induced ASR modifications on PPI was excluded by measuring this index both as percent (%PPI) and absolute values (ΔPPI). In both orchidectomized and sham-operated rats, FIN prevented the %PPI deficits induced by the dopamine (DA) receptor agonists apomorphine (APO, 0.25 mg/kg, SC) and d-amphetamine (AMPH, 2.5 mg/kg, SC), although the latter effect was not corroborated by ΔPPI analysis. Conversely, APO-induced PPI deficits were countered by FIN infusions in the brain ventricles (10 μg/1 μl) and in the nucleus accumbens (NAc) shell and core (0.5 μg/0.5 μl/side). No significant PPI-ameliorating effect was observed following FIN injections in other brain regions, including dorsal caudate, basolateral amygdala, ventral hippocampus and medial prefrontal cortex, although a statistical trend was observed for the latter region. The efflux of DA in NAc was increased by systemic, but not intracerebral FIN administration. Taken together, these findings suggest that the role of 5αR in gating regulation is based on post-synaptic mechanisms in the NAc, and is not directly related to alterations in DA efflux in this region. PMID:22029952

Comparative Analysis of Three Brevetoxin-Associated Bottlenose Dolphin (Tursiops truncatus) Mortality Events in the Florida Panhandle Region (USA)

PubMed Central

Twiner, Michael J.; Flewelling, Leanne J.; Fire, Spencer E.; Bowen-Stevens, Sabrina R.; Gaydos, Joseph K.; Johnson, Christine K.; Landsberg, Jan H.; Leighfield, Tod A.; Mase-Guthrie, Blair; Schwacke, Lori; Van Dolah, Frances M.; Wang, Zhihong; Rowles, Teresa K.

2012-01-01

In the Florida Panhandle region, bottlenose dolphins (Tursiops truncatus) have been highly susceptible to large-scale unusual mortality events (UMEs) that may have been the result of exposure to blooms of the dinoflagellate Karenia brevis and its neurotoxin, brevetoxin (PbTx). Between 1999 and 2006, three bottlenose dolphin UMEs occurred in the Florida Panhandle region. The primary objective of this study was to determine if these mortality events were due to brevetoxicosis. Analysis of over 850 samples from 105 bottlenose dolphins and associated prey items were analyzed for algal toxins and have provided details on tissue distribution, pathways of trophic transfer, and spatial-temporal trends for each mortality event. In 1999/2000, 152 dolphins died following extensive K. brevis blooms and brevetoxin was detected in 52% of animals tested at concentrations up to 500 ng/g. In 2004, 105 bottlenose dolphins died in the absence of an identifiable K. brevis bloom; however, 100% of the tested animals were positive for brevetoxin at concentrations up to 29,126 ng/mL. Dolphin stomach contents frequently consisted of brevetoxin-contaminated menhaden. In addition, another potentially toxigenic algal species, Pseudo-nitzschia, was present and low levels of the neurotoxin domoic acid (DA) were detected in nearly all tested animals (89%). In 2005/2006, 90 bottlenose dolphins died that were initially coincident with high densities of K. brevis. Most (93%) of the tested animals were positive for brevetoxin at concentrations up to 2,724 ng/mL. No DA was detected in these animals despite the presence of an intense DA-producing Pseudo-nitzschia bloom. In contrast to the absence or very low levels of brevetoxins measured in live dolphins, and those stranding in the absence of a K. brevis bloom, these data, taken together with the absence of any other obvious pathology, provide strong evidence that brevetoxin was the causative agent involved in these bottlenose dolphin mortality events. PMID:22916189

RAPD and SCAR markers as potential tools for detection of milk origin in dairy products: Adulterant sheep breeds in Serra da Estrela cheese production.

PubMed

Cunha, Joana T; Ribeiro, Tânia I B; Rocha, João B; Nunes, João; Teixeira, José A; Domingues, Lucília

2016-11-15

Serra da Estrela Protected Designation of Origin (PDO) cheese is the most famous Portuguese cheese and has a high commercial value. However, the adulteration of production with cheaper/lower-quality milks from non-autochthones ovine breeds compromises the quality of the final product and undervalues the original PDO cheese. A Randomly Amplified Polymorphic DNA (RAPD) method was developed for efficient detection of adulterant breeds in milk mixtures used for fraudulent production of this cheese. Furthermore, Sequence Characterized Amplified Region (SCAR) markers were designed envisioning the detection of milk adulteration in processed dairy foods. The RAPD-SCAR technique is here described, for the first time, to be potentially useful for detection of milk origin in dairy products. In this sense, our findings will play an important role on the valorization of Serra da Estrela cheese, as well as on other high-quality dairy products prone to adulteration, contributing to the further development of the dairy industry. Copyright © 2016 Elsevier Ltd. All rights reserved.

Examining Troughs in the Mass Distribution of All Theoretically Possible Tryptic Peptides

PubMed Central

Nefedov, Alexey V.; Mitra, Indranil; Brasier, Allan R.; Sadygov, Rovshan G.

2011-01-01

This work describes the mass distribution of all theoretically possibly tryptic peptides made of 20 amino acids, up to the mass of 3 kDa, with resolution of 0.001 Da. We characterize regions between the peaks of the distribution, including gaps (forbidden zones) and low-populated areas (quiet zones). We show how the gaps shrink over the mass range, and when they completely disappear. We demonstrate that peptide compositions in quiet zones are less diverse than those in the peaks of the distribution, and that by eliminating certain types of unrealistic compositions the gaps in the distribution may be increased. The mass distribution is generated using a parallel implementation of a recursive procedure that enumerates all amino acid compositions. It allows us to enumerate all compositions of tryptic peptides below 3 kDa in 48 minutes using a computer cluster with 12 Intel Xeon X5650 CPUs (72 cores). The results of this work can be used to facilitate protein identification and mass defect labeling in mass spectrometry-based proteomics experiments. PMID:21780838

1H nuclear magnetic resonance-based metabolomic characterization of wines by grape varieties and production areas.

PubMed

Son, Hong-Seok; Kim, Ki Myong; van den Berg, Frans; Hwang, Geum-Sook; Park, Won-Mok; Lee, Cherl-Ho; Hong, Young-Shick

2008-09-10

(1)H NMR spectroscopy was used to investigate the metabolic differences in wines produced from different grape varieties and different regions. A significant separation among wines from Campbell Early, Cabernet Sauvignon, and Shiraz grapes was observed using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The metabolites contributing to the separation were assigned to be 2,3-butanediol, lactate, acetate, proline, succinate, malate, glycerol, tartarate, glucose, and phenolic compounds by PCA and PLS-DA loading plots. Wines produced from Cabernet Sauvignon grapes harvested in the continental areas of Australia, France, and California were also separated. PLS-DA loading plots revealed that the level of proline in Californian Cabernet Sauvignon wines was higher than that in Australian and French Cabernet Sauvignon, Australian Shiraz, and Korean Campbell Early wines, showing that the chemical composition of the grape berries varies with the variety and growing area. This study highlights the applicability of NMR-based metabolomics with multivariate statistical data sets in determining wine quality and product origin.

The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity.

PubMed

Zhang, Yiguo; Hayes, John D

2013-01-01

The integral membrane-bound Nrf1 transcription factor fulfils important functions in maintaining cellular homeostasis and organ integrity, but how it is controlled vectorially is unknown. Herein, creative use of Gal4-based reporter assays with protease protection assays (GRAPPA), and double fluorescence protease protection (dFPP), reveals that the membrane-topogenic vectorial behaviour of Nrf1 dictates its post-translational modification and transactivation activity. Nrf1 is integrated within endoplasmic reticulum (ER) membranes through its NHB1-associated TM1 in cooperation with other semihydrophobic amphipathic regions. The transactivation domains (TADs) of Nrf1, including its Asn/Ser/Thr-rich (NST) glycodomain, are transiently translocated into the ER lumen, where it is glycosylated in the presence of glucose to become a 120-kDa isoform. Thereafter, the NST-adjoining TADs are partially repartitioned out of membranes into the cyto/nucleoplasmic side, where Nrf1 is subject to deglycosylation and/or proteolysis to generate 95-kDa and 85-kDa isoforms. Therefore, the vectorial process of Nrf1 controls its target gene expression.

Design Calculation Procedure for Passive Solar Houses at Navy Installations in Regions with Cold Climate. Volume I.

DTIC Science & Technology

1981-10-01

8217.nd So,,,g.YPFREO T1 PRO CVRC Design Calculation Procedure for Passive Preliminary Solar Houses at Navy Installations in Apr zO STpiPOR NUBE Regions...unlimited I7 DISTRIBUTION STATEMENT (of the WAtract ente~red InI 81-1, 20, it diferent from Report) 18 SUPPLEMENTARY NOTES 19P KEY WORDS ( Con ,,nUe on~df -1...agl Figure ~ ~ 5. Deiiino ybl sdi Swot pcn aclto 59/ condition) for oorthern latitudes and different times of da are listed in .11 lable 5.4

A Numerical Study of Heat and Water Vapor Transfer in MDCT-Based Human Airway Models

PubMed Central

Wu, Dan; Tawhai, Merryn H.; Hoffman, Eric A.; Lin, Ching-Long

2014-01-01

A three-dimensional (3D) thermo-fluid model is developed to study regional distributions of temperature and water vapor in three multi-detector row computed-tomography (MDCT)-basedhuman airwayswith minute ventilations of 6, 15 and 30 L/min. A one-dimensional (1D) model is also solved to provide necessary initial and boundary conditionsforthe 3D model. Both 3D and 1D predicted temperature distributions agree well with available in vivo measurement data. On inspiration, the 3D cold high-speed air stream is split at the bifurcation to form secondary flows, with its cold regions biased toward the inner wall. The cold air flowing along the wall is warmed up more rapidly than the air in the lumen center. The repeated splitting pattern of air streams caused by bifurcations acts as an effective mechanism for rapid heat and mass transfer in 3D. This provides a key difference from the 1D model, where heating relies largely on diffusion in the radial direction, thus significantly affecting gradient-dependent variables, such as energy flux and water loss rate. We then propose the correlations for respective heat and mass transfer in the airways of up to 6 generations: Nu=3.504(ReDaDt)0.277, R = 0.841 and Sh=3.652(ReDaDt)0.268, R = 0.825, where Nu is the Nusselt number, Sh is the Sherwood number, Re is the branch Reynolds number, Da is the airway equivalent diameter, and Dt is the tracheal equivalentdiameter. PMID:25081386

Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: preliminary evidence of axonal degeneration in the temporal lobe.

PubMed

Huang, J; Friedland, R P; Auchus, A P

2007-01-01

Diffusion tensor imaging (DTI) is a sensitive technique for studying cerebral white matter. We used DTI to characterize microstructural white matter changes and their associations with cognitive dysfunction in Alzheimer disease (AD) and mild cognitive impairment (MCI). We studied elderly subjects with mild AD (n = 6), MCI (n = 11), or normal cognition (n = 8). A standardized clinical and neuropsychological evaluation was conducted on each subject. DTI images were acquired, and fractional anisotropy (FA), axial diffusivity (DA), and radial diffusivity (DR) of normal-appearing white matter (NAWM) in frontal, temporal, parietal, and occipital lobes were determined. These diffusion measurements were compared across the 3 groups, and significant differences were further examined for correlations with tests of cognitive function. Compared with normal controls, AD subjects demonstrated decreased FA and increased DR in the temporal, parietal, and frontal NAWM and decreased DA in temporal NAWM. MCI subjects also showed decreased FA and decreased DA in temporal NAWM, with decreased FA and increased DR in parietal NAWM. Diffusion measurements showed no differences in occipital NAWM. Across all subjects, temporal lobe FA and DR correlated with episodic memory, frontal FA and DR correlated with executive function, and parietal DR significantly correlated with visuospatial ability. We found evidence for functionally relevant microstructural changes in the NAWM of patients with AD and MCI. These changes were present in brain regions serving higher cortical functions, but not in regions serving primary functions, and are consistent with a hypothesized loss of axonal processes in the temporal lobe.

A role for tight junction-associated MARVEL proteins in larval sea lamprey (Petromyzon marinus) osmoregulation.

PubMed

Kolosov, Dennis; Bui, Phuong; Donini, Andrew; Wilkie, Mike P; Kelly, Scott P

2017-10-15

This study reports on tight junction-associated MARVEL proteins of larval sea lamprey ( Petromyzon marinus ) and their potential role in ammocoete osmoregulation. Two occludin isoforms (designated Ocln and Ocln-a) and a tricellulin (Tric) were identified. Transcripts encoding ocln , ocln-a and tric were broadly expressed in larval lamprey, with the greatest abundance of ocln in the gut, liver and kidney, ocln-a in the gill and skin, and tric in the kidney. Ocln and Ocln-a resolved as ∼63 kDa and ∼35 kDa MW proteins, respectively, while Tric resolved as a ∼50 kDa protein. Ocln immunolocalized to the gill vasculature and in gill mucous cells while Ocln-a localized to the gill pouch and gill epithelium. Both Ocln and Ocln-a localized in the nephron, the epidermis and the luminal side of the gut. In branchial tissue, Tric exhibited punctate localization, consistent with its presence at regions of tricellular contact. Following ion-poor water (IPW) acclimation of ammocoetes, serum [Na + ] and [Cl - ] decreased, but not [Ca 2+ ], and carcass moisture content increased. In association, Ocln abundance increased in the skin and kidney, but reduced in the gill of IPW-acclimated ammocoetes while Ocln-a abundance reduced in the kidney only. Tric abundance increased in the gill. Region-specific alterations in ocln , ocln-a and tric mRNA abundance were also observed in the gut. Data support a role for Ocln, Ocln-a and Tric in the osmoregulatory strategies of a basal vertebrate. © 2017. Published by The Company of Biologists Ltd.

Sequence diversity among badnavirus isolates infecting yam (Dioscorea spp.) in Ghana, Togo, Benin and Nigeria.

PubMed

Eni, A O; Hughes, J d'A; Asiedu, R; Rey, M E C

2008-01-01

We analysed the sequence diversity in the reverse transcriptase (RT)/ribonuclease H (RNaseH) coding region of 19 badnavirus isolates infecting yam (Dioscorea spp.) in Ghana, Togo, Benin, and Nigeria. Phylogenetic analysis of the deduced amino acid sequences revealed that the isolates are broadly divided into two distinct species, each clustering with Dioscorea alata bacilliform virus (DaBV) and Dioscorea sansibarensis bacilliform virus (DsBV). Fourteen isolates had 90-96% amino acid identity with DaBV, while four isolates had 83-84% amino acid identity with DsBV. One isolate from Benin, BN4Dr, was distinct and had 77 and 75% amino acid identity with DaBV and DsBV, respectively, and may be a member of a new badnavirus species infecting yam in West Africa. Viruses of the two main species were present in Ghana, Togo and Benin and were observed to infect both D. alata and D. rotundata indiscriminately. This is the first confirmed report of DsBV infection in yam in Ghana and Togo. The results of this study demonstrate that members of two distinct species of badnaviruses infect yam in the West African yam zone and suggest a putative new species, BN4Dr. We also conclude that these species are not confined to limited geographic regions or specific for yam host species. However, the three badnavirus species are serologically related. The sequence information obtained from this study can be used to develop PCR-based diagnostics to detect members of the various species and/or strains of badnaviruses infecting yam in West Africa.

Characterization of gene encoding amylopullulanase from plant-originated lactic acid bacterium, Lactobacillus plantarum L137.

PubMed

Kim, Jong-Hyun; Sunako, Michihiro; Ono, Hisayo; Murooka, Yoshikatsu; Fukusaki, Eiichiro; Yamashita, Mitsuo

2008-11-01

A starch-hydrolyzing lactic acid bacterium, Lactobacillus plantarum L137, was isolated from traditional fermented food made from fish and rice in the Philippines. A gene (apuA) encoding an amylolytic enzyme from Lactobacillus plantarum L137 was cloned, and its nucleotide sequence was determined. The apuA gene consisted of an open reading frame of 6171 bp encoding a protein of 2056 amino acids, the molecular mass of which was calculated to be 215,625 Da. The catalytic domains of amylase and pullulanase were located in the same region within the middle of the N-terminal region. The deduced amino acid sequence revealed four highly conserved regions that are common among amylolytic enzymes. In the N-terminal region, a six-amino-acid sequence (Asp-Ala/Thr-Ala-Asn-Ser-Thr) is repeated 39 times, and a three-amino-acid sequence (Gln-Pro-Thr) is repeated 50 times in the C-terminal region. The apuA gene was subcloned in L. plantarum NCL21, which is a plasmid-cured derivative of the wild-type L137 strain and has no amylopullulanase activity, and the gene was overexpressed under the control of its own promoter. The ApuA enzyme from this recombinant L. plantarum NCL21 harboring apuA gene was purified. The enzyme has both alpha-amylase and pullulanase activities. The N-terminal sequence of the purified enzyme showed that the signal peptide was cleaved at Ala(36) and the molecular mass of the mature extracellular enzyme is 211,537 Da. The major reaction products from soluble starch were maltotriose (G3) and maltotetraose (G4). Only maltotriose (G3) was produced from pullulan. From these results, we concluded that ApuA is an amylolytic enzyme belonging to the amylopullulanase family.

Extraction of Features from High-resolution 3D LiDaR Point-cloud Data

NASA Astrophysics Data System (ADS)

Keller, P.; Kreylos, O.; Hamann, B.; Kellogg, L. H.; Cowgill, E. S.; Yikilmaz, M. B.; Hering-Bertram, M.; Hagen, H.

2008-12-01

Airborne and tripod-based LiDaR scans are capable of producing new insight into geologic features by providing high-quality 3D measurements of the landscape. High-resolution LiDaR is a promising method for studying slip on faults, erosion, and other landscape-altering processes. LiDaR scans can produce up to several billion individual point returns associated with the reflection of a laser from natural and engineered surfaces; these point clouds are typically used to derive a high-resolution digital elevation model (DEM). Currently, there exist only few methods that can support the analysis of the data at full resolution and in the natural 3D perspective in which it was collected by working directly with the points. We are developing new algorithms for extracting features from LiDaR scans, and present method for determining the local curvature of a LiDaR data set, working directly with the individual point returns of a scan. Computing the curvature enables us to rapidly and automatically identify key features such as ridge-lines, stream beds, and edges of terraces. We fit polynomial surface patches via a moving least squares (MLS) approach to local point neighborhoods, determining curvature values for each point. The size of the local point neighborhood is defined by a user. Since both terrestrial and airborne LiDaR scans suffer from high noise, we apply additional pre- and post-processing smoothing steps to eliminate unwanted features. LiDaR data also captures objects like buildings and trees complicating greatly the task of extracting reliable curvature values. Hence, we use a stochastic approach to determine whether a point can be reliably used to estimate curvature or not. Additionally, we have developed a graph-based approach to establish connectivities among points that correspond to regions of high curvature. The result is an explicit description of ridge-lines, for example. We have applied our method to the raw point cloud data collected as part of the GeoEarthScope B-4 project on a section of the San Andreas Fault (Segment SA09). This section provides an excellent test site for our method as it exposes the fault clearly, contains few extraneous structures, and exhibits multiple dry stream-beds that have been off-set by motion on the fault.

Corticostriatal and Dopaminergic Response to Beer Flavor with Both fMRI and [(11) C]raclopride Positron Emission Tomography.

PubMed

Oberlin, Brandon G; Dzemidzic, Mario; Harezlak, Jaroslaw; Kudela, Maria A; Tran, Stella M; Soeurt, Christina M; Yoder, Karmen K; Kareken, David A

2016-09-01

Cue-evoked drug-seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine (DA) transmission. Using [(11) C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST DA release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST blood oxygenation level-dependent (BOLD) responses to beer flavor are related to VST DA release and motivation to drink. Male beer drinkers (n = 28, age = 24 ± 2, drinks/wk = 16 ± 10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade(®) (appetitive control). We tested for correlations between BOLD activation in fMRI and VST DA responses in PET, and drinking-related variables. Compared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest. Both imaging modalities showed a right-lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males) and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting. Copyright © 2016 by the Research Society on Alcoholism.

Evidence for Sprouting of Dopamine and Serotonin Axons in the Pallidum of Parkinsonian Monkeys

PubMed Central

Gagnon, Dave; Eid, Lara; Coudé, Dymka; Whissel, Carl; Di Paolo, Thérèse; Parent, André; Parent, Martin

2018-01-01

This light and electron microscopie immunohistochemical quantitative study aimed at determining the state of the dopamine (DA) and serotonin (5-HT) innervations of the internal (GPi) and external (GPe) segments of the pallidum in cynomolgus monkeys (Macaca fascicularis) rendered parkinsonian by systemic injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In contrast to the prominent DA denervation of striatum, the GPi in MPTP monkeys was found to be markedly enriched in DA (TH+) axon varicosities. The posterior sensorimotor region of this major output structure of the basal ganglia was about 8 times more intensely innervated in MPTP monkeys (0.71 ± 0.08 × 106 TH+ axon varicosities/mm3) than in controls (0.09 ± 0.01 × 106). MPTP intoxication also induced a two-fold increase in the density of 5-HT (SERT+) axon varicosities in both GPe and GPi. This augmentation was particularly pronounced anteriorly in the so-called associative and limbic pallidal territories. The total length of the labeled pallidal axons was also significantly increased in MPTP monkeys compared to controls, but the number of DA and 5-HT axon varicosities per axon length unit remained the same in the two groups, indicating that the DA and 5-HT pallidal hyperinnervations seen in MPTP monkeys result from axon sprouting rather than from the appearance of newly formed axon varicosities on non-growing axons. At the ultrastructural level, pallidal TH+ and SERT+ axons were morphologically similar in MPTP and controls, and their synaptic incidence was very low suggesting a volumic mode of transmission. Altogether, our data reveal a significant sprouting of DA and 5-HT pallidal afferents in parkinsonian monkeys, the functional significance of which remains to be determined. We suggest that the marked DA hyperinnervation of the GPi represents a neuroadaptive change designed to normalize pallidal firing patterns associated with the delayed appearance of motor symptoms, whereas the 5-HT hyperinnervation might be involved in the early expression of non-motor symptoms in Parkinson's disease. PMID:29867377

Clinicopathological characteristics of desmoplastic ameloblastoma: A systematic review.

PubMed

Anand, Rahul; Sarode, Gargi S; Sarode, Sachin C; Reddy, Mamatha; Unadkat, Hemant V; Mushtaq, Shazia; Deshmukh, Revati; Choudhary, Shakira; Gupta, Nitin; Ganjre, Anjali P; Patil, Shankargouda

2018-02-01

The aim of the present review was to systematically present the clinicopathological data of desmoplastic ameloblastoma (DA) from articles published in the literature. A comprehensive search of the databases (PubMed, Medline, SCOPUS, Web of Science, and Google Scholar) for published articles on DA was conducted. A total of 238 cases were identified and analyzed from 76 published papers. DA showed a slight male predilection (male: female=1.07:1) with a predominance in the fourth and fifth decades of life. Mandibular involvement (52.55%) was most commonly seen with a marked tendency for the anterior region (mandible: 40.9%, maxilla: 48.07%). The size of the lesion ranged from .5 cm to 20.4 cm, with the majority of cases measuring more than 3 cm in size (53.84%). Radiologically, most of the lesions presented mixed radiolucency and radiopacity (62%), and root resorption was observed in only seven cases. The majority of the lesions showed ill-defined margins upon radiographic examination (65.78%). Most of the cases were treated with resection (78.57%), and five of the 10 recurrent cases were treated by enucleation/curettage. DA is characterized by the unique presentation of clinicopathological parameters. It is not possible to comment on its aggressive/recurrent nature and best treatment modality due to inadequate follow-up data. © 2017 John Wiley & Sons Australia, Ltd.

Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry as a Platform for Characterizing Multimeric Membrane Protein Complexes

NASA Astrophysics Data System (ADS)

Lippens, Jennifer L.; Nshanian, Michael; Spahr, Chris; Egea, Pascal F.; Loo, Joseph A.; Campuzano, Iain D. G.

2018-01-01

Membrane protein characterization is consistently hampered by challenges with expression, purification, and solubilization. Among several biophysical techniques employed for their characterization, native-mass spectrometry (MS) has emerged as a powerful tool for the analysis of membrane proteins and complexes. Here, two MS platforms, the FT-ICR and Q-ToF, have been explored to analyze the homotetrameric water channel protein, AquaporinZ (AqpZ), under non-denaturing conditions. This 97 kDa membrane protein complex can be readily liberated from the octylglucoside (OG) detergent micelle under a range of instrument conditions on both MS platforms. Increasing the applied collision energy of the FT-ICR collision cell yielded varying degrees of tetramer (97 kDa) liberation from the OG micelles, as well as dissociation into the trimeric (72 kDa) and monomeric (24 kDa) substituents. Tandem-MS on the Q-ToF yielded higher intensity tetramer signal and, depending on the m/z region selected, the observed monomer signal varied in intensity. Precursor ion selection of an m/z range above the expected protein signal distribution, followed by mild collisional activation, is able to efficiently liberate AqpZ with a high S/N ratio. The tetrameric charge state distribution obtained on both instruments demonstrated superpositioning of multiple proteoforms due to varying degrees of N-terminal formylation. [Figure not available: see fulltext.

Detection and effects of harmful algal toxins in Scottish harbour seals and potential links to population decline.

PubMed

Jensen, Silje-Kristin; Lacaze, Jean-Pierre; Hermann, Guillaume; Kershaw, Joanna; Brownlow, Andrew; Turner, Andrew; Hall, Ailsa

2015-04-01

Over the past 15 years or so, several Scottish harbour seal (Phoca vitulina) populations have declined in abundance and several factors have been considered as possible causes, including toxins from harmful algae. Here we explore whether a link could be established between two groups of toxins, domoic acid (DA) and saxitoxins (STXs), and the decline in the harbour seal populations in Scotland. We document the first evidence that harbour seals are exposed to both DA and STXs from consuming contaminated fish. Both groups of toxins were found in urine and faeces sampled from live captured (n = 162) and stranded animals (n = 23) and in faecal samples collected from seal haul-out sites (n = 214) between 2008 and 2013. The proportion of positive samples and the toxins levels measured in the excreta were significantly higher in areas where harbour seal abundance is in decline. There is also evidence that DA has immunomodulatory effects in harbour seals, including lymphocytopenia and monocytosis. Scottish harbour seals are exposed to DA and STXs through contaminated prey at potentially lethal levels and with this evidence we suggest that exposure to these toxins are likely to be important factors driving the harbour seal decline in some regions of Scotland. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exploring the relationship between social attachment and dopamine D2/3 receptor availability in the brains of healthy humans using [11C]-(+)-PHNO

PubMed Central

Caravaggio, Fernando; Chung, Jun Ku; Gerretsen, Philip; Fervaha, Gagan; Nakajima, Shinichiro; Plitman, Eric; Iwata, Yusuke; Wilson, Alan; Graff-Guerrero, Ariel

2017-01-01

Differences in striatal dopamine (DA) function may be related to differences in the degree of social attachment to others. Using positron emission tomography (PET), socially detached persons demonstrate reduced DA D2/3 receptor (D2/3R) availability in the striatum. However, previous PET studies have only used antagonist radiotracers for D2/3R and have not specifically examined regions of interest (ROIs) such as the ventral striatum (VS). In 32 healthy persons, we investigated the relationship between self-reported attachment and DA D2/3R availability in striatal and extrastriatal ROIs as measured using the agonist radiotracer [11C]-(+)-PHNO. Surprisingly, more social attachment—as measured by the attachment subscale of the temperament and character inventory—was related to less [11C]-(+)-PHNO binding in the VS (r(30) =−.43, p = .01). This relationship held in a subsample who also completed the detachment subscale of the Karolinska Scales of Personality (r(10) = .62, p = .03). However, no relationships were observed with BPND in the dorsal striatum or D3R-specific ROIs. One potential explanation for these findings is that persons who are more socially detached have less endogenous DA occupying D2/3R in the VS. This interpretation warrants investigation by future research. These findings may help us better understand the neurochemical basis of attachment. PMID:26873034

Hibiscus latent Fort Pierce virus in Brazil and synthesis of its biologically active full-length cDNA clone.

PubMed

Gao, Ruimin; Niu, Shengniao; Dai, Weifang; Kitajima, Elliot; Wong, Sek-Man

2016-10-01

A Brazilian isolate of Hibiscus latent Fort Pierce virus (HLFPV-BR) was firstly found in a hibiscus plant in Limeira, SP, Brazil. RACE PCR was carried out to obtain the full-length sequences of HLFPV-BR which is 6453 nucleotides and has more than 99.15 % of complete genomic RNA nucleotide sequence identity with that of HLFPV Japanese isolate. The genomic structure of HLFPV-BR is similar to other tobamoviruses. It includes a 5' untranslated region (UTR), followed by open reading frames encoding for a 128-kDa protein and a 188-kDa readthrough protein, a 38-kDa movement protein, 18-kDa coat protein, and a 3' UTR. Interestingly, the unique feature of poly(A) tract is also found within its 3'-UTR. Furthermore, from the total RNA extracted from the local lesions of HLFPV-BR-infected Chenopodium quinoa leaves, a biologically active, full-length cDNA clone encompassing the genome of HLFPV-BR was amplified and placed adjacent to a T7 RNA polymerase promoter. The capped in vitro transcripts from the cloned cDNA were infectious when mechanically inoculated into C. quinoa and Nicotiana benthamiana plants. This is the first report of the presence of an isolate of HLFPV in Brazil and the successful synthesis of a biologically active HLFPV-BR full-length cDNA clone.

Criteria for recognition and taphonomy of coprolites from the Serra da Galga Member, Marília Formation (Upper Cretaceous), Minas Gerais, Brazil

NASA Astrophysics Data System (ADS)

de Oliveira, Fábio Antônio; Santucci, Rodrigo Miloni

2017-10-01

The Cretaceous sedimentary rocks from Uberaba, Minas Gerais, have provided a rich vertebrate fauna unearthed from rocks of the Serra da Galga Member, Marília Formation, Bauru Group, of Maastrichtian age. Together with these fossils, a large number of coprolites have also been found from two main localities, here called the Peirópolis and Serra da Galga sites. During field trips carried out in the last few years, 340 samples have been collected, prepared, and analyzed in laboratory. By using parameters such as weight, density, mineralogical composition, and content, we identified 199 coprolites and 141 inorganic nodules (pseudocoprolites). The coprolites have been divided into four morphotypes, which suggest their producers varied in feeding strategies and size. The taphonomic study, based on morphological characters such as wear, presence of pebbles or pebble marks, and desiccation cracks, suggests they underwent temporal and spatial-mixing, and that the material from the Peirópolis Site were transported essentially by alluvial processes (alluvial fans), whereas the material from the Serra da Galga Site were reworked mainly by fluvial streams. The same taphonomic processes may well have affected other fossils from these sites, which are highly abundant in the rocks of this area. Because of that, this taphonomic aspect becomes an important parameter to be taken into account in future studies on the biota of the region.

Dose-response and histopathological study, with special attention to the hypophysis, of the differential effects of domoic acid on rats and mice.

PubMed

Vieira, Andrés Crespo; Martínez, J Manuel Cifuentes; Pose, Roberto Bermúdez; Queijo, Álvaro Antelo; Posadas, Nuria Alemañ; López, Luis M Botana

2015-05-01

The effects of the neurotoxin domoic acid (DA) in the central nervous system of rodents (essentially rats and mice) after intraperitoneal administration have been profusely studied in the past. These observations have shown that the toxin induces similar symptoms and pathology in both species, but the lethality varies greatly. This article addresses the common and specific histopathological effects in rats and mice and the difference in sensitivity of these species to DA. Various sublethal and lethal doses were employed in mice (from 3 mg/kg to 8 mg/kg) to observe their neurotoxicity by using different histological techniques, and these results were compared with the pathological effects after the administration of LD50 in rats (2.5 mg/kg). Additionally we also detected the presence of this toxin in various tissues by means of immunohistochemistry. Our results showed that rats are more vulnerable than mice to the neurotoxic effects of DA after intraperitoneal inoculation: lethality was extremely high in rats and the toxin produced hippocampal damage in rats surviving the intoxication, while lesions were not observed in DA-inoculated mice. As for similarities between rats and mice, both displayed similar clinical signs and in both the toxin was detected in the hypophysis by immunohistochemistry, a brain region not reported to date as target of the toxin. © 2015 Wiley Periodicals, Inc.

Multivariate and Multiscale Data Assimilation in Terrestrial Systems: A Review

PubMed Central

Montzka, Carsten; Pauwels, Valentijn R. N.; Franssen, Harrie-Jan Hendricks; Han, Xujun; Vereecken, Harry

2012-01-01

More and more terrestrial observational networks are being established to monitor climatic, hydrological and land-use changes in different regions of the World. In these networks, time series of states and fluxes are recorded in an automated manner, often with a high temporal resolution. These data are important for the understanding of water, energy, and/or matter fluxes, as well as their biological and physical drivers and interactions with and within the terrestrial system. Similarly, the number and accuracy of variables, which can be observed by spaceborne sensors, are increasing. Data assimilation (DA) methods utilize these observations in terrestrial models in order to increase process knowledge as well as to improve forecasts for the system being studied. The widely implemented automation in observing environmental states and fluxes makes an operational computation more and more feasible, and it opens the perspective of short-time forecasts of the state of terrestrial systems. In this paper, we review the state of the art with respect to DA focusing on the joint assimilation of observational data precedents from different spatial scales and different data types. An introduction is given to different DA methods, such as the Ensemble Kalman Filter (EnKF), Particle Filter (PF) and variational methods (3/4D-VAR). In this review, we distinguish between four major DA approaches: (1) univariate single-scale DA (UVSS), which is the approach used in the majority of published DA applications, (2) univariate multiscale DA (UVMS) referring to a methodology which acknowledges that at least some of the assimilated data are measured at a different scale than the computational grid scale, (3) multivariate single-scale DA (MVSS) dealing with the assimilation of at least two different data types, and (4) combined multivariate multiscale DA (MVMS). Finally, we conclude with a discussion on the advantages and disadvantages of the assimilation of multiple data types in a simulation model. Existing approaches can be used to simultaneously update several model states and model parameters if applicable. In other words, the basic principles for multivariate data assimilation are already available. We argue that a better understanding of the measurement errors for different observation types, improved estimates of observation bias and improved multiscale assimilation methods for data which scale nonlinearly is important to properly weight them in multiscale multivariate data assimilation. In this context, improved cross-validation of different data types, and increased ground truth verification of remote sensing products are required. PMID:23443380

Multivariate and multiscale data assimilation in terrestrial systems: a review.

PubMed

Montzka, Carsten; Pauwels, Valentijn R N; Franssen, Harrie-Jan Hendricks; Han, Xujun; Vereecken, Harry

2012-11-26

More and more terrestrial observational networks are being established to monitor climatic, hydrological and land-use changes in different regions of the World. In these networks, time series of states and fluxes are recorded in an automated manner, often with a high temporal resolution. These data are important for the understanding of water, energy, and/or matter fluxes, as well as their biological and physical drivers and interactions with and within the terrestrial system. Similarly, the number and accuracy of variables, which can be observed by spaceborne sensors, are increasing. Data assimilation (DA) methods utilize these observations in terrestrial models in order to increase process knowledge as well as to improve forecasts for the system being studied. The widely implemented automation in observing environmental states and fluxes makes an operational computation more and more feasible, and it opens the perspective of short-time forecasts of the state of terrestrial systems. In this paper, we review the state of the art with respect to DA focusing on the joint assimilation of observational data precedents from different spatial scales and different data types. An introduction is given to different DA methods, such as the Ensemble Kalman Filter (EnKF), Particle Filter (PF) and variational methods (3/4D-VAR). In this review, we distinguish between four major DA approaches: (1) univariate single-scale DA (UVSS), which is the approach used in the majority of published DA applications, (2) univariate multiscale DA (UVMS) referring to a methodology which acknowledges that at least some of the assimilated data are measured at a different scale than the computational grid scale, (3) multivariate single-scale DA (MVSS) dealing with the assimilation of at least two different data types, and (4) combined multivariate multiscale DA (MVMS). Finally, we conclude with a discussion on the advantages and disadvantages of the assimilation of multiple data types in a simulation model. Existing approaches can be used to simultaneously update several model states and model parameters if applicable. In other words, the basic principles for multivariate data assimilation are already available. We argue that a better understanding of the measurement errors for different observation types, improved estimates of observation bias and improved multiscale assimilation methods for data which scale nonlinearly is important to properly weight them in multiscale multivariate data assimilation. In this context, improved cross-validation of different data types, and increased ground truth verification of remote sensing products are required.

Emerging issues in Integrated Pest Management implementation and adoption in the North Central USA

USDA-ARS?s Scientific Manuscript database

There is a long tradition of integrated pest management (IPM) in the North Central region of the U.S. IPM is difficult to define, and it means different things to different people. But in general it is a philosophy based on multiple tactics to prevent a population from building up to unacceptable da...

Rickettsia asembonensis Characterization by Multilocus Sequence Typing of Complete Genes, Peru.

PubMed

Loyola, Steev; Flores-Mendoza, Carmen; Torre, Armando; Kocher, Claudine; Melendrez, Melanie; Luce-Fedrow, Alison; Maina, Alice N; Richards, Allen L; Leguia, Mariana

2018-05-01

While studying rickettsial infections in Peru, we detected Rickettsia asembonensis in fleas from domestic animals. We characterized 5 complete genomic regions (17kDa, gltA, ompA, ompB, and sca4) and conducted multilocus sequence typing and phylogenetic analyses. The molecular isolate from Peru is distinct from the original R. asembonensis strain from Kenya.

A Causal Inference Analysis of the Effect of Wildland Fire Smoke on Ambient Air Pollution Levels and Health Burden

EPA Science Inventory

Wildfire smoke is a major contributor to ambient air pollution levels. In this talk, we develop a spatio-temporal model to estimate the contribution of fire smoke to overall air pollution in different regions of the country. We combine numerical model output with observational da...

76 FR 43372 - Notice of Final Federal Agency Actions on Proposed Highway in Indiana

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

... and its project records, referenced as Department of the Army (DA) Permit, Number LRL-2007-1043. That... four (4) unnamed tributaries to Smith Creek for Section 1 I-69 project, Number LRL-2007-1043, as... Counties via the Regional General Permit No. 1 (LRL-2007-1043-djd) issued jointly by the Louisville...

Energy Conversion and Combustion Sciences

DTIC Science & Technology

2013-03-08

Property issues Flameholding (flammability limit) Flame propagation (turbulent-flame speed) combustion-Mixing interaction shock Cavity Based Scramjet ...focusing: • “Very-high” speed (space access) region • Overlapping interests and close coordination with AF programs ( scramjet , rockets etc.). • NSF...and Relevant Conditions Hypersonics Gas Turbines Rockets M > 0.1 Re ? Da ? wrinkled flame ball laminar flame Auto Engines PGC (1

NuSTAR timing of NGC 300 ULX-1 / Supernova Impostor SN2010da

NASA Astrophysics Data System (ADS)

Bachetti, Matteo; Grefenstette, Brian W.; Walton, Dominic J.; Fuerst, Felix; Heida, Marianne; Kennea, Jaime A.; Lau, Ryan

2018-02-01

NuSTAR observed NGC 300 on UT 2018-01-31T01:23:50 - 2018-02-01T06:39:02. We used the cleaned event files provided by HEASARC, ran barycorr to refer the times to the Solar System Barycenter, and filtered a region of 30" around the transient source.

Cannabinoid reward and aversion effects in the posterior ventral tegmental area are mediated through dissociable opiate receptor subtypes and separate amygdalar and accumbal dopamine receptor substrates.

PubMed

Ahmad, Tasha; Laviolette, Steven R

2017-08-01

The ventral tegmental area (VTA) and its projections to the basolateral amygdala (BLA) and nucleus accumbens (NAc) are critical for cannabinoid-related motivational effects. Cannabinoid CB1 receptor (CB1R) transmission modulates VTA dopamine (DA) neuron activity and previous reports demonstrate anatomically segregated effects of CB1R transmission in the VTA. However, the underlying pharmacological and anatomical regions responsible for these effects are currently unknown. The objective of the study is to characterize the motivational effects of localized anterior vs. posterior intra-VTA activation vs. blockade of CB1R transmission and the potential role of intra-BLA and intra-NAc DA transmission in these phenomena. Using a conditioned place preference (CPP) procedure, we administered a CB1 agonist (WIN-55,212-2) or antagonist (AM 251) into the posterior VTA (pVTA) or anterior VTA (aVTA) of rats, combined with intra-BLA or intra-NAc DA receptor blockade and intra-VTA co-administration of selective mu vs. kappa opiate-receptor antagonists. Intra-pVTA CB1R activation produced robust rewarding effects through a mu-opiate receptor mechanism whereas CB1R blockade produced conditioned place aversions (CPA) through a kappa-opiate receptor substrate. In contrast, modulation of aVTA CB1R transmission produced no observable effects. Intra-BLA DA receptor blockade prevented the rewarding effects of pVTA CB1R activation, but had no effects on CB1R blockade-induced aversions. In contrast, intra-NAc DA receptor blockade selectively blocked the aversive effects of pVTA CB1R antagonism. Activation vs. blockade of CB1R transmission in the posterior VTA produces bivalent rewarding or aversive effects through separate mu vs. kappa-opiate receptor substrates. These dissociable effects depend on separate DA receptor transmission substrates in the BLA or NAc, respectively.

A novel TNNI2 mutation causes Freeman-Sheldon syndrome in a Chinese family with an affected adult with only facial contractures.

PubMed

Li, Xuefu; Jiang, Miao; Han, Weitian; Zhao, Ning; Liu, Wei; Sui, Yu; Lu, Yongping; Li, Jianxin

2013-09-25

Distal arthrogryposes (DAs), a clinically and genetically heterogeneous group of disorders characterized by congenital contractures with predominant involvement of the hands and feet, can be classified into at least 12 different forms. These autosomal dominant disorders are of variable expressivity and reduced penetrance. Mutations in sarcomeric protein genes, including troponin I2 (TNNI2), troponin T3 (TNNT3), tropomyosin 2 (TPM2), embryonic myosin heavy chain 3 (MYH3), and myosin binding protein C1 (MYBPC1), have been identified in distal arthrogryposis type 1 (DA1, MIM 108120), type 2B (DA2B, MIM 601680) and type 2A (DA2A)/Freeman-Sheldon syndrome (FSS, MIM 193700). However, mutations causing FSS have only been reported in MYH3. Herein we describe a Chinese DA family whose members meet classical strict criteria for FSS, as well as one member of the family who has isolated facial features consistent with FSS. No disease-causing mutation was found in MYH3. Segregation of microsatellite markers flanking the TNNI2 and TNNT3 genes at 11p15.5 was compatible with linkage. Subsequent sequencing of TNNI2 revealed a novel mutation, c.A493T (p.I165F), located in the C-terminal region, which is critical for proper protein function. This mutation was found to cosegregate with the FSS phenotype in this family, and assessment using SIFT and PolyPhen-2 predicted a damaging effect. To the best of our knowledge, we report the first TNNI2 mutation in classical FSS and describe an atypical adult FSS case with only facial contractures resulting from somatic mosaicism. We infer that DA1, DA2B and FSS represent a phenotypic continuum of the same disorder and provide further genetic evidence for this hypothesis. © 2013.

RISING FROM THE ASHES: MID-INFRARED RE-BRIGHTENING OF THE IMPOSTOR SN 2010da IN NGC 300

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

Lau, Ryan M.; Ressler, Michael E.; Kasliwal, Mansi M.

2016-10-20

We present multi-epoch mid-infrared (IR) photometry and the optical discovery observations of the “impostor” supernova (SN) 2010da in NGC 300 using new and archival Spitzer Space Telescope images and ground-based observatories. The mid-infrared counterpart of SN 2010da was detected as Spitzer Infrared Intensive Transient Survey (SPIRITS) 14bme in the SPIRITS, an ongoing systematic search for IR transients. Before erupting on 2010 May 24, the SN 2010da progenitor exhibited a constant mid-IR flux at 3.6 and only a slight ∼10% decrease at 4.5 μ m between 2003 November and 2007 December. A sharp increase in the 3.6 μ m flux followedmore » by a rapid decrease measured ∼150 days before and ∼80 days after the initial outburst, respectively, reveal a mid-IR counterpart to the coincident optical and high luminosity X-ray outbursts. At late times, after the outburst (∼2000 days), the 3.6 and 4.5 μ m emission increased to over a factor of two times the progenitor flux and is currently observed (as of 2016 Feb) to be fading, but still above the progenitor flux. We attribute the re-brightening mid-IR emission to continued dust production and increasing luminosity of the surviving system associated with SN 2010da. We analyze the evolution of the dust temperature ( T {sub d} ∼ 700–1000 K), mass ( M {sub d} ∼ 0.5–3.8 × 10{sup −7} M {sub ⊙}), luminosity ( L {sub IR} ∼ 1.3–3.5 × 10{sup 4} L {sub ⊙}), and the equilibrium temperature radius ( R {sub eq} ∼ 6.4–12.2 au) in order to resolve the nature of SN 2010da. We address the leading interpretation of SN 2010da as an eruption from a luminous blue variable high-mass X-ray binary (HMXB) system. We propose that SN 2010da is instead a supergiant (sg)B[e]-HMXB based on similar luminosities and dust masses exhibited by two other known sgB[e]-HMXB systems. Additionally, the SN 2010da progenitor occupies a similar region on a mid-IR color–magnitude diagram (CMD) with known sgB[e] stars in the Large Magellanic Cloud. The lower limit estimated for the orbital eccentricity of the sgB[e]-HMXB ( e > 0.82) from X-ray luminosity measurements is high compared to known sgHMXBs and supports the claim that SN 2010da may be associated with a newly formed HMXB system.« less

Mitochondrial control region haplotypes of the South American sea lion Otaria flavescens (Shaw, 1800).

PubMed

Artico, L O; Bianchini, A; Grubel, K S; Monteiro, D S; Estima, S C; Oliveira, L R de; Bonatto, S L; Marins, L F

2010-09-01

The South American sea lion, Otaria flavescens, is widely distributed along the Pacific and Atlantic coasts of South America. However, along the Brazilian coast, there are only two nonbreeding sites for the species (Refúgio de Vida Silvestre da Ilha dos Lobos and Refúgio de Vida Silvestre do Molhe Leste da Barra do Rio Grande), both in Southern Brazil. In this region, the species is continuously under the effect of anthropic activities, mainly those related to environmental contamination with organic and inorganic chemicals and fishery interactions. This paper reports, for the first time, the genetic diversity of O. flavescens found along the Southern Brazilian coast. A 287-bp fragment of the mitochondrial DNA control region (D-loop) was analyzed. Seven novel haplotypes were found in 56 individuals (OFA1-OFA7), with OFA1 being the most frequent (47.54%). Nucleotide diversity was moderate (π = 0.62%) and haplotype diversity was relatively low (67%). Furthermore, the median joining network analysis indicated that Brazilian haplotypes formed a reciprocal monophyletic clade when compared to the haplotypes from the Peruvian population on the Pacific coast. These two populations do not share haplotypes and may have become isolated some time back. Further genetic studies covering the entire species distribution are necessary to better understand the biological implications of the results reported here for the management and conservation of South American sea lions.

Alterations in monoamines level in discrete brain regions and other peripheral tissues in young and adult male rats during experimental hyperthyroidism.

PubMed

Hassan, Wafaa A; Rahman, Taghride Abdel; Aly, Mona S; Shahat, Asmaa S

2013-08-01

The present study was conducted to investigate the effect of experimentally-induced hyperthyroidism on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats (60 rats of each age). Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 500 μg/kg body wt.) for 21 consecutive days. Induction of hyperthyroidism caused a significant elevation in DA and 5-HT levels in most of the tissues studied of both young and adult animals after 7, 14, and 21 days. NE content significantly decreased after 21 days in most of the brain regions examined and after 14 and 21 days in blood plasma of young rats following hyperthyroidism. In adult rats, NE content decreased after 14 and 21 days in cardiac muscle and after 21 days only in adrenal gland. It may be suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

[Ecological observations on Biomphalaria straminea (Dunker, 1848) in areas of the northeast, Brazil].

PubMed

Rosas, E

1987-01-01

The different climatic regions determine the zoogeographic distribution of various animal species depending on their particular conditions and ecological preferences. The host schistosomiasis planorbid is one of these species. This paper deals with the distribution of Biomphalaria straminea in northeast Brazil. It starts from the analysis of different climatic peculiarities in this region, associated to limnological observation done by the author in three different hydric collections in the state of Sergipe. It has been concluded that this is an "eurióioca" species. Its broad ecological valence permits this species to survive in regions where climate asperties are evident, requiring behavior and physiological adaptations. The species survives in all northeast region, from "zona da mata", in the coast, to the semi-arid "sertão".

Human neural stem cells survive long term in the midbrain of dopamine-depleted monkeys after GDNF overexpression and project neurites toward an appropriate target.

PubMed

Wakeman, Dustin R; Redmond, D Eugene; Dodiya, Hemraj B; Sladek, John R; Leranth, Csaba; Teng, Yang D; Samulski, R Jude; Snyder, Evan Y

2014-06-01

Transplanted multipotent human fetal neural stem cells (hfNSCs) significantly improved the function of parkinsonian monkeys in a prior study primarily by neuroprotection, with only 3%-5% of cells expressing a dopamine (DA) phenotype. In this paper, we sought to determine whether further manipulation of the neural microenvironment by overexpression of a developmentally critical molecule, glial cell-derived neurotrophic factor (GDNF), in the host striatum could enhance DA differentiation of hfNSCs injected into the substantia nigra and elicit growth of their axons to the GDNF-expressing target. hfNSCs were transplanted into the midbrain of 10 green monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine. GDNF was delivered concomitantly to the striatum via an adeno-associated virus serotype 5 vector, and the fate of grafted cells was assessed after 11 months. Donor cells remained predominantly within the midbrain at the injection site and sprouted numerous neurofilament-immunoreactive fibers that appeared to course rostrally toward the striatum in parallel with tyrosine hydroxylase-immunoreactive fibers from the host substantia nigra but did not mature into DA neurons. This work suggests that hfNSCs can generate neurons that project long fibers in the adult primate brain. However, in the absence of region-specific signals and despite GDNF overexpression, hfNSCs did not differentiate into mature DA neurons in large numbers. It is encouraging, however, that the adult primate brain appeared to retain axonal guidance cues. We believe that transplantation of stem cells, specifically instructed ex vivo to yield DA neurons, could lead to reconstruction of some portion of the nigrostriatal pathway and prove beneficial for the parkinsonian condition. ©AlphaMed Press.

Trans-blood brain barrier delivery of dopamine-loaded nanoparticles reverses functional deficits in parkinsonian rats.

PubMed

Pahuja, Richa; Seth, Kavita; Shukla, Anshi; Shukla, Rajendra Kumar; Bhatnagar, Priyanka; Chauhan, Lalit Kumar Singh; Saxena, Prem Narain; Arun, Jharna; Chaudhari, Bhushan Pradosh; Patel, Devendra Kumar; Singh, Sheelendra Pratap; Shukla, Rakesh; Khanna, Vinay Kumar; Kumar, Pradeep; Chaturvedi, Rajnish Kumar; Gupta, Kailash Chand

2015-05-26

Sustained and safe delivery of dopamine across the blood brain barrier (BBB) is a major hurdle for successful therapy in Parkinson's disease (PD), a neurodegenerative disorder. Therefore, in the present study we designed neurotransmitter dopamine-loaded PLGA nanoparticles (DA NPs) to deliver dopamine to the brain. These nanoparticles slowly and constantly released dopamine, showed reduced clearance of dopamine in plasma, reduced quinone adduct formation, and decreased dopamine autoxidation. DA NPs were internalized in dopaminergic SH-SY5Y cells and dopaminergic neurons in the substantia nigra and striatum, regions affected in PD. Treatment with DA NPs did not cause reduction in cell viability and morphological deterioration in SH-SY5Y, as compared to bulk dopamine-treated cells, which showed reduced viability. Herein, we report that these NPs were able to cross the BBB and capillary endothelium in the striatum and substantia nigra in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Systemic intravenous administration of DA NPs caused significantly increased levels of dopamine and its metabolites and reduced dopamine-D2 receptor supersensitivity in the striatum of parkinsonian rats. Further, DA NPs significantly recovered neurobehavioral abnormalities in 6-OHDA-induced parkinsonian rats. Dopamine delivered through NPs did not cause additional generation of ROS, dopaminergic neuron degeneration, and ultrastructural changes in the striatum and substantia nigra as compared to 6-OHDA-lesioned rats. Interestingly, dopamine delivery through nanoformulation neither caused alterations in the heart rate and blood pressure nor showed any abrupt pathological change in the brain and other peripheral organs. These results suggest that NPs delivered dopamine into the brain, reduced dopamine autoxidation-mediated toxicity, and ultimately reversed neurochemical and neurobehavioral deficits in parkinsonian rats.

Heat shock proteins on the human sperm surface.

PubMed

Naaby-Hansen, Soren; Herr, John C

2010-01-01

The sperm plasma membrane is known to be critical to fertilization and to be highly regionalized into domains of head, mid- and principal pieces. However, the molecular composition of the sperm plasma membrane and its alterations during genital tract passage, capacitation and the acrosome reaction remains to be fully dissected. A two-dimensional gel-based proteomic study previously identified 98 human sperm proteins which were accessible for surface labelling with both biotin and radioiodine. In this report twelve dually labelled protein spots were excised from stained gels or PDVF membranes and analysed by mass spectrometry (MS) and Edman degradation. Seven members from four different heat shock protein (HSP) families were identified including HYOU1 (ORP150), HSPC1 (HSP86), HSPA5 (Bip), HSPD1 (HSP60), and several isoforms of the two testis-specific HSP70 chaperones HSPA2 and HSPA1L. An antiserum raised against the testis-specific HSPA2 chaperone reacted with three 65kDa HSPA2 isoforms and three high molecular weight surface proteins (78-79kDa, 84kDa and 90-93kDa). These proteins, together with seven 65kDa HSP70 forms, reacted with human anti-sperm IgG antibodies that blocked in vitro fertilization in humans. Three of these surface biotinylated human sperm antigens were immunoprecipitated with a rabbit antiserum raised against a linear peptide epitope in Chlamydia trachomatis HSP70. The results indicate diverse HSP chaperones are accessible for surface labelling on human sperm. Some of these share epitopes with C. trachomatis HSP70, suggesting an association between genital tract infection, immunity to HSP70 and reproductive failure. 2009 Elsevier Ireland Ltd. All rights reserved.

The effect of chronic fluoxetine on social isolation-induced changes on sucrose consumption, immobility behavior, and on serotonin and dopamine function in hippocampus and ventral striatum.

PubMed

Brenes, Juan C; Fornaguera, Jaime

2009-03-02

This study examined the effect of fluoxetine, a selective serotonin (5-HT) reuptake inhibitor, on isolation-induced changes on sucrose consumption and preference, spontaneous open-field activity, forced swimming behavior, and on tissue levels of 5-HT and dopamine (DA) in hippocampus and ventral striatum (VS). Male Sprague-Dawley rats were reared in social isolation or group housing from postnatal day 28. Thirty-two days later, half of the isolated animals were orally treated with fluoxetine (10mg/kg/day) during the following 34 days. At the end of this period, behavior was assessed and afterward ex-vivo tissue samples were obtained. It was found that fluoxetine restored isolation-increased sucrose consumption and immobility behavior, without affecting locomotor activity, which appeared slightly increased in isolated groups both treated and untreated. In the hippocampus, isolation rearing depleted 5-HT contents and increased 3,4-dihydroxyphenylacetic acid (DOPAC) levels, as well as 5-HT and DA turnover. These neurochemical alterations were reversed by fluoxetine. In VS, treated and untreated isolated rats showed higher 5-HT levels than grouped congeners. Although fluoxetine did not affect 5-HT and DA contents in this region, it slightly reversed the alterations in the 5-HT and DA turnover observed in isolated rats. Overall, social isolation impaired incentive and escape motivated behaviors. At the neurochemical level, isolation rearing affected 5-HT rather than DA activity, and this differential effect was more noticeable in hippocampus than in VS. The chronic treatment with fluoxetine during the last month of rearing somewhat prevented these behavioral and neurochemical alterations. Our data suggest that isolation rearing is an appropriate procedure to model some developmental-related alterations underlying depression disorders.

Oligomeric properties and DNA binding specificities of repressor isoforms from the Streptomyces bacteriophage phiC31.

PubMed

Wilson, S E; Smith, M C

1998-05-15

Three protein isoforms (74, 54 and 42 kDa) are expressed from repressor gene c in the Streptomyces temperate bacteriophage phiC31. Because expression of the two smaller isoforms, 54 and 42 kDa, is sufficient for superinfection immunity, the interaction between these isoforms was studied. The native 42 kDa repressor (Nat42) and an N-terminally 6x histidine-tagged 54 kDa isoform (His54) were shown by co-purification on a Ni-NTA column to interact in Streptomyces lividans . In vitro three repressor preparations, containing Nat42, His54 and the native 54 and 42 kDa isoforms expressed together (Nat54&42), were subjected to chemical crosslinking and gel filtration analysis. Homo- and hetero-tetramers were observed. Previous work showed that the smallest isoform bound to 17 bp operators containing aconservedinvertedrepeat (CIR) and that the CIRs were located at 16 loci throughout the phiC31 genome. One of the CIRs (CIR6) is believed to be critical for regulating the lytic pathway. The DNA binding activities of the three repressor preparations were studied using fragments containing CIRs (CIR3-CIR6) from the essential early region as templates for DNase I footprinting. Whereas Nat42 bound to CIR6, poorly to CIR5 but undetectably to CIR3 or CIR4, the Nat54&42 preparation could bind to all CIRs tested, albeit poorly to CIR3 and CIR4. The His54 isoform bound all CIRs tested. Isoforms expressed from the phiC31 repressor gene, like those which are expressed from many eukaryotic transcription factor genes, apparently have different binding specificities.

Person-organization fit and turnover intention: exploring the mediating effect of work engagement and the moderating effect of demand-ability fit.

PubMed

Peng, Jui-Chen; Lee, Yin-Ling; Tseng, Mei-Man

2014-03-01

Person-organization (P-O) fit is an important influencing factor on the intentions and attitudes of hospital nurses. The authors used a motivation-mechanism approach to conceptualize work engagement as a mediator and demand-ability (D-A) fit as a moderator to elicit the role of P-O fit in the turnover intention of nurses. This article explores whether the work engagement of nurses mediates the relationship between P-O fit and turnover intention and examines whether D-A fit moderates this relationship. The sample comprised 349 nurses working for two regional hospitals in Yilan County, Taiwan. Linear regression modeling analysis was conducted to test the proposed hypotheses. Results indicate that P-O fit has a negative effect on participant turnover intention. In addition, the work engagement of participants was found to mediate the impact of P-O fit on turnover intention. A new significant interactive relationship was discovered such that high D-A fit strengthened the negative relationship between P-O fit and turnover intention. The work engagement of professional nurses has attracted increasing attention in the literature on fit, particularly with regard to the linkage between P-O and fit-turnover intention. This study enhances the understanding of the function of P-O fit by considering perceived D-A fit. Nurse turnover is the main reason for the current shortage of nurses in Taiwan. Therefore, if the cognitive values of nurses and the organizational culture fit with hospital value systems, common values may facilitate a higher degree of nurse work engagement and, in turn, decrease turnover intention. In addition, recruiting employees with high D-A fit may help hospitals enhance the negative relationship between P-O fit and nurse turnover intention.

Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

PubMed

Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

2016-04-04

The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

Insights into the Structure of the Vip3Aa Insecticidal Protein by Protease Digestion Analysis

PubMed Central

Bel, Yolanda; Banyuls, Núria; Chakroun, Maissa; Escriche, Baltasar; Ferré, Juan

2017-01-01

Vip3 proteins are secretable proteins from Bacillus thuringiensis whose mode of action is still poorly understood. In this study, the activation process for Vip3 proteins was closely examined in order to better understand the Vip3Aa protein stability and to shed light on its structure. The Vip3Aa protoxin (of 89 kDa) was treated with trypsin at concentrations from 1:100 to 120:100 (trypsin:Vip3A, w:w). If the action of trypsin was not properly neutralized, the results of SDS-PAGE analysis (as well as those with Agrotis ipsilon midgut juice) equivocally indicated that the protoxin could be completely processed. However, when the proteolytic reaction was efficiently stopped, it was revealed that the protoxin was only cleaved at a primary cleavage site, regardless of the amount of trypsin used. The 66 kDa and the 19 kDa peptides generated by the proteases co-eluted after gel filtration chromatography, indicating that they remain together after cleavage. The 66 kDa fragment was found to be extremely resistant to proteases. The trypsin treatment of the protoxin in the presence of SDS revealed the presence of secondary cleavage sites at S-509, and presumably at T-466 and V-372, rendering C-terminal fragments of approximately 29, 32, and 42 kDa, respectively. The fact that the predicted secondary structure of the Vip3Aa protein shows a cluster of beta sheets in the C-terminal region of the protein might be the reason behind the higher stability to proteases compared to the rest of the protein, which is mainly composed of alpha helices. PMID:28387713

The VPH1 gene encodes a 95-kDa integral membrane polypeptide required for in vivo assembly and activity of the yeast vacuolar H(+)-ATPase.

PubMed

Manolson, M F; Proteau, D; Preston, R A; Stenbit, A; Roberts, B T; Hoyt, M A; Preuss, D; Mulholland, J; Botstein, D; Jones, E W

1992-07-15

Yeast vacuolar acidification-defective (vph) mutants were identified using the pH-sensitive fluorescence of 6-carboxyfluorescein diacetate (Preston, R. A., Murphy, R. F., and Jones, E. W. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 7027-7031). Vacuoles purified from yeast bearing the vph1-1 mutation had no detectable bafilomycin-sensitive ATPase activity or ATP-dependent proton pumping. The peripherally bound nucleotide-binding subunits of the vacuolar H(+)-ATPase (60 and 69 kDa) were no longer associated with vacuolar membranes yet were present in wild type levels in yeast whole cell extracts. The VPH1 gene was cloned by complementation of the vph1-1 mutation and independently cloned by screening a lambda gt11 expression library with antibodies directed against a 95-kDa vacuolar integral membrane protein. Deletion disruption of the VPH1 gene revealed that the VPH1 gene is not essential for viability but is required for vacuolar H(+)-ATPase assembly and vacuolar acidification. VPH1 encodes a predicted polypeptide of 840 amino acid residues (molecular mass 95.6 kDa) and contains six putative membrane-spanning regions. Cell fractionation and immunodetection demonstrate that Vph1p is a vacuolar integral membrane protein that co-purifies with vacuolar H(+)-ATPase activity. Multiple sequence alignments show extensive homology over the entire lengths of the following four polypeptides: Vph1p, the 116-kDa polypeptide of the rat clathrin-coated vesicles/synaptic vesicle proton pump, the predicted polypeptide encoded by the yeast gene STV1 (Similar To VPH1, identified as an open reading frame next to the BUB2 gene), and the TJ6 mouse immune suppressor factor.

Protein shift and antigenic variation in the S-layer of Campylobacter fetus subsp. venerealis during bovine infection accompanied by genomic rearrangement of sapA homologs.

PubMed Central

Garcia, M M; Lutze-Wallace, C L; Denes, A S; Eaglesome, M D; Holst, E; Blaser, M J

1995-01-01

Campylobacter fetus subsp. venerealis isolated from a case of human vaginosis was inoculated into the uterus of a C. fetus-negative heifer. Isolates obtained weekly from the vaginal mucus exhibited variations in high-molecular-mass-protein profiles from that of the original inoculum, which had a dominant 110-kDa S-layer protein. Immunoblots of the weekly isolates with monoclonal antibody probes against the 110-kDa S-layer protein and other C. fetus S-layer proteins demonstrated antigenic shifts. Genomic digests of the isolates probed with a 75-mer oligonucleotide of the conserved sapA region also indicated that antigenic variation of the S-layer is accompanied by DNA rearrangement. PMID:7721688

Toward the S3DVAR data assimilation software for the Caspian Sea

NASA Astrophysics Data System (ADS)

Arcucci, Rossella; Celestino, Simone; Toumi, Ralf; Laccetti, Giuliano

2017-07-01

Data Assimilation (DA) is an uncertainty quantification technique used to incorporate observed data into a prediction model in order to improve numerical forecasted results. The forecasting model used for producing oceanographic prediction into the Caspian Sea is the Regional Ocean Modeling System (ROMS). Here we propose the computational issues we are facing in a DA software we are developing (we named S3DVAR) which implements a Scalable Three Dimensional Variational Data Assimilation model for assimilating sea surface temperature (SST) values collected into the Caspian Sea with observations provided by the Group of High resolution sea surface temperature (GHRSST). We present the algorithmic strategies we employ and the numerical issues on data collected in two of the months which present the most significant variability in water temperature: August and March.

[Development, science, and politics: the debate surrounding creation of the Instituto Internacional da Hiléia Amazônica].

PubMed

Magalhães, Rodrigo Cesar da Silva; Maio, Marcos Chor

2007-12-01

The article uses the debate surrounding creation of the Instituto Internacional da Hiléia Amazônica (International Institute of the Hylean Amazon--IIHA) as a point of departure for analyzing the topic of development. We first address post-World War II relations between science and development. Next, we examine the Brazilian government's initiatives in the Amazon during the 1940s and how the IIHA project was received. Lastly, we analyze the controversies ignited in Brazil by Unesco's plan. The IIHA project was a catalyst of the development debate in post-World War II Brazil. The discussions then sparked in Brazil and the project's denouement solidified a development model for the Amazon that even today underpins initiatives taken in the region.

Violence against Amazon women.

PubMed

Lima, Vera Lúcia de Azevedo; Souza, Maria de Lourdes de; Monticelli, Marisa; Oliveira, Marília de Fátima Vieira de; Souza, Carlos Benedito Marinho de; Costa, Carlos Alberto Leal da; Brüggemann, Odaléa Maria

2009-01-01

This quantitative and exploratory study analyzed violence against Amazon women presented in print media according to type and severity, and whether aggressors fell under the Maria da Penha law. A total of 181 issues of a regional newspaper were consulted. Based on content analysis, 164 items addressing violence against women were selected and 46 were included in the corpus of analysis. Results were gathered in three thematic groups: women killed with cruelty, sexual violence against women regardless of age, and violence against women and the limitations of the Maria da Penha law. Violence against these women varied in terms of form and severity, including up to homicide. Women are submitted to sexual violence from childhood through adulthood. The enforcement of this law shows the community it has a means to cope with this social phenomenon.

Effect of the inclusion of mobile phone interviews to Vigitel.

PubMed

Bernal, Regina Tomie Ivata; Malta, Deborah Carvalho; Claro, Rafael Moreira; Monteiro, Carlos Augusto

2017-06-01

To evaluate the impact on the prevalence changes of risk factors for chronic diseases, published in the Surveillance System of Risk and Protection Factors for Chronic Diseases by Telephone Survey (Vigitel), after the inclusion of data from the population only with mobile phone. Our study used data from the 26 State capitals and Federal District of Brazil obtained by the National Survey on Health (PNS) and Vigitel, both held in 2013. In each capital, we added a subsample of 200 adults living in households with only mobile phones, extracted from PNS, to the Vigitel 2013 database, with approximately 1,900 households, named Vigitel dual frame. Vigitel results showed absolute relative biases between 0.18% and 14.85%. The system underestimated the frequency of adult smokers (10.77%), whole milk consumption (52.82%), and soft drink consumption (22.22%). Additionally, it overestimated the prevalence of hypertension (25.46%). In the simulations using Vigitel dual frame, with inclusion of the sample of adults living in households with only mobile phones, the bias of estimates was reduced in five out of eight analyzed indicators, with greater effects in regions with lower rates of landline coverage. In comparing regions, we observed negative correlation (ρ = -0.91) between the percentage of indicators with presence of bias and the percentage of households with only mobile phone. The results of this study indicate the benefits of including a subsample of 200 adults with only mobile phone on the Vigitel sample, especially in the capitals of the North and Northeast regions. Avaliar o impacto nas mudanças das prevalências de fatores de risco de doenças crônicas, divulgadas no Vigitel, após a inclusão de dados provenientes da população com somente telefone celular. O estudo utilizou os dados das capitais obtidos da Pesquisa Nacional de Saúde e do Vigitel, que foram realizados em 2013. Em cada capital, acrescentou-se uma subamostra de 200 adultos residentes em domicílios com somente celular, extraída da PNS, à base de dados do Vigitel 2013, com aproximadamente 1.900 domicílios, denominado Vigitel cadastro duplo. Os resultados do Vigitel mostraram vícios relativos absolutos entre 0,18% e 14,85%. O sistema subestimou a frequência de adultos fumantes (10,77%), o consumo de leite com teor integral de gordura (52,82%) e o consumo de refrigerante (22,22%). Adicionalmente, superestimou a prevalência de hipertensão (25,46%). Nas simulações utilizando o Vigitel cadastro duplo, com inclusão da amostra de adultos residentes em domicílios com somente celular, o vício das estimativas foi reduzido em cinco de oito indicadores analisados, com maiores efeitos nas regiões com menores taxas de cobertura de telefonia fixa. Na comparação entre as regiões, observa-se correlação negativa (ρ = -0,91) entre o percentual de indicadores com presença de vício e o percentual de cobertura de domicílios com somente celular. Os resultados do presente estudo indicam os benefícios da inclusão de uma subamostra de 200 adultos com somente celular na amostra do Vigitel, especialmente nas capitais das regiões Norte e Nordeste.

Protein-protein interaction studies reveal the Plasmodium falciparum merozoite surface protein-1 region involved in a complex formation that binds to human erythrocytes.

PubMed

Paul, Gourab; Deshmukh, Arunaditya; Kumar Chourasia, Bishwanath; Kalamuddin, Md; Panda, Ashutosh; Kumar Singh, Susheel; Gupta, Puneet K; Mohmmed, Asif; Chauhan, Virender S; Theisen, Michael; Malhotra, Pawan

2018-03-29

Plasmodium falciparum merozoite surface protein (PfMSP) 1 has been studied extensively as a vaccine candidate antigen. PfMSP-1 undergoes proteolytic processing into four major products, such as p83, p30, p38, and p42, that are associated in the form of non-covalent complex(s) with other MSPs. To delineate MSP1 regions involved in the interaction with other MSPs, here we expressed recombinant proteins (PfMSP-1 65 ) encompassing part of p38 and p42 regions and PfMSP-1 19 PfMSP-1 65 interacted strongly with PfMSP-3, PfMSP-6, PfMSP-7, and PfMSP-9, whereas PfMSP-1 19 did not interact with any of these proteins. Since MSP-1 complex binds human erythrocytes, we examined the ability of these proteins to bind human erythrocyte. Among the proteins of MSP-1 complex, PfMSP-6 and PfMSP-9 bound to human erythrocytes. Serological studies showed that PfMSP-1 65 was frequently recognized by sera from malaria endemic regions, whereas this was not the case for PfMSP-1 19 In contrast, antibodies against PfMSP-1 19 showed much higher inhibition of merozoite invasion compared with antibodies against the larger PfMSP-1 65 fragment. Importantly, anti-PfMSP-1 19 antibodies recognized both recombinant proteins, PfMSP-1 19 and PfMSP-1 65 ; however, anti-PfMSP-1 65 antibody failed to recognize the PfMSP-1 19 protein. Taken together, these results demonstrate that PfMSP-1 sequences upstream of the 19 kDa C-terminal region are involved in molecular interactions with other MSPs, and these sequences may probably serve as a smoke screen to evade antibody response to the membrane-bound C-terminal 19 kDa region. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Variation of δ2H, δ18O & δ13C in crude palm oil from different regions in Malaysia: Potential of stable isotope signatures as a key traceability parameter.

PubMed

Muhammad, Syahidah Akmal; Seow, Eng-Keng; Mohd Omar, A K; Rodhi, Ainolsyakira Mohd; Mat Hassan, Hasnuri; Lalung, Japareng; Lee, Sze-Chi; Ibrahim, Baharudin

2018-01-01

A total of 33 crude palm oil samples were randomly collected from different regions in Malaysia. Stable carbon isotopic composition (δ 13 C) was determined using Flash 2000 elemental analyzer while hydrogen and oxygen isotopic compositions (δ 2 H and δ 18 O) were analyzed by Thermo Finnigan TC/EA, wherein both instruments were coupled to an isotope ratio mass spectrometer. The bulk δ 2 H, δ 18 O and δ 13 C of the samples were analyzed by Hierarchical Cluster Analysis (HCA), Principal Component Analysis (PCA) and Orthogonal Partial Least Square-Discriminant Analysis (OPLS-DA). Unsupervised HCA and PCA methods have demonstrated that crude palm oil samples were grouped into clusters according to respective state. A predictive model was constructed by supervised OPLS-DA with good predictive power of 52.60%. Robustness of the predictive model was validated with overall accuracy of 71.43%. Blind test samples were correctly assigned to their respective cluster except for samples from southern region. δ 18 O was proposed as the promising discriminatory marker for discerning crude palm oil samples obtained from different regions. Stable isotopes profile was proven to be useful for origin traceability of crude palm oil samples at a narrower geographical area, i.e. based on regions in Malaysia. Predictive power and accuracy of the predictive model was expected to improve with the increase in sample size. Conclusively, the results in this study has fulfilled the main objective of this work where the simple approach of combining stable isotope analysis with chemometrics can be used to discriminate crude palm oil samples obtained from different regions in Malaysia. Overall, this study shows the feasibility of this approach to be used as a traceability assessment of crude palm oils. Copyright © 2017 The Chartered Society of Forensic Sciences. Published by Elsevier B.V. All rights reserved.

Dynamics of Flow in the Region of the Tsugaru Strait.

DTIC Science & Technology

1981-03-01

possessed sufficient initial vrticity at a strait outlet. Beardslev and Hart (1978) pro- duced anal yr i c sol It i ons -t the out t low ci rcul at ion for a...38. ’da , M . , 1934, Hlydrographical studies based on simll taneous oceano - ,graphi cal surveys made in the Japan Sea and i ts adjacent waters during

Infectivity titration of a prototype strain of hepatitis E virus in cynomolgus monkeys.

PubMed

Tsarev, S A; Tsareva, T S; Emerson, S U; Yarbough, P O; Legters, L J; Moskal, T; Purcell, R H

1994-06-01

The infectivity titer of a standard stock of the SAR-55 strain of hepatitis E virus (HEV) was determined in cynomolgus macaques (Macaca fascicularis) and the effect of dose on the course of the infection was examined by weekly monitoring of alanine aminotransferase (ALT) and anti-HEV levels. Antibody to HEV (anti-HEV) was measured with ELISAs based on ORF-2 recombinant antigens consisting of either a 55 kDa region expressed in insect cells or shorter regions expressed as fusion proteins in bacteria. The ELISA based on the 55 kDa antigen was generally more sensitive. The infectivity titer of SAR-55 was 10(6) cynomolgus 50% infectious doses per gram of feces. The infectivity titer corresponded to the HEV genome titer of the inoculum as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Anti-HEV IgM was detected in only a portion of the animals that had an anti-HEV IgG response. Biochemical evidence of hepatitis was most prominent in animals that were inoculated with the higher concentrations of virus and the incubation period to seroconversion was prolonged in animals that received the lower doses.

Molecular substrates of action control in cortico-striatal circuits.

PubMed

Shiflett, Michael W; Balleine, Bernard W

2011-09-15

The purpose of this review is to describe the molecular mechanisms in the striatum that mediate reward-based learning and action control during instrumental conditioning. Experiments assessing the neural bases of instrumental conditioning have uncovered functional circuits in the striatum, including dorsal and ventral striatal sub-regions, involved in action-outcome learning, stimulus-response learning, and the motivational control of action by reward-associated cues. Integration of dopamine (DA) and glutamate neurotransmission within these striatal sub-regions is hypothesized to enable learning and action control through its role in shaping synaptic plasticity and cellular excitability. The extracellular signal regulated kinase (ERK) appears to be particularly important for reward-based learning and action control due to its sensitivity to combined DA and glutamate receptor activation and its involvement in a range of cellular functions. ERK activation in striatal neurons is proposed to have a dual role in both the learning and performance factors that contribute to instrumental conditioning through its regulation of plasticity-related transcription factors and its modulation of intrinsic cellular excitability. Furthermore, perturbation of ERK activation by drugs of abuse may give rise to behavioral disorders such as addiction. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Sexuality and STD/AIDS prevention: social representations by rural men in a county in the Zona da Mata region in Pernambuco, Brazil].

PubMed

Alves, Maria de Fátima Paz

2003-01-01

This study analyzes the concepts displayed by rural men in the Zona da Mata region in the State of Pernambuco, Brazil, concerning their sexual practices and STD/AIDS prevention. The study adopts a qualitative methodology, having interviewed 22 men According to the interviews, their first sexual intercourse is characterized as a learning experience and is sometimes marked by violence. They make a distinction between the "woman at home" and "street women"; they acknowledge women's sexual desire and value reciprocity in sexual relations, differentiating between the kinds of sex they have with different categories of women. Seven men report homoerotic experiences during adolescence, which they ascribe to immaturity, not affecting their heterosexual identity. Condom use, perceived in a negative light, is inconstant and irregular, inversely proportional to knowing the female partner. STDs in general inspire little fear, while AIDS is associated with death; the interviewees do not see themselves at risk of acquiring HIV. Ambiguities in the men's discourse, together with a basically ineffective approach by health services and preventive campaigns, reveal a high level of exposure to the risk of contracting STDs/AIDS among the interviewees and their female or male partners.

Genetic Diversity and Natural Selection in 42 kDa Region of Plasmodium vivax Merozoite Surface Protein-1 from China-Myanmar Endemic Border.

PubMed

Zhou, Xia; Tambo, Ernest; Su, Jing; Fang, Qiang; Ruan, Wei; Chen, Jun-Hu; Yin, Ming-Bo; Zhou, Xiao-Nong

2017-10-01

Plasmodium vivax merozoite surface protein-1 (PvMSP1) gene codes for a major malaria vaccine candidate antigen. However, its polymorphic nature represents an obstacle to the design of a protective vaccine. In this study, we analyzed the genetic polymorphism and natural selection of the C-terminal 42 kDa fragment within PvMSP1 gene (Pv MSP142) from 77 P. vivax isolates, collected from imported cases of China-Myanmar border (CMB) areas in Yunnan province and the inland cases from Anhui, Yunnan, and Zhejiang province in China during 2009-2012. Totally, 41 haplotypes were identified and 30 of them were new haplotypes. The differences between the rates of non-synonymous and synonymous mutations suggest that PvMSP142 has evolved under natural selection, and a high selective pressure preferentially acted on regions identified of PvMSP133. Our results also demonstrated that PvMSP142 of P. vivax isolates collected on China-Myanmar border areas display higher genetic polymorphisms than those collected from inland of China. Such results have significant implications for understanding the dynamic of the P. vivax population and may be useful information towards China malaria elimination campaign strategies.

A metal-linked gapped zipper model is proposed for the 90 kDa heat shock protein-estrogen receptor interface.

PubMed

Schwartz, J A; Mizukami, H

1991-06-01

A novel arrangement is proposed for the association of the 90 kDa heat shock protein (hsp 90) dimer and the human estrogen receptor (hER) monomer. Secondary structure analyses of the hsp 90 molecule reveal the presence of a cysteine-containing, leucine-rich, heptad repeat, which we refer to as region C. Similar analyses on the hER, at its hormone binding domain (HBD), have indicated the presence of a central subdomain bordered by 2 alpha-helical flanking segments which also display the heptad substructure. Due to its predicted potential for conformational change (1) we refer to this central subdomain as the Helix Conversion Unit or HCU. It contains an HX5C peptide and shares significant homology with the metal-binding domain of a gag-encoded HIV-LAV protein (2). We predict that, by virtue of its presence in duplicate, region C may be capable of simultaneous leucine zipper-like pairing with the hER at its flanking helices, as well as the formation of a shared CCHC-box-type metal binding link with the same hER at the putative HCU which lies in between.

Flaxseed oil as a neuroprotective agent on lead acetate-induced monoamineric alterations and neurotoxicity in rats.

PubMed

Abdel Moneim, Ahmed E

2012-09-01

Lead remains a considerable occupational and public health problem, which is known to cause a number of adverse effects in both man and animals. Here, the neuroprotective effect of flaxseed oil (1,000 mg/kg) on lead acetate (20 mg/kg) induced alternation in monoamines and brain oxidative stress was examined in rats. The levels of lead, dopamine (DA), norepinephrine (NE), serotonin (5-HT), lipid peroxidation, nitrite/nitrate (NO), and glutathione (GSH) were determined; also, the activity of acetylcholinesterase (AChE) and Na(+)-K(+)-ATPase were estimated on different brain regions of adult male albino rats. The level of lead was markedly elevated in different brain regions of rats. This leads to enhancement of lipid peroxidation and NO production in brain with concomitant reduction in AChE activity and GSH level. In addition, the levels of DA, NE, and 5-HT were decreased in the brain. These findings were associated with BAX over expression. Treatment of rats with flaxseed oil induced a marked improvement in most of the studied parameters as well as the immunohistochemistry features. These data indicated that dietary flaxseed oil provide protection against lead-induced oxidative stress and neurotoxic effects.

Protective immunity provided by a new modified SERA protein peptide: its immunogenetic characteristics and correlation with 3D structure.

PubMed

Bermúdez, Adriana; Moreno-Vranich, Armando; Patarroyo, Manuel E

2012-07-01

The serine repeat antigen (SERA) protein is a leading candidate molecule for inclusion as a component in a multi-antigen, multi-stage, minimal subunit-based, chemically synthesised anti-malarial vaccine. Peptides having high red blood cell binding affinity (known as HABPs) have been identified in this protein. The 6733 HABP was located in the C-terminal portion of the 47-kDa fragment while HABP 6754 was located in the C-terminal region of the 56-kDa fragment. These conserved HABPs failed to induce an immune response. Critical red blood cell binding residues and/or their neighbours (assessed by glycine-analogue scanning) were replaced by others having the same mass, volume and surface but different polarity, rendering some of them highly immunogenic when assessed by antibody production against the parasite or its proteins and protection-inducers against experimental challenge with a highly infectious Aotus monkey-adapted Plasmodium falciparum strain. This manuscript presents some modified HABPs as vaccine candidate components for enriching our tailor-made anti-malarial vaccine repertoire, as well as their 3D structure obtained by 1H-NMR displaying a short-structured region, differently from the native ones having random structures.

Weathering phases recorded by gnammas developed since last glaciation at Serra da Estrela, Portugal

NASA Astrophysics Data System (ADS)

Domínguez-Villar, David; Razola, Laura; Carrasco, Rosa M.; Jennings, Carrie E.; Pedraza, Javier

2009-09-01

The morphometrical analysis of gnammas (weathering pits) in granite landscapes has been used to establish the relative chronology of recent erosive surfaces and to provide the weathering history in a region. To test the validity of gnammas as relative chronometer indicators, and the reliability of the obtained weathering record, two sites have been studied in Serra da Estrela, Portugal. The first site is within the limits of the glacier that existed in these mountains during the last glaciation, whereas the second site is located in an unglaciated sector of the mountains, which preserves a longer record of weathering in the bedrock surface. The number of gnamma weathering phases recorded in the latter site (8) is larger than those from the former (6). Correlation between both measurement stations based on morphometrical criteria is excellent for the younger six weathering phases (1 to 6). Consequently, the parameter used for relative chronology ( δ-value) has been verified to be age dependent, although absolute values are modulated by microclimate due to altitude variations. The weathering record was essentially duplicated once the surfaces at both sites were exposed, demonstrating the reliability of gnamma evolution as a post-glacial environmental indicator for the region.

Modeling serotonin uptake in the lung shows endothelial transporters dominate over cleft permeation

PubMed Central

Bassingthwaighte, James B.

2013-01-01

A four-region (capillary plasma, endothelium, interstitial fluid, cell) multipath model was configured to describe the kinetics of blood-tissue exchange for small solutes in the lung, accounting for regional flow heterogeneity, permeation of cell membranes and through interendothelial clefts, and intracellular reactions. Serotonin uptake data from the Multiple indicator dilution “bolus sweep” experiments of Rickaby and coworkers (Rickaby DA, Linehan JH, Bronikowski TA, Dawson CA. J Appl Physiol 51: 405–414, 1981; Rickaby DA, Dawson CA, and Linehan JH. J Appl Physiol 56: 1170–1177, 1984) and Malcorps et al. (Malcorps CM, Dawson CA, Linehan JH, Bronikowski TA, Rickaby DA, Herman AG, Will JA. J Appl Physiol 57: 720–730, 1984) were analyzed to distinguish facilitated transport into the endothelial cells (EC) and the inhibition of tracer transport by nontracer serotonin in the bolus of injectate from the free uninhibited permeation through the clefts into the interstitial fluid space. The permeability-surface area products (PS) for serotonin via the inter-EC clefts were ∼0.3 ml·g−1·min−1, low compared with the transporter-mediated maximum PS of 13 ml·g−1·min−1 (with Km = ∼0.3 μM and Vmax = ∼4 nmol·g−1·min−1). The estimates of serotonin PS values for EC transporters from their multiple data sets were similar and were influenced only modestly by accounting for the cleft permeability in parallel. The cleft PS estimates in these Ringer-perfused lungs are less than half of those for anesthetized dogs (Yipintsoi T. Circ Res 39: 523–531, 1976) with normal hematocrits, but are compatible with passive noncarrier-mediated transport observed later in the same laboratory (Dawson CA, Linehan JH, Rickaby DA, Bronikowski TA. Ann Biomed Eng 15: 217–227, 1987; Peeters FAM, Bronikowski TA, Dawson CA, Linehan JH, Bult H, Herman AG. J Appl Physiol 66: 2328–2337, 1989) The identification and quantitation of the cleft pathway conductance from these studies affirms the importance of the cleft permeation. PMID:23645496

The prion protein protease sensitivity, stability and seeding activity in variably protease sensitive prionopathy brain tissue suggests molecular overlaps with sporadic Creutzfeldt-Jakob disease.

PubMed

Peden, Alexander H; Sarode, Deep P; Mulholland, Carl R; Barria, Marcelo A; Ritchie, Diane L; Ironside, James W; Head, Mark W

2014-10-21

Variably protease sensitive prionopathy (VPSPr) is a recently described, sporadic human prion disease that is pathologically and biochemically distinct from the currently recognised sporadic Creutzfeldt-Jakob disease (sCJD) subtypes. The defining biochemical features of the abnormal form of the prion protein (PrPSc) in VPSPr are increased sensitivity to proteolysis and the presence of an N- and C-terminally cleaved ~8 kDa protease resistant PrPSc (PrPres) fragment. The biochemical and neuropathological profile of VPSPr has been proposed to resemble either Gerstmann-Sträussler-Scheinker syndrome (GSS) or familial CJD with the PRNP-V180I mutation. However, in some cases of VPSPr two protease resistant bands have been observed in Western blots that co-migrate with those of type 2 PrPres, suggesting that a proportion of the PrPSc present in VPSPr has properties similar to those of sCJD. Here, we have used conformation dependent immunoassay to confirm the presence of PrPSc in VPSPr that is more protease sensitive compared with sCJD. However, CDI also shows that a proportion of PrPSc in VPSPr resists PK digestion of its C-terminus, distinguishing it from GSS associated with ~8 kDa PrPres, and showing similarity to sCJD. Intensive investigation of a single VPSPr case with frozen tissue from multiple brain regions shows a broad, region-specific spectrum of protease sensitivity and differential stability of PrPSc in the absence of PK treatment. Finally, using protein misfolding cyclic amplification and real-time quaking induced conversion, we show that VPSPr PrPSc has the potential to seed conversion in vitro and that seeding activity is dispersed through a broad range of aggregate sizes. We further propose that seeding activity is associated with the ~19 and ~23 kDa PrPres rather than the ~8 kDa fragment. Therefore, PrPSc in VPSPr is heterogeneous in terms of protease sensitivity and stability to denaturation with the chaotrope GdnHCl and includes a proportion with similar properties to that found in sCJD.

Brain Region-Specific Trafficking of the Dopamine Transporter

PubMed Central

Block, Ethan R.; Nuttle, Jacob; Balcita-Pedicino, Judith Joyce; Caltagarone, John; Watkins, Simon C.

2015-01-01

The dopamine (DA) transporter (DAT) controls dopaminergic neurotransmission by removing extracellular DA. Although DA reuptake is proposed to be regulated by DAT traffic to and from the cell surface, the membrane trafficking system involved in the endocytic cycling of DAT in the intact mammalian brain has not been characterized. Hence, we performed immunolabeling and quantitative analysis of the subcellular and regional distribution of DAT using the transgenic knock-in mouse expressing hemagglutinin (HA) epitope-tagged DAT (HA-DAT) and by using a combination of electron microscopy and a novel method for immunofluorescence labeling of HA-DAT in acute sagittal brain slices. Both approaches demonstrated that, in midbrain somatodendritic regions, HA-DAT was present in the plasma membrane, endoplasmic reticulum, and Golgi complex, with a small fraction in early and recycling endosomes and an even smaller fraction in late endosomes and lysosomes. In the striatum and in axonal tracts between the midbrain and striatum, HA-DAT was detected predominantly in the plasma membrane, and quantitative analysis revealed increased DAT density in striatal compared with midbrain plasma membranes. Endosomes were strikingly rare and lysosomes were absent in striatal axons, in which there was little intracellular HA-DAT. Acute administration of amphetamine in vivo (60 min) or to slices ex vivo (10–60 min) did not result in detectable changes in DAT distribution. Altogether, these data provide evidence for regional differences in DAT plasma membrane targeting and retention and suggest a surprisingly low level of endocytic trafficking of DAT in the striatum along with limited DAT endocytic activity in somatodendritic areas. SIGNIFICANCE STATEMENT The dopamine transporter (DAT) is the key regulator of the dopamine neurotransmission in the CNS. In the present study, we developed a new approach for studying DAT localization and dynamics in intact neurons in acute sagittal brain slices from the knock-in mouse expressing epitope-tagged DAT. For the first time, the fluorescence imaging analysis of DAT was combined with the immunogold labeling of DAT and quantitative electron microscopy. In contrast to numerous studies of DAT trafficking in heterologous expression systems and dissociated cultured neurons, studies in intact neurons revealed a surprisingly low amount of endocytic trafficking of DAT at steady state and after acute amphetamine treatment and suggested that non-vesicular transport could be the main mechanism establishing DAT distribution within the dopaminergic neuron. PMID:26377471

Induction of an interleukin-1 receptor (IL-1R) on monocytic cells. Evidence that the receptor is not encoded by a T cell-type IL-1R mRNA.

PubMed

Spriggs, M K; Lioubin, P J; Slack, J; Dower, S K; Jonas, U; Cosman, D; Sims, J E; Bauer, J

1990-12-25

Primary human monocytes and the human monocytic cell line THP-1 were induced to express receptors for interleukin-1 alpha (IL-1 alpha) and IL-1 beta. Treatment of primary monocytes with dexamethasone resulted in a 10-fold increase in receptor number over untreated cells, to approximately 2,000 receptors/cell. Treatment of THP-1 cells with phorbol ester followed by prostaglandin E2 and dexamethasone resulted in the expression of approximately 30,000 receptors/cell. Competitive binding assays on THP-1 cells showed that both IL-1 alpha and IL-1 beta bind to the same receptor. The monocyte IL-1R is significantly smaller (63 kDa) than the T cell IL-1R (80 kDa) and is immunologically distinct. However, induction of monocytes and monocytic cell lines leads to the appearance of an abundant mRNA of approximately 5,000 bases which hybridizes to a cDNA probe from the T cell-type IL-1R. Sequence data obtained from a cDNA clone of this mRNA indicate that the message is identical to the T cell IL-1R mRNA throughout the coding region. A smaller mRNA, also homologous to the T cell IL-1R mRNA, accumulated in induced THP-1 cells and has a shorter 3'-untranslated region than the larger. Data are presented which suggest that neither form of this message encodes the 63-kDa IL-1R, but rather that this protein is the product of a separate nonhomologous mRNA.

Production of recombinant botulism antigens: a review of expression systems.

PubMed

Moreira, G M S G; Cunha, C E P; Salvarani, F M; Gonçalves, L A; Pires, P S; Conceição, F R; Lobato, F C F

2014-08-01

Botulism is a paralytic disease caused by intoxication with neurotoxins produced by Clostridium botulinum. Despite their similar mechanism of action, the botulinum neurotoxins (BoNT) are classified in eight serotypes (A to H). As to veterinary medicine, the impact of this disease is essentially economic, since different species of production animals can be affected, especially by BoNT/C and D. In human health, botulism is feared in a possible biological warfare, what would involve mainly the BoNT/A, B, E and F. In both cases, the most effective way to deal with botulism is through prevention, which involves vaccination. However, the current vaccines against this disease have several drawbacks on their process of production and, besides this, can be dangerous to producers since it requires certain level of biosafety. This way, recombinant vaccines have been shown to be a great alternative for the development of vaccines against both animal and human botulism. All BoNTs have a 50-kDa light chain (LC) and a 100-kDa heavy chain (HC). The latter one presents two domains of 50 kDa, called the N-terminal (HN) and C-terminal (HC) halves. Among these regions, the HC alone seem to confer the proper immune response against intoxication. Since innumerous studies describe the expression of these distinct regions using different systems, strategies, and protocols, it is difficult to define the best option for a viable vaccine production. Thereby, the present review describes the problematic of botulism and discusses the main advances for the viable production of vaccines for both human and veterinary medicine using recombinant antigens. Copyright © 2014 Elsevier Ltd. All rights reserved.

PAK2 is cleaved and activated during hyperosmotic shock-induced apoptosis via a caspase-dependent mechanism: evidence for the involvement of oxidative stress.

PubMed

Chan, W H; Yu, J S; Yang, S D

1999-03-01

Hyperosmotic shock elicits a stress response in mammalian cells and can lead to apoptotic cell death. In the present study, we report that hyperosmotic shock can induce activation of a 36 kDa kinase detected by an in-gel kinase assay in several cell types, including mouse Balb/c 3T3 fibroblasts, and human Hep 3B and A431 cells. This 36 kDa kinase can be recognized by an antibody against the C-terminal region of a family of p21Cdc42/Rac-activated kinases (PAKs) on immunoblot. Further studies with this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 demonstrate that hyperosmotic shock can induce cleavage of PAK2 to generate a 36 kDa C-terminal catalytic fragment in cells. The cleavage and activation of PAK2 was found to be closely associated with both DNA fragmentation and activation of an ICE/CED-3 family cysteine protease termed caspase-3 in hyperosmotically shocked cells. Furthermore, pretreating the cells with two caspase inhibitors (Ac-DEVD-cho and Ac-YVAD-cmk) could inhibit both cleavage/activation of PAK2 and DNA fragmentation induced by hyperosmotic shock. Moreover, all these hyperosmotic shock-induced changes (i.e., activation of caspase-3, cleavage/activation of PAK2, and DNA fragmentation) in cells could be blocked by antioxidants such as ascorbic acid (vitamine C), alpha-tocopherol (vitamine E), dithiothreitol, beta-mercaptoethanol, and glutathione. Taken together, our results show that PAK2 is cleaved and activated via a caspase-dependent mechanism during hyperosmotic shock-induced apoptosis and suggest the involvement of antioxidant-preventable oxidative stress in inducing this process.

Decoding the individual finger movements from single-trial functional magnetic resonance imaging recordings of human brain activity.

PubMed

Shen, Guohua; Zhang, Jing; Wang, Mengxing; Lei, Du; Yang, Guang; Zhang, Shanmin; Du, Xiaoxia

2014-06-01

Multivariate pattern classification analysis (MVPA) has been applied to functional magnetic resonance imaging (fMRI) data to decode brain states from spatially distributed activation patterns. Decoding upper limb movements from non-invasively recorded human brain activation is crucial for implementing a brain-machine interface that directly harnesses an individual's thoughts to control external devices or computers. The aim of this study was to decode the individual finger movements from fMRI single-trial data. Thirteen healthy human subjects participated in a visually cued delayed finger movement task, and only one slight button press was performed in each trial. Using MVPA, the decoding accuracy (DA) was computed separately for the different motor-related regions of interest. For the construction of feature vectors, the feature vectors from two successive volumes in the image series for a trial were concatenated. With these spatial-temporal feature vectors, we obtained a 63.1% average DA (84.7% for the best subject) for the contralateral primary somatosensory cortex and a 46.0% average DA (71.0% for the best subject) for the contralateral primary motor cortex; both of these values were significantly above the chance level (20%). In addition, we implemented searchlight MVPA to search for informative regions in an unbiased manner across the whole brain. Furthermore, by applying searchlight MVPA to each volume of a trial, we visually demonstrated the information for decoding, both spatially and temporally. The results suggest that the non-invasive fMRI technique may provide informative features for decoding individual finger movements and the potential of developing an fMRI-based brain-machine interface for finger movement. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Exploring the relationship between social attachment and dopamine D2/3 receptor availability in the brains of healthy humans using [11C]-(+)-PHNO.

PubMed

Caravaggio, Fernando; Chung, Jun Ku; Gerretsen, Philip; Fervaha, Gagan; Nakajima, Shinichiro; Plitman, Eric; Iwata, Yusuke; Wilson, Alan; Graff-Guerrero, Ariel

2017-04-01

Differences in striatal dopamine (DA) function may be related to differences in the degree of social attachment to others. Using positron emission tomography (PET), socially detached persons demonstrate reduced DA D 2/3 receptor (D 2/3 R) availability in the striatum. However, previous PET studies have only used antagonist radiotracers for D 2/3 R and have not specifically examined regions of interest (ROIs) such as the ventral striatum (VS). In 32 healthy persons, we investigated the relationship between self-reported attachment and DA D 2/3 R availability in striatal and extrastriatal ROIs as measured using the agonist radiotracer [ 11 C]-(+)-PHNO. Surprisingly, more social attachment-as measured by the attachment subscale of the temperament and character inventory-was related to less [ 11 C]-(+)-PHNO binding in the VS (r(30) = -.43, p = .01). This relationship held in a subsample who also completed the detachment subscale of the Karolinska Scales of Personality (r(10) = .62, p = .03). However, no relationships were observed with BP ND in the dorsal striatum or D 3 R-specific ROIs. One potential explanation for these findings is that persons who are more socially detached have less endogenous DA occupying D 2/3 R in the VS. This interpretation warrants investigation by future research. These findings may help us better understand the neurochemical basis of attachment.

Perinatal methadone exposure affects dopamine, norepinephrine, and serotonin in the weanling rat.

PubMed

Robinson, S E; Maher, J R; Wallace, M J; Kunko, P M

1997-01-01

On gestational day 7 pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. On postnatal day 21, dopamine (DA), norepinephrine (NE), serotonin (5-HT), and their metabolites were analyzed. Perinatal methadone exposure disrupted dopaminergic, noradrenergic, and serotonergic activity in a brain region- and gender-specific fashion. The ratio of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) to DA was reduced in the frontal cortex of males exposed to methadone postnatally. No effects of perinatal methadone exposure were observed on DA and DOPAC in the striatum. The ratio of 3-methoxy-4-hydroxyphenylglycol (MOPEG) to NE in the hippocampus was increased significantly in males exposed to methadone prenatally. Striatal and parietal cortical 5-hydroxyindoleacetic acid (5-HIAA), but not its ratio to 5-HT, was increased slightly in rats exposed to methadone postnatally. Although parietal cortical 5-HT, 5-HIAA, and 5-hydroxytryptophan were all affected by perinatal methadone exposure, the ratios of metabolite and precursor to 5-HT were not affected. Effects of methadone exposure appeared to depend upon the developmental stage at which exposure occurred and did not appear to result from the phenomenon of neonatal withdrawal. Changes in activity of these three neurotransmitter systems may contribute to the effect of perinatal methadone on the activity of other neurons, such as cholinergic neurons.

Development and Implementation of Dynamic Scripts to Execute Cycled WRF/GSI Forecasts

NASA Technical Reports Server (NTRS)

Zavodsky, Bradley; Srikishen, Jayanthi; Berndt, Emily; Li, Quanli; Watson, Leela

2014-01-01

Automating the coupling of data assimilation (DA) and modeling systems is a unique challenge in the numerical weather prediction (NWP) research community. In recent years, the Development Testbed Center (DTC) has released well-documented tools such as the Weather Research and Forecasting (WRF) model and the Gridpoint Statistical Interpolation (GSI) DA system that can be easily downloaded, installed, and run by researchers on their local systems. However, developing a coupled system in which the various preprocessing, DA, model, and postprocessing capabilities are all integrated can be labor-intensive if one has little experience with any of these individual systems. Additionally, operational modeling entities generally have specific coupling methodologies that can take time to understand and develop code to implement properly. To better enable collaborating researchers to perform modeling and DA experiments with GSI, the Short-term Prediction Research and Transition (SPoRT) Center has developed a set of Perl scripts that couple GSI and WRF in a cycling methodology consistent with the use of real-time, regional observation data from the National Centers for Environmental Prediction (NCEP)/Environmental Modeling Center (EMC). Because Perl is open source, the code can be easily downloaded and executed regardless of the user's native shell environment. This paper will provide a description of this open-source code and descriptions of a number of the use cases that have been performed by SPoRT collaborators using the scripts on different computing systems.

Neurochemical changes following a single dose of polybrominated diphenyl ether 47 in mice.

PubMed

Gee, Jillian R; Moser, Virginia C; McDanie, Katherine L; Herr, David W

2011-04-01

Polybrominated diphenyl ethers (PBDEs) are commonly used as commercial flame retardants in a variety of products, including plastics and textiles. Previous studies in our laboratory, and in the literature, showed that exposure to a specific PBDE congener (PBDE 47) during a critical period of brain development may lead to developmental delays and hyperactivity in adulthood. To date, the underlying causes of these behavioral alterations are unknown, although in vitro studies linked PBDEs with potential alterations in neurotransmitter levels, particularly acetylcholine (ACh) and dopamine (DA). Alterations in DA function have also been noted in cases of hyperactivity in rodents and humans. The current study examined monoamine levels in male mice acutely exposed to corn oil vehicle or PBDE 47 (1, 10, or 30 mg/kg) on postnatal day (PND) 10. Animals were sacrificed on PND 15, PND 20, and in adulthood (131-159 days old). The cortex, striatum, and cerebellum were isolated and analyzed by high-performance liquid chromatography to determine the concentration of monoamines within each brain region. A statistically significant increase in DA levels was seen within the cortex, regardless of age, but only in the 10-mg/kg PBDE treatment group. While these effects did not show a monotonic dose response, we previously reported hyperactivity in littermates in the same dose group, but not at the lower or higher dose. Thus, early developmental exposure to PBDE 47 alters the levels of cortical DA in male mice, which may correlate with behavioral observations in littermates.

Identification of extracellular surface-layer associated proteins in Lactobacillus acidophilus NCFM

PubMed Central

Johnson, Brant; Selle, Kurt; O’Flaherty, Sarah; Goh, Yong Jun

2013-01-01

Bacterial surface (S-) layers are crystalline arrays of self-assembling, proteinaceous subunits called S-layer proteins (Slps), with molecular masses ranging from 40 to 200 kDa. The S-layer-forming bacterium Lactobacillus acidophilus NCFM expresses three major Slps: SlpA (46 kDa), SlpB (47 kDa) and SlpX (51 kDa). SlpA has a demonstrated role in adhesion to Caco-2 intestinal epithelial cells in vitro, and has been shown to modulate dendritic cell (DC) and T-cell functionalities with murine DCs. In this study, a modification of a standard lithium chloride S-layer extraction revealed 37 proteins were solubilized from the S-layer wash fraction. Of these, 30 have predicted cleavage sites for secretion, 24 are predicted to be extracellular, six are lipid-anchored, three have N-terminal hydrophobic membrane spanning regions and four are intracellular, potentially moonlighting proteins. Some of these proteins, designated S-layer associated proteins (SLAPs), may be loosely associated with or embedded within the bacterial S-layer complex. Lba-1029, a putative SLAP gene, was deleted from the chromosome of L. acidophilus. Phenotypic characterization of the deletion mutant demonstrated that the SLAP LBA1029 contributes to a pro-inflammatory TNF-α response from murine DCs. This study identified extracellular proteins and putative SLAPs of L. acidophilus NCFM using LC-MS/MS. SLAPs appear to impart important surface display features and immunological properties to microbes that are coated by S-layers. PMID:24002751

RGS10 exerts a neuroprotective role through the PKA/c-AMP response-element (CREB) pathway in dopaminergic neuron-like cells

PubMed Central

Lee, Jae-Kyung; Chung, Jaegwon; Druey, Kirk M.; Tansey, Malú G.

2012-01-01

Regulator of G-protein signaling-10 (RGS10) is a GTPase activating protein (GAP) for Gαi/q/z subunits that is highly expressed in the immune system and in a broad range of brain regions including the hippocampus, striatum, dorsal raphe, and ventral midbrain. Previously, we reported that RGS10-null mice display increased vulnerability to chronic systemic inflammation-induced degeneration of nigral dopaminergic (DA) neurons. Given that RGS10 is expressed in DA neurons, we investigated the extent to which RGS10 regulates cell survival under conditions of inflammatory stress. Because of the inherent limitations associated with use of primary DA neurons for biochemical analyses, we employed a well-characterized ventral mesencephalon DA neuroblastoma cell line (MN9D) for our studies. We found that stable over-expression of RGS10 rendered them resistant to TNF-induced cytotoxicity; whereas MN9D cells expressing mutant RGS10-S168A (which is resistant to phosphorylation by protein kinase A (PKA) at a serine residue that promotes its nuclear translocation) showed similar sensitivity to TNF as the parental MN9D cells. Using biochemical and pharmacological approaches, we identified protein kinase A (PKA) and the downstream phospho-cAMP response element-binding (CREB) signaling pathway (and ruled out ERK 1/2, JNK, and NFkB) as key mediators of the neuroprotective effect of RGS10 against inflammatory stress. PMID:22564151

Isobaric Tags for Relative and Absolute Quantitation-Based Proteomic Analysis of Patent and Constricted Ductus Arteriosus Tissues Confirms the Systemic Regulation of Ductus Arteriosus Closure.

PubMed

Hong, Haifa; Ye, Lincai; Chen, Huiwen; Xia, Yu; Liu, Yue; Liu, Jinfen; Lu, Yanan; Zhang, Haibo

2015-08-01

We aimed to evaluate global changes in protein expression associated with patency by undertaking proteomic analysis of human constricted and patent ductus arteriosus (DA). Ten constricted and 10 patent human DAs were excised from infants with ductal-dependent heart disease during surgery. Using isobaric tags for relative and absolute quantitation-based quantitative proteomics, 132 differentially expressed proteins were identified. Of 132 proteins, voltage-gated sodium channel 1.3 (SCN3A), myosin 1d (Myo1d), Rho GTPase activating protein 26 (ARHGAP26), and retinitis pigmentosa 1 (RP1) were selected for validation by Western blot and quantitative real-time polymerase chain reaction analyses. Significant upregulation of SCN3A, Myo1d, and RP1 messenger RNA, and protein levels was observed in the patent DA group (all P ≤ 0.048). ARHGAP26 messenger RNA and protein levels were decreased in patent DA tissue (both P ≤ 0.018). Immunohistochemistry analysis revealed that Myo1d, ARHGAP26, and RP1 were specifically expressed in the subendothelial region of constricted DAs; however, diffuse expression of these proteins was noted in the patent group. Proteomic analysis revealed global changes in the expression of proteins that regulate oxygen sensing, ion channels, smooth muscle cell migration, nervous system, immune system, and metabolism, suggesting a basis for the systemic regulation of DA patency by diverse signaling pathways, which will be confirmed in further studies.

Prominent alterations of wild barley leaf transcriptome in response to individual and combined drought acclimation and heat shock conditions.

PubMed

Ashoub, Ahmed; Müller, Niels; Jiménez-Gómez, José M; Brüggemann, Wolfgang

2018-05-01

Under field conditions, drought and heat stress typically happen simultaneously and their negative impact on the agricultural production is expected to increase worldwide under the climate change scenario. In this study, we performed RNA-sequencing analysis on leaves of wild barley (Hordeum spontaneum) originated from the northern coastal region of Egypt following individual drought acclimation (DA) and heat shock (HS) treatments and their combination (CS, combined stresses) to distinguish the unique and shared differentially expressed genes (DEG). Results indicated that the number of unique genes that were differentially expressed following HS treatment exceeded the number of those expressed following DA. In addition, the number of genes that were uniquely differentially expressed in response to CS treatment exceeded the number of those of shared responses to individual DA and HS treatments. These results indicate a better adaptation of the Mediterranean wild barley to drought conditions when compared with heat stress. It also manifests that the wild barley response to CS tends to be unique rather than common. Annotation of DEG showed that metabolic processes were the most influenced biological function in response to the applied stresses. © 2017 Scandinavian Plant Physiology Society.

CHOQUES AGREGADOS E INVERSIÓN EN CAPITAL HUMANO: EL LOGRO EDUCATIVO SUPERIOR DURANTE LA DÉCADA PERDIDA EN MÉXICO

PubMed Central

Peña, Pablo A.

2014-01-01

Este artículo documenta una respuesta agregada negativa del logro educativo superior (más de 12 años de escolaridad) en México a la recesión de 1982–83 y el estancamiento que le siguió. La respuesta no fue homogénea entre géneros, regiones y entornos familiares. Los hombres experimentaron una caída en el logro mientras que las mujeres experimentaron un crecimiento más lento. En promedio, los estados con un mayor logro antes del choque experimentaron mayores caídas. La respuesta entre distintos entornos familiares no presenta un patrón claro. Sin embargo, el efecto negativo en el logro se observa incluso entre hermanos. La evidencia sugiere una historia por el lado de la demanda: la caída en el ingreso de los hogares parece ser el determinante de la caída/desaceleración del logro educativo superior. La conclusión es que la recesión y la falta de crecimiento que le siguió tuvieron un efecto negativo importante y duradero en la formación de capacidades en México. PMID:25328251

Surgical treatment of gastroesophageal reflux disease and upside-down stomach using the Da Vinci robotic system. A prospective study.

PubMed

Hartmann, Jens; Jacobi, Christoph A; Menenakos, Charalambos; Ismail, Mahmoud; Braumann, Chris

2008-03-01

So far, the impact of telematic surgical approach in Gastroesophageal Reflux Disease (GERD) is still obscure. In this prospective study, we analyzed the Da Vinci Intuitive Surgical robotic system for antireflux surgery. In April 2003, we set up a pilot study to evaluate the efficacy of laparoscopic telerobotic surgery using the three-arm Da Vinci system. Optimal trocar positions, operating and setup times, conversion rate, intraoperative complications, and perioperative morbidity, as well as mortality rate, were analyzed. The median age was 53 years (range 25-74) in 118 patients (52 female/66 male). In 17 patients, an upside-down stomach- and in 101 GERD was surgical indication. The median operating time has been reduced from 105 min to 91 min after 40 procedures and setup time from 24.5 min to 10.4 min after 10 procedures. The system is safe and it seems to be superior to traditional laparoscopy during dissection in the esophageal hiatus region. This compensates long setup- and operating times. Disadvantages are the high costs, the time to master the setup/system and the necessity of exact trocar positioning.

Multiple toxic doses of methamphetamine alter neurotensin concentrations in various region of the rat brain

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

Hanson, G.R.; Merchant, K.; Gibb, J.W.

1986-03-05

The authors have previously reported that multiple high doses of methamphetamine (METH) alter neuronal monoamine metabolism and release. Recently, Hokfelt et al. showed that neurotensin, a tridecapeptide, has neurotransmitter properties which may be involved with DA neuronal activity. In the present study they investigated the possible effects of METH on the CNS neurotensin system. Five doses of METH (15 mg/kg) were administered every 6 h; control and treated rats were sacrificed 18 h after the last dose and concentrations of neurotensin-like immuno-reactivity (NTLI) were measured by radioimmunoassay. NTLI was elevated 200-300% in the nucleus accumbens, neostriatum, and substantia nigra; 30-40%more » increases in NTLI were measured in the hippocampus and hypothalamus. No change was observed in amygdala, A-10 or periaqueductal gray. In contrast to the above measured areas, the frontal lobe and olfactory bulb showed decreases of 25-35%. These findings demonstrate that METH treatment alters the activities of several CNS neurotensin systems, possibly due to the influence of this drug on DA pathways. The variability in the type and magnitude of these responses suggests that DA and neurotensin systems interact by more than one mechanism.« less

Music and the nucleus accumbens.

PubMed

Mavridis, Ioannis N

2015-03-01

Music is a universal feature of human societies over time, mainly because it allows expression and regulation of strong emotions, thus influencing moods and evoking pleasure. The nucleus accumbens (NA), the most important pleasure center of the human brain (dominates the reward system), is the 'king of neurosciences' and dopamine (DA) can be rightfully considered as its 'crown' due to the fundamental role that this neurotransmitter plays in the brain's reward system. Purpose of this article was to review the existing literature regarding the relation between music and the NA. Studies have shown that reward value for music can be coded by activity levels in the NA, whose functional connectivity with auditory and frontal areas increases as a function of increasing musical reward. Listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the NA. The functional connectivity between brain regions mediating reward, autonomic and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. Musical stimuli can significantly increase extracellular DA levels in the NA. NA DA and serotonin were found significantly higher in animals exposed to music. Finally, passive listening to unfamiliar although liked music showed activations in the NA.

S-(N, N-diethylcarbamoyl)glutathione (carbamathione), a disulfiram metabolite and its effect on nucleus accumbens and prefrontal cortex dopamine, GABA, and glutamate: A microdialysis study

PubMed Central

Faiman, Morris D.; Kaul, Swetha; Latif, Shaheen A.; Williams, Todd D.; Lunte, Craig E.

2015-01-01

Disulfiram (DSF), used for the treatment of alcohol use disorders (AUDs) for over six decades, most recently has shown promise for treating cocaine dependence. Although DSF’s mechanism of action in alcohol abuse is due to the inhibition of liver mitochondrial aldehyde dehydrogenase (ALDH2), its mechanism of action in the treatment of cocaine dependence is unknown. DSF is a pro-drug, forming a number of metabolites each with discrete pharmacological actions. One metabolite formed during DSF bioactivation is S-(N, N-diethylcarbamoyl) glutathione (carbamathione) (carb). We previously showed that carb affects glutamate binding. In the present studies, we employed microdialysis techniques to investigate the effect of carb administration on dopamine (DA), GABA, and glutamate (Glu) in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), two brain regions implicated in substance abuse dependence. The effect of DSF on DA, GABA, and Glu in the NAc also was determined. Both studies were carried out in male rats. Carb (20, 50, 200 mg/kg i v) in a dose-dependent manner increased DA, decreased GABA, and had a biphasic effect on Glu, first increasing and then decreasing Glu in both the NAc and mPFC. These changes all occurred concurrently. After carb administration, NAc and mPFC carb, as well as carb in plasma, were rapidly eliminated with a half-life for each approximately 4 min, while the changes in DA, GABA, and GLu in the NAc and mPFC persisted for approximately two hours. The maximal increase in carb (Cmax) in the NAc and mPFC after carb administration was dose-dependent, as was the area under the curve (AUC). DSF (200 mg/kg i p) also increased DA, decreased GABA, and had a biphasic effect on Glu in the NAc similar to that observed in the NAc after carb administration. When the cytochrome P450 inhibitor N-benzylimidazole (NBI) (20 mg/kg i p) was administered before DSF dosing, no carb could be detected in the NAc and plasma and also no changes in NAc DA, GABA, and GLu occurred. Changes in these neurotransmitters occurred only if carb was formed from DSF. When NBI was administered prior to dosing with carb, the increase in DA, decrease in GABA, and biphasic effect on GLu was similar to that seen after dosing with carb only. The i p or i v administration of carb showed similar changes in DA, GABA, and GLu, except the time to reach Cmax for DA as well as the changes in GABA, and GLu after i p administration occurred later. The elimination half-life of carb and the area under the curve (AUC) were similar after both routes of administration. It is concluded that carb must be formed from DSF before any changes in DA, GABA, and GLu in the NAc and mPFC are observed. DSF and carb, when administered to rats, co-release DA, GABA, and GLu. Carb, once formed can cross the blood brain barrier and enter the brain. Although inhibition of liver ALDH2 is the accepted mechanism for DSF’s action in treating AUDs, the concurrent changes in DA, GABA, and GLu in the NAc and mPFC after DSF administration suggest that changes in these neurotransmitters as a potential mechanism of action not only for AUDs, but also for cocaine dependence cannot be excluded. PMID:23891816

Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia

PubMed Central

Borroto-Escuela, Dasiel O.; Pintsuk, Julia; Schäfer, Thorsten; Friedland, Kristina; Ferraro, Luca; Tanganelli, Sergio; Liu, Fang; Fuxe, Kjell

2016-01-01

The dopamine (DA) neuron system most relevant for schizophrenia is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions. The field of dopamine D2 receptors and schizophrenia changed markedly with the discovery of many types of D2 heteroreceptor complexes in subcortical limbic areas as well as the dorsal striatum. The results indicate that the D2 is a hub receptor which interacts not only with many other G protein-coupled receptors (GPCRs) including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2 heteroreceptor complexes may contribute to the development of schizophrenia through changes in the balance of diverse D2 homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal γ-aminobutyric acid (GABA) pathway. This will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Agonist activation of the A2A protomer in the A2A–D2 heteroreceptor complex inhibits D2 Gi/o mediated signaling but increases the D2 β-arrestin2 mediated signaling. Through this allosteric receptor–receptor interaction, the A2A agonist becomes a biased inhibitory modulator of the Gi/o mediated D2 signaling, which may the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2A–D2 heterocomplexes. The DA and glutamate hypotheses of schizophrenia come together in the signal integration in D2–N-methyl-d-aspartate (NMDA) and A2A–D2–metabotropic glutamate receptor 5 (mGlu5) heteroreceptor complexes, especially in the ventral striatum. 5-Hydroxytryptamine 2A (5-HT2A)–D2 heteroreceptor complexes are special targets for atypical antipsychotics with high potency to block their 5-HT2A protomer signaling in view of the potential development of pathological allosteric facilitatory 5-HT2A–D2 interaction increasing D2 protomer signaling. Neurotensin (NTS1)–D2 heterocomplexes also exist in the ventral and dorsal striatum, and likely also in midbrain DA nerve cells as NTS1-D2 autoreceptor complexes where neurotensin produces antipsychotic and propsychotic actions, respectively. PMID:27141290

Chromosome localization of human genes for clathrin adaptor polypeptides AP2{beta} and AP50 and the clathrin-binding protein, VCP

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

Druck, T.; Gu, Y.; Prabhala, G.

1995-11-01

Clathrin-coated vesicles, involved in endocytosis and Golgi processing, have a surface lattice containing clathrin triskelia and stoichiometric amounts of additional components termed {open_quotes}assembly proteins,{close_quotes} or APs. The AP form at the plasma membrane, AP2, is composed of two large subunits of 100-115 kDa, denoted AP2{alpha} and AP2{beta}, a medium chain of 50 kDa, designated AP50, and a small chain. We have determined human chromosomal locations of genes for a large AP2{beta} (CLAPB1) and a medium (CLAPM1) AP subunit and of a novel clathrin-binding protein, VCP, that binds clathrin simultaneously with A1`s. Chromosomal in situ hybridization of a human genomic clonemore » demonstrated that the CLAPM1 gene mapped to chromosome region 3q28. The gene for the CLAPB1 large subunit was mapped to 17q11.2-q12 by PCR amplification of an AP2{beta} fragment from a panel of rodent-human hybrid DNAs. To map the human VCP sequence, a human-specific probe was made by RT-PCR of human mRNA using oligonucleotide primers from conserved regions of the porcine sequence. The amplified human fragment served as probe on Southern blots of hybrid DNAs to determine that the human VCP locus maps to chromosome region 9pter-q34. 13 refs., 2 figs.« less

Influence of the ventilatory mode on acute adverse effects and facial thermography after noninvasive ventilation.

PubMed

Pontes, Suzy Maria Montenegro; Melo, Luiz Henrique de Paula; Maia, Nathalia Parente de Sousa; Nogueira, Andrea da Nóbrega Cirino; Vasconcelos, Thiago Brasileiro; Pereira, Eanes Delgado Barros; Bastos, Vasco Pinheiro Diógenes; Holanda, Marcelo Alcantara

2017-01-01

To compare the incidence and intensity of acute adverse effects and the variation in the temperature of facial skin by thermography after the use of noninvasive ventilation (NIV). We included 20 healthy volunteers receiving NIV via oronasal mask for 1 h. The volunteers were randomly divided into two groups according to the ventilatory mode: bilevel positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP). Facial thermography was performed in order to determine the temperature of the face where it was in contact with the mask and of the nasal dorsum at various time points. After removal of the mask, the volunteers completed a questionnaire about adverse effects of NIV. The incidence and intensity of acute adverse effects were higher in the individuals receiving BiPAP than in those receiving CPAP (16.1% vs. 5.6%). Thermographic analysis showed a significant cooling of the facial skin in the two regions of interest immediately after removal of the mask. The more intense acute adverse effects occurred predominantly among the participants in whom the decrease in the mean temperature of the nasal dorsum was lower (14.4% vs. 7.2%). The thermographic visual analysis of the zones of cooling and heating on the face identified areas of hypoperfusion or reactive hyperemia. The use of BiPAP mode was associated with a higher incidence and intensity of NIV-related acute adverse effects. There was an association between acute adverse effects and less cooling of the nasal dorsum immediately after removal of the mask. Cutaneous thermography can be an additional tool to detect adverse effects that the use of NIV has on facial skin. Comparar a incidência e a intensidade de efeitos adversos agudos e a variação da temperatura da pele da face através da termografia após a aplicação de ventilação não invasiva (VNI). Foram incluídos 20 voluntários sadios, de ambos os gêneros, submetidos à VNI com máscara oronasal por 1 h e divididos aleatoriamente em dois grupos de acordo com o modo ventilatório: bilevel positive airway pressure (BiPAP) ou continuous positive airway pressure (CPAP). A termografia da face foi realizada para determinar a temperatura na região de contato da máscara e no dorso do nariz em momentos diferentes. Os voluntários preencheram um questionário de efeitos adversos após a retirada da VNI. A incidência e a intensidade dos efeitos adversos agudos foram maiores naqueles submetidos a BiPAP em relação aos submetidos a CPAP (16,1% vs. 5,6%). A análise termográfica evidenciou um esfriamento significativo da pele facial nas duas regiões de estudo imediatamente após a retirada da máscara. Os efeitos adversos agudos em maior intensidade ocorreram predominantemente no grupo de participantes cuja redução da temperatura média no dorso do nariz foi menor (14,4% vs. 7,2%). A análise visual termográfica de zonas de esfriamento e aquecimento na face identificou regiões de hipoperfusão ou hiperemia reativa. O uso do modo BiPAP associou-se a maior incidência e intensidade de efeitos adversos agudos associados à VNI. Houve associação entre efeitos adversos agudos e menor esfriamento da pele do dorso do nariz imediatamente após a retirada da máscara. A termografia cutânea pode ser uma ferramenta adicional na detecção de efeitos adversos na pele da face associados ao uso da VNI.

Background Noise of the Aldeia da Serra Region (Portugal) from a temporary broad band network

NASA Astrophysics Data System (ADS)

Wachilala, Piedade; Borges, José; Caldeira, Bento; Bezzeghoud, Mourad

2017-04-01

In this study, we analyse seismic background noise to assess the effect of noise based on the detectability of a temporary network constituted by DOCTAR (Deep Ocean Test Array), who have been deployed in a period between 2011 and 2012 in Portugal mainland, and the Évora permanent seismic station. This network is constituted by 14 digital broadband stations (14 CMG-3ESP and one STS2 sensors) with a flat response between the 60 sec to 50 Hz, 24-bit and 120s to 60Hz respectively. The temporary network was operated in continuous recording mode (three-components) in a region located in the north of the region of Évora, within a radius of about 30 km around the village of Aldeia da Serra, region in which there is an important seismic activity in the context of Portugal mainland. We calculated power spectral densities of background noise for each station/component and compare them with high-noise model and low-noise model of Peterson (1993). We consider different for day and night local and for different periods of the year. Power spectral density estimates show moderate noise levels with all stations falling within the high and low bounds of Peterson (1993). Considering the results of the noise, we estimate the detection limit of each station and consequently the detectability of the network. From this information and taking in attention the events recorded during the period of DOCTAR operation we analyse the improvement promoted by this temporary network regarding the existent seismic networks to the local seismicity study. This work was partially supported by COMPETE 2020 program (POCI-01-0145-FEDER-007690 project). We acknowledge GFZ Potsdam for providing part of the data used in this study.

Standardized Bacopa monnieri extract ameliorates acute paraquat-induced oxidative stress, and neurotoxicity in prepubertal mice brain.

PubMed

Hosamani, Ravikumar; Krishna, Gokul; Muralidhara

2016-12-01

Bacopa monnieri (BM), an ayurvedic medicinal plant, has attracted considerable interest owing to its diverse neuropharmacological properties. Epidemiological studies have shown significant correlation between paraquat (PQ) exposure and increased risk for Parkinson's disease in humans. In this study, we examined the propensity of standardized extract of BM to attenuate acute PQ-induced oxidative stress, mitochondrial dysfunctions, and neurotoxicity in the different brain regions of prepubertal mice. To test this hypothesis, prepubertal mice provided orally with standardized BM extract (200 mg/kg body weight/day for 4 weeks) were challenged with an acute dose (15 mg/kg body weight, intraperitoneally) of PQ after 3 hours of last dose of extract. Mice were sacrificed after 48 hours of PQ injection, and different brain regions were isolated and subjected to biochemical determinations/quantification of central monoamine (dopamine, DA) levels (by high-performance liquid chromatography). Oral supplementation of BM for 4 weeks resulted in significant reduction in the basal levels of oxidative markers such as reactive oxygen species (ROS), malondialdehyde (MDA), and hydroperoxides (HP) in various brain regions. PQ at the administered dose elicited marked oxidative stress within 48 hours in various brain regions of mice. However, BM prophylaxis significantly improved oxidative homeostasis by restoring PQ-induced ROS, MDA, and HP levels and also by attenuating mitochondrial dysfunction. Interestingly, BM supplementation restored the activities of cholinergic enzymes along with the restoration of striatal DA levels among the PQ-treated mice. Based on these findings, we infer that BM prophylaxis renders the brain resistant to PQ-mediated oxidative perturbations and thus may be better exploited as a preventive approach to protect against oxidative-mediated neuronal dysfunctions.

Identification of an anti-sperm auto-monoclonal antibody (Ts4)-recognized molecule in the mouse sperm acrosomal region and its inhibitory effect on fertilization in vitro.

PubMed

Yoshitake, Hiroshi; Oda, Risako; Yanagida, Mitsuaki; Kawasaki, Yu; Sakuraba, Mayumi; Takamori, Kenji; Hasegawa, Akiko; Fujiwara, Hiroshi; Araki, Yoshihiko

2016-06-01

We previously established an anti-mouse sperm auto-monoclonal antibody, Ts4, which shows immunoreactivity against several kinds of glycoproteins in the acrosomal region of epididymal spermatozoa, testicular germ cells, and early embryo, via binding to an epitope containing a common N-linked oligosaccharide (OS) chain on the molecules. In mice, we have already demonstrated that the OS chain in the epitope for Ts4 is a fucosylated agalacto-complex-type biantennary glycan carrying bisecting N-acetylglucosamine. In the testis, one of the specific OS chain-conjugated molecules is TEX101, a germ cell-marker glycoprotein, which is expressed in spermatocytes, spermatids, and testicular spermatozoa, but not in epididymal spermatozoa. In this study, we identified a Ts4-reactive glycoprotein in mouse cauda epididymal sperm. An immunoprecipitation method together with liquid chromatography-tandem mass spectrometry showed that alpha-N-acetylglucosaminidase (Naglu; a degradation enzyme of heparan sulfate) is one of the glycoproteins recognized by Ts4 in the epididymal spermatozoa. Western blot and immunohistochemical analyses revealed that mouse Naglu exists in two forms (82 and 77kDa) and is expressed in the acrosomal region and the flagellum of cauda epididymal sperm. Of the two Naglu-forms expressed in sperm, Ts4 immunoreacted against only the 82-kDa form located on the acrosomal region. The Ts4 mAb and anti-Naglu pAb negatively affected mouse fertilization in vitro. In addition, Ts4 inhibited sperm acrosome reaction induced by heparan sulfate. The Ts4-recognized fucosylated agalactobiantennary complex-type glycan with bisecting N-acetylglucosamine and Naglu on cauda epididymal spermatozoa may play a role in the process of fertilization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Forty keratin-associated beta-proteins (beta-keratins) form the hard layers of scales, claws, and adhesive pads in the green anole lizard, Anolis carolinensis.

PubMed

Dalla Valle, Luisa; Nardi, Alessia; Bonazza, Giulia; Zucal, Chiara; Zuccal, Chiara; Emera, Deena; Alibardi, Lorenzo

2010-01-15

Using bioinformatic methods we have detected the genes of 40 keratin-associated beta-proteins (KAbetaPs) (beta-keratins) from the first available draft genome sequence of a reptile, the lizard Anolis carolinensis (Broad Institute, Boston). All genes are clustered in a single but not yet identified chromosomal locus, and contain a single intron of variable length. 5'-RACE and RT-PCR analyses using RNA from different epidermal regions show tissue-specific expression of different transcripts. These results were confirmed from the analysis of the A. carolinensis EST libraries (Broad Institute). Most deduced proteins are 12-16 kDa with a pI of 7.5-8.5. Two genes encoding putative proteins of 40 and 45 kDa are also present. Despite variability in amino acid sequences, four main subfamilies can be described. The largest subfamily includes proteins high in glycine, a small subfamily contains proteins high in cysteine, a third large subfamily contains proteins high in cysteine and glycine, and the fourth, smallest subfamily comprises proteins low in cysteine and glycine. An inner region of high amino acid identity is the most constant characteristic of these proteins and maps to a region with two to three close beta-folds in the proteins. This beta-fold region is responsible for the formation of filaments of the corneous material in all types of scales in this species. Phylogenetic analysis shows that A. carolinensis KAbetaPs are more similar to those of other lepidosaurians (snake, lizard, and gecko lizard) than to those of archosaurians (chick and crocodile) and turtles. (c) 2009 Wiley-Liss, Inc.

Enteroaggregative Escherichia coli strains secrete a heat-labile toxin antigenically related to E. coli hemolysin.

PubMed Central

Baldwin, T J; Knutton, S; Sellers, L; Hernandez, H A; Aitken, A; Williams, P H

1992-01-01

A protein toxin of approximately 120,000 Da secreted by nonhemolytic enteroaggregative Escherichia coli strains cross-reacted in Western blots (immunoblots) with antibodies raised against the C-terminal region of E. coli hemolysin. Treatment of HEp-2 cells with enteroaggregative E. coli or culture supernatants caused elevation of intracellular calcium and stimulated calcium-dependent protein phosphorylation. Images PMID:1563799

Novel Insights into Fur Regulation in Helicobacter pylori

DTIC Science & Technology

2013-01-10

Distribution of prominent bacterial phyla ...................................................... 271   Figure 27. β-diversity between PMP communities ...and can be readily acquired by most microbes that thrive in these situations. H. pylori encodes a single ferrous iron transport protein (FeoB...junctions. The approximate amplified regions are indicated by the small black bars (not drawn to scale ). (B) PCR amplification of the oorDA, oorAB, and

Molecular mechanism of the relation of monoamine oxidase B and its inhibitors to Parkinson's disease: possible implications of glial cells.

PubMed

Nagatsu, T; Sawada, M

2006-01-01

Monoamine oxidases A and B (MAO A and MAO B) are the major enzymes that catalyze the oxidative deamination of monoamine neurotaransmitters such as dopamine (DA), noradrenaline, and serotonin in the central and peripheral nervous systems. MAO B is mainly localized in glial cells. MAO B also oxidizes the xenobiotic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to a parkinsonism-producing neurotoxin, 1-methyl-4-phenyl-pyridinium (MPP+). MAO B may be closely related to the pathogenesis of Parkinson's disease (PD), in which neuromelanin-containing DA neurons in the substantia nigra projecting to the striatum in the brain selectively degenerate. MAO B degrades the neurotransmitter DA that is deficient in the nigro-striatal region in PD, and forms H2O2 and toxic aldehyde metabolites of DA. H2O2 produces highly toxic reactive oxygen species (ROS) by Fenton reaction that is catalyzed by iron and neuromelanin. MAO B inhibitors such as L-(-)-deprenyl (selegiline) and rasagiline are effective for the treatment of PD. Concerning the mechanism of the clinical efficacy of MAO B inhibitors in PD, the inhibition of DA degradation (a symptomatic effect) and also the prevention of the formation of neurotoxic DA metabolites, i.e., ROS and dopamine derived aldehydes have been speculated. As another mechanism of clinical efficacy, MAO B inhibitors such as selegiline are speculated to have neuroprotective effects to prevent progress of PD. The possible mechanism of neuroprotection of MAO B inhibitors may be related not only to MAO B inhibition but also to induction and activation of multiple factors for anti-oxidative stress and anti-apoptosis: i.e., catalase, superoxide dismutase 1 and 2, thioredoxin, Bcl-2, the cellular poly(ADP-ribosyl)ation, and binding to glyceraldehydes-3-phosphate dehydrogenase (GAPDH). Furthermore, it should be noted that selegiline increases production of neurotrophins such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrphic factor (GDNF), possibly from glial cells, to protect neurons from inflammatory process.

An evaluation of the potential of Sentinel 1 for improving flash flood predictions via soil moisture-data assimilation

NASA Astrophysics Data System (ADS)

Cenci, Luca; Pulvirenti, Luca; Boni, Giorgio; Chini, Marco; Matgen, Patrick; Gabellani, Simone; Squicciarino, Giuseppe; Pierdicca, Nazzareno

2017-11-01

The assimilation of satellite-derived soil moisture estimates (soil moisture-data assimilation, SM-DA) into hydrological models has the potential to reduce the uncertainty of streamflow simulations. The improved capacity to monitor the closeness to saturation of small catchments, such as those characterizing the Mediterranean region, can be exploited to enhance flash flood predictions. When compared to other microwave sensors that have been exploited for SM-DA in recent years (e.g. the Advanced SCATterometer - ASCAT), characterized by low spatial/high temporal resolution, the Sentinel 1 (S1) mission provides an excellent opportunity to monitor systematically soil moisture (SM) at high spatial resolution and moderate temporal resolution. The aim of this research was thus to evaluate the impact of S1-based SM-DA for enhancing flash flood predictions of a hydrological model (Continuum) that is currently exploited for civil protection applications in Italy. The analysis was carried out in a representative Mediterranean catchment prone to flash floods, located in north-western Italy, during the time period October 2014-February 2015. It provided some important findings: (i) revealing the potential provided by S1-based SM-DA for improving discharge predictions, especially for higher flows; (ii) suggesting a more appropriate pre-processing technique to be applied to S1 data before the assimilation; and (iii) highlighting that even though high spatial resolution does provide an important contribution in a SM-DA system, the temporal resolution has the most crucial role. S1-derived SM maps are still a relatively new product and, to our knowledge, this is the first work published in an international journal dealing with their assimilation within a hydrological model to improve continuous streamflow simulations and flash flood predictions. Even though the reported results were obtained by analysing a relatively short time period, and thus should be supported by further research activities, we believe this research is timely in order to enhance our understanding of the potential contribution of the S1 data within the SM-DA framework for flash flood risk mitigation.

Litho-tectonic mapping of the North Afar region from Sentinel-2A multispectral imagery and ALOS AW3D30 digital elevation data: Controls on Danakil-Nubia plate motion between the Erta'Ale ridge and the Gulf of Zula

NASA Astrophysics Data System (ADS)

Hartnady, Chris; Hartnady, Michael; Wise, Edward; Blake, Dylan; McGibbon, David; Hay, E. Rowena

2017-04-01

The Danakil Depression in the North Afar region of Ethiopia reaches elevations deeper than 120 m below sea level and contains a Pleistocene-Holocene evaporite sequence currently investigated for potash mineral deposits. Separated from the main Ethiopian escarpment by the Dogua horst mountains, the asymmetric half-graben is bordered on its western (Nubian) side by the active, normal Main Danakil Rift-border Fault (MDRF). Above the MDRF, a series of piedmont alluvial fans (bajadas) fringes the Dogua Horst, emanating from a series of wadi catchments between the larger perennial rivers (Ragali, Saba) that drain from the high (>2000 m) Ethiopian Plateau. On its eastern side, the Danakil block contains Proterozoic-Palaeozoic sequences correlated with similar units in the Dogua range, and forms a microplate rotating independently between the larger Nubian and Arabian plates (McClusky et al., 2010). An understanding of the sedimentary and tectonic evolution of the Danakil-Nubia (DA-NU) plate system is crucial to the beneficial development of fresh groundwater resources and to an assessment of seismotectonic and volcanic geohazards in the area. Between the Mt Alid caldera in the Dandeiro graben and the Erta'Ale crater in the south Danakil, the rate of present-day DA-NU motion is 10.9 - 13.5 mm/yr, with direction azimuths N106E- N096E (after Schettino et al., 2016). DA-NU relative motion is focussed along the east-dipping MDRF in the Danakil but switches to an eastern (west-dipping) rift-border normal fault in the Dandiero, a northward extension of the Renda-Maglalla-Coma graben, separating the Dogua Horst from the main part of the NU plate. This change in rifting asymmetry occurs across a WNW/ESE-striking zone of basement faulting that terminates the Dogua Horst and functions as a left-stepping proto-transform fault zone, across the NNW direction of DA-NU proto-rift propagation. From 13-channel multispectral data of the European Space Agency satellite Sentinel-2A, a false-colour composite image, centred about MDRF and covering a wide region across the Ethiopia-Eritrea border, was created by combination of selected spectral band-ratios. This Sentinel-2A-based lithological mapping is integrated with the new ALOS AW3D30 digital elevation model, providing geomorphometric analysis and morphotectonic interpretations that allow 1) revision of previous fault-zone mapping, 2) seismotectonic contextualization of the earthquake record, and 3) improved discrimination of volcanic units and centres, both basaltic and silicic, along the northward propagating DA-NU rift zone. References McClusky, S., et al., 2010. Kinematics of the southern Red Sea-Afar Triple Junction and implications for plate dynamics. Geophys. Res. Lett., 37, L05301, doi:10.1029/2009GL041127 Schettino, A., Macchiavelli, C., Pierantoni, P.P., Zanoni, D., and Rasul, N., 2016. Recent kinematics of the tectonic plates surrounding the Red Sea and Gulf of Aden. Geophys. J. Int., 207, 457-480, doi: 10.1093/gji/gg

Use of Yohkoh SXT in Measuring the Net Current and CME Productivity of Active Regions

NASA Technical Reports Server (NTRS)

Falconer, D. A.; Moore, R. L.; Gary, G. A.; Six, N. Frank (Technical Monitor)

2001-01-01

In our investigation of the correlation of global nonpotentiality of active regions to their CME productivity (Falconer, D.A. 2001, JGR, in press, and Falconer, Moore, & Gary, 2000, EOS 82, 20 S323), we use Yohkoh SXT images for two purposes. The first use is to help resolve the 180 degree ambiguity in the direction of the observed transverse magnetic field. Resolution of the 180 degree ambiguity is important, since the net current, one of our measures of global nonpotentiality, is derived from integrating the dot product of the transverse field around a contour (I(sub N)=(integral)BT(raised dot)dl). The ambiguity results from the observed transverse field being determined from the linear polarization, which gives the plane of the direction, but leaves a 180 degrees ambiguity. Automated methods to resolve the ambiguity ranging from the simple acute angle rule (Falconer, D.A. 2001) to the more sophisticated annealing method (Metcalf T.R. 1994). For many active regions, especially ones that are nearly potential these methods work well. But for very nonpotential active regions where the shear angle (the angle between the observed and potential transverse field) is near 90 degrees throughout large swaths along the main neutral line, both methods can resolve the ambiguity incorrectly for long segments of the neutral line. By determining from coronal images, such as those from Yohkoh/SXT, the sense of shear along the main neutral line in the active region, these cases can be identified and corrected by a modification of the acute angle rule described here. The second use of Yohkoh/SXT in this study is to check for the cusped coronal arcades of long-duration eruptive flares. This signature is an excellent proxy for CMEs, and was used by Canfield, Hudson, and McKenzie (1999 GRL V26, 6, 627-630). This work is funded by NSF through the Space Weather Program and by NASA through the Solar Physics Supporting Research and Technology Program.

Establishment and Comparison of Two Different Diagnostic Platforms for Detection of DENV1 NS1 Protein

PubMed Central

Tang, Yin-Liang; Chiu, Chien-Yu; Lin, Chun-Yu; Huang, Chung-Hao; Chen, Yen-Hsu; Destura, Raul V.; Chao, Day-Yu; Wu, Han-Chung

2015-01-01

Dengue virus (DENV) infection is currently at pandemic levels, with populations in tropical and subtropical regions at greatest risk of infection. Early diagnosis and management remain the cornerstone for good clinical outcomes, thus efficient and accurate diagnostic technology in the early stage of the disease is urgently needed. Serotype-specific monoclonal antibodies (mAbs) against the DENV1 nonstructural protein 1 (NS1), DA12-4, DA13-2, and DA15-3, which were recently generated using the hybridoma technique, are suitable for use in diagnostic platforms. Immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis further confirmed the serotype specificity of these three monoclonal antibodies. The ELISA-based diagnostic platform was established using the combination of two highly sensitive mAbs (DA15-3 and DB20-6). The same combination was also used for the flow cytometry-based diagnostic platform. We report here the detection limits of flow cytometry-based and ELISA-based diagnostic platforms using these mAbs to be 0.1 and 1 ng/mL, respectively. The collected clinical patient serum samples were also assayed by these two serotyping diagnostic platforms. The sensitivity and specificity for detecting NS1 protein of DENV1 are 90% and 96%, respectively. The accuracy of our platform for testing clinical samples is more advanced than that of the two commercial NS1 diagnostic platforms. In conclusion, our platforms are suitable for the early detection of NS1 protein in DENV1 infected patients. PMID:26610481

"Liking" and "wanting" linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry.

PubMed

Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

2012-01-01

In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: "liking,"learning," and "wanting" [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or "wanting" hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily selfadministered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens (NAC), and they stimulate the functioning of brain reward circuitry (producing the "high" that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions.

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

Haas, M.; Forbush, B. III

(Na + K + Cl) cotransport is the major mechanism of salt transport across the apical membrane of the epithelial cells of the thick ascending limb of Henle's loop of mammalian kidney and the site of action of loop diuretics such as furosemide and bumetanide. We have identified a 150-kDa protein in membranes from dog kidney cortex that is photolabeled by a radiolabeled, benzophenone analogue of bumetanide, (/sup 3/H)4-benzoyl-5-sulfamoyl-3-(3-thenyloxy)benzoic acid ((/sup 3/H)BSTBA). Several pieces of evidence strongly suggest that this 150-kDa protein is at least part of the (Na + K + Cl) cotransport system. 1) Photoincorporation of (/sup 3/H)BSTBAmore » into this protein is completely blocked by inclusion of 10 microM unlabeled bumetanide in the photolysis medium. 2) Photoincorporation of (/sup 3/H)BSTBA into this protein shows a saturable dependence on (/sup 3/H)BSTBA concentration, with a K 1/2 (approximately 0.1 microM) very similar to that for reversible (/sup 3/H)BSTBA binding to kidney membranes. 3) Photolabeling of this protein by (/sup 3/H)BSTBA requires the simultaneous presence of Na, K, and Cl in the photolysis medium. 4) When crude membranes from dog kidney cortex are centrifuged on sucrose density gradients, saturable (/sup 3/H)bumetanide binding and photoincorporation of (/sup 3/H)BSTBA in the 150-kDa region show a very similar distribution among the 15 gradient fractions collected. (/sup 3/H)BSTBA is also photoincorporated into at least two lower molecular mass proteins, the largest of which is approximately 50 kDa.« less

Differential dopamine function in fibromyalgia.

PubMed

Albrecht, Daniel S; MacKie, Palmer J; Kareken, David A; Hutchins, Gary D; Chumin, Evgeny J; Christian, Bradley T; Yoder, Karmen K

2016-09-01

Approximately 30 % of Americans suffer from chronic pain disorders, such as fibromyalgia (FM), which can cause debilitating pain. Many pain-killing drugs prescribed for chronic pain disorders are highly addictive, have limited clinical efficacy, and do not treat the cognitive symptoms reported by many patients. The neurobiological substrates of chronic pain are largely unknown, but evidence points to altered dopaminergic transmission in aberrant pain perception. We sought to characterize the dopamine (DA) system in individuals with FM. Positron emission tomography (PET) with [(18)F]fallypride (FAL) was used to assess changes in DA during a working memory challenge relative to a baseline task, and to test for associations between baseline D2/D3 availability and experimental pain measures. Twelve female subjects with FM and 11 female controls completed study procedures. Subjects received one FAL PET scan while performing a "2-back" task, and one while performing a "0-back" (attentional control, "baseline") task. FM subjects had lower baseline FAL binding potential (BP) in several cortical regions relative to controls, including anterior cingulate cortex. In FM subjects, self-reported spontaneous pain negatively correlated with FAL BP in the left orbitofrontal cortex and parahippocampal gyrus. Baseline BP was significantly negatively correlated with experimental pain sensitivity and tolerance in both FM and CON subjects, although spatial patterns of these associations differed between groups. The data suggest that abnormal DA function may be associated with differential processing of pain perception in FM. Further studies are needed to explore the functional significance of DA in nociception and cognitive processing in chronic pain.

A membrane-anchored E-type endo-1,4-beta-glucanase is localized on Golgi and plasma membranes of higher plants.

PubMed

Brummell, D A; Catala, C; Lashbrook, C C; Bennett, A B

1997-04-29

Endo-1,4-beta-D-glucanases (EGases, EC 3.2.1.4) are enzymes produced in bacteria, fungi, and plants that hydrolyze polysaccharides possessing a 1,4-beta-D-glucan backbone. All previously identified plant EGases are E-type endoglucanases that possess signal sequences for endoplasmic reticulum entry and are secreted to the cell wall. Here we report the characterization of a novel E-type plant EGase (tomato Cel3) with a hydrophobic transmembrane domain and structure typical of type II integral membrane proteins. The predicted protein is composed of 617 amino acids and possesses seven potential sites for N-glycosylation. Cel3 mRNA accumulates in young vegetative tissues with highest abundance during periods of rapid cell expansion, but is not hormonally regulated. Antibodies raised to a recombinant Cel3 protein specifically recognized three proteins, with apparent molecular masses of 93, 88, and 53 kDa, in tomato root microsomal membranes separated by sucrose density centrifugation. The 53-kDa protein comigrated in the gradient with plasma membrane markers, the 88-kDa protein with Golgi membrane markers, and the 93-kDa protein with markers for both Golgi and plasma membranes. EGase enzyme activity was also found in regions of the density gradient corresponding to both Golgi and plasma membranes, suggesting that Cel3 EGase resides in both membrane systems, the sites of cell wall polymer biosynthesis. The in vivo function of Cel3 is not known, but the only other known membrane-anchored EGase is present in Agrobacterium tumefaciens where it is required for cellulose biosynthesis.

A geochemical and geophysical approach to derive a conceptual circulation model of CO2-rich mineral waters: A case study of Vilarelho da Raia, northern Portugal

NASA Astrophysics Data System (ADS)

Marques, J. M.; Santos, Monteiro; Graça, R. C.; Castro, R.; Aires-Barros, L.; Mendes Victor, L. A.

2001-11-01

The Vilarelho da Raia-Chaves region, located in northern Portugal adjacent to the Spanish border, is characterized by both hot and cold CO2-rich mineral waters issuing from springs and drilled wells. The present paper updates the conceptual circulation model of the Vilarelho da Raia cold CO2-rich mineral waters. Vilarelho da Raia mineral waters, dominated by Na and HCO3 ions, have formed mainly by interaction with CO2 of deep-seated mantle origin. The δ18O, δ2H and 3H values indicate that these waters are the result of meteoric waters infiltrating into Larouco Mountain, NW of Vilarelho da Raia, circulating at shallow depths in granitic rocks and moving into Vilarelho da Raia area. The conceptual geochemical and geophysical circulation model indicates that the hot and cold CO2-rich mineral waters of Chaves (76 °C) and Vilarelho da Raia (17 °C) should be considered manifestations of similar but not the same geohydrological systems. Résumé. La région de Vilarelho da Raia - Chaves, située au Portugal près de la frontière Espagnole, est caractérisée par des eaux carbogazeuses, chaudes et froides, émergeant à des sources et dans des puits. Ce travail constitue une mise au point du modèle conceptuel de circulation des eaux minérales carbogazeuses froides de Vilarelho da Raia. Les eaux minérales de Vilarelho da Raia, dans lesquelles les ions Na and HCO3 sont dominants, résultent principalement d'interactions avec du CO2 d'origine mantellique. Les δ18O, les δ2H, et les teneurs en 3H indiquent que ces eaux proviennent de l'infiltration d'eaux météoriques dans le Mont Larouco au NW de Vilarelho da Raia, circulant à faible profondeur dans les granites en direction de la région de Vilarelho da Raia. Le modèle de circulation géochimique et géophysique conduit à penser que les eaux minérales carbogazeuses chaudes et froides de Chaves (76 °C) et de Vilarelho da Raia (17 °C) doivent être considérées comme des manifestations de systèmes hydrogéologiques similaires, mais non identiques. Resumen. La región de Vilarelho-Chaves está situada en el Norte de Portugal, junto a la frontera con España. Se caracteriza por la existencia de aguas minerales calientes y frías enriquecidas en CO2, que descargan mediante manantiales y pozos. El artículo tiene como objetivo la actualización del modelo conceptual de flujo de las aguas frías de Vilarelho de Raia, que son ricas en CO2. Dichas aguas se han formado fundamentalmente por la interacción con el CO2 procedente del manto profundo, y son del tipo bicarbonatado sódico. Los valores de δ18O, δ2H y 3H indican que proceden de la infiltración de agua meteórica en la Montaña Larouco -al Noroeste de Vilarelho de Raia-, que circulan a poca profundidad en un medio formado por de rocas graníticas y se mueven hacia el área de Vilarelho de Raia. El modelo conceptual de flujo, basado en datos geoquímicos y geofísicos, indica que las aguas minerales calientes de Chaves (76 °C) y las frías de Vilarelho de Raia (17 °C), ambas enriquecidas en CO2, no deben ser consideradas como manifestaciones de un único sistema hidrogeológico, sino de dos similares.

Neural and Behavioral Correlates of PTSD and Alcohol Use

DTIC Science & Technology

2014-12-01

monoamines to the amygdala arise from monoaminergic cell body regions in the brainstem. Specifically, the dorsal raphe nucleus (dRN) provides 5- HT ... effects of 5- HT manipulations within the different amygdala subregions across several well-validated tests of anxiety-like behaviors will better...antipsychotics also have high affinity for 5- HT receptors, the contribution of DA modulation to their anxiolytic effects in humans is currently unknown

Ethnobotanical Survey, Preliminary Physico-Chemical and Phytochemical Screening of Salvia argentea (L.) Used by Herbalists of the Saïda Province in Algeria.

PubMed

Benabdesslem, Yasmina; Hachem, Kadda; Kahloula, Khaled; Slimani, Miloud

2017-12-05

An ethnobotanical study was carried out in the Saïda region among herbalists to evaluate the use of Salvia argentea (L.), a plant species native from North Africa belonging to the Lamiaceae family. Forty-two herbalists were interviewed individually, aged between 30 and 70 years, all males, 52.38% of them having received a secondary education level and having performing their duties for more than a decade. This study showed that Salvia argentea is used specifically in the treatment of diseases of the respiratory system. The leaves are the most commonly used part, usually in the form of powder and exclusively administered orally. The preliminary results of the physicochemical characterization and the phytochemical screening of the powdered leaves of Salvia argentea attest to their safety and confer them a guarantee of phytotherapeutic quality.

Parvalbumin increases in the caudate putamen of rats with vitamin D hypervitaminosis.

PubMed Central

de Viragh, P A; Haglid, K G; Celio, M R

1989-01-01

The influence of chronic vitamin D3 application on the concentration of the four calcium-binding proteins parvalbumin, the 28-kDa calbindin-D, calmodulin, and S-100 was studied in various brain regions and in the kidney. Young rats were administered daily 20,000 international units of vitamin D3 per kg (body weight) over a period of 4 months. This chronic treatment resulted in a clinically mild hypervitaminosis that did not affect the content of calmodulin, the 28-kDa calbindin-D, and S-100. Also the concentration of parvalbumin in the cerebral cortex, hippocampus, and kidney remained unchanged. On the other hand, parvalbumin was increased about 50% in the caudate putamen of hypervitaminotic animals as compared to controls. Our results indicate that the metabolism of parvalbumin in the caudate putamen can be influenced by variations of the blood level of this steroid hormone. PMID:2542952

Multi-element fingerprinting as a tool in origin authentication of four east China marine species.

PubMed

Guo, Lipan; Gong, Like; Yu, Yanlei; Zhang, Hong

2013-12-01

The contents of 25 elements in 4 types of commercial marine species from the East China Sea were determined by inductively coupled plasma mass spectrometry and atomic absorption spectrometry. The elemental composition was used to differentiate marine species according to geographical origin by multivariate statistical analysis. The results showed that principal component analysis could distinguish samples from different areas and reveal the elements which played the most important role in origin diversity. The established models by partial least squares discriminant analysis (PLS-DA) and by probabilistic neural network (PNN) can both precisely predict the origin of the marine species. Further study indicated that PLS-DA and PNN were efficacious in regional discrimination. The models from these 2 statistical methods, with an accuracy of 97.92% and 100%, respectively, could both distinguish samples from different areas without the need for species differentiation. © 2013 Institute of Food Technologists®

Attribution of Observed Streamflow Changes in Key British Columbia Drainage Basins

NASA Astrophysics Data System (ADS)

Najafi, Mohammad Reza; Zwiers, Francis W.; Gillett, Nathan P.

2017-11-01

We study the observed decline in summer streamflow in four key river basins in British Columbia (BC), Canada, using a formal detection and attribution (D&A) analysis procedure. Reconstructed and simulated streamflow is generated using the semidistributed variable infiltration capacity hydrologic model, which is driven by 1/16° gridded observations and downscaled climate model data from the Coupled Model Intercomparison Project phase 5 (CMIP5), respectively. The internal variability of the regional hydrologic components using 5100 years of streamflow was simulated using CMIP5 preindustrial control runs. Results show that the observed changes in summer streamflow are inconsistent with simulations representing the responses to natural forcing factors alone, while the response to anthropogenic and natural forcing factors combined is detected in these changes. A two-signal D&A analysis indicates that the effects of anthropogenic (ANT) forcing factors are discernable from natural forcing in BC, albeit with large uncertainties.

Fatty acid composition and conjugated linoleic acid content in different carcass parts of Dağlıç lambs.

PubMed

Karabacak, Ali; Aytekin, İbrahim; Boztepe, Saim

2014-01-01

This study was conducted to compare fatty acid composition and content of conjugated linoleic acid (CLA) in different regions of sheep carcasses. Lambs of the Dağlıç breed were used for this purpose. Subsequent to a 68-day period of intensive fattening, fatty acids were examined in samples taken from the legs, shoulders, breasts, and ribs of lamb carcasses. According to the analysis, in leg, shoulder, breast, and rib, respectively, total saturated fatty acids (SFA) were found to be 40.38, 42.69, 42.56, and 40.27%, unsaturated fatty acids (MUFA) were found to be 40.38, 44.17, 46.17, and 49.50%, polyunsaturated fatty acids (PUFA) were found to be 4.79, 4.29, 3.80, and 3.72%, and CLAs were found to be 1.49, 1.69, 1.53, and 1.59%.

Characterization of calcineurin-dependent response element binding protein and its involvement in copper-metallothionein gene expression in Neurospora

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

Kumar, Kalari Satish; Ravi Kumar, B.; Siddavattam, Dayananda

2006-07-07

In continuation of our recent observations indicating the presence of a lone calcineurin-dependent response element (CDRE) in the -3730 bp upstream region of copper-induced metallothionein (CuMT) gene of Neurospora [K.S. Kumar, S. Dayananda, C. Subramanyam, Copper alone, but not oxidative stress, induces copper-metallothionein gene in Neurospora crassa, FEMS Microbiol. Lett. 242 (2005) 45-50], we isolated and characterized the CDRE-binding protein. The cloned upstream region of CuMT gene was used as the template to specifically amplify CDRE element, which was immobilized on CNBr-activated Sepharose 4B for use as the affinity matrix to purify the CDRE binding protein from nuclear extracts obtainedmore » from Neurospora cultures grown in presence of copper. Two-dimensional gel electrophoresis of the affinity purified protein revealed the presence of a single 17 kDa protein, which was identified and characterized by MALDI-TOF. Peptide mass finger printing of tryptic digests and analysis of the 17 kDa protein matched with the regulatory {beta}-subunit of calcineurin (Ca{sup 2+}-calmodulin dependent protein phosphatase). Parallel identification of nuclear localization signals in this protein by in silico analysis suggests a putative role for calcineurin in the regulation of CuMT gene expression.« less

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

Swanson, James

The Dopamine (DA) Hypothesis of ADHD (Wender, 1971; Levy, 1990) suggests that abnormalities in the synaptic mechanisms of DA transmission may be disrupted, and specific abnormalities in DA receptors and DA transporters (DAT) have been proposed (see Swanson et al, 1998). Early studies with small samples (e.g., n = 6, Dougherty et al, 1999) used single photon emission tomography (SPECT) and the radioligand (123I Altropane) to test a theory that ADHD may be caused by an over expression of DAT and reported 'a 70% increase in age-corrected dopamine transporter density in patients with attention deficit hyperactivity disorder compared with healthymore » controls' and suggested that treatment with stimulant medication decreased DAT density in ADHD patients and corrected an underlying abnormality (Krause et al, 2000). The potential importance of these findings was noted by Swanson (1999): 'If true, this is a major finding and points the way for new investigations of the primary pharmacological treatment for ADHD (with the stimulant drugs - e.g., methylphenidate), for which the dopamine transporter is the primary site of action. The potential importance of this finding demands special scrutiny'. This has been provided over the past decade using Positron Emission Tomography (PET). Brain imaging studies were conducted at Brookhaven National Laboratory (BNL) in a relatively large sample of stimulant-naive adults assessed for DAT (11C cocaine) density and DA receptors (11C raclopride) availability. These studies (Volkow et al, 2007; Volkow et al, 2009) do not confirm the hypothesis of increased DAT density and suggest the opposite (i.e., decreased rather than increased DAT density), and follow-up after treatment (Wang et al, 2010) does not confirm the hypothesis that therapeutic doses of methylphenidate decrease DAT density and suggests the opposite (i.e., increased rather than decreased DAT density). The brain regions implicated by these PET imaging studies also suggest that a motivation deficit may contribute as much as an attention deficit to the manifestation of behaviors that underlie the symptoms of ADHD.« less

Identification and characterization of a serpin from Eimeria acervulina.

PubMed

Fetterer, R H; Miska, K B; Jenkins, M C; Barfield, R C; Lillehoj, H

2008-12-01

Serpins are serine protease inhibitors that are widely distributed in metazoans but have not been previously characterized in Eimeria spp. A serpin from Eimeria acervulina was cloned, expressed and characterized. Random screening of an E.acervulina sporozoite cDNA library identified a single clone (D14) whose coding region shared high similarity to consensus structure of serpins. Clone D14 contained an entire open reading frame (ORF) consisting of 1,245 nts that encode a peptide 413 amino acids in length with a predicted molecular weight of 45.5 kDa and containing a signal peptide 28 residues in length. By Western blot analysis, polyclonal antiserum to the recombinant serpin (rbSp) recognized a major 55 kDa protein band in unsporulated oocysts and in oocysts sporulated up to 24 hr (fully sporulated). The anti-rbSp detected bands of 55 kDa and 48 kDa in sporozoites (SZ) and merozoites (MZ) respectively. Analysis of MZ secretion products revealed a single protein of 48 kDa which may correspond to secreted serpin. By immuno-staining the serpin was located in granules distributed throughout both the SZ and MZ but granules appeared to be concentrated in the parasite's anterior. Analysis of the structure predicts that the E. acervulina serpin should be an active inhibitor. However, rbSp was without inhibitory activity against common serine proteases. By Western blot analysis the endogenous serpin in MZ extracts did not form the expected high molecular weight complex when coincubated with either trypsin or subtilisin. The results demonstrate that E. acervulina contains a serpin gene and expresses a protein with structural properties similar to an active serine protease inhibitor. Although the function of the E. acervulina serpin remains unknown the results further suggest that serpin is secreted by the parasite where it may be involved in cell invasion and other basic developmental processes.

Relational learning and transitive expression in aging and amnesia

PubMed Central

D'Angelo, Maria C.; Kamino, Daphne; Ostreicher, Melanie; Moses, Sandra N.; Rosenbaum, R. Shayna

2016-01-01

ABSTRACT Aging has been associated with a decline in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm (Bunsey and Eichenbaum (1996) Nature 379:255‐257), which traditionally has been used in nonhuman animal research, this work examined the extent to which aging is accompanied by deficits in relational learning and flexible expression of relational information. Older adults' performance was additionally contrasted with that of amnesic case DA to understand the critical contributions of the medial temporal lobe, and specifically, the hippocampus, which endures structural and functional changes in healthy aging. Participants were required to select the correct choice item (B versus Y) based on the presented sample item (e.g., A). Pairwise relations must be learned (A‐>B, B‐>C, C‐>D) so that ultimately, the correct relations can be inferred when presented with a novel probe item (A‐>C?Z?). Participants completed four conditions of transitivity that varied in terms of the degree to which the stimuli and the relations among them were known pre‐experimentally. Younger adults, older adults, and DA performed similarly when the condition employed all pre‐experimentally known, semantic, relations. Older adults and DA were less accurate than younger adults when all to‐be‐learned relations were arbitrary. However, accuracy improved for older adults when they could use pre‐experimentally known pairwise relations to express understanding of arbitrary relations as indexed through inference judgments. DA could not learn arbitrary relations nor use existing knowledge to support novel inferences. These results suggest that while aging has often been associated with an emerging decline in hippocampal function, prior knowledge can be used to support novel inferences. However, in case DA, significant damage to the hippocampus likely impaired his ability to learn novel relations, while additional damage to ventromedial prefrontal and anterior temporal regions may have resulted in an inability to use prior knowledge to flexibly express indirect relational knowledge. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:26234960

Neural Mechanisms of the Transformation from Objective Value to Subjective Utility: Converting from Count to Worth.

PubMed

Kurnianingsih, Yoanna A; Mullette-Gillman, O'Dhaniel A

2016-01-01

When deciding, we aim to choose the "best" possible outcome. This is not just selection of the option that is the most numerous or physically largest, as options are translated from objective value (count) to subjective value (worth or utility). We localized the neural instantiation of the value-to-utility transformation to the dorsal anterior midcingulate cortex (daMCC), with independent replication. The daMCC encodes the context-specific information necessary to convert from count to worth. This encoding is not simply a representation of utility or preference, but the interaction of the two. Specifically, the relationship of brain activation to value is dependent on individual preference, with both positive and negative slopes across the population depending on whether each individual's preference results in enhancement or diminishment of the valuation. For a given value, across participants, enhanced daMCC activation corresponds to diminished subjective valuation, deactivation to enhanced subjective valuation, and non-modulated activation with non-modulated subjective valuation. Further, functional connectivity analyses identified brain regions (positive connectivity with the inferior frontal gyrus and negative connectivity with the nucleus accumbens) through which contextual information may be integrated into the daMCC and allow for outputs to modulate valuation signals. All analyses were replicated through an independent within-study replication, with initial testing in the gains domain and replication in the intermixed and mirrored losses trials. We also present and discuss an ancillary finding: we were unable to identify parametric value signals for losses through whole-brain analyses, and ROI analyses of the vmPFC presented non-modulation across loss value levels. These results identify the neural locus of the value-to-utility transformation, and provide a specific computational function for the daMCC in the production of subjective valuation through the integration of value, context, and preferences.

Dissolved organic carbon content and characteristics in relation to carbon dioxide partial pressure across Poyang Lake wetlands and adjacent aquatic systems in the Changjiang basin.

PubMed

Wang, Huaxin; Jiao, Ruyuan; Wang, Fang; Zhang, Lu; Yan, Weijin

2016-12-01

Dissolved organic carbon (DOC) plays diverse roles in carbon biogeochemical cycles. Here, we explored the link between DOC and pCO 2 using high-performance size-exclusion chromatography (HPSEC) with UV 254 detection and excitation emission matrix (EEM) fluorescence spectroscopy to determine the molecular weight distribution (MW) and the spectral characteristics of DOC, respectively. The relationship between DOC and pCO 2 was investigated in the Poyang Lake wetlands and their adjacent aquatic systems. The results indicated significant spatial variation in the DOC concentrations, MW distributions, and pCO 2 . The DOC concentration was higher in the wetlands than in the rivers and lakes. pCO 2 was high in wetlands in which the dominant vegetation was Phragmites australis, whereas it was low in wetlands in which Carex tristachya was the dominant species. DOC was divided into five fractions according to MW, as follows: super-low MW (SLMW, <1 kDa); low MW (LMW, 1-2.5 kDa); intermediate MW (IMW, 2.5-3.5 kDa); high MW (HMW, 3.5-6 kDa); and super-high MW (SMW, > 40 kDa). Rivers contained high proportions of HMW and extremely low amounts of SLMW, whereas wetlands had relatively high proportions of SLMW. The proportion of SMW (SMW p ) was particularly high in wetlands. We found that pCO 2 significantly positively correlated with the proportion of IMW, and significantly negatively correlated with SMW p . These data improve our understanding of the MW of bioavailable DOC and its conversion to CO 2 . The present results demonstrate that both the content and characteristics of DOC significantly affect pCO 2 . pCO 2 and DOC must be studied further to help understanding the role of the wetland on the regional CO 2 budget. Copyright © 2016 Elsevier Ltd. All rights reserved.