Automated object-based classification of topography from SRTM data

PubMed Central

Drăguţ, Lucian; Eisank, Clemens

2012-01-01

We introduce an object-based method to automatically classify topography from SRTM data. The new method relies on the concept of decomposing land-surface complexity into more homogeneous domains. An elevation layer is automatically segmented and classified at three scale levels that represent domains of complexity by using self-adaptive, data-driven techniques. For each domain, scales in the data are detected with the help of local variance and segmentation is performed at these appropriate scales. Objects resulting from segmentation are partitioned into sub-domains based on thresholds given by the mean values of elevation and standard deviation of elevation respectively. Results resemble reasonably patterns of existing global and regional classifications, displaying a level of detail close to manually drawn maps. Statistical evaluation indicates that most of classes satisfy the regionalization requirements of maximizing internal homogeneity while minimizing external homogeneity. Most objects have boundaries matching natural discontinuities at regional level. The method is simple and fully automated. The input data consist of only one layer, which does not need any pre-processing. Both segmentation and classification rely on only two parameters: elevation and standard deviation of elevation. The methodology is implemented as a customized process for the eCognition® software, available as online download. The results are embedded in a web application with functionalities of visualization and download. PMID:22485060

Automated object-based classification of topography from SRTM data

NASA Astrophysics Data System (ADS)

Drăguţ, Lucian; Eisank, Clemens

2012-03-01

We introduce an object-based method to automatically classify topography from SRTM data. The new method relies on the concept of decomposing land-surface complexity into more homogeneous domains. An elevation layer is automatically segmented and classified at three scale levels that represent domains of complexity by using self-adaptive, data-driven techniques. For each domain, scales in the data are detected with the help of local variance and segmentation is performed at these appropriate scales. Objects resulting from segmentation are partitioned into sub-domains based on thresholds given by the mean values of elevation and standard deviation of elevation respectively. Results resemble reasonably patterns of existing global and regional classifications, displaying a level of detail close to manually drawn maps. Statistical evaluation indicates that most of classes satisfy the regionalization requirements of maximizing internal homogeneity while minimizing external homogeneity. Most objects have boundaries matching natural discontinuities at regional level. The method is simple and fully automated. The input data consist of only one layer, which does not need any pre-processing. Both segmentation and classification rely on only two parameters: elevation and standard deviation of elevation. The methodology is implemented as a customized process for the eCognition® software, available as online download. The results are embedded in a web application with functionalities of visualization and download.

Topographical Hill Shading Map Production Based Tianditu (map World)

NASA Astrophysics Data System (ADS)

Wang, C.; Zha, Z.; Tang, D.; Yang, J.

2018-04-01

TIANDITU (Map World) is the public version of National Platform for Common Geospatial Information Service, and the terrain service is an important channel for users on the platform. With the development of TIANDITU, topographical hill shading map production for providing and updating global terrain map on line becomes necessary for the characters of strong intuition, three-dimensional sense and aesthetic effect. As such, the terrain service of TIANDITU focuses on displaying the different scales of topographical data globally. And this paper mainly aims to research the method of topographical hill shading map production globally using DEM (Digital Elevation Model) data between the displaying scales about 1 : 140,000,000 to 1 : 4,000,000, corresponded the display level from 2 to 7 on TIANDITU website.

Oral vaccine of Lactococcus lactis harbouring pandemic H1N1 2009 haemagglutinin1 and nisP anchor fusion protein elevates anti-HA1 sIgA levels in mice.

PubMed

Joan, Stella Siaw Xiu; Pui-Fong, Jee; Song, Adelene Ai-Lian; Chang, Li-Yen; Yusoff, Khatijah; AbuBakar, Sazaly; Rahim, Raha Abdul

2016-05-01

An oral lactococcal-based vaccine which haboured the haemagglutinin1 (HA1) antigen fused to nisP anchor protein for the purpose of surface displaying the HA1 antigen was developed against H1N1 virus. Recombinant L. lactis strains expressed HA1-nisP fusion proteins when induced with nisin, as confirmed through western blotting. However, immunofluorescense did not detect any surface-displayed proteins, suggesting that the protein was either unsuccessfully translocated or improperly displayed. Despite this, oral administration of recombinant L. lactis strains to BALB/c mice revealed that significant levels of anti-HA1 sIgA antibodies were detected in mice fecal suspension samples of mice group NZ9000 (pNZ:HN) when compared to the negative control NZ9000 (pNZ8048) group. Specific anti-HA1 sIgA antibodies were locally produced and live recombinant lactococcal vaccine was able to elicit humoral response of BALB/c mice despite unsuccessful surface display of the HA1 epitope.

Hypereosinophilia with abnormal T cells, trisomy 7 and elevated TARC serum level.

PubMed

Roumier, A S; Grardel, N; Laï, J L; Becqueriaux, I; Ghomari, K; de Lavareille, A; Roufosse, F; Prin, L; Capron, M

2003-07-01

The idiopathic hypereosinophilic syndrome (HES) is a rare heterogeneous disorder, characterized by persistent blood eosinophilia with possible organ involvement. We describe here the case of a 20-year-old atopic male presenting chronic hypereosinophilia and eczema since childhood. Biological findings included hypereosinophilia (9.5 x 10(9)/L), hyperlymphocytosis (10.9 x 10(9)/L), polyclonal hypergammaglobulinemia and elevated IgE serum level. Flow cytometric analysis of blood lymphoid cells showed a population of CD2+CD3-CD4+TCRab-TCRgd- lymphocytes. These cells displayed a Th0/Th2 cytokine profile, and a clonal TCR rearrangement pattern. A high serum TARC level was observed. Karyotype studies on blood stimulated culture or lymph nodes revealed a cellular hyperdiploïd clone 47, XY, +7. To our knowledge, this chromosomal aberration has never been reported in such case.

Growth habit and leaf economics determine gas exchange responses to high elevation in an evergreen tree, a deciduous shrub and a herbaceous annual

PubMed Central

Shi, Zuomin; Haworth, Matthew; Feng, Qiuhong; Cheng, Ruimei; Centritto, Mauro

2015-01-01

Plant growth at high elevations necessitates physiological and morphological plasticity to enable photosynthesis (A) under conditions of reduced temperature, increased radiation and the lower partial pressure of atmospheric gases, in particular carbon dioxide (pCO2). Previous studies have observed a wide range of responses to elevation in plant species depending on their adaptation to temperature, elevational range and growth habit. Here, we investigated the effect of an increase in elevation from 2500 to 3500 m above sea level (a.s.l.) on three montane species with contrasting growth habits and leaf economic strategies. While all of the species showed identical increases in foliar δ13C, dark respiration and nitrogen concentration with elevation, contrasting leaf gas exchange and photosynthetic responses were observed between species with different leaf economic strategies. The deciduous shrub Salix atopantha and annual herb Rumex dentatus exhibited increased stomatal (Gs) and mesophyll (Gm) conductance and enhanced photosynthetic capacity at the higher elevation. However, evergreen Quercus spinosa displayed reduced conductance to CO2 that coincided with lower levels of photosynthetic carbon fixation at 3500 m a.s.l. The lower Gs and Gm values of evergreen species at higher elevations currently constrains their rates of A. Future rises in the atmospheric concentration of CO2 ([CO2]) will likely predominantly affect evergreen species with lower specific leaf areas (SLAs) and levels of Gm rather than deciduous species with higher SLA and Gm values. We argue that climate change may affect plant species that compose high-elevation ecosystems differently depending on phenotypic plasticity and adaptive traits affecting leaf economics, as rising [CO2] is likely to benefit evergreen species with thick sclerophyllous leaves. PMID:26433706

Regional rat brain noradrenaline turnover in response to restraint stress.

PubMed

Glavin, G B; Tanaka, M; Tsuda, A; Kohno, Y; Hoaki, Y; Nagasaki, N

1983-08-01

Male Wistar rats were starved for 12 hr and then subjected to either 2 hr of wire mesh "envelope" restraint at room temperature; 2 hr of supine restraint in a specially constructed harness at room temperature or were not restrained. Eight brain regions were examined for NA level and the level of its major metabolite, MHPG-SO4. Plasma corticosterone and gastric ulcer incidence were also measured. All restrained rats displayed marked elevations in MHPG-SO4 levels in most brain regions. In addition, several brain regions in restrained animals showed a reduction in NA level. All restrained rats showed elevated plasma corticosterone levels and evidence of gastric lesions. In general, supine restraint produced greater alterations in regional brain NA turnover, greater evidence of ulcer disease, and higher plasma corticosterone levels than did wire mesh restraint. These data suggest that acute but intense stress in the form of restraint causes markedly altered brain NA activity--a possible neurochemical mechanism underlying the phenomenon of stress-induced disease.

Developing a Game Interface to Assess Risk Perception with Respect to Two Key Dimensions of Risk (Frequency and Severity) in Contexts Where Risks Are Elevated from Their Accepted, "Typical" Values.

PubMed

Goodman, William M; Ma, Zhenfeng; Andrade, Angie

2015-06-01

This four-stage study culminated in a game interface designed to calibrate people's perceptions of net risk (combining frequency and severity), in contexts where risks are elevated from their accepted, "typical" values, as when avalanche threats elevate the risks of "skiing" above levels skiers normally accept. Risk prompts are displayed dynamically, in naturalistic language, and not, for example, as static displays of dollar amounts or probabilities. Individual differences are measured. In Stage 1 (pilot), focus groups (n=9) piloted procedures, visual prompts, and examples of contexts where risks elevated from the "usual," for use in upcoming stages. In Stage 2 (exploratory), participants (primarily students; n=119; mean age, 20.1 years; 64 percent male) were assigned to risk contexts, answered demographic and risk-history questions, and then matched risk-description prompts to perceived "appropriate" levels along an ordinal risk scale. Descriptive measures and graphs showed response distributions; chi-squared analyses compared responses for different demographics. In Stage 3 (manipulating "cards"), participants (n=80; mean age, 37 years; 60 percent male) matched naturalistic risk prompts with ordinal risk positions. Regressions compared cards' placements with their "expected" (per exploratory Stage 2) placements. In Stage 4, the interface was coded in the Unity(®) (implemented at Business and IT Capstone, University of Ontario Institute of Technology, Oshawa, ON, Canada) development environment. In Stage 1, ambiguities in draft wordings/displays for Stage 2 were identified and corrected. Three risk contexts emerged: traffic/hidden intersection; skiing/avalanche; and swimming/drowning. In Stage 2, for traffic and skiing contexts, responses relating ordinal risk categories to realistic examples were observed to cluster around values potentially usable as markers. No associations appeared with demographic variables. In Stage 3, actual and "expected" ordinal-risk-category assignments for naturalistic risk markers were well correlated. "Approximate mappings" between markers and categories appeared stable. In Stage 4, the interface design incorporated the "approximate mappings"-yet also incorporated a "tuning phase," for measuring and recording individual differences. The interface can capture individual differences in risk perception on two key dimensions (frequency and severity)-viewed in dynamic, naturalistic scenarios, where risk levels are increased.

Vegetation engineers marsh morphology through multiple competing stable states

NASA Astrophysics Data System (ADS)

Marani, Marco; Da Lio, Cristina; D'Alpaos, Andrea

2013-02-01

Marshes display impressive biogeomorphic features, such as zonation, a mosaic of extensive vegetation patches of rather uniform composition, exhibiting sharp transitions in the presence of extremely small topographic gradients. Although generally associated with the accretion processes necessary for marshes to keep up with relative sea level rise, competing environmental constraints, and ecologic controls, zonation is still poorly understood in terms of the underlying biogeomorphic mechanisms. Here we find, through observations and modeling interpretation, that zonation is the result of coupled geomorphological-biological dynamics and that it stems from the ability of vegetation to actively engineer the landscape by tuning soil elevation within preferential ranges of optimal adaptation. We find multiple peaks in the frequency distribution of observed topographic elevation and identify them as the signature of biologic controls on geomorphodynamics through competing stable states modulated by the interplay of inorganic and organic deposition. Interestingly, the stable biogeomorphic equilibria correspond to suboptimal rates of biomass production, a result coherent with recent observations. The emerging biogeomorphic structures may display varying degrees of robustness to changes in the rate of sea level rise and sediment availability, with implications for the overall resilience of marsh ecosystems to climatic changes.

Vegetation engineers marsh morphology through multiple competing stable states

PubMed Central

Marani, Marco; Da Lio, Cristina; D’Alpaos, Andrea

2013-01-01

Marshes display impressive biogeomorphic features, such as zonation, a mosaic of extensive vegetation patches of rather uniform composition, exhibiting sharp transitions in the presence of extremely small topographic gradients. Although generally associated with the accretion processes necessary for marshes to keep up with relative sea level rise, competing environmental constraints, and ecologic controls, zonation is still poorly understood in terms of the underlying biogeomorphic mechanisms. Here we find, through observations and modeling interpretation, that zonation is the result of coupled geomorphological–biological dynamics and that it stems from the ability of vegetation to actively engineer the landscape by tuning soil elevation within preferential ranges of optimal adaptation. We find multiple peaks in the frequency distribution of observed topographic elevation and identify them as the signature of biologic controls on geomorphodynamics through competing stable states modulated by the interplay of inorganic and organic deposition. Interestingly, the stable biogeomorphic equilibria correspond to suboptimal rates of biomass production, a result coherent with recent observations. The emerging biogeomorphic structures may display varying degrees of robustness to changes in the rate of sea level rise and sediment availability, with implications for the overall resilience of marsh ecosystems to climatic changes. PMID:23401529

Elevated Mitochondrial Reactive Oxygen Species and Cellular Redox Imbalance in Human NADPH-Oxidase-Deficient Phagocytes

PubMed Central

Sundqvist, Martina; Christenson, Karin; Björnsdottir, Halla; Osla, Veronica; Karlsson, Anna; Dahlgren, Claes; Speert, David P.; Fasth, Anders; Brown, Kelly L.; Bylund, Johan

2017-01-01

Chronic granulomatous disease (CGD) is caused by mutations in genes that encode the NADPH-oxidase and result in a failure of phagocytic cells to produce reactive oxygen species (ROS) via this enzyme system. Patients with CGD are highly susceptible to infections and often suffer from inflammatory disorders; the latter occurs in the absence of infection and correlates with the spontaneous production of inflammatory cytokines. This clinical feature suggests that NADPH-oxidase-derived ROS are not required for, or may even suppress, inflammatory processes. Experimental evidence, however, implies that ROS are in fact required for inflammatory cytokine production. By using a myeloid cell line devoid of a functional NADPH-oxidase and primary CGD cells, we analyzed intracellular oxidants, signs of oxidative stress, and inflammatory cytokine production. Herein, we demonstrate that phagocytes lacking a functional NADPH-oxidase, namely primary CGD phagocytes and a gp91phox-deficient cell line, display elevated levels of ROS derived from mitochondria. Accordingly, these cells, despite lacking the major source of cellular ROS, display clear signs of oxidative stress, including an induced expression of antioxidants and altered oxidation of cell surface thiols. These observed changes in redox state were not due to abnormalities in mitochondrial mass or membrane integrity. Finally, we demonstrate that increased mitochondrial ROS enhanced phosphorylation of ERK1/2, and induced production of IL8, findings that correlate with previous observations of increased MAPK activation and inflammatory cytokine production in CGD cells. Our data show that elevated baseline levels of mitochondria-derived oxidants lead to the counter-intuitive observation that CGD phagocytes are under oxidative stress and have enhanced MAPK signaling, which may contribute to the elevated basal production of inflammatory cytokines and the sterile inflammatory manifestations in CGD. PMID:29375548

Striking changes in tea metabolites due to elevational effects.

PubMed

Kfoury, Nicole; Morimoto, Joshua; Kern, Amanda; Scott, Eric R; Orians, Colin M; Ahmed, Selena; Griffin, Timothy; Cash, Sean B; Stepp, John Richard; Xue, Dayuan; Long, Chunlin; Robbat, Albert

2018-10-30

Climate effects on crop quality at the molecular level are not well-understood. Gas and liquid chromatography-mass spectrometry were used to measure changes of hundreds of compounds in tea at different elevations in Yunnan Province, China. Some increased in concentration while others decreased by 100's of percent. Orthogonal projection to latent structures-discriminant analysis revealed compounds exhibiting analgesic, antianxiety, antibacterial, anticancer, antidepressant, antifungal, anti-inflammatory, antioxidant, anti-stress, and cardioprotective properties statistically (p = 0.003) differentiated high from low elevation tea. Also, sweet, floral, honey-like notes were higher in concentration in the former while the latter displayed grassy, hay-like aroma. In addition, multivariate analysis of variance showed low elevation tea had statistically (p = 0.0062) higher concentrations of caffeine, epicatechin gallate, gallocatechin, and catechin; all bitter compounds. Although volatiles represent a small fraction of the total mass, this is the first comprehensive report illustrating how normal variations in temperature, 5 °C, due to elevational effects impact tea quality. Copyright © 2018 Elsevier Ltd. All rights reserved.

Calcification in Caribbean reef-building corals at high pCO2 levels in a recirculating ocean acidification exposure system.

PubMed

Enzor, Laura A; Hankins, Cheryl; Vivian, Deborah N; Fisher, William S; Barron, Mace G

2018-02-01

Projected increases in ocean p CO 2 levels are anticipated to affect calcifying organisms more rapidly and to a greater extent than other marine organisms. The effects of ocean acidification (OA) have been documented in numerous species of corals in laboratory studies, largely tested using flow-through exposure systems. We developed a recirculating ocean acidification exposure system that allows precise p CO 2 control using a combination of off-gassing measures including aeration, water retention devices, venturi injectors, and CO 2 scrubbing. We evaluated the recirculating system performance in off-gassing effectiveness and maintenance of target p CO 2 levels over an 84-day experiment. The system was used to identify changes in calcification and tissue growth in response to elevated p CO 2 (1000 μatm) in three reef-building corals of the Caribbean: Pseudodiploria clivosa , Montastraea cavernosa , and Orbicella faveolata . All three species displayed an overall increase in net calcification over the 84-day exposure period regardless of p CO 2 level (control +0.28- 1.12 g, elevated p CO 2 +0.18- 1.16 g), and the system was effective at both off-gassing acidified water to ambient p CO 2 levels, and maintaining target elevated p CO 2 levels over the 3-month experiment.

Everglades Depth Estimation Network (EDEN) Applications: Tools to View, Extract, Plot, and Manipulate EDEN Data

USGS Publications Warehouse

Telis, Pamela A.; Henkel, Heather

2009-01-01

The Everglades Depth Estimation Network (EDEN) is an integrated system of real-time water-level monitoring, ground-elevation data, and water-surface elevation modeling to provide scientists and water managers with current on-line water-depth information for the entire freshwater part of the greater Everglades. To assist users in applying the EDEN data to their particular needs, a series of five EDEN tools, or applications (EDENapps), were developed. Using EDEN's tools, scientists can view the EDEN datasets of daily water-level and ground elevations, compute and view daily water depth and hydroperiod surfaces, extract data for user-specified locations, plot transects of water level, and animate water-level transects over time. Also, users can retrieve data from the EDEN datasets for analysis and display in other analysis software programs. As scientists and managers attempt to restore the natural volume, timing, and distribution of sheetflow in the wetlands, such information is invaluable. Information analyzed and presented with these tools is used to advise policy makers, planners, and decision makers of the potential effects of water management and restoration scenarios on the natural resources of the Everglades.

Excess Coenzyme A Reduces Skeletal Muscle Performance and Strength in Mice Overexpressing Human PANK2

PubMed Central

Corbin, Deborah R.; Rehg, Jerold E.; Shepherd, Danielle L.; Stoilov, Peter; Percifield, Ryan J.; Horner, Linda; Frase, Sharon; Zhang, Yong-Mei; Rock, Charles O.; Hollander, John M.; Jackowski, Suzanne; Leonardi, Roberta

2017-01-01

Coenzyme A (CoA) is a cofactor that is central to energy metabolism and CoA synthesis is controlled by the enzyme pantothenate kinase (PanK). A transgenic mouse strain expressing human PANK2 was derived to determine the physiological impact of PANK overexpression and elevated CoA levels. The Tg(PANK2) mice expressed high levels of the transgene in skeletal muscle and heart; however, CoA was substantially elevated only in skeletal muscle, possibly associated with the comparatively low endogenous levels of acetyl-CoA, a potent feedback inhibitor of PANK2. Tg(PANK2) mice were smaller, had less skeletal muscle mass and displayed significantly impaired exercise tolerance and grip strength. Skeletal myofibers were characterized by centralized nuclei and aberrant mitochondria. Both the content of fully assembled complex I of the electron transport chain and ATP levels were reduced, while markers of oxidative stress were elevated in Tg(PANK2) skeletal muscle. These abnormalities were not detected in the Tg(PANK2) heart muscle, with the exception of spotty loss of cristae organization in the mitochondria. The data demonstrate that excessively high CoA may be detrimental to skeletal muscle function. PMID:28189602

Patterns of Adolescent Regulatory Responses during Family Conflict and Mental Health Trajectories

PubMed Central

Koss, Kalsea J.; Cummings, E. Mark; Davies, Patrick T.; Cicchetti, Dante

2016-01-01

Four distinct patterns of adolescents’ behavioral, emotional, and physiological responses to family conflict were identified during mother-father-adolescent (M=13.08 years) interactions. Most youth displayed adaptively-regulated patterns comprised of low overt and subjective distress. Under-controlled adolescents exhibited elevated observable and subjective anger. Over-controlled adolescents were withdrawn and reported heightened subjective distress. Physiologically reactive adolescents had elevated cortisol coupled with low overt and subjective distress. Regulation patterns were associated with unique mental health trajectories. Under-controlled adolescents had elevated conduct and peer problems whereas over-controlled adolescents had higher anxiety and depressive symptoms. Physiologically reactive adolescents had low concurrent, but increasing levels of depressive, anxiety, and peer problem symptoms. Findings underscore the importance of examining organizations of regulatory strategies in contributing to adolescent mental health. PMID:28498540

Identification of plexin A4 as a novel clusterin receptor links two Alzheimer’s disease risk genes

PubMed Central

Kang, Silvia S.; Kurti, Aishe; Wojtas, Aleksandra; Baker, Kelsey E.; Liu, Chia-Chen; Kanekiyo, Takahisa; Deming, Yuetiva; Cruchaga, Carlos; Estus, Steven; Bu, Guojun; Fryer, John D.

2016-01-01

Although abundant genetic and biochemical evidence strongly links Clusterin (CLU) to Alzheimer disease (AD) pathogenesis, the receptor for CLU within the adult brain is currently unknown. Using unbiased approaches, we identified Plexin A4 (PLXNA4) as a novel, high-affinity receptor for CLU in the adult brain. PLXNA4 protein expression was high in brain with much lower levels in peripheral organs. CLU protein levels were significantly elevated in the cerebrospinal fluid (CSF) of Plxna4-/- mice and, in humans, CSF levels of CLU were also associated with PLXNA4 genotype. Human AD brains had significantly increased the levels of CLU protein but decreased levels of PLXNA4 by ∼50%. To determine whether PLXNA4 levels influenced cognition, we analyzed the behaviour of Plxna4+/+, Plxna4+/-, and Plxna4-/- mice. In comparison to WT controls, both Plxna4+/- and Plxna4-/- mice were hyperactive in the open field assay while Plxna4-/- mice displayed a hyper-exploratory (low-anxiety phenotype) in the elevated plus maze. Importantly, both Plxna4+/- and Plxna4-/- mice displayed prominent deficits in learning and memory in the contextual fear-conditioning paradigm. Thus, even a 50% reduction in the level of PLXNA4 is sufficient to cause memory impairments, raising the possibility that memory problems seen in AD patients could be due to reductions in the level of PLXNA4. Both CLU and PLXNA4 have been genetically associated with AD risk and our data thus provide a direct relationship between two AD risk genes. Our data suggest that increasing the levels of PLXNA4 or targeting CLU-PLXNA4 interactions may have therapeutic value in AD. PMID:27378688

Identification of plexin A4 as a novel clusterin receptor links two Alzheimer's disease risk genes.

PubMed

Kang, Silvia S; Kurti, Aishe; Wojtas, Aleksandra; Baker, Kelsey E; Liu, Chia-Chen; Kanekiyo, Takahisa; Deming, Yuetiva; Cruchaga, Carlos; Estus, Steven; Bu, Guojun; Fryer, John D

2016-08-15

Although abundant genetic and biochemical evidence strongly links Clusterin (CLU) to Alzheimer disease (AD) pathogenesis, the receptor for CLU within the adult brain is currently unknown. Using unbiased approaches, we identified Plexin A4 (PLXNA4) as a novel, high-affinity receptor for CLU in the adult brain. PLXNA4 protein expression was high in brain with much lower levels in peripheral organs. CLU protein levels were significantly elevated in the cerebrospinal fluid (CSF) of Plxna4 -/- mice and, in humans, CSF levels of CLU were also associated with PLXNA4 genotype. Human AD brains had significantly increased the levels of CLU protein but decreased levels of PLXNA4 by ∼50%. To determine whether PLXNA4 levels influenced cognition, we analyzed the behaviour of Plxna4 +/+ , Plxna4 +/- , and Plxna4 -/- mice. In comparison to WT controls, both Plxna4 +/- and Plxna4 -/- mice were hyperactive in the open field assay while Plxna4 -/- mice displayed a hyper-exploratory (low-anxiety phenotype) in the elevated plus maze. Importantly, both Plxna4 +/- and Plxna4 -/- mice displayed prominent deficits in learning and memory in the contextual fear-conditioning paradigm. Thus, even a 50% reduction in the level of PLXNA4 is sufficient to cause memory impairments, raising the possibility that memory problems seen in AD patients could be due to reductions in the level of PLXNA4. Both CLU and PLXNA4 have been genetically associated with AD risk and our data thus provide a direct relationship between two AD risk genes. Our data suggest that increasing the levels of PLXNA4 or targeting CLU-PLXNA4 interactions may have therapeutic value in AD. © The Author 2016. Published by Oxford University Press.

Oxygen consumption of animals under conditions of hypokinesia

NASA Technical Reports Server (NTRS)

Loginova, Y. N.; Volozhin, A. I.; Krasnyku, I. G.; Stroganova, Y. A.

1980-01-01

The influence of hypokinesia on the oxygen consumption of rats, dog, and squirrels was investigated. Three periods of gaseous exchange were revealed in rats under conditions of a limited motor activity. During the first 10-15 days O2 consumption displayed a sharp elevation; on the 20th-30th day, it became stabilized at a higher level (in comparison with control) and it sharply rose again on the 40th-100th day. In dogs, hypokinesia produced a reduction of O2 consumption and then a tendency to its elevation was seen. A short period of physical exercises in squirrels after hypokinesia led to increased oxygen consumption at rest.

Limited tolerance by insects to high temperatures across tropical elevational gradients and the implications of global warming for extinction.

PubMed

García-Robledo, Carlos; Kuprewicz, Erin K; Staines, Charles L; Erwin, Terry L; Kress, W John

2016-01-19

The critical thermal maximum (CTmax), the temperature at which motor control is lost in animals, has the potential to determine if species will tolerate global warming. For insects, tolerance to high temperatures decreases with latitude, suggesting that similar patterns may exist along elevational gradients as well. This study explored how CTmax varies among species and populations of a group of diverse tropical insect herbivores, the rolled-leaf beetles, across both broad and narrow elevational gradients. Data from 6,948 field observations and 8,700 museum specimens were used to map the elevational distributions of rolled-leaf beetles on two mountains in Costa Rica. CTmax was determined for 1,252 individual beetles representing all populations across the gradients. Initial morphological identifications suggested a total of 26 species with populations at different elevations displaying contrasting upper thermal limits. However, compared with morphological identifications, DNA barcodes (cytochrome oxidase I) revealed significant cryptic species diversity. DNA barcodes identified 42 species and haplotypes across 11 species complexes. These 42 species displayed much narrower elevational distributions and values of CTmax than the 26 morphologically defined species. In general, species found at middle elevations and on mountaintops are less tolerant to high temperatures than species restricted to lowland habitats. Species with broad elevational distributions display high CTmax throughout their ranges. We found no significant phylogenetic signal in CTmax, geography, or elevational range. The narrow variance in CTmax values for most rolled-leaf beetles, especially high-elevation species, suggests that the risk of extinction of insects may be substantial under some projected rates of global warming.

Limited tolerance by insects to high temperatures across tropical elevational gradients and the implications of global warming for extinction

PubMed Central

García-Robledo, Carlos; Kuprewicz, Erin K.; Staines, Charles L.; Erwin, Terry L.; Kress, W. John

2016-01-01

The critical thermal maximum (CTmax), the temperature at which motor control is lost in animals, has the potential to determine if species will tolerate global warming. For insects, tolerance to high temperatures decreases with latitude, suggesting that similar patterns may exist along elevational gradients as well. This study explored how CTmax varies among species and populations of a group of diverse tropical insect herbivores, the rolled-leaf beetles, across both broad and narrow elevational gradients. Data from 6,948 field observations and 8,700 museum specimens were used to map the elevational distributions of rolled-leaf beetles on two mountains in Costa Rica. CTmax was determined for 1,252 individual beetles representing all populations across the gradients. Initial morphological identifications suggested a total of 26 species with populations at different elevations displaying contrasting upper thermal limits. However, compared with morphological identifications, DNA barcodes (cytochrome oxidase I) revealed significant cryptic species diversity. DNA barcodes identified 42 species and haplotypes across 11 species complexes. These 42 species displayed much narrower elevational distributions and values of CTmax than the 26 morphologically defined species. In general, species found at middle elevations and on mountaintops are less tolerant to high temperatures than species restricted to lowland habitats. Species with broad elevational distributions display high CTmax throughout their ranges. We found no significant phylogenetic signal in CTmax, geography, or elevational range. The narrow variance in CTmax values for most rolled-leaf beetles, especially high-elevation species, suggests that the risk of extinction of insects may be substantial under some projected rates of global warming. PMID:26729867

Quantification of extracellular levels of corticosterone in the basolateral amygdaloid complex of freely-moving rats: a dialysis study of circadian variation and stress-induced modulation.

PubMed

Bouchez, Gaëlle; Millan, Mark J; Rivet, Jean-Michel; Billiras, Rodolphe; Boulanger, Raphaël; Gobert, Alain

2012-05-03

Corticosterone influences emotion and cognition via actions in a diversity of corticolimbic structures, including the amygdala. Since extracellular levels of corticosterone in brain have rarely been studied, we characterized a specific and sensitive enzymatic immunoassay for microdialysis quantification of corticosterone in the basolateral amygdaloid complex of freely-moving rats. Corticosterone levels showed marked diurnal variation with an evening (dark phase) peak and stable, low levels during the day (light phase). The "anxiogenic agents", FG7142 (20 mg/kg) and yohimbine (10 mg/kg), and an environmental stressor, 15-min forced-swim, induced marked and sustained (1-3 h) increases in dialysis levels of corticosterone in basolateral amygdaloid complex. They likewise increased dialysis levels of dopamine and noradrenaline, but not serotonin and GABA. As compared to basal corticosterone levels of ~200-300 pg/ml, the elevation provoked by forced-swim was ca. 20-fold and this increase was abolished by adrenalectomy. Interestingly, stress-induced rises of corticosterone levels in basolateral amygdaloid complex were abrogated by combined but not separate administration of the corticotrophin releasing factor(1) (CRF(1)) receptor antagonist, CP154,526, and the vasopressin(1b) (V(1b)) receptor antagonist, SSR149,415. Underpinning their specificity, they did not block forced-swim-induced elevations in dopamine and noradrenaline. In conclusion, extracellular levels of corticosterone in the basolateral amygdaloid complex display marked diurnal variation. Further, they are markedly elevated by acute stressors, the effects of which are mediated (in contrast to concomitant elevations in levels of monoamines) by co-joint recruitment of CRF(1) and V(1b) receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

Deficits in acetylcholine homeostasis, receptors and behaviors in choline transporter heterozygous mice.

PubMed

Bazalakova, M H; Wright, J; Schneble, E J; McDonald, M P; Heilman, C J; Levey, A I; Blakely, R D

2007-07-01

Cholinergic neurons elaborate a hemicholinium-3 (HC-3) sensitive choline transporter (CHT) that mediates presynaptic, high-affinity choline uptake (HACU) in support of acetylcholine (ACh) synthesis and release. Homozygous deletion of CHT (-/-) is lethal shortly after birth (Ferguson et al. 2004), consistent with CHT as an essential component of cholinergic signaling, but precluding functional analyses of CHT contributions in adult animals. In contrast, CHT+/- mice are viable, fertile and display normal levels of synaptosomal HACU, yet demonstrate reduced CHT protein and increased sensitivity to HC-3, suggestive of underlying cholinergic hypofunction. We find that CHT+/- mice are equivalent to CHT+/+ siblings on measures of motor co-ordination (rotarod), general activity (open field), anxiety (elevated plus maze, light/dark paradigms) and spatial learning and memory (Morris water maze). However, CHT+/- mice display impaired performance as a result of physical challenge in the treadmill paradigm, as well as reduced sensitivity to challenge with the muscarinic receptor antagonist scopolamine in the open field paradigm. These behavioral alterations are accompanied by significantly reduced brain ACh levels, elevated choline levels and brain region-specific decreased expression of M1 and M2 muscarinic acetylcholine receptors. Our studies suggest that CHT hemizygosity results in adequate baseline ACh stores, sufficient to sustain many phenotypes, but normal sensitivities to physical and/or pharmacological challenge require full cholinergic signaling capacity.

Radioactivity in fossils at the Hagerman Fossil Beds National Monument.

PubMed

Farmer, C Neal; Kathren, Ronald L; Christensen, Craig

2008-08-01

Since 1996, higher than background levels of naturally occurring radioactivity have been documented in both fossil and mineral deposits at Hagerman Fossil Beds National Monument in south-central Idaho. Radioactive fossil sites occur primarily within an elevation zone of 900-1000 m above sea level and are most commonly found associated with ancient river channels filled with sand. Fossils found in clay rich deposits do not exhibit discernable levels of radioactivity. Out of 300 randomly selected fossils, approximately three-fourths exhibit detectable levels of natural radioactivity ranging from 1 to 2 orders of magnitude above ambient background levels when surveyed with a portable hand held Geiger-Muller survey instrument. Mineral deposits in geologic strata also show above ambient background levels of radioactivity. Radiochemical lab analysis has documented the presence of numerous natural radioactive isotopes. It is postulated that ancient groundwater transported radioactive elements through sand bodies containing fossils which precipitated out of solution during the fossilization process. The elevated levels of natural radioactivity in fossils may require special precautions to ensure that exposures to personnel from stored or displayed items are kept as low as reasonably achievable (ALARA).

A Graphics Facility for Integration, Editing, and Display of Slope, Curvature, and Contours from a Digital Terrain Elevation Database

DTIC Science & Technology

1988-06-01

DETAILED PROBLEM STATEM ENT ......................................................... 23 A . INTRODUCTION...assorted information about the world land masses. When this is done, the problem of storage, manipulation, and display of realistic, dense, and accurate...elevation data becomes a problem of paramount importance. If the data which is stored can be utilized to recreate specific information about certain

Cortistatin Is a Key Factor Regulating the Sex-Dependent Response of the GH and Stress Axes to Fasting in Mice.

PubMed

Cordoba-Chacón, José; Gahete, Manuel D; Pozo-Salas, Ana I; de Lecea, Luis; Castaño, Justo P; Luque, Raúl M

2016-07-01

Cortistatin (CORT) shares high structural and functional similarities with somatostatin (SST) but displays unique sex-dependent pituitary actions. Indeed, although female CORT-knockout (CORT-KO) mice exhibit enhanced GH expression/secretion, Proopiomelanocortin expression, and circulating ACTH/corticosterone/ghrelin levels, male CORT-KO mice only display increased plasma GH/corticosterone levels. Changes in peripheral ghrelin and SST (rather than hypothalamic levels) seem to regulate GH/ACTH axes in CORT-KOs under fed conditions. Because changes in GH/ACTH axes during fasting provide important adaptive mechanisms, we sought to determine whether CORT absence influences GH/ACTH axes during fasting. Accordingly, fed and fasted male/female CORT-KO were compared with littermate controls. Fasting increased circulating GH levels in male/female controls but not in CORT-KO, suggesting that CORT can be a relevant regulator of GH secretion during fasting. However, GH levels were already higher in CORT-KO than in controls in fed state, which might preclude a further elevation in GH levels. Interestingly, although fasting-induced pituitary GH expression was elevated in both male/female controls, GH expression only increased in fasted female CORT-KOs, likely owing to specific changes observed in key factors controlling somatotrope responsiveness (ie, circulating ghrelin and IGF-1, and pituitary GHRH and ghrelin receptor expression). Fasting increased corticosterone levels in control and, most prominently, in CORT-KO mice, which might be associated with a desensitization to SST signaling and to an augmentation in CRH and ghrelin-signaling regulating corticotrope function. Altogether, these results provide compelling evidence that CORT plays a key, sex-dependent role in the regulation of the GH/ACTH axes in response to fasting.

Osmotic adjustment in five tree species under elevated CO sub 2 and water stress. [Platanus occidentalis L. ; Liquidambar styraciflua L. ; Quercus rubra L. ; Acer saccharum Marsh; Liriodendron tulipifera L

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

Tschaplinski, T.J.; Hanson, P.J.; Norby, R.J.

1991-05-01

Since osmotic adjustment to water stress requires carbon assimilation during stress, the stimulation of photosynthesis by elevated CO{sub 2} may enhance osmotic adjustment. Osmotic adjustment of American sycamore (Platanus occidentalis L.), sweetgum (Liquidambar styraciflua L.), sugar maple (Acer saccharum Marsh.), yellow-poplar (Liriodendron tulipifera L.), and northern red oak (Quercus rubra L.) to water stress was assessed under ambient and elevated CO{sub 2} (ambient +300 {mu}L L{sup {minus}1}), with seedlings grown in 8-L pots in four open-top chambers, fitted with rain exclusion canopies. Trees were subjected to repeated water stress cycles over a six-week period. Well-watered trees were watered daily tomore » maintain a soil matric potential > {minus}0.3 MPa, whereas stressed trees were watered when soil matric potential declined to < {minus}0.9 MPa. Gas exchange and water relations were monitored at the depth of stress and after rewatering. All species displayed an increase in leaf-level water-use efficiency (net photosynthesis/transpiration). Leaves of sycamore and sweetgum displayed an adjustment in osmotic potential at saturation (pressure-volume analysis) of 0.3 MPa and 0.6 MPa, respectively. Elevated CO{sub 2} did not enhance osmotic adjustment in leaves of any of the species studied. Studies to characterize organic solute concentrations in roots are ongoing to determine if osmotic adjustment occurred in the roots.« less

Tactile Cueing for Target Acquisition and Identification

DTIC Science & Technology

2005-09-01

method of coding tactile information, and the method of presenting elevation information were studied. Results: Subjects were divided into video game experienced...VGP) subjects and non- video game (NVGP) experienced subjects. VGPs showed a significantly lower’ target acquisition time with the 12...that video game players performed better with the highest level of tactile resolution, while non- video game players performed better with simpler pattern and a lower resolution display.

Signaling via the Trichoderma atroviride mitogen-activated protein kinase Tmk 1 differentially affects mycoparasitism and plant protection.

PubMed

Reithner, Barbara; Schuhmacher, Rainer; Stoppacher, Norbert; Pucher, Marion; Brunner, Kurt; Zeilinger, Susanne

2007-11-01

Trichoderma atroviride is a mycoparasite of a number of plant pathogenic fungi thereby employing morphological changes and secretion of cell wall degrading enzymes and antibiotics. The function of the tmk 1 gene encoding a mitogen-activated protein kinase (MAPK) during fungal growth, mycoparasitic interaction, and biocontrol was examined in T. atroviride. Deltatmk 1 mutants exhibited altered radial growth and conidiation, and displayed de-regulated infection structure formation in the absence of a host-derived signal. In confrontation assays, tmk 1 deletion caused reduced mycoparasitic activity although attachment to Rhizoctonia solani and Botrytis cinerea hyphae was comparable to the parental strain. Under chitinase-inducing conditions, nag 1 and ech 42 transcript levels and extracellular chitinase activities were elevated in a Deltatmk 1 mutant, whereas upon direct confrontation with R. solani or B. cinerea a host-specific regulation of ech 42 transcription was found and nag 1 gene transcription was no more inducible over an elevated basal level. Deltatmk 1 mutants exhibited higher antifungal activity caused by low molecular weight substances, which was reflected by an over-production of 6-pentyl-alpha-pyrone and peptaibol antibiotics. In biocontrol assays, a Deltatmk 1 mutant displayed a higher ability to protect bean plants against R. solani.

Signaling via the Trichoderma atroviride mitogen-activated protein kinase Tmk1 differentially affects mycoparasitism and plant protection

PubMed Central

Reithner, Barbara; Schuhmacher, Rainer; Stoppacher, Norbert; Pucher, Marion; Brunner, Kurt; Zeilinger, Susanne

2015-01-01

Trichoderma atroviride is a mycoparasite of a number of plant pathogenic fungi thereby employing morphological changes and secretion of cell wall degrading enzymes and antibiotics. The function of the tmk1 gene encoding a mitogen-activated protein kinase (MAPK) during fungal growth, mycoparasitic interaction, and biocontrol was examined in T. atroviride. Δtmk1 mutants exhibited altered radial growth and conidiation, and displayed de-regulated infection structure formation in the absence of a host-derived signal. In confrontation assays, tmk1 deletion caused reduced mycoparasitic activity although attachment to Rhizoctonia solani and Botrytis cinerea hyphae was comparable to the parental strain. Under chitinase-inducing conditions, nag1 and ech42 transcript levels and extracellular chitinase activities were elevated in a Δtmk1 mutant, whereas upon direct confrontation with R. solani or B. cinerea a host-specific regulation of ech42 transcription was found and nag1 gene transcription was no more inducible over an elevated basal level. Δtmk1 mutants exhibited higher antifungal activity caused by low molecular weight substances, which was reflected by an over-production of 6-pentyl-α-pyrone and peptaibol antibiotics. In biocontrol assays, a Δtmk1 mutant displayed a higher ability to protect bean plants against R. solani. PMID:17509915

Role of TGR-B1-Mediated Down Regulation of NF-kB/Rel Activity During Growth Arrest of Breast Cancer Cells

DTIC Science & Technology

2001-05-01

gallate ( EGCG ), which has been shown to inhibit the induction of NF-KB and growth of breast cancer cell lines in vitro. EGCG reduced NF-KB levels in the...demonstrated activation of NF-KB is induced upon over-expression of Her-2/neu. Thus, studies were initiated with green tea pholyphenol, epigallocatechin -3...NF639 cell line derived from an MMTV-Her-2/neu mouse tumor. NF639 clonal isolates resistant to EGCG appear to display elevated levels of NF-KB. Overall

Spatial patterns of wet season precipitation vertical gradients on the Tibetan Plateau and the surroundings.

PubMed

Cuo, Lan; Zhang, Yongxin

2017-07-11

The Tibetan Plateau and the surrounding (TPS) with its vast land mass and high elevation affects regional climate and weather. The TPS is also the headwater of 9 major Asian rivers that provide fresh water for 1.65 billion people and many ecosystems, with wet season (May-September) precipitation being the critical component of the fresh water. Using station observations, ERA-Interim and MERRA2 reanalysis, we find that wet season precipitation displays vertical gradients (i.e., changes with elevation) that vary within the region on the TPS. The decrease of precipitation with elevation occurs in the interior TPS with elevation larger than 4000 m, little or no change over the southeastern TPS, and increase elsewhere. The increase of precipitation with elevation is caused by increasing convective available potential energy (CAPE) and decreasing lifting condensation level (LCL) with elevation overwhelming the effects of decreasing total column water vapor (TCWV) with elevation. The decreasing precipitation with elevation is due to the combined effects of increasing LCL and decreasing TCWV. LCL and CAPE play a more important role than TCWV in determining the spatial patterns. These findings are important for hydrology study in observation scarce mountainous areas, water resources and ecosystem managements in the region.

Elevated oxidized glutathione in cystinotic proximal tubular epithelial cells.

PubMed

Wilmer, Martijn J G; de Graaf-Hess, Adriana; Blom, Henk J; Dijkman, Henry B P M; Monnens, Leo A; van den Heuvel, Lambertus P; Levtchenko, Elena N

2005-11-18

Cystinosis, the most frequent cause of inborn Fanconi syndrome, is characterized by the lysosomal cystine accumulation, caused by mutations in the CTNS gene. To elucidate the pathogenesis of cystinosis, we cultured proximal tubular cells from urine of cystinotic patients (n = 9) and healthy controls (n = 9), followed by immortalization with human papilloma virus (HPV E6/E7). Obtained cell lines displayed basolateral polarization, alkaline phosphatase activity, and presence of aminopeptidase N (CD-13) and megalin, confirming their proximal tubular origin. Cystinotic cell lines exhibited elevated cystine levels (0.86 +/- 0.95 nmol/mg versus 0.09 +/- 0.01 nmol/mg protein in controls, p = 0.03). Oxidized glutathione was elevated in cystinotic cells (1.16 +/- 0.83 nmol/mg versus 0.29 +/- 0.18 nmol/mg protein, p = 0.04), while total glutathione, free cysteine, and ATP contents were normal in these cells. In conclusion, elevated oxidized glutathione in cystinotic proximal tubular epithelial cell lines suggests increased oxidative stress, which may contribute to tubular dysfunction in cystinosis.

Seasonal plasticity of auditory hair cell frequency sensitivity correlates with plasma steroid levels in vocal fish

PubMed Central

Rohmann, Kevin N.; Bass, Andrew H.

2011-01-01

SUMMARY Vertebrates displaying seasonal shifts in reproductive behavior provide the opportunity to investigate bidirectional plasticity in sensory function. The midshipman teleost fish exhibits steroid-dependent plasticity in frequency encoding by eighth nerve auditory afferents. In this study, evoked potentials were recorded in vivo from the saccule, the main auditory division of the inner ear of most teleosts, to test the hypothesis that males and females exhibit seasonal changes in hair cell physiology in relation to seasonal changes in plasma levels of steroids. Thresholds across the predominant frequency range of natural vocalizations were significantly less in both sexes in reproductive compared with non-reproductive conditions, with differences greatest at frequencies corresponding to call upper harmonics. A subset of non-reproductive males exhibiting an intermediate saccular phenotype had elevated testosterone levels, supporting the hypothesis that rising steroid levels induce non-reproductive to reproductive transitions in saccular physiology. We propose that elevated levels of steroids act via long-term (days to weeks) signaling pathways to upregulate ion channel expression generating higher resonant frequencies characteristic of non-mammalian auditory hair cells, thereby lowering acoustic thresholds. PMID:21562181

Aerobic capacity and hepatic mitochondrial lipid oxidation alters susceptibility for chronic high-fat diet-induced hepatic steatosis.

PubMed

Morris, E Matthew; Meers, Grace M E; Koch, Lauren G; Britton, Steven L; Fletcher, Justin A; Fu, Xiaorong; Shankar, Kartik; Burgess, Shawn C; Ibdah, Jamal A; Rector, R Scott; Thyfault, John P

2016-10-01

Rats selectively bred for high capacity running (HCR) or low capacity running (LCR) display divergence for intrinsic aerobic capacity and hepatic mitochondrial oxidative capacity, both factors associated with susceptibility for nonalcoholic fatty liver disease. Here, we tested if HCR and LCR rats display differences in susceptibility for hepatic steatosis after 16 wk of high-fat diets (HFD) with either 45% or 60% of kcals from fat. HCR rats were protected against HFD-induced hepatic steatosis, whereas only the 60% HFD induced steatosis in LCR rats, as marked by a doubling of liver triglycerides. Hepatic complete fatty acid oxidation (FAO) and mitochondrial respiratory capacity were all lower in LCR compared with HCR rats. LCR rats also displayed lower hepatic complete and incomplete FAO in the presence of etomoxir, suggesting a reduced role for noncarnitine palmitoyltransferase-1-mediated lipid catabolism in LCR versus HCR rats. Hepatic complete FAO and mitochondrial respiration were largely unaffected by either chronic HFD; however, 60% HFD feeding markedly reduced 2-pyruvate oxidation, a marker of tricarboxylic acid (TCA) cycle flux, and mitochondrial complete FAO only in LCR rats. LCR rats displayed lower levels of hepatic long-chain acylcarnitines than HCR rats but maintained similar levels of hepatic acetyl-carnitine levels, further supporting lower rates of β-oxidation, and TCA cycle flux in LCR than HCR rats. Finally, only LCR rats displayed early reductions in TCA cycle genes after the acute initiation of a HFD. In conclusion, intrinsically high aerobic capacity confers protection against HFD-induced hepatic steatosis through elevated hepatic mitochondrial oxidative capacity.

Aerobic capacity and hepatic mitochondrial lipid oxidation alters susceptibility for chronic high-fat diet-induced hepatic steatosis

PubMed Central

Morris, E. Matthew; Meers, Grace M. E.; Koch, Lauren G.; Britton, Steven L.; Fletcher, Justin A.; Fu, Xiaorong; Shankar, Kartik; Burgess, Shawn C.; Ibdah, Jamal A.; Rector, R. Scott

2016-01-01

Rats selectively bred for high capacity running (HCR) or low capacity running (LCR) display divergence for intrinsic aerobic capacity and hepatic mitochondrial oxidative capacity, both factors associated with susceptibility for nonalcoholic fatty liver disease. Here, we tested if HCR and LCR rats display differences in susceptibility for hepatic steatosis after 16 wk of high-fat diets (HFD) with either 45% or 60% of kcals from fat. HCR rats were protected against HFD-induced hepatic steatosis, whereas only the 60% HFD induced steatosis in LCR rats, as marked by a doubling of liver triglycerides. Hepatic complete fatty acid oxidation (FAO) and mitochondrial respiratory capacity were all lower in LCR compared with HCR rats. LCR rats also displayed lower hepatic complete and incomplete FAO in the presence of etomoxir, suggesting a reduced role for noncarnitine palmitoyltransferase-1-mediated lipid catabolism in LCR versus HCR rats. Hepatic complete FAO and mitochondrial respiration were largely unaffected by either chronic HFD; however, 60% HFD feeding markedly reduced 2-pyruvate oxidation, a marker of tricarboxylic acid (TCA) cycle flux, and mitochondrial complete FAO only in LCR rats. LCR rats displayed lower levels of hepatic long-chain acylcarnitines than HCR rats but maintained similar levels of hepatic acetyl-carnitine levels, further supporting lower rates of β-oxidation, and TCA cycle flux in LCR than HCR rats. Finally, only LCR rats displayed early reductions in TCA cycle genes after the acute initiation of a HFD. In conclusion, intrinsically high aerobic capacity confers protection against HFD-induced hepatic steatosis through elevated hepatic mitochondrial oxidative capacity. PMID:27600823

Sustaining Pinus flexilis ecosystems of the southern Rocky Mountains (USA) in the presence of Cronartium ribicola and Dendroctonus ponderosae in a changing climate

Treesearch

Anna W. Schoettle; Richard A. Sniezko; Kelly S. Burns

2009-01-01

Limber pine, Pinus flexilis James, is characterized by a patchy distribution that displays metapopulation dynamics and spans a broad latitudinal and elevational range in North America (Webster and Johnson 2000). In the southern Rocky Mountains limber pine grows from below the forest-grassland ecotone up to the forest-alpine ecotone, from ~1600 m above sea level in the...

Quantifying the behavioral response of spawning chum salmon to elevated discharges from Bonneville Dam, Columbia River, USA

USGS Publications Warehouse

Tiffan, K.F.; Haskell, C.A.; Kock, T.J.

2010-01-01

Chum salmon Oncorhynchus keta that spawn in main-stem habitats below Bonneville Dam on the Columbia River, USA, are periodically subjected to elevated discharges that may alter spawning behaviour. We investigated behavioural responses of spawning chum salmon to increased water velocities associated with experimental increases in tailwater elevation using acoustic telemetry and a dual-frequency identification sonar. Chum salmon primarily remained near their redds at base tailwater elevations (3.5 m above mean sea level), but displayed different movement and behavioural responses as elevations were increased to either 4.1 or 4.7m for 8-h periods. When velocities remained suitable (<0.8m s-1) during elevated-tailwater tests, female chum salmon remained near their redds but exhibited reduced digging activity as water velocities increased. However, when velocities exceeded 0.8m s-1, the females that remained on their redds exhibited increased swimming activity and digging virtually ceased. Female and male chum salmon that left their redds when velocities became unsuitable moved mean distances ranging from 32 to 58 m to occupy suitable velocities, but returned to their redds after tailwaters returned to base levels. Spawning events (i.e. egg deposition) were observed for five of nine pairs of chum salmon following tests indicating any disruptions to normal behaviour caused by elevated tailwaters were likely temporary. We believe a chum salmon's decision to either remain on, or leave, its redd during periods of unsuitably high water velocities reflects time invested in the redd and the associated energetic costs it is willing to incur. ?? 2009 John Wiley & Sons, Ltd.

State of Louisiana - Highlighting low-lying areas derived from USGS Digital Elevation Data

USGS Publications Warehouse

Kosovich, John J.

2008-01-01

In support of U.S. Geological Survey (USGS) disaster preparedness efforts, this map depicts a color shaded relief representation highlighting the State of Louisiana and depicts the surrounding areas using muted elevation colors. The first 30 feet of relief above mean sea level are displayed as brightly colored 5-foot elevation bands, which highlight low-elevation areas at a coarse spatial resolution. Areas below sea level typically are surrounded by levees or some other type of flood-control structures. Standard USGS National Elevation Dataset (NED) 1 arc-second (nominally 30-meter) digital elevation model (DEM) data are the basis for the map, which is designed to be used at a broad scale and for informational purposes only. The NED data are a mixture of data and were derived from the original 1:24,000-scale USGS topographic map bare-earth contours, which were converted into gridded quadrangle-based DEM tiles at a constant post spacing (grid cell size) of either 30 meters (data before the mid-1990s) or 10 meters (mid-1990s and later data). These individual-quadrangle DEMs were then converted to spherical coordinates (latitude/longitude decimal degrees) and edge-matched to ensure seamlessness. Approximately one-half of the area shown on this map has DEM source data at a 30-meter resolution, with the remaining half consisting of mostly 10-meter contour-derived DEM data and some small areas of higher-resolution LIght Detection And Ranging (LIDAR) data along parts of the coastline. Areas below sea level typically are surrounded by levees or some other type of flood-control structures. State and parish boundary, hydrography, city, and road layers were modified from USGS National Atlas data downloaded in 2003. The NED data were downloaded in 2007.

The relationship among psychological and psychophysiological characteristics of fibromyalgia patients.

PubMed

Thieme, Kati; Turk, Dennis C; Gracely, Richard H; Maixner, William; Flor, Herta

2015-02-01

This study examined the relationship of psychophysiological response patterns in fibromyalgia with psychological characteristics and comorbid mental disorders. Surface electromyographic data, systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels were recorded continuously during baseline, stress, and relaxation tasks. Cluster analysis revealed 4 subgroups of patients who differed on pain characteristics and cognitive, affective, and behavioral responses to pain and stress. The largest group (46.7%) was characterized by elevated blood pressure levels and stress reactivity (a disposition assumed to be a vulnerability factor for the development of diseases) associated with pain, anxiety, physical interference, low activity, and pain behaviors. A second group (41.6%) showed low baseline blood pressure and reactivity, and high activity and stress. A third group (9.2%) displayed high baseline skin conductance level, reactivity, and depression, and a fourth small group (2.5%) displayed elevated baseline electromyographic response and reactivity with high levels of anxiety and depression. These data suggest that unique psychophysiological response patterns are associated with psychological coping and mental disorders in fibromyalgia patients. The identification of the mechanisms that contribute to these group differences will further our understanding of the mechanisms involved in the development and maintenance of fibromyalgia and suggest differential treatment strategies. This article presents psychological characteristics and comorbidity with mental disorders of psychophysiological subgroups of fibromyalgia patients. This mechanistic analysis will assist scientific identification of systems-based pathways that contribute to autonomic and stress mechanisms that mediate chronic pain. Demonstration of distinct, homogeneous subgroups is an important step towards personalized, mechanism-oriented treatments. Copyright © 2015 American Pain Society. All rights reserved.

Genetic analysis of mouse embryonic stem cells bearing Msh3 and Msh2 single and compound mutations.

PubMed

Abuin, A; Zhang, H; Bradley, A

2000-01-01

We have previously described the use of homologous recombination and CRE-loxP-mediated marker recycling to generate mouse embryonic stem (ES) cell lines homozygous for mutations at the Msh3, Msh2, and both Msh3 and Msh2 loci (2). In this study, we describe the analysis of these ES cells with respect to processes known to be affected by DNA mismatch repair. ES cells homozygous for the Msh2 mutation displayed increased resistance to killing by the cytotoxic drug 6-thioguanine (6TG), indicating that the 6TG cytotoxic mechanism is mediated by Msh2. The mutation rate of the herpes simplex virus thymidine kinase 1 (HSV-tk1) gene was unchanged in Msh3-deficient ES cell lines but markedly elevated in Msh2-deficient and Msh3 Msh2 double-mutant cells. Notably, the HSV-tk1 mutation rate was 11-fold higher, on average, than that of the hypoxanthine-guanine phosphoribosyl transferase (Hprt) locus in Msh2-deficient cells. Sequence analysis of HSV-tk1 mutants from these cells indicated the presence of a frameshift hotspot within the HSV-tk1 coding region. Msh3-deficient cells displayed a modest (16-fold) elevation in the instability of a dinucleotide repeat, whereas Msh2-deficient and Msh2 Msh3 double-mutant cells displayed markedly increased levels of repeat instability. Targeting frequencies of nonisogenic vectors were elevated in Msh2-deficient ES cell lines, confirming the role of Msh2 in blocking recombination between diverged sequences (homeologous recombination) in mammalian cells. These results are consistent with accumulating data from other laboratories and support the current model of DNA mismatch repair in mammalian cells.

Genetic Analysis of Mouse Embryonic Stem Cells Bearing Msh3 and Msh2 Single and Compound Mutations

PubMed Central

Abuin, Alejandro; Zhang, HeJu; Bradley, Allan

2000-01-01

We have previously described the use of homologous recombination and CRE-loxP-mediated marker recycling to generate mouse embryonic stem (ES) cell lines homozygous for mutations at the Msh3, Msh2, and both Msh3 and Msh2 loci (2). In this study, we describe the analysis of these ES cells with respect to processes known to be affected by DNA mismatch repair. ES cells homozygous for the Msh2 mutation displayed increased resistance to killing by the cytotoxic drug 6-thioguanine (6TG), indicating that the 6TG cytotoxic mechanism is mediated by Msh2. The mutation rate of the herpes simplex virus thymidine kinase 1 (HSV-tk1) gene was unchanged in Msh3-deficient ES cell lines but markedly elevated in Msh2-deficient and Msh3 Msh2 double-mutant cells. Notably, the HSV-tk1 mutation rate was 11-fold higher, on average, than that of the hypoxanthine-guanine phosphoribosyl transferase (Hprt) locus in Msh2-deficient cells. Sequence analysis of HSV-tk1 mutants from these cells indicated the presence of a frameshift hotspot within the HSV-tk1 coding region. Msh3-deficient cells displayed a modest (16-fold) elevation in the instability of a dinucleotide repeat, whereas Msh2-deficient and Msh2 Msh3 double-mutant cells displayed markedly increased levels of repeat instability. Targeting frequencies of nonisogenic vectors were elevated in Msh2-deficient ES cell lines, confirming the role of Msh2 in blocking recombination between diverged sequences (homeologous recombination) in mammalian cells. These results are consistent with accumulating data from other laboratories and support the current model of DNA mismatch repair in mammalian cells. PMID:10594017

Terrain Portrayal for Synthetic Vision Systems Head-Down Displays Evaluation Results

NASA Technical Reports Server (NTRS)

Hughes, Monica F.; Glaab, Louis J.

2007-01-01

A critical component of SVS displays is the appropriate presentation of terrain to the pilot. At the time of this study, the relationship between the complexity of the terrain presentation and resulting enhancements of pilot SA and pilot performance had been largely undefined. The terrain portrayal for SVS head-down displays (TP-HDD) simulation examined the effects of two primary elements of terrain portrayal on the primary flight display (PFD): variations of digital elevation model (DEM) resolution and terrain texturing. Variations in DEM resolution ranged from sparsely spaced (30 arc-sec) to very closely spaced data (1 arc-sec). Variations in texture involved three primary methods: constant color, elevation-based generic, and photo-realistic, along with a secondary depth cue enhancer in the form of a fishnet grid overlay.

SLC34A3 Intronic Deletion in an Iranian Kindred with Hereditary Hypophosphatemic Rickets with Hypercalciuria and Review of Reported Cases.

PubMed

Hasani-Ranjbar, Shirin; Ejtahed, Hanieh Sadat; Amoli, Mahsa M; Bitarafan, Fatemeh; Qorbani, Mostafa; Soltani, Akbar; Yarjoo, Bahareh

2018-05-29

Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) is a very rare inheritable hypophosphatemic rickets/osteomalacia characterized by decreased renal phosphate reabsorption, hypophosphatemia, vitamin D refractory rickets, hyperphosphaturia, hypercalciuria, elevated circulating 1, 25-dihydroxy vitamin D levels and low serum parathyroid hormone (PTH) levels, leading to growth retardation, limb deformities, bone pain, muscle weakness, rickets and osteomalacia. Biallelic mutations in SLC34A3/NPT2c gene are responsible for the occurrence of the disease. In this paper we describe the clinical examination, biochemical profile and gene analysis of Iranian kindred with a 101bp deletion in SLC34A3 gene. 12 members of a family of previously reported patient with HHRH (3 homozygote and 7 heterozygote) and 10 healthy controls were evaluated. All patients had significantly increased risk of kidney stone formation, bone deformities and short stature compared with unrelated healthy controls. The heterozygous patients displayed milder clinical symptoms compared with homozygous patients. These patients displayed mild or no hypophosphatemia and they did not develop skeletal deformities. Recurrent renal stones and hypercalciuria were the main presentations of heterozygous patients which could be confused with familial hypercalciuria. In addition, biochemical analysis showed significantly low serum sodium level and elevated alkaline phosphatase in patients. Genetic counseling and screening for SLC34A3 mutations can be helpful in adult onset phenotype with unexplained osteoporosis, bone deformities and especial recurrent renal stones. In subjects with vitamin D deficiency the results should be interpreted cautiously.

The effect of forging history on the strength and microstructure of TDNiCr /Ni-20Cr-2ThO2/

NASA Technical Reports Server (NTRS)

Filippi, A. M.

1975-01-01

Forging variables were evaluated to determine their influence on the elevated temperature strength and microstructure of TDNiCr. Grain size was the principal microstructural feature related to elevated temperature strength and was controlled primarily by the thermomechanical variables of forging temperature and final annealing condition. Tests at 1366 K revealed a factor of eight increase in tensile strength as grain size increased from 1 to 150 microns, while stress-rupture strength improved by three to five times as grain size increased from 15 to 150 microns. Forged material of grain size greater than or equal to about 150 microns displayed a level of elevated temperature strength comparable to that of optimized TDNiCr sheet. The presence of a preponderance of small twins and a strong preferred orientation may have also been factors contributing to the excellent high temperature strength of large grain forged material.

Assessment of bone dysplasia by micro-CT and glycosaminoglycan levels in mouse models for mucopolysaccharidosis type I, IIIA, IVA, and VII

PubMed Central

Rowan, Daniel J.; Tomatsu, Shunji; Grubb, Jeffrey H.; Montaño, Adriana M.; Sly, William S.

2012-01-01

Summary Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases caused by mutations in lysosomal enzymes involved in degradation of glycosaminoglycans (GAGs). Patients with MPS grow poorly and become physically disabled due to systemic bone disease. While many of the major skeletal effects in mouse models for MPS have been described, no detailed analysis that compares GAGs levels and characteristics of bone by micro-CT has been done. The aims of this study were to assess severity of bone dysplasia among four MPS mouse models (MPS I, IIIA, IVA and VII), to determine the relationship between severity of bone dysplasia and serum keratan sulfate (KS) and heparan sulfate (HS) levels in those models, and to explore the mechanism of KS elevation in MPS I, IIIA, and VII mouse models. Clinically, MPS VII mice had the most severe bone pathology; however, MPS I and IVA mice also showed skeletal pathology. MPS I and VII mice showed severe bone dysplasia, higher bone mineral density, narrowed spinal canal, and shorter sclerotic bones by micro-CT and radiographs. Serum KS and HS levels were elevated in MPS I, IIIA, and VII mice. Severity of skeletal disease displayed by micro-CT, radiographs and histopathology correlated with the level of KS elevation. We showed that elevated HS levels in MPS mouse models could inhibit N-acetylgalactosamine-6-sulfate sulfatase enzyme. These studies suggest that KS could be released from chondrocytes affected by accumulation of other GAGs and that KS could be useful as a biomarker for severity of bone dysplasia in MPS disorders. PMID:22971960

The distribution and utility of sea-level indicators in Eurasian sub-Arctic salt marshes (White Sea, Russia).

NASA Astrophysics Data System (ADS)

Nikitina, Daria; Kemp, Andrew; Horton, Benjamin; Van, Christopher; Potapova, Marina; Culver, Stephen; Repkina, Tatyana; Hill, David

2017-04-01

We investigated the utility of foraminifera, diatoms and bulk-sediment geochemistry (δ13C and parameters measured by RockEval pyrolysis) as sea-level indicators in Eurasian sub-Arctic salt marshes. At three salt marshes in Dvina Bay (White Sea, Russia), we collected surface sediment samples along transects sequentially crossing sub-tidal, tidal-flat, salt-marsh and Taiga forest environments. Foraminifera formed bipartite assemblages, where elevations below mean high higher water (MHHW) were dominated by Miliammina spp. and elevations between MHHW and the highest occurrence of foraminifera were dominated by Jadammina macrescens and Balticammina pseudomacrescens. Both assemblages existed on all three transects and we conclude that foraminifera are sea-level indicators in Eurasian sub-Arctic salt marshes. Five, high-diversity groups of diatoms were identified and they displayed geographic variability among the study sites (<15 km apart). RockEval pyrolysis and δ13C measurements recognized two groups (clastic-dominated environments below MHHW and organic-rich environments above MHHW). Since one group included sub-tidal elevations and the other supra-tidal elevations, we conclude that the measured geochemical parameters do not meet the criteria for being stand-alone sea-level indicators. Core JT2012 captured a regressive sediment sequence of clastic, tidal-flat sediment overlain by salt-marsh organic silt and freshwater peat. The salt-marsh sediment accumulated at 2804 ± 52 years BP years before present and preserved foraminifera (J. macrescens and B. pseudomacrescens) with a high degree of analogy to modern assemblages indicating that relative sea level was 2.60 ± 0.47 m above present at this time. Diatoms confirm that marine influence decreased through time, but the lack of analogy between modern and core assemblages limits their utility as sea-level indicators in this setting.

Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior.

PubMed

Hansen, Rolf T; Conti, Marco; Zhang, Han-Ting

2014-08-01

Phosphodiesterases (PDEs) are a super family of enzymes responsible for the halting of intracellular cyclic nucleotide signaling and may represent novel therapeutic targets for treatment of cognitive disorders. PDE4 is of considerable interest to cognitive research because it is highly expressed in the brain, particularly in the cognition-related brain regions. Recently, the functional role of PDE4B and PDE4D, two of the four PDE4 subtypes (PDE4A, B, C, and D), in behavior has begun to be identified; however, the role of PDE4A in the regulation of behavior is still unknown. The purpose of this study was to characterize the functional role of PDE4A in behavior. The role of PDE4A in behavior was evaluated through a battery of behavioral tests using PDE4A knockout (KO) mice; urine corticosterone levels were also measured. PDE4A KO mice exhibited improved memory in the step-through-passive-avoidance test. They also displayed anxiogenic-like behavior in elevated-plus maze, holeboard, light-dark transition, and novelty suppressed feeding tests. Consistent with the anxiety profile, PDE4A KO mice had elevated corticosterone levels compared with wild-type controls post-stress. Interestingly, PDE4A KO mice displayed no change in object recognition, Morris water maze, forced swim, tail suspension, and duration of anesthesia induced by co-administration of xylazine and ketamine (suggesting that PDE4A KO may not be emetic). These results suggest that PDE4A may be important in the regulation of emotional memory and anxiety-like behavior, but not emesis. PDE4A could possibly represent a novel therapeutic target in the future for anxiety or disorders affecting memory.

Getting better, but not well: A 1.5 year follow-up of cognitive performance and cortisol levels in clinical and non-Clinical burnout.

PubMed

Oosterholt, Bart G; Maes, Joseph H R; Van der Linden, Dimitri; Verbraak, Marc J P M; Kompier, Michiel A J

2016-05-01

The purpose was to reexamine cognitive performance and cortisol levels of initial clinical burnout patients, non-clinical burnout individuals, and healthy controls. After 1.5-years of the initial measurement, clinical burnout patients showed a reduction of burnout symptoms and general physical and psychological complaints, but these were still elevated compared with controls. Nonetheless, they continued to report cognitive problems and still showed a minor impaired cognitive test performance. However, they no longer reported larger subjective costs associated with cognitive test performance and their cortisol awakening response (CAR) returned to a normal level. Compared with controls, non-clinical burnout individuals still reported the same, elevated, level of burnout symptoms, general physical and psychological complaints, and cognitive problems. Their cognitive test performance and associated subjective costs remained normal. However, they seemed to continue to display a lowered CAR. To conclude, after 1.5-years, clinical burnout patients got better, but not 'well', and non-clinical burnout individuals remained not 'well'. Copyright © 2016 Elsevier B.V. All rights reserved.

Detection of the value of consecutive serum total light chain (sTLC) in patients diagnosed with diffuse large B cell lymphoma.

PubMed

Zhai, Linzhu; Zhao, Yuanyuan; Peng, Songguo; Zhu, Ke; Yu, Rongjian; Chen, Hailong; Lin, Tongyu; Lin, Lizhu

2016-12-01

There are limited data on serum total light chain (sTLC) in lymphoma and its relative role on the outcome of diffuse large B cell lymphoma (DLBCL) patients. Blood samples from 46 cases newly diagnosed with DLBCL were collected consecutively during chemotherapy to detect sTLC, IgG, IgA, and IgM levels. Clinical data and survival outcomes were analyzed according to the results of sTLC measurements. In summary, 22 patients (47.8 %) had abnormal k or λ light chain, respectively, and 6 patients (13.0 %) had both abnormal k and λ light chains before chemotherapy. Patients with elevated k light chain more frequently displayed multiple extra-nodal organ involvement (P = 0.01) and had an inferior overall survival (OS) (P = 0.041) and progression-free survival (PFS) (P = 0.044) compared to patients with normal level of k light chain. Furthermore, patients with elevated level of both k and λ also exhibited significant association with shorter OS (P = 0.002) and PFS (P = 0.009). Both elevated k alone and concurrent elevated k and λ had independent adverse effects on PFS (P = 0.031 and P = 0.019, respectively). sTLC level was reduced gradually by treatment in this study and reached the lowest point after the fourth cycle of chemotherapy, which was consistent with the disease behavior during chemotherapy. Considering the small sample size of this study, these results should be confirmed in a larger prospective study.

Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines.

PubMed

Edvardsen, Kine; Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S; Bratland, Eirik

2015-10-01

Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10.

The significance and predictive value of free light chains in the urine of patients with chronic inflammatory rheumatic disease.

PubMed

Bramlage, Carsten Paul; Froelich, Britta; Wallbach, Manuel; Minguet, Joan; Grupp, Clemens; Deutsch, Cornelia; Bramlage, Peter; Koziolek, Michael; Müller, Gerhard Anton

2016-12-01

In patients with rheumatic diseases, reliable markers for determining disease activity are scarce. One potential parameter is the level of immunoglobulin free light chains (FLCs), which is known to be elevated in the blood of patients with certain rheumatic diseases. Few studies have quantified FLCs in urine, a convenient source of test sample, in patients with different rheumatic diseases. We carried out a retrospective analysis of patients with rheumatic disease attending the University hospital of Goettingen, Germany. Subjects were included if they had urine levels of both κ and λ FLCs available and did not have myeloma. Data regarding systemic inflammation and kidney function were recorded, and FLC levels were correlated with inflammatory markers. Of the 382 patients with rheumatic disease, 40.1 % had chronic polyarthritis, 21.2 % connective tissue disease, 18.6 % spondyloarthritis and 15.7 % vasculitis. Elevated levels of κ FLCs were found for 84 % of patients and elevated λ for 52.7 %. For the patients with rheumatoid arthritis, FLCs correlated with C-reactive protein (κ, r = 0.368, p < 0.001; λ, r = 0.398, p < 0.001) and erythrocyte sedimentation rate (κ, r = 0.692, p < 0.001; λ, r = 0.612, p < 0.001). Patients being treated with rituximab displayed FLC levels similar to those of the reference group. There were clear elevations in both κ and λ FLCs in patients with rheumatic disease, but not in κ/λ ratio. The correlation between FLCs and inflammatory markers in patients with rheumatoid arthritis demonstrates their potential for predicting disease activity.

Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities.

PubMed

Katayama, K; Yamada, K; Ornthanalai, V G; Inoue, T; Ota, M; Murphy, N P; Aruga, J

2010-02-01

Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an alpha2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plus-maze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.

Climate data by elevation in the Great Smoky Mountains: a database and graphical displays for 1947 - 1950 with comparison to long-term data

USGS Publications Warehouse

Busing, Richard T.; Stephens, Luther A.; Clebsch, Edward E.C.

2004-01-01

A climate data set is presented for four sites spanning the elevation gradient in the Great Smoky Mountains from Gatlinburg to Clingmans Dome. Monthly mean values for cloud cover, temperature, humidity, precipitation, and soil moisture are included. Stephens (1969) is the source of all summarized mean monthly data. Values are the averages of four years (1947-1950) with moderate to high precipitation. Graphical displays show strong climatic patterns of variation among seasons and elevations. The upper stations had lower temperatures and higher precipitation totals; however, temperature lapse rates and variation in vapor pressure deficits decreased at upper elevations. To examine how well the four-year sample represents the long-term climate, temperature and precipitation for the Gatlinburg (1460 ft elevation at park headquarters) station were compared between the years in the sample and the years in the full record from 1928 to 2003. Trends related to season and elevation are consistent with earlier studies and provide a basis for interpretation of climate dynamics in the southern Appalachian Mountains.

Gulf of Mexico region - Highlighting low-lying areas derived from USGS Digital Elevation Data

USGS Publications Warehouse

Kosovich, John J.

2008-01-01

In support of U.S. Geological Survey (USGS) disaster preparedness efforts, this map depicts a color shaded relief representation of the area surrounding the Gulf of Mexico. The first 30 feet of relief above mean sea level are displayed as brightly colored 5-foot elevation bands, which highlight low-elevation areas at a coarse spatial resolution. Standard USGS National Elevation Dataset (NED) 1 arc-second (nominally 30-meter) digital elevation model (DEM) data are the basis for the map, which is designed to be used at a broad scale and for informational purposes only. The NED data were derived from the original 1:24,000-scale USGS topographic map bare-earth contours, which were converted into gridded quadrangle-based DEM tiles at a constant post spacing (grid cell size) of either 30 meters (data before the mid-1990s data) or 10 meters (mid-1990s and later data). These individual-quadrangle DEMs were then converted to spherical coordinates (latitude/longitude decimal degrees) and edge-matched to ensure seamlessness. Approximately one-half of the area shown on this map has DEM source data at a 30-meter resolution, with the remaining half consisting of 10-meter contour-derived DEM data or higher-resolution LIDAR data. Areas below sea level typically are surrounded by levees or some other type of flood-control structures. State and county boundary, hydrography, city, and road layers were modified from USGS National Atlas data downloaded in 2003. The NED data were downloaded in 2005.

Transgenic overexpression of the presynaptic choline transporter elevates acetylcholine levels and augments motor endurance

PubMed Central

Holmstrand, Ericka C.; Lund, David; Cherian, Ajeesh Koshy; Wright, Jane; Martin, Rolicia F.; Ennis, Elizabeth A.; Stanwood, Gregg D.; Sarter, Martin; Blakely, Randy D.

2014-01-01

The hemicholinium-3 (HC-3) sensitive, high-affinity choline transporter (CHT) sustains cholinergic signaling via the presynaptic uptake of choline derived from dietary sources or from acetylcholinesterase (AChE)-mediated hydrolysis of acetylcholine (ACh). Loss of cholinergic signaling capacity is associated with cognitive and motor deficits in humans and in animal models. Whereas genetic elimination of CHT has revealed the critical nature of CHT in maintaining ACh stores and sustaining cholinergic signaling, the consequences of elevating CHT expression have yet to be studied. Using bacterial artificial chromosome (BAC)-mediated transgenic methods, we generated mice with integrated additional copies of the mouse Slc5a7 gene. BAC–CHT mice are viable, appear to develop normally, and breed at wild-type (WT) rates. Biochemical studies revealed a 2 to 3-fold elevation in CHT protein levels in the CNS and periphery, paralleled by significant increases in [3H]HC-3 binding and synaptosomal choline transport activity. Elevations of ACh in the BAC–CHT mice occurred without compensatory changes in the activity of either choline acetyltransferase (ChAT) or AChE. Immunohistochemistry for CHT in BAC–CHT brain sections revealed markedly elevated CHT expression in the cell bodies of cholinergic neurons and in axons projecting to regions known to receive cholinergic innervation. Behaviorally, BAC–CHT mice exhibited diminished fatigue and increased speeds on the treadmill test without evidence of increased strength. Finally, BAC–CHT mice displayed elevated horizontal activity in the open field test, diminished spontaneous alteration in the Y-maze, and reduced time in the open arms of the elevated plus maze. Together, these studies provide biochemical, pharmacological and behavioral evidence that CHT protein expression and activity can be elevated beyond that seen in wild-type animals. BAC–CHT mice thus represent a novel tool to examine both the positive and negative impact of constitutively elevated cholinergic signaling capacity. PMID:24274995

Evidence for Alterations in Stimulatory G proteins and Oxytocin Levels in Children with Autism

PubMed Central

Jacobson, Jill D.; Ellerbeck, Kathryn A.; Kelly, Kelsie A.; Fleming, Kandace K.; Jamison, T. Rene; Coffey, Charles W.; Smith, Catherine M.; Reese, R. Matthew; Sands, Scott A.

2014-01-01

The neurotransmitter oxytocin plays an important role in social affiliation. Low oxytocin levels and defects in the oxytocin receptor have been reported in childhood autism. However, little is known about oxytocin’s post-receptor signaling pathways in autism. Oxytocin signals via stimulatory and inhibitory G proteins. c-fos mRNA expression has been used as a marker of OT signaling as well as of G protein signaling. Herein, we hypothesized that oxytocin and its signaling pathways would be altered in children with autism. We measured plasma oxytocin levels by ELISA, G-protein and c-fos mRNA by PCR, and G proteins by immunoblot in cultured peripheral blood mononuclear cells (PBMCs) in children with autism and in age-matched controls. Males with autism displayed elevated oxytocin levels compared to controls (p<0.05). Children with autism displayed significantly higher mRNA for stimulatory G proteins compared to controls (p<0.05). Oxytocin levels correlated strongly positively with c-fos mRNA levels, but only in control participants (p<0.01). Oxytocin, G-protein, and c-fos mRNA levels correlated inversely with measures of social and emotional behaviors, but only in control participants. These data suggest that children with autism may exhibit a dysregulation in oxytocin and/or its signaling pathways. PMID:24485488

The Efficacy of Using Synthetic Vision Terrain-Textured Images to Improve Pilot Situation Awareness

NASA Technical Reports Server (NTRS)

Uenking, Michael D.; Hughes, Monica F.

2002-01-01

The General Aviation Element of the Aviation Safety Program's Synthetic Vision Systems (SVS) Project is developing technology to eliminate low visibility induced General Aviation (GA) accidents. SVS displays present computer generated 3-dimensional imagery of the surrounding terrain on the Primary Flight Display (PFD) to greatly enhance pilot's situation awareness (SA), reducing or eliminating Controlled Flight into Terrain, as well as Low-Visibility Loss of Control accidents. SVS-conducted research is facilitating development of display concepts that provide the pilot with an unobstructed view of the outside terrain, regardless of weather conditions and time of day. A critical component of SVS displays is the appropriate presentation of terrain to the pilot. An experimental study is being conducted at NASA Langley Research Center (LaRC) to explore and quantify the relationship between the realism of the terrain presentation and resulting enhancements of pilot SA and performance. Composed of complementary simulation and flight test efforts, Terrain Portrayal for Head-Down Displays (TP-HDD) experiments will help researchers evaluate critical terrain portrayal concepts. The experimental effort is to provide data to enable design trades that optimize SVS applications, as well as develop requirements and recommendations to facilitate the certification process. In this part of the experiment a fixed based flight simulator was equipped with various types of Head Down flight displays, ranging from conventional round dials (typical of most GA aircraft) to glass cockpit style PFD's. The variations of the PFD included an assortment of texturing and Digital Elevation Model (DEM) resolution combinations. A test matrix of 10 terrain display configurations (in addition to the baseline displays) were evaluated by 27 pilots of various backgrounds and experience levels. Qualitative (questionnaires) and quantitative (pilot performance and physiological) data were collected during the experimental runs. This paper focuses on the experimental set-up and final physiological results of the TP-HDD simulation experiment. The physiological measures of skin temperature, heart rate, and muscle response, show a decreased engagement (while using the synthetic vision displays as compared to the baseline conventional display) of the sympathetic and somatic nervous system responses which, in turn, indicates a reduced level of mental workload. This decreased level of workload is expected to enable improvement in the pilot's situation and terrain awareness.

Effects of genotype, elevated CO2 and elevated O3 on aspen phytochemistry and aspen leaf beetle Chrysomela crotchi performance

Treesearch

Leanne M. Vigue; Richard L. Lindroth

2010-01-01

Trembling aspen Populus tremuloides Michaux is an important forest species in the Great Lakes region and displays tremendous genetic variation in foliar chemistry. Elevated carbon dioxide (CO2) and ozone (O3) may also influence phytochemistry and thereby alter the performance of insect herbivores such as...

Credit PSR. Photograph displays the west and south elevations as ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit PSR. Photograph displays the west and south elevations as seen when looking east northeast (56°). The small doors at the left lead to the building equipment room which houses heating and cooling equipment (part of which is visible outdoors along adjacent exterior wall). High double doors lead to the dryer room; a 1-ton hoist is used to move heavy containers and dryer trays within the building. Note the lightning rods on roof corners - Jet Propulsion Laboratory Edwards Facility, Oxidizer Dryer Building, Edwards Air Force Base, Boron, Kern County, CA

Elevated intracellular pH appears in aged oocytes and causes oocyte aneuploidy associated with the loss of cohesion in mice

PubMed Central

Cheng, Jin-Mei; Li, Jian; Tang, Ji-Xin; Chen, Su-Ren; Deng, Shou-Long; Jin, Cheng; Zhang, Yan; Wang, Xiu-Xia; Zhou, Chen-Xi; Liu, Yi-Xun

2016-01-01

ABSTRACT Increases in the aneuploidy rate caused by the deterioration of cohesion with increasing maternal age have been well documented. However, the molecular mechanism for the loss of cohesion in aged oocytes remains unknown. In this study, we found that intracellular pH (pHi) was elevated in aged oocytes, which might disturb the structure of the cohesin ring to induce aneuploidy. We observed for the first time that full-grown germinal vesicle (GV) oocytes displayed an increase in pHi with advancing age in CD1 mice. Furthermore, during the in vitro oocyte maturation process, the pHi was maintained at a high level, up to ∼7.6, in 12-month-old mice. Normal pHi is necessary to maintain protein localization and function. Thus, we put forward a hypothesis that the elevated oocyte pHi might be related to the loss of cohesion and the increased aneuploidy in aged mice. Through the in vitro alkalinization treatment of young oocytes, we observed that the increased pHi caused an increase in the aneuploidy rate and the sister inter-kinetochore (iKT) distance associated with the strength of cohesion and caused a decline in the cohesin subunit SMC3 protein level. Young oocytes with elevated pHi exhibited substantially the increase in chromosome misalignment. PMID:27472084

Biodiversity of Costa Rican salamanders: Implications of high levels of genetic differentiation and phylogeographic structure for species formation

PubMed Central

García-París, Mario; Good, David A.; Parra-Olea, Gabriela; Wake, David B.

2000-01-01

Although salamanders are characteristic amphibians in Holarctic temperate habitats, in tropical regions they have diversified evolutionarily only in tropical America. An adaptive radiation centered in Middle America occurred late in the history of a single clade, the supergenus Bolitoglossa (Plethodontidae), and large numbers of species now occur in diverse habitats. Sublineages within this clade decrease in number from the northern to southern parts of Middle America, and in Costa Rica, there are but three. Despite this phylogenetic constraint, Costa Rica has many species; the number of salamander species on one local elevational transect in the Cordillera de Talamanca may be the largest for any such transect in the world. Extraordinary variation in sequences of the mitochondrial gene cytochrome b within a clade of the genus Bolitoglossa in Costa Rica reveals strong phylogeographic structure within a single species, Bolitoglossa pesrubra. Allozymic variation in 19 proteins reveals a pattern largely concordant with the mitochondrial DNA phylogeography. More species exist than are currently recognized. Diversification occurs in restricted geographic areas and involves sharp geographic and elevational differentiation and zonation. In their degree of genetic differentiation at a local scale, these species of the deep tropics exceed the known variation of extratropical salamanders, which also differ in being less restricted in elevational range. Salamanders display “tropicality” in that although speciose, they are usually local in distribution and rare. They display strong ecological and physiological differentiation that may contribute importantly to morphological divergence and species formation. PMID:10677512

Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimer's Disease

PubMed Central

Astarita, Giuseppe; Jung, Kwang-Mook; Vasilevko, Vitaly; DiPatrizio, Nicholas V.; Martin, Sarah K.; Cribbs, David H.; Head, Elizabeth; Cotman, Carl W.; Piomelli, Daniele

2011-01-01

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio (‘desaturation index’) – displayed a strong negative correlation with measures of cognition: the Mini Mental State Examination test (r = −0.80; P = 0.0001) and the Boston Naming test (r = −0.57; P = 0.0071). Our results reveal a previously unrecognized role for the lipogenic enzyme SCD in AD. PMID:22046234

Deoxysphingolipid precursors indicate abnormal sphingolipid metabolism in individuals with primary and secondary disturbances of serine availability.

PubMed

Ferreira, C R; Goorden, S M I; Soldatos, A; Byers, H M; Ghauharali-van der Vlugt, J M M; Beers-Stet, F S; Groden, C; van Karnebeek, C D; Gahl, W A; Vaz, F M; Jiang, X; Vernon, H J

2018-05-07

Patients with primary serine biosynthetic defects manifest with intellectual disability, microcephaly, ichthyosis, seizures and peripheral neuropathy. The underlying pathogenesis of peripheral neuropathy in these patients has not been elucidated, but could be related to a decrease in the availability of certain classical sphingolipids, or to an increase in atypical sphingolipids. Here, we show that patients with primary serine deficiency have a statistically significant elevation in specific atypical sphingolipids, namely deoxydihydroceramides of 18-22 carbons in acyl length. We also show that patients with aberrant plasma serine and alanine levels secondary to mitochondrial disorders also display peripheral neuropathy along with similar elevations of atypical sphingolipids. We hypothesize that the etiology of peripheral neuropathy in patients with primary mitochondrial disorders is related to this elevation of deoxysphingolipids, in turn caused by increased availability of alanine and decreased availability of serine. These findings could have important therapeutic implications for the management of these patients. Copyright © 2018 Elsevier Inc. All rights reserved.

A Whole-Cell Surface Plasmon Resonance Sensor Based on a Leucine Auxotroph of Escherichia coli Displaying a Gold-Binding Protein: Usefulness for Diagnosis of Maple Syrup Urine Disease.

PubMed

Woo, Min-Ah; Park, Jung Hun; Cho, Daeyeon; Sim, Sang Jun; Kim, Moon Il; Park, Hyun Gyu

2016-03-01

We developed a whole-cell surface plasmon resonance (SPR) sensor based on a leucine auxotroph of Escherichia coli displaying a gold-binding protein (GBP) in response to cell growth and applied this sensor to the diagnosis of maple syrup urine disease, which is represented by the elevated leucine level in blood. The leucine auxotroph was genetically engineered to grow displaying GBP in a proportion to the concentration of target amino acid leucine. The GBP expressed on the surface of the auxotrophs directly bound to the golden surface of an SPR chip without the need for any additional treatment or reagents, which consequently produced SPR signals used to determine leucine levels in a test sample. Gold nanoparticles (GNPs) were further applied to the SPR system, which significantly enhanced the signal intensity up to 10-fold by specifically binding to GBP expressed on the cell surface. Finally, the diagnostic utility of our system was demonstrated by its employment in reliably determining different statuses of maple syrup urine disease based on a known cutoff level of leucine. This new approach based on an amino acid-auxotrophic E. coli strain expressing a GBP that binds to an SPR sensor holds great promise for detection of other metabolic diseases of newborn babies including homocystinuria and phenylketonuria, which are also associated with abnormal levels of amino acids.

Body mass index influences infliximab post-infusion levels and correlates with prospective loss of response to the drug in a cohort of inflammatory bowel disease patients under maintenance therapy with Infliximab.

PubMed

Scaldaferri, Franco; D'Ambrosio, Daria; Holleran, Grainne; Poscia, Andrea; Petito, Valentina; Lopetuso, Loris; Graziani, Cristina; Laterza, Lucrezia; Pistone, Maria Teresa; Pecere, Silvia; Currò, Diego; Gaetani, Eleonora; Armuzzi, Alessandro; Papa, Alfredo; Cammarota, Giovanni; Gasbarrini, Antonio

2017-01-01

Infliximab is an effective treatment for inflammatory bowel disease (IBD). Studies differ regarding the influence of body mass index (BMI) on the response to infliximab, with the majority of studies indicating that increased BMI may be associated with a poorer response to Infliximab. However, the pharmacokinetic mechanisms causing this have not yet been reported. Examine the correlation between BMI/immunosuppressant use with clinical response, trough and post-infusion levels of infliximab, tumour necrosis factor-α(TNF-α) and anti-drug antibodies(ATI), and determine if these factors can predict future response. We collected serum from 24 patients receiving Infliximab before and 30 minutes following infusion. Clinical parameters were collected retrospectively and prospectively. ELISA measurements of infliximab, TNF-α and ATI were performed. We confirmed that patients with higher infliximab trough levels have a better response rate and that patients with an elevated BMI display a higher rate of loss of response (20%). Patients with a higher BMI had elevated post-infusion levels of infliximab. Additionally, the ratio of IFX/TNF-α trough levels correlated with clinical response to the following infusion. This study confirms that an elevated BMI is associated with a poorer response to infliximab. For the first time, we describe that a higher BMI correlates with higher post-infusion levels, however this does not correlate with a higher rate of response to the drug, suggesting that circulating drug levels do not correlate with tissue levels. Furthermore, in our small cohort of patients, we identified a possible predictive marker of future response to treatment which may be used to guide dose escalation and predict non-response to infliximab.

Impulsivity and cognitive distortions in pathological gamblers attending the UK National Problem Gambling Clinic: a preliminary report.

PubMed

Michalczuk, R; Bowden-Jones, H; Verdejo-Garcia, A; Clark, L

2011-12-01

Pathological gambling (PG) is a form of behavioural addiction that has been associated with elevated impulsivity and also cognitive distortions in the processing of chance, probability and skill. We sought to assess the relationship between the level of cognitive distortions and state and trait measures of impulsivity in treatment-seeking pathological gamblers. Thirty pathological gamblers attending the National Problem Gambling Clinic, the first National Health Service clinic for gambling problems in the UK, were compared with 30 healthy controls in a case-control design. Cognitive distortions were assessed using the Gambling-Related Cognitions Scale (GRCS). Trait impulsivity was assessed using the UPPS-P, which includes scales of urgency, the tendency to be impulsive in positive or negative mood states. Delay discounting rates were taken as a state measure of impulsive choice. Pathological gamblers had elevated impulsivity on several UPPS-P subscales but effect sizes were largest (Cohen's d>1.4) for positive and negative urgency. The pathological gamblers also displayed higher levels of gambling distortions, and elevated preference for immediate rewards, compared to controls. Within the pathological gamblers, there was a strong relationship between the preference for immediate rewards and the level of cognitive distortions (R2=0.41). Impulsive choice in the gamblers was correlated with the level of gambling distortions, and we hypothesize that an impulsive decision-making style may increase the acceptance of erroneous beliefs during gambling play.

The Calcium-Dependent Protein Kinase CPK28 Regulates Development by Inducing Growth Phase-Specific, Spatially Restricted Alterations in Jasmonic Acid Levels Independent of Defense Responses in Arabidopsis[OPEN

PubMed Central

Matschi, Susanne; Hake, Katharina; Herde, Marco; Hause, Bettina; Romeis, Tina

2015-01-01

Phytohormones play an important role in development and stress adaptations in plants, and several interacting hormonal pathways have been suggested to accomplish fine-tuning of stress responses at the expense of growth. This work describes the role played by the CALCIUM-DEPENDENT PROTEIN KINASE CPK28 in balancing phytohormone-mediated development in Arabidopsis thaliana, specifically during generative growth. cpk28 mutants exhibit growth reduction solely as adult plants, coinciding with altered balance of the phytohormones jasmonic acid (JA) and gibberellic acid (GA). JA-dependent gene expression and the levels of several JA metabolites were elevated in a growth phase-dependent manner in cpk28, and accumulation of JA metabolites was confined locally to the central rosette tissue. No elevated resistance toward herbivores or necrotrophic pathogens was detected for cpk28 plants, either on the whole-plant level or specifically within the tissue displaying elevated JA levels. Abolishment of JA biosynthesis or JA signaling led to a full reversion of the cpk28 growth phenotype, while modification of GA signaling did not. Our data identify CPK28 as a growth phase-dependent key negative regulator of distinct processes: While in seedlings, CPK28 regulates reactive oxygen species-mediated defense signaling; in adult plants, CPK28 confers developmental processes by the tissue-specific balance of JA and GA without affecting JA-mediated defense responses. PMID:25736059

Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines

PubMed Central

Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S.; Bratland, Eirik

2015-01-01

Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10. PMID:25978633

Corticosterone response to the plus-maze: high correlation with risk assessment in rats and mice.

PubMed

Rodgers, R J; Haller, J; Holmes, A; Halasz, J; Walton, T J; Brain, P F

Exposure to the elevated plus-maze induces behavioural and physiological effects in rodents consistent with fear/anxiety. Maze-naive animals display high levels of risk assessment towards the open arms, and explore these areas less extensively than other parts of the maze while, immediately following the test, pain latencies, skin conductance levels, and plasma corticosterone titres (CORT) are significantly elevated. Although previous research has suggested a link between the plasma CORT response and open-arm exploration, significant elevations in CORT have also been found with restricted exposure to the closed arms. The present study employed ethological measures in an attempt to further characterise the relationship between behavioural and CORT responses to this widely used animal model of anxiety. Our results confirm that, relative to home-cage controls, 5-min exposure to the plus-maze significantly increases plasma CORT levels in test-naive male Wistar rats and male Swiss-Webster mice. Furthermore, in both species, the CORT response was found to be highly correlated with measures of risk assessment (mice: rs = +0.87; rats: rs = +0.58), but not with measures of open-arm activity (entries, time), general locomotor activity, rearing, or head dipping. Findings are discussed in relation to the functional significance of risk assessment in potentially dangerous situations and the potential involvement of glucocorticoids in this process. All rights reserved.

Aviation Security: Background and Policy Options for Screening and Securing Air Cargo

DTIC Science & Technology

2008-02-25

today, employees with unescorted access privileges to security identification display areas ( SIDAs ) may access secured areas and aircraft without...where all-cargo aircraft are loaded and unloaded, as security identification display areas ( SIDAs ). This effectively elevates the required security

Variation in torpor patterns of free-ranging black-tailed and Utah prairie dogs across gradients of elevation

USGS Publications Warehouse

Lehmer, E.M.; Biggins, D.E.

2005-01-01

We compared over-winter body temperature (Tb) patterns for more than 6 months in adult (> 1 year) black-tailed (Cynomys ludovicianus) and Utah (C. parvidens) prairie dogs from colonies located along gradients of elevation in northern Colorado and southern Utah. In general, black-tailed prairie dogs entered torpor facultatively during winter, whereas Utah prairie dogs hibernated continuously for extended periods. Both black-tailed and Utah prairie dogs displayed significant differences in Tb patterns across elevations, with lower elevation populations entering more shallow and infrequent torpor than prairie dogs at higher elevations. Tb patterns of black-tailed prairie dogs followed 24-h cycles, as most prairie dogs entered into and aroused from torpor between 1100 and 1700 h and bout lengths were clustered around 24-h intervals and multiples thereof. Torpor in Utah prairie dogs did not display the same daily patterns; they entered into and aroused from torpor at all times of the day, and bout lengths were variable. Although black-tailed and Utah prairie dogs are closely related, mechanisms that stimulate and control torpor might differ between them.

Stranger Fear and Early Risk for Social Anxiety in Preschoolers with Fragile X Syndrome Contrasted to Autism Spectrum Disorder.

PubMed

Scherr, Jessica F; Hogan, Abigail L; Hatton, Deborah; Roberts, Jane E

2017-12-01

This study investigated behavioral indicators of social fear in preschool boys with fragile X syndrome (FXS) with a low degree of autism spectrum disorder (ASD) symptoms (FXS-Low; n = 29), FXS with elevated ASD symptoms (FXS-High; n = 25), idiopathic ASD (iASD; n = 11), and typical development (TD; n = 36). Gaze avoidance, escape behaviors, and facial fear during a stranger approach were coded. Boys with elevated ASD symptoms displayed more avoidant gaze, looking less at the stranger and parent than those with low ASD symptoms across etiologies. The iASD group displayed more facial fear than the other groups. Results suggest etiologically distinct behavioral patterns of social fear in preschoolers with elevated ASD symptoms.

Blood serotonin levels in autism spectrum disorder: a systematic review and meta-analysis.

PubMed

Gabriele, Stefano; Sacco, Roberto; Persico, Antonio M

2014-06-01

Elevated blood serotonin (5-HT) levels were the first biomarker identified in autism research. Many studies have contrasted blood 5-HT levels in autistic patients and controls, but different measurement protocols, technologies, and biomaterials have been used through the years. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and between-study heterogeneity, while verifying whether and to what extent different methodological approaches influence the strength of this association. Our literature search strategy identified 551 papers, from which 22 studies providing patient and control blood 5-HT values were selected for meta-analysis. Significantly higher 5-HT levels in autistic patients compared to controls were recorded both in whole blood (WB) [O.R.=4.6; (3.1-5.2); P=1.0×10(-12]), and in platelet-rich plasma (PRP) [O.R.=2.6 (1.8-3.9); P=2.7×10(-7)]. Predictably, studies measuring 5-HT levels in platelet-poor plasma (PPP) yielded no significant group difference [O.R.=0.54 (0.2-2-0); P=0.36]. Altogether, elevated 5-HT blood levels were recorded in 28.3% in WB and 22.5% in PRP samples of autistic individuals, as reported in 15 and 4 studies, respectively. Studies employing HPLC vs fluorometric assays yield similar cumulative effect sizes, but the former display much lower variability. In summary, despite some limitations mainly due to small study sample sizes, our results significantly reinforce the reliability of elevated 5-HT blood levels as a biomarker in ASD, providing practical indications potentially useful for its inclusion in multi-marker diagnostic panels for clinical use. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Effects of dietary hexachlorobenzene exposure on regional brain biogenic amine concentrations in mink and European ferrets

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

Bleavins, M.R.; Bursian, S.J.; Brewster, J.S.

1984-01-01

In the initial trial, adult mink and ferrets were administered hexachlorobenzene (HCB) via the feed at concentrations of 1, 5, or 25 ppm for 47 wk. Animals receiving 125 and 625 ppm HCB in the diet died before termination of the experiment, with female ferrets at the 125 ppm level displaying abnormal aggressiveness and hyperexcitability just prior to death. Hypothalamic serotonin (5-HT) was significantly elevated at all dose levels in mink, and cerebellar 5-HT was significantly elevated at 1 ppm in the ferret. Regional brain biogenic amine concentrations were also determined in the offspring of the female mink that weremore » administered 1 and 5 ppm HCB. Hypothalamic dopamine (DA) concentrations were significantly depressed by 1 and 5 ppm in these kits. In a second study, adult male and female ferrets were administered 250 or 500 ppm HCB via the diet for 7 wk. Two animals at the 250-ppm level and 3 animals at the 500-ppm level died before termination of the experiment without showing behavioral changes. Of the remaining animals, 3 ferrets at 250 ppm and 1 ferret at 500 ppm showed slight aggressiveness and hyperexcitability during the last week of the experiment. Concentrations of 5-HT were significantly elevated at 500 ppm in the cerebral hemispheres and at 250 ppm in the midbrain of male ferrets, while in the females, 5-HT was elevated in the cerebral hemispheres at 250 ppm and in the hypothalamus at both 250 and 500 ppm. Norepinephrine (NE) concentrations were significantly elevated in the cerebellum of males exposed to 250 and 500 ppm, as were NE concentrations in the midbrain. HCB at 500 ppm caused a significant increase in medullary NE, while 250 ppm caused an increase in hypothalamic NE in males. The only change in regional brain dopamine (DA) concentrations occurred at 500 ppm HCB in the midbrain of males, where there was a significant elevation of this neurotransmitter. 34 references, 7 tables.« less

Mice overexpressing corticotropin-releasing factor show brain atrophy and motor dysfunctions.

PubMed

Goebel, Miriam; Fleming, Sheila M; Million, Mulugeta; Stengel, Andreas; Taché, Yvette; Wang, Lixin

2010-03-31

Chronic stress and persistently high glucocorticoid levels can induce brain atrophy. Corticotropin-releasing factor (CRF)-overexpressing (OE) mice are a genetic model of chronic stress with elevated brain CRF and plasma corticosterone levels and Cushing's syndrome. The brain structural alterations in the CRF-OE mice, however, are not well known. We found that adult male and female CRF-OE mice had significantly lower whole brain and cerebellum weights than their wild type (WT) littermates (347.7+/-3.6mg vs. 460.1+/-4.3mg and 36.3+/-0.8mg vs. 50.0+/-1.3mg, respectively) without sex-related difference. The epididymal/parametrial fat mass was significantly higher in CRF-OE mice. The brain weight was inversely correlated to epididymal/parametrial fat weight, but not to body weight. Computerized image analysis system in Nissl-stained brain sections of female mice showed that the anterior cingulate and sensorimotor cortexes of CRF-OE mice were significantly thinner, and the volumes of the hippocampus, hypothalamic paraventricular nucleus and amygdala were significantly reduced compared to WT, while the locus coeruleus showed a non-significant increase. Motor functions determined by beam crossing and gait analysis showed that CRF-OE mice took longer time and more steps to traverse a beam with more errors, and displayed reduced stride length compared to their WT littermates. These data show that CRF-OE mice display brain size reduction associated with alterations of motor coordination and an increase in visceral fat mass providing a novel animal model to study mechanisms involved in brain atrophy under conditions of sustained elevation of brain CRF and circulating glucocorticoid levels. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Evidence for retrovirus infections in green turtles Chelonia mydas from the Hawaiian islands

USGS Publications Warehouse

Casey, R.N.; Quackenbush, S.L.; Work, Thierry M.; Balazs, G.H.; Bowser, P.R.; Casey, J.W.

1997-01-01

Apparently normal Hawaiian green turtles Chelonia mydas and those displaying fibropapillomas were analyzed for infection by retroviruses. Strikingly, all samples were positive for polymerase enhanced reverse transcriptase (PERT) with levels high enough to quantitate by the conventional reverse transcriptase (RT) assay. However, samples of skin, even from asymptomatic turtles, were RT positive, although the levels of enzyme activity in healthy turtles hatched and raised in captivity were much lower than those observed in asymptomatic free-ranging turtles. Turtles with fibropapillomas displayed a broad range of reverse transcriptase activity. Skin and eye fibropapillomas and a heart tumor were further analyzed and shown to have reverse transcriptase activity that banded in a sucrose gradient at 1.17 g ml-1. The reverse transcriptase activity purified from the heart tumor displayed a temperature optimum of 37??C and showed a preference for Mn2+ over Mg2+. Sucrose gradient fractions of this sample displaying elevated reverse transcriptase activity contained primarily retrovitalsized particles with prominent envelope spikes, when negatively stained and examined by electron microscopy. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of gradient-purified virions revealed a conserved profile among 4 independent tumors and showed 7 prominent proteins having molecular weights of 116, 83, 51, 43, 40, 20 and 14 kDa. The data suggest that retroviral infections are widespread in Hawaiian green turtles and a comprehensive investigation is warranted to address the possibility that these agents cause green turtle fibropapillomatosis (GTFP).

Highway proximity associations with blood markers of inflammation: evidence for a role for IL-1β.

PubMed

Brugge, Doug; Lane, Kevin J; Stewart, Andrea; Tai, Albert K; Woodin, Mark

2013-01-01

Cardiovascular disease is known to be associated with proximity to major roadways and highways. Thus, blood samples from 20 near highway and 20 urban background residents were analyzed for presence of cytokines and other biomarkers. Near-highway participants displayed significantly lower socioeconomic status (SES) and significantly higher occupational vehicle exhaust exposure and higher low-density lipoprotein (LDL) levels. Controlling for exposure to vehicle exhaust on the job, interleukin-6 (IL-6) was numerically higher in near highway participants. Using logistic regression analyses, IL-1β was significantly elevated near highway. It is interesting that elevations were found in IL-1β, a key cytokine linked to inflammation from particulate matter (PM). More studies are needed with larger sample sizes to assess the possible role of IL-1β.

Antidepressant-like effects of mild hypoxia preconditioning in the learned helplessness model in rats.

PubMed

Rybnikova, Elena; Mironova, Vera; Pivina, Svetlana; Tulkova, Ekaterina; Ordyan, Natalia; Vataeva, Ludmila; Vershinina, Elena; Abritalin, Eugeny; Kolchev, Alexandr; Nalivaeva, Natalia; Turner, Anthony J; Samoilov, Michail

2007-05-07

The effects of preconditioning using mild repetitive hypobaric hypoxia (360 Torr for 2 h each of 3 days) have been studied in the learned helplessness model of depression in rats. Male Wistar rats displayed persistent depressive symptoms (depressive-like behaviour in open field, increased anxiety levels in elevated plus maze, ahedonia, elevated plasma glucocorticoids and impaired dexamethasone test) following the exposure to unpredictable and inescapable footshock in the learned helplessness paradigm. Antidepressant treatment (ludiomil, 5 mg/kg i.p.) augmented the development of the depressive state. The hypoxic preconditioning had a clear antidepressive action returning the behavioural and hormonal parameters to the control values and was equally effective in terms of our study as the antidepressant. The findings suggest hypoxic preconditioning as an effective tool for the prophylaxis of post-stress affective pathologies in humans.

Rail inspection system based on iGPS

NASA Astrophysics Data System (ADS)

Fu, Xiaoyan; Wang, Mulan; Wen, Xiuping

2018-05-01

Track parameters include gauge, super elevation, cross level and so on, which could be calculated through the three-dimensional coordinates of the track. The rail inspection system based on iGPS (indoor/infrared GPS) was composed of base station, receiver, rail inspection frame, wireless communication unit, display and control unit and data processing unit. With the continuous movement of the inspection frame, the system could accurately inspect the coordinates of rail; realize the intelligent detection and precision measurement. According to principle of angle intersection measurement, the inspection model was structured, and detection process was given.

α-Synuclein induced toxicity in brain stem serotonin neurons mediated by an AAV vector driven by the tryptophan hydroxylase promoter.

PubMed

Wan, Oi Wan; Shin, Eunju; Mattsson, Bengt; Caudal, Dorian; Svenningsson, Per; Björklund, Anders

2016-05-23

We studied the impact of α-synuclein overexpression in brainstem serotonin neurons using a novel vector construct where the expression of human wildtype α-synuclein is driven by the tryptophan hydroxylase promoter, allowing expression of α-synuclein at elevated levels, and with high selectivity, in serotonergic neurons. α-Synuclein induced degenerative changes in axons and dendrites, displaying a distorted appearance, suggesting accumulation and aggregation of α-synuclein as a result of impaired axonal transport, accompanied by a 40% loss of terminals, as assessed in the hippocampus. Tissue levels of serotonin and its major metabolite 5-HIAA remained largely unaltered, and the performance of the α-synuclein overexpressing rats in tests of spatial learning (water maze), anxiety related behavior (elevated plus maze) and depressive-like behavior (forced swim test) was not different from control, suggesting that the impact of the developing axonal pathology on serotonin neurotransmission was relatively mild. Overexpression of α-synuclein in the raphe nuclei, combined with overexpression in basal forebrain cholinergic neurons, resulted in more pronounced axonal pathology and significant impairment in the elevated plus maze. We conclude that α-synuclein pathology in serotonergic or cholinergic neurons alone is not sufficient to impair non-motor behaviors, but that it is their simultaneous involvement that determines severity of such symptoms.

Metabolic profile of long-distance migratory flight and stopover in a shorebird.

PubMed

Landys, Meta M; Piersma, Theunis; Guglielmo, Christopher G; Jukema, Joop; Ramenofsky, Marilyn; Wingfield, John C

2005-02-07

Migrating birds often complete long non-stop flights during which body energy stores exclusively support energetic demands. The metabolic correlates of such long-distance travel in free-living migrants are as yet poorly studied. Bar-tailed godwits, Limosa lapponica taymyrensis, undertake a 4500 km flight to their single spring stopover site and thus provide an excellent model in which to determine the energy fuels associated with endurance travel. To this end, we evaluated plasma concentrations of six key metabolites in arriving godwits caught immediately upon landing near their stopover site. Initial metabolite levels were compared with levels after 5 h of inactive rest to determine how flight per se affects energy metabolism. Birds refuelling on the stopover site were also examined. Arriving godwits displayed elevated plasma free fatty acids, glycerol and butyrate, confirming the importance of lipid fuel in the support of extended migratory activity. Further-more, elevated plasma triglycerides in these birds suggest that fatty acid provisioning is facilitated through hepatic synthesis and release of neutral lipids, as previously hypothesized for small migrants with high mass-specific metabolic rates. Finally, elevations in plasma uric acid suggest that protein breakdown contributes to the support of long-distance movement, to possibly maintain citric acid cycle intermediates, gluconeogenesis and/or water balance.

Metabolic profile of long-distance migratory flight and stopover in a shorebird

PubMed Central

Landys, Mėta M.; Piersma, Theunis; Guglielmo, Christopher G.; Jukema, Joop; Ramenofsky, Marilyn; Wingfield, John C.

2005-01-01

Migrating birds often complete long non-stop flights during which body energy stores exclusively support energetic demands. The metabolic correlates of such long-distance travel in free-living migrants are as yet poorly studied. Bar-tailed godwits, Limosa lapponica taymyrensis, undertake a 4500 km flight to their single spring stopover site and thus provide an excellent model in which to determine the energy fuels associated with endurance travel. To this end, we evaluated plasma concentrations of six key metabolites in arriving godwits caught immediately upon landing near their stopover site. Initial metabolite levels were compared with levels after 5 h of inactive rest to determine how flight per se affects energy metabolism. Birds refuelling on the stopover site were also examined. Arriving godwits displayed elevated plasma free fatty acids, glycerol and butyrate, confirming the importance of lipid fuel in the support of extended migratory activity. Furthermore, elevated plasma triglycerides in these birds suggest that fatty acid provisioning is facilitated through hepatic synthesis and release of neutral lipids, as previously hypothesized for small migrants with high mass-specific metabolic rates. Finally, elevations in plasma uric acid suggest that protein breakdown contributes to the support of long-distance movement, to possibly maintain citric acid cycle intermediates, gluconeogenesis and/or water balance. PMID:15705555

Aged PROP1 Deficient Dwarf Mice Maintain ACTH Production

PubMed Central

Bavers, David L.; Beuschlein, Felix; Mortensen, Amanda H.; Keegan, Catherine E.; Hammer, Gary D.; Camper, Sally A.

2011-01-01

Humans with PROP1 mutations have multiple pituitary hormone deficiencies (MPHD) that typically advance from growth insufficiency diagnosed in infancy to include more severe growth hormone (GH) deficiency and progressive reduction in other anterior pituitary hormones, eventually including adrenocorticotropic hormone (ACTH) deficiency and hypocortisolism. Congenital deficiencies of GH, prolactin, and thyroid stimulating hormone have been reported in the Prop1null (Prop1-/-) and the Ames dwarf (Prop1df/df) mouse models, but corticotroph and pituitary adrenal axis function have not been thoroughly investigated. Here we report that the C57BL6 background sensitizes mutants to a wasting phenotype that causes approximately one third to die precipitously between weaning and adulthood, while remaining homozygotes live with no signs of illness. The wasting phenotype is associated with severe hypoglycemia. Circulating ACTH and corticosterone levels are elevated in juvenile and aged Prop1 mutants, indicating activation of the pituitary-adrenal axis. Despite this, young adult Prop1 deficient mice are capable of responding to restraint stress with further elevation of ACTH and corticosterone. Low blood glucose, an expected side effect of GH deficiency, is likely responsible for the elevated corticosterone level. These studies suggest that the mouse model differs from the human patients who display progressive hormone loss and hypocortisolism. PMID:22145038

Radial growth of two dominant montane conifer tree species in response to climate change in North-Central China.

PubMed

Jiang, Yuan; Zhang, Wentao; Wang, Mingchang; Kang, Muyi; Dong, Manyu

2014-01-01

North-Central China is a region in which the air temperature has clearly increased for several decades. Picea meyeri and Larix principis-rupprechtii are the most dominant co-occurring tree species within the cold coniferous forest belt ranging vertically from 1800 m to 2800 m a.s.l. in this region. Based on a tree-ring analysis of 292 increment cores sampled from 146 trees at different elevations, this study aimed to examine if the radial growth of the two species in response to climate is similar, whether the responses are consistent along altitudinal gradients and which species might be favored in the future driven by the changing climate. The results indicated the following: (1) The two species grew in different rhythms at low and high elevation respectively; (2) Both species displayed inconsistent relationships between radial growth and climate data along altitudinal gradients. The correlation between radial growth and the monthly mean temperature in the spring or summer changed from negative at low elevation into positive at high elevation, whereas those between the radial growth and the total monthly precipitation displayed a change from positive into negative along the elevation gradient. These indicate the different influences of the horizontal climate and vertical mountainous climate on the radial growth of the two species; (3) The species-dependent different response to climate in radial growth appeared mainly in autumn of the previous year. The radial growth of L. principis-rupprechtii displayed negative responses both to temperature and to precipitation in the previous September, October or November, which was not observed in the radial growth of P. meyeri. (4) The radial growth of both species will tend to be increased at high elevation and limited at low elevation, and L. principis-rupprechtii might be more favored in the future, if the temperature keeps rising.

Elevated phthalates' exposure in children with constitutional delay of growth and puberty.

PubMed

Xie, Changming; Zhao, Yan; Gao, Lianlian; Chen, Jiao; Cai, Depei; Zhang, Yunhui

2015-05-15

Phthalates have been proven to be antiandrogenic, which may interfere with the timing of puberty. Children with Constitutional Delay of Growth and Puberty (CDGP) typically display short stature and pubertal delay. This study investigated whether phthalate's exposure was associated with CDGP, and evaluated the potential mediator role of testosterone. In this case-control study, a total of 167 boys, including 57 boys with CDGP (cases) and 110 controls were enrolled. We measured six major phthalate metabolites in urine samples using high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). The serum testosterone level was determined by radioimmunoassay. Children in the CDGP group were determined to have significantly elevated urinary phthalates concentration compared with control subjects (total phthalates median: case, 107.00 ng/ml; control, 62.22 ng/ml, p = 0.001). After adjustment for BMI and other confounding factors: mono-n-butyl phthalate (MBP), monoethyl phthalate (MEP) and total phthalate concentrations were significantly negatively associated with serum testosterone level (MBP: β = -45.7, p = 0.017; MEP: β = -31.6, p = 0.022; total phthalates: β = -24.6, p = 0.011); MBP, MEP, mono (2-ethylhexyl) phthalate (MEHP) and total phthalates were significantly associated with CDGP (odds ratio: MBP: 8.30, p = 0.002; MEP: 5.43, p = 0.002; MEHP: 3.83, p = 0.017; total phthalates: 9.09, p = 0.001). Serum testosterone level acted as a mediator of the association between phthalates' exposure and CDGP (p = 0.002) (proportion mediated: 34.4%). In this case-control study, elevated phthalates' level was detected in children with CDGP in Shanghai, China and phthalate level was associated with CDGP, which appeared to be mediated by circulating testosterone level. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cultivar specific variations in antioxidative defense system, genome and proteome of two tropical rice cultivars against ambient and elevated ozone.

PubMed

Sarkar, Abhijit; Singh, Aditya Abha; Agrawal, Shashi Bhushan; Ahmad, Altaf; Rai, Shashi Pandey

2015-05-01

For the past few decades continuous increase in the levels of tropospheric ozone (O3) concentrations is posing to be a threat for agricultural productivity. Two high yielding tropical rice cultivars (Malviya dhan 36 and Shivani) were evaluated against different concentrations of O3 under field conditions. Experimental design included filtered chambers, non-filtered chambers having ambient O3 and 10 and 20ppb elevated O3 above the ambient. Study was conducted to assess differential response if any in induction of antioxidative defense system, genome stability, leaf proteome, yield and quality of the product in both the test cultivars. Superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), ascorbate peroxidase (APX), and glutathione reductase (GR) were induced under ambient and elevated levels of O3. Native polyacrylamide gel electrophoresis (PAGE) of SOD, CAT and POD also displayed increased enzymatic activity along with associated alterations in specific isoforms. Ascorbic acid, thiols and phenolics were also stimulated at ambient and elevated O3. Structural alterations in DNA of rice plants due to O3 affecting its genome template stability (GTS) was examined using RAPD technique. 2-D PAGE revealed 25 differential spots in Malviya dhan 36 and 36 spots in Shivani after O3 treatment with reductions in RuBisCO subunits. Reductions in yield and change in the quality of grains were also noticed. Copyright © 2015 Elsevier Inc. All rights reserved.

A whole-tree chamber system for examining tree-level physiological responses of field-grown trees to environmental variation and climate change.

PubMed

Medhurst, Jane; Parsby, Jan; Linder, Sune; Wallin, Göran; Ceschia, Eric; Slaney, Michelle

2006-09-01

A whole-tree chamber (WTC) system was installed at Flakaliden in northern Sweden to examine the long-term physiological responses of field-grown 40-year-old Norway spruce trees [Picea abies (L.) Karst.] to climate change. The WTCs were designed as large cuvettes to allow the net tree-level CO(2) and water fluxes to be measured on a continuous basis. A total of 12 WTCs were used to impose combinations of atmospheric carbon dioxide concentration, [CO(2)], and air temperature treatments. The air inside the ambient and elevated [CO(2)] WTCs was maintained at 365 and 700 micromol mol(-1), respectively. The air temperature inside the ambient temperature WTCs tracked air temperature outside the WTCs. Elevated temperatures were altered on a monthly time-step and ranged between +2.8 and +5.6 degrees C above ambient temperature. The system allowed continuous, long-term measurement of whole-tree photosynthesis, night-time respiration and transpiration. The performance of the WTCs was assessed using winter and spring data sets. The ability of the WTC system to measure tree-level physiological responses is demonstrated. All WTCs displayed a high level of control over tracking of air temperatures. The set target of 365 micromol mol(-1) in the ambient [CO(2)] chambers was too low to be maintained during winter because of tree dormancy and the high natural increase in [CO(2)] over winter at high latitudes such as the Flakaliden site. Accurate control over [CO(2)] in the ambient [CO(2)] chambers was restored during the spring and the system maintained the elevated [CO(2)] target of 700 micromol mol(-1) for both measurement periods. Air water vapour deficit (VPD) was accurately tracked in ambient temperature WTCs. However, as water vapour pressure in all 12 WTCs was maintained at the level of non-chambered (reference) air, VPD of elevated temperature WTCs was increased.

Astroglial CB1 Receptors Determine Synaptic D-Serine Availability to Enable Recognition Memory.

PubMed

Robin, Laurie M; Oliveira da Cruz, José F; Langlais, Valentin C; Martin-Fernandez, Mario; Metna-Laurent, Mathilde; Busquets-Garcia, Arnau; Bellocchio, Luigi; Soria-Gomez, Edgar; Papouin, Thomas; Varilh, Marjorie; Sherwood, Mark W; Belluomo, Ilaria; Balcells, Georgina; Matias, Isabelle; Bosier, Barbara; Drago, Filippo; Van Eeckhaut, Ann; Smolders, Ilse; Georges, Francois; Araque, Alfonso; Panatier, Aude; Oliet, Stéphane H R; Marsicano, Giovanni

2018-06-06

Bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. D-serine is a necessary co-agonist of synaptic N-methyl-D-aspartate receptors (NMDARs), but the physiological factors regulating its impact on memory processes are scantly known. We show that astroglial CB 1 receptors are key determinants of object recognition memory by determining the availability of D-serine at hippocampal synapses. Mutant mice lacking CB 1 receptors from astroglial cells (GFAP-CB 1 -KO) displayed impaired object recognition memory and decreased in vivo and in vitro long-term potentiation (LTP) at CA3-CA1 hippocampal synapses. Activation of CB 1 receptors increased intracellular astroglial Ca 2+ levels and extracellular levels of D-serine in hippocampal slices. Accordingly, GFAP-CB 1 -KO displayed lower occupancy of the co-agonist binding site of synaptic hippocampal NMDARs. Finally, elevation of D-serine levels fully rescued LTP and memory impairments of GFAP-CB 1 -KO mice. These data reveal a novel mechanism of in vivo astroglial control of memory and synaptic plasticity via the D-serine-dependent control of NMDARs. Copyright © 2018 Elsevier Inc. All rights reserved.

Low Soluble Fms-Like Tyrosine Kinase-1, Endoglin, and Endothelin-1 Levels in Women With Confirmed or Suspected Preeclampsia Using Proton Pump Inhibitors.

PubMed

Saleh, Langeza; Samantar, Raaho; Garrelds, Ingrid M; van den Meiracker, Anton H; Visser, Willy; Danser, A H Jan

2017-09-01

Patients with preeclampsia display elevated placenta-derived sFlt-1 (soluble Fms-like tyrosine kinase-1) and endoglin levels and decreased placental growth factor levels. Proton pump inhibitors (PPIs) decrease trophoblast sFlt-1 and endoglin secretion in vitro. PPIs are used during pregnancy to combat reflux disease. Here, we investigated whether PPIs affect sFlt-1 in women with confirmed/suspected preeclampsia, making use of a prospective cohort study involving 430 women. Of these women, 40 took PPIs (6 esomeprazole, 32 omeprazole, and 2 pantoprazole) for 8 to 45 (median 29) days before sFlt-1 measurement. Measurements were only made once, at study entry between weeks 20 and 41 (median 33 weeks). PPI use was associated with lower sFlt-1 levels, with no change in placental growth factor levels, both when compared with all non-PPI users and with 80 gestational age-matched controls selected from the non-PPI users. No sFlt-1/placental growth factor alterations were observed in women using ferrous fumarate or macrogol while, as expected, women using antihypertensive medication displayed higher sFlt-1 levels and lower placental growth factor levels. The PPI use-associated decrease in sFlt-1 was independent of the application of antihypertensive drugs and also occurred when restricting our analysis to patients with hypertensive disease of pregnancy at study entry. PPI users displayed more cases with preexisting proteinuria, less gestational hypertension, and a lower number of neonatal sepsis cases. Finally, their plasma endoglin and endothelin-1 levels were lower while sFlt-1 levels correlated positively with both. In conclusion, PPI use associates with low sFlt-1, endoglin, and endothelin-1 levels, warranting prospective trials to investigate the therapeutic potential of PPIs in preeclampsia. © 2017 American Heart Association, Inc.

ELEVATION OF FACILITY 667 WITH GRADUATED SCALE IN 1' INCREMENTS. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ELEVATION OF FACILITY 667 WITH GRADUATED SCALE IN 1' INCREMENTS. NOTE: THE TORPEDO IN THE FOREGROUND IS A DISPLAY ASSOCIATED WITH FACILITY 683. VIEW FACING NORTHEAST - U.S. Naval Base, Pearl Harbor, Gymnasium Building, North Waterfront & Pierce Street near Berth S-13, Pearl City, Honolulu County, HI

Breakfast skippers display a disrupted cortisol rhythm and elevated blood pressure

USDA-ARS?s Scientific Manuscript database

Chronic stress and over-activity in the hypothalamic-pituitary-adrenal (HPA) axis may link breakfast skipping and poor cardiometabolic health. Missing the first major meal of the day in rodents prolongs elevated circulating corticosterone at a time when it’s normally decreasing. To extend these fi...

Oxytocin and Social Sensitivity: Gene Polymorphisms in Relation to Depressive Symptoms and Suicidal Ideation

PubMed Central

McQuaid, Robyn J.; McInnis, Opal A.; Matheson, Kimberly; Anisman, Hymie

2016-01-01

Although the neuropeptide oxytocin has been associated with enhanced prosocial behaviors, it has also been linked to aggression and mental health disorders. Thus, it was suggested that oxytocin might act by increasing the salience of social stimuli, irrespective of whether these are positive or negative, thus increasing vulnerability to negative mental health outcomes. The current study (N = 243), conducted among white university students, examined the relation of trauma, depressive symptoms including suicidal ideation in relation to a single nucleotide polymorphism (SNP) within the oxytocin receptor gene (OXTR), rs53576, and a SNP on the CD38 gene that controls oxytocin release, rs3796863. Individuals with the polymorphism on both alleles (AA genotype) of the CD38 SNP had previously been linked to elevated plasma oxytocin levels. Consistent with the social sensitivity perspective, however, in the current study, individuals carrying the AA genotype displayed elevated feelings of alienation from parents and peers as well as increased levels of suicidal ideation. Moreover, they tended to report elevated depressive symptoms compared to CC homozygotes. It was also observed that the CD38 genotype moderated the relation between trauma and suicidal ideation scores, such that high levels of trauma were associated with elevated suicidal ideation among all CD38 genotypes, but this relationship was stronger among individuals with the AA genotype. In contrast, there was no relationship between the OXTR SNP, rs53576, depression or suicidal ideation. These findings support a social sensitivity hypothesis of oxytocin, wherein the AA genotype of the CD38 SNP, which has been considered the “protective allele” was associated with increased sensitivity and susceptibility to disturbed social relations and suicidal ideation. PMID:27486392

Peroxyacetyl nitrate in the North Atlantic marine boundary layer (GBC #10)

NASA Astrophysics Data System (ADS)

Gallagher, Michael S.; Carsey, Thomas P.; Farmer, Michael L.

1990-09-01

An automated system utilizing packed column gas chromatography and electron capture detection for the determination of peroxyacetyl nitrate (PAN) is described. The system was calibrated with a cryogenic PAN sublimation device, a molybdenum catalyst, and a chemiluminescent nitric oxide detector. Computer control of the analysis resulted in an analytical precision level of ˜1%. A total of 1178 PAN measurements were made from August 6 to September 5, 1988, in the marine boundary layer during the GCE/CASE/WATOX cruise (66°N to 7°N). Overall, PAN concentrations were highest at high latitudes (up to 40 ppt); PAN levels in the lower latitudes of the cruise track were usually <10 ppt. A number of episodes of elevated PAN are described which were characterized by elevated radon concentrations and a discernible diurnal cycle in the PAN concentration. These higher PAN levels are attributed to air masses with some continental influence, and to the enhanced stability of PAN at the cooler temperatures characteristic of the sub-Arctic region. In aged air masses of marine origin, PAN concentrations were significantly less and did not display diel changes; this is interpreted as a measure of the "background" PAN signal.

Relationships among Blood Pressure, Triglycerides and Verbal Learning in African Americans

PubMed Central

Sims, Regina C.; Madhere, Serge; Gordon, Shalanda; Clark, Elijah; Abayomi, Kobi A.; Callender, Clive O.; Campbell, Alfonso L.

2013-01-01

Background Individuals at greater risk for cardiovascular disease (CVD) display poorer cognitive functioning across various cognitive domains. This finding is particularly prevalent among older adults; however, few studies examine these relationships among younger adults or among African Americans. Purpose The objective was to examine the relationships among 2 cardiovascular risk factors, elevated blood pressure and elevated triglycerides, and verbal learning in a community-based sample of African Americans. Methods Measurements of blood pressure and triglycerides were obtained in 121 African-American adults and compared to performance on 3 domains of the California Verbal Learning Test-II (CVLT-II). Results Blood pressure was not related to CVLT-II performance. Triglyceride levels were inversely related to CVLT-II performance. Higher triglyceride levels were associated with poorer immediate, short delay and long delay recall. Conclusions Consistent with studies involving older participants, the current investigation shows that in a nonelderly sample of African Americans, triglyceride levels may be related to cognitive functioning. Because early detection and intervention of vascular-related cognitive impairment may have a salutary effect, future studies should include younger adults to highlight the impact of cardiovascular risk on cognition. PMID:18942281

Elevated gene expression levels distinguish human from non-human primate brains

PubMed Central

Cáceres, Mario; Lachuer, Joel; Zapala, Matthew A.; Redmond, John C.; Kudo, Lili; Geschwind, Daniel H.; Lockhart, David J.; Preuss, Todd M.; Barlow, Carrolee

2003-01-01

Little is known about how the human brain differs from that of our closest relatives. To investigate the genetic basis of human specializations in brain organization and cognition, we compared gene expression profiles for the cerebral cortex of humans, chimpanzees, and rhesus macaques by using several independent techniques. We identified 169 genes that exhibited expression differences between human and chimpanzee cortex, and 91 were ascribed to the human lineage by using macaques as an outgroup. Surprisingly, most differences between the brains of humans and non-human primates involved up-regulation, with ≈90% of the genes being more highly expressed in humans. By contrast, in the comparison of human and chimpanzee heart and liver, the numbers of up- and down-regulated genes were nearly identical. Our results indicate that the human brain displays a distinctive pattern of gene expression relative to non-human primates, with higher expression levels for many genes belonging to a wide variety of functional classes. The increased expression of these genes could provide the basis for extensive modifications of cerebral physiology and function in humans and suggests that the human brain is characterized by elevated levels of neuronal activity. PMID:14557539

3xTgAD mice exhibit altered behavior and elevated Aβ after chronic mild social stress

PubMed Central

Rothman, Sarah M.; Herdener, Nathan; Camandola, Simonetta; Texel, Sarah J.; Mughal, Mohamed R.; Cong, Wei-Na; Martin, Bronwen; Mattson, Mark P

2014-01-01

Chronic stress may be a risk factor for developing Alzheimer’s disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety and hippocampal Aβ, ptau and BDNF levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6 week stress period 3xTgAD mice displayed increased anxiety, elevated levels of Aβ oligomers and intraneuronal Aβ, and decreased BDNF levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates Aβ accumulation and impairs neurotrophic signaling. PMID:21855175

Cytoplasmic sequestration of the tumor suppressor p53 by a heat shock protein 70 family member, mortalin, in human colorectal adenocarcinoma cell lines

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

Gestl, Erin E., E-mail: egestl@wcupa.edu; Anne Boettger, S., E-mail: aboettger@wcupa.edu

2012-06-29

Highlights: Black-Right-Pointing-Pointer Eight human colorectal cell lines were evaluated for p53 and mortalin localization. Black-Right-Pointing-Pointer Six cell lines displayed cytoplasmic sequestration of the tumor suppressor p53. Black-Right-Pointing-Pointer Direct interaction between mortalin and p53 was shown in five cell lines. Black-Right-Pointing-Pointer Cell lines positive for p53 sequestration yielded elevated p53 expression levels. Black-Right-Pointing-Pointer This study yields the first evidence of cytoplasmic sequestration p53 by mortalin. -- Abstract: While it is known that cytoplasmic retention of p53 occurs in many solid tumors, the mechanisms responsible for this retention have not been positively identified. Since heatshock proteins like mortalin have been associated withmore » p53 inactivation in other tumors, the current study sought to characterize this potential interaction in never before examined colorectal adenocarcinoma cell lines. Six cell lines, one with 3 different fractions, were examined to determine expression of p53 and mortalin and characterize their cellular localization. Most of these cell lines displayed punctate p53 and mortalin localization in the cell cytoplasm with the exception of HCT-8 and HCT116 379.2 cells, where p53 was not detected. Nuclear p53 was only observed in HCT-116 40-16, LS123, and HT-29 cell lines. Mortalin was only localized in the cytoplasm in all cell lines. Co-immunoprecipitation and immunohistochemistry revealed that p53 and mortalin were bound and co-localized in the cytoplasmic fraction of four cell lines, HCT-116 (40-16 and 386; parental and heterozygous fractions respectively of the same cell line), HT-29, LS123 and LoVo, implying that p53 nuclear function is limited in those cell lines by being restricted to the cytoplasm. Mortalin gene expression levels were higher than gene expression levels of p53 in all cell lines. Cell lines with cytoplasmic sequestration of p53, however, also displayed elevated p53 gene expression levels compared to cell lines without p53 sequestration. Our data reveal the characteristic cytoplasmic sequestration of p53 by the heat shock protein mortalin in human colorectal adenocarcinoma cell lines, as is the case for other cancers, such as glioblastomas and hepatocellular carcinomas.« less

DNA-dependent protein kinase (DNA-PK)-deficient human glioblastoma cells are preferentially sensitized by Zebularine

PubMed Central

Meador, Jarah A.; Su, Yanrong; Ravanat, Jean-Luc; Balajee, Adayabalam S.

2010-01-01

Brain tumor cells respond poorly to radiotherapy and chemotherapy due to inherently efficient anti-apoptotic and DNA repair mechanisms. This necessitates the development of new strategies for brain cancer therapy. Here, we report that the DNA-demethylating agent Zebularine preferentially sensitizes the killing of human glioblastomas deficient in DNA-dependent protein kinase (DNA-PK). In contrast to DNA-PK-proficient human glioblastoma cells (MO59K), cytotoxicity assay with increasing Zebularine concentrations up to 300 μM resulted in a specific elevation of cell killing in DNA-PK-deficient MO59J cells. Further, an elevated frequency of polyploid cells observed in MO59J cells after Zebularine treatment pointed out a deficiency in mitotic checkpoint control. Existence of mitotic checkpoint deficiency in MO59J cells was confirmed by the abnormal centrosome number observed in Zebularine-treated MO59J cells. Although depletion of DNA methyltransferase 1 by Zebularine occurred at similar levels in both cell lines, MO59J cells displayed increased extent of DNA demethylation detected both at the gene promoter-specific level and at the genome overall level. Consistent with increased sensitivity, deoxy-Zebularine adduct level in the genomic DNA was 3- to 6-fold higher in MO59J than in MO59K cells. Elevated micronuclei frequency observed after Zebularine treatment in MO59J cells indicates the impairment of DNA repair response in MO59J cells. Collectively, our study suggests that DNA-PK is the major determining factor for cellular response to Zebularine. PMID:19933707

Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure.

PubMed

Leonis, Mike A; Toney-Earley, Kenya; Degen, Sandra J F; Waltz, Susan E

2002-11-01

The targeted deletion of the cytoplasmic domain of the Ron receptor tyrosine kinase (TK) in mice leads to exaggerated responses to injury in several murine models of inflammation as well as increased lethality in response to endotoxin (lipopolysaccharide [LPS]). Using a well-characterized model of LPS-induced acute liver failure (ALF) in galactosamine (GalN)-sensitized mice, we show that Ron TK(-/-) mice display marked protection compared with control Ron TK(+/+) mice. Whereas control mice have profound elevation of serum aminotransferase levels (a marker of hepatocyte injury) and hemorrhagic necrosis of the liver, in dramatic contrast, Ron TK(-/-) mice have mild elevation of aminotransferase levels and relatively normal liver histology. These findings are associated with a reduction in the number of liver cells undergoing apoptosis in Ron TK(-/-) mice. Paradoxically, treatment of Ron TK(-/-) mice with LPS/GalN leads to markedly elevated (3.5-fold) serum levels of tumor necrosis factor (TNF) alpha, a key inflammatory mediator in this liver injury model, as well as reduced amounts of interleukin (IL) 10 (a suppressor of TNF-alpha production) and interferon (IFN)-gamma (a TNF-alpha sensitizer). These results show that ablation of the TK activity of the Ron receptor leads to protection from the development of hepatocellular apoptosis in response to treatment with LPS/GalN, even in the presence of excessive levels of serum TNF-alpha. In conclusion, our studies show that the Ron receptor TK plays a critical role in modulating the response of the liver to endotoxin.

The Characteristics of Air Pollutants during Two Distinct Episodes of Fireworks Burning in a Valley City of North China

PubMed Central

Song, Yang; Wan, Xiaoming; Bai, Shuoxin; Guo, Dong; Ren, Ci; Zeng, Yu; Li, Yirui; Li, Xuewen

2017-01-01

Background The elevation and dissipation of pollutants after the ignition of fireworks in different functional areas of a valley city were investigated. Methods The Air Quality Index (AQI) as well as inter-day and intra-day concentrations of various air pollutants (PM10, PM2.5, SO2, NO2, CO, O3) were measured during two episodes that took place during Chinese New Year festivities. Results For the special terrain of Jinan, the mean concentrations of pollutants increased sharply within 2–4 h of the firework displays, and concentrations were 4–6 times higher than the usual levels. It took 2–3 d for the pollutants to dissipate to background levels. Compared to Preliminary Eve (more fireworks are ignited on New Year’s Eve, but the amounts of other human activities are also lesser), the primary pollutants PM2.5, PM10, and CO reached higher concentrations on New Year’s Eve, and the highest concentrations of these pollutants were detected in living quarters. All areas suffered from serious pollution problems on New Year’s Eve (rural = urban for PM10, but rural > urban for PM2.5). However, SO2 and NO2 levels were 20%–60% lower in living quarters and industrial areas compared to the levels in these same areas on Preliminary Eve. In contrast to the other pollutants, O3 concentrations fell instead of rising with the firework displays. Conclusion Interactions between firework displays and other human activities caused different change trends of pollutants. PM2.5 and PM10 were the main pollutants, and the rural living quarter had some of the highest pollution levels. PMID:28045925

The Characteristics of Air Pollutants during Two Distinct Episodes of Fireworks Burning in a Valley City of North China.

PubMed

Song, Yang; Wan, Xiaoming; Bai, Shuoxin; Guo, Dong; Ren, Ci; Zeng, Yu; Li, Yirui; Li, Xuewen

2017-01-01

The elevation and dissipation of pollutants after the ignition of fireworks in different functional areas of a valley city were investigated. The Air Quality Index (AQI) as well as inter-day and intra-day concentrations of various air pollutants (PM10, PM2.5, SO2, NO2, CO, O3) were measured during two episodes that took place during Chinese New Year festivities. For the special terrain of Jinan, the mean concentrations of pollutants increased sharply within 2-4 h of the firework displays, and concentrations were 4-6 times higher than the usual levels. It took 2-3 d for the pollutants to dissipate to background levels. Compared to Preliminary Eve (more fireworks are ignited on New Year's Eve, but the amounts of other human activities are also lesser), the primary pollutants PM2.5, PM10, and CO reached higher concentrations on New Year's Eve, and the highest concentrations of these pollutants were detected in living quarters. All areas suffered from serious pollution problems on New Year's Eve (rural = urban for PM10, but rural > urban for PM2.5). However, SO2 and NO2 levels were 20%-60% lower in living quarters and industrial areas compared to the levels in these same areas on Preliminary Eve. In contrast to the other pollutants, O3 concentrations fell instead of rising with the firework displays. Interactions between firework displays and other human activities caused different change trends of pollutants. PM2.5 and PM10 were the main pollutants, and the rural living quarter had some of the highest pollution levels.

Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice.

PubMed

Iñiguez, Sergio D; Riggs, Lace M; Nieto, Steven J; Dayrit, Genesis; Zamora, Norma N; Shawhan, Kristi L; Cruz, Bryan; Warren, Brandon L

2014-05-01

Abstract Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35-44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7-12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence.

Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice

PubMed Central

Iñiguez, Sergio D.; Riggs, Lace M.; Nieto, Steven J.; Dayrit, Genesis; Zamora, Norma N.; Shawhan, Kristi L.; Cruz, Bryan; Warren, Brandon L.

2016-01-01

Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35–44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7–12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence. PMID:24689732

Stress axis regulation during social ascension in a group-living cichlid fish.

PubMed

Culbert, Brett M; Gilmour, Kathleen M; Balshine, Sigal

2018-06-19

Animals living in groups often form social hierarchies, with characteristic behaviours and physiologies associated with rank. However, when social opportunities arise and a subordinate ascends into a dominant position, quick adjustments are necessary to secure this position. Such periods of social transition are typically associated with elevated glucocorticoid production, but the precise regulation of the stress axis during these occasions is not well understood. Using the group-living cichlid, Neolamprologus pulcher, the effects of social ascension on the stress axis were assessed. Ascenders rapidly filled experimentally created vacancies, adopting a dominant behavioural phenotype within 72 h-elevating aggression, activity, and workload, while receiving high rates of affiliative behaviours from their group members. Despite assuming behavioural dominance within their groups, ascenders displayed higher cortisol levels than dominants three days post-ascension. Additionally, compared to subordinates, ascenders had increased transcript abundance of steroidogenic acute regulatory protein (star) and cytochrome p450 side-chain cleavage enzyme (p450scc) in the head kidney, indicating activation of the stress axis. Cortisol levels were lowest in ascenders that displayed low rates of aggression, potentially reflecting the reestablishment of social stability in these groups. Increased transcript abundance of both glucocorticoid receptors (gr1 and gr2) in the brain's preoptic area (POA) of ascenders compared to dominants suggested an enhanced capacity for cortisol regulation via negative feedback. Our results reveal a regulatory cascade of behavioural and physiological interactions and highlight the importance of investigating the underlying mechanisms regulating the stress axis. Copyright © 2018. Published by Elsevier Inc.

State of Florida 1:24,000- and 1:100,000-scale quadrangle index map - Highlighting low-lying areas derived from USGS Digital Elevation Models

USGS Publications Warehouse

Kosovich, John J.

2008-01-01

In support of U.S. Geological Survey (USGS) disaster preparedness efforts, this map depicts 1:24,000- and 1:100,000-scale quadrangle footprints over a color shaded relief representation of the State of Florida. The first 30 feet of relief above mean sea level are displayed as brightly colored 5-foot elevation bands, which highlight low-elevation areas at a coarse spatial resolution. Standard USGS National Elevation Dataset (NED) 1 arc-second (nominally 30-meter) digital elevation model (DEM) data are the basis for the map, which is designed to be used at a broad scale and for informational purposes only. The NED source data for this map consists of a mixture of 30-meter- and 10-meter-resolution DEMs. The NED data were derived from the original 1:24,000-scale USGS topographic map bare-earth contours, which were converted into gridded quadrangle-based DEM tiles at a constant post spacing (grid cell size) of either 30 meters (data before the mid-1990s) or 10 meters (mid-1990s and later data). These individual-quadrangle DEMs were then converted to spherical coordinates (latitude/longitude decimal degrees) and edge-matched to ensure seamlessness. Figure 1 shows a similar representation for the entire U.S. Gulf Coast, using coarsened 30-meter NED data. Areas below sea level typically are surrounded by levees or some other type of flood-control structures. State and county boundary, hydrography, city, and road layers were modified from USGS National Atlas data downloaded in 2003. Quadrangle names, dated April, 2006, were obtained from the Federal Geographic Names Information System. The NED data were downloaded in 2004.

ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice.

PubMed

Xiao, Hong-Bo; Wang, Ji-Ying; Sun, Zhi-Liang

2017-12-01

Previous investigations have shown that inflammation induces changes in lipid and lipoprotein metabolism, and increased expression of angiopoietin-like protein 3 (ANGPTL3) contributes to the development of dyslipidemia. Here we investigated whether there is a correlation between increased ANGPTL3 expression and dyslipidemia in mastitis mice. Thirty mice were divided into two groups: control group and Staphylococcus aureus (S. aureus)-induced mastitis mice group. Changes in the levels of blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)]; activity of myeloperoxidase (MPO); concentrations of plasma inflammation biomarkers [interferon-γ (IFNγ), tumor necrosis factor α (TNFα), and interleukin-1α (IL-1α)]; concentration of plasma ANGPTL3 protein; lipoprotein lipase (LPL) activities in postheparin plasma; expressions of hepatic N-acetylgalactosaminyltransferase 2 (GALNT2), hepatic ANGPTL3 and adipose LPL were determined. The major results indicated specific pathological mammary tissue changes, elevated MPO activity, reduced GALNT2 mRNA expression, elevated ANGPTL3 mRNA and protein expression and reduced LPL mRNA and protein expression. In plasma samples the S.aureus infused mice displayed elevated ANGPTL3 protein concentration, TG, TC and LDL-C levels, and reduced postheparin LPL activities and HDL-C level. The data suggests that ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Physiological acclimation to elevated temperature in a reef-building coral from an upwelling environment

NASA Astrophysics Data System (ADS)

Mayfield, A. B.; Fan, T.-Y.; Chen, C.-S.

2013-12-01

Recent work has found that pocilloporid corals from regions characterized by unstable temperatures, such as those exposed to periodic upwelling, display a remarkable degree of phenotypic plasticity. In order to understand whether important reef builders from these upwelling reefs remain physiologically uncompromised at temperatures they will experience in the coming decades as a result of global climate change, a long-term elevated temperature experiment was conducted with Pocillopora damicornis specimens collected from Houbihu, a small embayment within Nanwan Bay, southern Taiwan that is characterized by 8-9 °C temperature changes during upwelling events. Upon nine months of exposure to nearly 30 °C, all colony (mortality and surface area), polyp ( Symbiodinium density and chlorophyll a content), tissue (total thickness), and molecular (gene expression and molecular composition)-level parameters were documented at similar levels between experimental corals and controls incubated at 26.5 °C, suggesting that this species can readily acclimate to elevated temperatures that cause significant degrees of stress, or even bleaching and mortality, in conspecifics of other regions of the Indo-Pacific. However, the gastrodermal tissue layer was relatively thicker in corals of the high temperature treatment sampled after nine months, possibly as an adaptive response to shade Symbiodinium from the higher photosynthetically active radiation levels that they were experiencing at that sampling time. Such shading may have prevented high light and high temperature-induced photoinhibition, and consequent bleaching, in these samples.

PDF receptor signaling in Drosophila contributes to both circadian and geotactic behaviors.

PubMed

Mertens, Inge; Vandingenen, Anick; Johnson, Erik C; Shafer, Orie T; Li, W; Trigg, J S; De Loof, Arnold; Schoofs, Liliane; Taghert, Paul H

2005-10-20

The neuropeptide Pigment-Dispersing Factor (PDF) is a principle transmitter regulating circadian locomotor rhythms in Drosophila. We have identified a Class II (secretin-related) G protein-coupled receptor (GPCR) that is specifically responsive to PDF and also to calcitonin-like peptides and to PACAP. In response to PDF, the PDF receptor (PDFR) elevates cAMP levels when expressed in HEK293 cells. As predicted by in vivo studies, cotransfection of Neurofibromatosis Factor 1 significantly improves coupling of PDFR to adenylate cyclase. pdfr mutant flies display increased circadian arrhythmicity, and also display altered geotaxis that is epistatic to that of pdf mutants. PDFR immunosignals are expressed by diverse neurons, but only by a small subset of circadian pacemakers. These data establish the first synapse within the Drosophila circadian neural circuit and underscore the importance of Class II peptide GPCR signaling in circadian neural systems.

Corticosteroid modulation and testosterone changes during alcohol intoxication affects voluntary alcohol drinking.

PubMed

Eriksson, C J P; Etelälahti, T J; Apter, S J

2017-06-01

A number of studies have shown that stress and an activated hypothalamic-pituitary-adrenal (HPA) axis are associated with increased voluntary alcohol drinking. Recently, associations have been found between activated HPA and hypothalamic-pituitary-gonadal (HPG) axes in alcohol-preferring AA and non-preferring ANA, F2 (crossbred second generation from original AA and ANA), and Wistar rats. The aim of the present study has been to determine the role of corticosterone and alcohol-related testosterone-effects in subsequent alcohol drinking in AA, ANA, F2 and Wistar rats. The present study comprises of four substudies presenting new analyses of existing data, by which correlations between basal corticosterone levels, changes in testosterone levels during alcohol intoxications and subsequent voluntary alcohol consumption are investigated. The results displayed positive correlations between basal corticosterone levels and subsequent alcohol-mediated testosterone elevations, which was positively associated with voluntary alcohol consumption. The results also showed a negative correlation between basal corticosterone levels and alcohol-mediated testosterone decreases, which was negatively associated with alcohol consumption. In conclusion, the present study displays novel results, according to which the HPA axis, one hand, relates to testosterone elevation (potentially causing and/or strengthening reinforcement) during alcohol intoxication, which in turn may relate to higher voluntary alcohol consumption (AA rats). Vice versa, the HPA axis may also relate to alcohol-mediated testosterone decrease (causing testosterone reduction and disinforcement) and low-alcohol drinking (ANA, F2 and Wistar rats). In addition, the present results showed that alcohol-mediated testosterone changes may also, independently of the HPA axis, correlate with voluntary alcohol drinking, which indicate the impact of genetic factors. Thus, the role of the HPA-axis may be more related to situational stress than to intrinsic factors. In further studies, it should be investigated, whether the present results also apply to stress and human alcohol drinking. Copyright © 2017 Elsevier Inc. All rights reserved.

Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction in mice selectively bred for low levels of anxiety.

PubMed

Yen, Yi-Chun; Anderzhanova, Elmira; Bunck, Mirjam; Schuller, Julia; Landgraf, Rainer; Wotjak, Carsten T

2013-01-01

We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB) coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania, and attention deficit hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically examined LAB mice with respect to unique and overlapping endophenotypes of the three diseases. To this end Venn diagrams were used as an instrument for discrimination of possible models. We arranged the endophenotypes in Venn diagrams and translated them into different behavioral tests. LAB mice showed elevated levels of locomotion in the open field (OF) test with deficits in habituation, compared to mice bred for normal (NAB) and high anxiety-related behavior (HAB). Cross-breeding of hypoactive HAB and hyperactive LAB mice resulted in offspring showing a low level of locomotion comparable to HAB mice, indicating that the HAB alleles are dominant over LAB alleles in determining the level of locomotion. In a holeboard test, LAB mice spent less time in hole exploration, as shown in patients with schizophrenia and ADHD; however, LAB mice displayed no impairments in social interaction and prepulse inhibition (PPI), implying a unlikelihood of LAB as an animal model of schizophrenia. Although LAB mice displayed hyperarousal, active coping styles, and cognitive deficits, symptoms shared by mania and ADHD, they failed to reveal the classic manic endophenotypes, such as increased hedonia and object interaction. The neuroleptic haloperidol reduced locomotor activity in all mouse lines. The mood stabilizer lithium and the psychostimulant amphetamine, in contrast, selectively reduced hyperactivity in LAB mice. Based on the behavioral and pharmacological profiles, LAB mice are suggested as a novel rodent model of ADHD-like symptoms.

Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction in mice selectively bred for low levels of anxiety

PubMed Central

Yen, Yi-Chun; Anderzhanova, Elmira; Bunck, Mirjam; Schuller, Julia; Landgraf, Rainer; Wotjak, Carsten T.

2013-01-01

We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB) coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania, and attention deficit hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically examined LAB mice with respect to unique and overlapping endophenotypes of the three diseases. To this end Venn diagrams were used as an instrument for discrimination of possible models. We arranged the endophenotypes in Venn diagrams and translated them into different behavioral tests. LAB mice showed elevated levels of locomotion in the open field (OF) test with deficits in habituation, compared to mice bred for normal (NAB) and high anxiety-related behavior (HAB). Cross-breeding of hypoactive HAB and hyperactive LAB mice resulted in offspring showing a low level of locomotion comparable to HAB mice, indicating that the HAB alleles are dominant over LAB alleles in determining the level of locomotion. In a holeboard test, LAB mice spent less time in hole exploration, as shown in patients with schizophrenia and ADHD; however, LAB mice displayed no impairments in social interaction and prepulse inhibition (PPI), implying a unlikelihood of LAB as an animal model of schizophrenia. Although LAB mice displayed hyperarousal, active coping styles, and cognitive deficits, symptoms shared by mania and ADHD, they failed to reveal the classic manic endophenotypes, such as increased hedonia and object interaction. The neuroleptic haloperidol reduced locomotor activity in all mouse lines. The mood stabilizer lithium and the psychostimulant amphetamine, in contrast, selectively reduced hyperactivity in LAB mice. Based on the behavioral and pharmacological profiles, LAB mice are suggested as a novel rodent model of ADHD-like symptoms. PMID:23966915

Genetic inactivation of the transcription factor TIF-IA leads to nucleolar disruption, cell cycle arrest, and p53-mediated apoptosis.

PubMed

Yuan, Xuejun; Zhou, Yonggang; Casanova, Emilio; Chai, Minqiang; Kiss, Eva; Gröne, Hermann-Josef; Schütz, Günter; Grummt, Ingrid

2005-07-01

Growth-dependent regulation of rRNA synthesis is mediated by TIF-IA, a basal transcription initiation factor for RNA polymerase I. We inactivated the murine TIF-IA gene by homologous recombination in mice and embryonic fibroblasts (MEFs). TIF-IA-/- embryos die before or at embryonic day 9.5 (E9.5), displaying retardation of growth and development. In MEFs, Cre-mediated depletion of TIF-IA leads to disruption of nucleoli, cell cycle arrest, upregulation of p53, and induction of apoptosis. Elevated levels of p53 after TIF-IA depletion are due to increased binding of ribosomal proteins, such as L11, to MDM2 and decreased interaction of MDM2 with p53 and p19(ARF). RNAi-induced loss of p53 overcomes proliferation arrest and apoptosis in response to TIF-IA ablation. The striking correlation between perturbation of nucleolar function, elevated levels of p53, and induction of cell suicide supports the view that the nucleolus is a stress sensor that regulates p53 activity.

Hepatoprotective effects of fermented Curcuma longa L. on carbon tetrachloride-induced oxidative stress in rats.

PubMed

Kim, Yongjae; You, Yanghee; Yoon, Ho-Geun; Lee, Yoo-Hyun; Kim, Kyungmi; Lee, Jeongmin; Kim, Min Soo; Kim, Jong-Choon; Jun, Woojin

2014-05-15

The hepatoprotective effect of fermented Curcuma longa L. (FC) was investigated in rats under CCl4-induced oxidative stress. FC at a dose of 30 or 300 mg/kg body weight (b.w.) was orally administered for 14 days followed by a single dose of CCl4 (1.25 mL/kg b.w. in 20% corn oil) on day 14. Pretreatment with FC drastically prevented the elevated activities of serum AST, ALT, LDH, and ALP caused by CCl4-induced hepatotoxicity. Histopathologically evident hepatic necrosis was significantly ameliorated by FC pretreatment. When compared to the CCl4-alone treated group, rats pretreated with FC displayed the reduced level of malondialdehyde. Furthermore, FC enhanced antioxidant capacities with higher activities of catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase, and level of reduced glutathione. These results suggest that FC could be a candidate used for the prevention against various liver diseases induced by oxidative stress via elevating antioxidative potentials and decreasing lipid peroxidation. Copyright © 2013 Elsevier Ltd. All rights reserved.

S100B overexpression increases behavioral and neural plasticity in response to the social environment during adolescence.

PubMed

Buschert, Jens; Hohoff, Christa; Touma, Chadi; Palme, Rupert; Rothermundt, Matthias; Arolt, Volker; Zhang, Weiqi; Ambrée, Oliver

2013-11-01

Genetic variants as well as increased serum levels of the neurotrophic factor S100B are associated with different psychiatric disorders. However, elevated S100B levels are also related to a better therapeutic outcome in psychiatric patients. The functional role of elevated S100B in psychiatric disorders is still unclear. Hence, this study was designed in order to elucidate the differential effects of S100B overexpression in interaction with chronic social stress during adolescence on emotional behavior and adult neurogenesis. S100B transgenic and wild-type mice were housed either in socially stable or unstable environments during adolescence, between postnatal days 28 and 77. In adulthood, anxiety-related behavior in the open field, dark-light, and novelty-induced suppression of feeding test as well as survival of proliferating hippocampal progenitor cells were assessed. S100B transgenic mice revealed significantly reduced anxiety-related behavior in the open field compared to wild-types when reared in stable social conditions. In contrast, when transgenic mice grew up in unstable social conditions, their level of anxiety-related behavior was comparable to the levels of wild-type mice. In addition, S100B overexpressing mice from unstable housing conditions displayed higher numbers of surviving newborn cells in the adult hippocampus which developed into mature neurons. In conclusion, elevated S100B levels increase the susceptibility to environmental stimuli during adolescence resulting in more variable behavioral and neural phenotypes in adulthood. In humans, this increased plasticity might lead to both, enhanced risk for psychiatric disorders in negative environments and improved therapeutic outcome in positive environments. Copyright © 2013 Elsevier Ltd. All rights reserved.

49 CFR 172.325 - Elevated temperature materials.

Code of Federal Regulations, 2010 CFR

2010-10-01

... square-on-point configuration having the same outside dimensions as a placard. (See § 172.302(b) for size... paragraph (a) of this section. (c) If the identification number is displayed on a white-square-on-point... of the same white-square-on-point display configuration. The word “HOT” must be in black letters...

49 CFR 172.325 - Elevated temperature materials.

Code of Federal Regulations, 2011 CFR

2011-10-01

... square-on-point configuration having the same outside dimensions as a placard. (See § 172.302(b) for size... paragraph (a) of this section. (c) If the identification number is displayed on a white-square-on-point... of the same white-square-on-point display configuration. The word “HOT” must be in black letters...

49 CFR 172.325 - Elevated temperature materials.

Code of Federal Regulations, 2014 CFR

2014-10-01

... square-on-point configuration having the same outside dimensions as a placard. (See § 172.302(b) for size... paragraph (a) of this section. (c) If the identification number is displayed on a white-square-on-point... of the same white-square-on-point display configuration. The word “HOT” must be in black letters...

State of Texas - Highlighting low-lying areas derived from USGS Digital Elevation Data

USGS Publications Warehouse

Kosovich, John J.

2008-01-01

In support of U.S. Geological Survey (USGS) disaster preparedness efforts, this map depicts a color shaded relief representation of Texas and a grayscale relief of the surrounding areas. The first 30 feet of relief above mean sea level are displayed as brightly colored 5-foot elevation bands, which highlight low-elevation areas at a coarse spatial resolution. Standard USGS National Elevation Dataset (NED) 1 arc-second (nominally 30-meter) digital elevation model (DEM) data are the basis for the map, which is designed to be used at a broad scale and for informational purposes only. The NED data were derived from the original 1:24,000-scale USGS topographic map bare-earth contours, which were converted into gridded quadrangle-based DEM tiles at a constant post spacing (grid cell size) of either 30 meters (data before the mid-1990s) or 10 meters (mid-1990s and later data). These individual-quadrangle DEMs were then converted to spherical coordinates (latitude/longitude decimal degrees) and edge-matched to ensure seamlessness. The NED source data for this map consists of a mixture of 30-meter- and 10-meter-resolution DEMs. State and county boundary, hydrography, city, and road layers were modified from USGS National Atlas data downloaded in 2003. The NED data were downloaded in 2002. Shaded relief over Mexico was obtained from the USGS National Atlas.

Flight Test Results of a Synthetic Vision Elevation Database Integrity Monitor

NASA Technical Reports Server (NTRS)

deHaag, Maarten Uijt; Sayre, Jonathon; Campbell, Jacob; Young, Steve; Gray, Robert

2001-01-01

This paper discusses the flight test results of a real-time Digital Elevation Model (DEM) integrity monitor for Civil Aviation applications. Providing pilots with Synthetic Vision (SV) displays containing terrain information has the potential to improve flight safety by improving situational awareness and thereby reducing the likelihood of Controlled Flight Into Terrain (CFIT). Utilization of DEMs, such as the digital terrain elevation data (DTED), requires a DEM integrity check and timely integrity alerts to the pilots when used for flight-critical terrain-displays, otherwise the DEM may provide hazardous misleading terrain information. The discussed integrity monitor checks the consistency between a terrain elevation profile synthesized from sensor information, and the profile given in the DEM. The synthesized profile is derived from DGPS and radar altimeter measurements. DEMs of various spatial resolutions are used to illustrate the dependency of the integrity monitor s performance on the DEMs spatial resolution. The paper will give a description of proposed integrity algorithms, the flight test setup, and the results of a flight test performed at the Ohio University airport and in the vicinity of Asheville, NC.

Investigating the 'jumping to conclusions' bias in people with anorexia nervosa.

PubMed

McKenna, Gráinne; Fox, John R E; Haddock, Gillian

2014-09-01

'Jumping to conclusions' (JTC) is an established reasoning bias in people with psychosis and delusion proneness. Research investigating the JTC bias in other clinical populations remains in its infancy. This study investigated whether individuals with anorexia (AN) displayed the JTC bias compared with healthy controls and, if so, whether the bias was greater in relation to emotionally salient information. The study also investigated whether delusionality was correlated with the JTC bias. JTC was measured using the 'beads task'. Three versions were employed: the standard version and two emotionally salient tasks. Results indicated that a majority (55.6%) of people with AN (n=26) displayed poor insight into their eating disorder beliefs but did not display an elevated JTC compared with healthy controls (n=33) on any task. The level of delusionality in the AN group was not correlated with JTC bias. Findings suggest that although a majority of people with AN demonstrated limited insight, they did not display the JTC bias. This may suggest that poor insight in eating disorders has different characteristics to that found in psychotic disorders, which may suggest that differences are needed in relation to how they are treated using psychological means. However, this was a small study, and study replication is required. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

Seasonal and interannual evolution of Jakobshavn Isbrae, Greenland from a 2008-2015 high-res DEM and velocity time series

NASA Astrophysics Data System (ADS)

Shean, D. E.; Joughin, I.; Smith, B.; Floricioiu, D.

2015-12-01

Greenland's large marine-terminating outlet glaciers have displayed marked retreat, speedup, and thinning in recent decades. Jakobshavn Isbrae, one of Greenland's largest outlet glaciers, has retreated ~15 km, accelerated ~150%, and thinned ~200 m since the early 1990s. Here, we present a comprehensive analysis of high-resolution elevation (~2-5 m/px) and velocity (~100 m/px) time series with dense temporal coverage (daily-monthly). The Jakobshavn DEM time series consists of >70 WorldView-1/2/3 stereo DEMs and >11 TanDEM-X DEMs spanning 2008-2015. Complementary point elevation data from Operation IceBridge (ATM, LVIS), pre-IceBridge ATM flights, and ICESat-1 GLAS extend the surface elevation record to 1999 and provide essential absolute control data, enabling sub-meter horizontal/vertical accuracy for gridded DEMs. Velocity data are primarily derived from TerraSAR-X/TanDEM-X image pairs with 11-day interval from 2009-2015. These elevation and velocity data capture outlet glacier evolution with unprecedented detail during the post-ICESat era. The lower trunk of Jakobshavn displays significant seasonal velocity variations, with recent rates of ~8 km/yr during winter and >17 km/yr during summer. DEM data show corresponding seasonal elevation changes of -30 to -45 m in summer and +15 to +20 m in winter, with decreasing magnitude upstream. Seasonal discharge varies from ~30-35 Gt/yr in winter to ~45-55 Gt/yr in summer, and we integrate these measurements for improved long-term mass-balance estimates. Recent interannual trends show increased discharge, velocity, and thinning (-15 to -20 m/yr), which is consistent with long-term altimetry records. The DEM time series also reveal new details about calving front and mélange evolution during the seasonal cycle. Similar time series are available for Kangerdlugssuaq and Helheim Glaciers. These observations are improving our understanding of outlet glacier dynamics, while complementing ongoing efforts to constrain estimates for ice-sheet mass balance and present/future sea level rise contributions.

Imbalanced gp130 signalling in ApoE-deficient mice protects against atherosclerosis.

PubMed

Jones, Gareth W; McLeod, Louise; Kennedy, Catherine L; Bozinovski, Steven; Najdovska, Meri; Jenkins, Brendan J

2015-02-01

Interleukin (IL)-6 is a key modulator of the acute phase response (APR), and while both are implicated in atherosclerosis, the pathological role of specific IL-6 signalling cascades is ill-defined. Since IL-6 employs the cytokine receptor gp130 to primarily activate the STAT3 pathway, here we evaluate whether gp130-dependent STAT3 activation modulates atherosclerosis. High-fat diet-induced atherosclerosis was established in ApoE(-/-) mice crossed with gp130(F/F) knock-in mice displaying elevated gp130-dependent STAT3 activation and production of the APR protein, serum amyloid A (SAA). Also generated were gp130(F/F):Stat3(-/+):ApoE(-/-) mice displaying genetically-normalised STAT3 activation and SAA levels, and bone marrow chimeras involving ApoE(-/-) and gp130(F/F):ApoE(-/-) mice. At 10 weeks post high-fat diet, aortic atherosclerotic lesions, including the presence of CD68(+) macrophages, and plasma lipid and SAA profiles, were assessed. Aortic plaque development and plasma triglyceride levels in gp130(F/F):ApoE(-/-) mice were significantly reduced (3-fold, P < 0.001) compared to ApoE(-/-) littermates. By contrast, in gp130(F/F):ApoE(-/-) mice, atherosclerotic plaques contained augmented CD68(+) macrophage infiltrates, and plasma SAA levels were elevated, compared to ApoE(-/-) mice. Atherosclerotic lesion development and plasma triglyceride levels in gp130(F/F):ApoE(-/-) and gp130(F/F):Stat3(-/+):ApoE(-/-) mice were comparable, despite a significant (P < 0.05) reduction in macrophage numbers in lesions, and also plasma SAA levels, in gp130(F/F):Stat3(-/+):ApoE(-/-) mice. Aortic plaque development and plasma triglyceride levels were comparable in ApoE(-/-) mice reconstituted with gp130(F/F):ApoE(-/-) (ApoE(F/F:ApoE)) or ApoE(-/-) (ApoE(ApoE)) bone marrow cells. Deregulation of gp130/STAT3 signalling augments the APR and macrophage infiltration during atherosclerosis without impacting on the development of aortic plaques. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

High fat diet feeding results in gender specific steatohepatitis and inflammasome activation.

PubMed

Ganz, Michal; Csak, Timea; Szabo, Gyongyi

2014-07-14

To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis (NASH), which has been a challenge. In this study, we used a high fat diet (HFD) feeding supplemented with fructose and sucrose in the water mimicking the high-fructose corn syrup that is abundant in the diet in the United States. We used C57Bl/6 wild-type mice for short and long-term feedings of 6 and 16 wk respectively, and evaluated the extent of liver damage, steatosis, and inflammasome activation. Our methods included histopathological analysis to assess liver damage and steatosis, which involved H and E and oil-red-o staining; biochemical studies to look at ALT and triglyceride levels; RNA analysis using quantitative polymerase chain reaction; and cytokine analysis, which included the enzyme-linked immunosorbent assay method to look at interleukin (IL)-1β and tumor necrosis factor-α (TNFα) levels. Furthermore, at each length of feeding we also looked at insulin resistance and glucose tolerance using insulin tolerance tests (ITT) and glucose tolerance tests. There was no insulin resistance, steatosis, or inflammasome activation at 6 wk. In contrast, at 16 wk we found significant insulin resistance demonstrated by impaired glucose and ITT in male, but not female mice. In males, elevated alanine aminotransferase and triglyceride levels, indicated liver damage and steatosis, respectively. Increased liver TNFα and monocyte chemoattractant protein-1 mRNA and protein, correlated with steatohepatitis. The inflammasome components, adaptor molecule, Aim2, and NOD-like receptor 4, increased at the mRNA level, and functional inflammasome activation was indicated by increased caspase-1 activity and IL-1β protein levels in male mice fed a long-term HFD. Male mice on HFD had increased α-smooth muscle actin and pro-collagen-1 mRNA indicating evolving fibrosis. In contrast, female mice displayed only elevated triglyceride levels, steatosis, and no fibrosis. Our data indicate gender differences in NASH. Male mice fed a long-term HFD display steatohepatitis and inflammasome activation, whereas female mice have steatosis without inflammation.

Heavy metals distribution in the coral reef ecosystems of the Northern Red Sea

NASA Astrophysics Data System (ADS)

Ali, Abdel-Hamid A. M.; Hamed, Mohamed A.; Abd El-Azim, Hoda

2011-03-01

Concentrations of seven heavy metals (Cu, Zn, Pb, Cd, Ni, Co and Fe) were measured in the seawater, sediments, common scleractinian reef-building corals and soft corals (Octocorallia : Alcyonacea) at seven reef sites in the Northern Red Sea: I (Hurghada), II (Ras Za'farana), III (El-Ain Al-Sukhna), IV (El-Tur), V (Sha'b Rashdan), VI (Sharm El-Sheikh) and VII (Dahab). Levels of heavy metals were considerably elevated in seawater, sediments and corals collected from reef sites exposed to increased environmental contamination, as a result of diversified natural and anthropogenic inputs. Soft corals of genera Lithophyton, Sarcophyton and Sinularia showed higher concentrations of Zn, Pb, Cd and Ni than hard coral genera Acropora and Stylophora. Soft coral Sarcophyton trocheliophorum collected from El Ain Al-Suhkna (Gulf of Suez) had greater concentration of Cu, followed by hard corals Acropora pharaonis and Acropora hemprichi. The elevated levels of Zn, Cd and Ni were reported in the dry tissue of soft coral Sinularia spp. On the other hand, the soft coral Lithophyton arboreum displayed the highest concentration of Pb at Sha'b Rashdan (Gulf of Suez) and elevated concentration of Zn at Sharm El-Sheikh. Sediments showed significantly higher concentration of Fe than corals. The higher levels of Fe in hard corals than soft corals reflected the incorporation of Fe into the aragonite and the chelation with the organic matrix of the skeleton. The greater abundance of soft corals in metal-contaminated reef sites and the elevated levels of metals in their tissue suggesting that the soft corals could develop a tolerance mechanism to relatively high concentrations of metals. Although the effects of heavy metals on reef corals were not isolated from the possible effects of other stresses, the percentage cover of dead corals were significantly higher as the concentrations of heavy metals increased.

Ameliorative effect of hydro-methanolic extract from roots of Rauwolfia serpentina on some biochemical parameters of type 1 diabetic mice.

PubMed

Azmi, Muhammad Bilal; Qureshi, Shamim A; Ahmed, Syed Danish Haseen; Mudassir, Hina Akram; Imtiaz, Fauzia; Rais, Sumera; Khan, Auwais Ahmed; Ahsan, Muhammad

2018-03-01

Present work seeks to investigate the biochemical parameters in terms of hypoglycemic and hypolipidemic effects of hydro-methanolic roots extract (HyMREt) of Rauwolfia serpentina in type 1 (alloxan induced) diabetic mice. Animals were divided into seven groups, four control groups, and three were test groups (HyMREt at 50, 100, & 150mg/kg). Each treatment was repeated for 14 days regularly in all seven respective groups and afterwards the body weights, fasting blood glucose (FBG), insulin, and serum lipid levels were determined. Total body weights of diabetic mice treated with HyMREt extract were dose dependently (p<0.05) improved. FBG of test groups were significantly (p<0.0001) reduced in comparison with diabetic controls which displayed elevated fasting blood glucose level. The insulin levels of HyMREt treated groups were significantly (p<0.0001) higher than those of diabetic controls. Lower triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and very low density lipoprotein cholesterol (VLDL-c) whereas elevated level of high density lipoprotein cholesterol (HDL-c) were observed in test dose treated groups. In comparison with diabetic controls, the converse levels of serum lipid were observed. Significant improvement in cardio-protective indices and coronary risk index was also observed. Findings of present study support the hypoglycemic and hypolipidemic potential of HyMREt of R. serpentina.

Different Effects of Oral Contraceptive and Dydrogesterone Treatment on Oxidative Stress Levels in Premenopausal Women.

PubMed

Chen, Jui-Tung; Kotani, Kazuhiko

2018-02-01

The aim of the study was to observe the changes in blood oxidative stress levels by oral contraceptive (OC) and/or dydrogesterone (DG) treatment. A retrospective cohort of 27 premenopausal women with primary dysmenorrhea consisted of the OC treatment group (N = 17) and the DG treatment group (N = 10) by choice of the initial treatment. The OC group included two subgroups: patients with continuous OC treatment (treated for at least 15 months, N = 10) and patients with discontinuous OC treatment (switched to DG treatment after approximately 6 months of initial OC treatment: N = 7). The DG group had 15 months of continuous DG treatment. Blood parameters, including diacron-reactive oxygen metabolites (d-ROMs: an oxidative stress marker), were measured. The d-ROMs level was elevated in the OC group 3 months after initial treatment (mean: from 321 (at baseline) to 512 Carratelli Units (Carr U); P < 0.01), while such changes were not observed in the DG group. The d-ROMs level was reduced in the discontinuous OC subgroup 15 months after initial treatment (from 508 (3 months after initial treatment) to 372 Carr U; P < 0.01), while such changes were not observed in the continuous OC subgroup. The DG group displayed unchanged the d-ROMs level. Replacing OC with DG can attenuate oxidative stress as elevated by OC, thereby alleviating the possible vascular risks with OC treatment.

Effects of thyroid hormone status on metabolic pathways of arachidonic acid in mice and humans: A targeted metabolomic approach.

PubMed

Yao, Xuan; Sa, Rina; Ye, Cheng; Zhang, Duo; Zhang, Shengjie; Xia, Hongfeng; Wang, Yu-cheng; Jiang, Jingjing; Yin, Huiyong; Ying, Hao

2015-01-01

Symptoms of cardiovascular diseases are frequently found in patients with hypothyroidism and hyperthyroidism. However, it is unknown whether arachidonic acid metabolites, the potent mediators in cardiovascular system, are involved in cardiovascular disorders caused by hyperthyroidism and hypothyroidism. To answer this question, serum levels of arachidonic acid metabolites in human subjects with hypothyroidism, hyperthyroidism and mice with hypothyroidism or thyroid hormone treatment were determined by a mass spectrometry-based method. Over ten arachidonic acid metabolites belonging to three catalytic pathways: cyclooxygenases, lipoxygenases, and cytochrome P450, were quantified simultaneously and displayed characteristic profiles under different thyroid hormone status. The level of 20-hydroxyeicosatetraenoic acid, a cytochrome P450 metabolite, was positively correlated with thyroid hormone level and possibly contributed to the elevated blood pressured in hyperthyroidism. The increased prostanoid (PG) I2 and decreased PGE2 levels in hypothyroid patients might serve to alleviate atherosclerosis associated with dyslipidemia. The elevated level of thromboxane (TX) A2, as indicated by TXB2, in hyperthyroid patients and mice treated with thyroid hormone might bring about pulmonary hypertension frequently found in hyperthyroid patients. In conclusion, our prospective study revealed that arachidonic acid metabolites were differentially affected by thyroid hormone status. Certain metabolites may be involved in cardiovascular disorders associated with thyroid diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

The ICAM-1 expression level determines the susceptibility of human endothelial cells to simulated microgravity.

PubMed

Buravkova, Ludmila B; Rudimov, Eugene G; Andreeva, Elena R; Grigoriev, Anatoly I

2018-03-01

Microgravity is a principal risk factor hampering human cardiovascular regulation during space flights. Endothelial dysfunction associated with the impaired integrity and uniformity of the monolayer represents a potential trigger for vascular damage. We characterized the expression profile of the multi-step cascade of adhesion molecules (ICAM-1, VCAM-1, E-selectin, VE-cadherin) in umbilical cord endothelial cells (ECs) after 24 h of exposure to simulated microgravity (SMG), pro-inflammatory cytokine TNF-α, and the combination of the two. Random Positioning Machine (RPM)-mediated SMG was used to mimic microgravity effects. SMG stimulated the expression of E-selectin, which is known to be involved in slowing leukocyte rolling. Primary ECs displayed heterogeneity with respect to the proportion of ICAM-1-positive cells. ECs were divided into two groups: pre-activated ECs displaying high proportion of ICAM-1 + -cells (ECs-1) (greater than 50%) and non-activated ECs with low proportion of ICAM-1 + -cells (ECs-2) (less than 25%). Only non-activated ECs-2 responded to SMG by elevating gene transcription and increasing ICAM-1 and VE-cadherin expression. This effect was enhanced after cumulative SMG-TNF-α exposure. ECs-1 displayed an unexpected decrease in number of E-selectin- and ICAM-1-positive ECs and pronounced up-regulation of VCAM1 upon activation of inflammation, which was partially abolished by SMG. Thus, non-activated ECs-2 are quite resistant to the impacts of microgravity and even exhibited an elevation of the VE-cadherin gene and protein expression, thus improving the integrity of the endothelial monolayer. Pre-activation of ECs with inflammatory stimuli may disturb the EC adhesion profile, attenuating its barrier function. These alterations may be among the mechanisms underlying cardiovascular dysregulation in real microgravity conditions. © 2017 Wiley Periodicals, Inc.

Met synergizes with p53 loss to induce mammary tumors that possess features of claudin-low breast cancer

PubMed Central

Knight, Jennifer F.; Lesurf, Robert; Zhao, Hong; Pinnaduwage, Dushanthi; Davis, Ryan R.; Saleh, Sadiq M. I.; Zuo, Dongmei; Naujokas, Monica A.; Chughtai, Naila; Herschkowitz, Jason I.; Prat, Aleix; Mulligan, Anna Marie; Muller, William J.; Cardiff, Robert D.; Gregg, Jeff P.; Andrulis, Irene L.; Hallett, Michael T.; Park, Morag

2013-01-01

Triple-negative breast cancer (TNBC) accounts for ∼20% of cases and contributes to basal and claudin-low molecular subclasses of the disease. TNBCs have poor prognosis, display frequent mutations in tumor suppressor gene p53 (TP53), and lack targeted therapies. The MET receptor tyrosine kinase is elevated in TNBC and transgenic Met models (Metmt) develop basal-like tumors. To investigate collaborating events in the genesis of TNBC, we generated Metmt mice with conditional loss of murine p53 (Trp53) in mammary epithelia. Somatic Trp53 loss, in combination with Metmt, significantly increased tumor penetrance over Metmt or Trp53 loss alone. Unlike Metmt tumors, which are histologically diverse and enriched in a basal-like molecular signature, the majority of Metmt tumors with Trp53 loss displayed a spindloid pathology with a distinct molecular signature that resembles the human claudin-low subtype of TNBC, including diminished claudins, an epithelial-to-mesenchymal transition signature, and decreased expression of the microRNA-200 family. Moreover, although mammary specific loss of Trp53 promotes tumors with diverse pathologies, those with spindloid pathology and claudin-low signature display genomic Met amplification. In both models, MET activity is required for maintenance of the claudin-low morphological phenotype, in which MET inhibitors restore cell-cell junctions, rescue claudin 1 expression, and abrogate growth and dissemination of cells in vivo. Among human breast cancers, elevated levels of MET and stabilized TP53, indicative of mutation, correlate with highly proliferative TNBCs of poor outcome. This work shows synergy between MET and TP53 loss for claudin-low breast cancer, identifies a restricted claudin-low gene signature, and provides a rationale for anti-MET therapies in TNBC. PMID:23509284

Noncanonical autophagy inhibits the auto-inflammatory, lupus-like response to dying cells

PubMed Central

Martinez, Jennifer; Cunha, Larissa D.; Park, Sunmin; Yang, Mao; Lu, Qun; Orchard, Robert; Li, Quan-Zhen; Yan, Mei; Janke, Laura; Guy, Cliff; Linkermann, Andreas; Virgin, Herbert W.; Green, Douglas R.

2016-01-01

Defects in dying cell clearance are postulated to underlie the pathogenesis of systemic lupus erythematosus (SLE)1. Mice lacking molecules associated with dying cell clearance develop SLE-like disease2, and phagocytes from SLE patients often display defective clearance and increased inflammatory cytokine production when exposed to dying cells in vitro. Previously, we3–6 and others7 described a form of noncanonical autophagy called “LC3-associated phagocytosis” (LAP), wherein phagosomes containing engulfed particles, including dying cells3,4,7, recruit elements of the autophagy pathway to facilitate phagosome maturation and digestion of cargo. Genome-wide association studies have identified polymorphisms in atg58 and possibly atg79, involved in both canonical autophagy and LAP3–7, as predisposition markers for SLE. Here, we describe the consequences of defective LAP in vivo. Mice lacking any of several components of the LAP pathway display elevated serum inflammatory cytokines, autoantibodies, glomerular immune complex deposition, and evidence of kidney damage. Dying cells, injected into LAP-deficient animals, are engulfed but not efficiently degraded, and trigger acute elevation of pro-inflammatory cytokines but not the anti-inflammatory interleukin (IL)-10. Repeated injection of dying cells into LAP-deficient, but not LAP-sufficient animals accelerated SLE-like disease, including increased serum levels of autoantibodies. In contrast, animals deficient for genes required for canonical autophagy but not LAP do not display defective dead cell clearance, inflammatory cytokine production, or SLE-like disease, and like wild-type animals, produce IL-10 in response to dying cells. Therefore, defects in LAP, rather than canonical autophagy, can cause SLE-like phenomena, and may contribute to the pathogenesis of SLE. PMID:27096368

The roles of sex and serotonin transporter levels in age- and stress-related emotionality in mice.

PubMed

Joeyen-Waldorf, Jennifer; Edgar, Nicole; Sibille, Etienne

2009-08-25

Mood disorders are influenced by genetic make-up and differentially affect men and women. The s/l promoter polymorphism in the serotonin transporter (SERT) gene moderates both trait emotion and the vulnerability to develop depressive states in humans. Similarly, male mice lacking SERT (Knockout/KO) display an elevated emotionality phenotype. We now report that the SERT-KO phenotype is maintained throughout late-adulthood, and that female KO mice develop a larger emotionality phenotype with increasing age. Thus, to test the hypothesis that these findings reflected a putative sexual dimorphism in SERT-mediated modulation of emotionality, we submitted adult male and female wild-type, heterozygous (HZ) and KO mice to unpredictable chronic mild stress (UCMS) and assessed behavioral changes. In males, the elevated SERT-KO emotion-related behavior converged with other groups after UCMS. Conversely, female SERT-KO displayed a normal non-stressed baseline, but highest UCMS-induced emotionality. SERT-HZ displayed variable and intermediate phenotypes in both experiments. Thus, consistent results across different biological modalities (age, stress) revealed a high contribution of SERT genotype for baseline "trait" emotionality in males, and low contribution for females. In contrast, age-correlated and stress-induced behavioral changes resulted in a high SERT genotype-mediated behavioral variance in females, but low in males. This suggests that high emotionality states associated with low SERT were differentially achieved in males (high baseline/trait) compared to females (increased vulnerability to develop high emotionality). This sex-by-SERT double dissociation provides a framework to investigate molecular substrates of emotionality regulation in concert with serotonin function and may contribute to the sexually dimorphic features of mood disorders.

Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling

PubMed Central

Mi, Tiejuan; Abbasi, Shahrzad; Zhang, Hong; Uray, Karen; Chunn, Janci L.; Xia, Ling Wei; Molina, Jose G.; Weisbrodt, Norman W.; Kellems, Rodney E.; Blackburn, Michael R.; Xia, Yang

2008-01-01

Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. It is common among males with sickle cell disease (SCD), and SCD transgenic mice are an accepted model of the disorder. Current strategies to manage priapism suffer from a poor fundamental understanding of the molecular mechanisms underlying the disorder. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy successfully corrected the priapic activity both in vivo and in vitro, suggesting that it was dependent on elevated adenosine levels. Further genetic and pharmacologic evidence demonstrated that A2B adenosine receptor–mediated (A2BR-mediated) cAMP and cGMP induction was required for elevated adenosine–induced prolonged penile erection. Finally, priapic activity in SCD transgenic mice was also caused by elevated adenosine levels and A2BR activation. Thus, we have shown that excessive adenosine accumulation in the penis contributes to priapism through increased A2BR signaling in both Ada–/– and SCD transgenic mice. These findings provide insight regarding the molecular basis of priapism and suggest that strategies to either reduce adenosine or block A2BR activation may prove beneficial in the treatment of this disorder. PMID:18340377

Ionoregulatory and endocrine responses to disturbed salt and water balance in Mozambique tilapia exposed to confinement and handling stress.

PubMed

Breves, Jason P; Hirano, Tetsuya; Grau, E Gordon

2010-03-01

This study assessed the endocrine and ionoregulatory responses by tilapia (Oreochromis mossambicus) to disturbances of hydromineral balance during confinement and handling. In fresh water (FW), confinement and handling for 0.5, 1, 2 and 6h produced elevations in plasma cortisol and glucose; a reduction in plasma osmolality was observed at 6h. Elevations in plasma prolactins (PRL(177) and PRL(188)) accompanied this fall in osmolality while no effect upon growth hormone (GH) was evident; an increase in insulin-like growth-factor I (IGF-I) occurred at 0.5h. In seawater (SW), confinement and handling increased plasma osmolality and glucose between 0.5 and 6h; no effect on plasma cortisol was seen due to variable control levels. Concurrently, both PRLs were reduced in stressed fish with only transient changes in the GH/IGF-I axis. Next, the branchial expression of Na(+)/K(+)/2Cl(-) cotransporter (NKCC) and Na(+)/Cl(-) cotransporter (NCC) was characterized following confinement and handling for 6h. In SW, NKCC mRNA levels increased in stressed fish concurrently with elevated plasma osmolality and diminished gill Na(+), K(+)-ATPase activity; NCC was unchanged in stressed fish irrespective of salinity. Taken together, PRL and NKCC participate in restoring osmotic balance during acute stress while the GH/IGF-I axis displays only modest responses. Copyright 2009 Elsevier Inc. All rights reserved.

Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility

PubMed Central

Mor, I; Sklan, EH; Podoly, E; Pick, M; Kirschner, M; Yogev, L; Bar-Sheshet Itach, S; Schreiber, L; Geyer, B; Mor, T; Grisaru, D; Soreq, H

2008-01-01

Abstract Changes in protein subdomains through alternative splicing often modify protein-protein interactions, altering biological processes. A relevant example is that of the stress-induced up-regulation of the acetylcholinesterase (AChE-R) splice variant, a common response in various tissues. In germ cells of male transgenic TgR mice, AChE-R excess associates with reduced sperm differentiation and sperm counts. To explore the mechanism(s) by which AChE-R up-regulation affects spermatogenesis, we identified AChE-R's protein partners through a yeast two-hybrid screen. In meiotic spermatocytes from TgR mice, we detected AChE-R interaction with the scaffold protein RACK1 and elevated apoptosis. This correlated with reduced scavenging by RACK1 of the pro-apoptotic TAp73, an outcome compatible with the increased apoptosis. In contrast, at later stages in sperm development, AChE-R's interaction with the glycolytic enzyme enolase-α elevates enolase activity. In transfected cells, enforced AChE-R excess increased glucose uptake and adenosine tri-phosphate (ATP) levels. Correspondingly, TgR sperm cells display elevated ATP levels, mitochondrial hyperactivity and increased motility. In human donors' sperm, we found direct association of sperm motility with AChE-R expression. Interchanging interactions with RACK1 and enolase-α may hence enable AChE-R to affect both sperm differentiation and function by participating in independent cellular pathways. PMID:18194455

The effects of elevated temperature and ocean acidification on the metabolic pathways of notothenioid fish

PubMed Central

Enzor, Laura A.; Hunter, Evan M.

2017-01-01

Abstract The adaptations used by notothenioid fish to combat extreme cold may have left these fish poorly poised to deal with a changing environment. As such, the expected environmental perturbations brought on by global climate change have the potential to significantly affect the energetic demands and subsequent cellular processes necessary for survival. Despite recent lines of evidence demonstrating that notothenioid fish retain the ability to acclimate to elevated temperatures, the underlying mechanisms responsible for temperature acclimation in these fish remain largely unknown. Furthermore, little information exists on the capacity of Antarctic fish to respond to changes in multiple environmental variables. We have examined the effects of increased temperature and pCO2 on the rate of oxygen consumption in three notothenioid species, Trematomus bernacchii, Pagothenia borchgrevinki, and Trematomus newnesi. We combined these measurements with analysis of changes in aerobic and anaerobic capacity, lipid reserves, fish condition, and growth rates to gain insight into the metabolic cost associated with acclimation to this dual stress. Our findings indicated that temperature is the major driver of the metabolic responses observed in these fish and that increased pCO2 plays a small, contributing role to the energetic costs of the acclimation response. All three species displayed varying levels of energetic compensation in response to the combination of elevated temperature and pCO2. While P. borchgrevinki showed nearly complete compensation of whole animal oxygen consumption rates and aerobic capacity, T. newnesi and T. bernacchii displayed only partial compensation in these metrics, suggesting that at least some notothenioids may require physiological trade-offs to fully offset the energetic costs of long-term acclimation to climate change related stressors. PMID:28852515

The effects of elevated temperature and ocean acidification on the metabolic pathways of notothenioid fish.

PubMed

Enzor, Laura A; Hunter, Evan M; Place, Sean P

2017-01-01

The adaptations used by notothenioid fish to combat extreme cold may have left these fish poorly poised to deal with a changing environment. As such, the expected environmental perturbations brought on by global climate change have the potential to significantly affect the energetic demands and subsequent cellular processes necessary for survival. Despite recent lines of evidence demonstrating that notothenioid fish retain the ability to acclimate to elevated temperatures, the underlying mechanisms responsible for temperature acclimation in these fish remain largely unknown. Furthermore, little information exists on the capacity of Antarctic fish to respond to changes in multiple environmental variables. We have examined the effects of increased temperature and p CO 2 on the rate of oxygen consumption in three notothenioid species, Trematomus bernacchii , Pagothenia borchgrevinki , and Trematomus newnesi . We combined these measurements with analysis of changes in aerobic and anaerobic capacity, lipid reserves, fish condition, and growth rates to gain insight into the metabolic cost associated with acclimation to this dual stress. Our findings indicated that temperature is the major driver of the metabolic responses observed in these fish and that increased p CO 2 plays a small, contributing role to the energetic costs of the acclimation response. All three species displayed varying levels of energetic compensation in response to the combination of elevated temperature and p CO 2 . While P. borchgrevinki showed nearly complete compensation of whole animal oxygen consumption rates and aerobic capacity, T. newnesi and T. bernacchii displayed only partial compensation in these metrics, suggesting that at least some notothenioids may require physiological trade-offs to fully offset the energetic costs of long-term acclimation to climate change related stressors.

Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.

PubMed

Ravenelle, Rebecca; Berman, Ariel K; La, Jeffrey; Mason, Briana; Asumadu, Evans; Yelleswarapu, Chandra; Donaldson, S Tiffany

2018-04-01

In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala, while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Co-ordination of physiological and morphological responses of stomata to elevated [CO2] in vascular plants.

PubMed

Haworth, Matthew; Elliott-Kingston, Caroline; McElwain, Jennifer C

2013-01-01

Plant stomata display a wide range of short-term behavioural and long-term morphological responses to atmospheric carbon dioxide concentration ([CO(2)]). The diversity of responses suggests that plants may have different strategies for controlling gas exchange, yet it is not known whether these strategies are co-ordinated in some way. Here, we test the hypothesis that there is co-ordination of physiological (via aperture change) and morphological (via stomatal density change) control of gas exchange by plants. We examined the response of stomatal conductance (G(s)) to instantaneous changes in external [CO(2)] (C(a)) in an evolutionary cross-section of vascular plants grown in atmospheres of elevated [CO(2)] (1,500 ppm) and sub-ambient [O(2)] (13.0 %) compared to control conditions (380 ppm CO(2), 20.9 % O(2)). We found that active control of stomatal aperture to [CO(2)] above current ambient levels was not restricted to angiosperms, occurring in the gymnosperms Lepidozamia peroffskyana and Nageia nagi. The angiosperm species analysed appeared to possess a greater respiratory demand for stomatal movement than gymnosperm species displaying active stomatal control. Those species with little or no control of stomatal aperture (termed passive) to C(a) were more likely to exhibit a reduction in stomatal density than species with active stomatal control when grown in atmospheres of elevated [CO(2)]. The relationship between the degree of stomatal aperture control to C(a) above ambient and the extent of any reduction in stomatal density may suggest the co-ordination of physiological and morphological responses of stomata to [CO(2)] in the optimisation of water use efficiency. This trade-off between stomatal control strategies may have developed due to selective pressures exerted by the costs associated with passive and active stomatal control.

Aircraft control position indicator

NASA Technical Reports Server (NTRS)

Dennis, Dale V. (Inventor)

1987-01-01

An aircraft control position indicator was provided that displayed the degree of deflection of the primary flight control surfaces and the manner in which the aircraft responded. The display included a vertical elevator dot/bar graph meter display for indication whether the aircraft will pitch up or down, a horizontal aileron dot/bar graph meter display for indicating whether the aircraft will roll to the left or to the right, and a horizontal dot/bar graph meter display for indicating whether the aircraft will turn left or right. The vertical and horizontal display or displays intersect to form an up/down, left/right type display. Internal electronic display driver means received signals from transducers measuring the control surface deflections and determined the position of the meter indicators on each dot/bar graph meter display. The device allows readability at a glance, easy visual perception in sunlight or shade, near-zero lag in displaying flight control position, and is not affected by gravitational or centrifugal forces.

Regulator of calmodulin signaling (RCS) knockout mice display anxiety-like behavior and motivational deficits

PubMed Central

Davis, Maya M.; Olausson, Peter; Greengard, Paul; Taylor, Jane R.; Nairn, Angus C.

2013-01-01

Regulator of calmodulin (CaM) signaling (RCS), when phosphorylated by protein kinase A (PKA) on Ser55, binds to CaM and inhibits CaM-dependent signaling. RCS expression is high in the dorsal striatum, nucleus accumbens and amygdala, suggesting that the protein is involved in limbic-striatal function. To test this hypothesis, we examined RCS knockout (KO) mice in behavioral models dependent on these brain areas. Mice were tested for food-reinforced instrumental conditioning and responding under a progressive ratio (PR) schedule of reinforcement and in models of anxiety (elevated plus maze and open field). While RCS KO mice showed normal acquisition of a food-motivated instrumental response, they exhibited a lower breakpoint value when tested on responding under a PR schedule of reinforcement. RCS KO mice also displayed decreased exploration in both the open arms of an elevated plus maze and in the center region of an open field, suggesting an enhanced anxiety response. Biochemical studies revealed a reduction in the levels of dopamine and cAMP-regulated phosphoprotein (DARPP-32) in the striatum of RCS KO mice. DARPP-32 is important in reward-mediated behavior, suggestive of a possible role for DARPP-32 in mediating some of the effects of RCS. Together these results implicate a novel PKA-regulated phosphoprotein, RCS, in the etiology of motivational deficits and anxiety. PMID:22250817

Dietary silymarin supplementation promotes growth performance and improves lipid metabolism and health status in grass carp (Ctenopharyngodon idellus) fed diets with elevated lipid levels.

PubMed

Xiao, Peizhen; Ji, Hong; Ye, Yuantu; Zhang, Baotong; Chen, Yongsheng; Tian, Jingjing; Liu, Pin; Chen, Liqiao; Du, Zhenyu

2017-02-01

This study was carried out to evaluate whether silymarin supplementation influences growth, lipid metabolism, and health status in grass carp fed elevated dietary lipid levels. The juvenile fish (27.43 ± 0.17 g/tail) were fed six isonitrogenous and isocaloric diets in a factorial design containing 0, 100, or 200 mg kg -1 silymarin (SM0, SM100, SM200) associated with either 4 or 8 % lipid level (low lipid, LL, and high lipid, HL, respectively) for 82 days. The results showed that both dietary silymarin supplementation and high lipid level significantly enhanced growth performance (WG, SGR), protein efficiency ratio, and feed utilization. Silymarin supplementation significantly reduced the VSI, hepatic lipid content, and the total bilirubin concentration in the serum. The gallbladdersomatic index displayed higher in the SM100 groups than SM200 groups. Serum total cholesterol content exhibited lower in the SM100 groups than SM0 groups. Meanwhile, significant interactions were shown for hepatic gene expression of HSL and CPT1 by two factors, and SM100 group had higher hepatic gene expression of HSL and CPT1 in fish fed with the HL diets. The SM100 groups up-regulated hepatic gene expressions of HMGCR and CYP7A1 compared with the SM0 groups. Silymarin supplementation notably reduced the elevated serum MDA content induced by HL treatments. Thus, silymarin supplementation markedly promoted growth and protein efficiency, suppressed lipid accumulation, and improved health status in grass carp fed with high-lipid diets, which might be associated with its enhancement of lipolysis and β-oxidation, antioxidant capacity.

Preoperative Statin Therapy in Cardiac Surgery Is More Effective in Patients Who Display Preoperative Activation of the Inflammatory System

PubMed Central

Martínez-Comendador, José; Alvarez, José Rubio; Sierra, Juan; Teijeira, Elvis; Adrio, Belén

2013-01-01

We sought to determine whether preoperative statin treatment is more effective in reducing, after cardiac surgery with cardiopulmonary bypass, systemic inflammatory response and myocardial damage markers in patients who have elevated preoperative interleukin-6 levels than in patients who have normal preoperative interleukin-6 levels. The study involved a prospective cohort of 164 patients who underwent coronary and valvular surgery with cardiopulmonary bypass. There were 2 study groups: group A (n = 60), patients with elevated preoperative interleukin-6 levels; and group B (n = 104), patients with normal preoperative interleukin-6 levels. Each group was subdivided according to whether patients were (group 1) or were not (group 2) treated preoperatively with statins. Accordingly, the subdivided study groups were A1 (n = 40), A2 (n = 20), B1 (n = 56), and B2 (n = 48). The plasma levels of proinflammatory interleukin-6 were measured 1, 6, 24, and >72 hours after surgery. The baseline, operative, and postoperative morbidity and mortality characteristics were similar in all groups. Group A1 had significantly lower levels of interleukin-6 and troponin I than did group A2 at all postoperative time points. Group B1 had significantly lower levels of interleukin-6 than did group B2 postoperatively. There were no significant differences in troponin I levels between groups B1 and B2. We conclude that, in patients with preoperative activation of the inflammatory system, preoperative treatment with statins is associated with lower postoperative interleukin-6 and troponin I levels after cardiac surgery with cardiopulmonary bypass. PMID:23466655

Preoperative statin therapy in cardiac surgery is more effective in patients who display preoperative activation of the inflammatory system.

PubMed

Martínez-Comendador, José; Alvarez, José Rubio; Sierra, Juan; Teijeira, Elvis; Adrio, Belén

2013-01-01

We sought to determine whether preoperative statin treatment is more effective in reducing, after cardiac surgery with cardiopulmonary bypass, systemic inflammatory response and myocardial damage markers in patients who have elevated preoperative interleukin-6 levels than in patients who have normal preoperative interleukin-6 levels. The study involved a prospective cohort of 164 patients who underwent coronary and valvular surgery with cardiopulmonary bypass. There were 2 study groups: group A (n = 60), patients with elevated preoperative interleukin-6 levels; and group B (n = 104), patients with normal preoperative interleukin-6 levels. Each group was subdivided according to whether patients were (group 1) or were not (group 2) treated preoperatively with statins. Accordingly, the subdivided study groups were A1 (n = 40), A2 (n = 20), B1 (n = 56), and B2 (n = 48). The plasma levels of proinflammatory interleukin-6 were measured 1, 6, 24, and >72 hours after surgery. The baseline, operative, and postoperative morbidity and mortality characteristics were similar in all groups. Group A1 had significantly lower levels of interleukin-6 and troponin I than did group A2 at all postoperative time points. Group B1 had significantly lower levels of interleukin-6 than did group B2 postoperatively. There were no significant differences in troponin I levels between groups B1 and B2. We conclude that, in patients with preoperative activation of the inflammatory system, preoperative treatment with statins is associated with lower postoperative interleukin-6 and troponin I levels after cardiac surgery with cardiopulmonary bypass.

Mixed housing with DBA/2 mice induces stress in C57BL/6 mice: implications for interventions based on social enrichment

PubMed Central

Kulesskaya, Natalia; Karpova, Nina N.; Ma, Li; Tian, Li; Voikar, Vootele

2014-01-01

Several behavioral interventions, based on social enrichment and observational learning are applied in treatment of neuropsychiatric disorders. However, the mechanism of such modulatory effect and the safety of applied methods on individuals involved in social support need further investigation. We took advantage of known differences between inbred mouse strains to reveal the effect of social enrichment on behavior and neurobiology of animals with different behavioral phenotypes. C57BL/6 and DBA/2 female mice displaying multiple differences in cognitive, social, and emotional behavior were group-housed either in same-strain or in mixed-strain conditions. Comprehensive behavioral phenotyping and analysis of expression of several plasticity- and stress-related genes were done to measure the reciprocal effects of social interaction between the strains. Contrary to our expectation, mixed housing did not change the behavior of DBA/2 mice. Nevertheless, the level of serum corticosterone and the expression of glucocorticoid receptor Nr3c1 in the brain were increased in mixed housed DBA/2 as compared with those of separately housed DBA/2 mice. In contrast, socially active C57BL/6 animals were more sensitive to the mixed housing, displaying several signs of stress: alterations in learning, social, and anxiety-like behavior and anhedonia. These behavioral impairments were accompanied by the elevated serum corticosterone and the reduced expression of Nr3c1, as well as the elevated Bdnf levels in the cortex and hippocampus. Our results demonstrate the importance of social factors in modulation of both behavior and the underlying neurobiological mechanisms in stress response, and draw attention to the potential negative impact of social interventions for individuals involved in social support. PMID:25147512

Projected near-future CO2 levels increase activity and alter defensive behaviours in the tropical squid Idiosepius pygmaeus

PubMed Central

Spady, Blake L.; Watson, Sue-Ann; Chase, Tory J.; Munday, Philip L.

2014-01-01

ABSTRACT Carbon dioxide (CO2) levels projected to occur in the oceans by the end of this century cause a range of behavioural effects in fish, but whether other highly active marine organisms, such as cephalopods, are similarly affected is unknown. We tested the effects of projected future CO2 levels (626 and 956 µatm) on the behaviour of male two-toned pygmy squid, Idiosepius pygmaeus. Exposure to elevated CO2 increased the number of active individuals by 19–25% and increased movement (number of line-crosses) by nearly 3 times compared to squid at present-day CO2. Squid vigilance and defensive behaviours were also altered by elevated CO2 with >80% of individuals choosing jet escape responses over defensive arm postures in response to a visual startle stimulus, compared with 50% choosing jet escape responses at control CO2. In addition, more escape responses were chosen over threat behaviours in body pattern displays at elevated CO2 and individuals were more than twice as likely to use ink as a defence strategy at 956 µatm CO2, compared with controls. Increased activity could lead to adverse effects on energy budgets as well as increasing visibility to predators. A tendency to respond to a stimulus with escape behaviours could increase survival, but may also be energetically costly and could potentially lead to more chases by predators compared with individuals that use defensive postures. These results demonstrate that projected future ocean acidification affects the behaviours of a tropical squid species. PMID:25326517

Estimating the Spatial and Temporal Distribution of Species Richness within Sequoia and Kings Canyon National Parks

PubMed Central

Wathen, Steve; Thorne, James H.; Holguin, Andrew; Schwartz, Mark W.

2014-01-01

Evidence for significant losses of species richness or biodiversity, even within protected natural areas, is mounting. Managers are increasingly being asked to monitor biodiversity, yet estimating biodiversity is often prohibitively expensive. As a cost-effective option, we estimated the spatial and temporal distribution of species richness for four taxonomic groups (birds, mammals, herpetofauna (reptiles and amphibians), and plants) within Sequoia and Kings Canyon National Parks using only existing biological studies undertaken within the Parks and the Parks' long-term wildlife observation database. We used a rarefaction approach to model species richness for the four taxonomic groups and analyzed those groups by habitat type, elevation zone, and time period. We then mapped the spatial distributions of species richness values for the four taxonomic groups, as well as total species richness, for the Parks. We also estimated changes in species richness for birds, mammals, and herpetofauna since 1980. The modeled patterns of species richness either peaked at mid elevations (mammals, plants, and total species richness) or declined consistently with increasing elevation (herpetofauna and birds). Plants reached maximum species richness values at much higher elevations than did vertebrate taxa, and non-flying mammals reached maximum species richness values at higher elevations than did birds. Alpine plant communities, including sagebrush, had higher species richness values than did subalpine plant communities located below them in elevation. These results are supported by other papers published in the scientific literature. Perhaps reflecting climate change: birds and herpetofauna displayed declines in species richness since 1980 at low and middle elevations and mammals displayed declines in species richness since 1980 at all elevations. PMID:25469873

Estimating the spatial and temporal distribution of species richness within Sequoia and Kings Canyon National Parks.

PubMed

Wathen, Steve; Thorne, James H; Holguin, Andrew; Schwartz, Mark W

2014-01-01

Evidence for significant losses of species richness or biodiversity, even within protected natural areas, is mounting. Managers are increasingly being asked to monitor biodiversity, yet estimating biodiversity is often prohibitively expensive. As a cost-effective option, we estimated the spatial and temporal distribution of species richness for four taxonomic groups (birds, mammals, herpetofauna (reptiles and amphibians), and plants) within Sequoia and Kings Canyon National Parks using only existing biological studies undertaken within the Parks and the Parks' long-term wildlife observation database. We used a rarefaction approach to model species richness for the four taxonomic groups and analyzed those groups by habitat type, elevation zone, and time period. We then mapped the spatial distributions of species richness values for the four taxonomic groups, as well as total species richness, for the Parks. We also estimated changes in species richness for birds, mammals, and herpetofauna since 1980. The modeled patterns of species richness either peaked at mid elevations (mammals, plants, and total species richness) or declined consistently with increasing elevation (herpetofauna and birds). Plants reached maximum species richness values at much higher elevations than did vertebrate taxa, and non-flying mammals reached maximum species richness values at higher elevations than did birds. Alpine plant communities, including sagebrush, had higher species richness values than did subalpine plant communities located below them in elevation. These results are supported by other papers published in the scientific literature. Perhaps reflecting climate change: birds and herpetofauna displayed declines in species richness since 1980 at low and middle elevations and mammals displayed declines in species richness since 1980 at all elevations.

The spatial and temporal trends of Cd, Cu, Hg, Pb and Zn in Seine River floodplain deposits (1994-2000)

USGS Publications Warehouse

Grosbois, C.; Meybeck, Michel; Horowitz, A.; Ficht, A.

2006-01-01

Fresh floodplain deposits (FD), from 11 key stations, covering the Seine mainstem and its major tributaries (Yonne, Marne and Oise Rivers), were sampled from 1994 to 2000. Background levels for Cd, Cu, Hg, Pb, and Zn were established using prehistoric FD and actual bed sediments collected in small forested sub-basins in the most upstream part of the basin. Throughout the Seine River Basin, FD contain elevated concentrations of Cd, Cu, Hg, Pb and Zn compared to local background values (by factors > twofold). In the Seine River Basin, trace element concentrations display substantial downstream increases as a result of increasing population densities, particularly from Greater Paris (10 million inhabitants), and reach their maxima at the river mouth (Poses). These elevated levels make the Seine one of the most heavily impacted rivers in the world. On the other hand, floodplain-associated trace element levels have declined over the past 7 years. This mirrors results from contemporaneous suspended sediment surveys at the river mouth for the 1984-1999 period. Most of these temporal declines appear to reflect reductions in industrial and domestic solid wastes discharged from the main Parisian sewage plant (Seine Aval). ?? 2005 Elsevier B.V. All rights reserved.

Metabolic effects of physiological levels of caffeine in myotubes.

PubMed

Schnuck, Jamie K; Gould, Lacey M; Parry, Hailey A; Johnson, Michele A; Gannon, Nicholas P; Sunderland, Kyle L; Vaughan, Roger A

2018-02-01

Caffeine has been shown to stimulate multiple major regulators of cell energetics including AMP-activated protein kinase (AMPK) and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII). Additionally, caffeine induces peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial biogenesis. While caffeine enhances oxidative metabolism, experimental concentrations often exceed physiologically attainable concentrations through diet. This work measured the effects of low-level caffeine on cellular metabolism and gene expression in myotubes, as well as the dependence of caffeine's effects on the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARβ/δ). C2C12 myotubes were treated with various doses of caffeine for up to 24 h. Gene and protein expression were measured via qRT-PCR and Western blot, respectively. Cellular metabolism was determined via oxygen consumption and extracellular acidification rate. Caffeine significantly induced regulators of mitochondrial biogenesis and oxidative metabolism. Mitochondrial staining was suppressed in PPARβ/δ-inhibited cells which was rescued by concurrent caffeine treatment. Caffeine-treated cells also displayed elevated peak oxidative metabolism which was partially abolished following PPARβ/δ inhibition. Similar to past observations, glucose uptake and GLUT4 content were elevated in caffeine-treated cells, however, glycolytic metabolism was unaltered following caffeine treatment. Physiological levels of caffeine appear to enhance cell metabolism through mechanisms partially dependent on PPARβ/δ.

Evidence for label-retaining tumour-initiating cells in human glioblastoma

PubMed Central

Deleyrolle, Loic P.; Harding, Angus; Cato, Kathleen; Siebzehnrubl, Florian A.; Rahman, Maryam; Azari, Hassan; Olson, Sarah; Gabrielli, Brian; Osborne, Geoffrey; Vescovi, Angelo

2011-01-01

Individual tumour cells display diverse functional behaviours in terms of proliferation rate, cell–cell interactions, metastatic potential and sensitivity to therapy. Moreover, sequencing studies have demonstrated surprising levels of genetic diversity between individual patient tumours of the same type. Tumour heterogeneity presents a significant therapeutic challenge as diverse cell types within a tumour can respond differently to therapies, and inter-patient heterogeneity may prevent the development of general treatments for cancer. One strategy that may help overcome tumour heterogeneity is the identification of tumour sub-populations that drive specific disease pathologies for the development of therapies targeting these clinically relevant sub-populations. Here, we have identified a dye-retaining brain tumour population that displays all the hallmarks of a tumour-initiating sub-population. Using a limiting dilution transplantation assay in immunocompromised mice, label-retaining brain tumour cells display elevated tumour-initiation properties relative to the bulk population. Importantly, tumours generated from these label-retaining cells exhibit all the pathological features of the primary disease. Together, these findings confirm dye-retaining brain tumour cells exhibit tumour-initiation ability and are therefore viable targets for the development of therapeutics targeting this sub-population. PMID:21515906

Sustained enhancement of photosynthesis in coffee trees grown under free-air CO2 enrichment conditions: disentangling the contributions of stomatal, mesophyll, and biochemical limitations

PubMed Central

DaMatta, Fábio M.; Godoy, Alice G.; Menezes-Silva, Paulo E.; Martins, Samuel C.V.; Sanglard, Lílian M.V.P.; Morais, Leandro E.; Torre-Neto, André; Ghini, Raquel

2016-01-01

Coffee (Coffea spp.), a globally traded commodity, is a slow-growing tropical tree species that displays an improved photosynthetic performance when grown under elevated atmospheric CO2 concentrations ([CO2]). To investigate the mechanisms underlying this response, two commercial coffee cultivars (Catuaí and Obatã) were grown using the first free-air CO2 enrichment (FACE) facility in Latin America. Measurements were conducted in two contrasting growth seasons, which were characterized by the high (February) and low (August) sink demand. Elevated [CO2] led to increases in net photosynthetic rates (A) in parallel with decreased photorespiration rates, with no photochemical limitations to A. The stimulation of A by elevated CO2 supply was more prominent in August (56% on average) than in February (40% on average). Overall, the stomatal and mesophyll conductances, as well as the leaf nitrogen and phosphorus concentrations, were unresponsive to the treatments. Photosynthesis was strongly limited by diffusional constraints, particularly at the stomata level, and this pattern was little, if at all, affected by elevated [CO2]. Relative to February, starch pools (but not soluble sugars) increased remarkably (>500%) in August, with no detectable alteration in the maximum carboxylation capacity estimated on a chloroplast [CO2] basis. Upregulation of A by elevated [CO2] took place with no signs of photosynthetic downregulation, even during the period of low sink demand, when acclimation would be expected to be greatest. PMID:26503540

The impact of cortisol in steatotic and non-steatotic liver surgery.

PubMed

Cornide-Petronio, María Eugenia; Bujaldon, Esther; Mendes-Braz, Mariana; Avalos de León, Cindy G; Jiménez-Castro, Mónica B; Álvarez-Mercado, Ana I; Gracia-Sancho, Jordi; Rodés, Juan; Peralta, Carmen

2017-10-01

The intent of this study was to examine the effects of regulating cortisol levels on damage and regeneration in livers with and without steatosis subjected to partial hepatectomy under ischaemia-reperfusion. Ultimately, we found that lean animals undergoing liver resection displayed no changes in cortisol, whereas cortisol levels in plasma, liver and adipose tissue were elevated in obese animals undergoing such surgery. Such elevations were attributed to enzymatic upregulation, ensuring cortisol production, and downregulation of enzymes controlling cortisol clearance. In the absence of steatosis, exogenous cortisol administration boosted circulating cortisol, while inducing clearance of hepatic cortisol, thus maintaining low cortisol levels and preventing related hepatocellular harm. In the presence of steatosis, cortisol administration was marked by a substantial rise in intrahepatic availability, thereby exacerbating tissue damage and regenerative failure. The injurious effects of cortisol were linked to high hepatic acethylcholine levels. Upon administering an α7 nicotinic acethylcholine receptor antagonist, no changes in terms of tissue damage or regenerative lapse were apparent in steatotic livers. However, exposure to an M3 muscarinic acetylcholine receptor antagonist protected livers against damage, enhancing parenchymal regeneration and survival rate. These outcomes for the first time provide new mechanistic insight into surgically altered steatotic livers, underscoring the compelling therapeutic potential of cortisol-acetylcholine-M3 muscarinic receptors. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Two adult siblings with atypical cryopyrin-associated periodic syndrome due to a novel M299V mutation in NLRP3.

PubMed

Verma, Deepti; Eriksson, Per; Sahdo, Berolla; Persson, Alexander; Ejdebäck, Mikael; Särndahl, Eva; Söderkvist, Peter

2010-07-01

The NALP3 inflammasome is a multiprotein complex that triggers caspase 1-mediated interleukin-1beta (IL-1beta) release. Mutations in the gene encoding NALP3 (NLRP3) underlie the cryopyrin-associated periodic syndrome (CAPS). The aim of this study was to report a novel NLRP3 mutation in 2 siblings of Swedish descent in whom symptoms first presented in adulthood. Mutation analysis of NLRP3 was performed on DNA from patients with CAPS and 100 control subjects. For assessment of caspase 1 and IL-1beta, blood was collected from patients and age- and sex-matched healthy control subjects. Genetic constructs containing mutant or wild-type NLRP3 were transduced into THP-1 cells, followed by assessment of IL-1beta levels in cell supernatant. Both siblings carried a novel M299V mutation in NLRP3, which was not present in the control population. The samples obtained from the patients displayed increased caspase 1 activity and elevated IL-1beta levels at basal conditions as compared with healthy control subjects. THP-1 cells expressing mutated M299V revealed almost 10-fold higher IL-1beta production compared with the wild-type construct. M299V is an activating mutation in NLRP3 resulting in elevated spontaneous caspase 1 activity and IL-1beta levels. The classic CAPS phenotype was lacking in these adult siblings. Whereas one sibling displayed a milder phenotype that has so far responded satisfactorily to oral nonsteroidal antiinflammatory drugs in combination with low-dose corticosteroids, the inflammatory symptoms in the sibling with the more severe case responded well to IL-1beta blockade. Understanding the pathogenic mechanism underlying such disorders can be helpful for the physician. Our study reinforces the importance of genetic testing and laboratory investigations in combination with careful phenotypic evaluation for the diagnosis of such patients.

Increased linear bone growth by GH in the absence of SOCS2 is independent of IGF-1.

PubMed

Dobie, Ross; Ahmed, Syed F; Staines, Katherine A; Pass, Chloe; Jasim, Seema; MacRae, Vicky E; Farquharson, Colin

2015-11-01

Growth hormone (GH) signaling is essential for postnatal linear bone growth, but the relative importance of GHs actions on the liver and/or growth plate cartilage remains unclear. The importance of liver derived insulin like-growth factor-1 (IGF-1) for endochondral growth has recently been challenged. Here, we investigate linear growth in Suppressor of Cytokine Signaling-2 (SOCS2) knockout mice, which have enhanced growth despite normal systemic GH/IGF-1 levels. Wild-type embryonic ex vivo metatarsals failed to exhibit increased linear growth in response to GH, but displayed increased Socs2 transcript levels (P < 0.01). In the absence of SOCS2, GH treatment enhanced metatarsal linear growth over a 12 day period. Despite this increase, IGF-1 transcript and protein levels were not increased in response to GH. In accordance with these data, IGF-1 levels were unchanged in GH-challenged postnatal Socs2(-/-) conditioned medium despite metatarsals showing enhanced linear growth. Growth-plate Igf1 mRNA levels were not elevated in juvenile Socs2(-/-) mice. GH did however elevate IGF-binding protein 3 levels in conditioned medium from GH challenged metatarsals and this was more apparent in Socs2(-/-) metatarsals. GH did not enhance the growth of Socs2(-/-) metatarsals when the IGF receptor was inhibited, suggesting that IGF receptor mediated mechanisms are required. IGF-2 may be responsible as IGF-2 promoted metatarsal growth and Igf2 expression was elevated in Socs2(-/-) (but not WT) metatarsals in response to GH. These studies emphasise the critical importance of SOCS2 in regulating GHs ability to promote bone growth. Also, GH appears to act directly on the metatarsals of Socs2(-/-) mice, promoting growth via a mechanism that is independent of IGF-1. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients.

PubMed

Danese, S; Katz, J A; Saibeni, S; Papa, A; Gasbarrini, A; Vecchi, M; Fiocchi, C

2003-10-01

The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. CD, UC, and normal control subjects were studied. The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

Temporal patterns of rat behaviour in the central platform of the elevated plus maze. Comparative analysis between male subjects of strains with different basal levels of emotionality.

PubMed

Casarrubea, M; Faulisi, F; Caternicchia, F; Santangelo, A; Di Giovanni, G; Benigno, A; Magnusson, M S; Crescimanno, G

2016-08-01

We have analyzed the temporal patterns of behaviour of male rats of the Wistar and DA/Han strains on the central platform of the elevated plus maze. The ethogram encompassed 10 behavioural elements. Durations, frequencies and latencies showed quantitative differences as to walking and sniffing activities. Wistar rats displayed significantly lower latency and significantly higher durations and frequencies of walking activities. DA/Han rats showed a significant increase of sniffing duration. In addition, DA/Han rats showed a significantly higher amount of time spent in the central platform. Multivariate T-pattern analysis revealed differences in the temporal organization of behaviour of the two rat strains. DA/Han rats showed (a) higher behavioural complexity and variability and (b) a significantly higher mean number of T-patterns than Wistar rats. Taken together, T-pattern analysis of behaviour in the centre of the elevated plus maze can noticeably improve the detection of subtle features of anxiety related behaviour. We suggest that T-pattern analysis could be used as sensitive tool to test the action of anxiolytic and anxiogenic manipulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

PubMed

Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

2005-09-08

It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

[A case of hypothyroidism displaying "dropped head" syndrome].

PubMed

Furutani, Rikiya; Ishihara, Kenji; Miyazawa, Yumi; Suzuki, Yoshio; Shiota, Jun-Ichi; Kawamur, Mitsuru

2007-01-01

We describe a patient with hypothyroidism displaying "dropped head" syndrome. A 50-year-old man visited our clinic because he was unable to hold his head in the natural position. He had weakness and hypertrophy of the neck extensor muscles. Tendon reflexes were diminished or absent in all limbs. Mounding phenomena were observed in the bilateral upper extremities. Blood biochemical analysis revealed hypothyroidism, hyperlipidemia, and elevated levels of muscle-derived enzymes. Magnetic resonance imaging (MRI) of the neck demonstrated swelling and hyperintensity of the neck extensor muscles on T2-weighted images. The result of biopsy of the right biceps brachii muscle suggested mild atrophy of type 2 fibers. The diameters of the muscle fibers exhibited mild variation. No inflammatory changes were observed. We diagnosed hin as having "dropped head" syndrome due to hypothyroidism. Administration of thyroid hormone agent gradually improved his condition, and he became able to hold his head in the natural position. Levels of muscle-derived enzymes normalized and his hyperlipidemia remitted. Neck MRI also revealed improvement. Our findings suggest that hypothyroidism should be considered in the differential diagnosis of "dropped head" syndrome, although only a few cases like ours have been reported.

Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly.

PubMed

Martín-Rodríguez, Juan F; Muñoz-Bravo, Jose L; Ibañez-Costa, Alejandro; Fernandez-Maza, Laura; Balcerzyk, Marcin; Leal-Campanario, Rocío; Luque, Raúl M; Castaño, Justo P; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso; Cano, David A

2015-11-09

Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors.

Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly

PubMed Central

Martín-Rodríguez, Juan F.; Muñoz-Bravo, Jose L.; Ibañez-Costa, Alejandro; Fernandez-Maza, Laura; Balcerzyk, Marcin; Leal-Campanario, Rocío; Luque, Raúl M.; Castaño, Justo P.; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso; Cano, David A.

2015-01-01

Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors. PMID:26549306

Optical and morpho-functional traits of the leaves of tree species growing in a mountain cloud forest

NASA Astrophysics Data System (ADS)

Velázquez-Rosas, Noé; Barradas, Víctor L.; Vázquez-Santana, Sonia; Cruz-Ortega, Rocio; García-Jiménez, Federico; Toledo-Alvarado, Edith; Orozco-Segovia, Alma

2010-11-01

The physiological, anatomical and optical leaf properties relative to photosynthetically active (PAR) and ultraviolet (UV-B) radiation were assessed in Ticodendron incognitum, Drimys granadensis, Podocarpus matudae var. macrocarpus and Vaccinium consanguineum, growing along an elevation gradient (1520-2550 m asl) in a montane cloud forest in México. PAR and UV-B absorptance, transmittance and reflectance, UV-B absorptance by foliar compounds, chlorophylls, carotenoids, leaf nitrogen, leaf mass per area, leaf blades, cuticles, epidermis and parenchymas thickness were measured. PAR absorptance efficiencies were calculated. Among the evaluated morpho-functional traits, the studied species displayed different patterns of variation with elevation. Leaf traits could be explained in part by changes in elevation or the distribution of PAR and UV-B in the elevation gradient. Ticodendron and Drimys leaf traits were likely determined by two cloud banks located at 1940 and 2380 m. In Vaccinium, eight traits were related to elevation and PAR or UV-B. Contrary to this, in Podocarpus, most of the nine leaf traits could be explained by only one of these factors. The morphological traits of the studied species were similar to those of species growing in other oligotrophic ecosystems. Significant differences between sun exposed and shade leaves were limited to particular elevations or to particular traits of each species. Vaccinium showed more significant differences between sun and shade leaves than did the other species growing along the gradient. The morpho-functional traits measured in Podocarpus and Vaccinium showed that, some leaf traits did not change linearly with elevation or PAR. At elevation levels where species co-occur, the species ranking with respect to evaluated traits varied from trait to trait. This indicate that each species copes with light and other environmental factors, that vary with elevation, according to its morpho-functional plasticity and susceptibility to these factors; which may determine the distribution of these species along the gradient.

Expression of hypoxia-inducible carbonic anhydrases in brain tumors

PubMed Central

Proescholdt, Martin A.; Mayer, Christina; Kubitza, Marion; Schubert, Thomas; Liao, Shu-Yuan; Stanbridge, Eric J.; Ivanov, Sergey; Oldfield, Edward H.; Brawanski, Alexander; Merrill, Marsha J.

2005-01-01

Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel–Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-1α staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target. PMID:16212811

Can motivational signs prompt increases in incidental physical activity in an Australian health-care facility?

PubMed

Marshall, A L; Bauman, A E; Patch, C; Wilson, J; Chen, J

2002-12-01

This study aimed to evaluate whether a stair-promoting signed intervention could increase the use of the stairs over the elevator in a health-care facility. A time-series design was conducted over 12 weeks. Data were collected before, during and after displaying a signed intervention during weeks 4-5 and 8-9. Evaluation included anonymous counts recorded by an objective unobtrusive motion-sensing device of people entering the elevator or the stairs. Self-report data on stair use by hospital staff were also collected. Stair use significantly increased after the first intervention phase (P = 0.02), but after the intervention was removed stair use decreased back towards baseline levels. Moreover, stair use did not significantly change after the re-introduction of the intervention. Lastly, stair use decreased below the initial baseline level during the final weeks of evaluation. Furthermore, there was no significant change in self-reported stair use by hospital staff. Therefore, the signed intervention aimed at promoting an increase in incidental physical activity produced small brief effects, which were not maintained. Further research is required to find more effective 'point of choice' interventions to increase incidental physical activity participation with more sustainable impact.

Using X-band Weather Radar Measurements to Monitor the Integrity of Digital Elevation Models for Synthetic Vision Systems

NASA Technical Reports Server (NTRS)

Young, Steve; UijtdeHaag, Maarten; Sayre, Jonathon

2003-01-01

Synthetic Vision Systems (SVS) provide pilots with displays of stored geo-spatial data representing terrain, obstacles, and cultural features. As comprehensive validation is impractical, these databases typically have no quantifiable level of integrity. Further, updates to the databases may not be provided as changes occur. These issues limit the certification level and constrain the operational context of SVS for civil aviation. Previous work demonstrated the feasibility of using a realtime monitor to bound the integrity of Digital Elevation Models (DEMs) by using radar altimeter measurements during flight. This paper describes an extension of this concept to include X-band Weather Radar (WxR) measurements. This enables the monitor to detect additional classes of DEM errors and to reduce the exposure time associated with integrity threats. Feature extraction techniques are used along with a statistical assessment of similarity measures between the sensed and stored features that are detected. Recent flight-testing in the area around the Juneau, Alaska Airport (JNU) has resulted in a comprehensive set of sensor data that is being used to assess the feasibility of the proposed monitor technology. Initial results of this assessment are presented.

ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors

PubMed Central

Becker, Amy M.; Walcheck, Bruce; Bhattacharya, Deepta

2014-01-01

All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through post-transcriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of Csf1r transcripts than their upstream precursors, yet show limited cell surface protein expression of CSF1R. ALPs and other hematopoietic progenitors deficient in ADAM17, a metalloprotease that can cleave CSF1R, display elevated cell surface CSF1R expression. Adam17−/− ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, Adam17−/− ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of M-CSF. Mice with hematopoietic-specific deletion of Adam17 have grossly normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. PMID:25308957

Progesterone modulation of alpha5 nAChR subunits influences anxiety-related behavior during estrus cycle.

PubMed

Gangitano, D; Salas, R; Teng, Y; Perez, E; De Biasi, M

2009-06-01

Smokers often report an anxiolytic effect of cigarettes. In addition, stress-related disorders such as anxiety, post-traumatic stress syndrome and depression are often associated with chronic nicotine use. To study the role of the alpha5 nicotinic acetylcholine receptor subunit in anxiety-related responses, control and alpha5 subunit null mice (alpha5(-/-)) were subjected to the open field activity (OFA), light-dark box (LDB) and elevated plus maze (EPM) tests. In the OFA and LDB, alpha5(-/-) behaved like wild-type controls. In the EPM, female alpha5(-/-) mice displayed an anxiolytic-like phenotype, while male alpha5(-/-) mice were undistinguishable from littermate controls. We studied the hypothalamus-pituitary-adrenal axis by measuring plasma corticosterone and hypothalamic corticotropin-releasing factor. Consistent with an anxiolytic-like phenotype, female alpha5(-/-) mice displayed lower basal corticosterone levels. To test whether gonadal steroids regulate the expression of alpha5, we treated cultured NTera 2 cells with progesterone and found that alpha5 protein levels were upregulated. In addition, brain levels of alpha5 mRNA increased upon progesterone injection into ovariectomized wild-type females. Finally, we tested anxiety levels in the EPM during the estrous cycle. The estrus phase (when progesterone levels are low) is anxiolytic-like in wild-type mice, but no cycle-dependent fluctuations in anxiety levels were found in alpha5(-/-) females. Thus, alpha5-containing neuronal nicotinic acetylcholine receptors may be mediators of anxiogenic responses, and progesterone-dependent modulation of alpha5 expression may contribute to fluctuations in anxiety levels during the ovarian cycle.

Impact on sediments and water by release of copper from chalcopyrite bearing rock due to acidic mine drainage

NASA Astrophysics Data System (ADS)

Shukla, Anoop Kant; Pradhan, Manoj; Tiwari, Onkar Nath

2018-04-01

Mining activity causes transition of rock-mass from its original position in earth into open environment. The action of environmental elements such air, water, microorganisms leads to oxidation of minerals which constitute the rock. The oxidation of sulphide minerals in presence of moisture releases acidic mine discharge (AMD). The acidic nature of AMD causes leaching of metals from rock minerals. Dissolution of other minerals may occur upon reaction with AMD. Chalcopyrite (CuFeS2) undergoes oxidation in acidic condition releasing copper among other products. This study reveals contamination of copper in sediment samples and seepage water from the tailing dam of a large copper project in located in central India. Elevation was studied using GIS to ascertain to the topographic elevation of tailing dam area. It was located at relatively high altitude causing seepage to flow away from tailing dam. The seepage water from tailing dam was found to be acidic with mean pH value of 4.0 and elevated copper content. Similarly, sediments from seepage water flow displayed elevated copper concentration. The copper concentration in seepage water was found with a mean value of 10.73 mg/l. The sediments from seepage water flow also displayed elevated copper concentration with mean value of 26.92 g/kg. This indicates impact on sediments by release of copper due to acidic mine drainage.

A moderate diet restriction during pregnancy alters the levels of endocannabinoids and endocannabinoid-related lipids in the hypothalamus, hippocampus and olfactory bulb of rat offspring in a sex-specific manner

PubMed Central

Ramírez-López, María Teresa; Vázquez, Mariam; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosario Noemi; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Bindila, Laura

2017-01-01

Undernutrition during pregnancy has been associated to increased vulnerability to develop metabolic and behavior alterations later in life. The endocannabinoid system might play an important role in these processes. Therefore, we investigated the effects of a moderate maternal calorie-restricted diet on the levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), arachidonic acid (AA) and the N-acylethanolamines (NAEs) anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the brain of newborn rat offspring. We focused on brain structures involved in metabolism, feeding behavior, as well as emotional and cognitive responses. Female Wistar rats were assigned during the entire pregnancy to either control diet (C) or restriction diet (R), consisting of a 20% calorie-restricted diet. Weight gain and caloric intake of rat dams were monitored and birth outcomes were assessed. 2-AG, AA and NAE levels were measured in hypothalamus, hippocampus and olfactory bulb of the offspring. R dams displayed lower gain weight from the middle pregnancy and consumed less calories during the entire pregnancy. Offspring from R dams were underweight at birth, but litter size was unaffected. In hypothalamus, R male offspring displayed decreased levels of AA and OEA, with no change in the levels of the endocannabinoids 2-AG and AEA. R female exhibited decreased 2-AG and PEA levels. The opposite was found in the hippocampus, where R male displayed increased 2-AG and AA levels, and R female exhibited elevated levels of AEA, AA and PEA. In the olfactory bulb, only R female presented decreased levels of AEA, AA and PEA. Therefore, a moderate diet restriction during the entire pregnancy alters differentially the endocannabinoids and/or endocannabinoid-related lipids in hypothalamus and hippocampus of the underweight offspring, similarly in both sexes, whereas sex-specific alterations occur in the olfactory bulb. Consequently, endocannabinoid and endocannabinoid-related lipid signaling alterations might be involved in the long-term and sexual dimorphism effects commonly observed after undernutrition and low birth weight. PMID:28346523

A moderate diet restriction during pregnancy alters the levels of endocannabinoids and endocannabinoid-related lipids in the hypothalamus, hippocampus and olfactory bulb of rat offspring in a sex-specific manner.

PubMed

Ramírez-López, María Teresa; Vázquez, Mariam; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosario Noemi; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Bindila, Laura; Rodríguez de Fonseca, Fernando

2017-01-01

Undernutrition during pregnancy has been associated to increased vulnerability to develop metabolic and behavior alterations later in life. The endocannabinoid system might play an important role in these processes. Therefore, we investigated the effects of a moderate maternal calorie-restricted diet on the levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), arachidonic acid (AA) and the N-acylethanolamines (NAEs) anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the brain of newborn rat offspring. We focused on brain structures involved in metabolism, feeding behavior, as well as emotional and cognitive responses. Female Wistar rats were assigned during the entire pregnancy to either control diet (C) or restriction diet (R), consisting of a 20% calorie-restricted diet. Weight gain and caloric intake of rat dams were monitored and birth outcomes were assessed. 2-AG, AA and NAE levels were measured in hypothalamus, hippocampus and olfactory bulb of the offspring. R dams displayed lower gain weight from the middle pregnancy and consumed less calories during the entire pregnancy. Offspring from R dams were underweight at birth, but litter size was unaffected. In hypothalamus, R male offspring displayed decreased levels of AA and OEA, with no change in the levels of the endocannabinoids 2-AG and AEA. R female exhibited decreased 2-AG and PEA levels. The opposite was found in the hippocampus, where R male displayed increased 2-AG and AA levels, and R female exhibited elevated levels of AEA, AA and PEA. In the olfactory bulb, only R female presented decreased levels of AEA, AA and PEA. Therefore, a moderate diet restriction during the entire pregnancy alters differentially the endocannabinoids and/or endocannabinoid-related lipids in hypothalamus and hippocampus of the underweight offspring, similarly in both sexes, whereas sex-specific alterations occur in the olfactory bulb. Consequently, endocannabinoid and endocannabinoid-related lipid signaling alterations might be involved in the long-term and sexual dimorphism effects commonly observed after undernutrition and low birth weight.

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

PubMed Central

Hellwinkel, Olaf J. C.; Sellier, Christina; Sylvester, Yu-Mi Jessica; Brase, Jan C.; Isbarn, Hendrik; Erbersdobler, Andreas; Steuber, Thomas; Sültmann, Holger; Schlomm, Thorsten; Wagner, Christina

2013-01-01

We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ. PMID:23459235

Different Effects of Oral Contraceptive and Dydrogesterone Treatment on Oxidative Stress Levels in Premenopausal Women

PubMed Central

Chen, Jui-Tung; Kotani, Kazuhiko

2018-01-01

Background The aim of the study was to observe the changes in blood oxidative stress levels by oral contraceptive (OC) and/or dydrogesterone (DG) treatment. Methods A retrospective cohort of 27 premenopausal women with primary dysmenorrhea consisted of the OC treatment group (N = 17) and the DG treatment group (N = 10) by choice of the initial treatment. The OC group included two subgroups: patients with continuous OC treatment (treated for at least 15 months, N = 10) and patients with discontinuous OC treatment (switched to DG treatment after approximately 6 months of initial OC treatment: N = 7). The DG group had 15 months of continuous DG treatment. Blood parameters, including diacron-reactive oxygen metabolites (d-ROMs: an oxidative stress marker), were measured. Results The d-ROMs level was elevated in the OC group 3 months after initial treatment (mean: from 321 (at baseline) to 512 Carratelli Units (Carr U); P < 0.01), while such changes were not observed in the DG group. The d-ROMs level was reduced in the discontinuous OC subgroup 15 months after initial treatment (from 508 (3 months after initial treatment) to 372 Carr U; P < 0.01), while such changes were not observed in the continuous OC subgroup. The DG group displayed unchanged the d-ROMs level. Conclusion Replacing OC with DG can attenuate oxidative stress as elevated by OC, thereby alleviating the possible vascular risks with OC treatment. PMID:29317960

Physiological Response of Crocosphaera watsonii to Enhanced and Fluctuating Carbon Dioxide Conditions

PubMed Central

Gradoville, Mary R.; White, Angelicque E.; Letelier, Ricardo M.

2014-01-01

We investigated the effects of elevated pCO2 on cultures of the unicellular N2-fixing cyanobacterium Crocosphaera watsonii WH8501. Using CO2-enriched air, cultures grown in batch mode under high light intensity were exposed to initial conditions approximating current atmospheric CO2 concentrations (∼400 ppm) as well as CO2 levels corresponding to low- and high-end predictions for the year 2100 (∼750 and 1000 ppm). Following acclimation to CO2 levels, the concentrations of particulate carbon (PC), particulate nitrogen (PN), and cells were measured over the diurnal cycle for a six-day period spanning exponential and early stationary growth phases. High rates of photosynthesis and respiration resulted in biologically induced pCO2 fluctuations in all treatments. Despite this observed pCO2 variability, and consistent with previous experiments conducted under stable pCO2 conditions, we observed that elevated mean pCO2 enhanced rates of PC production, PN production, and growth. During exponential growth phase, rates of PC and PN production increased by ∼1.2- and ∼1.5-fold in the mid- and high-CO2 treatments, respectively, when compared to the low-CO2 treatment. Elevated pCO2 also enhanced PC and PN production rates during early stationary growth phase. In all treatments, PC and PN cellular content displayed a strong diurnal rhythm, with particulate C:N molar ratios reaching a high of 22∶1 in the light and a low of 5.5∶1 in the dark. The pCO2 enhancement of metabolic rates persisted despite pCO2 variability, suggesting a consistent positive response of Crocosphaera to elevated and fluctuating pCO2 conditions. PMID:25343645

Airborne observed solar elevation and row direction effects on the near-IR/red ratio of cotton

NASA Technical Reports Server (NTRS)

Millard, J. P.; Jackson, R. D.; Goettelman, R. C.; Leroy, M. J. (Principal Investigator)

1981-01-01

An airborne multispectral scanner was used to obtain data over two adjacent cotton fields having rows perpendicular to one another, at three times of day (different solar elevations), and on two dates (different plant size). The near IR/red ratios were displayed in image form, so that within-field variations and differences between fields could be easily assessed. The ratio varied with changing Sun elevation for north-south oriented rows, but no variation was detected for east-west oriented rows.

Endocrine correlates of susceptibility to motion sickness

NASA Technical Reports Server (NTRS)

Kohl, R. L.

1985-01-01

Motion sickness releases ACTH, epinerphrine, and norepinephrine. The endocrine responses to motion sickness, adaptive responses leading to the resolution of the syndrome, and the way in which antimotion-sickness drugs influence the endocrine responses were studied. Susceptible or insusceptible subjects were administered antimotion-sickness drugs prior to stressful stimulation. Insusceptible subjects displayed more pronounced elevations of ACTH, epinephrine, and norepinephrine after stressful motion. Predrug levels of ACTH were higher in insusceptible subjects (p less than 0.01). Acute blockade of hormone responses to stressful motion or alteration of levels of ACTH by drugs were not correlated with individual susceptibility. No correlation was apparent between epinephrine and ACTH release. These endocrine differences may represent neurochemical markers for susceptibility to motion, stress, or general adaptability, and it may be that the chronic modulation of their levels might be more effective in preventing motion sickness than the acute blockage or stimulation of specific receptors.

Mycorrhizal fungal communities respond to experimental elevation of soil pH and P availability in temperate hardwood forests

DOE PAGES

Carrino-Kyker, Sarah R.; Kluber, Laurel A.; Petersen, Sheryl M.; ...

2016-02-04

Many forests are affected by chronic acid deposition, which can lower soil pH and limit the availability of nutrients such as phosphorus (P), but the response of mycorrhizal fungi to changes in soil pH and P availability and how this affects tree acquisition of nutrients is not well understood. Here, we describe an ecosystem-level manipulation in 72 plots, which increased pH and/or P availability across six forests in Ohio, USA. Two years after treatment initiation, mycorrhizal fungi on roots were examined with molecular techniques, including 454-pyrosequencing. Elevating pH significantly increased arbuscular mycorrhizal (AM) fungal colonization and total fungal biomass, andmore » affected community structure of AM and ectomycorrhizal (EcM) fungi, suggesting that raising soil pH altered both mycorrhizal fungal communities and fungal growth. AM fungal taxa were generally negatively correlated with recalcitrant P pools and soil enzyme activity, whereas EcM fungal taxa displayed variable responses, suggesting that these groups respond differently to P availability. Additionally, the production of extracellular phosphatase enzymes in soil decreased under elevated pH, suggesting a shift in functional activity of soil microbes with pH alteration. Furthermore, our findings suggest that elevating pH increased soil P availability, which may partly underlie the mycorrhizal fungal responses we observed.« less

Mycorrhizal fungal communities respond to experimental elevation of soil pH and P availability in temperate hardwood forests.

PubMed

Carrino-Kyker, Sarah R; Kluber, Laurel A; Petersen, Sheryl M; Coyle, Kaitlin P; Hewins, Charlotte R; DeForest, Jared L; Smemo, Kurt A; Burke, David J

2016-03-01

Many forests are affected by chronic acid deposition, which can lower soil pH and limit the availability of nutrients such as phosphorus (P), but the response of mycorrhizal fungi to changes in soil pH and P availability and how this affects tree acquisition of nutrients is not well understood. Here, we describe an ecosystem-level manipulation in 72 plots, which increased pH and/or P availability across six forests in Ohio, USA. Two years after treatment initiation, mycorrhizal fungi on roots were examined with molecular techniques, including 454-pyrosequencing. Elevating pH significantly increased arbuscular mycorrhizal (AM) fungal colonization and total fungal biomass, and affected community structure of AM and ectomycorrhizal (EcM) fungi, suggesting that raising soil pH altered both mycorrhizal fungal communities and fungal growth. AM fungal taxa were generally negatively correlated with recalcitrant P pools and soil enzyme activity, whereas EcM fungal taxa displayed variable responses, suggesting that these groups respond differently to P availability. Additionally, the production of extracellular phosphatase enzymes in soil decreased under elevated pH, suggesting a shift in functional activity of soil microbes with pH alteration. Thus, our findings suggest that elevating pH increased soil P availability, which may partly underlie the mycorrhizal fungal responses we observed. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mycorrhizal fungal communities respond to experimental elevation of soil pH and P availability in temperate hardwood forests

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

Carrino-Kyker, Sarah R.; Kluber, Laurel A.; Petersen, Sheryl M.

Many forests are affected by chronic acid deposition, which can lower soil pH and limit the availability of nutrients such as phosphorus (P), but the response of mycorrhizal fungi to changes in soil pH and P availability and how this affects tree acquisition of nutrients is not well understood. Here, we describe an ecosystem-level manipulation in 72 plots, which increased pH and/or P availability across six forests in Ohio, USA. Two years after treatment initiation, mycorrhizal fungi on roots were examined with molecular techniques, including 454-pyrosequencing. Elevating pH significantly increased arbuscular mycorrhizal (AM) fungal colonization and total fungal biomass, andmore » affected community structure of AM and ectomycorrhizal (EcM) fungi, suggesting that raising soil pH altered both mycorrhizal fungal communities and fungal growth. AM fungal taxa were generally negatively correlated with recalcitrant P pools and soil enzyme activity, whereas EcM fungal taxa displayed variable responses, suggesting that these groups respond differently to P availability. Additionally, the production of extracellular phosphatase enzymes in soil decreased under elevated pH, suggesting a shift in functional activity of soil microbes with pH alteration. Furthermore, our findings suggest that elevating pH increased soil P availability, which may partly underlie the mycorrhizal fungal responses we observed.« less

Computer Programs to Display and Modify Data in Geographic Coordinates and Methods to Transfer Positions to and from Maps, with Applications to Gravity Data Processing, Global Positioning Systems, and 30-Meter Digital Elevation Models

USGS Publications Warehouse

Plouff, Donald

1998-01-01

Computer programs were written in the Fortran language to process and display gravity data with locations expressed in geographic coordinates. The programs and associated processes have been tested for gravity data in an area of about 125,000 square kilometers in northwest Nevada, southeast Oregon, and northeast California. This report discusses the geographic aspects of data processing. Utilization of the programs begins with application of a template (printed in PostScript format) to transfer locations obtained with Global Positioning Systems to and from field maps and includes a 5-digit geographic-based map naming convention for field maps. Computer programs, with source codes that can be copied, are used to display data values (printed in PostScript format) and data coverage, insert data into files, extract data from files, shift locations, test for redundancy, and organize data by map quadrangles. It is suggested that 30-meter Digital Elevation Models needed for gravity terrain corrections and other applications should be accessed in a file search by using the USGS 7.5-minute map name as a file name, for example, file '40117_B8.DEM' contains elevation data for the map with a southeast corner at lat 40? 07' 30' N. and lon 117? 52' 30' W.

Increased clutter level in echocardiography due to specular reflection

NASA Astrophysics Data System (ADS)

Fatemi, Ali; Torp, Hans; Aakhus, Svend; Rodriguez-Molares, Alfonso

2017-03-01

State-of-the-art echocardiography allows to correctly diagnose most of cardiovascular diseases. An unknown source of clutter, however, hinders the visualization of the heart in some cases. We believe this clutter is caused by the ultrasound beam being partially reflected by the ribs into the elevation direction, so that structures outside the imaging plane are displayed on top of the heart image as clutter noise. We conducted in vitro experiments in a water tank using a synthetic ventricle and pig ribs. By partially blocking the probe with the ribs in the elevation direction, objects outside the imaging plane were rendered in the B-mode image, which confirms that the ribs can behave as specular reflectors. In addition, we succeeded in reproducing clutter noise using a piece of polystyrene to simulate the reflections from the lungs. This indicates that the origin of the clutter noise in echocardiograms can be reverberation coming from the lungs via specular reflection at the ribs.

Thyroid hormone fluctuations indicate a thermoregulatory function in both a tropical (Alouatta palliata) and seasonally cold-habitat (Macaca fuscata) primate.

PubMed

Thompson, Cynthia L; Powell, Brianna L; Williams, Susan H; Hanya, Goro; Glander, Kenneth E; Vinyard, Christopher J

2017-11-01

Thyroid hormones boost animals' basal metabolic rate and represent an important thermoregulatory pathway for mammals that face cold temperatures. Whereas the cold thermal pressures experienced by primates in seasonal habitats at high latitudes and elevations are often apparent, tropical habitats also display distinct wet and dry seasons with modest changes in thermal environment. We assessed seasonal and temperature-related changes in thyroid hormone levels for two primate species in disparate thermal environments, tropical mantled howlers (Alouatta palliata), and seasonally cold-habitat Japanese macaques (Macaca fuscata). We collected urine and feces from animals and used ELISA to quantify levels of the thyroid hormone triiodothyronine (fT 3 ). For both species, fT 3 levels were significantly higher during the cooler season (wet/winter), consistent with a thermoregulatory role. Likewise, both species displayed greater temperature deficits (i.e., the degree to which animals warm their body temperature relative to ambient) during the cooler season, indicating greater thermoregulatory pressures during this time. Independently of season, Japanese macaques displayed increasing fT 3 levels with decreasing recently experienced maximum temperatures, but no relationship between fT 3 and recently experienced minimum temperatures. Howlers increased fT 3 levels as recently experienced minimum temperatures decreased, although demonstrated the opposite relationship with maximum temperatures. This may reflect natural thermal variation in howlers' habitat: wet seasons had cooler minimum and mean temperatures than the dry season, but similar maximum temperatures. Overall, our findings support the hypothesis that both tropical howlers and seasonally cold-habitat Japanese macaques utilize thyroid hormones as a mechanism to boost metabolism in response to thermoregulatory pressures. This implies that cool thermal pressures faced by tropical primates are sufficient to invoke an energetically costly and relatively longer-term thermoregulatory pathway. The well-established relationship between thyroid hormones and energetics suggests that the seasonal hormonal changes we observed could influence many commonly studied behaviors including food choice, range use, and activity patterns. © 2017 Wiley Periodicals, Inc.

Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults

PubMed Central

Nusslock, Robin; Almeida, Jorge RC; Forbes, Erika E; Versace, Amelia; Frank, Ellen; LaBarbara, Edmund J; Klein, Crystal R; Phillips, Mary L

2012-01-01

Objective Bipolar disorder may be characterized by a hypersensitivity to reward-relevant stimuli, potentially underlying the emotional lability and dysregulation that characterizes the illness. In parallel, research highlights the predominant role of striatal and orbitofrontal cortical (OFC) regions in reward-processing and approach-related affect. We aimed to examine whether bipolar disorder, relative to healthy, participants displayed elevated activity in these regions during reward processing. Methods Twenty-one euthymic bipolar I disorder and 20 healthy control participants with no lifetime history of psychiatric disorder underwent functional magnetic resonance imaging (fMRI) scanning during a card-guessing paradigm designed to examine reward-related brain function to anticipation and receipt of monetary reward and loss. Data were collected using a 3T Siemens Trio scanner. Results Region-of-interest analyses revealed that bipolar disorder participants displayed greater ventral striatal and right-sided orbitofrontal [Brodmann area (BA) 11] activity during anticipation, but not outcome, of monetary reward, relative to healthy controls (p < 0.05, corrected). Wholebrain analyses indicated that bipolar disorder, relative to healthy, participants also displayed elevated left-lateral OFC activity (BA 47) activity during reward anticipation (p < 0.05, corrected). Conclusions Elevated ventral striatal and OFC activity during reward anticipation may represent a neural mechanism for predisposition to expansive mood and hypo/mania in response to reward-relevant cues that characterizes bipolar disorder. Our findings contrast with research reporting blunted activity in the ventral striatum during reward processing in unipolar depressed individuals, relative to healthy controls. Examination of reward-related neural activity in bipolar disorder is a promising research focus to facilitate identification of biological markers of the illness. PMID:22548898

Overexpression of a partial fragment of the salt-responsive gene OsNUC1 enhances salt adaptation in transgenic Arabidopsis thaliana and rice (Oryza sativa L.) during salt stress.

PubMed

Sripinyowanich, Siriporn; Chamnanmanoontham, Nontalee; Udomchalothorn, Thanikarn; Maneeprasopsuk, Somporn; Santawee, Panudda; Buaboocha, Teerapong; Qu, Li-Jia; Gu, Hongya; Chadchawan, Supachitra

2013-12-01

The rice (Oryza sativa L.) nucleolin gene, OsNUC1, transcripts were expressed in rice leaves, flowers, seeds and roots but differentially expressed within and between two pairs of salt-sensitive and salt-resistant rice lines when subjected to salt stress. Salt-resistant lines exhibited higher OsNUC1 transcript expression levels than salt-sensitive lines during 0.5% (w/v) NaCl salt stress for 6d. Two sizes of OsNUC1 full-length cDNA were found in the rice genome database and northern blot analysis confirmed their existence in rice tissues. The longer transcript (OsNUC1-L) putatively encodes for a protein with a serine rich N-terminal, RNA recognition motifs in the central domain and a glycine- and arginine-rich repeat in the C-terminal domain, while the shorter one (OsNUC1-S) putatively encodes for the similar protein without the N-terminus. Without salt stress, OsNUC1-L expressing Arabidopsis thaliana Atnuc1-L1 plants displayed a substantial but incomplete revertant phenotype, whereas OsNUC1-S expression only induced a weak effect. However, under 0.5% (w/v) NaCl salt stress they displayed a higher relative growth rate, longer root length and a lower H2O2 level than the wild type plants, suggesting a higher salt resistance. Moreover, they displayed elevated AtSOS1 and AtP5CS1 transcript levels. We propose that OsNUC1-S plays an important role in salt resistance during salt stress, a new role for nucleolin in plants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Aberrantly regulated dysadherin and B-cell lymphoma 2/B-cell lymphoma 2-associated X enhances tumorigenesis and DNA targeting drug resistance of liver cancer stem cells

PubMed Central

JIANG, NAN; CHEN, WEI; ZHANG, JIAN-WEN; LI, YANG; ZENG, XIAN-CHENG; ZHANG, TONG; FU, BIN-SHENG; YI, HUI-MIN; ZHANG, QI

2015-01-01

Cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) are frequently resistant to current therapeutic regimens and therefore responsible for tumor recurrence. Previous studies have reported that expression levels of dysadherin in CSCs may be used as a prognostic indicator, which is also responsible for treatment failure and poor survival rates. The present study analyzed the association of enhanced dysadherin levels with drug resistance and evasion of apoptosis in human HCC SP cells. An SP of 3.7% was isolated from human HCC cells using fluorescence-activated cell sorting. These SP cells displayed elevated levels of dysadherin and stemness proteins as well as high resistance to chemotherapeutic drugs and apoptosis. In order to reveal the possible link between dysadherin levels and tumorigenesis of SP cells, small interfering RNA technology was used to knockdown the expression of dysadherin in SP cells. Of note, the siRNA-transfected SP cells showed significantly reduced levels of stemness proteins, and were more sensitive to DNA-targeting drugs and apoptotic cell death as compared to non-transfected cells. Furthermore, in vivo experiments in NON/SCID mice indicated that dysadherin-expressing SP cells were highly tumorigenic, as they were able to induce tumor growth. The SP cell-derived tumor tissues in turn showed elevated dysadherin levels. The results of the present study therefore suggested that knockdown of dysadherin suppressed the tumorigenic properties of cancer stem-like SP cells. Hence, dysadherin is a valuable potential target for the development of novel anti-cancer drugs. PMID:26458963

Type 3 Deiodinase Role on Central Thyroid Hormone Action Affects the Leptin-Melanocortin System and Circadian Activity

PubMed Central

Wu, Zhaofei; Martinez, M. Elena; St. Germain, Donald L.

2017-01-01

The role of thyroid hormones (THs) in the central regulation of energy balance is increasingly appreciated. Mice lacking the type 3 deiodinase (DIO3), which inactivates TH, have decreased circulating TH levels relative to control mice as a result of defects in the hypothalamic-pituitary-thyroid axis. However, we have shown that the TH status of the adult Dio3−/− brain is opposite that of the serum, exhibiting enhanced levels of TH action. Because the brain, particularly the hypothalamus, harbors important circuitries that regulate metabolism, we aimed to examine the energy balance phenotype of Dio3−/− mice and determine whether it is associated with hypothalamic abnormalities. Here we show that Dio3−/− mice of both sexes exhibit decreased adiposity, reduced brown and white adipocyte size, and enhanced fat loss in response to triiodothyronine (T3) treatment. They also exhibit increased TH action in the hypothalamus, with abnormal expression and T3 sensitivity of genes integral to the leptin-melanocortin system, including Agrp, Npy, Pomc, and Mc4r. The normal to elevated serum levels of leptin, and elevated and repressed expression of Agrp and Pomc, respectively, suggest a profile of leptin resistance. Interestingly, Dio3−/− mice also display elevated locomotor activity and increased energy expenditure. This occurs in association with expanded nighttime activity periods, suggesting a disrupted circadian rhythm. We conclude that DIO3-mediated regulation of TH action in the central nervous system influences multiple critical determinants of energy balance. Those influences may partially compensate each other, with the result likely contributing to the decreased adiposity observed in Dio3−/− mice. PMID:27911598

Type 3 Deiodinase Role on Central Thyroid Hormone Action Affects the Leptin-Melanocortin System and Circadian Activity.

PubMed

Wu, Zhaofei; Martinez, M Elena; St Germain, Donald L; Hernandez, Arturo

2017-02-01

The role of thyroid hormones (THs) in the central regulation of energy balance is increasingly appreciated. Mice lacking the type 3 deiodinase (DIO3), which inactivates TH, have decreased circulating TH levels relative to control mice as a result of defects in the hypothalamic-pituitary-thyroid axis. However, we have shown that the TH status of the adult Dio3-/- brain is opposite that of the serum, exhibiting enhanced levels of TH action. Because the brain, particularly the hypothalamus, harbors important circuitries that regulate metabolism, we aimed to examine the energy balance phenotype of Dio3-/- mice and determine whether it is associated with hypothalamic abnormalities. Here we show that Dio3-/- mice of both sexes exhibit decreased adiposity, reduced brown and white adipocyte size, and enhanced fat loss in response to triiodothyronine (T3) treatment. They also exhibit increased TH action in the hypothalamus, with abnormal expression and T3 sensitivity of genes integral to the leptin-melanocortin system, including Agrp, Npy, Pomc, and Mc4r. The normal to elevated serum levels of leptin, and elevated and repressed expression of Agrp and Pomc, respectively, suggest a profile of leptin resistance. Interestingly, Dio3-/- mice also display elevated locomotor activity and increased energy expenditure. This occurs in association with expanded nighttime activity periods, suggesting a disrupted circadian rhythm. We conclude that DIO3-mediated regulation of TH action in the central nervous system influences multiple critical determinants of energy balance. Those influences may partially compensate each other, with the result likely contributing to the decreased adiposity observed in Dio3-/- mice. Copyright © 2017 by the Endocrine Society.

Increased Expression of PcG Protein YY1 Negatively Regulates B Cell Development while Allowing Accumulation of Myeloid Cells and LT-HSC Cells

PubMed Central

Pan, Xuan; Jones, Morgan; Jiang, Jie; Zaprazna, Kristina; Yu, Duonan; Pear, Warren; Maillard, Ivan; Atchison, Michael L.

2012-01-01

Ying Yang 1 (YY1) is a multifunctional Polycomb Group (PcG) transcription factor that binds to multiple enhancer binding sites in the immunoglobulin (Ig) loci and plays vital roles in early B cell development. PcG proteins have important functions in hematopoietic stem cell renewal and YY1 is the only mammalian PcG protein with DNA binding specificity. Conditional knock-out of YY1 in the mouse B cell lineage results in arrest at the pro-B cell stage, and dosage effects have been observed at various YY1 expression levels. To investigate the impact of elevated YY1 expression on hematopoetic development, we utilized a mouse in vivo bone marrow reconstitution system. We found that mouse bone marrow cells expressing elevated levels of YY1 exhibited a selective disadvantage as they progressed from hematopoietic stem/progenitor cells to pro-B, pre-B, immature B and re-circulating B cell stages, but no disadvantage of YY1 over-expression was observed in myeloid lineage cells. Furthermore, mouse bone marrow cells expressing elevated levels of YY1 displayed enrichment for cells with surface markers characteristic of long-term hematopoietic stem cells (HSC). YY1 expression induced apoptosis in mouse B cell lines in vitro, and resulted in down-regulated expression of anti-apoptotic genes Bcl-xl and NFκB2, while no impact was observed in a mouse myeloid line. B cell apoptosis and LT-HSC enrichment induced by YY1 suggest that novel strategies to induce YY1 expression could have beneficial effects in the treatment of B lineage malignancies while preserving normal HSCs. PMID:22292011

The impact of computer display height and desk design on 3D posture during information technology work by young adults.

PubMed

Straker, L; Burgess-Limerick, R; Pollock, C; Murray, K; Netto, K; Coleman, J; Skoss, R

2008-04-01

Computer display height and desk design to allow forearm support are two critical design features of workstations for information technology tasks. However there is currently no 3D description of head and neck posture with different computer display heights and no direct comparison to paper based information technology tasks. There is also inconsistent evidence on the effect of forearm support on posture and no evidence on whether these features interact. This study compared the 3D head, neck and upper limb postures of 18 male and 18 female young adults whilst working with different display and desk design conditions. There was no substantial interaction between display height and desk design. Lower display heights increased head and neck flexion with more spinal asymmetry when working with paper. The curved desk, designed to provide forearm support, increased scapula elevation/protraction and shoulder flexion/abduction.

Earth Observations taken by Expedition 38 crewmember

NASA Image and Video Library

2013-11-15

ISS038-E-003612 (15 Nov. 2013) --- Islands of the Four Mountains are featured in this image photographed by an Expedition 38 crew member on the International Space Station. Morning sunlight illuminates the southeast-facing slopes of the islands in the photograph. The islands, part of the Aleutian Island chain, are actually the upper slopes of volcanoes rising from the sea floor; Carlisle, Cleveland, Herbert, and Tana. Carlisle and Herbert volcanoes are distinct cones and form separate islands. Cleveland volcano and the Tana volcanic complex form the eastern and western ends respectively of Chuginadak Island; a cloud bank obscures the connecting land mass in this image. Cleveland volcano (peak elevation 1,730 meters above sea level) is one of the most active in the Aleutian chain, with its most recent activity--eruptions and lava flow emplacement--taking place in May of 2013. The northernmost of the islands, Carlisle volcano's (peak elevation 1,620 meters above sea level) last confirmed eruption occurred in 1828, with unconfirmed reports of activity in 1987. Herbert volcano (peak elevation 1,280 meters above sea level) to the southwest displays a classic cone structure breached by a two-kilometer wide summit caldera (upper right), but there are no historical records of volcanic activity. The easternmost peak, Tana (1,170 meters above sea level) is a volcanic complex comprised of two east-west trending volcanoes and associated younger cinder cones; like Herbert volcano, there is no historical record of activity at Tana. A layer of low clouds and/or fog obscures much of the lower elevations of the islands and the sea surface, but the clouds also indicate the general airflow pattern around and through the islands. Directly to the south-southeast of Cleveland volcano a Von Karman vortex "street" is visible. Shadows cast by the morning sun extend from the peaks towards the northwest. The peaks of all of the Four Islands have snow cover; this is distinct from the clouds due to both higher brightness (white versus gray) and specific location on the landscape.

Proof of concept for the simplified breakdown of cellulose by combining Pseudomonas putida strains with surface displayed thermophilic endocellulase, exocellulase and β-glucosidase.

PubMed

Tozakidis, Iasson E P; Brossette, Tatjana; Lenz, Florian; Maas, Ruth M; Jose, Joachim

2016-06-10

The production and employment of cellulases still represents an economic bottleneck in the conversion of lignocellulosic biomass to biofuels and other biocommodities. This process could be simplified by displaying the necessary enzymes on a microbial cell surface. Such an approach, however, requires an appropriate host organism which on the one hand can withstand the rough environment coming along with lignocellulose hydrolysis, and on the other hand does not consume the generated glucose so that it remains available for subsequent fermentation steps. The robust soil bacterium Pseudomonas putida showed a strongly reduced uptake of glucose above a temperature of 50 °C, while remaining structurally intact hence recyclable, which makes it suitable for cellulose hydrolysis at elevated temperatures. Consequently, three complementary, thermophilic cellulases from Ruminiclostridium thermocellum were displayed on the surface of the bacterium. All three enzymes retained their activity on the cell surface. A mixture of three strains displaying each one of these enzymes was able to synergistically hydrolyze filter paper at 55 °C, producing 20 μg glucose per mL cell suspension in 24 h. We could establish Pseudomonas putida as host for the surface display of cellulases, and provided proof-of-concept for a fast and simple cellulose breakdown process at elevated temperatures. This study opens up new perspectives for the application of P. putida in the production of biofuels and other biotechnological products.

Disturbance is the key to plant invasions in cold environments.

PubMed

Lembrechts, Jonas J; Pauchard, Aníbal; Lenoir, Jonathan; Nuñez, Martín A; Geron, Charly; Ven, Arne; Bravo-Monasterio, Pablo; Teneb, Ernesto; Nijs, Ivan; Milbau, Ann

2016-12-06

Until now, nonnative plant species were rarely found at high elevations and latitudes. However, partly because of climate warming, biological invasions are now on the rise in these extremely cold environments. These plant invasions make it timely to undertake a thorough experimental assessment of what has previously been holding them back. This knowledge is key to developing efficient management of the increasing risks of cold-climate invasions. Here, we integrate human interventions (i.e., disturbance, nutrient addition, and propagule input) and climatic factors (i.e., temperature) into one seed-addition experiment across two continents: the subantarctic Andes and subarctic Scandinavian mountains (Scandes), to disentangle their roles in limiting or favoring plant invasions. Disturbance was found as the main determinant of plant invader success (i.e., establishment, growth, and flowering) along the entire cold-climate gradient, explaining 40-60% of the total variance in our models, with no indication of any facilitative effect from the native vegetation. Higher nutrient levels additionally stimulated biomass production and flowering. Establishment and flowering displayed a hump-shaped response with increasing elevation, suggesting that competition is the main limit on invader success at low elevations, as opposed to low-growing-season temperatures at high elevations. Our experiment showed, however, that nonnative plants can establish, grow, and flower well above their current elevational limits in high-latitude mountains. We thus argue that cold-climate ecosystems are likely to see rapid increases in plant invasions in the near future as a result of a synergistic interaction between increasing human-mediated disturbances and climate warming.

Emotional display rules as work unit norms: a multilevel analysis of emotional labor among nurses.

PubMed

Diefendorff, James M; Erickson, Rebecca J; Grandey, Alicia A; Dahling, Jason J

2011-04-01

Emotional labor theory has conceptualized emotional display rules as shared norms governing the expression of emotions at work. Using a sample of registered nurses working in different units of a hospital system, we provided the first empirical evidence that display rules can be represented as shared, unit-level beliefs. Additionally, controlling for the influence of dispositional affectivity, individual-level display rule perceptions, and emotion regulation, we found that unit-level display rules are associated with individual-level job satisfaction. We also showed that unit-level display rules relate to burnout indirectly through individual-level display rule perceptions and emotion regulation strategies. Finally, unit-level display rules also interacted with individual-level dispositional affectivity to predict employee use of emotion regulation strategies. We discuss how future research on emotional labor and display rules, particularly in the health care setting, can build on these findings.

The effect of alcohol and hydrogen peroxide on liver hepcidin gene expression in mice lacking antioxidant enzymes, glutathione peroxidase-1 or catalase.

PubMed

Harrison-Findik, Duygu Dee; Lu, Sizhao

2015-05-06

This study investigates the regulation of hepcidin, the key iron-regulatory molecule, by alcohol and hydrogen peroxide (H2O2) in glutathione peroxidase-1 (gpx-1(-/-)) and catalase (catalase(-/-)) knockout mice. For alcohol studies, 10% ethanol was administered in the drinking water for 7 days. Gpx-1(-/-) displayed significantly higher hepatic H2O2 levels than catalase(-/-) compared to wild-type mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The basal level of liver hepcidin expression was attenuated in gpx-1(-/-) mice. Alcohol increased H2O2 production in catalase(-/-) and wild-type, but not gpx-1(-/-), mice. Hepcidin expression was inhibited in alcohol-fed catalase(-/-) and wild-type mice. In contrast, alcohol elevated hepcidin expression in gpx-1(-/-) mice. Gpx-1(-/-) mice also displayed higher level of basal liver CHOP protein expression than catalase(-/-) mice. Alcohol induced CHOP and to a lesser extent GRP78/BiP expression, but not XBP1 splicing or binding of CREBH to hepcidin gene promoter, in gpx-1(-/-) mice. The up-regulation of hepatic ATF4 mRNA levels, which was observed in gpx-1(-/-) mice, was attenuated by alcohol. In conclusion, our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo. Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1, stimulates liver hepcidin gene expression by ER stress independent of CREBH.

Psychosocial stress but not exercise increases cortisol and reduces state anxiety levels in school classes - results from a stressor applicable in large group settings.

PubMed

Wegner, Mirko; Müller-Alcazar, Anett; Jäger, Anika; Machado, Sergio; Arias-Carrión, Oscar; Budde, Henning

2014-01-01

Both, psychosocial stress and exercise in the past have been used as stressors to elevate saliva cortisol and change state anxiety levels. In the present study, high-school students at the age of 14 were randomly assigned to three experimental groups: (1) an exercise group (n = 18), that was running 15 minutes at a medium intensity level of 65-75% HRmax, (2) a psychosocial stress group (n = 19), and (3) a control group (n = 18). The psychosocial stress was induced to the students by completing a standardized intelligence test under the assumption that their IQ scores would be made public in class. Results display that only psychosocial stress but not exercise was able to significantly increase cortisol levels but decreased cognitive state anxiety in adolescents. The psychosocial stress protocol applied here is proposed for use in future stress studies with children or adolescents in group settings, e.g., in school.

Therapists' and patients' stress responses during graduated versus flooding in vivo exposure in the treatment of specific phobia: A preliminary observational study.

PubMed

Schumacher, Sarah; Miller, Robert; Fehm, Lydia; Kirschbaum, Clemens; Fydrich, Thomas; Ströhle, Andreas

2015-12-15

Exposure therapy is considered an effective treatment strategy for phobic anxiety, however, it is rarely applied in clinical practice. The under-usage might be due to various factors of which heightened stress levels not only in patients but also in therapists are presumed to be of particular relevance. The present study aimed to investigate whether different forms of exposure might lead to varying physiological and psychological stress responses in therapists and phobic patients. 25 patients with specific phobia underwent individual cognitive behavioural therapy, performed by 25 psychotherapist trainees, applying exposure sessions in graduated form or the flooding technique. Patients and therapists provided subjective evaluations of stress and five saliva samples for analysis of salivary cortisol and alpha-amylase either during two graduated exposure sessions or during one flooding session, while a regular therapy session served as control condition. Therapists displayed heightened salivary alpha-amylase release during exposure of the flooding, but not the graduated, type. Patients showed elevated salivary cortisol during flooding exposure numerically, however, not on a statistically significant level. Therapists reported more pronounced subjective stress during flooding compared to graduated exposure. Elevated stress levels should be addressed in clinical training in order to improve application of exposure in routine practice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Hepatoprotective effect of 10% ethanolic extract from Curdrania tricuspidata leaves against ethanol-induced oxidative stress through suppression of CYP2E1.

PubMed

You, Yanghee; Min, Seoyoung; Lee, Yoo-Hyun; Hwang, Kwontack; Jun, Woojin

2017-10-01

The hepatoprotective effect of 10% ethanolic extract of Curdrania tricuspidata (CTE) was investigated in HepG2/2E1 cells and C57BL/6 J mice. When compared ethanol-only treated HepG2/2E1 cells, pretreatment of CTE prevented increased intra-cellular reactive oxygen species levels and decreased antioxidant activities by ethanol-induced oxidative stress. In C57BL/6 J mice, CTE at a dose of 250 mg/kg/day was administered for 10 days, with ethanol (5 g/kg/day) administered for the final 3 days. Pretreatment with CTE prevented the elevated activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase caused by ethanol-induced hepatic damage. CTE-treated mice displayed a reduced level of malondialdehyde and increased antioxidant activities of catalase, glutathione S-transferase, glutathione peroxidase, and superoxide dismutase, as well as a reduced level of glutathione as compared with ethanol-only-treated mice. CTE-treated mice exhibited significant inhibition of CYP2E1 activities and expression. These results suggest that CTE could be a useful agent for the prevention of ethanol-induced oxidative damage in the liver, elevating antioxidative potentials and alleviating oxidative stress by suppressing CYP2El. Copyright © 2017 Elsevier Ltd. All rights reserved.

DspaceOgreTerrain 3D Terrain Visualization Tool

NASA Technical Reports Server (NTRS)

Myint, Steven; Jain, Abhinandan; Pomerantz, Marc I.

2012-01-01

DspaceOgreTerrain is an extension to the DspaceOgre 3D visualization tool that supports real-time visualization of various terrain types, including digital elevation maps, planets, and meshes. DspaceOgreTerrain supports creating 3D representations of terrains and placing them in a scene graph. The 3D representations allow for a continuous level of detail, GPU-based rendering, and overlaying graphics like wheel tracks and shadows. It supports reading data from the SimScape terrain- modeling library. DspaceOgreTerrain solves the problem of displaying the results of simulations that involve very large terrains. In the past, it has been used to visualize simulations of vehicle traverses on Lunar and Martian terrains. These terrains were made up of billions of vertices and would not have been renderable in real-time without using a continuous level of detail rendering technique.

Catecholaminergic responses to stressful motion stimuli, scopolamine plus amphetamine, and dexamethasone

NASA Technical Reports Server (NTRS)

Kohl, R. L.; Chelen, W. E.

1992-01-01

Peripheral levels of epinephrine (EPI) and neoepinephrine (NE) generally rise following stressful motion stimuli. Effective anti-motion sickness drugs, scopolamine plus, d-amphetamine (S/D) and dexamthasone (DEX) modulate release of EPI and NE. This modulation may be of etiological relevance. Methods: Severe nausea was induced by exposure to coriolis simulation using a rotating chair. Chronic administration of S/D (0.4 and 5 mg/da) DEX (3 mg/day) and placebo preceded coriolis simulation. EPI and NE were measured immediately before and after simulation. A double-blind crossover design was used. Results: Nausea-induced elevations of EPI (2.5 fold, p less than .01) and NE were not diminished upon repeated exposure and adaptation to the stressor. Subjects with more pronounced elevations of EPI following simulation displayed higher resistance to stressful motion (p less .05). Alteration of peripheral catechlomaine levels following drug suggested that motion sickness was not mediated by peripheral catechlolamine receptor simulation. EPI and NE levels were 2.8 and 3.6-fold higher (p less than .03 and .01) after nausea without DEX treatment. DEX loading halved pre-stress levels of EPI and NE (p less than .05). Conclusions: Marked differences were noted in individual responses to drug and systematic responses of EPI and NE. It is possible that the responses of EPI to motion sickness may predict resistance to stressful motion and represent a peripheral manifestation of some as yet unknown central event of etiologic relevance.

Response to fasting in an unnaturally obese carnivore, the captive European polecat Mustela putorius.

PubMed

Mustonen, Anne-Mari; Puukka, Matti; Rouvinen-Watt, Kirsti; Aho, Jari; Asikainen, Juha; Nieminen, Petteri

2009-11-01

The European polecat (Mustela putorius) is a naturally lean carnivore prone to excessive weight gain in captivity. This study assessed its suitability to investigate the natural history of the obese phenotype displayed in overweight humans, domestic animals, and seasonally obese wild mammals. Ten farm-bred polecats were subjected to a 5-day fast with 10 controls. Obesity (40% body fat) was associated with an unfavorable plasma lipid profile and high glucose and insulin concentrations. The polecats were in phase II of fasting with normoglycemia, low liver carbohydrate stores, and decreased plasma concentrations of urea and most amino acids. Although the plasma nonesterified fatty acid (NEFA) levels were elevated, the adipose tissue lipase activities suggested a blunted lipolytic response. Lipid mobilization was more efficient from intraabdominal fat. The animals developed hepatic lipidosis with elevated NEFA influx into the liver and losses of n-3 polyunsaturated fatty acids and arginine as hypothetical etiological factors. The plasma leptin, insulin, and triiodothyronine levels decreased but were not accompanied by reduced sex steroid or increased stress hormone concentrations. The blunted lipolytic response often encountered in obesity suggests that the organism is trying to defend the obese phenotype. Liver lipidosis and decreased insulin and triiodothyronine levels seem to be among the most consistent responses to fasting manifested in diverse mammalian orders and different levels of body fatness. The polecat could be recommended as an easily accessible carnivorean model to study the natural history of the obese phenotype and its comorbidities.

Use of modified lip repositioning technique associated with esthetic crown lengthening for treatment of excessive gingival display: A case report of multiple etiologies

PubMed Central

Mantovani, Matheus Bortoluzzi; Souza, Eduardo Clemente; Marson, Fabiano Carlos; Corrêa, Giovani Oliveira; Progiante, Patrícia Saram; Silva, Cléverson Oliveira

2016-01-01

Excessive gingival display during smile can result in compromised esthetics. This study aims to report a case of excessive gingival display with multiple etiologies treated by means of modified lip repositioning technique associated with esthetic crown lengthening. A 23-year-old female patient, with 5-mm gingival display during smile caused by altered passive eruption and hypermobility of the upper lip, underwent the modified lip repositioning technique associated with gingivectomy followed by flap elevation and ostectomy/osteoplasty. Seven months after the second procedure, the patient had her esthetic complaint solved appearing stable in the observation period. The modified lip repositioning technique is an effective procedure employed to reduce gingival display and when associated with esthetic clinical crown lengthening, can appropriately treat cases of gummy smile. PMID:27041845

Subsidence (2004-2009) in and near lakebeds of the Mojave River and Morongo groundwater basins, southwest Mojave Desert, California

USGS Publications Warehouse

Solt, Mike; Sneed, Michelle

2014-01-01

Subsidence, in the vicinity of dry lakebeds, within the Mojave River and Morongo groundwater basins of the southwest Mojave Desert has been measured by Interferometric Synthetic Aperture Radar (InSAR). The investigation has focused on determining the location, extent, and magnitude of changes in land-surface elevation. In addition, the relation of changes in land-surface elevation to changes in groundwater levels and lithology was explored. This report is the third in a series of reports investigating land-surface elevation changes in the Mojave and Morongo Groundwater Basins, California. The first report, U.S. Geological Survey (USGS) Water-Resources Investigations Report 03-4015 by Sneed and others (2003), describes historical subsidence and groundwater-level changes in the southwest Mojave Desert from 1969 to 1999. The second report, U.S. Geological Survey Water-Resources Investigations Report 07-5097, an online interactive report and map, by Sneed and Brandt (2007), describes subsidence and groundwater-level changes in the southwest Mojave Desert from 1999 to 2004. The purpose of this report is to document an updated assessment of subsidence in these lakebeds and selected neighboring areas from 2004 to 2009 as measured by InSAR methods. In addition, continuous Global Positioning System (GPS)(2005-10), groundwater level (1951-2010), and lithologic data, if available, were used to characterize compaction mechanisms in these areas. The USGS California Water Science Center’s interactive website for the Mojave River and Morongo groundwater basins was created to centralize information pertaining to land subsidence and water levels and to allow readers to access available data and related reports online. An interactive map of land subsidence and water levels in the Mojave River and Morongo groundwater basins displays InSAR interferograms, subsidence areas, subsidence contours, hydrographs, well information, and water-level contours. Background information, including a basic description of the mechanics of land subsidence and InSAR, as well as a description of the study area, is presented within the Mojave Water Resources Interactive Map and report.

Scandinavia

Atmospheric Science Data Center

2013-04-17

... Terrain Elevation Model from the United States Geological Survey. It is displayed in an equidistant conic projection. The image area ... MD. The MISR data were obtained from the NASA Langley Research Center Atmospheric Science Data Center in Hampton, VA. Image ...

Neonatal exposure to fenoterol and betamethasone: effects on the behavioral development in the rat.

PubMed

Pitzer, Martina; Schmidt, Martin H

2009-01-01

We investigated longitudinally the behavioral development in the rat following exposure to beta-agonists and glucocorticoids (GC). Neonatal rats received either 1 mg/kg fenoterol (FEN), 0.3 mg/kg betamethasone (BET), or saline (SAL). Weanling and young adult rats were tested in the open field, the elevated-plus maze, and the water maze. FEN-treated as well as BET-treated animals displayed increased anxiety-like behavior. Furthermore, BET-treated adult animals showed a reduced locomotor activity. An enhanced 24-h memory in the water maze in both treatment groups may be facilitated by emotional arousal due to the increased anxiety levels. The possible neurobiological underpinnings are discussed in detail.

Adolescent activity-based anorexia increases anxiety-like behavior in adulthood.

PubMed

Kinzig, Kimberly P; Hargrave, Sara L

2010-09-01

Activity-based anorexia is a paradigm that induces increased physical activity, reduced food intake, and heightened activity of the hypothalamic-pituitary-adrenal axis in adult rats. To investigate whether experience with activity-based anorexia produced enduring effects on brain and behavior, female adolescent rats experienced activity-based anorexia during adolescence and were tested in adulthood for anxiety-like behavior on an elevated plus maze and in an open field. Analysis of elevated plus maze and open field behavior in adulthood revealed that rats that experienced activity-based anorexia during adolescence, but not rats that were simply food restricted, displayed increased anxiety-like behavior in adulthood. Plasma corticosterone and expression levels of corticotropin-releasing hormone mRNA in the hypothalamic paraventricular nucleus and in the central nucleus of the amygdala were significantly elevated in adult rats that had undergone activity-based anorexia in adolescence in response to the open field exposure, as compared to control rats. These data demonstrate enduring effects of adolescent activity-based anorexia on anxiety-like behavior and neuroendocrine factors critical in stress responsivity in adulthood. Furthermore, we demonstrate that activity-based anorexia during adolescence serves as a model whereby prolonged anxiety is induced, allowing for evaluation of the behavioral and neural correlates of mediating anxiety-like behaviors in adulthood. Copyright 2010 Elsevier Inc. All rights reserved.

Adolescent Activity-Based Anorexia Increases Anxiety-Like Behavior in Adulthood

PubMed Central

Kinzig, Kimberly P.; Hargrave, Sara L.

2010-01-01

Activity-based anorexia is a paradigm that induces increased physical activity, reduced food intake, and heightened activity of the hypothalamic-pituitary-adrenal axis in adult rats. To investigate whether experience with activity-based anorexia produced enduring effects on brain and behavior, female adolescent rats experienced activity-based anorexia during adolescence and were tested in adulthood for anxiety-like behavior on an elevated plus maze and in an open field. Analysis of elevated plus maze and open field behavior in adulthood revealed that rats that experienced activity-based anorexia during adolescence, but not rats that were simply food restricted, displayed increased anxiety-like behavior in adulthood. Plasma corticosterone and expression levels of corticotropin- releasing hormone mRNA in the hypothalamic paraventricular nucleus and in the central nucleus of the amygdala were significantly elevated in adult rats that had undergone activity-based anorexia in adolescence in response to the open field exposure, as compared to control rats. These data demonstrate enduring effects of adolescent activity-based anorexia on anxiety-like behavior and neuroendocrine factors critical in stress responsivity in adulthood. Furthermore, we demonstrate that activity-based anorexia during adolescence serves as a model whereby prolonged anxiety is induced, allowing for evaluation of the behavioral and neural correlates of mediating anxiety-like behaviors in adulthood. PMID:20566408

Bathymetric and underwater video survey of Lower Granite Reservoir and vicinity, Washington and Idaho, 2009-10

USGS Publications Warehouse

Williams, Marshall L.; Fosness, Ryan L.; Weakland, Rhonda J.

2012-01-01

The U.S. Geological Survey conducted a bathymetric survey of the Lower Granite Reservoir, Washington, using a multibeam echosounder, and an underwater video mapping survey during autumn 2009 and winter 2010. The surveys were conducted as part of the U.S. Army Corps of Engineer's study on sediment deposition and control in the reservoir. The multibeam echosounder survey was performed in 1-mile increments between river mile (RM) 130 and 142 on the Snake River, and between RM 0 and 2 on the Clearwater River. The result of the survey is a digital elevation dataset in ASCII coordinate positioning data (easting, northing, and elevation) useful in rendering a 3×3-foot point grid showing bed elevation and reservoir geomorphology. The underwater video mapping survey was conducted from RM 107.73 to 141.78 on the Snake River and RM 0 to 1.66 on the Clearwater River, along 61 U.S. Army Corps of Engineers established cross sections, and dredge material deposit transects. More than 900 videos and 90 bank photographs were used to characterize the sediment facies and ground-truth the multibeam echosounder data. Combined, the surveys were used to create a surficial sediment facies map that displays type of substrate, level of embeddedness, and presence of silt.

Prevalence and causes of abnormal liver function in patients with coeliac disease.

PubMed

Casella, Giovanni; Antonelli, Elisabetta; Di Bella, Camillo; Villanacci, Vincenzo; Fanini, Lucia; Baldini, Vittorio; Bassotti, Gabrio

2013-08-01

Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten-free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten-free diet. Data from 245 untreated CD patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed. Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis. In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

How Varroa Parasitism Affects the Immunological and Nutritional Status of the Honey Bee, Apis mellifera.

PubMed

Aronstein, Katherine A; Saldivar, Eduardo; Vega, Rodrigo; Westmiller, Stephanie; Douglas, Angela E

2012-06-27

We investigated the effect of the parasitic mite Varroa destructor on the immunological and nutritional condition of honey bees, Apis mellifera, from the perspective of the individual bee and the colony. Pupae, newly-emerged adults and foraging adults were sampled from honey bee colonies at one site in S. Texas, USA. Varroa‑infested bees displayed elevated titer of Deformed Wing Virus (DWV), suggestive of depressed capacity to limit viral replication. Expression of genes coding three anti-microbial peptides (defensin1, abaecin, hymenoptaecin) was either not significantly different between Varroa-infested and uninfested bees or was significantly elevated in Varroa-infested bees, varying with sampling date and bee developmental age. The effect of Varroa on nutritional indices of the bees was complex, with protein, triglyceride, glycogen and sugar levels strongly influenced by life-stage of the bee and individual colony. Protein content was depressed and free amino acid content elevated in Varroa-infested pupae, suggesting that protein synthesis, and consequently growth, may be limited in these insects. No simple relationship between the values of nutritional and immune-related indices was observed, and colony-scale effects were indicated by the reduced weight of pupae in colonies with high Varroa abundance, irrespective of whether the individual pupa bore Varroa.

How Varroa Parasitism Affects the Immunological and Nutritional Status of the Honey Bee, Apis mellifera

PubMed Central

Aronstein, Katherine A.; Saldivar, Eduardo; Vega, Rodrigo; Westmiller, Stephanie; Douglas, Angela E.

2012-01-01

We investigated the effect of the parasitic mite Varroadestructor on the immunological and nutritional condition of honey bees, Apis mellifera, from the perspective of the individual bee and the colony. Pupae, newly-emerged adults and foraging adults were sampled from honey bee colonies at one site in S. Texas, USA. Varroa‑infested bees displayed elevated titer of Deformed Wing Virus (DWV), suggestive of depressed capacity to limit viral replication. Expression of genes coding three anti-microbial peptides (defensin1, abaecin, hymenoptaecin) was either not significantly different between Varroa-infested and uninfested bees or was significantly elevated in Varroa-infested bees, varying with sampling date and bee developmental age. The effect of Varroa on nutritional indices of the bees was complex, with protein, triglyceride, glycogen and sugar levels strongly influenced by life-stage of the bee and individual colony. Protein content was depressed and free amino acid content elevated in Varroa-infested pupae, suggesting that protein synthesis, and consequently growth, may be limited in these insects. No simple relationship between the values of nutritional and immune-related indices was observed, and colony-scale effects were indicated by the reduced weight of pupae in colonies with high Varroa abundance, irrespective of whether the individual pupa bore Varroa. PMID:26466617

Assessment of anxiety in open field and elevated plus maze using infrared thermography.

PubMed

Lecorps, Benjamin; Rödel, Heiko G; Féron, Christophe

2016-04-01

Due to their direct inaccessibility, affective states are classically assessed by gathering concomitant physiological and behavioral measures. Although such a dual approach to assess emotional states is frequently used in different species including humans, the invasiveness of procedures for physiological recordings particularly in smaller-sized animals strongly restricts their application. We used infrared thermography, a non-invasive method, to assess physiological arousal during open field and elevated plus maze tests in mice. By measuring changes in surface temperature indicative of the animals' emotional response, we aimed to improve the inherently limited and still controversial information provided by behavioral parameters commonly used in these tests. Our results showed significant and consistent thermal responses during both tests, in accordance with classical physiological responses occurring in stressful situations. Besides, we found correlations between these thermal responses and the occurrence of anxiety-related behaviors. Furthermore, initial temperatures measured at the start of each procedure (open field, elevated plus maze), which can be interpreted as a measure of the animals' initial physiological arousal, predicted the levels of activity and of anxiety-related behaviors displayed during the tests. Our results stress the strong link between physiological correlates of emotions and behaviors expressed during unconditioned fear tests. Copyright © 2016 Elsevier Inc. All rights reserved.

EarthObserver: Bringing the world to your fingertips

NASA Astrophysics Data System (ADS)

Ryan, W. B.; Goodwillie, A. M.; Coplan, J.; Carbotte, S. M.; Arko, R. A.; Ferrini, V.; O'hara, S. H.; Chan, S.; Bonczkowski, J.; Nitsche, F. O.; Morton, J. J.; McLain, K.; Weissel, R.

2011-12-01

EarthObserver (http://www.earth-observer.org/), developed by the Lamont-Doherty Earth Observatory of Columbia University, brings a wealth of geoscience data to Apple iPad, iPhone and iPod Touch mobile devices. Built around an easy-to-use interface, EarthObserver allows users to explore and visualise a wide range of data sets superimposed upon a detailed base map of land elevations and ocean depths - tapping the screen will instantly return the height or depth at that point. A simple transparency function allows direct comparison of built-in content. Data sets include high-resolution coastal bathymetry of bays, sounds, estuaries, harbors and rivers; geological maps of the US states and world - tapping the screen displays the rock type, and full legends can be viewed; US Topo sheets; and, geophysical content including seafloor crustal age and sediment thickness, earthquake and volcano data, gravity and magnetic anomalies, and plate boundary descriptions. The names of physiographic features are automatically displayed. NASA Visible Earth images along with ocean temperature, salinity and productivity maps and precipitation information expose data sets of interest to the atmospheric, oceanic and biological communities. Natural hazard maps, population information and political boundaries allow users to explore impacts upon society. EarthObserver, so far downloaded by more than 55,000 users, offers myriad ways for educators at all levels to bring research-quality geoscience data into the learning environment, whether for use as an in-class illustration or for extensive exploration of earth sciences data. By using cutting-edge mobile app technology, EarthObserver boosts access to relevant earth science content. The EarthObserver base map is the Global Multi-Resolution Topography digital elevation model (GMRT; http://www.marine-geo.org/portals/gmrt/), also developed at LDEO and updated regularly. It provides land elevations with horizontal resolution as high as 10m for mainland USA and 30m globally, and detailed oceanic depths derived from numerous sources including multibeam echo-soundings data.

Mice with Sort1 deficiency display normal cognition but elevated anxiety-like behavior.

PubMed

Ruan, Chun-Sheng; Yang, Chun-Rui; Li, Jia-Yi; Luo, Hai-Yun; Bobrovskaya, Larisa; Zhou, Xin-Fu

2016-07-01

Exposure to stressful life events plays a central role in the development of mood disorders in vulnerable individuals. However, the mechanisms that link mood disorders to stress are poorly understood. Brain-derived neurotrophic factor (BDNF) has long been implicated in positive regulation of depression and anxiety, while its precursor (proBDNF) recently showed an opposing effect on such mental illnesses. P75(NTR) and sortilin are co-receptors of proBDNF, however, the role of these receptors in mood regulation is not established. Here, we aimed to investigate the role of sortilin in regulating mood-related behaviors and its role in the proBDNF-mediated mood abnormality in mice. We found that sortilin was up-regulated in neocortex (by 78.3%) and hippocampus (by 111%) of chronically stressed mice as assessed by western blot analysis. These changes were associated with decreased mobility in the open field test and increased depression-like behavior in the forced swimming test. We also found that sortilin deficiency in mice resulted in hyperlocomotion in the open field test and increased anxiety-like behavior in both the open field and elevated plus maze tests. No depression-like behavior in the forced swimming test and no deficit in spatial cognition in the Morris water maze test were found in the Sort1-deficient mice. Moreover, the intracellular and extracellular levels of mature BDNF and proBDNF were not changed when sortilin was absent in vivo and in vitro. Finally, we found that both WT and Sort1-deficient mice injected with proBDNF in lateral ventricle displayed increased depression-like behavior in the forced swimming test but not anxiety-like behaviors in the open field and elevated plus maze tests. The present study suggests that sortilin functions as a negative regulator of mood performance and can be a therapeutic target for the treatment of mental illness. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

The New USGS Volcano Hazards Program Web Site

NASA Astrophysics Data System (ADS)

Venezky, D. Y.; Graham, S. E.; Parker, T. J.; Snedigar, S. F.

2008-12-01

The U.S. Geological Survey's (USGS) Volcano Hazard Program (VHP) has launched a revised web site that uses a map-based interface to display hazards information for U.S. volcanoes. The web site is focused on better communication of hazards and background volcano information to our varied user groups by reorganizing content based on user needs and improving data display. The Home Page provides a synoptic view of the activity level of all volcanoes for which updates are written using a custom Google® Map. Updates are accessible by clicking on one of the map icons or clicking on the volcano of interest in the adjacent color-coded list of updates. The new navigation provides rapid access to volcanic activity information, background volcano information, images and publications, volcanic hazards, information about VHP, and the USGS volcano observatories. The Volcanic Activity section was tailored for emergency managers but provides information for all our user groups. It includes a Google® Map of the volcanoes we monitor, an Elevated Activity Page, a general status page, information about our Volcano Alert Levels and Aviation Color Codes, monitoring information, and links to monitoring data from VHP's volcano observatories: Alaska Volcano Observatory (AVO), Cascades Volcano Observatory (CVO), Long Valley Observatory (LVO), Hawaiian Volcano Observatory (HVO), and Yellowstone Volcano Observatory (YVO). The YVO web site was the first to move to the new navigation system and we are working on integrating the Long Valley Observatory web site next. We are excited to continue to implement new geospatial technologies to better display our hazards and supporting volcano information.

BIG: a calossin-like protein required for polar auxin transport in Arabidopsis

PubMed Central

Gil, Pedro; Dewey, Elizabeth; Friml, Jiri; Zhao, Yunde; Snowden, Kimberley C.; Putterill, Jo; Palme, Klaus; Estelle, Mark; Chory, Joanne

2001-01-01

Polar auxin transport is crucial for the regulation of auxin action and required for some light-regulated responses during plant development. We have found that two mutants of Arabidopsis—doc1, which displays altered expression of light-regulated genes, and tir3, known for its reduced auxin transport—have similar defects and define mutations in a single gene that we have renamed BIG. BIG is very similar to the Drosophila gene Calossin/Pushover, a member of a gene family also present in Caenorhabditis elegans and human genomes. The protein encoded by BIG is extraordinary in size, 560 kD, and contains several putative Zn-finger domains. Expression-profiling experiments indicate that altered expression of multiple light-regulated genes in doc1 mutants can be suppressed by elevated levels of auxin caused by overexpression of an auxin biosynthetic gene, suggesting that normal auxin distribution is required to maintain low-level expression of these genes in the dark. Double mutants of tir3 with the auxin mutants pin1, pid, and axr1 display severe defects in auxin-dependent growth of the inflorescence. Chemical inhibitors of auxin transport change the intracellular localization of the auxin efflux carrier PIN1 in doc1/tir3 mutants, supporting the idea that BIG is required for normal auxin efflux. PMID:11485992

Terrestrial-passage theory: failing a test.

PubMed

Reed, Charles F; Krupinski, Elizabeth A

2009-01-01

Terrestrial-passage theory proposes that the 'moon' and 'sky' illusions occur because observers learn to expect an elevation-dependent transformation of visual angle. The transformation accompanies daily movement through ordinary environments of fixed-altitude objects. Celestial objects display the same visual angle at all elevations, and hence are necessarily non-conforming with the ordinary transformation. On hypothesis, observers should target angular sizes to appear greater at elevation than at horizon. However, in a sample of forty-eight observers there was no significant difference between the perceived angular size of a constellation of stars at horizon and that predicted for a specific elevation. Occurrence of the illusion was not restricted to those observers who expected angular expansion. These findings fail to support the terrestrial-passage theory of the illusion.

Vertical and Horizontal Vegetation Structure across Natural and Modified Habitat Types at Mount Kilimanjaro.

PubMed

Rutten, Gemma; Ensslin, Andreas; Hemp, Andreas; Fischer, Markus

2015-01-01

In most habitats, vegetation provides the main structure of the environment. This complexity can facilitate biodiversity and ecosystem services. Therefore, measures of vegetation structure can serve as indicators in ecosystem management. However, many structural measures are laborious and require expert knowledge. Here, we used consistent and convenient measures to assess vegetation structure over an exceptionally broad elevation gradient of 866-4550 m above sea level at Mount Kilimanjaro, Tanzania. Additionally, we compared (human)-modified habitats, including maize fields, traditionally managed home gardens, grasslands, commercial coffee farms and logged and burned forests with natural habitats along this elevation gradient. We distinguished vertical and horizontal vegetation structure to account for habitat complexity and heterogeneity. Vertical vegetation structure (assessed as number, width and density of vegetation layers, maximum canopy height, leaf area index and vegetation cover) displayed a unimodal elevation pattern, peaking at intermediate elevations in montane forests, whereas horizontal structure (assessed as coefficient of variation of number, width and density of vegetation layers, maximum canopy height, leaf area index and vegetation cover) was lowest at intermediate altitudes. Overall, vertical structure was consistently lower in modified than in natural habitat types, whereas horizontal structure was inconsistently different in modified than in natural habitat types, depending on the specific structural measure and habitat type. Our study shows how vertical and horizontal vegetation structure can be assessed efficiently in various habitat types in tropical mountain regions, and we suggest to apply this as a tool for informing future biodiversity and ecosystem service studies.

Insulin has a biphasic effect on the ability of human chorionic gonadotropin to induce ovarian cysts in the rat.

PubMed

Bogovich, K; Clemons, J; Poretsky, L

1999-08-01

Hyperinsulinemia enhances the ability of subovulatory doses of human chorionic gonadotropin (hCG) to induce ovarian follicular cysts in the rat. To determine the relative contribution of these hormones to the development of ovarian cysts, adult female rats were treated with either (1) vehicle alone (controls), (2) a high-fat diet (HFD) to control for the effects of weight gain, (3) 1.5 to 6 IU hCG twice daily plus 6 U insulin (Ins)/d, or (4) 1.5 to 9 U Ins/d plus 3 IU hCG twice daily. On day 23 of the in vivo treatments, all groups that received at least 6 U Ins/d displayed increased body weight compared with control and HFD rats (P < or = .05). No control rats and only one HFD rat displayed ovarian cysts on this day. Plasma estrone (E1) and androstenedione (A4) were elevated in HFD rats with noncystic follicles compared with control rats (P < or = .05). Between 64% and 80% of rats on 6 U Ins/d plus twice-daily injections of 1.5 to 6 IU hCG displayed ovarian cysts on day 23. Plasma estradiol (E2) concentrations for these treatment groups were similar to those of control rats. Of the hormonally treated animals, only those that had ovarian cysts in response to twice-daily injections of 4.5 or 6 IU hCG plus 6 U Ins/d displayed elevated plasma A4 and/or testosterone compared with controls. In contrast, plasma E1 concentrations were elevated on day 23 for animals bearing ovarian cysts in response to increasing doses of hCG plus the fixed dose of 6 U Ins/d. Between 70% and 80% of rats treated twice daily with 3 IU hCG plus a daily dose of 1.5 to 6 U Ins displayed ovarian cysts on day 23. In marked contrast, only 25% of rats treated with this dose of hCG plus 9 U Ins/d developed cystic follicles. Of the plasma steroids tested, only E1 and A4 were elevated in these treatment groups compared with controls. However, these increases in plasma steroid concentrations did not correlate with the dose of insulin. We conclude from these data that, although the mechanisms remain to be elucidated, extreme hyperinsulinemia has the paradoxical ability to attenuate the induction of ovarian cysts by hCG in some animals.

Extremely Long-Lived Stigmas Allow Extended Cross-Pollination Opportunities in a High Andean Plant

PubMed Central

Torres-Díaz, Cristian; Gómez-González, Susana; Stotz, Gisela C.; Torres-Morales, Patricio; Paredes, Brayam; Pérez-Millaqueo, Matías; Gianoli, Ernesto

2011-01-01

High-elevation ecosystems are traditionally viewed as environments in which predominantly autogamous breeding systems should be selected because of the limited pollinator availability. Chaetanthera renifolia (Asteraceae) is an endemic monocarpic triennial herb restricted to a narrow altitudinal range within the high Andes of central Chile (3300–3500 m a.s.l.), just below the vegetation limit. This species displays one of the larger capitulum within the genus. Under the reproductive assurance hypothesis, and considering its short longevity (monocarpic triennial), an autogamous breeding system and low levels of pollen limitation would be predicted for C. renifolia. In contrast, considering its large floral size, a xenogamous breeding system, and significant levels of pollen limitation could be expected. In addition, the increased pollination probability hypothesis predicts prolonged stigma longevity for high alpine plants. We tested these alternative predictions by performing experimental crossings in the field to establish the breeding system and to measure the magnitude of pollen limitation in two populations of C. renifolia. In addition, we measured the stigma longevity in unpollinated and open pollinated capitula, and pollinator visitation rates in the field. We found low levels of self-compatibility and significant levels of pollen limitation in C. renifolia. Pollinator visitation rates were moderate (0.047–0.079 visits per capitulum per 30 min). Although pollinator visitation rate significantly differed between populations, they were not translated into differences in achene output. Finally, C. renifolia stigma longevity of unpollinated plants was extremely long and significantly higher than that of open pollinated plants (26.3±2.8 days vs. 10.1±2.2, respectively), which gives support to the increased pollination probability hypothesis for high-elevation flowering plants. Our results add to a growing number of studies that show that xenogamous breeding systems and mechanisms to increase pollination opportunities can be selected in high-elevation ecosystems. PMID:21573159

Polyphenolics from mango (Mangifera indica L.) suppress breast cancer ductal carcinoma in situ proliferation through activation of AMPK pathway and suppression of mTOR in athymic nude mice.

PubMed

Nemec, Matthew J; Kim, Hyemee; Marciante, Alexandria B; Barnes, Ryan C; Hendrick, Erik D; Bisson, William H; Talcott, Stephen T; Mertens-Talcott, Susanne U

2017-03-01

The objective of this study was to assess the underlying mechanisms of mango polyphenol decreased cell proliferation and tumor volume in ductal carcinoma in situ breast cancer. We hypothesized that mango polyphenols suppress signaling along the AKT/mTOR axis while up-regulating AMPK. To test this hypothesis, mango polyphenols (0.8 mg gallic acid equivalents per day) and pyrogallol (0.2 mg/day) were administered for 4 weeks to mice xenografted with MCF10DCIS.com cells subcutaneously (n=10 per group). Tumor volumes were significantly decreased, both mango and pyrogallol groups displayed greater than 50% decreased volume compared to control. There was a significant reduction of phosphorylated protein levels of IR, IRS1, IGF-1R, and mTOR by mango; while pyrogallol significantly reduced the phosphorylation levels of IR, IRS1, IGF-1R, p70S6K, and ERK. The protein levels of Sestrin2, which is involved in AMPK-signaling, were significantly elevated in both groups. Also, mango significantly elevated AMPK phosphorylation and pyrogallol significantly elevated LKB1 protein levels. In an in vitro model, mango and pyrogallol increased reactive oxygen species (ROS) generation and arrested cells in S phase. In silico modeling indicates that pyrogallol has the potential to bind directly to the allosteric binding site of AMPK, inducing activation. When AMPK expression was down-regulated using siRNA in vitro, pyrogallol reversed the reduced expression of AMPK. This indicates that pyrogallol not only activates AMPK, but also increases constitutive protein expression. These results suggest that mango polyphenols and their major microbial metabolite, pyrogallol, inhibit proliferation of breast cancer cells through ROS-dependent up-regulation of AMPK and down-regulation of the AKT/mTOR pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Terrain Portrayal for Head-Down Displays Experiment

NASA Technical Reports Server (NTRS)

Hughes, Monica F.; Takallu, M. A.

2002-01-01

The General Aviation Element of the Aviation Safety Program's Synthetic Vision Systems (SVS) Project is developing technology to eliminate low visibility induced General Aviation (GA) accidents. SVS displays present computer generated 3-dimensional imagery of the surrounding terrain on the Primary Flight Display (PFD) to greatly enhance pilot's situation awareness (SA), reducing or eliminating Controlled Flight into Terrain, as well as Low-Visibility Loss of Control accidents. SVS-conducted research is facilitating development of display concepts that provide the pilot with an unobstructed view of the outside terrain, regardless of weather conditions and time of day. A critical component of SVS displays is the appropriate presentation of terrain to the pilot. An experimental study has been conducted at NASA Langley Research Center (LaRC) to explore and quantify the relationship between the realism of the terrain presentation and resulting enhancements of pilot SA and pilot performance. Composed of complementary simulation and flight test efforts, Terrain Portrayal for Head-Down Displays (TP-HDD) experiments will help researchers evaluate critical terrain portrayal concepts. The experimental effort is to provide data to enable design trades that optimize SVS applications, as well as develop requirements and recommendations to facilitate the certification process. This paper focuses on the experimental set-up and preliminary qualitative results of the TP-HDD simulation experiment. In this experiment a fixed based flight simulator was equipped with various types of Head Down flight displays, ranging from conventional round dials (typical of most GA aircraft) to glass cockpit style PFD's. The variations of the PFD included an assortment of texturing and Digital Elevation Model (DEM) resolution combinations. A test matrix of 10 terrain display configurations (in addition to the baseline displays) were evaluated by 27 pilots of various backgrounds and experience levels. Qualitative (questionnaires) and quantitative (pilot performance and physiological) data were collected during the experimental runs. Preliminary results indicate that all of the evaluation pilots favored SVS displays over standard gauges, in terms of terrain awareness, SA, and perceived pilot performance. Among the terrain portrayal concepts tested, most pilots preferred the higher-resolution DEM. In addition, with minimal training, low-hour VFR evaluation pilots were able to negotiate a precision approach using SVS displays with a tunnel in the sky guidance concept.

An APOA1 promoter polymorphism is associated with cognitive performance in patients with multiple sclerosis.

PubMed

Koutsis, G; Panas, M; Giogkaraki, E; Karadima, G; Sfagos, C; Vassilopoulos, D

2009-02-01

Elevated ApoA1 levels have been associated with decreased dementia risk. The A-allele of the APOA1 -75G/A promoter polymorphism has been associated with elevated ApoA1 levels. We sought to investigate the effect of the APOA1 -75G/A promoter polymorphism on cognitive performance in patients with multiple sclerosis (MS). A total of 138 patients with MS and 43 controls were studied and underwent neuropsychological assessment with Rao's Brief Repeatable Battery and the Stroop test. All patients were genotyped for APOA1. APOA1 A-allele carriers displayed superior overall cognitive performance compared with non-carriers (P 0.008) and had a three-fold decrease in the relative risk of overall cognitive impairment (OR 0.29, 95% CI 0.11-0.74). Regarding performance on individual cognitive domains, although APOA1 A-allele carriers performed better than non-carriers on all tests, this was significant only for semantic verbal fluency and the Stroop interference task (P 0.036 and 0.018, respectively). We found an association of the APOA1 -75G/A promoter polymorphism with cognitive performance in MS. This effect was most prominent on semantic verbal fluency and the Stroop interference task.

Genetic and morphologic variation in 'Phyllodoce empetriformis' and 'P. glanduliflora' (Ericaceae) in Mount Rainier National Park, Washington

USGS Publications Warehouse

Rochefort, Regina M.; Peterson, D.L.

2001-01-01

Genetic and morphological diversity of Phyllodoce empetriformis (Sw.) D. Don and Phyllodoce glanduliflora (hook.) Cov. were surveyed in Mount Rainier National Park in the Cascade Mountains of Washington State. Paired populations at high and low elevations were sampled at three study areas between 1720- and 2451-m elevation. Allozyme analysis of four polymorphic loci indicates high levels of genetic diversity within populations (P. empetriformis = 94.2% and P. glanduliflora = 93.4% of total diversity) and significant differences in allele frequencies among populations and study areas. Individual populations are composed of multiple clones with high ratios of local to widespread genotypes. The proportion of distinguishable clones ranges from 32 to 83% within individual populations. Within individual populations, 18-67% of genotypes were restricted to one population. Patterns of morphologic variation, estimated through measurements of leaf width, leaf length, stem extension, and plant height paralleled those displayed by allozyme analysis. Significant differences were found in leaf width and stem length for P. empetriformis and among greenhouse populations for leaf width (P. empetriformis) and leaf length (P. glanduliflora). Species conservation strategies for Phyllodoce should concentrate on the maintenance of within-population levels of diversity, protection of adjacent populations, and protection of safe sites for recruitment of new populations.

A reconnaissance analysis of groundwater quality in the Eagle Ford shale region reveals two distinct bromide/chloride populations.

PubMed

Hildenbrand, Zacariah L; Carlton, Doug D; Meik, Jesse M; Taylor, Josh T; Fontenot, Brian E; Walton, Jayme L; Henderson, Drew; Thacker, Jonathan B; Korlie, Stephanie; Whyte, Colin J; Hudak, Paul F; Schug, Kevin A

2017-01-01

The extraction of oil and natural gas from unconventional shale formations has prompted a series of investigations to examine the quality of the groundwater in the overlying aquifers. Here we present a reconnaissance analysis of groundwater quality in the Eagle Ford region of southern Texas. These data reveal two distinct sample populations that are differentiable by bromide/chloride ratios. Elevated levels of fluoride, nitrate, sulfate, various metal ions, and the detection of exotic volatile organic compounds highlight a high bromide group of samples, which is geographically clustered, while encompassing multiple hydrogeological strata. Samples with bromide/chloride ratios representative of connate water displayed elevated levels of total organic carbon, while revealing the detection of alcohols and chlorinated compounds. These findings suggest that groundwater quality in the Western Gulf Basin is, for the most part, controlled by a series of natural processes; however, there is also evidence of episodic contamination events potentially attributed to unconventional oil and gas development or other anthropogenic activities. Collectively, this characterization of natural groundwater constituents and exogenous compounds will guide targeted remediation efforts and provides insight for agricultural entities, industrial operators, and rural communities that rely on groundwater in southern Texas. Copyright © 2016 Elsevier B.V. All rights reserved.

Mipomersen sodium: a new option for the treatment of familial hypercholesterolemia.

PubMed

Haddley, K

2011-12-01

In collaboration with Genzyme, Isis Pharmaceuticals has developed mipomersen sodium (ISIS-310312), a synthetic second-generation 20-base phosphorothioate antisense oligonucleotide (ASO) that targets messenger RNA encoding apolipoprotein B-100 (Apo B-100). Elevated cholesterol levels, in particular low-density lipoprotein cholesterol (LDL-C) which contains a single apolipoprotein B (ApoB) molecule, have been directly correlated with the incidence of cardiovascular events. Preclinical investigations in transgenic mice have demonstrated that lowering LDL-C or ApoB can reduce aortic plaque formation associated with atherosclerosis. Mipomersen pharmacokinetics showed a wide and rapid tissue distribution and a slow prolonged elimination phase of several days in a range of species. Mipomersen displayed dose-dependent efficacy in lowering LDL-C, ApoB, triglycerides, total cholesterol and other low-density lipoproteins in healthy volunteers with mild hyperlipidemia. Similar decreases were observed in patients on stable lipid-lowering therapy for familial hypercholesterolemia with baseline LDL-C levels declining towards clinically desirable concentrations of 70 mg/dL. The efficacy of mipomersen in treating patients with severe heterozygous or homozygous familial hypercholesterolemia with cardiovascular complications has been recently assessed. There have been no serious adverse events noted with treatment and mipomersen can be administered in combination with other lipid-lowering therapies. One concern noted was an elevation in liver transaminase concentrations, although these increases were reversible.

Cortisol elevation post-hatch affects behavioural performance in zebrafish larvae.

PubMed

Best, Carol; Vijayan, Mathilakath M

2018-02-01

Maternal cortisol is essential for cortisol stress axis development and de novo production of this steroid commences only after hatch in zebrafish (Danio rerio). However, very little is known about the effect of elevated cortisol levels, during the critical period of stress axis activation, on larval performance. We tested the hypothesis that elevated cortisol levels post-hatch affect behavioural performance and this is mediated by glucocorticoid receptor (GR) activation in zebrafish larvae. The behavioural response included measuring larval activity in response to alternating light and dark cycles, as well as thigmotaxis. Zebrafish larvae at 3days post-fertilization were exposed to waterborne cortisol for 24h to mimic a steroid response to an early-life stressor exposure. Also, larvae were exposed to waterborne RU-486 (a GR antagonist) either in the presence or absence of cortisol to confirm GR activation. Co-treatment with RU-486 completely abolished the upregulation of cortisol-induced 11β-hydroxysteroid dehydrogenase type 2 transcript abundance, confirming GR signalling. Cortisol-exposed larvae displayed increased locomotor activity irrespective of light condition, but showed no changes in thigmotaxis. This cortisol-mediated behavioural response was not affected by co-treatment with RU-486. Cortisol exposure also did not modify the transcript abundances of GR and mineralocorticoid receptor (MR) in zebrafish larvae. Altogether, cortisol stress axis activation post-hatch increases locomotor activity in zebrafish larvae. Our results suggest that GR signalling may not be involved in this behavioural response, leading to the proposal that cortisol action via MR signalling may influence locomotor activity in zebrafish larvae. Copyright © 2017 Elsevier Inc. All rights reserved.

Protein expression profiling of the drosophila fragile X mutant brain reveals up-regulation of monoamine synthesis.

PubMed

Zhang, Yong Q; Friedman, David B; Wang, Zhe; Woodruff, Elvin; Pan, Luyuan; O'donnell, Janis; Broadie, Kendal

2005-03-01

Fragile X syndrome is the most common form of inherited mental retardation, associated with both cognitive and behavioral anomalies. The disease is caused by silencing of the fragile X mental retardation 1 (fmr1) gene, which encodes the mRNA-binding, translational regulator FMRP. Previously we established a disease model through mutation of Drosophila fmr1 (dfmr1) and showed that loss of dFMRP causes defects in neuronal structure, function, and behavioral output similar to the human disease state. To uncover molecular targets of dFMRP in the brain, we use here a proteomic approach involving two-dimensional difference gel electrophoresis analyses followed by mass spectrometry identification of proteins with significantly altered expression in dfmr1 null mutants. We then focus on two misregulated enzymes, phenylalanine hydroxylase (Henna) and GTP cyclohydrolase (Punch), both of which mediate in concert the synthetic pathways of two key monoamine neuromodulators, dopamine and serotonin. Brain enzymatic assays show a nearly 2-fold elevation of Punch activity in dfmr1 null mutants. Consistently brain neurochemical assays show that both dopamine and serotonin are significantly increased in dfmr1 null mutants. At a cellular level, dfmr1 null mutant neurons display a highly significant elevation of the dense core vesicles that package these monoamine neuromodulators for secretion. Taken together, these data indicate that dFMRP normally down-regulates the monoamine pathway, which is consequently up-regulated in the mutant condition. Elevated brain levels of dopamine and serotonin provide a plausible mechanistic explanation for aspects of cognitive and behavioral deficits in human patients.

The stomatal CO2 proxy does not saturate at high atmospheric CO2 concentrations: evidence from stomatal index responses of Araucariaceae conifers.

PubMed

Haworth, Matthew; Elliott-Kingston, Caroline; McElwain, Jennifer C

2011-09-01

The inverse relationship between the number of stomata on a leaf surface and the atmospheric carbon dioxide concentration ([CO(2)]) in which the leaf developed allows plants to optimise water-use efficiency (WUE), but it also permits the use of fossil plants as proxies of palaeoatmospheric [CO(2)]. The ancient conifer family Araucariaceae is often represented in fossil floras and may act as a suitable proxy of palaeo-[CO(2)], yet little is known regarding the stomatal index (SI) responses of extant Araucariaceae to [CO(2)]. Four Araucaria species (Araucaria columnaris, A. heterophylla, A. angustifolia and A. bidwillii) and Agathis australis displayed no significant relationship in SI to [CO(2)] below current ambient levels (~380 ppm). However, representatives of the three extant genera within the Araucariaceae (A. bidwillii, A. australis and Wollemia nobilis) all exhibited significant reductions in SI when grown in atmospheres of elevated [CO(2)] (1,500 ppm). Stomatal conductance was reduced and WUE increased when grown under elevated [CO(2)]. Stomatal pore length did not increase alongside reduced stomatal density (SD) and SI in the three araucariacean conifers when grown at elevated [CO(2)]. These pronounced SD and SI reductions occur at higher [CO(2)] levels than in other species with more recent evolutionary origins, and may reflect an evolutionary legacy of the Araucariaceae in the high [CO(2)] world of the Mesozoic Era. Araucariacean conifers may therefore be suitable stomatal proxies of palaeo-[CO(2)] during periods of "greenhouse" climates and high [CO(2)] in the Earth's history.

Adiponectin gene therapy ameliorates high-fat, high-sucrose diet-induced metabolic perturbations in mice

PubMed Central

Kandasamy, A D; Sung, M M; Boisvenue, J J; Barr, A J; Dyck, J R B

2012-01-01

Background and Design: Adiponectin is an adipokine secreted primarily from adipose tissue that can influence circulating plasma glucose and lipid levels through multiple mechanisms involving a variety of organs. In humans, reduced plasma adiponectin levels induced by obesity are associated with insulin resistance and type 2 diabetes, suggesting that low adiponectin levels may contribute the pathogenesis of obesity-related insulin resistance. Methods and Results: The objective of the present study was to investigate whether gene therapy designed to elevate circulating adiponectin levels is a viable strategy for ameliorating insulin resistance in mice fed a high-fat, high-sucrose (HFHS) diet. Electroporation-mediated gene transfer of mouse adiponectin plasmid DNA into gastrocnemius muscle resulted in elevated serum levels of globular and high-molecular weight adiponectin compared with control mice treated with empty plasmid. In comparison to HFHS-fed mice receiving empty plasmid, mice receiving adiponectin gene therapy displayed significantly decreased weight gain following 13 weeks of HFHS diet associated with reduced fat accumulation, and exhibited increased oxygen consumption and locomotor activity as measured by indirect calorimetry, suggesting increased energy expenditure in these mice. Consistent with improved whole-body metabolism, mice receiving adiponectin gene therapy also had lower blood glucose and insulin levels, improved glucose tolerance and reduced hepatic gluconeogenesis compared with control mice. Furthermore, immunoblot analysis of livers from mice receiving adiponectin gene therapy showed an increase in insulin-stimulated phosphorylation of insulin signaling proteins. Conclusion: Based on these data, we conclude that adiponectin gene therapy ameliorates the metabolic abnormalities caused by feeding mice a HFHS diet and may be a potential therapeutic strategy to improve obesity-mediated impairments in insulin sensitivity. PMID:23446660

Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis.

PubMed

Li, Hong-Yan; Zhao, Ying-Hua; Zeng, Min-Jie; Fang, Fang; Li, Min; Qin, Ting-Ting; Ye, Lu-Yu; Li, Hong-Wei; Qu, Rong; Ma, Shi-Ping

2017-11-01

Saikosaponin D (SSD), a major bioactive component isolated from Radix Bupleuri, has been reported to exert neuroprotective properties. The present study was designed to investigate the anti-depressant-like effects and the potential mechanisms of SSD. Behavioural tests including sucrose preference test (SPT), open field test (OFT) and forced swim test (FST) were performed to study the antidepressant-like effects of SSD. In addition, we examined corticosterone and glucocorticoid receptor (GR) levels to evaluate hypothalamic-pituitary-adrenal (HPA) axis function. Furthermore, hippocampal neurogenesis was assessed by testing doublecortin (DCX) levels, and neurotrophic molecule levels were also investigated in the hippocampus of rats. We found that unpredictable chronic mild stress (UCMS) rats displayed lost body weight, decreased sucrose consumption in SPT, reduced locomotive activity in OFT, and increased immobility time in FST. Chronic treatment with SSD (0.75, 1.50 mg/kg) remarkably ameliorated the behavioral deficiency induced by UCMS procedure. SSD administration downregulated elevated serum corticosterone levels, as well as alleviated the suppression of GR expression and nuclear translocation caused by UCMS, suggesting that SSD is able to remit the dysfunction of HPA axis. In addition, Western blot and immunohistochemistry analysis showed that SSD treatment significantly increased the generation of neurons in the hippocampus of UCMS rats indicated by elevated DCX levels. Moreover, hippocampal neurotrophic molecule levels of UCMS rats such as phosphorylated cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were raised after SSD treatment. Together, Our results suggest that SSD opposed UCMS-induced depressive behaviors in rats, which was mediated, partially, by the enhancement of HPA axis function and consolidation of hippocampal neurogenesis.

Depolarization- and transmitter-induced changes in intracellular Ca2+ of rat cerebellar granule cells in explant cultures.

PubMed

Connor, J A; Tseng, H Y; Hockberger, P E

1987-05-01

Digital imaging of the Ca indicator fura-2 has been used to study the responses of developing granule cells in culture to depolarization and transmitter action. Unstimulated cells bathed in Krebs saline exhibited cytoplasmic Ca ion concentrations, [Ca2+], that were generally in the 30-60 nM range. Exposure of cells to high-potassium (25 mM) saline depolarized the membrane potential and produced an immediate rise in [Ca2+] that recovered within 2-3 min in normal saline. The response grew progressively larger over the first 20 d in culture. Transient increases in [Ca2+] to levels greater than 1 microM were observed after 12-14 d in vitro, at which time the cells displayed intense electrical activity when exposed to high K. At this stage, the increases were attenuated by blocking action potential activity with TTX. In TTX-treated or immature cells, in which the transient phase of the Ca change was relatively small, a second exposure to high K typically produced a much larger Ca response that the initial exposure. The duration of this facilitation of the response persisted for periods longer than 5 min. Application of the neurotransmitter GABA induced a transient increase in membrane conductance, with a reversal potential near resting potential (approx. -60 mV), and caused an intracellular Ca2+ increase that outlasted the exposure to GABA by several minutes. Glutamate, or kainate, induced an increase in membrane conductance but with a reversal potential more positive than spike threshold. These agents also elevated intracellular Ca2+, but unlike the case with GABA, this Ca response reversed rapidly upon removal of the transmitter. The facilitatory effect of repeated exposures to high-K saline, as well as the persistent Ca elevation following a brief GABA application, suggests that granule cells possess the capability of displaying activity-dependent changes in Ca levels in culture.

Enrichment of Arsenic in Surface Water, Stream Sediments and Soils in Tibet.

PubMed

Li, Shehong; Wang, Mingguo; Yang, Qiang; Wang, Hui; Zhu, Jianming; Zheng, Baoshan; Zheng, Yan

2013-12-01

Groundwater in sedimentary deposits in China, Southern, and Southeast Asia down gradient from the Tibetan plateau contain elevated As concentrations on a regional scale. To ascertain the possibility of source region As enrichment, samples of water (n=86), stream sediment (n=77) and soil (n=73) were collected from the Singe Tsangpo (upstream of the Indus River), Yarlung Tsangpo (upstream of the Brahmaputra River) and other drainage basins in Tibet in June of 2008. The average arsenic concentration in stream waters, sediments and soils was 58±70 μg/L (n=39, range 2-252 μg/L), 42±40 mg/kg (n=37, range 12-227 mg/kg), and 44±27mg/kg (n=28, range 12-84 mg/kg) respectively for the Singe Tsangpo and was 11±17 μg/L (n=30, range 2-83 μg/L), 28±11 mg/kg (n=28, range 2-61 mg/kg), and 30±34 mg/kg (n=21, range 6-173 mg/kg) respectively for the Yarlung Tsangpo. A dug well contained 195 μg/L of As. In addition to elevated As levels in surface and shallow groundwater of Tibet, hot spring and alkaline salt lake waters displayed very high As levels, reaching a maximum value of 5,985 μg/L and 10,626 μg/L As, respectively. The positive correlation between [As] and [Na]+[K] in stream waters indicates that these surface water arsenic enrichments are linked to the hot springs and/or salt lakes. Further, 24% of As in stream sediment is reductively leachable, with bulk As displaying a positive correlation with stream water As, suggesting sorption from stream water. In contrast, the fraction of reductively leachable As is negligible for soils and several rock samples, suggesting that As in them are associated with unweathered minerals. Whether the pronounced As anomaly found in Tibet affects the sedimentary As content in deltas downstream or not requires further study.

Enrichment of Arsenic in Surface Water, Stream Sediments and Soils in Tibet

PubMed Central

Li, Shehong; Wang, Mingguo; Yang, Qiang; Wang, Hui; Zhu, Jianming; Zheng, Baoshan; Zheng, Yan

2013-01-01

Groundwater in sedimentary deposits in China, Southern, and Southeast Asia down gradient from the Tibetan plateau contain elevated As concentrations on a regional scale. To ascertain the possibility of source region As enrichment, samples of water (n=86), stream sediment (n=77) and soil (n=73) were collected from the Singe Tsangpo (upstream of the Indus River), Yarlung Tsangpo (upstream of the Brahmaputra River) and other drainage basins in Tibet in June of 2008. The average arsenic concentration in stream waters, sediments and soils was 58±70 μg/L (n=39, range 2-252 μg/L), 42±40 mg/kg (n=37, range 12-227 mg/kg), and 44±27mg/kg (n=28, range 12-84 mg/kg) respectively for the Singe Tsangpo and was 11±17 μg/L (n=30, range 2-83 μg/L), 28±11 mg/kg (n=28, range 2-61 mg/kg), and 30±34 mg/kg (n=21, range 6-173 mg/kg) respectively for the Yarlung Tsangpo. A dug well contained 195 μg/L of As. In addition to elevated As levels in surface and shallow groundwater of Tibet, hot spring and alkaline salt lake waters displayed very high As levels, reaching a maximum value of 5,985 μg/L and 10,626 μg/L As, respectively. The positive correlation between [As] and [Na]+[K] in stream waters indicates that these surface water arsenic enrichments are linked to the hot springs and/or salt lakes. Further, 24% of As in stream sediment is reductively leachable, with bulk As displaying a positive correlation with stream water As, suggesting sorption from stream water. In contrast, the fraction of reductively leachable As is negligible for soils and several rock samples, suggesting that As in them are associated with unweathered minerals. Whether the pronounced As anomaly found in Tibet affects the sedimentary As content in deltas downstream or not requires further study. PMID:24367140

Maternal obesity in the rat programs male offspring exploratory, learning and motivation behavior: prevention by dietary intervention pre-gestation or in gestation.

PubMed

Rodriguez, J S; Rodríguez-González, G L; Reyes-Castro, L A; Ibáñez, C; Ramírez, A; Chavira, R; Larrea, F; Nathanielsz, P W; Zambrano, E

2012-04-01

We studied the effects of maternal high fat diet (HFD, 25% calories from fat administered before and during pregnancy and lactation) and dietary intervention (switching dams from HFD to control diet) at different periconceptional periods on male offspring anxiety related behavior, exploration, learning, and motivation. From weaning at postnatal day (PND) 21, female subjects produced to be the mothers in the study received either control diet (CTR - 5% calories from fat), HFD through pregnancy and lactation (MO), HFD during PNDs 21-90 followed by CTR diet (pre-gestation (PG) intervention) or HFD from PND 21 to 120 followed by CTR diet (gestation and lactation (G) intervention) and bred at PND 120. At 19 days of gestation maternal serum corticosterone was increased in MO and the PG and G dams showed partial recovery with intermediate levels. In offspring, no effects were found in the elevated plus maze test. In the open field test, MO and G offspring showed increase zone entries, displaying less thigmotaxis; PG offspring showed partial recuperation of this behavior. During initial operant conditioning MO, PG and G offspring displayed decreased approach behavior with subsequent learning impairment during the acquisition of FR-1 and FR-5 operant conditioning for sucrose reinforcement. Motivation during the progressive ratio test increased in MO offspring; PG and G intervention recuperated this behavior. We conclude that dietary intervention can reverse negative effects of maternal HFD and offspring outcomes are potentially due to elevated maternal corticosterone. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Neuropsychological dysfunction in patients suffering from end-stage chronic obstructive pulmonary disease

PubMed Central

Crews, W. David; Jefferson, Angela L.; Bolduc, Tara; Elliott, Jennifer B.; Ferro, Nikola M.; Broshek, Donna K.; Barth, Jeffrey T.; Robbins, Mark K.

2009-01-01

Few studies have examined the neuropsychological sequelae associated with end-stage pulmonary disease. Neuropsychological data are presented for 47 patients with end-stage chronic obstructive pulmonary disease (COPD) who were being evaluated as potential candidates for lung transplantation. Although patients exhibited a diversity of neurocognitive deficits, their highest frequencies of impairment were found on the Selective Reminding Test (SRT). Specifically, over 50% of the patients completing the SRT exhibited impaired immediate free recall and consistent long-term retrieval deficits, while more than 44% of these individuals displayed deficient long-term retrieval. Deficient SRT long-term storage strategies, cued recall, and delayed recall were exhibited by between 26% and 35% of these patients, while more than 32% of this sample displayed elevated numbers of intrusion errors. Over 31% of the patients completing the Wisconsin Card Sorting Test (WCST) failed to achieve the expected number of categories on this measure, while more than 23% of these individuals demonstrated elevated numbers of perseverative errors and total errors. Clinically notable frequencies of impairment (greater than 20% of the sample) were also found on the Trail Making Test (TMT): Part B and the Wechsler Memory Scale-R (WMS-R) Visual Reproduction II subtest. Minnesota Multiphasic Personality Inventory-2 (MMPI-2) personality assessments indicated that patients were experiencing a diversity of somatic complaints and that they may have been functioning at a reduced level of efficiency. These findings are discussed in light of patients’ end-stage COPD and factors possibly contributing to their neuropsychological test performances. Implications for clinical practice and future research are also included. PMID:14589783

Anxiety-like behaviour in adult rats perinatally exposed to maternal calorie restriction.

PubMed

Levay, Elizabeth A; Paolini, Antonio G; Govic, Antonina; Hazi, Agnes; Penman, Jim; Kent, Stephen

2008-08-22

Environmental stimuli such as caloric availability during the perinatal period exert a profound influence on the development of an organism. Studies in this domain have focused on the effects of under- and malnutrition while the effects of more mild levels of restriction have not been delineated. Rat dams and their offspring were subjected to one of five dietary regimens: control, CR50% for 3 days preconception, CR25% during gestation, CR25% during lactation, and CR25% during gestation, lactation, and post-weaning (lifelong). The pup retrieval test and maternal observations were conducted during lactation to quantify maternal care. In the pup retrieval test, dams that were concurrently experiencing CR (i.e., from the lactation and lifelong groups) displayed shorter latencies to retrieve all pups than the control and preconception groups and the lactation group constructed better nests than all groups. Adult offspring were tested in three tests of anxiety: the elevated plus maze, open field, and emergence test. No differences were observed in the elevated plus maze; however, in the open field preconception animals made fewer entries and spent more time in the central zone than controls. In addition, preconception offspring exhibited longer latencies to full body emergence, spent less time fully emerged, and spent more time engaged in risk assessment behaviours than all other groups. Offspring from the preconception group were also on average 11% heavier than control rats throughout life and displayed 37% higher serum leptin concentrations than controls. A potential role for leptin in the anxiogenic effect of preconception CR is discussed.

Organized proteomic heterogeneity in colorectal cancer liver metastases and implications for therapies.

PubMed

Turtoi, Andrei; Blomme, Arnaud; Debois, Delphine; Somja, Joan; Delvaux, David; Patsos, Georgios; Di Valentin, Emmanuel; Peulen, Olivier; Mutijima, Eugène Nzaramba; De Pauw, Edwin; Delvenne, Philippe; Detry, Olivier; Castronovo, Vincent

2014-03-01

Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis displayed increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demonstrate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications. The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of targetable antigens. © 2014 by the American Association for the Study of Liver Diseases.

Poor comprehenders in the classroom: teacher ratings of behavior in children with poor reading comprehension and its relationship with individual differences in working memory.

PubMed

Pimperton, Hannah; Nation, Kate

2014-01-01

Differing etiological explanations have been proposed to account for poor comprehenders' difficulties with reading comprehension, with some researchers emphasizing working memory deficits and others arguing for oral language weaknesses playing a key causal role. The authors contrasted these two theoretical accounts using data obtained from direct measures of working memory and from teacher ratings of poor comprehenders' behavior in the classroom. At the group level, poor comprehenders showed weaknesses on verbal but not nonverbal working memory tasks, in keeping with the "language account." However, they also showed evidence of elevated levels of problem behaviors specifically associated with working memory deficits. Further analysis revealed that these group differences in working-memory-related problem behaviors were carried by a small subgroup of poor comprehenders who also displayed domain-general (verbal and nonverbal) working memory problems, argued to be reflective of "genuine" underlying working memory deficits.

Bilirubin measurements in neonates

NASA Astrophysics Data System (ADS)

Newman, Gregory J.

2000-04-01

Infant Jaundice is a physiologic condition of elevated bilirubin in the tissue that affects nearly 60 percent of all term newborns and virtually 100 percent of premature infants. The high production of bilirubin in the newborn circulatory system and the inability of the immature liver to process and eliminate it case the condition. When the bilirubin levels rise, it starts to deposit in the baby's skin and in the brain. The deposits in the brain can cause neurologic impairment and death. The BiliCheck is a handheld, battery-powered device that measures the level of jaundice non-invasively using BioPhotonics at the point of care. The result is displayed on an LCD screen immediately, so physicians can now make treatment decision without waiting for results to return from the lab. The BiliCheck System has been marketed worldwide since April of 1998 and has received FDA clearance for use in the USA on pre-photo therapy infants in March of 1999.

Quantitative assessment of serum-specific IgE in the diagnosis of human cystic echinococcosis.

PubMed

Marinova, I; Nikolov, G; Michova, A; Kurdova, R; Petrunov, B

2011-07-01

Anti-Echinococcus serum immunoglobulin (Ig)E was assessed by the ImmunoCAP system and compared with anti-Echinococcus serum IgG assessed by enzyme-linked immunosorbent assay (ELISA) and Western blot. The ImmunoCAP system revealed very high specificity (one false positive of 110 healthy individuals), low cross-reactivity (one false positive of 58 patients with other diseases) and decreased sensitivity (73.55%). Receiver operating characteristic analysis displayed a beneficial diagnostic value with high accuracy. Comparison of the ImmunoCAP system with ELISA and Western blot showed significantly higher specificity and significantly lower cross-reactivity compared with the ELISA. Examination of sera from 155 patients with cystic echinococcosis (CE) showed varying levels of anti-Echinococcus IgE (range, 0.01-118.33 kUA/L). However, most samples had moderately elevated IgE levels. Analysis of serum-specific IgE revealed significantly higher sensitivity of the ImmunoCAP system and significantly higher antibody levels in hepatic CE compared with pulmonary CE. © 2011 Blackwell Publishing Ltd.

Accumulation of senescent cells in mitotic tissue of aging primates.

PubMed

Jeyapalan, Jessie C; Ferreira, Mark; Sedivy, John M; Herbig, Utz

2007-01-01

Cellular senescence, a stress induced growth arrest of somatic cells, was first documented in cell cultures over 40 years ago, however its physiological significance has only recently been demonstrated. Using novel biomarkers of cellular senescence we examined whether senescent cells accumulate in tissues from baboons of ages encompassing the entire lifespan of this species. We show that dermal fibroblasts, displaying markers of senescence such as telomere damage, active checkpoint kinase ATM, high levels of heterochromatin proteins and elevated levels of p16, accumulate in skin biopsies from baboons with advancing age. The number of dermal fibroblasts containing damaged telomeres reaches a value of over 15% of total fibroblasts, whereas 80% of cells contain high levels of the heterochromatin protein HIRA. In skeletal muscle, a postmitotic tissue, only a small percentage of myonuclei containing damaged telomeres were detected regardless of animal age. The presence of senescent cells in mitotic tissues might therefore be a contributing factor to aging and age related pathology and provides further evidence that cellular senescence is a physiological event.

Cytosolic Accumulation of L-Proline Disrupts GABA-Ergic Transmission through GAD Blockade.

PubMed

Crabtree, Gregg W; Park, Alan J; Gordon, Joshua A; Gogos, Joseph A

2016-10-04

Proline dehydrogenase (PRODH), which degrades L-proline, resides within the schizophrenia-linked 22q11.2 deletion suggesting a role in disease. Supporting this, elevated L-proline levels have been shown to increase risk for psychotic disorders. Despite the strength of data linking PRODH and L-proline to neuropsychiatric diseases, targets of disease-relevant concentrations of L-proline have not been convincingly described. Here, we show that Prodh-deficient mice with elevated CNS L-proline display specific deficits in high-frequency GABA-ergic transmission and gamma-band oscillations. We find that L-proline is a GABA-mimetic and can act at multiple GABA-ergic targets. However, at disease-relevant concentrations, GABA-mimesis is limited to competitive blockade of glutamate decarboxylase leading to reduced GABA production. Significantly, deficits in GABA-ergic transmission are reversed by enhancing net GABA production with the clinically relevant compound vigabatrin. These findings indicate that accumulation of a neuroactive metabolite can lead to molecular and synaptic dysfunction and help to understand mechanisms underlying neuropsychiatric disease. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Arabidopsis PIZZA has the capacity to acylate brassinosteroids.

PubMed

Schneider, Katja; Breuer, Christian; Kawamura, Ayako; Jikumaru, Yusuke; Hanada, Atsushi; Fujioka, Shozo; Ichikawa, Takanari; Kondou, Youichi; Matsui, Minami; Kamiya, Yuji; Yamaguchi, Shinjiro; Sugimoto, Keiko

2012-01-01

Brassinosteroids (BRs) affect a wide range of developmental processes in plants and compromised production or signalling of BRs causes severe growth defects. To identify new regulators of plant organ growth, we searched the Arabidopsis FOX (Full-length cDNA Over-eXpressor gene) collection for mutants with altered organ size and isolated two overexpression lines that display typical BR deficient dwarf phenotypes. The phenotype of these lines, caused by an overexpression of a putative acyltransferase gene PIZZA (PIZ), was partly rescued by supplying exogenous brassinolide (BL) and castasterone (CS), indicating that endogenous BR levels are rate-limiting for the growth of PIZ overexpression lines. Our transcript analysis further showed that PIZ overexpression leads to an elevated expression of genes involved in BR biosynthesis and a reduced expression of BR inactivating hydroxylases, a transcriptional response typical to low BR levels. Taking the advantage of relatively high endogenous BR accumulation in a mild bri1-301 background, we found that overexpression of PIZ results in moderately reduced levels of BL and CS and a strong reduction of typhasterol (TY) and 6-deoxocastasterone (6-deoxoCS), suggesting a role of PIZ in BR metabolism. We tested a set of potential substrates in vitro for heterologously expressed PIZ and confirmed its acyltransferase activity with BL, CS and TY. The PIZ gene is expressed in various tissues but as reported for other genes involved in BR metabolism, the loss-of-function mutants did not display obvious growth phenotypes under standard growth conditions. Together, our data suggest that PIZ can modify BRs by acylation and that these properties might help modulating endogenous BR levels in Arabidopsis.

Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells

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

Luo, Yi, E-mail: yi.luo@pfizer.com; Rana, Payal; Will, Yvonne

Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting thatmore » fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients. -- Highlights: ► Palmitic acid and cyclosporine (CsA) synergistically increased cytotoxicity. ► The impairment of mitochondrial functions may contribute to the enhanced toxicity. ► Inhibition of JNK activity attenuated palmitate/ CsA induced toxicity. ► Palmitate sensitizes cells to the toxicity induced by CsA at therapeutic exposure. ► Elevated free fatty acids may predispose the patients to CsA-induced toxicity.« less

Impact of ocean acidification on energy metabolism of oyster, Crassostrea gigas--changes in metabolic pathways and thermal response.

PubMed

Lannig, Gisela; Eilers, Silke; Pörtner, Hans O; Sokolova, Inna M; Bock, Christian

2010-08-11

Climate change with increasing temperature and ocean acidification (OA) poses risks for marine ecosystems. According to Pörtner and Farrell, synergistic effects of elevated temperature and CO₂-induced OA on energy metabolism will narrow the thermal tolerance window of marine ectothermal animals. To test this hypothesis, we investigated the effect of an acute temperature rise on energy metabolism of the oyster, Crassostrea gigas chronically exposed to elevated CO₂ levels (partial pressure of CO₂ in the seawater ~0.15 kPa, seawater pH ~ 7.7). Within one month of incubation at elevated PCo₂ and 15 °C hemolymph pH fell (pH(e) = 7.1 ± 0.2 (CO₂-group) vs. 7.6 ± 0.1 (control)) and P(e)CO₂ values in hemolymph increased (0.5 ± 0.2 kPa (CO₂-group) vs. 0.2 ± 0.04 kPa (control)). Slightly but significantly elevated bicarbonate concentrations in the hemolymph of CO₂-incubated oysters ([HCO₃⁻](e) = 1.8 ± 0.3 mM (CO₂-group) vs. 1.3 ± 0.1 mM (control)) indicate only minimal regulation of extracellular acid-base status. At the acclimation temperature of 15 °C the OA-induced decrease in pH(e) did not lead to metabolic depression in oysters as standard metabolism rates (SMR) of CO₂-exposed oysters were similar to controls. Upon acute warming SMR rose in both groups, but displayed a stronger increase in the CO₂-incubated group. Investigation in isolated gill cells revealed a similar temperature dependence of respiration between groups. Furthermore, the fraction of cellular energy demand for ion regulation via Na+/K+-ATPase was not affected by chronic hypercapnia or temperature. Metabolic profiling using ¹H-NMR spectroscopy revealed substantial changes in some tissues following OA exposure at 15 °C. In mantle tissue alanine and ATP levels decreased significantly whereas an increase in succinate levels was observed in gill tissue. These findings suggest shifts in metabolic pathways following OA-exposure. Our study confirms that OA affects energy metabolism in oysters and suggests that climate change may affect populations of sessile coastal invertebrates such as mollusks.

Saltmarsh Boundary Modulates Dispersal of Mangrove Propagules: Implications for Mangrove Migration with Sea-Level Rise

PubMed Central

Peterson, Jennifer M.; Bell, Susan S.

2015-01-01

Few studies have empirically examined the suite of mechanisms that underlie the distributional shifts displayed by organisms in response to changing climatic condition. Mangrove forests are expected to move inland as sea-level rises, encroaching on saltmarsh plants inhabiting higher elevations. Mangrove propagules are transported by tidal waters and propagule dispersal is likely modified upon encountering the mangrove-saltmarsh ecotone, the implications of which are poorly known. Here, using an experimental approach, we record landward and seaward dispersal and subsequent establishment of mangrove propagules that encounter biotic boundaries composed of two types of saltmarsh taxa: succulents and grasses. Our findings revealed that propagules emplaced within saltmarsh vegetation immediately landward of the extant mangrove fringe boundary frequently dispersed in the seaward direction. However, propagules moved seaward less frequently and over shorter distances upon encountering boundaries composed of saltmarsh grasses versus succulents. We uniquely confirmed that the small subset of propagules dispersing landward displayed proportionately higher establishment success than those transported seaward. Although impacts of ecotones on plant dispersal have rarely been investigated in situ, our experimental results indicate that the interplay between tidal transport and physical attributes of saltmarsh vegetation influence boundary permeability to propagules, thereby directing the initial phase of shifting mangrove distributions. The incorporation of tidal inundation information and detailed data on landscape features, such as the structure of saltmarsh vegetation at mangrove boundaries, should improve the accuracy of models that are being developed to forecast mangrove distributional shifts in response to sea-level rise. PMID:25760867

a Novel Methodology for Developing Inundation Maps Under Climate Change Scenarios Using One-Dimensional Model

NASA Astrophysics Data System (ADS)

Vu, M. T.; Liong, S. Y.; Raghavan, V. S.; Liew, S. C.

2011-07-01

Climate change is expected to cause increases in extreme climatic events such as heavy rainstorms and rising tidal level. Heavy rainstorms are known to be serious causes of flooding problems in big cities. Thus, high density residential and commercial areas along the rivers are facing risks of being flooded. For that reason, inundated area determination is now being considered as one of the most important areas of research focus in flood forecasting. In such a context, this paper presents the development of a floodmap in determining flood-prone areas and its volumes. The areas and volumes of flood are computed by the inundated level using the existing digital elevation model (DEM) of a hypothetical catchment chosen for study. The study focuses on the application of Flood Early Warning System (Delft — FEWS, Deltares), which is designated to work with the SOBEK (Delft) to simulate the extent of stormwater on the ground surface. The results from FEWS consist of time-series of inundation maps in Image file format (PNG) and ASCII format, which are subsequently imported to ArcGIS for further calculations. In addition, FEWS results provide options to export the video clip of water spreading out over the catchment. Consequently, inundated area and volume will be determined by the water level on the ground. Final floodmap is displayed in colors created by ArcGIS. Various flood map results corresponding to climate change scenarios will be displayed in the main part of the paper.

Saltmarsh boundary modulates dispersal of mangrove propagules: implications for mangrove migration with sea-level rise.

PubMed

Peterson, Jennifer M; Bell, Susan S

2015-01-01

Few studies have empirically examined the suite of mechanisms that underlie the distributional shifts displayed by organisms in response to changing climatic condition. Mangrove forests are expected to move inland as sea-level rises, encroaching on saltmarsh plants inhabiting higher elevations. Mangrove propagules are transported by tidal waters and propagule dispersal is likely modified upon encountering the mangrove-saltmarsh ecotone, the implications of which are poorly known. Here, using an experimental approach, we record landward and seaward dispersal and subsequent establishment of mangrove propagules that encounter biotic boundaries composed of two types of saltmarsh taxa: succulents and grasses. Our findings revealed that propagules emplaced within saltmarsh vegetation immediately landward of the extant mangrove fringe boundary frequently dispersed in the seaward direction. However, propagules moved seaward less frequently and over shorter distances upon encountering boundaries composed of saltmarsh grasses versus succulents. We uniquely confirmed that the small subset of propagules dispersing landward displayed proportionately higher establishment success than those transported seaward. Although impacts of ecotones on plant dispersal have rarely been investigated in situ, our experimental results indicate that the interplay between tidal transport and physical attributes of saltmarsh vegetation influence boundary permeability to propagules, thereby directing the initial phase of shifting mangrove distributions. The incorporation of tidal inundation information and detailed data on landscape features, such as the structure of saltmarsh vegetation at mangrove boundaries, should improve the accuracy of models that are being developed to forecast mangrove distributional shifts in response to sea-level rise.

Coagulation Alteration and Deep Vein Thrombosis in Brain Tumor Patients During the Perioperative Period.

PubMed

Guo, Xiaopeng; Zhang, Fa; Wu, Yue; Gao, Lu; Wang, Qiang; Wang, Zihao; Feng, Chenzhe; Yang, Yi; Xing, Bing; Xu, Zhiqin

2018-06-01

To explore coagulation function in patients with brain tumors before and after craniotomy and tumor resection and to analyze its correlation with deep vein thrombosis (DVT). This study enrolled 133 consecutive patients with brain tumors. Coagulation evaluation and limb venous ultrasonography were performed before and after surgery. Clinical characteristics and dynamic changes in coagulation parameters were recorded, and their correlations with DVT were analyzed. The incidence of postoperative DVT in patients with brain tumors was 10.5%. The average age of patients with DVT was older compared with patients without DVT (63.21 ± 11.21 years vs. 50.24 ± 11.95 years, P < 0.001), and the incidence of hepatitis B (21% vs. 4%, P = 0.035) was higher in patients with DVT compared with patients without DVT. D-dimer and fibrinogen were the most variable parameters during the perioperative period. In patients with DVT, D-dimer levels displayed a "zigzagging-rise" trend and were significantly higher than levels in patients without DVT. Platelet levels displayed a "first-descend-then-rise" trend and were significantly lower in patients with DVT on the second and third postoperative days. In patients with brain tumors, D-dimer and fibrinogen were elevated postoperatively, manifesting as hypercoagulability. Postoperative DVT was correlated with aging and hepatitis B. A "zigzagging-rise" trend of D-dimer and a "sharp-descent" trend of platelets in the early postoperative period might predict DVT in patients with brain tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

Physiological plasticity related to zonation affects hsp70 expression in the reef-building coral Pocillopora verrucosa

PubMed Central

Poli, Davide; Fabbri, Elena; Goffredo, Stefano; Airi, Valentina

2017-01-01

This study investigates for the first time the transcriptional regulation of a stress-inducible 70-kDa heat shock protein (hsp70) in the scleractinian coral Pocillopora verrucosa sampled at three locations and two depths (3 m and 12 m) in Bangka Island waters (North Sulawesi, Indonesia). Percentage of coral cover indicated reduced habitat suitability with depth and at the Tanjung Husi (TA) site, which also displayed relatively higher seawater temperatures. Expression of the P. verrucosa hsp70 transcript evaluated under field conditions followed a depth-related profile, with relatively higher expression levels in 3-m collected nubbins compared to the 12-m ones. Expression levels of metabolism-related transcripts ATP synthase and NADH dehydrogenase indicated metabolic activation of nubbins to cope with habitat conditions of the TA site at 3 m. After a 14-day acclimatization to common and fixed temperature conditions in the laboratory, corals were subjected for 7 days to an altered thermal regime, where temperature was elevated at 31°C during the light phase and returned to 28°C during the dark phase. Nubbins collected at 12 m were relatively more sensitive to thermal stress, as they significantly over-expressed the selected transcripts. Corals collected at 3 m appeared more resilient, as they showed unaffected mRNA expressions. The results indicated that local habitat conditions may influence transcription of stress-related genes in P. verrucosa. Corals exhibiting higher basal hsp70 levels may display enhanced tolerance towards environmental stressors. PMID:28199351

Horizon Brightness Revisited: Measurements and a Model of Clear-Sky Radiances

DTIC Science & Technology

1994-07-20

Clear daytime skies persistently display a subtle local maximum of radiance near the astronomical horizon. Spectroradiometry and digital image analysis confirm this maximum’s reality, and they show that its angular width and elevation vary with solar elevation, azimuth relative to the Sun, and aerosol optical depth. Many existing models of atmospheric scattering do not generate this near-horizon radiance maximum, but a simple second-order scattering model does, and it reproduces many of the maximum’s details.

19. The first floor. A photo image of the public ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

19. The first floor. A photo image of the public entry, elevator foyer and the rear of the central display windows. - John T. Beasley Building, 632 Cherry Street (between Sixth & Seventh Streets), Terre Haute, Vigo County, IN

INTERMITTENT ACCESS TO A NUTRITIONALLY COMPLETE HIGH-FAT DIET ATTENUATES ALCOHOL DRINKING IN RATS

PubMed Central

Sirohi, Sunil; Van Cleef, Arriel; Davis, Jon F.

2017-01-01

Binge eating disorder and alcohol use disorder (AUD) frequently co-occur in the presence of other psychiatric conditions. Data suggest that binge eating engages similar behavioral and neurochemical processes common to AUD, which might contribute to the etiology or maintenance of alcoholism. However, it is unclear how binge feeding behavior and alcohol intake interact to promote initiation or maintenance of AUD. We investigated the impact of binge-like feeding on alcohol intake and anxiety-like behavior in male Long Evans rats. Rats received chow (controls) or extended intermittent access (24 hr twice a week; Int-HFD) to a nutritionally complete high-fat diet for six weeks. Standard rodent chow was available ad-libitum to all groups and food intake was measured. Following HFD exposure, 20.0% ethanol, 2.0% sucrose intake and endocrine peptide levels were evaluated. Anxiety-like behavior was measured using a light-dark (LD) box apparatus. Rats in the Int-HFD group displayed a binge-like pattern of feeding (alternations between caloric overconsumption and voluntary caloric restriction). Surprisingly, alcohol intake was significantly attenuated in the Int-HFD group whereas sugar consumption was unaffected. Plasma acyl-ghrelin levels were significantly elevated in the Int-HFD group, whereas glucagon-like peptide-1 levels did not change. Moreover, rats in the Int-HFD group spent more time in the light side of the LD box compared to controls, indicating that binge-like feeding induced anxiolytic effects. Collectively, these data suggest that intermittent access to HFD attenuates alcohol intake through reducing anxiety-like behavior, a process potentially controlled by elevated plasma ghrelin levels. PMID:27998722

Extracellular matrix metalloproteinase inducer expression in the baboon endometrium: menstrual cycle and endometriosis

PubMed Central

Braundmeier, A G; Fazleabas, A T; Nowak, R A

2016-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN; BSG) regulates tissue remodeling through matrix metalloproteinases (MMPs). In human and non-human primates, endometrial remodeling is important for menstruation and the pathogenesis of endometriosis. We hypothesized that as in humans, BSG and MMPs are expressed in the endometrium of cycling baboons, and their expression is hormonally regulated by ovarian hormones, but endometriosis disrupts this regulation. BSG expression was evaluated in the baboon endometrium by q-PCR and immunohistochemistry. In the endometrium of control cycling animals, BSG mRNA levels were highest in late secretory stage tissue. BSG protein localized to glandular epithelial cells during the proliferative phase; whereas, secretory stage tissues expressed BSG in glandular and luminal epithelia with weak stromal staining. Several MMPs were differentially expressed throughout the menstrual cycle with the highest levels found during menstruation. In ovariectomized animals, BSG endometrial mRNA levels were highest with treatment of both estrogen and progesterone than that with only estrogen. Estrogen alone resulted in BSG protein localization primarily in the endometrial glandular epithelia, while estrogen and progesterone treatment displayed BSG protein localization in both the glandular and stromal cells. Exogenous hormone treatment resulted in differential expression patterns of all MMPs compared with the control cycling animals. In the eutopic endometrium of endometriotic animals, BSG mRNA levels and protein were elevated early but decreased later in disease progression. Endometriosis elevated the expression of all MMPs except MMP7 compared with the control animals. In baboons, BSG and MMP endometrial expression is regulated by both ovarian hormones, and their expression patterns are dysregulated in endometriotic animals. PMID:20841363

Elevated Thyroid Peroxidase Antibody Increases Risk of Post-partum Depression by Decreasing Prefrontal Cortex BDNF and 5-HT Levels in Mice.

PubMed

Zhou, Yingying; Wang, Xinyi; Zhao, Yuhang; Liu, Aihua; Zhao, Tong; Zhang, Yuanyuan; Shan, Zhongyan; Teng, Weiping

2016-01-01

Post-partum depression (PPD) is a common mental disease in the perinatal period that profoundly affects mothers and their offspring. Some clinical studies have found that PPD is related to thyroid peroxidase antibodies (TPOAbs); however, the mechanism underlying this relationship is unclear. Female C57BL/6 mice immunized with adenovirus encoding the cDNA of the full-length mTPO (mTPO-Ad) were used to establish the isolated TPOAb-positive mouse model in the present study. Maternal depressive-like behaviors were assessed using the forced swimming test (FST), sucrose preference test (SPT), and tail suspension test (TST) post-partum. The serum TPOAb titer was measured by enzyme-linked immunosorbent assay (ELISA) before pregnancy and post-partum. Furthermore, in the prefrontal cortex, the mRNA and protein expression levels of brain-derived neurotrophic factor (BDNF) were measured, serotonin (5-HT) levels were measured by ultra-high-performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS), and total thyroxine (TT4) levels were determined by ELISA. Compared with the controls, the mice immunized with mTPO-Ad displayed depressive behaviors, with a significantly lower sucrose preference (SP) at the 12-h time point and a longer immobility time in the FST and TST, which were accompanied by a lower expression of BDNF and 5-HT but no change in the TT4 concentration in the prefrontal cortex. Together, these findings suggest that elevated TPOAb may increase the risk of subsequent PPD and decrease the concentration of BDNF and 5-HT in the prefrontal cortex.

Synergistic effect of Ebselen and gamma radiation on breast cancer cells.

PubMed

Thabet, Noura M; Moustafa, Enas M

2017-08-01

To explore the synergistic effect of a seleno-organic compound Ebselen (Ebs) and/or γ-radiation to exert antitumor effects on human breast cancer (MCF-7) cell line in vitro. Ebs cytotoxicity at various concentrations (10, 25, 50 and 75 μg), cell proliferation and clonogenic assay of Ebs and/or γ-radiation (at 1, 3 and 6 Gy), expression of p-IκBα and NF-κB, inflammatory cytokines levels (TNF-α, IL-2, INF-γ, IL-10 and TGF-β), apoptotic factors (Caspase-3, Granzyme-B and TRAIL) and angiogenic factor (VEGF) were investigated. The results showed that the effective dosage of this combination was observed at 25 μg/ml of Ebs with γ-radiation at 6 Gy. Data displayed a significant reduction in NF-κB mRNA along with an elevation in granzyme-B mRNA and TRAIL mRNA expression. Furthermore, protein expression of caspase-3 was elevated, whereas p-IκBα and p-NF-κB(p65) protein expression was reduced significantly. Also, a significant decline in TNF-α, IL-2, INF-γ, TGF-β with a significant increase in IL-10 levels were revealed. Meanwhile, a significant decrease in VEGF level and proliferation capacity were observed. We conclude that a combination of Ebs with radiotherapy has a major antitumor efficiency in inducing apoptosis and inhibiting cancer cell progression, due to the synergistic effect in regulating gene and protein expression, and in a modulating response of pro-and anti-inflammatory cytokines.

Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus

PubMed Central

Mamenko, Mykola; Dhande, Isha; Tomilin, Viktor; Zaika, Oleg; Boukelmoune, Nabila; Zhu, Yaming; Gonzalez-Garay, Manuel L.

2016-01-01

Store-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca2+) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca2+ levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca2+ mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca2+ levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling. PMID:26574044

Resting-State Functional Connectivity Differentiates Anxious Apprehension and Anxious Arousal

PubMed Central

Burdwood, Erin N.; Infantolino, Zachary P.; Crocker, Laura D.; Spielberg, Jeffrey M.; Banich, Marie T.; Miller, Gregory A.; Heller, Wendy

2016-01-01

Brain regions in the default mode network (DMN) display greater functional connectivity at rest or during self-referential processing than during goal-directed tasks. The present study assessed resting-state connectivity as a function of anxious apprehension and anxious arousal, independent of depressive symptoms, in order to understand how these dimensions disrupt cognition. Whole-brain, seed-based analyses indicated differences between anxious apprehension and anxious arousal in DMN functional connectivity. Lower connectivity associated with higher anxious apprehension suggests decreased adaptive, inner-focused thought processes, whereas higher connectivity at higher levels of anxious arousal may reflect elevated monitoring of physiological responses to threat. These findings further the conceptualization of anxious apprehension and anxious arousal as distinct psychological dimensions with distinct neural instantiations. PMID:27406406

The austral peregrine falcon: Color variation, productivity, and pesticides

USGS Publications Warehouse

Ellis, D.H.

1985-01-01

The austral peregrine falcon (Falco peregrinus cassini) was studied in the Andean foot- hills and across the Patagonian steppe from November to December 1981. The birds under study (18 pairs) were reproducing at or near normal (pre-DDT) levels for other races. Pesticide residues, while elevated, were well below the values associated with reproductive failure in other populations. With one exception, eggshells were not abnormally thin. The peregrine falcon in Patagonia exhibits extreme color variation. Pallid birds are nearly pure white below (light cream as juveniles), whereas normally pigmented birds are black-crowned and conspicuously barred with black ventrally. Rare individuals of the Normal Phase display black heads, broad black ventral barring, and warm reddish-brown ventral background coloration.

Application of Raman spectroscopy in type 2 diabetes screening in blood using leucine and isoleucine amino-acids as biomarkers and in comparative anti-diabetic drugs efficacy studies.

PubMed

Birech, Zephania; Mwangi, Peter Waweru; Bukachi, Fredrick; Mandela, Keith Makori

2017-01-01

Diabetes is an irreversible condition characterized by elevated blood glucose levels. Currently, there are no predictive biomarkers for this disease and the existing ones such as hemoglobin A1c and fasting blood glucose are used only when diabetes symptoms are noticed. The objective of this work was first to explore the potential of leucine and isoleucine amino acids as diabetes type 2 biomarkers using their Raman spectroscopic signatures. Secondly, we wanted to explore whether Raman spectroscopy can be applied in comparative efficacy studies between commercially available anti-diabetic drug pioglitazone and the locally used anti-diabetic herbal extract Momordica spinosa (Gilg.)Chiov. Sprague Dawley (SD) rat's blood was used and were pipetted onto Raman substrates prepared from conductive silver paste smeared glass slides. Prominent Raman bands associated with glucose (926, 1302, 1125 cm-1), leucine (1106, 1248, 1302, 1395 cm-1) and isolecucine (1108, 1248, 1437 and 1585 cm-1) were observed. The Raman bands centered at 1125 cm-1, 1395 cm-1 and 1437 cm-1 associated respectively to glucose, leucine and isoleucine were chosen as biomarker Raman peaks for diabetes type 2. These Raman bands displayed decreased intensities in blood from diabetic SD rats administered antidiabetic drugs pioglitazone and herbal extract Momordica spinosa (Gilg.)Chiov. The intensity decrease indicated reduced concentration levels of the respective biomarker molecules: glucose (1125 cm-1), leucine (1395 cm-1) and isoleucine (1437 cm-1) in blood. The results displayed the power and potential of Raman spectroscopy in rapid (10 seconds) diabetes and pre-diabetes screening in blood (human or rat's) with not only glucose acting as a biomarker but also leucine and isoleucine amino-acids where intensities of respectively assigned bands act as references. It also showed that using Raman spectroscopic signatures of the chosen biomarkers, the method can be an alternative for performing comparative efficacy studies between known and new anti-diabetic drugs. Reports on use of Raman spectroscopy in type 2 diabetes mellitus screening with Raman bands associated with leucine and isoleucine molecules acting as reference is rare in literature. The use of Raman spectroscopy in pre-diabetes screening of blood for changes in levels of leucine and isoleucine amino acids is particularly interesting as once elevated levels are noticed, necessary interventions to prevent diabetes development can be initiated.

A study of the prostate, androgens and sexual activity of male rats

PubMed Central

Hernandez, Maria Elena; Soto-Cid, Abraham; Aranda-Abreu, Gonzalo E; Díaz, Rosaura; Rojas, Fausto; Garcia, Luis I; Toledo, Rebeca; Manzo, Jorge

2007-01-01

Background The prostate is a sexual gland that produces important substances for the potency of sperm to fertilize eggs within the female reproductive tract, and is under complex endocrine control. Taking advantage of the peculiar behavioral pattern of copulating male rats, we developed experimental paradigms to determine the influence of sexual behavior on the level of serum testosterone, prostate androgen receptors, and mRNA for androgen receptors in male rats displaying up to four consecutive ejaculations. Methods The effect of four consecutive ejaculations was investigated by determining levels of (i) testosterone in serum by solid phase RIA, (ii) androgen receptors at the ventral prostate with Western Blots, and (iii) androgen receptors-mRNA with RT-PCR. Data were analyzed with a one-way ANOVA followed by a post hoc application of Dunnett's test if required. Results The constant execution of sexual behavior did not produce any change in the weight of the ventral prostate. Serum testosterone increased after the second ejaculation, and remained elevated even after four ejaculations. The androgen receptor at the ventral prostate was higher after the first to third ejaculations, but returned suddenly to baseline levels after the fourth ejaculation. The level of mRNA increased after the first ejaculation, continued to increase after the second, and reached the highest peak after the third ejaculation; however, it returned suddenly to baseline levels after the fourth ejaculation. Conclusion Four consecutive ejaculations by sexually experienced male rats had important effects on the physiological responses of the ventral prostate. Fast responses were induced as a result of sexual behavior that involved an increase and decrease in androgen receptors after one and four ejaculations, respectively. However, a progressive response was observed in the elevation of mRNA for androgen receptors, which also showed a fast decrease after four ejaculations. All of these changes with the prostate gland occurred in the presence of a sustained elevation of testosterone in the serum that started after two ejaculations. A consideration of these fast-induced changes suggests that the nerve supply plays a key role in prostate physiology during the sexual behavior of male rats. PMID:17367532

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

PubMed Central

2012-01-01

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

A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice1

PubMed Central

Kauffman, Alexander S.; Thackray, Varykina G.; Ryan, Genevieve E.; Tolson, Kristen P.; Glidewell-Kenney, Christine A.; Semaan, Sheila J.; Poling, Matthew C.; Iwata, Nahoko; Breen, Kellie M.; Duleba, Antoni J.; Stener-Victorin, Elisabet; Shimasaki, Shunichi; Webster, Nicholas J.; Mellon, Pamela L.

2015-01-01

Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice. Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in increased serum testosterone and normal diestrus levels of estradiol, similar to the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea versus controls. Most LET females were acyclic, and all were infertile. LET females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary. In contrast, serum FSH and Fshb were significantly reduced in LET females, demonstrating differential effects on gonadotropins, as in PCOS. Within the ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but lower progesterone receptor mRNA levels. LET females also gained more weight than controls, had increased abdominal adiposity and adipocyte size, elevated adipose inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic phenotype in PCOS women. This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition. PMID:26203175

A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo

PubMed Central

Machado, Danielle S.; Sabet, Amin; Santiago, Leticia A.; Sidhaye, Aniket R.; Chiamolera, Maria I.; Ortiga-Carvalho, Tania M.; Wondisford, Fredric E.

2009-01-01

Resistance to thyroid hormone (RTH) is most often due to point mutations in the β-isoform of the thyroid hormone (TH) receptor (TR-β). The majority of mutations involve the ligand-binding domain, where they block TH binding and receptor function on both stimulatory and inhibitory TH response elements. In contrast, a few mutations in the ligand-binding domain are reported to maintain TH binding and yet cause RTH in certain tissues. We introduced one such naturally occurring human RTH mutation (R429Q) into the germline of mice at the TR-β locus. R429Q knock-in (KI) mice demonstrated elevated serum TH and inappropriately normal thyroid-stimulating hormone (TSH) levels, consistent with hypothalamic–pituitary RTH. In contrast, 3 hepatic genes positively regulated by TH (Dio1, Gpd1, and Thrsp) were increased in R429Q KI animals. Mice were then rendered hypothyroid, followed by graded T3 replacement. Hypothyroid R429Q KI mice displayed elevated TSH subunit mRNA levels, and T3 treatment failed to normally suppress these levels. T3 treatment, however, stimulated pituitary Gh levels to a greater degree in R429Q KI than in control mice. Gsta, a hepatic gene negatively regulated by TH, was not suppressed in R429Q KI mice after T3 treatment, but hepatic Dio1 and Thrsp mRNA levels increased in response to TH. Cardiac myosin heavy chain isoform gene expression also showed a specific defect in TH inhibition. In summary, the R429Q mutation is associated with selective impairment of TH-mediated gene repression, suggesting that the affected domain, necessary for TR homodimerization and corepressor binding, has a critical role in negative gene regulation by TH. PMID:19439650

Improved preoperative iron status assessment by soluble transferrin receptor in elderly patients undergoing knee and hip replacement.

PubMed

Basora, M; Deulofeu, R; Salazar, F; Quinto, L; Gomar, C

2006-12-01

A poor preoperative haemoglobin (Hb) status is frequently encountered among adult patients scheduled for corrective surgery of the locomotive system, representing the main risk factor for blood transfusion. The soluble transferrin receptor (sTfR) has become a highly specific parameter for the detection of iron deficits as it can differentiate between iron deficiency anaemia and anaemia of chronic disease, because of the lack of effect by associated inflammation, unlike ferritin. The objectives of this study were to evaluate patients with the prevalence of risk for transfusion, the effect of inflammation on ferritin (F) values and functional iron deficiency in elderly patients with advanced degenerative arthropathy scheduled for hip or knee replacement. This observational, prospective study included patients over 50 years, operated for hip or knee replacements between April and June 2004. Of 218 patients studied, 87 (39%) presented with Hb levels between 10 and 13 g/dl. The prevalence of functional iron deficit was 27% (sTfR > 1.76 mg/l), while only 8.6% of patients displayed F levels below normal. As expected, C-reactive protein levels were elevated in 24.8% of patients and erythrocyte sedimentation rate was elevated in 50%. These inflammatory markers did not correlate with levels of either F or sTfR. Multiple factors can affect F levels, such as the inflammatory status of osteoarthritis in the elderly, obesity, nonsteroidal anti-inflammatory drugs therapy and low physical performance. As sTfR is not affected by inflammation, it has emerged as a primary parameter for the evaluation of iron status during preoperative assessment among patients scheduled for arthroplasty surgery. Our data strongly suggest that sTfR measurement contributes to improve patient management.

Hematologic responses to hypobaric hyperoxia.

NASA Technical Reports Server (NTRS)

Larkin, E. C.; Adams, J. D.; Williams, W. T.; Duncan, D. M.

1972-01-01

Study of the effects of hypoxia, activity, and G forces on human hematopoiesis in an attempt to elucidate these phenomena more precisely. Eight subjects were exposed to an atmosphere of 100% O2 at 258 mm Hg for 30 days, and thereafter immediately exposed to transverse G forces, simulating the Gemini flights' reentry profile. All subjects displayed a significant continuous decline in red cell mass during the exposure period, as measured by the carbon monoxide-dilution method. The Cr51 method also indicated a decline in red blood corpuscle mass. The decrease in red cell mass was due to suppression of erythropoiesis and to hemolysis. After exposure to hyperoxia, all subjects exhibited elevated plasma hemoglobin levels, decreased reticulocyte counts, and decreased red cell survivals. CO production rates and urine erythropoietin levels were unchanged. Two hours after termination of exposure to hyperoxia, all subjects exhibited increased reticulocyte counts which were sustained for longer than two weeks. The progressive decrease in red cell mass was promptly arrested on return to ground level atmospheres. Within 116 days after exposure to hyperoxia, the hematologic parameters of all eight subjects had returned to control levels.

Social isolation alters central nervous system monoamine content in prairie voles following acute restraint.

PubMed

McNeal, Neal; Anderson, Eden M; Moenk, Deirdre; Trahanas, Diane; Matuszewich, Leslie; Grippo, Angela J

2018-04-01

Animal models have shown that social isolation and other forms of social stress lead to depressive- and anxiety-relevant behaviors, as well as neuroendocrine and physiological dysfunction. The goal of this study was to investigate the effects of prior social isolation on neurotransmitter content following acute restraint in prairie voles. Animals were either paired with a same-sex sibling or isolated for 4 weeks. Plasma adrenal hormones and ex vivo tissue concentrations of monoamine neurotransmitters and their metabolites were measured following an acute restraint stressor in all animals. Isolated prairie voles displayed significantly increased circulating adrenocorticotropic hormone levels, as well as elevated serotonin and dopamine levels in the hypothalamus, and potentially decreased levels of serotonin in the frontal cortex. However, no group differences in monoamine levels were observed in the hippocampus or raphe. The results suggest that social stress may bias monoamine neurotransmission and stress hormone function to subsequent acute stressors, such as restraint. These findings improve our understanding of the neurobiological mechanisms underlying the consequences of social stress.

An Evaluation of Detect and Avoid Displays for UAS: The Effect of Information Level and Display Location on Pilot Performance

NASA Technical Reports Server (NTRS)

Rorie, Conrad; Fern, Lisa; Pack, Jessica; Shively, Jay; Draper, Mark H.

2015-01-01

The pilot-in-the-loop Detect-and-Avoid (DAA) task requires the pilot to carry out three major functions: 1) detect a potential threat, 2) determine an appropriate resolution maneuver, and 3) execute that resolution maneuver via the GCS control and navigation interface(s). The purpose of the present study was to examine two main questions with respect to DAA display considerations that could impact pilots ability to maintain well clear from other aircraft. First, what is the effect of a minimum (or basic) information display compared to an advanced information display on pilot performance? Second, what is the effect of display location on UAS pilot performance? Two levels of information level (basic, advanced) were compared across two levels of display location (standalone, integrated), for a total of four displays. The results indicate that the advanced displays had faster overall response times compared to the basic displays, however, there were no significant differences between the standalone and integrated displays.

Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton.

PubMed

Haffner-Luntzer, Melanie; Heilmann, Aline; Heidler, Verena; Liedert, Astrid; Schinke, Thorsten; Amling, Michael; Yorgan, Timur Alexander; Vom Scheidt, Annika; Ignatius, Anita

2016-11-01

Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914-1921, 2016. © 2016 The Authors. Journal of Orthopaedic Research Published by by Wiley Periodicals, Inc.

Treatment of gummy smile: Gingival recontouring with the containment of the elevator muscle of the upper lip and wing of nose. A surgery innovation technique.

PubMed

Storrer, Carmen Lucia Mueller; Valverde, Fabiane Kristine Bochenek; Santos, Felipe Rychuv; Deliberador, Tatiana Miranda

2014-09-01

The containment of the elevator muscle of the upper lip and wing of nose was used for the treatment of patients with gummy smile. This technique had corrected esthetic alterations of smile, reducing the upper lip elevation, which results in a smaller gingival display. An upper lip lengthening as well as a reduction in the upper lip shortening when the patient smiled could be observed. The high smile line was corrected without compromising the labial harmony. This study presents an innovative and effective therapeutic option to obtain a natural and harmonious smile. The patient expressed a high degree of satisfaction.

Vertical and Horizontal Vegetation Structure across Natural and Modified Habitat Types at Mount Kilimanjaro

PubMed Central

Rutten, Gemma; Ensslin, Andreas; Hemp, Andreas; Fischer, Markus

2015-01-01

In most habitats, vegetation provides the main structure of the environment. This complexity can facilitate biodiversity and ecosystem services. Therefore, measures of vegetation structure can serve as indicators in ecosystem management. However, many structural measures are laborious and require expert knowledge. Here, we used consistent and convenient measures to assess vegetation structure over an exceptionally broad elevation gradient of 866–4550m above sea level at Mount Kilimanjaro, Tanzania. Additionally, we compared (human)-modified habitats, including maize fields, traditionally managed home gardens, grasslands, commercial coffee farms and logged and burned forests with natural habitats along this elevation gradient. We distinguished vertical and horizontal vegetation structure to account for habitat complexity and heterogeneity. Vertical vegetation structure (assessed as number, width and density of vegetation layers, maximum canopy height, leaf area index and vegetation cover) displayed a unimodal elevation pattern, peaking at intermediate elevations in montane forests, whereas horizontal structure (assessed as coefficient of variation of number, width and density of vegetation layers, maximum canopy height, leaf area index and vegetation cover) was lowest at intermediate altitudes. Overall, vertical structure was consistently lower in modified than in natural habitat types, whereas horizontal structure was inconsistently different in modified than in natural habitat types, depending on the specific structural measure and habitat type. Our study shows how vertical and horizontal vegetation structure can be assessed efficiently in various habitat types in tropical mountain regions, and we suggest to apply this as a tool for informing future biodiversity and ecosystem service studies. PMID:26406985

Effects of an early intervention on perceived stress and diurnal cortisol in pregnant women with elevated stress, anxiety, and depressive symptomatology.

PubMed

Richter, Judith; Bittner, Antje; Petrowski, Katja; Junge-Hoffmeister, Juliane; Bergmann, Sybille; Joraschky, Peter; Weidner, Kerstin

2012-12-01

The goal of the present investigation was to examine effects of a cognitive-behavioral group intervention for pregnant women with subclinically elevated stress, anxiety and/or depression on perceived stress and salivary cortisol levels. Expectant mothers were recruited in gynaecologist practices. They participated in a screening, a standardized diagnostic interview (Munich-Composite Diagnostic Interview, M-CIDI), and were randomly assigned to an intervention (N = 21) and treatment as usual control group (N = 40). The intervention consisted of a manualized cognitive-behavioral group program for expectant mothers with subclinically elevated stress, depression, and/or anxiety symptoms. Stress questionnaire (prenatal distress (PDQ), perceived stress (PSS)) as well as diurnal salivary cortisol assessment took place at T1 (antenatal, preintervention), at T2 (antenatal, post-intervention) and T3 (3-month postpartum). Subjects that participated in the intervention exhibited a significant post-treatment change in morning cortisol (cortisol awakening response, CAR) in contrast to control subjects, F(8,51) = 2.300, p = 0.047. Intervention participants showed a smaller CAR subsequent to the intervention, displaying a lessened stress reaction. This effect was not observed in the control group. In contrast, we failed in discovering a significant difference between the research groups regarding the cortisol area under curve parameter (AUC) and the applied subjective stress questionnaires. Evaluation results were thus heterogeneous. Nevertheless, intervention effects on the CAR are promising. Our results suggest that a cognitive-behavioral intervention might lead to an improvement in the biological stress response of pregnant women with subclinically elevated stress, anxiety, or depressive symptoms.

Increased levels of conditioned fear and avoidance behavior coincide with changes in phosphorylation of the protein kinase B (AKT) within the amygdala in a mouse model of extremes in trait anxiety.

PubMed

Yen, Yi-Chun; Mauch, Christoph P; Dahlhoff, Maik; Micale, Vincenzo; Bunck, Mirjam; Sartori, Simone B; Singewald, Nicolas; Landgraf, Rainer; Wotjak, Carsten T

2012-07-01

Patients diagnosed for anxiety disorders often display faster acquisition and slower extinction of learned fear. To gain further insights into the mechanisms underlying these phenomenona, we studied conditioned fear in mice originating form a bi-directional selective breeding approach, which is based on elevated plus-maze behavior and results in CD1-derived high (HAB), normal (NAB), and low (LAB) anxiety-related behavior mice. HAB mice displayed pronounced cued-conditioned fear compared to NAB/CD1 and LAB mice that coincided with increased phosphorylation of the protein kinase B (AKT) in the basolateral amygdala 45 min after conditioning. No similar changes were observed after non-associative immediate shock presentations. Fear extinction of recent but not older fear memories was preserved. However, HAB mice were more prone to relapse of conditioned fear with the passage of time. HAB mice also displayed higher levels of contextual fear compared to NAB and LAB mice and exaggerated avoidance following step-down avoidance training. Interestingly, HAB mice showed lower and LAB mice higher levels of acoustic startle responses compared to NAB controls. The increase in arousal observed in LAB mice coincided with the general absence of conditioned freezing. Taken together, our results suggest that the genetic predisposition to high anxiety-related behavior may increase the risk of forming traumatic memories, phobic-like fear and avoidance behavior following aversive encounters, with a clear bias towards passive coping styles. In contrast, genetic predisposition to low anxiety-related and high risk-taking behavior seems to be associated with an increase in active coping styles. Our data imply changes in AKT phosphorylation as a therapeutic target for the prevention of exaggerated fear memories. Copyright © 2012 Elsevier Inc. All rights reserved.

Targeted overexpression of Tumor Necrosis Factor-α increases Cyclin-dependent kinase 5 activity and TRPV1-dependent Ca2+ influx in trigeminal neurons

PubMed Central

Rozas, Pablo; Lazcano, Pablo; Piña, Ricardo; Cho, Andrew; Terse, Anita; Pertusa, Maria; Madrid, Rodolfo; Gonzalez-Billault, Christian; Kulkarni, Ashok B.; Utreras, Elias

2016-01-01

We reported earlier that TNF-α, a proinflammatory cytokine implicated in many inflammatory disorders causing orofacial pain increases Cdk5 activity, a key kinase involved in brain development and function and recently in pain signaling. To investigate a potential mechanism underlying inflammatory pain in trigeminal ganglia (TG), we engineered a transgenic mouse model (TNFglo) that can conditionally overexpresses TNF-α upon genomic recombination by Cre recombinase. TNFglo mice were bred with Nav1.8-Cre mouse line that expresses the Cre recombinase in sensory neurons to obtain TNF-α:Nav1.8-Cre (TNF-α cTg) mice. Although TNF-α cTg mice appeared normal without any gross phenotype, they displayed a significant increase in TNF-α levels after activation of NFκB signaling in the TG. IL-6 and MCP-1 levels were also increased along with intense immunostaining for Iba1 and GFAP in TG, indicating the presence of infiltrating macrophages and the activation of satellite glial cells. TNF-α cTg mice displayed increased trigeminal Cdk5 activity, and this increase was associated with elevated levels of phospho-T407-TRPV1 and capsaicin-evocated Ca2+ influx in cultured trigeminal neurons. Remarkably, this effect was prevented by roscovitine, an inhibitor of Cdk5, suggesting that TNF-α overexpression induced sensitization of the TRPV1 channel. Furthermore, TNF-α cTg mice displayed more aversive behavior to noxious thermal stimulation (45°C) of the face in an operant pain assessment device as compared with control mice. In summary, TNF-α overexpression in the sensory neurons of TNF-α cTg mice results in inflammatory sensitization and increased Cdk5 activity, therefore this mouse model would be valuable for investigating mechanism involved TNF-α in orofacial pain. PMID:26894912

Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model.

PubMed

Monyak, R E; Emerson, D; Schoenfeld, B P; Zheng, X; Chambers, D B; Rosenfelt, C; Langer, S; Hinchey, P; Choi, C H; McDonald, T V; Bolduc, F V; Sehgal, A; McBride, S M J; Jongens, T A

2017-08-01

Fragile X syndrome (FXS) is an undertreated neurodevelopmental disorder characterized by low intelligence quotent and a wide range of other symptoms including disordered sleep and autism. Although FXS is the most prevalent inherited cause of intellectual disability, its mechanistic underpinnings are not well understood. Using Drosophila as a model of FXS, we showed that select expression of dfmr1 in the insulin-producing cells (IPCs) of the brain was sufficient to restore normal circadian behavior and to rescue the memory deficits in the fragile X mutant fly. Examination of the insulin signaling (IS) pathway revealed elevated levels of Drosophila insulin-like peptide 2 (Dilp2) in the IPCs and elevated IS in the dfmr1 mutant brain. Consistent with a causal role for elevated IS in dfmr1 mutant phenotypes, the expression of dfmr1 specifically in the IPCs reduced IS, and genetic reduction of the insulin pathway also led to amelioration of circadian and memory defects. Furthermore, we showed that treatment with the FDA-approved drug metformin also rescued memory. Finally, we showed that reduction of IS is required at different time points to rescue circadian behavior and memory. Our results indicate that insulin misregulation underlies the circadian and cognitive phenotypes displayed by the Drosophila fragile X model, and thus reveal a metabolic pathway that can be targeted by new and already approved drugs to treat fragile X patients.

Are Elevations in ADHD Symptoms Associated with Physiological Reactivity and Emotion Dysregulation in Children?

PubMed

McQuade, Julia D; Breaux, Rosanna P

2017-08-01

The present study examined whether children with elevated attention-deficit/hyperactivity disorder (ADHD) symptoms display a unique pattern of emotion dysregulation as indexed by both parent report and physiological reactivity during experiences of failure. A sample of 61 children (9 to 13 years; M = 11.62, SD = 1.29; 48 % male) with and without clinical elevations in ADHD symptoms participated. Parent and teacher report of ADHD and oppositional defiant disorder (ODD) symptoms and parent report of internalizing problems were collected. Parents also provided ratings of children's emotional negativity/lability and emotion regulation. Children's physiological reactivity, based on changes in respiratory sinus arrhythmia (RSA) and skin conductance level (SCL), were assessed while they completed a manipulated social rejection task and impossible puzzle task. Regression analyses indicated that ADHD symptoms were associated with higher parent-rated emotional negativity/lability and with blunted RSA withdrawal in response to social rejection; these effects were not accounted for by co-occurring ODD symptoms or internalizing problems. ODD symptoms also were uniquely associated with parent ratings of poor emotion regulation. Internalizing problems were uniquely associated with emotional negativity/lability, poor emotion regulation, and increased SCL activity in response to social rejection. Results suggest that there may be a pattern of emotion dysregulation that is specific to ADHD symptomatology. The importance of contextual factors when examining physiological reactivity to stress in youth with ADHD is discussed.

Regulation of GPR119 receptor activity with endocannabinoid-like lipids.

PubMed

Syed, Samreen K; Bui, Hai Hoang; Beavers, Lisa S; Farb, Thomas B; Ficorilli, James; Chesterfield, Amy K; Kuo, Ming-Shang; Bokvist, Krister; Barrett, David G; Efanov, Alexander M

2012-12-15

The GPR119 receptor plays an important role in the secretion of incretin hormones in response to nutrient consumption. We have studied the ability of an array of naturally occurring endocannabinoid-like lipids to activate GPR119 and have identified several lipid receptor agonists. The most potent receptor agonists identified were three N-acylethanolamines: oleoylethanolamine (OEA), palmitoleoylethanolamine, and linoleylethanolamine (LEA), all of which displayed similar potency in activating GPR119. Another lipid, 2-oleoylglycerol (2-OG), also activated GPR119 receptor but with significantly lower potency. Endogenous levels of endocannabinoid-like lipids were measured in intestine in fasted and refed mice. Of the lipid GPR119 agonists studied, the intestinal levels of only OEA, LEA, and 2-OG increased significantly upon refeeding. Intestinal levels of OEA and LEA in the fasted mice were low. In the fed state, OEA levels only moderately increased, whereas LEA levels rose drastically. 2-OG was the most abundant of the three GPR119 agonists in intestine, and its levels were radically elevated in fed mice. Our data suggest that, in lean mice, 2-OG and LEA may serve as physiologically relevant endogenous GPR119 agonists that mediate receptor activation upon nutrient uptake.

Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery.

PubMed

Duarte, João M N; Morgenthaler, Florence D; Gruetter, Rolf

2017-06-01

Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

The role of insulin growth factor-1 on the vascular regenerative effect of MAA coated disks and macrophage-endothelial cell crosstalk.

PubMed

Talior-Volodarsky, Ilana; Mahou, Redouan; Zhang, David; Sefton, Michael

2017-11-01

The IGF-1 signaling pathway and IGF-1-dependent macrophage/endothelial cell crosstalk was found to be critical features of the vascular regenerative effect displayed by implanted methacrylic acid -co-isodecyl acrylate (MAA-co-IDA; 40% MAA) coated disks in CD1 mice. Inhibition of IGF-1 signaling using AG1024 an IGF1-R tyrosine kinase inhibitor abrogated vessel formation 14 days after disk implantation in a subcutaneous pocket. Explanted tissue had increased arginase 1 expression and reduced iNOS expression consistent with the greater shift from "M1" ("pro-inflammatory") macrophages to "M2" ("pro-angiogenic") macrophages for MAA coated disks relative to control MM (methyl methacrylate-co-IDA) disks; the latter did not generate a vascular response and the polarization shift was muted with AG1024. In vitro, medium conditioned by macrophages (both human dTHP1 cells and mouse bone marrow derived macrophages) had elevated IGF-1 mRNA and protein levels, while the cells had reduced IGF1-R but elevated IGFBP-3 mRNA levels. These cells also had reduced iNOS and elevated Arg1 expression, consistent with the in vivo polarization results, including the inhibitory effects of AG1024. On the other hand, HUVEC exposed to dTHP1 conditioned medium migrated and proliferated faster suggesting that the primary target of the macrophage released IGF-1 was endothelial cells. Although further investigation is warranted, IGF-1 appears to be a key feature underpinning the observed vascularization. Why MAA based materials have this effect remains to be defined, however. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dextran Sulfate Sodium-Induced Colonic Histopathology, but not Altered Epithelial Ion Transport, Is Reduced by Inhibition of Phosphodiesterase Activity

PubMed Central

Diaz-Granados, Natalia; Howe, Kathryn; Lu, Jun; McKay, Derek M.

2000-01-01

Inhibition of phosphodiesterase (PDE) activity is beneficial in models of arthritis and airway inflammation. Here we assessed the ability of PDE inhibitors to modulate colitis by exposing mice to 4% (w/v) dextran sulfate sodium (DSS) drinking water for 5 days with or without rolipram, an inhibitor of PDE type 4, or the nonselective PDE inhibitor, pentoxifylline (both at 5 mg/kg, i.p., twice daily). Controls received saline, vehicle, or drug only. Colonic histology, myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) levels, and epithelial ion transport (baseline and stimulated by electrical nerve stimulation, carbachol, and forskolin) were examined. DSS-treated mice displayed a variable diarrhea, significant histopathology in the mid-distal colon, elevated MPO activity, and reduced (>50%) responses to all three pro-secretory stimuli. Treatment with rolipram, and to a lesser extent pentoxifylline, significantly reduced the severity of the colonic histopathology and MPO levels. Neither PDE inhibitor had any affect on the diminished ion transport events caused by DSS-induced colitis. However, although stimulated ion transport events were still reduced 3 days after DSS treatment, colonic segments from DSS + rolipram-treated mice displayed enhanced recovery in their secretory responsiveness, particularly to carbachol. These findings indicate that specific PDE4 inhibition can significantly reduce the tissue damage that accompanies colitis and enhance recovery of normal colonic function. PMID:10854237

IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis.

PubMed

Mittal, Rahul; Gonzalez-Gomez, Ignacio; Panigrahy, Ashok; Goth, Kerstin; Bonnet, Richard; Prasadarao, Nemani V

2010-06-07

Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resistant E. coli from blood of infected mice. Micro-CT studies of brains from infected animals displayed gross morphological changes similar to those observed in infected human neonates. In mice, IL-10, but not antibiotic or anti-TNF antibody treatment prevented brain damage caused by E. coli. IL-10 administration elevated CR3 expression in neutrophils and macrophages of infected mice, whereas infected and untreated mice displayed increased expression of FcgammaRI and TLR2. Neutrophils or macrophages pretreated with IL-10 ex vivo exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type or IL-10-/- mice. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages upon E. coli infection. These findings describe a novel modality of IL-10-mediated E. coli clearance by diverting the entry of bacteria via CR3 and preventing PGE-2 formation in neonatal meningitis.

Factors determining extreme brain natriuretic peptide elevation.

PubMed

Guglin, Maya; Hourani, Rayan; Pitta, Sridevi

2007-01-01

Brain natriuretic peptide (BNP) level is elevated in heart failure and reflects its severity. It is unknown why some patients have extremely high BNP levels. The authors retrospectively reviewed data on 179 consecutive patients whose BNP levels fell within one of several predetermined ranges: mild elevation, 500 to 1000 pg/mL (n=82); moderate elevation, 2000 to 3000 pg/mL (n=48); and high elevation, 4000 to 20,000 pg/mL (n=49). The statistical analysis was conducted with the unpaired t test and Pearson's correlation coefficient. Adjustments were made for age, sex, and serum creatinine level. Patients with moderate BNP elevation were more symptomatic and had more advanced structural and hemodynamic changes than did patients with lower BNP elevation. Characteristics of the high BNP level group did not differ from those of the moderate BNP level group. Serum creatinine level correlated with BNP level, but neither age nor sex did. High BNP level (4000-20,000 pg/mL) is determined more by renal dysfunction than by the severity of heart failure.

Coral Energy Reserves and Calcification in a High-CO2 World at Two Temperatures

PubMed Central

Schoepf, Verena; Grottoli, Andréa G.; Warner, Mark E.; Cai, Wei-Jun; Melman, Todd F.; Hoadley, Kenneth D.; Pettay, D. Tye; Hu, Xinping; Li, Qian; Xu, Hui; Wang, Yongchen; Matsui, Yohei; Baumann, Justin H.

2013-01-01

Rising atmospheric CO2 concentrations threaten coral reefs globally by causing ocean acidification (OA) and warming. Yet, the combined effects of elevated pCO2 and temperature on coral physiology and resilience remain poorly understood. While coral calcification and energy reserves are important health indicators, no studies to date have measured energy reserve pools (i.e., lipid, protein, and carbohydrate) together with calcification under OA conditions under different temperature scenarios. Four coral species, Acropora millepora, Montipora monasteriata, Pocillopora damicornis, Turbinaria reniformis, were reared under a total of six conditions for 3.5 weeks, representing three pCO2 levels (382, 607, 741 µatm), and two temperature regimes (26.5, 29.0°C) within each pCO2 level. After one month under experimental conditions, only A. millepora decreased calcification (−53%) in response to seawater pCO2 expected by the end of this century, whereas the other three species maintained calcification rates even when both pCO2 and temperature were elevated. Coral energy reserves showed mixed responses to elevated pCO2 and temperature, and were either unaffected or displayed nonlinear responses with both the lowest and highest concentrations often observed at the mid-pCO2 level of 607 µatm. Biweekly feeding may have helped corals maintain calcification rates and energy reserves under these conditions. Temperature often modulated the response of many aspects of coral physiology to OA, and both mitigated and worsened pCO2 effects. This demonstrates for the first time that coral energy reserves are generally not metabolized to sustain calcification under OA, which has important implications for coral health and bleaching resilience in a high-CO2 world. Overall, these findings suggest that some corals could be more resistant to simultaneously warming and acidifying oceans than previously expected. PMID:24146747

Deficiency of base excision repair enzyme NEIL3 drives increased predisposition to autoimmunity

PubMed Central

Massaad, Michel J.; Zhou, Jia; Tsuchimoto, Daisuke; Chou, Janet; Jabara, Haifa; Janssen, Erin; Glauzy, Salomé; Olson, Brennan G.; Morbach, Henner; Ohsumi, Toshiro K.; Schmitz, Klaus; Kane, Jennifer; Torisu, Kumiko; Chouery, Eliane; Megarbane, Andre; Kang, Peter B.; Al-Idrissi, Eman; Aldhekri, Hasan; Meffre, Eric; Mizui, Masayuki; Manis, John P.; Al-Herz, Waleed; Wallace, Susan S.; Geha, Raif S.

2016-01-01

Alterations in the apoptosis of immune cells have been associated with autoimmunity. Here, we have identified a homozygous missense mutation in the gene encoding the base excision repair enzyme Nei endonuclease VIII-like 3 (NEIL3) that abolished enzymatic activity in 3 siblings from a consanguineous family. The NEIL3 mutation was associated with fatal recurrent infections, severe autoimmunity, hypogammaglobulinemia, and impaired B cell function in these individuals. The same homozygous NEIL3 mutation was also identified in an asymptomatic individual who exhibited elevated levels of serum autoantibodies and defective peripheral B cell tolerance, but normal B cell function. Further analysis of the patients revealed an absence of LPS-responsive beige-like anchor (LRBA) protein expression, a known cause of immunodeficiency. We next examined the contribution of NEIL3 to the maintenance of self-tolerance in Neil3–/– mice. Although Neil3–/– mice displayed normal B cell function, they exhibited elevated serum levels of autoantibodies and developed nephritis following treatment with poly(I:C) to mimic microbial stimulation. In Neil3–/– mice, splenic T and B cells as well as germinal center B cells from Peyer’s patches showed marked increases in apoptosis and cell death, indicating the potential release of self-antigens that favor autoimmunity. These findings demonstrate that deficiency in NEIL3 is associated with increased lymphocyte apoptosis, autoantibodies, and predisposition to autoimmunity. PMID:27760045

Mean Cancer Mortality Rates in Low Versus High Elevation Counties in Texas

PubMed Central

Hart, John

2010-01-01

There is controversy as to whether low levels of radiation (i.e., < 5 rem) pose a health risk. This brief inquiry compares archived cancer mortality data in counties having relatively low (0–250 feet above sea level), medium (500–1000 feet above sea level), and high (3000+ feet above sea level) elevations also having corresponding greater natural background levels of radiation respectively. Cancer mortality was found to be lowest in the high elevation counties (mean = 58.2) followed by low elevation counties (67.5) and then medium elevation counties (70.4). Statistically significant differences were found between low –high elevations (p = 0.003), and medium – high elevations (p = 0.010), but not between low and medium elevations (p = 0.5). More rigorous research, with an accounting of confounding variables, is indicated. PMID:21191484

Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.

PubMed

Geng, Biao; Liang, Man-Man; Ye, Xiao-Bing; Zhao, Wen-Ying

2015-01-01

The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.

Multifactorial modulation of susceptibility to l-lysine in an animal model of glutaric aciduria type I.

PubMed

Sauer, Sven W; Opp, Silvana; Komatsuzaki, Shoko; Blank, Anna-Eva; Mittelbronn, Michel; Burgard, Peter; Koeller, D M; Okun, Jürgen G; Kölker, Stefan

2015-05-01

Glutaric aciduria type I is an inherited defect in L-lysine, L-hydroxylysine and L-tryptophan degradation caused by deficiency of glutaryl-CoA dehydrogenase (GCDH). The majority of untreated patients presents with accumulation of neurotoxic metabolites - glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) - and striatal injury. Gcdh(-/-) mice display elevated levels of GA and 3-OH-GA but do not spontaneously develop striatal lesions. L-lysine-enriched diets (appr. 235 mg/d) were suggested to induce a neurological phenotype similar to affected patients. In our hands 93% of mice stressed according to the published protocol remained asymptomatic. To understand the underlying mechanism, we modified their genetic background (F1 C57BL6/Jx129/SvCrl) and increased the daily oral L-lysine supply (235-433 mg). We identified three modulating factors, (1) gender, (2) genetic background, and (3) amount of L-lysine. Male mice displayed higher vulnerability and inbreeding for more than two generations as well as elevating L-lysine supply increased the diet-induced mortality rate (up to 89%). Onset of first symptoms leads to strongly reduced intake of food and, thus, L-lysine suggesting a threshold for toxic metabolite production to induce neurological disease. GA and 3-OH-GA tissue concentrations did not correlate with dietary L-lysine supply but differed between symptomatic and asymptomatic mice. Cerebral activities of glyceraldehyde 3-phosphate dehydrogenase, 2-oxoglutarate dehydrogenase complex, and aconitase were decreased. Symptomatic mice did not develop striatal lesions or intracerebral hemorrhages. We found severe spongiosis in the hippocampus of Gcdh(-/-) mice which was independent of dietary L-lysine supply. In conclusion, the L-lysine-induced pathology in Gcdh(-/-) mice depends on genetic and dietary parameters. Copyright © 2014. Published by Elsevier B.V.

Olympus propagation studies in the US: Receiver development and the data acquisition system

NASA Technical Reports Server (NTRS)

Mckeeman, John C.

1990-01-01

Virginia Tech has developed two types of receivers to monitor the Olympus beacons, as well as a custom data acquisition system to store and display propagation data. Each of the receiver designs uses new hybrid analog/digital techniques. The data acquisition system uses a stand alone processor to collect and format the data for display and subsequent processing. The launch of the Olympus satellite with its coherent beacons offers new opportunities to study propagation effects at 12.5, 20, and 30 GHz. At Virginia Tech, the satellite is at 14 degrees in elevation, which allows us to measure low elevation angle effects. However, to make these measurements, a very accurate and stable measurement system is required. Virginia Tech has constructed a complex receiving system which monitors the Olympus beacons and all parameters associated with propagation research. In the current configuration, researchers have developed a receiver which frequency locks to the less fade susceptible 12.5 GHz beacon. Since all beacons on the satellite are driven from a single master oscillator, drift in the 12.5 GHz beacon implies corresponding drifts in the 20, and 30 GHz beacons. The receivers for the 20 and 30 GHz systems derive their frequency locking information from the 12.5 GHz system. This widens the dynamic range of the receivers and allows the receivers to maintain lock in severe fade conditions. In addition to monitoring the beacons, the sky noise is monitored with radiometers at each frequency. The radiometer output is used to set the clear air level for each beacon measurement. Researchers also measure the rain rate with several tipping bucket rain gauges placed along the propagation path.

Genomic instability in mice is greater in Fanconi anemia caused by deficiency of Fancd2 than Fancg.

PubMed

Reliene, Ramune; Yamamoto, Mitsuko L; Rao, P Nagesh; Schiestl, Robert H

2010-12-01

Fanconi anemia (FA) results from mutations in the FANC genes and is characterized by bone marrow failure, birth defects, and a high incidence of cancer. FANCG is a part of the FA core complex that is responsible for monoubiquitination of FANCD2 and FANCI. The precise role of the FA pathway is not well understood, although it may be involved in homologous recombination (HR), nonhomologous end joining, and translesion synthesis (TLS). Fancd2(-/-) mice have a more severe phenotype than Fancg(-/-), and other FA core complex-deficient mice, although both Fancg and Fancd2 belong to the same FA pathway. We hypothesized that Fancd2 deficiency results in a more severe phenotype because Fancd2 also has a FA pathway-independent function in the maintenance of genomic integrity. To test this hypothesis, we determined the level of DNA damage and genomic instability in Fancd2(-/-), Fancg(-/-), and wild-type controls. Fancd2(-/-) mice displayed a higher magnitude of chromosomal breakage and micronucleus formation than the wild-type or Fancg(-/-) mice. Also, DNA strand breaks were increased in Fancd2(-/-) but not in Fancg(-/-) mice. In addition, Fancd2(-/-) mice displayed an elevated frequency of DNA deletions, resulting from HR at the endogenous p(un) locus. In contrast, in Fancg(-/-) mice, the frequency of DNA deletions was decreased. Thus, Fancd2 but not Fancg deficiency results in elevated chromosomal/DNA breakage and permanent genome rearrangements. This provides evidence that Fancd2 plays an additional role in the maintenance of genomic stability than Fancg, which might explain the higher predisposition to cancer seen in the Fancd2(-/-) mice.

Practical low-cost stereo head-mounted display

NASA Astrophysics Data System (ADS)

Pausch, Randy; Dwivedi, Pramod; Long, Allan C., Jr.

1991-08-01

A high-resolution head-mounted display has been developed from substantially cheaper components than previous systems. Monochrome displays provide 720 by 280 monochrome pixels to each eye in a one-inch-square region positioned approximately one inch from each eye. The display hardware is the Private Eye, manufactured by Reflection Technologies, Inc. The tracking system uses the Polhemus Isotrak, providing (x,y,z, azimuth, elevation and roll) information on the user''s head position and orientation 60 times per second. In combination with a modified Nintendo Power Glove, this system provides a full-functionality virtual reality/simulation system. Using two host 80386 computers, real-time wire frame images can be produced. Other virtual reality systems require roughly 250,000 in hardware, while this one requires only 5,000. Stereo is particularly useful for this system because shading or occlusion cannot be used as depth cues.

Field Feasibility Study on the Use of Existing Commercially Available Instrumentation to Detect Fine-Scale ( or = 1 mm) Bottom Elevation Changes: Currituck Sound, North Carolina

DTIC Science & Technology

2014-08-01

resuspended into plumes. The transport of these plumes via currents can have physical, biological, and chemical impacts on habitats downstream of...other provision of law , no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a...elevation changes as dredged material is pumped into areas such as wetlands. They could also be used to evaluate the geomorphic stability of marshes and

Use of slope, aspect, and elevation maps derived from digital elevation model data in making soil surveys

USGS Publications Warehouse

Klingebiel, A.A.; Horvath, E.H.; Moore, D.G.; Reybold, W.U.

1987-01-01

Maps showing different classes of slope, aspect, and elevation were developed from U.S. Geological Survey digital elevation model data. The classes were displayed on clear Mylar at 1:24 000-scale and registered with topographic maps and orthophotos. The maps were used with aerial photographs, topographic maps, and other resource data to determine their value in making order-three soil surveys. They were tested on over 600 000 ha in Wyoming, Idaho, and Nevada under various climatic and topographic conditions. Field evaluations showed that the maps developed from digital elevation model data were accurate, except for slope class maps where slopes were <4%. The maps were useful to soil scientists, especially where (i) class boundaries coincided with soil changes, landform delineations, land use and management separations, and vegetation changes, and (ii) rough terrain and dense vegetation made it difficult to traverse the area. In hot, arid areas of sparse vegetation, the relationship of slope classes to kinds of soil and vegetation was less significant.

Relations between open-field, elevated plus-maze, and emergence tests as displayed by C57/BL6J and BALB/c mice.

PubMed

Lalonde, R; Strazielle, C

2008-06-15

The relations between open-field, elevated plus-maze, and emergence tests were examined in two strains of mice. In the open-field, C57BL/6J mice had more ambulatory movements and rears but not stereotyped movements relative to BALB/c. In addition, C57BL/6J mice entered more often than BALB/c into enclosed and open arms of the elevated plus-maze. When placed inside a large enclosure, C57BL/6J mice emerged more quickly than BALB/c from a small toy object. In the entire series of mice, ambulation and rears in the open-field were linearly correlated with open and enclosed arm visits in the elevated plus-maze. Ambulatory movements and rears were also correlated with emergence latencies. In contrast, stereotyped movements were correlated with emergence latencies, but not with any elevated plus-maze value. These results specify the extent and limits of association between the three tests.

Endocrine systems in juvenile anadromous and landlocked Atlantic salmon (Salmo salar): Seasonal development and seawater acclimation

USGS Publications Warehouse

Nilsen, Tom O.; Ebbesson, Lars O.E.; Kiilerich, P.; Bjornsson, B. Th; Madsen, Steffen S.; McCormick, S.D.; Stefansson, S.O.

2008-01-01

The present study compares developmental changes in plasma levels of growth hormone (GH), insulin-like growth factor I (IGF-I) and cortisol, and mRNA levels of their receptors and the prolactin receptor (PRLR) in the gill of anadromous and landlocked Atlantic salmon during the spring parr-smolt transformation (smoltification) period and following four days and one month seawater (SW) acclimation. Plasma GH and gill GH receptor (GHR) mRNA levels increased continuously during the spring smoltification period in the anadromous, but not in landlocked salmon. There were no differences in plasma IGF-I levels between strains, or any increase during smoltification. Gill IGF-I and IGF-I receptor (IGF-IR) mRNA levels increased in anadromous salmon during smoltification, with no changes observed in landlocked fish. Gill PRLR mRNA levels remained stable in both strains during spring. Plasma cortisol levels in anadromous salmon increased 5-fold in May and June, but not in landlocked salmon. Gill glucocorticoid receptor (GR) mRNA levels were elevated in both strains at the time of peak smoltification in anadromous salmon, while mineralocorticoid receptor (MR) mRNA levels remained stable. Only anadromous salmon showed an increase of gill 11??-hydroxysteroid dehydrogenase type-2 (11??-HSD2) mRNA levels in May. GH and gill GHR mRNA levels increased in both strains following four days of SW exposure in mid-May, whereas only the anadromous salmon displayed elevated plasma GH and GHR mRNA after one month in SW. Plasma IGF-I increased after four days in SW in both strains, decreasing in both strains after one month in SW. Gill IGF-I mRNA levels were only increased in landlocked salmon after 4 days in SW. Gill IGF-IR mRNA levels in SW did not differ from FW levels in either strain. Gill PRLR mRNA did not change after four days of SW exposure, and decreased in both strains after one month in SW. Plasma cortisol levels did not change following SW exposure in either strain. Gill GR, 11??-HSD2 and MR mRNA levels increased after four days in SW in both strains, whereas only the anadromous strain maintained elevated gill GR and 11??-HSD2 mRNA levels after one month in SW. The results indicate that hormones and receptors of the GH and cortisol axes are present at significantly lower levels during spring development and SW acclimation in landlocked relative to anadromous salmon. These findings suggest that attenuation of GH and cortisol axes may, at least partially, result in reduced preparatory upregulation of key gill ion-secretory proteins, possibly a result of reduced selection pressure for marine adaptations in landlocked salmon. ?? 2007 Elsevier Inc. All rights reserved.

Bioavailable copper modulates oxidative phosphorylation and growth of tumors

PubMed Central

Ishida, Seiko; Andreux, Pénélope; Poitry-Yamate, Carole; Auwerx, Johan; Hanahan, Douglas

2013-01-01

Copper is an essential trace element, the imbalances of which are associated with various pathological conditions, including cancer, albeit via largely undefined molecular and cellular mechanisms. Here we provide evidence that levels of bioavailable copper modulate tumor growth. Chronic exposure to elevated levels of copper in drinking water, corresponding to the maximum allowed in public water supplies, stimulated proliferation of cancer cells and de novo pancreatic tumor growth in mice. Conversely, reducing systemic copper levels with a chelating drug, clinically used to treat copper disorders, impaired both. Under such copper limitation, tumors displayed decreased activity of the copper-binding mitochondrial enzyme cytochrome c oxidase and reduced ATP levels, despite enhanced glycolysis, which was not accompanied by increased invasiveness of tumors. The antiproliferative effect of copper chelation was enhanced when combined with inhibitors of glycolysis. Interestingly, larger tumors contained less copper than smaller tumors and exhibited comparatively lower activity of cytochrome c oxidase and increased glucose uptake. These results establish copper as a tumor promoter and reveal that varying levels of copper serves to regulate oxidative phosphorylation in rapidly proliferating cancer cells inside solid tumors. Thus, activation of glycolysis in tumors may in part reflect insufficient copper bioavailability in the tumor microenvironment. PMID:24218578

Clinical implication of elevated human cervical cancer oncogene-1 expression in esophageal squamous cell carcinoma.

PubMed

Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

2012-07-01

The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantitative RT-PCR and Western blotting methods; Kaplan-Meier curve was used to evaluate the prognostic value of HCCR-1 level in patients with ESCC using log-rank test. HCCR-1 displayed high levels in ESCC tissues compared to squamous dysplasia tissues and normal esophageal epithelial tissues. No significant correlation was observed between the levels of HCCR-1 mRNA and protein and gender and age (all p>0.05) but obviously related to histological grade, clinical stage, and lymph node metastasis (all p<0.001). Moreover, the survival rate of the patients with low HCCR-1 levels was higher than that of the patients with high HCCR-1 levels (both p<0.05). These data demonstrate that HCCR-1 may be used as a novel predictor for the prognosis of the patients with ESCC.

Bifurcation of potential vorticity gradients across the Southern Hemisphere stratospheric polar vortex

NASA Astrophysics Data System (ADS)

Conway, Jonathan; Bodeker, Greg; Cameron, Chris

2018-06-01

The wintertime stratospheric westerly winds circling the Antarctic continent, also known as the Southern Hemisphere polar vortex, create a barrier to mixing of air between middle and high latitudes. This dynamical isolation has important consequences for export of ozone-depleted air from the Antarctic stratosphere to lower latitudes. The prevailing view of this dynamical barrier has been an annulus compromising steep gradients of potential vorticity (PV) that create a single semi-permeable barrier to mixing. Analyses presented here show that this barrier often displays a bifurcated structure where a double-walled barrier exists. The bifurcated structure manifests as enhanced gradients of PV at two distinct latitudes - usually on the inside and outside flanks of the region of highest wind speed. Metrics that quantify the bifurcated nature of the vortex have been developed and their variation in space and time has been analysed. At most isentropic levels between 395 and 850 K, bifurcation is strongest in mid-winter and decreases dramatically during spring. From August onwards a distinct structure emerges, where elevated bifurcation remains between 475 and 600 K, and a mostly single-walled barrier occurs at other levels. While bifurcation at a given level evolves from month to month, and does not always persist through a season, interannual variations in the strength of bifurcation display coherence across multiple levels in any given month. Accounting for bifurcation allows the region of reduced mixing to be better characterised. These results suggest that improved understanding of cross-vortex mixing requires consideration of the polar vortex not as a single mixing barrier but as a barrier with internal structure that is likely to manifest as more complex gradients in trace gas concentrations across the vortex barrier region.

Mondo/ChREBP-Mlx-Regulated Transcriptional Network Is Essential for Dietary Sugar Tolerance in Drosophila

PubMed Central

Havula, Essi; Teesalu, Mari; Hyötyläinen, Tuulia; Seppälä, Heini; Hasygar, Kiran; Auvinen, Petri; Orešič, Matej; Sandmann, Thomas; Hietakangas, Ville

2013-01-01

Sugars are important nutrients for many animals, but are also proposed to contribute to overnutrition-derived metabolic diseases in humans. Understanding the genetic factors governing dietary sugar tolerance therefore has profound biological and medical significance. Paralogous Mondo transcription factors ChREBP and MondoA, with their common binding partner Mlx, are key sensors of intracellular glucose flux in mammals. Here we report analysis of the in vivo function of Drosophila melanogaster Mlx and its binding partner Mondo (ChREBP) in respect to tolerance to dietary sugars. Larvae lacking mlx or having reduced mondo expression show strikingly reduced survival on a diet with moderate or high levels of sucrose, glucose, and fructose. mlx null mutants display widespread changes in lipid and phospholipid profiles, signs of amino acid catabolism, as well as strongly elevated circulating glucose levels. Systematic loss-of-function analysis of Mlx target genes reveals that circulating glucose levels and dietary sugar tolerance can be genetically uncoupled: Krüppel-like transcription factor Cabut and carbonyl detoxifying enzyme Aldehyde dehydrogenase type III are essential for dietary sugar tolerance, but display no influence on circulating glucose levels. On the other hand, Phosphofructokinase 2, a regulator of the glycolysis pathway, is needed for both dietary sugar tolerance and maintenance of circulating glucose homeostasis. Furthermore, we show evidence that fatty acid synthesis, which is a highly conserved Mondo-Mlx-regulated process, does not promote dietary sugar tolerance. In contrast, survival of larvae with reduced fatty acid synthase expression is sugar-dependent. Our data demonstrate that the transcriptional network regulated by Mondo-Mlx is a critical determinant of the healthful dietary spectrum allowing Drosophila to exploit sugar-rich nutrient sources. PMID:23593032

The Effect of Alcohol and Hydrogen Peroxide on Liver Hepcidin Gene Expression in Mice Lacking Antioxidant Enzymes, Glutathione Peroxidase-1 or Catalase

PubMed Central

Harrison-Findik, Duygu Dee; Lu, Sizhao

2015-01-01

This study investigates the regulation of hepcidin, the key iron-regulatory molecule, by alcohol and hydrogen peroxide (H2O2) in glutathione peroxidase-1 (gpx-1−/−) and catalase (catalase−/−) knockout mice. For alcohol studies, 10% ethanol was administered in the drinking water for 7 days. Gpx-1−/− displayed significantly higher hepatic H2O2 levels than catalase−/− compared to wild-type mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The basal level of liver hepcidin expression was attenuated in gpx-1−/− mice. Alcohol increased H2O2 production in catalase−/− and wild-type, but not gpx-1−/−, mice. Hepcidin expression was inhibited in alcohol-fed catalase−/− and wild-type mice. In contrast, alcohol elevated hepcidin expression in gpx-1−/− mice. Gpx-1−/− mice also displayed higher level of basal liver CHOP protein expression than catalase−/− mice. Alcohol induced CHOP and to a lesser extent GRP78/BiP expression, but not XBP1 splicing or binding of CREBH to hepcidin gene promoter, in gpx-1−/− mice. The up-regulation of hepatic ATF4 mRNA levels, which was observed in gpx-1−/− mice, was attenuated by alcohol. In conclusion, our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo. Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1, stimulates liver hepcidin gene expression by ER stress independent of CREBH. PMID:25955433

Carbonate deposition, Pyramid Lake subbasin, Nevada: 1. Sequence of formation and elevational distribution of carbonate deposits (Tufas)

USGS Publications Warehouse

Benson, L.

1994-01-01

During the late Quarternary, the elevation of terrace cutting and carbonate deposition in the Pyramid Lake subbasin were controlled by constancy of lake level imposed by spill to adjoining subbasins. Sill elevations are 1177-1183 m (Mud Lake Slough Sill), 1207 m (Emerson Pass Sill), and 1265 m (Darwin Pass Sill). Carbonate deposition was favored by: (1) hydrologic closure, (2) proximity to a source of calcium, (3) elevated water temperature, and (4) a solid substrate. The thickness and aspect of tufa are a function oflake-level dynamics. Relatively thin sheets and pendant sheets were deposited during a rising or falling lake. The upper parts of thick reef-form tufas have a horizontal aspect and were deposited in a lake which was stabilized by spill to the Carson Desert subbasin. The lower parts of the reef-form tufas are thinner and their outer surface has a vertical aspect, indicating that the lower part formed in a receding lake. The thickest and most complete sequences of tufa are mounds that border the Pyramid Lake shore. The tops of the tallest mounds reach the elevation of the Darwin Pass Sill and many mounds have been eroded to the elevations of the Mud Lake Slough Sill of the Emerson Pass Sill. The sequence of tufa formation (from oldest to youngest) displayed in these mounds is: (1) a beachrock containing carbonate-cemented volcanic cobbles, (2) broken and eroded old spheroids that contain thinolitic tufa and an outer rind of dense laminated tufa, (3) large cylindrical (tubular) tufas capped by (4) coatings of old dense tufas, and (5) several generations of old branching tufa commonly associated with thin, platy tufas and coatings of thinolitic tufa, (6) young spheroids that contain poorly oriented young thinolitic tufa in the center and several generations of radially oriented young thinolitic tufas near the outer edge, (7) a transitional thinolite-to-branching tufa, (8) two or more layers of young branching tufa, (9) a 0.5-cm-thick layer of fine-grained dolomite, (10) a 2-cm-thick layer of young dense laminated tufa, (11) a 0.1-cm-thick layer of encrusting tufa that was covered by a beach deposit and (12) a 1.0-cm-thick layer of porous encrusting tufa that coated the beach deposit and the sides of tufa mounds. The elevational ranges of the principal varieties of tufa are not related to terrace or spill elevations. It seems likely that the distribution of tufa varieties is related to variation in the thermal structure or chemistry of Lake Lahontan. It is hypothesized that the thinolitic tufa (ikaite) formed in the near freezing hypolimnion and the braching tufa (calcite) formed in the seasonally warmer epiliminion of the lake. ?? 1994.

Changes of arthropod diversity across an altitudinal ecoregional zonation in Northwestern Argentina

PubMed Central

González-Reyes, Andrea X.; Rodriguez-Artigas, Sandra M.

2017-01-01

This study examined arthropod community patterns over an altitudinal ecoregional zonation that extended through three ecoregions (Yungas, Monte de Sierras y Bolsones, and Puna) and two ecotones (Yungas-Monte and Prepuna) of Northwestern Argentina (altitudinal range of 2,500 m), and evaluated the abiotic and biotic factors and the geographical distance that could influence them. Pitfall trap and suction samples were taken seasonally in 15 sampling sites (1,500–4,000 m a.s.l) during one year. In addition to climatic variables, several soil and vegetation variables were measured in the field. Values obtained for species richness between ecoregions and ecotones and by sampling sites were compared statistically and by interpolation–extrapolation analysis based on individuals at the same sample coverage level. Effects of predictor variables and the similarity of arthropods were shown using non-metric multidimensional scaling, and the resulting groups were evaluated using a multi-response permutation procedure. Polynomial regression was used to evaluate the relationship between altitude with total species richness and those of hyperdiverse/abundant higher taxa and the latter taxa with each predictor variable. The species richness pattern displayed a decrease in species diversity as the elevation increased at the bottom wet part (Yungas) of our altitudinal zonation until the Monte, and a unimodal pattern of diversity in the top dry part (Monte, Puna). Each ecoregion and ecotonal zone evidenced a particular species richness and assemblage of arthropods, but the latter ones displayed a high percentage of species shared with the adjacent ecoregions. The arthropod elevational pattern and the changes of the assemblages were explained by the environmental gradient (especially the climate) in addition to a geographic gradient (the distance of decay of similarity), demonstrating that the species turnover is important to explain the beta diversity along the elevational gradient. This suggests that patterns of diversity and distribution of arthropods are regulated by the dissimilarity of ecoregional environments that establish a wide range of geographic and environmental barriers, coupled with a limitation of species dispersal. Therefore, the arthropods of higher taxa respond differently to the altitudinal ecoregional zonation. PMID:29230361

Volumetric visualization of multiple-return LIDAR data: Using voxels

USGS Publications Warehouse

Stoker, Jason M.

2009-01-01

Elevation data are an important component in the visualization and analysis of geographic information. The creation and display of 3D models representing bare earth, vegetation, and surface structures have become a major focus of light detection and ranging (lidar) remote sensing research in the past few years. Lidar is an active sensor that records the distance, or range, of a laser usually fi red from an airplane, helicopter, or satellite. By converting the millions of 3D lidar returns from a system into bare ground, vegetation, or structural elevation information, extremely accurate, high-resolution elevation models can be derived and produced to visualize and quantify scenes in three dimensions. These data can be used to produce high-resolution bare-earth digital elevation models; quantitative estimates of vegetative features such as canopy height, canopy closure, and biomass; and models of urban areas such as building footprints and 3D city models.

Video game violence use among "vulnerable" populations: the impact of violent games on delinquency and bullying among children with clinically elevated depression or attention deficit symptoms.

PubMed

Ferguson, Christopher J; Olson, Cheryl K

2014-01-01

The issue of children's exposure to violent video games has been a source of considerable debate for several decades. Questions persist whether children with pre-existing mental health problems may be influenced adversely by exposure to violent games, even if other children are not. We explored this issue with 377 children (62 % female, mixed ethnicity, mean age = 12.93) displaying clinically elevated attention deficit or depressive symptoms on the Pediatric Symptom Checklist. Results from our study found no evidence for increased bullying or delinquent behaviors among youth with clinically elevated mental health symptoms who also played violent video games. Our results did not support the hypothesis that children with elevated mental health symptoms constitute a "vulnerable" population for video game violence effects. Implications and suggestions for further research are provided.

Designing and creating Saccharomyces interspecific hybrids for improved, industry relevant, phenotypes.

PubMed

Bellon, Jennifer R; Yang, Fei; Day, Martin P; Inglis, Debra L; Chambers, Paul J

2015-10-01

To remain competitive in increasingly overcrowded markets, yeast strain development programmes are crucial for fermentation-based food and beverage industries. In a winemaking context, there are many yeast phenotypes that stand to be improved. For example, winemakers endeavouring to produce sweet dessert wines wrestle with fermentation challenges particular to fermenting high-sugar juices, which can lead to elevated volatile acidity levels and extended fermentation times. In the current study, we used natural yeast breeding techniques to generate Saccharomyces spp. interspecific hybrids as a non-genetically modified (GM) strategy to introduce targeted improvements in important, wine-relevant traits. The hybrids were generated by mating a robust wine strain of Saccharomyces cerevisiae with a wine isolate of Saccharomyces bayanus, a species previously reported to produce wines with low concentrations of acetic acid. Two hybrids generated from the cross showed robust fermentation properties in high-sugar grape juice and produced botrytised Riesling wines with much lower concentrations of acetic acid relative to the industrial wine yeast parent. The hybrids also displayed suitability for icewine production when bench-marked against an industry standard icewine yeast, by delivering icewines with lower levels of acetic acid. Additionally, the hybrid yeast produced wines with novel aroma and flavour profiles and established that choice of yeast strain impacts on wine colour. These new hybrid yeasts display the desired targeted fermentation phenotypes from both parents, robust fermentation in high-sugar juice and the production of wines with low volatile acidity, thus establishing their suitability for wine styles that are traditionally troubled by excessive volatile acidity levels.

Emotional and cardiovascular reactivity to a child-focused interpersonal stressor among depressed mothers of psychiatrically ill children.

PubMed

Cyranowski, Jill M; Swartz, Holly A; Hofkens, Tara L; Frank, Ellen

2009-01-01

Impairment in maternal interpersonal function represents a risk factor for poor psychiatric outcomes among children of depressed mothers. However, the mechanisms by which this effect occurs have yet to be fully elucidated. Elevated levels of emotional or physiological reactivity to interpersonal stress may impact depressed mothers' ability to effectively negotiate child-focused conflicts. This effect may become particularly pronounced when depressed mothers are parenting a psychiatrically ill child. The current feasibility study evaluated mothers' emotional and cardiovascular reactivity in response to an acute, child-focused stress task. Twenty-two depressed mothers of psychiatrically ill children were recruited from a larger clinical trial; half were randomly assigned to receive an adapted form of interpersonal psychotherapy (IPT-MOMS), while the other half received treatment as usual (TAU). For comparison purposes, a matched sample of 22 nondepressed mothers of psychiatrically healthy children was also evaluated. Depressed mothers receiving minimal-treatment TAU displayed the greatest increases in depressed mood, heart rate, and diastolic blood pressure in response to the child-focused stress task, and significantly differed from the relatively low levels of reactivity observed among nondepressed mothers of healthy children. In contrast, depressed mothers receiving IPT-MOMS displayed patterns of reactivity that fell between these extreme groups. Maternal stress reactivity was associated not only with maternal psychiatric symptoms, but also with levels of chronic parental stress and maternal history of childhood emotional abuse. Future, more definitive research is needed to evaluate depressed mothers' interpersonal stress reactivity, its amenability to treatment, and its long-term impact on child psychiatric outcomes. (c) 2008 Wiley-Liss, Inc.

GPER Deficiency in Male Mice Results in Insulin Resistance, Dyslipidemia, and a Proinflammatory State

PubMed Central

Sharma, Geetanjali; Hu, Chelin; Brigman, Jonathan L.; Zhu, Gang; Hathaway, Helen J.

2013-01-01

Estrogen is an important regulator of metabolic syndrome, a collection of abnormalities including obesity, insulin resistance/glucose intolerance, hypertension, dyslipidemia, and inflammation, which together lead to increased risk of cardiovascular disease and diabetes. The role of the G protein-coupled estrogen receptor (GPER/GPR30), particularly in males, in these pathologies remains unclear. We therefore sought to determine whether loss of GPER contributes to aspects of metabolic syndrome in male mice. Although 6-month-old male and female GPER knockout (KO) mice displayed increased body weight compared with wild-type littermates, only female GPER KO mice exhibited glucose intolerance at this age. Weight gain in male GPER KO mice was associated with increases in both visceral and sc fat. GPER KO mice, however, exhibited no differences in food intake or locomotor activity. One-year-old male GPER KO mice displayed an abnormal lipid profile with higher cholesterol and triglyceride levels. Fasting blood glucose levels remained normal, whereas insulin levels were elevated. Although insulin resistance was evident in GPER KO male mice from 6 months onward, glucose intolerance was pronounced only at 18 months of age. Furthermore, by 2 years of age, a proinflammatory phenotype was evident, with increases in the proinflammatory and immunomodulatory cytokines IL-1β, IL-6, IL-12, TNFα, monocyte chemotactic protein-1, interferon γ-induced protein 10, and monokine induced by interferon gamma and a concomitant decrease in the adipose-specific cytokine adiponectin. In conclusion, our study demonstrates for the first time that in male mice, GPER regulates metabolic parameters associated with obesity and diabetes. PMID:23970785

GPER deficiency in male mice results in insulin resistance, dyslipidemia, and a proinflammatory state.

PubMed

Sharma, Geetanjali; Hu, Chelin; Brigman, Jonathan L; Zhu, Gang; Hathaway, Helen J; Prossnitz, Eric R

2013-11-01

Estrogen is an important regulator of metabolic syndrome, a collection of abnormalities including obesity, insulin resistance/glucose intolerance, hypertension, dyslipidemia, and inflammation, which together lead to increased risk of cardiovascular disease and diabetes. The role of the G protein-coupled estrogen receptor (GPER/GPR30), particularly in males, in these pathologies remains unclear. We therefore sought to determine whether loss of GPER contributes to aspects of metabolic syndrome in male mice. Although 6-month-old male and female GPER knockout (KO) mice displayed increased body weight compared with wild-type littermates, only female GPER KO mice exhibited glucose intolerance at this age. Weight gain in male GPER KO mice was associated with increases in both visceral and sc fat. GPER KO mice, however, exhibited no differences in food intake or locomotor activity. One-year-old male GPER KO mice displayed an abnormal lipid profile with higher cholesterol and triglyceride levels. Fasting blood glucose levels remained normal, whereas insulin levels were elevated. Although insulin resistance was evident in GPER KO male mice from 6 months onward, glucose intolerance was pronounced only at 18 months of age. Furthermore, by 2 years of age, a proinflammatory phenotype was evident, with increases in the proinflammatory and immunomodulatory cytokines IL-1β, IL-6, IL-12, TNFα, monocyte chemotactic protein-1, interferon γ-induced protein 10, and monokine induced by interferon gamma and a concomitant decrease in the adipose-specific cytokine adiponectin. In conclusion, our study demonstrates for the first time that in male mice, GPER regulates metabolic parameters associated with obesity and diabetes.

The Implications of selenium deficiency for wild herbivore conservation: a review

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

Werner T. Flueck; J.M. Smith Flueck; J. Mionczynski

Selenium (Se) has been identified as an essential micronutrient in all animals. It is required at the most fundamental physiological level as a component of the selenoproteins containing the 21st amino acid, selenocysteine. Adequate levels of Se are vital to proper reproductive performance, bone metabolism, immune function and iodine metabolism. Yet, Se is a relatively rare element, and is often present at low concentrations in soil and vegetation. Selenium deficiencies are widespread in domestic stock and are unavoidable in some wildlife populations. This may be especially true for populations confined to high elevation ranges, or on areas with granitic bedrockmore » with low Se content, or that have lost access to Se-containing parts of their ranges such as mineral licks or low-elevation winter range. The condition may be exacerbated by increased levels of oxidative stress. Because our understanding of Se as a micronutrient is relatively new, many wildlife managers are unaware of the element’s importance in physiology and population dynamics. Severe deficiency results in obvious symptoms such as white muscle disease. However, more frequently, deficiency may be chronic and subclinical. Individuals then display no obvious signs of malady, yet performance suffers until their populations decline without apparent cause. While mysterious population declines are not always due to Se deficiency, the wildlife manager should be aware of the possibility. Therefore, this review presents not only a summary of the wildlife literature regarding Se nutrition, but also a comprehensive look at the role of Se in mammalian physiology, and the behavior of this important element in the environment. Finally, the role of the biogeochemical Se cycle is discussed, and evidence is provided that the levels of available Se in the environment are decreasing while physiological demands often are increasing.« less

CNTF-ACM promotes mitochondrial respiration and oxidative stress in cortical neurons through upregulating L-type calcium channel activity.

PubMed

Sun, Meiqun; Liu, Hongli; Xu, Huanbai; Wang, Hongtao; Wang, Xiaojing

2016-09-01

A specialized culture medium termed ciliary neurotrophic factor-treated astrocyte-conditioned medium (CNTF-ACM) allows investigators to assess the peripheral effects of CNTF-induced activated astrocytes upon cultured neurons. CNTF-ACM has been shown to upregulate neuronal L-type calcium channel current activity, which has been previously linked to changes in mitochondrial respiration and oxidative stress. Therefore, the aim of this study was to evaluate CNTF-ACM's effects upon mitochondrial respiration and oxidative stress in rat cortical neurons. Cortical neurons, CNTF-ACM, and untreated control astrocyte-conditioned medium (UC-ACM) were prepared from neonatal Sprague-Dawley rat cortical tissue. Neurons were cultured in either CNTF-ACM or UC-ACM for a 48-h period. Changes in the following parameters before and after treatment with the L-type calcium channel blocker isradipine were assessed: (i) intracellular calcium levels, (ii) mitochondrial membrane potential (ΔΨm), (iii) oxygen consumption rate (OCR) and adenosine triphosphate (ATP) formation, (iv) intracellular nitric oxide (NO) levels, (v) mitochondrial reactive oxygen species (ROS) production, and (vi) susceptibility to the mitochondrial complex I toxin rotenone. CNTF-ACM neurons displayed the following significant changes relative to UC-ACM neurons: (i) increased intracellular calcium levels (p < 0.05), (ii) elevation in ΔΨm (p < 0.05), (iii) increased OCR and ATP formation (p < 0.05), (iv) increased intracellular NO levels (p < 0.05), (v) increased mitochondrial ROS production (p < 0.05), and (vi) increased susceptibility to rotenone (p < 0.05). Treatment with isradipine was able to partially rescue these negative effects of CNTF-ACM (p < 0.05). CNTF-ACM promotes mitochondrial respiration and oxidative stress in cortical neurons through elevating L-type calcium channel activity.

Hypomorphic alleles reveal FCA-independent roles for FY in the regulation of FLOWERING LOCUS C.

PubMed

Feng, Wei; Jacob, Yannick; Veley, Kira M; Ding, Lei; Yu, Xuhong; Choe, Goh; Michaels, Scott D

2011-03-01

The autonomous floral promotion pathway plays a key role in the regulation of flowering in rapid-cycling Arabidopsis (Arabidopsis thaliana) by providing constitutive repression of the floral inhibitor FLOWERING LOCUS C (FLC). As a result, autonomous pathway mutants contain elevated levels of FLC and are late flowering. Winter annual Arabidopsis, in contrast, contain functional alleles of FRIGIDA (FRI), which acts epistatically to the autonomous pathway to up-regulate FLC and delay flowering. To further explore the relationship between FRI and the autonomous pathway, we placed autonomous pathway mutants in a FRI-containing background. Unexpectedly, we found that a hypomorphic allele of the autonomous pathway gene fy (fy null alleles are embryo lethal) displayed background-specific effects on FLC expression and flowering time; in a rapid-cycling background fy mutants contained elevated levels of FLC and were late flowering, whereas in a winter annual background fy decreased FLC levels and partially suppressed the late-flowering phenotype conferred by FRI. Because FY has been shown to have homology to polyadenylation factors, we examined polyadenylation site selection in FLC transcripts. In wild type, two polyadenylation sites were detected and used at similar levels. In fy mutant backgrounds, however, the ratio of products was shifted to favor the distally polyadenylated form. FY has previously been shown to physically interact with another member of the autonomous pathway, FCA. Interestingly, we found that fy can partially suppress FLC expression in an fca null background and promote proximal polyadenylation site selection usage in the absence of FCA. Taken together, these results indicate novel and FCA-independent roles for FY in the regulation of FLC.

Hypomorphic Alleles Reveal FCA-Independent Roles for FY in the Regulation of FLOWERING LOCUS C1[C][W][OA

PubMed Central

Feng, Wei; Jacob, Yannick; Veley, Kira M.; Ding, Lei; Yu, Xuhong; Choe, Goh; Michaels, Scott D.

2011-01-01

The autonomous floral promotion pathway plays a key role in the regulation of flowering in rapid-cycling Arabidopsis (Arabidopsis thaliana) by providing constitutive repression of the floral inhibitor FLOWERING LOCUS C (FLC). As a result, autonomous pathway mutants contain elevated levels of FLC and are late flowering. Winter annual Arabidopsis, in contrast, contain functional alleles of FRIGIDA (FRI), which acts epistatically to the autonomous pathway to up-regulate FLC and delay flowering. To further explore the relationship between FRI and the autonomous pathway, we placed autonomous pathway mutants in a FRI-containing background. Unexpectedly, we found that a hypomorphic allele of the autonomous pathway gene fy (fy null alleles are embryo lethal) displayed background-specific effects on FLC expression and flowering time; in a rapid-cycling background fy mutants contained elevated levels of FLC and were late flowering, whereas in a winter annual background fy decreased FLC levels and partially suppressed the late-flowering phenotype conferred by FRI. Because FY has been shown to have homology to polyadenylation factors, we examined polyadenylation site selection in FLC transcripts. In wild type, two polyadenylation sites were detected and used at similar levels. In fy mutant backgrounds, however, the ratio of products was shifted to favor the distally polyadenylated form. FY has previously been shown to physically interact with another member of the autonomous pathway, FCA. Interestingly, we found that fy can partially suppress FLC expression in an fca null background and promote proximal polyadenylation site selection usage in the absence of FCA. Taken together, these results indicate novel and FCA-independent roles for FY in the regulation of FLC. PMID:21209277

Influence of continuous illumination on estrous cycle of rats: time course of changes in levels of gonadotropins and ovarian steroids until occurrence of persistent estrus.

PubMed

Takeo, Y

1984-08-01

Plasma concentrations of LH, FSH, 17 beta-estradiol, estrone and progesterone were determined chronologically by radioimmunoassays in two groups of adult female rats exposed to continuous illumination (LL). Group 1 rats showing vaginal estrous cycles were sacrificed at 3- to 6-hour intervals during late proestrus through early estrus of the first 5 cycles after exposure to LL. Group 2 animals which displayed persistent vaginal estrus in an early period of exposure to LL were killed on the 2nd, 3rd, 4th, 5th and 7th days of vaginal estrus. In Group 1 rats, surges of the hormones, except estrone, took place in all the 5 cycles. The occurrence of peak hormone levels in each cycle was invariably delayed after transfer of animals to LL. According to regression analyses, the lengths of secretion cycles of LH, FSH, 17 beta-estradiol and progesterone in rats under LL were 100.89, 100.46, 101.14 and 101.06 h, respectively. Elevation of 17 beta-estradiol levels was observed prior to the LH surge, and peaks of progesterone and FSH occurred following it. However, the secretion patterns of these hormones appear to be disrupted with length of exposure to LL. In group 2 rats, the mean concentration of LH during persistent estrus was approximately similar to that on the morning of the days of proestrus of the 4-day cycles of rats placed under an alternating 12-hour light-dark regimen (LD), whereas the mean FSH concentration was continuously low. While the concentrations of 17 beta-estradiol and estrone in persistent-estrous rats were elevated, progesterone levels remained low.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective study of one-carbon metabolism biomarkers and cancer of the head and neck and esophagus.

PubMed

Fanidi, Anouar; Relton, Caroline; Ueland, Per Magne; Midttun, Øivind; Vollset, Stein Emil; Travis, Ruth C; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Bueno-de-Mesquita, H Bas; Ros, Martine; Boeing, Heiner; Tumino, Rosario; Panico, Salvatore; Palli, Domenico; Sieri, Sabina; Vineis, Paolo; Sánchez, María-José; Huerta, José María; Barricarte Gurrea, Aurelio; Luján-Barroso, Leila; Quirós, J Ramón; Tjønneland, Anne; Halkjær, Jytte; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Cadeau, Claire; Weiderpass, Elisabete; Johansson, Mikael; Riboli, Elio; Brennan, Paul; Johansson, Mattias

2015-02-15

Experimental and epidemiological data suggest that factors of one-carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre-diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post-diagnosis all-cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [ORQ4 vs. Q1 ] being 2.13 (95% confidence interval [95% CI] 1.13-4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (ORQ4 vs. Q1 0.63, 95% CI 0.35-1.16, p for trend 0.02). Subgroup analyses by anatomical sub-site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8×10(-4)), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck. © 2014 UICC.

Resting-state functional connectivity differentiates anxious apprehension and anxious arousal.

PubMed

Burdwood, Erin N; Infantolino, Zachary P; Crocker, Laura D; Spielberg, Jeffrey M; Banich, Marie T; Miller, Gregory A; Heller, Wendy

2016-10-01

Brain regions in the default mode network (DMN) display greater functional connectivity at rest or during self-referential processing than during goal-directed tasks. The present study assessed resting-state connectivity as a function of anxious apprehension and anxious arousal, independent of depressive symptoms, in order to understand how these dimensions disrupt cognition. Whole-brain, seed-based analyses indicated differences between anxious apprehension and anxious arousal in DMN functional connectivity. Lower connectivity associated with higher anxious apprehension suggests decreased adaptive, inner-focused thought processes, whereas higher connectivity at higher levels of anxious arousal may reflect elevated monitoring of physiological responses to threat. These findings further the conceptualization of anxious apprehension and anxious arousal as distinct psychological dimensions with distinct neural instantiations. © 2016 Society for Psychophysiological Research.

Miniaturized LEDs for flat-panel displays

NASA Astrophysics Data System (ADS)

Radauscher, Erich J.; Meitl, Matthew; Prevatte, Carl; Bonafede, Salvatore; Rotzoll, Robert; Gomez, David; Moore, Tanya; Raymond, Brook; Cok, Ronald; Fecioru, Alin; Trindade, António Jose; Fisher, Brent; Goodwin, Scott; Hines, Paul; Melnik, George; Barnhill, Sam; Bower, Christopher A.

2017-02-01

Inorganic light emitting diodes (LEDs) serve as bright pixel-level emitters in displays, from indoor/outdoor video walls with pixel sizes ranging from one to thirty millimeters to micro displays with more than one thousand pixels per inch. Pixel sizes that fall between those ranges, roughly 50 to 500 microns, are some of the most commercially significant ones, including flat panel displays used in smart phones, tablets, and televisions. Flat panel displays that use inorganic LEDs as pixel level emitters (μILED displays) can offer levels of brightness, transparency, and functionality that are difficult to achieve with other flat panel technologies. Cost-effective production of μILED displays requires techniques for precisely arranging sparse arrays of extremely miniaturized devices on a panel substrate, such as transfer printing with an elastomer stamp. Here we present lab-scale demonstrations of transfer printed μILED displays and the processes used to make them. Demonstrations include passive matrix μILED displays that use conventional off-the shelf drive ASICs and active matrix μILED displays that use miniaturized pixel-level control circuits from CMOS wafers. We present a discussion of key considerations in the design and fabrication of highly miniaturized emitters for μILED displays.

De novo microdeletion of Xp11.3 exclusively encompassing the monoamine oxidase A and B genes in a male infant with episodic hypotonia: A genomics approach to personalized medicine

PubMed Central

O’Leary, Ryan E.; Shih, Jean C.; Hyland, Keith; Kramer, Nancy; Asher, Y. Jane Tavyev; Graham, John M.

2012-01-01

Monoamine oxidase A and B (MAOA and MAOB) play key roles in deaminating neurotransmitters and various other biogenic amines. Patients deficient in one or both enzymes have distinct metabolic and neurologic profiles. MAOB deficient patients exhibit normal clinical characteristics and behavior, while MAOA deficient patients have borderline intellectual deficiency and impaired impulse control. Patients who lack both MAOA and MAOB have the most extreme laboratory values (urine, blood, and CSF serotonin 4–6 times normal, with elevated O-methylated amine metabolites and reduced deaminated metabolites) in addition to severe intellectual deficiency and behavioral problems. Mice lacking maoa and moab exhibit decreased proliferation of neural stem cells beginning in late gestation and persisting into adulthood These mice show significantly increased monoamine levels, particularly serotonin, as well as anxiety-like behaviors as adults, suggesting that brain maturation in late embryonic development is adversely affected by elevated serotonin levels. We report the case of a male infant with a de novo Xp11.3 microdeletion exclusively encompassing the MAOA and MAOB genes. This newly recognized X-linked disorder is characterized by severe intellectual disability and unusual episodes of hypotonia, which resemble atonic seizures, but have no EEG correlate. A customized low dietary amine diet was implemented in an attempt to prevent the cardiovascular complications that can result from the excessive intake of these compounds. This is the second report of this deletion and the first attempt to maintain the patient’s cardiovascular health through dietary manipulation. Even though a diet low in tyramine, phenylethylamine, and dopa/dopamine is necessary for long-term management, it will not rescue the abnormal monoamine profile seen in combined MAOA and MAOB deficiency. Our patient displays markedly elevated levels of serotonin in blood, serum, urine, and CSF while on this diet. Serotonin biosynthesis inhibitors like para-chlorophenylalanine and p-ethynylphenylalanine may be needed to lower serotonin levels in patients with absent monoamine oxidase enzymes. PMID:22365943

De novo microdeletion of Xp11.3 exclusively encompassing the monoamine oxidase A and B genes in a male infant with episodic hypotonia: a genomics approach to personalized medicine.

PubMed

O'Leary, Ryan E; Shih, Jean C; Hyland, Keith; Kramer, Nancy; Asher, Y Jane Tavyev; Graham, John M

2012-05-01

Monoamine oxidase A and B (MAOA and MAOB) play key roles in deaminating neurotransmitters and various other biogenic amines. Patients deficient in one or both enzymes have distinct metabolic and neurologic profiles. MAOB deficient patients exhibit normal clinical characteristics and behavior, while MAOA deficient patients have borderline intellectual deficiency and impaired impulse control. Patients who lack both MAOA and MAOB have the most extreme laboratory values (urine, blood, and CSF serotonin 4-6 times normal, with elevated O-methylated amine metabolites and reduced deaminated metabolites) in addition to severe intellectual deficiency and behavioral problems. Mice lacking maoa and moab exhibit decreased proliferation of neural stem cells beginning in late gestation and persisting into adulthood. These mice show significantly increased monoamine levels, particularly serotonin, as well as anxiety-like behaviors as adults, suggesting that brain maturation in late embryonic development is adversely affected by elevated serotonin levels. We report the case of a male infant with a de novo Xp11.3 microdeletion exclusively encompassing the MAOA and MAOB genes. This newly recognized X-linked disorder is characterized by severe intellectual disability and unusual episodes of hypotonia, which resemble atonic seizures, but have no EEG correlate. A customized low dietary amine diet was implemented in an attempt to prevent the cardiovascular complications that can result from the excessive intake of these compounds. This is the second report of this deletion and the first attempt to maintain the patient's cardiovascular health through dietary manipulation. Even though a diet low in tyramine, phenylethylamine, and dopa/dopamine is necessary for long-term management, it will not rescue the abnormal monoamine profile seen in combined MAOA and MAOB deficiency. Our patient displays markedly elevated levels of serotonin in blood, serum, urine, and CSF while on this diet. Serotonin biosynthesis inhibitors like para-chlorophenylalanine and p-ethynylphenylalanine may be needed to lower serotonin levels in patients with absent monoamine oxidase enzymes. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Does Domestication Cause Changes in Growth Reaction Norms? A Study of Farmed, Wild and Hybrid Atlantic Salmon Families Exposed to Environmental Stress

PubMed Central

Solberg, Monica Favnebøe; Skaala, Øystein; Nilsen, Frank; Glover, Kevin Alan

2013-01-01

One of the most important traits linked with the successful domestication of animals is reducing their sensitivity to environmental stressors in the human controlled environment. In order to examine whether domestication selection in Atlantic salmon Salmo salar L., over approximately ten generations, has inadvertently selected for reduced responsiveness to stress, we compared the growth reaction norms of 29 wild, hybrid and domesticated families reared together under standard hatchery conditions (control) and in the presence of a stressor (reduced water level twice daily). The experiment was conducted for a 14 week period. Farmed salmon outgrew wild salmon 1∶2.93 in the control tanks, and no overlap in mean weight was displayed between families representing the three groups. Thus, the elevation of the reaction norms differed among the groups. Overall, growth was approximately 25% lower in the stressed tanksl; however, farmed salmon outgrew wild salmon 1∶3.42 under these conditions. That farmed salmon maintained a relatively higher growth rate than the wild salmon in the stressed tanks demonstrates a lower responsiveness to stress in the farmed salmon. Thus, flatter reaction norm slopes were displayed in the farmed salmon, demonstrating reduced plasticity for this trait under these specific experimental conditions. For all growth measurements, hybrid salmon displayed intermediate values. Wild salmon displayed higher heritability estimates for body weight than the hybrid and farmed salmon in both environments. This suggests reduced genetic variation for body weight in the farmed contra wild salmon studied here. While these results may be linked to the specific families and stocks investigated, and verification in other stocks and traits is needed, these data are consistent with the theoretical predictions of domestication. PMID:23382901

Are attentional bias and memory bias for negative words causally related?

PubMed

Blaut, Agata; Paulewicz, Borysław; Szastok, Marta; Prochwicz, Katarzyna; Koster, Ernst

2013-09-01

In cognitive theories of depression, processing biases are assumed to be partly responsible for the onset and maintenance of mood disorders. Despite a wealth of studies examining the relation between depression and individual biases (at the level of attention, interpretation, and memory), little is known about relationships between different biases. The purpose of the present study was to assess if attentional bias is causally related to memory bias. 71 participants were randomly assigned to a control (n = 37) or attentional training group (n = 34). The attentional manipulation was followed by an explicit, intentional memory task during which novel neutral, negative, and positive words were presented. It was found that individuals with elevated depression score trained to orient away from negative words did not display a memory bias for negative words (adjectives) whereas similar individuals displayed this memory bias in the control condition. Generalization of the findings is limited because of the short study time frame and specific nature of the memory task. These results indicate that altering attentional bias can influence elaborative processing of emotional material and that this bias could be one of the causes of mood congruent memory in depression. Copyright © 2013 Elsevier Ltd. All rights reserved.

Transplantation of autoimmune regulator-encoding bone marrow cells delays the onset of experimental autoimmune encephalomyelitis.

PubMed

Ko, Hyun-Ja; Kinkel, Sarah A; Hubert, François-Xavier; Nasa, Zeyad; Chan, James; Siatskas, Christopher; Hirubalan, Premila; Toh, Ban-Hock; Scott, Hamish S; Alderuccio, Frank

2010-12-01

The autoimmune regulator (AIRE) promotes "promiscuous" expression of tissue-restricted antigens (TRA) in thymic medullary epithelial cells to facilitate thymic deletion of autoreactive T-cells. Here, we show that AIRE-deficient mice showed an earlier development of myelin oligonucleotide glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). To determine the outcome of ectopic Aire expression, we used a retroviral transduction system to over-express Aire in vitro, in cell lines and in bone marrow (BM). In the cell lines that included those of thymic medullary and dendritic cell origin, ectopically expressed Aire variably promoted expression of TRA including Mog and Ins2 (proII) autoantigens associated, respectively, with the autoimmune diseases multiple sclerosis and type 1 diabetes. BM chimeras generated from BM transduced with a retrovirus encoding Aire displayed elevated levels of Mog and Ins2 expression in thymus and spleen. Following induction of EAE with MOG(35-55), transplanted mice displayed significant delay in the onset of EAE compared with control mice. To our knowledge, this is the first example showing that in vivo ectopic expression of AIRE can modulate TRA expression and alter autoimmune disease development. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glucometabolic hormones and cardiovascular risk markers in antipsychotic-treated patients.

PubMed

Ebdrup, Bjørn H; Knop, Filip K; Madsen, Anna; Mortensen, Henrik B; Søgaard, Birgitte; Holst, Jens J; Szecsi, Pal B; Lublin, Henrik

2014-09-01

Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear. Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients (ICD-10 diagnosis code F20, F21, F22, F25, F28, or F60; mean ± SD age = 33.0 ± 6.7 years; body mass index [BMI; kg/m²] = 26.0 ± 4.7; waist circumference = 95.9 ± 13.3 cm; glycated hemoglobin A1c [HbA1c] = 5.7% ± 0.3%) and 93 age- and waist circumference-matched healthy male controls (age = 33 ± 7.3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones and cardiovascular risk markers. Data were collected between March 2008 and February 2010. Compared to healthy controls, patients were characterized by elevated fasting levels of proinsulin, C-peptide, and glucose-dependent insulinotropic polypeptide (GIP) (P < .05) and higher postprandial levels of insulin, proinsulin, C-peptide, and GIP (P ≤ .02). Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin, tumor necrosis factor-α, plasminogen activator inhibitor-1, and interleukin-6 and postprandial levels of glucagon, GLP-1, ghrelin, leptin, and adiponectin did not differ between groups. Presenting with an insulin resistant-like pattern, including beta cell hypersecretion and elevated GIP levels, nondiabetic antipsychotic-treated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology associated with metabolic side effects of antipsychotic treatment and put emphasis on the importance of implementing metabolic screening into psychiatric practice. ClinicalTrials.gov identifier NCT00627757. © Copyright 2014 Physicians Postgraduate Press, Inc.

Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution.

PubMed

Denoyer, Delphine; Pearson, Helen B; Clatworthy, Sharnel A S; Smith, Zoe M; Francis, Paul S; Llanos, Roxana M; Volitakis, Irene; Phillips, Wayne A; Meggyesy, Peter M; Masaldan, Shashank; Cater, Michael A

2016-06-14

Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed.

Contrasting stress responses of two co-occurring chipmunk species (Tamias alpinus and T. speciosus).

PubMed

Hammond, Talisin T; Palme, Rupert; Lacey, Eileen A

2015-01-15

Glucocorticoid (GC) hormones are important mediators of responses to environmental conditions. Accordingly, differences in GC physiology may contribute to interspecific variation in response to anthropogenically-induced patterns of climate change. To begin exploring this possibility, we validated the use of fecal cortisol/corticosterone metabolites (FCM) to measure baseline glucocorticoid levels in two species of co-occurring chipmunks that have exhibited markedly different patterns of response to environmental change. In Yosemite National Park, the alpine chipmunk (Tamias alpinus) has undergone a significant upward contraction of its elevational range over the past century; in contrast, the lodgepole chipmunk (Tamiasspeciosus) has experienced no significant change in elevational distribution over this period. To determine if GC levels in these species vary in response to external stimuli and to assess whether these responses differ between species, we compared FCM levels for the same individuals (1) at the time of capture in the field, (2) after a short period of captivity, and (3) after adrenocorticotropic hormone (ACTH), (4) handling, and (5) trapping challenges conducted while these animals were held in captivity. Our analyses indicate that T. alpinus was more responsive to several of these changes in external conditions. Although both species displayed a significant FCM response to ACTH challenge, only T. alpinus showed a significant response to our handling challenge and to captive housing conditions. These findings underscore the importance of species-specific validation studies and support the potential for studies of GC physiology to generate insights into interspecific differences in response to environmental change. Copyright © 2014 Elsevier Inc. All rights reserved.

Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease.

PubMed

Günther, A; Mosavi, P; Ruppert, C; Heinemann, S; Temmesfeld, B; Velcovsky, H G; Morr, H; Grimminger, F; Walmrath, D; Seeger, W

2000-06-01

Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant activity (PCA), tissue factor (TF) activity and F VII activity were assessed by means of specific recalcification assays. The overall fibrinolytic activity (FA) was measured using the (125)I-labeled fibrin plate assay. Fibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type (t-PA), PA-inhibitor I (PAI-1) and alpha2-antiplasmin (alpha2-AP) were determined by ELISA technique. As compared to Controls, all groups with interstitial lung disease (ILD) displayed an increase in BALF PCA by approximately one order of magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F VII-activity was increased in all ILD groups, and elevated FP-A levels were noted. There was no significant difference in procoagulant activities between the different ILD entities, but the increase in TF was significantly correlated with deterioration of lung compliance. Overall fibrinolytic activity did not significantly differ between ILD entities and Controls, although some reduction in IPF subjects was observed. Nevertheless, changes in the profile of the different pro- and antifibrinolytic compounds were noted. U-PA, but not t-PA levels were significantly reduced in all ILD groups. alpha2-AP was markedly elevated throughout, whereas PAI-1 levels were lowered. As a balance of

Sex-role reversal is reflected in the brain of African black coucals (Centropus grillii).

PubMed

Voigt, Cornelia; Goymann, Wolfgang

2007-10-01

In most bird species males compete over access to females and have elevated circulating androgen levels when they establish and defend a breeding territory or guard a mate. Testosterone is involved in the regulation of territorial aggression and sexual display in males. In few bird species the traditional sex-roles are reversed and females are highly aggressive and compete over access to males. Such species represent excellent models to study the hormonal modulation of aggressive behavior in females. Plasma sex steroid concentrations in sex-role reversed species follow the patterns of birds with "traditional" sex-roles. The neural mechanisms modulating endocrine secretion and hormone-behavior interactions in sex-role reversed birds are currently unknown. We investigated the sex differences in the mRNA expression of androgen receptors, estrogen receptor alpha, and aromatase in two brain nuclei involved in reproductive and aggressive behavior in the black coucal, the nucleus taeniae and the bed nucleus of the stria terminalis. In the bed nucleus there were no sex differences in the receptor or aromatase expression. In the nucleus taeniae, however, we show for the first time, that females have a higher mRNA expression of androgen receptors than males. These results suggest that the expression of agonistic and courtship behavior in females does not depend on elevated blood hormone levels, but may be regulated via increased steroid hormone sensitivity in particular target areas in the brain. Hence, aggression in females and males may indeed be modulated by the same hormones, but regulated at different levels of the neuroendocrine cascade. 2007 Wiley Periodicals, Inc.

Insulin resistance and the metabolism of branched-chain amino acids in humans.

PubMed

Adeva, María M; Calviño, Jesús; Souto, Gema; Donapetry, Cristóbal

2012-07-01

Peripheral resistance to insulin action is the major mechanism causing the metabolic syndrome and eventually type 2 diabetes mellitus. The metabolic derangement associated with insulin resistance is extensive and not restricted to carbohydrates. The branched-chain amino acids (BCAAs) are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in conditions featuring insulin resistance, insulin deficiency, or both. Obesity, the metabolic syndrome and diabetes mellitus display a gradual increase in the plasma concentration of BCAAs, from the obesity-related low-grade insulin-resistant state to the severe deficiency of insulin action in diabetes ketoacidosis. Obesity-associated hyperinsulinemia succeeds in maintaining near-normal or slightly elevated plasma concentration of BCAAs, despite the insulin-resistant state. The low circulating levels of insulin and/or the deeper insulin resistance occurring in diabetes mellitus are associated with more marked elevation in the plasma concentration of BCAAs. In diabetes ketoacidosis, the increase in plasma BCAAs is striking, returning to normal when adequate metabolic control is achieved. The metabolism of BCAAs is also disturbed in other situations typically featuring insulin resistance, including kidney and liver dysfunction. However, notwithstanding the insulin-resistant state, the plasma level of BCAAs in these conditions is lower than in healthy subjects, suggesting that these organs are involved in maintaining BCAAs blood concentration. The pathogenesis of the decreased BCAAs plasma level in kidney and liver dysfunction is unclear, but a decreased afflux of these amino acids into the blood stream has been observed.

Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus.

PubMed

Mamenko, Mykola; Dhande, Isha; Tomilin, Viktor; Zaika, Oleg; Boukelmoune, Nabila; Zhu, Yaming; Gonzalez-Garay, Manuel L; Pochynyuk, Oleh; Doris, Peter A

2016-07-01

Store-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca(2+)) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca(2+) levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca(2+) mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca(2+) levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling. Copyright © 2016 by the American Society of Nephrology.

Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution

PubMed Central

Denoyer, Delphine; Pearson, Helen B.; Clatworthy, Sharnel A.S.; Smith, Zoe M.; Francis, Paul S.; Llanos, Roxana M.; Volitakis, Irene; Phillips, Wayne A.; Meggyesy, Peter M.; Masaldan, Shashank; Cater, Michael A.

2016-01-01

Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed. PMID:27175597

Juvenile Atlantic cod behavior appears robust to near-future CO2 levels.

PubMed

Jutfelt, Fredrik; Hedgärde, Maria

2015-01-01

Ocean acidification caused by the anthropogenic release of CO2 is considered a major threat to marine ecosystems. One unexpected impact of elevated water CO2 levels is that behavioral alterations may occur in tropical reef fish and certain temperate fish species. These effects appear to alter many different types of sensory and cognitive functions; if widespread and persistent, they have the potential to cause ecosystem changes. We investigated whether economically and ecologically important Atlantic cod also display behavioral abnormalities by exposing 52 juvenile cod to control conditions (500 μatm, duplicate tanks) or an end-of-the-century ocean acidification scenario (1000 μatm, duplicate tanks) for one month, during which time the fish were examined for a range of behaviors that have been reported to be affected by elevated CO2 in other fish. The behaviors were swimming activity, as measured by number of lines crossed per minute, the emergence from shelter, determined by how long it took the fish to exit a shelter after a disturbance, relative lateralization (a measure of behavioral turning side preference), and absolute lateralization (the strength of behavioral symmetry). We found no effect of CO2 treatment on any of the four behaviors tested: activity (F = 1.61, p = 0.33), emergence from shelter (F = 0.13, p = 0.76), relative lateralization (F = 2.82, p = 0.50), and absolute lateralization (F = 0.80, p = 0.26). Our results indicate that the behavior of Atlantic cod could be resilient to the impacts of near-future levels of water CO2.

Heterologous desensitization of both phosphoinositide and Ca2+ signaling in SH-SY5Y neuroblastoma cells: a role for intracellular Ca2+ store depletion?

PubMed

Willars, G B; Nahorski, S R

1995-03-01

Measurement of the intracellular Ca2+ concentration ([Ca2+]i) in fura-2-loaded single cells of the human neuroblastoma line SH-SY5Y indicated coexpression of muscarinic and bradykinin receptors linked to activation of phosphoinositidase C (PIC). Both agonists elevated [Ca2+]i and inositol-1,4,5-trisphosphate [Ins(1,4,5)P3] levels in populations of adherent cells, although in cells used directly upon attainment of confluence the responses to carbachol were greater than those to bradykinin and displayed additional sustained components. This model system was used to examine heterologous interactions when a second PIC-linked agonist was added 100-300 sec after but in the continued presence of the first. Maximal (1 mM) carbachol concentrations abolished the elevation of [Ca2+]i produced by bradykinin but the muscarinic antagonist atropine (10 microM) restored the response, provided that extracellular Ca2+ was present throughout the experiment or was added before bradykinin. Carbachol also abolished bradykinin-mediated Ins(1,4,5)P3 elevation. In contrast, bradykinin did not influence [Ca2+]i or Ins(1,4,5)P3 responses to carbachol in the presence of extracellular Ca2+. In cells maintained at confluence for 2 weeks, the rapid peak elevations of [Ca2+]i and Ins(1,4,5)P3 levels induced by carbachol and bradykinin were approximately equivalent in magnitude. In these cells carbachol again abolished bradykinin-mediated elevation of [Ca2+]i but only attenuated, rather than abolished, the elevation of Ins(1,4,5)P3 levels. The [Ca2+]i and Ins(1,4,5)P3 responses to bradykinin were fully restored 100 sec after atropine only in the presence of extracellular Ca2+. Thus, depletion of an intracellular Ins(1,4,5)P3-sensitive Ca2+ store may underlie the ability of carbachol to produce not only heterologous desensitization of the [Ca2+]i elevation induced by bradykinin but also that of the Ins(1,4,5)P3 response. This suggests a feed-forward activation of PIC by Ca2+ released from Ins(1,4,5)P3-sensitive stores. Furthermore, studies in which Ins(1,4,5)P3-sensitive stores were depleted with thapsigargin and cells were challenged in the presence or absence of extracellular Ca2+ indicated that Ca2+, irrespective of its origin (intra- or extracellular), potentiated the Ins(1,4,5)P3 response to bradykinin alone. In cells maintained at confluence for 2 weeks, bradykinin was again unable to influence either [Ca2+]i or Ins(1,4,5)P3 responses to carbachol in the presence of Ca2+. This lack of heterologous desensitization may be due to the rapid, full, homologous desensitization of bradykinin receptors, compared with an incomplete homologous desensitization of muscarinic receptors.

Effects of dietary fat and crude protein on feedlot performance, carcass characteristics, and meat quality in finishing steers fed differing levels of dried distillers grains with solubles.

PubMed

Gunn, P J; Weaver, A D; Lemenager, R P; Gerrard, D E; Claeys, M C; Lake, S L

2009-09-01

The objective of this study was to evaluate the influence of dietary protein and fat from distillers dried grains with solubles (DDGS) on feedlot performance, carcass characteristics, and meat quality in finishing steers. Angus-cross steers (n = 105; 443 +/- 20 kg of BW) were blocked by BW and randomly assigned to 1 of 5 dietary treatments: 1) corn-based diet with DDGS included at 25% of DM (CON), 2) CON with DDGS included at twice the amount of CON (50% of DM; 50DDGS), 3) CON with added corn protein to equal the CP in the 50DDGS diet (CON+CP), 4) CON with added vegetable oil to equal the fat in the 50DDGS diet (CON+VO), and 5) CON with protein and fat added to equal the CP and fat in the 50DDGS diet (CON+CPVO). Steers were fed to a common 12th-rib fat depth endpoint (1.3 +/- 0.2 cm; 68 to 125 d on trial). Loins and rounds were collected from 44 carcasses for Warner-Bratzler shear force (WBSF), ether extract, and case-life analyses. Data were analyzed using the MIXED procedure of SAS. Contrasts between 1) CON vs. elevated CP diets (50DDGS, CON+CP, and CON+CPVO; EP), 2) CON vs. elevated fat diets (50DDGS, CON+VO, and CON+CPVO; EF) and 3) CON vs. diets with elevated CP and fat (50DDGS and CON+CPVO; EPF) were analyzed. There were no differences in days on feed or DMI among treatments. Steers fed CON had greater ADG (P or= 0.06). Steers fed the CON diet had greater marbling scores (P or= 0.44). However, CON steers had greater (P = 0.02) L* values than EF-fed steers and greater b* values than EP, EF, and EPF steers (P

Velocity, water-quality, and bathymetric surveys of the Grays Landing and Maxwell Navigation Pools, and Selected Tributaries to the Monongahela River, Pennsylvania, 2010–11

USGS Publications Warehouse

Hoffman, Scott A.; Roland, Mark A.; Schalk, Luther F.; Fulton, John W.

2013-01-01

The U.S. Geological Survey (USGS) conducted velocity, water-quality, and bathymetric surveys from spring 2010 to summer 2011 in the Grays Landing and Maxwell navigation pools of the Monongahela River, Pennsylvania, and selected tributaries in response to elevated levels of total dissolved solids (TDS) recorded in early September 2009. Velocity data were collected using an Acoustic Doppler Current Profiler. Water-quality surveys included the in-situ collection of specific-conductance, water-temperature, and turbidity data using a water-quality sonde. Additionally, discrete water samples were collected and analyzed for TDS, chloride, and sulfate. Bathymetric data were collected using an echo sounder, and the shoreline was delineated using a laser range finder and electronic compass. The data were geo-referenced using a differential global positioning system and navigational software. Horizontal (x, y) coordinates were referenced to the North American Datum of 1983. Depth (z) elevations were referenced to the North American Vertical Datum of 1988. The data are provided in electronic format (appendix 1) and may be downloaded and can be used in a geographic information system for cartographic display and data analysis.

Isolation and characterization of a novel ammonium overly sensitive mutant, amos2, in Arabidopsis thaliana.

PubMed

Li, Guangjie; Dong, Gangqiang; Li, Baohai; Li, Qing; Kronzucker, Herbert J; Shi, Weiming

2012-02-01

Ammonium (NH(4)(+)) toxicity is a significant agricultural problem globally, compromising crop growth and productivity in many areas. However, the molecular mechanisms of NH(4)(+) toxicity are still poorly understood, in part due to a lack of valuable genetic resources. Here, a novel Arabidopsis mutant, amos2 (ammonium overly sensitive 2), displaying hypersensitivity to NH(4) (+) in both shoots and roots, was isolated. The mutant exhibits the hallmarks of NH(4)(+) toxicity at significantly elevated levels: severely suppressed shoot biomass, increased leaf chlorosis, and inhibition of lateral root formation. Amos2 hypersensitivity is associated with excessive NH(4)(+) accumulation in shoots and a reduction in tissue potassium (K(+)), calcium (Ca(2+)), and magnesium (Mg(2+)). We show that the lesion is specific to the NH(4)(+) ion, is independent of NH(4)(+) metabolism, and can be partially rescued by elevated external K(+). The amos2 lesion was mapped to a 16-cM interval on top of chromosome 1, where no similar mutation has been previously mapped. Our study identifies a novel locus controlling cation homeostasis under NH(4)(+) stress and provides a tool for the future identification of critical genes involved in the development of NH(4)(+) toxicity.

Concomitant occurrence of macroprolactin, exercise-induced amenorrhea, and a pituitary lesion: a diagnostic pitfall. Case report.

PubMed

Cattaneo, F A; Fahie-Wilson, M N

2001-08-01

The authors report the case of a 37-year-old woman who presented with amenorrhea and an increased level of serum prolactin. Magnetic resonance images of the pituitary revealed a lesion with characteristics consistent with those of a microadenoma. Transsphenoidal exploration was performed, but a prolactinoma was not found. After endocrinological review, the patient's hyperprolactinemia was found to be caused by the presence of macroprolactin and her amenorrhea was due to intense exercise and low body weight. Macroprolactin is an isoform of prolactin that is variably reactive in assays for prolactin, but displays minimum bioactivity in vivo. Patients with macroprolactin are mostly asymptomatic. This phenomenon may cause elevated prolactin values, which the authors view as apparent hyperprolactinemia. The presence of macroprolactin is an underrecognized problem, occurring in as many as 15 to 20% of patients with elevated prolactin values and often leading to unnecessary, expensive diagnostic procedures and inappropriate treatment. The presence of macroprolactin should always be suspected when the patient's clinical history or clinical or radiological data are incompatible with the prolactin value. Physicians dealing with diagnosis and treatment of hyperprolactinemia (general practitioners, gynecologists, neurosurgeons, endocrinologists, and biochemists) should be aware of the potentially misleading nature of macroprolactin.

High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin)-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses

PubMed Central

Clark, Erica S.; Flannery, Brenna M.; Gardner, Elizabeth M.; Pestka, James J.

2015-01-01

Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg) and dietary (1, 2.5, 10 ppm) DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes. PMID:26492270

Growth and physiological responses of some Capsicum frutescens varieties to copper stress

NASA Astrophysics Data System (ADS)

Jadid, Nurul; Maziyah, Rizka; Nurcahyani, Desy Dwi; Mubarokah, Nilna Rizqiyah

2017-06-01

Copper (Cu) is an essential micronutrient participating in various physiological processes. However, excessive uptake of this micronutrient could potentially affect plant growth and development as well as plant productivity. In this present work, growth and physiological responses of some Capsicum frustescens varieties to Cu stress were determined. Three C. frutescens varieties used in this work were var. Bara, CF 291, and Genie. In addition, these varieties were treated with different concentration of Cu (0, 30, 70, and 120 ppm). The growth and physiological responses measured in this work included plant height, root length, malondialdehyde (MDA), and chlorophyll. The result showed that all varieties tested relatively displayed plant growth reduction including plant height and root length. Likewise, an increase of MDA level, a major bioindicator for oxidative damage was also found in all varieties following exposure to elevated Cu concentration. Finally, the chlorophyll content was also affected indicated by a decreased amount of chlorophyll, especially in var. CF291. The overall results demonstrated that elevated Cu concentration might decrease C. frutescens productivity where among the three varieties tested, var CF 291 seemed to be the most sensitive varieties to Cu stress.

Concomitant presentation of Anderson-Tawil syndrome and myasthenia gravis in an adult patient: A case report.

PubMed

Fan, Rui; Ji, Ruirui; Zou, Wenxin; Wang, Guoliang; Wang, Hu; Penney, Daniel James; Luo, Jin Jun; Fan, Yuxin

2016-10-01

Andersen-Tawil syndrome (ATS) is an autosomal dominant, multisystem channelopathy characterized by periodic paralysis, ventricular arrhythmias and distinctive dysmorphic facial or skeletal features. The disorder displays marked intrafamilial variability and incomplete penetrance. Myasthenia gravis (MG) is an autoimmune disorder that demonstrates progressive fatigability, in which the nicotinic acetylcholine receptor (AChR) at neuromuscular junctions is the primary autoantigen. The present study reports a rare case of a 31-year-old woman with a history of morbid obesity and periodic weakness, who presented with hemodynamic instability, cardiogenic shock and facial anomalies. Laboratory results revealed hypokalemia and an elevated anti-AChR antibody expression levels. Electrocardiography demonstrated prolonged QT-interval, ST-elevation, and subsequent third-degree atrioventricular block. Neurological examination revealed bilateral ptosis, horizontal diplopia, dysarthria and generalized weakness. No mutations in the potassium channel inwardly rectifying subfamily J member 2 gene were detected in the present case. The patient was treated with oral potassium supplementation and an acetylcholinesterase inhibitor (pyridostigmine), after which the symptoms were improved. To the best of our knowledge, the present case report was the first to describe concomitant presentation of both ATS and MG, which represents a diagnostic and therapeutic challenge.

The big lobe of 67P/Churyumov-Gerasimenko comet: morphological and spectrophotometric evidences of layering as from OSIRIS data

NASA Astrophysics Data System (ADS)

Ferrari, Sabrina; Penasa, L.; La Forgia, F.; Massironi, M.; Naletto, G.; Lazzarin, M.; Fornasier, S.; Hasselmann, P. H.; Lucchetti, A.; Pajola, M.; Ferri, F.; Cambianica, P.; Oklay, N.; Tubiana, C.; Sierks, H.; Lamy, P. L.; Rodrigo, R.; Koschny, D.; Davidsson, B.; Barucci, M. A.; Bertaux, J.-L.; Bertini, I.; Bodewits, D.; Cremonese, G.; Da Deppo, V.; Debei, S.; De Cecco, M.; Deller, J.; Franceschi, M.; Frattin, E.; Fulle, M.; Groussin, O.; Gutiérrez, P. J.; Güttler, C.; Hviid, S. F.; Ip, W.-H.; Jorda, L.; Keller, H. U.; Knollenberg, J.; Kührt, E.; Küppers, M.; Lara, L. M.; López-Moreno, J. J.; Marzari, F.; Shi, X.; Simioni, E.; Thomas, N.; Vincent, J.-B.

2018-06-01

Between 2014 and 2016, ESA's Rosetta OSIRIS cameras acquired multiple-filters images of the layered nucleus of comet 67P/Churyumov-Gerasimenko, ranging from ultraviolet to near-infrared wavelengths. No correlation between layers disposition and surface spectral variegation has been observed so far. This paper investigates possible spectral differences among decametre-thickness outcropping layers of the biggest lobe of the comet by means of OSIRIS image dataset. A two-classes Maximum Likelihood classification was applied on consolidated outcrops and relative deposits identified on post-perihelion multispectral images of the big lobe. We distinguished multispectral data on the basis of the structural elevation of the onion-shell Ellipsoidal Model of 67P. The spatial distribution of the two classes displays a clear dependence on the structural elevation, with the innermost class resulting over 50% brighter that the outermost one. Consolidated cometary materials located at different structural levels are characterized by different brightness and revealed due to the selective removal of large volumes. This variegation can be attributed to a different texture of the outcrop surface and/or to a different content of refractory materials.

High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin)-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses.

PubMed

Clark, Erica S; Flannery, Brenna M; Gardner, Elizabeth M; Pestka, James J

2015-10-19

Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg) and dietary (1, 2.5, 10 ppm) DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.

Increased anxiety in rats after 3,4-methylenedioxymethamphetamine: association with serotonin depletion.

PubMed

Gurtman, Clint G; Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; McGregor, Iain S

2002-06-20

The long-term behavioural and neurotoxic effects of 3,4-methlyenedioxymethampthetamine (MDMA, "Ecstasy") were examined in rats. Rats were given MDMA (5 mg/kg i.p. once per hour for 4 h) or vehicle injections on each of two consecutive days at an ambient temparature of 28 degrees C. MDMA caused acute hyperthermia and locomotor hyperactivity on both days. Four and six weeks after drug administration the rats previously treated with MDMA showed elevated levels of anxiety-like behaviour in the emergence and social interaction tests, respectively. At 9 weeks post-MDMA, the rats displayed an increase in anxiety on the elevated plus-maze test relative to controls. Ten weeks following treatment the rats were killed and their brains dissected and neurotramitter content analysed using High Performance Liquid Chromotography (HPLC). Rats previously given MDMA showed significantly decreased 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the amygdala, hippocampus and striatum relative to controls. This 5-HT depletion may have a causal role in producing increased anxiety-like behaviours in MDMA-treated rats. These results are consistent with human studies suggesting that exposure to high doses of MDMA may predispose to long-term psychological problems such as anxiety and depression.

MORIN MITIGATES OXIDATIVE STRESS, APOPTOSIS AND INFLAMMATION IN CEREBRAL ISCHEMIC RATS

PubMed Central

Chen, Yanrong; Li, Yanke; Xu, Huali; Li, Gang; Ma, Yunxia; Pang, Yu Jun

2017-01-01

Background: Morin is a flavanoid which exhibits potent antioxidant activity in various oxidative stress related diseases. The current study was attempted to scrutinize the preclinical bio-efficacy of morin on focal ischemia. Methods: The animal model of focal cerebral ischemic injury was done by midbrain carotid artery occlusion (MCAO) method, followed by Morin (30mg/kg) administration for seven days. Results: The outcome of the study showed that treatment with morin displayed positive effects in reducing the focal cerebral ischemia. This effect was evident with the improvements in neurological deficits, reduction in MDA content and elevation of antioxidant levels (SOD, GSH and Gpx). Furthermore, protein expression of Bax and caspase-3 were effectively down-regulated, whilst the expression of Bcl-2 was significantly elevated. On the other hand, the mRNA expression of proinflammatory cytokines was significantly reduced in focal cerebral ischemic rats upon morin intervention. Conclusion: Thus, the beneficial effects of morin on cerebral ischemia assault may result from the reduction of oxidative stress, inhibition of apoptosis and inflammation. The neuroprotective effects of morin supplement may serve as potent adjuvant in the amelioration of ischemic stroke. PMID:28573251

Mitochondrial oxidative stress is the achille's heel of melanoma cells resistant to Braf-mutant inhibitor

PubMed Central

André, Fanny; Jonneaux, Aurélie; Scalbert, Camille; Garçon, Guillaume; Malet-Martino, Myriam; Balayssac, Stéphane; Rocchi, Stephane; Savina, Ariel; Formstecher, Pierre; Mortier, Laurent; Kluza, Jérome; Marchetti, Philippe

2013-01-01

Vemurafenib/PLX4032, a selective inhibitor of mutant BRAFV600E, constitutes a paradigm shift in melanoma therapy. Unfortunately, acquired resistance, which unavoidably occurs, represents one major limitation to clinical responses. Recent studies have highlighted that vemurafenib activated oxidative metabolism in BRAFV600E melanomas expressing PGC1α. However, the oxidative state of melanoma resistant to BRAF inhibitors is unknown. We established representative in vitro and in vivo models of human melanoma resistant to vemurafenib including primary specimens derived from melanoma patients. Firstly, our study reveals that vemurafenib increased mitochondrial respiration and ROS production in BRAFV600E melanoma cell lines regardless the expression of PGC1α. Secondly, melanoma cells that have acquired resistance to vemurafenib displayed intrinsically high rates of mitochondrial respiration associated with elevated mitochondrial oxidative stress irrespective of the presence of vemurafenib. Thirdly, the elevated ROS level rendered vemurafenib-resistant melanoma cells prone to cell death induced by pro-oxidants including the clinical trial drug, elesclomol. Based on these observations, we propose that the mitochondrial oxidative signature of resistant melanoma constitutes a novel opportunity to overcome resistance to BRAF inhibition. PMID:24161908

Altered nutrient response of mTORC1 as a result of changes in REDD1 expression: effect of obesity vs. REDD1 deficiency

PubMed Central

Li, Zhuyun; Tuder, Rubin M.; Feinstein, Elena; Kimball, Scot R.; Dungan, Cory M.

2014-01-01

Although aberrant mTORC1 signaling has been well established in models of obesity, little is known about its repressor, REDD1. Therefore, the initial goal of this study was to determine the role of REDD1 on mTORC1 in obese skeletal muscle. REDD1 expression (protein and message) and mTORC1 signaling (S6K1, 4E-BP1, raptor-mTOR association, Rheb GTP) were examined in lean vs. ob/ob and REDD1 wild-type (WT) vs. knockout (KO) mice, under conditions of altered nutrient intake [fasted and fed or diet-induced obesity (10% vs. 60% fat diet)]. Despite higher (P < 0.05) S6K1 and 4E-BP1 phosphorylation, two models of obesity (ob/ob and diet-induced) displayed elevated (P < 0.05) skeletal muscle REDD1 expression compared with lean or low-fat-fed mouse muscle under fasted conditions. The ob/ob mice displayed elevated REDD1 expression (P < 0.05) that coincided with aberrant mTORC1 signaling (hyperactive S6K1, low raptor-mTOR binding, elevated Rheb GTP; P < 0.05) under fasted conditions, compared with the lean, which persisted in a dysregulated fashion under fed conditions. REDD1 KO mice gained limited body mass on a high-fat diet, although S6K1 and 4E-BP1 phosphorylation remained elevated (P < 0.05) in both the low-fat and high-fat-fed KO vs. WT mice. Similarly, the REDD1 KO mouse muscle displayed blunted mTORC1 signaling responses (S6K1 and 4E-BP1, raptor-mTOR binding) and circulating insulin under fed conditions vs. the robust responses (P < 0.05) in the WT fed mouse muscle. These studies suggest that REDD1 in skeletal muscle may serve to limit hyperactive mTORC1, which promotes aberrant mTORC1 signaling responses during altered nutrient states. PMID:24876363

Cardiorespiratory upregulation during seawater acclimation in rainbow trout: effects on gastrointestinal perfusion and postprandial responses.

PubMed

Brijs, Jeroen; Gräns, Albin; Ekström, Andreas; Olsson, Catharina; Axelsson, Michael; Sandblom, Erik

2016-05-01

Increased gastrointestinal blood flow is essential for euryhaline fishes to maintain osmotic homeostasis during the initial phase of a transition from freshwater to seawater. However, the cardiorespiratory responses and hemodynamic changes required for a successful long-term transition to seawater remain largely unknown. In the present study, we simultaneously measured oxygen consumption rate (ṀO2), cardiac output (CO), heart rate (HR), and gastrointestinal blood flow (GBF) in rainbow trout (Oncorhynchus mykiss) acclimated to either freshwater or seawater for at least 6 wk. Seawater-acclimated trout displayed significantly elevated ṀO2 (day: 18%, night: 19%), CO (day: 22%, night: 48%), and GBF (day: 96%, night: 147%), demonstrating that an overall cardiorespiratory upregulation occurs during seawater acclimation. The elevated GBF was achieved via a combination of increased CO, mediated through elevated stroke volume (SV), and a redistribution of blood flow to the gastrointestinal tract. Interestingly, virtually all of the increase in CO of seawater-acclimated trout was directed to the gastrointestinal tract. Although unfed seawater-acclimated trout displayed substantially elevated cardiorespiratory activity, the ingestion of a meal resulted in a similar specific dynamic action (SDA) and postprandial GBF response as in freshwater-acclimated fish. This indicates that the capacity for the transportation of absorbed nutrients, gastrointestinal tissue oxygen delivery, and acid-base regulation is maintained during digestion in seawater. The novel findings presented in this study clearly demonstrate that euryhaline fish upregulate cardiovascular function when in seawater, while retaining sufficient capacity for the metabolic and cardiovascular changes associated with the postprandial response. Copyright © 2016 the American Physiological Society.

The impact of numeric and graphic displays of ST-segment deviation levels on cardiologists' decisions of reperfusion therapy for patients with acute coronary occlusion.

PubMed

Nimmermark, Magnus O; Wang, John J; Maynard, Charles; Cohen, Mauricio; Gilcrist, Ian; Heitner, John; Hudson, Michael; Palmeri, Sebastian; Wagner, Galen S; Pahlm, Olle

2011-01-01

The study purpose is to determine whether numeric and/or graphic ST measurements added to the display of the 12-lead electrocardiogram (ECG) would influence cardiologists' decision to provide myocardial reperfusion therapy. Twenty ECGs with borderline ST-segment deviation during elective percutaneous coronary intervention and 10 controls before balloon inflation were included. Only 5 of the 20 ECGs during coronary balloon occlusion met the 2007 American Heart Association guidelines for ST-elevation myocardial infarction (STEMI). Fifteen cardiologists read 4 sets of these ECGs as the basis for a "yes/no" reperfusion therapy decision. Sets 1 and 4 were the same 12-lead ECGs alone. Set 2 also included numeric ST-segment measurements, and set 3 included both numeric and graphically displayed ST measurements ("ST Maps"). The mean (range) positive reperfusion decisions were 10.6 (2-15), 11.4 (1-19), 9.7 (2-14), and 10.7 (1-15) for sets 1 to 4, respectively. The accuracies of the observers for the 5 STEMI ECGs were 67%, 69%, and 77% for the standard format, the ST numeric format, and the ST graphic format, respectively. The improved detection rate (77% vs 67%) with addition of both numeric and graphic displays did achieve statistical significance (P < .025). The corresponding specificities for the 10 control ECGs were 85%, 79%, and 89%, respectively. In conclusion, a wide variation of reperfusion decisions was observed among clinical cardiologists, and their decisions were not altered by adding ST deviation measurements in numeric and/or graphic displays. Acute coronary occlusion detection rate was low for ECGs meeting STEMI criteria, and this was improved by adding ST-segment measurements in numeric and graphic forms. These results merit further study of the clinical value of this technique for improved acute coronary occlusion treatment decision support. Copyright © 2011 Elsevier Inc. All rights reserved.

Solid-state turn coordinator display

NASA Technical Reports Server (NTRS)

Meredith, B. D.; Crouch, R. K.; Kelly, W. L., IV

1975-01-01

A solid state turn coordinator display which employs light emitting diodes (LED's) as the display medium was developed to demonstrate the feasibility of such displays for aircraft applications. The input to the display is supplied by a fluidic inertial rate sensor used in an aircraft wing leveler system. The display is composed of the LED radial display face and the electronics necessary to address and drive the individual lines of LED's. Three levels of brightness are provided to compensate for the different amounts of ambient light present in the cockpit.

[Effect of student knowledge in gastronomy schools and origin of residence on their nutritional habits and nutritional status].

PubMed

Chalcarz, W; Klemczak, L; Krajewski, P

1991-01-01

Nutritional habits and nutritional status of 142 pupils of a Gastronomic School Complex were examined from the standpoint of the year of school, school marks and place of residence. It was found that the year of school and place of residence exerted an effect on the nutritional habits of pupils. These young people failed to prefer dishes and food products recommended in the prophylaxis of civilization diseases. In all subjects the levels of total lipids and beta-lipoproteins exceeded the upper range of the norm. Hemoglobin concentration fluctuated within the lower range of the norm, and that of glucose--within the upper range of the norm. When completing school, the pupils displayed a lowered protein level and elevated glucose level. Pupils inhabiting the school boarding house ought to take part in the decisions on the menu and on food purchases. Recommendations concerning nutrition in the prophylaxis of civilization diseases ought to be as soon as possible introduced into the teaching program of the Gastronomic School Complex.

Identification of sources of environmental lead in South Africa from surface soil geochemical maps.

PubMed

de Villiers, Stephanie; Thiart, Christien; Basson, Nicholas C

2010-10-01

The bioavailability of lead in soil is of considerable importance to human and animal health. Although selective extraction has been explored as a more appropriate technique than total heavy metal analysis in environmental pollution assessments, such studies remain scarce globally and are almost non-existent in developing countries. Results for a large-scale study of extractable lead levels in undisturbed soil samples in South Africa identify several geographic areas of concern. Lead levels are considerably elevated relative to background levels in the Johannesburg urban and industrial area. Areas of active lead mining also exhibit higher surface soil values. Interestingly, areas of active and intensive coal mining activity display relatively low soil Pb values, possibly attributable to the relatively low heavy metal content of South African coal. In all instances, distribution of cadmium, a carcinogenic element, correlates with that of lead. The results demonstrate the usefulness of the quick and easy Mehlich-3 single extractant technique, an established technique in micronutrient studies, to simultaneously provide valuable environmental data for toxic metals such as Pb and Cd.

Aqueous Extract of Phyllanthus niruri Leaves Displays In Vitro Antioxidant Activity and Prevents the Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats

PubMed Central

Giribabu, Nelli; Rao, Pasupuleti Visweswara; Kumar, Korla Praveen; Muniandy, Sekaran; Swapna Rekha, Somesula; Salleh, Naguib

2014-01-01

P. niruri has been reported to possess antidiabetic and kidney protective effects. In the present study, the phytochemical constituents and in vitro antioxidant activity of P. niruri leaf aqueous extract were investigated together with its effect on oxidative stress and antioxidant enzymes levels in diabetic rat kidney. Results. Treatment of diabetic male rats with P. niruri leaf aqueous extract (200 and 400 mg/kg) for 28 consecutive days prevents the increase in the amount of lipid peroxidation (LPO) product, malondialdehyde (MDA), and the diminution of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity levels in the kidney of diabetic rats. The amount of LPO showed strong negative correlation with SOD, CAT, and GPx activity levels. P. niruri leaf aqueous extract exhibits in vitro antioxidant activity with IC50 slightly lower than ascorbic acid. Phytochemical screening of plant extract indicates the presence of polyphenols. Conclusion. P. niruri leaf extract protects the kidney from oxidative stress induced by diabetes. PMID:24991228

Accumulation of Senescent Cells in Mitotic Tissue of Aging Primates

PubMed Central

Jeyapalan, Jessie C.; Ferreira, Mark; Sedivy, John M.; Herbig, Utz

2013-01-01

Cellular senescence, a stress induced growth arrest of somatic cells, was first documented in cell cultures over forty years ago, however its physiological significance has only recently been demonstrated. Using novel biomarkers of cellular senescence we examined whether senescent cells accumulate in tissues from baboons of ages encompassing the entire lifespan of this species. We show that dermal fibroblasts, displaying markers of senescence such as telomere damage, active checkpoint kinase ATM, high levels of heterochromatin proteins and elevated levels of p16, accumulate in skin biopsies from baboons with advancing age. The number of dermal fibroblasts containing damaged telomeres reaches a value of over 15% of total fibroblasts, whereas 80% of cells contain high levels of the heterochromatin protein HIRA. In skeletal muscle, a postmitotic tissue, only a small percentage of myonuclei containing damaged telomeres were detected regardless of animal age. The presence of senescent cells in mitotic tissues might therefore be a contributing factor to aging and age related pathology and provides further evidence that cellular senescence is a physiological event. PMID:17116315

Effects of elevated CO2 levels on root morphological traits and Cd uptakes of two Lolium species under Cd stress*

PubMed Central

Jia, Yan; Tang, Shi-rong; Ju, Xue-hai; Shu, Li-na; Tu, Shu-xing; Feng, Ren-wei; Giusti, Lorenzino

2011-01-01

This study was conducted to investigate the combined effects of elevated CO2 levels and cadmium (Cd) on the root morphological traits and Cd accumulation in Lolium multiflorum Lam. and Lolium perenne L. exposed to two CO2 levels (360 and 1000 μl/L) and three Cd levels (0, 4, and 16 mg/L) under hydroponic conditions. The results show that elevated levels of CO2 increased shoot biomass more, compared to root biomass, but decreased Cd concentrations in all plant tissues. Cd exposure caused toxicity to both Lolium species, as shown by the restrictions of the root morphological parameters including root length, surface area, volume, and tip numbers. These parameters were significantly higher under elevated levels of CO2 than under ambient CO2, especially for the number of fine roots. The increases in magnitudes of those parameters triggered by elevated levels of CO2 under Cd stress were more than those under non-Cd stress, suggesting an ameliorated Cd stress under elevated levels of CO2. The total Cd uptake per pot, calculated on the basis of biomass, was significantly greater under elevated levels of CO2 than under ambient CO2. Ameliorated Cd toxicity, decreased Cd concentration, and altered root morphological traits in both Lolium species under elevated levels of CO2 may have implications in food safety and phytoremediation. PMID:21462388

Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi syndrome.

PubMed

Burnett, Lisa C; LeDuc, Charles A; Sulsona, Carlos R; Paull, Daniel; Rausch, Richard; Eddiry, Sanaa; Carli, Jayne F Martin; Morabito, Michael V; Skowronski, Alicja A; Hubner, Gabriela; Zimmer, Matthew; Wang, Liheng; Day, Robert; Levy, Brynn; Fennoy, Ilene; Dubern, Beatrice; Poitou, Christine; Clement, Karine; Butler, Merlin G; Rosenbaum, Michael; Salles, Jean Pierre; Tauber, Maithe; Driscoll, Daniel J; Egli, Dieter; Leibel, Rudolph L

2017-01-03

Prader-Willi syndrome (PWS) is caused by a loss of paternally expressed genes in an imprinted region of chromosome 15q. Among the canonical PWS phenotypes are hyperphagic obesity, central hypogonadism, and low growth hormone (GH). Rare microdeletions in PWS patients define a 91-kb minimum critical deletion region encompassing 3 genes, including the noncoding RNA gene SNORD116. Here, we found that protein and transcript levels of nescient helix loop helix 2 (NHLH2) and the prohormone convertase PC1 (encoded by PCSK1) were reduced in PWS patient induced pluripotent stem cell-derived (iPSC-derived) neurons. Moreover, Nhlh2 and Pcsk1 expression were reduced in hypothalami of fasted Snord116 paternal knockout (Snord116p-/m+) mice. Hypothalamic Agrp and Npy remained elevated following refeeding in association with relative hyperphagia in Snord116p-/m+ mice. Nhlh2-deficient mice display growth deficiencies as adolescents and hypogonadism, hyperphagia, and obesity as adults. Nhlh2 has also been shown to promote Pcsk1 expression. Humans and mice deficient in PC1 display hyperphagic obesity, hypogonadism, decreased GH, and hypoinsulinemic diabetes due to impaired prohormone processing. Here, we found that Snord116p-/m+ mice displayed in vivo functional defects in prohormone processing of proinsulin, pro-GH-releasing hormone, and proghrelin in association with reductions in islet, hypothalamic, and stomach PC1 content. Our findings suggest that the major neuroendocrine features of PWS are due to PC1 deficiency.

Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi syndrome

PubMed Central

Burnett, Lisa C.; LeDuc, Charles A.; Sulsona, Carlos R.; Paull, Daniel; Rausch, Richard; Eddiry, Sanaa; Carli, Jayne F. Martin; Morabito, Michael V.; Skowronski, Alicja A.; Hubner, Gabriela; Zimmer, Matthew; Wang, Liheng; Day, Robert; Levy, Brynn; Dubern, Beatrice; Poitou, Christine; Clement, Karine; Rosenbaum, Michael; Salles, Jean Pierre; Tauber, Maithe; Egli, Dieter

2016-01-01

Prader-Willi syndrome (PWS) is caused by a loss of paternally expressed genes in an imprinted region of chromosome 15q. Among the canonical PWS phenotypes are hyperphagic obesity, central hypogonadism, and low growth hormone (GH). Rare microdeletions in PWS patients define a 91-kb minimum critical deletion region encompassing 3 genes, including the noncoding RNA gene SNORD116. Here, we found that protein and transcript levels of nescient helix loop helix 2 (NHLH2) and the prohormone convertase PC1 (encoded by PCSK1) were reduced in PWS patient induced pluripotent stem cell–derived (iPSC-derived) neurons. Moreover, Nhlh2 and Pcsk1 expression were reduced in hypothalami of fasted Snord116 paternal knockout (Snord116p–/m+) mice. Hypothalamic Agrp and Npy remained elevated following refeeding in association with relative hyperphagia in Snord116p–/m+ mice. Nhlh2-deficient mice display growth deficiencies as adolescents and hypogonadism, hyperphagia, and obesity as adults. Nhlh2 has also been shown to promote Pcsk1 expression. Humans and mice deficient in PC1 display hyperphagic obesity, hypogonadism, decreased GH, and hypoinsulinemic diabetes due to impaired prohormone processing. Here, we found that Snord116p–/m+ mice displayed in vivo functional defects in prohormone processing of proinsulin, pro-GH–releasing hormone, and proghrelin in association with reductions in islet, hypothalamic, and stomach PC1 content. Our findings suggest that the major neuroendocrine features of PWS are due to PC1 deficiency. PMID:27941249

Remarkable Changes in Behavior and Physiology of Laboratory Mice after the Massive 2011 Tohoku Earthquake in Japan

PubMed Central

Yanai, Shuichi; Semba, Yuki; Endo, Shogo

2012-01-01

A devastating earthquake and tsunami hit Japan on March 11, 2011, followed by several long and intense aftershocks. Laboratory mice housed in the Tokyo, located approximately 330 km south of this earthquake’s epicenter, displayed remarkable changes in a variety of behaviors and physiological measures. Although unusual pre-earthquake behaviors have been previously reported in laboratory animals, little is known about behavioral and physiological changes that occur after a great earthquake. In the present study, the effects of Tohoku earthquake on mice behavior were investigated. “Earthquake-experienced” mice displayed a marked increase in food consumption without gaining body weight in response to the earthquake. They also displayed enhanced anxiety, and in a formal fear memory task, showed significantly greater tone- and context-dependent conditioned freezing. Water maze performance of earthquake-experienced mice showed the quicker acquisition of the task, faster swim speed and longer swim distance than the naive mice. Serum corticosterone levels were elevated compared to the naive mice, indicating that the earthquake and aftershocks were stressful for the mice. These results demonstrate that great earthquakes strongly affect mouse behaviors and physiology. Although the effects of a variety of experimental manipulations on mouse behaviors in disease models or in models of higher cognitive functions have been extensively examined, researchers need to be aware how natural phenomena, such as earthquakes and perhaps other natural environmental factors, influence laboratory animal behaviors and physiology. PMID:22957073

Exposure of ova to cortisol pre-fertilisation affects subsequent behaviour and physiology of brown trout.

PubMed

Sloman, Katherine A

2010-08-01

Even before fertilisation, exposure of ova to high levels of stress corticosteroids can have significant effects on offspring in a variety of animals. In fish, high levels of cortisol in ovarian fluid can elicit morphological changes and reduce offspring survival. Whether there are other more subtle effects, including behavioural effects, of exposure to cortisol pre-fertilisation in fish is unclear. Here I demonstrate that a brief (3h) exposure of brown trout eggs to a physiologically relevant ( approximately 500 microg l(-)(1)) concentration of cortisol pre-fertilisation resulted in changes to developing offspring. Embryos exposed to cortisol pre-fertilisation displayed elevated oxygen consumption and ammonia excretion rates during development. After hatch, in contrast to the effects of cortisol exposure in juvenile fish, fish exposed to cortisol as eggs were more aggressive than control individuals and responded differently within a maze system. Thus, a transient exposure to corticosteroids in unfertilised eggs results in both physiological and behavioural alterations in fish. Copyright 2010 Elsevier Inc. All rights reserved.

Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior.

PubMed

Veenstra-VanderWeele, Jeremy; Muller, Christopher L; Iwamoto, Hideki; Sauer, Jennifer E; Owens, W Anthony; Shah, Charisma R; Cohen, Jordan; Mannangatti, Padmanabhan; Jessen, Tammy; Thompson, Brent J; Ye, Ran; Kerr, Travis M; Carneiro, Ana M; Crawley, Jacqueline N; Sanders-Bush, Elaine; McMahon, Douglas G; Ramamoorthy, Sammanda; Daws, Lynette C; Sutcliffe, James S; Blakely, Randy D

2012-04-03

Fifty years ago, increased whole-blood serotonin levels, or hyperserotonemia, first linked disrupted 5-HT homeostasis to Autism Spectrum Disorders (ASDs). The 5-HT transporter (SERT) gene (SLC6A4) has been associated with whole blood 5-HT levels and ASD susceptibility. Previously, we identified multiple gain-of-function SERT coding variants in children with ASD. Here we establish that transgenic mice expressing the most common of these variants, SERT Ala56, exhibit elevated, p38 MAPK-dependent transporter phosphorylation, enhanced 5-HT clearance rates and hyperserotonemia. These effects are accompanied by altered basal firing of raphe 5-HT neurons, as well as 5HT(1A) and 5HT(2A) receptor hypersensitivity. Strikingly, SERT Ala56 mice display alterations in social function, communication, and repetitive behavior. Our efforts provide strong support for the hypothesis that altered 5-HT homeostasis can impact risk for ASD traits and provide a model with construct and face validity that can support further analysis of ASD mechanisms and potentially novel treatments.

Elevated levels of 2-arachidonoylglycerol promote atherogenesis in ApoE-/- mice.

PubMed

Jehle, Julian; Schöne, Benedikt; Bagheri, Sayeh; Avraamidou, Elina; Danisch, Melina; Frank, Imke; Pfeifer, Philipp; Bindila, Laura; Lutz, Beat; Lütjohann, Dieter; Zimmer, Andreas; Nickenig, Georg

2018-01-01

The endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation and ligand to both, pro-inflammatory cannabinoid receptor 1 (CB1) and anti-inflammatory CB2. While the role of both receptors in atherogenesis has been studied extensively, the significance of 2-AG for atherogenesis is less well characterized. The impact of 2-AG on atherogenesis was studied in two treatment groups of ApoE-/- mice. One group received the monoacylglycerol lipase (MAGL)-inhibitor JZL184 [5 mg/kg i.p.], which impairs 2-AG degradation and thus causes elevated 2-AG levels, the other group received vehicle for four weeks. Simultaneously, both groups were fed a high-cholesterol diet. The atherosclerotic plaque burden was assessed in frozen sections through the aortic sinus following oil red O staining and infiltrating macrophages were detected by immunofluorescence targeting CD68. In vitro, the effect of 2-AG on B6MCL macrophage migration was assessed by Boyden chamber experiments. Transcription of adhesion molecules and chemokine receptors in macrophages was assessed by qPCR. As expected, application of the MAGL-inhibitor JZL184 resulted in a significant increase in 2-AG levels in vascular tissue (98.2 ± 16.1 nmol/g vs. 27.3 ± 4.5 nmol/g; n = 14-16; p < 0.001). ApoE-/- mice with elevated 2-AG levels displayed a significantly increased plaque burden compared to vehicle treated controls (0.44 ± 0.03 vs. 0.31 ± 0.04; n = 14; p = 0.0117). This was accompanied by a significant increase in infiltrating macrophages within the atherosclerotic vessel wall (0.33 ± 0.02 vs. 0.27 ± 0.01; n = 13-14; p = 0.0076). While there was no alteration to the white blood counts of JZL184-treated animals, 2-AG enhanced macrophage migration in vitro by 1.8 ± 0.2 -fold (n = 4-6; p = 0.0393) compared to vehicle, which was completely abolished by co-administration of either CB1- or CB2-receptor-antagonists. qPCR analyses of 2-AG-stimulated macrophages showed an enhanced transcription of the chemokine CCL5 (1.59 ± 0.23 -fold; n = 5-6; p = 0.0589) and its corresponding receptors CCR1 (2.04 ± 0.46 -fold; n = 10-11; p = 0.0472) and CCR5 (2.45 ± 0.62 -fold; n = 5-6; p = 0.0554). Taken together, elevated 2-AG levels appear to promote atherogenesis in vivo. Our data suggest that 2-AG promotes macrophage migration, possibly by the CCL5-CCR5/CCR1 axis, and thereby contributes to vascular inflammation. Thus, decreasing vascular 2-AG levels might represent a promising therapeutic strategy in patients suffering from atherosclerosis and coronary heart disease.

Differences in Salivary Alpha-Amylase and Cortisol Responsiveness following Exposure to Electrical Stimulation versus the Trier Social Stress Tests

PubMed Central

Maruyama, Yoshihiro; Kawano, Aimi; Okamoto, Shizuko; Ando, Tomoko; Ishitobi, Yoshinobu; Tanaka, Yoshihiro; Inoue, Ayako; Imanaga, Junko; Kanehisa, Masayuki; Higuma, Haruka; Ninomiya, Taiga; Tsuru, Jusen; Hanada, Hiroaki; Akiyoshi, Jotaro

2012-01-01

Background Cortisol is an essential hormone in the regulation of the stress response along the HPA axis, and salivary cortisol has been used as a measure of free circulating cortisol levels. Recently, salivary alpha-amylase (sAA) has also emerged as a novel biomarker for psychosocial stress responsiveness within the sympathetic adrenomedullary (SAM) system. Principal Findings We measured sAA and salivary cortisol in healthy volunteers after exposure to the Trier Social Stress Test (TSST) and electric stimulation stress. One hundred forty-nine healthy volunteers participated in this study. All subjects were exposed to both the TSST and electric stimulation stress on separate days. We measured sAA and salivary cortisol levels three times immediately before, immediately after, and 20 min after the stress challenge. The State (STAI-S) and Trait (STAI-T) versions of the Spielberger Anxiety Inventory test and the Profile of Mood State (POMS) tests were administered to participants before the electrical stimulation and TSST protocols. We also measured HF, LF and LF/HF Heart Rate Variability ratio immediately after electrical stimulation and TSST exposure. Following TSST exposure or electrical stimulation, sAA levels displayed a rapid increase and recovery, returning to baseline levels 20 min after the stress challenge. Salivary cortisol responses showed a delayed increase, which remained significantly elevated from baseline levels 20 min after the stress challenge. Analyses revealed no differences between men and women with regard to their sAA response to the challenges (TSST or electric stimulations), while we found significantly higher salivary cortisol responses to the TSST in females. We also found that younger subjects tended to display higher sAA activity. Salivary cortisol levels were significantly correlated with the strength of the applied electrical stimulation. Conclusions These preliminary results suggest that the HPA axis (but not the SAM system) may show differential response patterns to distinct kinds of stressors. PMID:22859941

Sunlight-readable display technology: a dual-use case study

NASA Astrophysics Data System (ADS)

Blanchard, Randall D.

1996-05-01

This paper describes our vision of sunlight readable color display requirements, an alternate technology that offers a high level of performance, and how we implemented it for the military avionics display market. This knowledge base and product development experience was then applied with a comparable level of performance to commercial applications. The successful dual use of this technology for these two diverse markets is presented. Details of the technical commonality and a comparison of the design and performance differences are presented. A basis for specifying the required level of performance for a sunlight readable full color display is discussed. With the objective of providing a high level of image brightness and high ambient light rejection, a display architecture using collimated light is used. The resulting designs of two military cockpit display products, with contrast ratios above 20:1 in sunlight are shown. The performance of a commercial display providing several thousand foot- Lamberts of image brightness is presented.

M13 bacteriophage coat proteins engineered for improved phage display.

PubMed

Sidhu, Sachdev S; Feld, Birte K; Weiss, Gregory A

2007-01-01

This chapter describes a method for increasing levels of protein fusions displayed on the surfaces of M13 bacteriophage particles. By introducing mutations into the anchoring M13 coat protein, protein display levels can be increased by up to two orders of magnitude. Experimental methods are presented for the design, construction, and screening of phage-displayed libraries for improved protein display.

Human-Computer Interactions: Are There Adverse Health Consequences?

ERIC Educational Resources Information Center

Emurian, Henry H.

1989-01-01

Discusses the hypothesis that similarities may exist between laboratory research paradigms evoking elevated blood pressure during task performance by normal subjects and video display terminal (VDT) work done by data clerks and college students. Type A behavior and the development of coronary heart disease are discussed, and further research needs…

Developmental Effects Of A Municipal Wastewater Effluent On Two Generations Of The Fathead Minnow, Pimephales promelas

EPA Science Inventory

Municipal wastewater effluents have been shown to contain a variety of anthropogenic compounds, many of which are know to display estrogenic properties. While multiple laboratory studies have shown the effects of such compounds on an individual basis at elevated concentrations, ...

Using Mental Health Consultation to Decrease Disruptive Behaviors in Preschoolers: Adapting an Empirically-Supported Intervention

ERIC Educational Resources Information Center

Williford, Amanda P.; Shelton, Terri L.

2008-01-01

Background: This study examined the effectiveness of an adaptation of an empirically-supported intervention delivered using mental health consultation to preschoolers who displayed elevated disruptive behaviors. Method: Ninety-six preschoolers, their teachers, and their primary caregivers participated. Children in the intervention group received…

Impact of Ocean Acidification on Energy Metabolism of Oyster, Crassostrea gigas—Changes in Metabolic Pathways and Thermal Response

PubMed Central

Lannig, Gisela; Eilers, Silke; Pörtner, Hans O.; Sokolova, Inna M.; Bock, Christian

2010-01-01

Climate change with increasing temperature and ocean acidification (OA) poses risks for marine ecosystems. According to Pörtner and Farrell [1], synergistic effects of elevated temperature and CO2-induced OA on energy metabolism will narrow the thermal tolerance window of marine ectothermal animals. To test this hypothesis, we investigated the effect of an acute temperature rise on energy metabolism of the oyster, Crassostrea gigas chronically exposed to elevated CO2 levels (partial pressure of CO2 in the seawater ~0.15 kPa, seawater pH ~ 7.7). Within one month of incubation at elevated Pco2 and 15 °C hemolymph pH fell (pHe = 7.1 ± 0.2 (CO2-group) vs. 7.6 ± 0.1 (control)) and Peco2 values in hemolymph increased (0.5 ± 0.2 kPa (CO2-group) vs. 0.2 ± 0.04 kPa (control)). Slightly but significantly elevated bicarbonate concentrations in the hemolymph of CO2-incubated oysters ([HCO− 3]e = 1.8 ± 0.3 mM (CO2-group) vs. 1.3 ± 0.1 mM (control)) indicate only minimal regulation of extracellular acid-base status. At the acclimation temperature of 15 °C the OA-induced decrease in pHe did not lead to metabolic depression in oysters as standard metabolism rates (SMR) of CO2-exposed oysters were similar to controls. Upon acute warming SMR rose in both groups, but displayed a stronger increase in the CO2-incubated group. Investigation in isolated gill cells revealed a similar temperaturedependence of respiration between groups. Furthermore, the fraction of cellular energy demand for ion regulation via Na+/K+-ATPase was not affected by chronic hypercapnia or temperature. Metabolic profiling using 1H-NMR spectroscopy revealed substantial changes in some tissues following OA exposure at 15 °C. In mantle tissue alanine and ATP levels decreased significantly whereas an increase in succinate levels was observed in gill tissue. These findings suggest shifts in metabolic pathways following OA-exposure. Our study confirms that OA affects energy metabolism in oysters and suggests that climate change may affect populations of sessile coastal invertebrates such as mollusks. PMID:20948910

Effects of Extensive Beetle-Induced Forest Mortality on Aromatic Organic Carbon Loading and Disinfection Byproduct Formation Potential

NASA Astrophysics Data System (ADS)

Brouillard, B.; Mikkelson, K. M.; Dickenson, E.; Sharp, J.

2015-12-01

Recent drought and warmer temperatures associated with climate change have caused increased pest-induced forest mortality with impacts on biogeochemical and hydrologic processes. To better understand the seasonal impacts of bark beetle infestation on water quality, samples were collected regularly over two overlapping snow free seasons at surface water intakes of six water treatment facilities in the Rocky Mountain region of Colorado displaying varying levels of bark beetle infestation (high >40%, moderate 20-40%, and low <20%). Organic carbon concentrations were typically 3 to 6 times higher in waters sourced from high beetle-impacted watersheds compared to moderate and low impact watersheds, revealing elevated specific ultraviolet absorbance, fluorescence, and humic-like intensity indicative of elevated aromatic carbon signatures. Accordingly, an increase in disinfection byproduct (DBP) formation potential of 400 to 600% was quantified when contrasted with watersheds containing less tree mortality. Beetle impact exasperated seasonal increases in carbon loading and DBP formation potential following both runoff and precipitation events indicating windows when enhanced water treatment may be utilized by water providers in highly infested regions. Additionally, elevated carbon concentrations throughout the summer and fall along with peaks following precipitation events provide evidence of shifting hydrologic flow paths in areas experiencing high forest mortality from decreased tree water uptake and interception. Collectively, these results demonstrate the need for continued watershed protection and monitoring with a changing climate as the resultant perturbations can have adverse effects on biogeochemistry and water quality in heavily impacted areas.

Consequences of continuous social defeat stress on anxiety- and depressive-like behaviors and ethanol reward in mice.

PubMed

Macedo, Giovana Camila; Morita, Gleice Midori; Domingues, Liz Paola; Favoretto, Cristiane Aparecida; Suchecki, Deborah; Quadros, Isabel Marian Hartmann

2018-01-01

This study employed the intruder-resident paradigm to evaluate the effects of continuous social defeat on depressive- and anxiety-like behaviors and the reinforcing and motivational actions of ethanol in male Swiss mice. Male Swiss mice were exposed to a 10-day social defeat protocol, while control mice cohabitated with a non-aggressive animal. Continuous defeat stress consisted of episodes of defeat, followed by 24h or 48h cohabitation with the aggressor until the following defeat. Mice were assessed for sucrose drinking (anhedonia), social investigation test, elevated plus-maze, conditioned place preference to ethanol, and locomotor response to ethanol. Plasma corticosterone was measured prior to, after the first and the final defeat, and 10days after the end of defeat. Defeated mice exhibited a depressive-like phenotype as indicated by social inhibition and reduced sucrose preference, relative to non-defeated controls. Defeated mice also displayed anxiety-like behavior when tested in the elevated plus-maze. Stressed animals failed to present ethanol-induced locomotor stimulation, but showed increased sensitivity for ethanol-induced conditioned place preference. Corticosterone response to defeat was the highest after the first defeat, but was still elevated after the last defeat (day 10) when compared to non-stressed controls. Baseline corticosterone levels were unchanged 10days after the final defeat. These data suggest that social defeat stress increased depressive- and anxiety-like behavior as well increased vulnerability to ethanol reward in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.

PubMed

Bharti, Rashmi; Dey, Goutam; Das, Anjan Kumar; Mandal, Mahitosh

2018-04-26

Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis. We employed various in-vitro and in-vivo techniques and clinical samples. We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1α was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen. Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.

Monocyte chemoattractant protein-1 and interleukin-8 levels in urine and serum of patents with hemolytic uremic syndrome.

PubMed

van Setten, P A; van Hinsbergh, V W; van den Heuvel, L P; Preyers, F; Dijkman, H B; Assmann, K J; van der Velden, T J; Monnens, L A

1998-06-01

The epidemic form of the hemolytic uremic syndrome (HUS) in children is hallmarked by endothelial cell damage, most predominantly displayed by the glomerular capillaries. The influx of mononuclear (MO) and polymorphonuclear cells (PMNs) into the glomeruli may be an important event in the initiation, prolongation, and progression of glomerular endothelial cell damage in HUS patients. The molecular mechanisms for the recruitment of these leukocytes into the kidney are unclear, but monocyte chemoattractant protein-1 (MCP-1) and IL-8 are suggested to be prime candidates. In this study, we analyzed the presence of both chemokines in 24-h urinary (n = 15) and serum (n = 14) samples of HUS children by specific ELISAs. Furthermore, kidney biopsies of three different HUS children were examined for MO and PMN cell infiltration by histochemical techniques and electron microscopy. Whereas the chemokines MCP-1 and IL-8 were present in only very limited amounts in urine of 17 normal control subjects, serial samples of HUS patients demonstrated significantly elevated levels of both chemokines. HUS children with anuria showed higher initial and maximum chemokine levels than their counterparts without anuria. A strong positive correlation was observed between urinary MCP-1 and IL-8 levels. Whereas initial serum IL-8 levels were significantly increased in HUS children, serum MCP-1 levels were only slightly elevated compared with serum MCP-1 in control children. No correlation was found between urinary and serum chemokine concentrations. Histologic and EM studies of HUS biopsy specimens clearly showed the presence of MOs and to a lesser extent of PMNs in the glomeruli. The present data suggest an important local role for MOs and PMNs in the process of glomerular endothelial-cell damage. The chemokines MCP-1 and IL-8 may possibly be implicated in the pathogenesis of HUS through the recruitment and activation of MOs and PMNs, respectively.

Immunological responses to Clostridium perfringens alpha-toxin in two genetically divergent lines of chickens as influenced by major histocompatibility complex genotype.

PubMed

Sumners, L H; Cox, C M; Kim, S; Salevsky, J E; Siegel, P B; Dalloul, R A

2012-03-01

Chickens genetically selected for low (LA) or high (HA) antibody response to SRBC displayed a correlated change in MHC, so that LA chickens were 96% B13 and HA chickens were 96% B21. The LA line appears to be less susceptible to invasion by extracellular pathogens, whereas HA chickens are more resistant to infection by intracellular organisms. Resistance to Clostridium perfringens is one instance in which the lines do not follow their established trend of pathogen susceptibility, where during a clinical outbreak of necrotic enteritis, B21B21 genotypes experienced significantly less mortality than B13B13 genotypes. A study was carried out to assess immunological differences between LA and HA lines during exposure to C. perfringens α-toxin. Peripheral blood mononuclear cells were isolated from each genetic line, cultured with or without lipopolysaccharide (4 h), and exposed to varying concentrations of α-toxin (1; 10; 100; and 1,000 U/L) for 2 and 4 h. Evaluation of cellular proliferation, percentage of cytotoxicity, and immunological gene expression was carried out in a series of experiments. Cells isolated from HA chickens had significantly increased proliferation than those from LA chickens at low toxin levels (1 and 10 U/L) and significantly decreased proliferation at high toxin levels (100 and 1,000 U/L). Following exposure to lipopolysaccharide, the percentage of cytotoxicity was higher for LA than HA cells. In both assays, HA cells displayed superior performance following lipopolysaccharide-stimulation. Gene expression analysis of immune transcripts by quantitative real-time PCR revealed significantly upregulated expression of interferon (IFN)-γ, interleukin (IL)-8, IL-13 (2 h), IL-15, and CXCLi1 (4 h) in HA than LA chickens. Cells isolated from the LA line displayed significantly elevated expression of IL-2, IL-10, IL-13 (4 h), IL-16, IL-18, inducible nitric oxide synthase (iNOS), CXCLi1 (2 h), and lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) compared with the HA line. Clearly, these 2 genetic lines display highly divergent immune responses in regards to C. perfringens toxin exposure.

Lead poisoning in United States-bound refugee children: Thailand-Burma border, 2009.

PubMed

Mitchell, Tarissa; Jentes, Emily; Ortega, Luis; Scalia Sucosky, Marissa; Jefferies, Taran; Bajcevic, Predrag; Parr, Valentina; Jones, Warren; Brown, Mary Jean; Painter, John

2012-02-01

Elevated blood lead levels lead to permanent neurocognitive sequelae in children. Resettled refugee children in the United States are considered at high risk for elevated blood lead levels, but the prevalence of and risk factors for elevated blood lead levels before resettlement have not been described. Blood samples from children aged 6 months to 14 years from refugee camps in Thailand were tested for lead and hemoglobin. Sixty-seven children with elevated blood lead levels (venous ≥10 µg/dL) or undetectable (capillary <3.3 µg/dL) blood lead levels participated in a case-control study. Of 642 children, 33 (5.1%) had elevated blood lead levels. Children aged <2 years had the highest prevalence (14.5%). Among children aged <2 years included in a case-control study, elevated blood lead levels risk factors included hemoglobin <10 g/dL, exposure to car batteries, and taking traditional medicines. The prevalence of elevated blood lead levels among tested US-bound Burmese refugee children was higher than the current US prevalence, and was especially high among children <2 years old. Refugee children may arrive in the United States with elevated blood lead levels. A population-specific understanding of preexisting lead exposures can enhance postarrival lead-poisoning prevention efforts, based on Centers for Disease Control and Prevention recommendations for resettled refugee children, and can lead to remediation efforts overseas.

Three-dimensional visualization of geographical terrain data using temporal parallax difference induction

NASA Astrophysics Data System (ADS)

Mayhew, Christopher A.; Mayhew, Craig M.

2009-02-01

Vision III Imaging, Inc. (the Company) has developed Parallax Image Display (PIDTM) software tools to critically align and display aerial images with parallax differences. Terrain features are rendered obvious to the viewer when critically aligned images are presented alternately at 4.3 Hz. The recent inclusion of digital elevation models in geographic data browsers now allows true three-dimensional parallax to be acquired from virtual globe programs like Google Earth. The authors have successfully developed PID methods and code that allow three-dimensional geographical terrain data to be visualized using temporal parallax differences.

Gaze-contingent displays: a review.

PubMed

Duchowski, Andrew T; Cournia, Nathan; Murphy, Hunter

2004-12-01

Gaze-contingent displays (GCDs) attempt to balance the amount of information displayed against the visual information processing capacity of the observer through real-time eye movement sensing. Based on the assumed knowledge of the instantaneous location of the observer's focus of attention, GCD content can be "tuned" through several display processing means. Screen-based displays alter pixel level information generally matching the resolvability of the human retina in an effort to maximize bandwidth. Model-based displays alter geometric-level primitives along similar goals. Attentive user interfaces (AUIs) manage object- level entities (e.g., windows, applications) depending on the assumed attentive state of the observer. Such real-time display manipulation is generally achieved through non-contact, unobtrusive tracking of the observer's eye movements. This paper briefly reviews past and present display techniques as well as emerging graphics and eye tracking technology for GCD development.

Transgenic Mouse Model for Reducing Oxidative Damage in Bone

NASA Technical Reports Server (NTRS)

Schreurs, Ann-Sofie; Torres, S.; Truong, T.; Moyer, E. L.; Kumar, A.; Tahimic, Candice C. G.; Alwood, J. S.; Limoli, C. L.; Globus, R. K.

2016-01-01

Bone loss can occur due to many challenges such age, radiation, microgravity, and Reactive Oxygen Species (ROS) play a critical role in bone resorption by osteoclasts (Bartell et al. 2014). We hypothesize that suppression of excess ROS in skeletal cells, both osteoblasts and osteoclasts, regulates skeletal growth and remodeling. To test our hypothesis, we used transgenic mCAT mice which overexpress the human anti-oxidant catalase gene targeted to the mitochondria, the main site for endogenous ROS production. mCAT mice have a longer life-span than wildtype controls and have been used to study various age-related disorders. To stimulate remodeling, 16 week old mCAT mice or wildtype mice were exposed to treatment (hindlimb-unloading and total body-irradiation) or sham treatment conditions (control). Tissues were harvested 2 weeks later for skeletal analysis (microcomputed tomography), biochemical analysis (gene expression and oxidative damage measurements), and ex vivo bone marrow derived cell culture (osteoblastogenesis and osteoclastogenesis). mCAT mice expressed the transgene and displayed elevated catalase activity in skeletal tissue and marrow-derived osteoblasts and osteoclasts grown ex vivo. In addition, when challenged with treatment, bone tissues from wildtype mice showed elevated levels of malondialdehyde (MDA), indicating oxidative damage) whereas mCAT mice did not. Correlation analysis revealed that increased catalase activity significantly correlated with decreased MDA levels and that increased oxidative damage correlated with decreased percent bone volume (BVTV). In addition, ex-vivo cultured osteoblast colony growth correlated with catalase activity in the osteoblasts. Thus, we showed that these transgenic mice can be used as a model to study the relationship between markers of oxidative damage and skeletal properties. mCAT mice displayed reduced BVTV and trabecular number relative to wildtype mice, as well as increased structural model index in the cancellous tibia. Treatment caused bone loss in wildtype mice, as expected. Treatment also caused deficits in microarchitecture of mCAT mice, although less severe than wildtype mice in some parameters (percent bone volume, structural model index and cortical area). In conclusion, our results indicate that endogenous ROS signaling in both osteoblast and osteoclast lineage cells contributes to skeletal growth and remodeling, and quenching oxidative damage could play a role in bone loss prevention.

The CHC22 Clathrin-GLUT4 Transport Pathway Contributes to Skeletal Muscle Regeneration

PubMed Central

Griffin, Christine A.; Esk, Christopher; Torres, Jorge A.; Ohkoshi, Norio; Ishii, Akiko; Tamaoka, Akira; Funke, Birgit H.; Kucherlapati, Raju; Margeta, Marta; Rando, Thomas A.; Brodsky, Frances M.

2013-01-01

Mobilization of the GLUT4 glucose transporter from intracellular storage vesicles provides a mechanism for insulin-responsive glucose import into skeletal muscle. In humans, clathrin isoform CHC22 participates in formation of the GLUT4 storage compartment in skeletal muscle and fat. CHC22 function is limited to retrograde endosomal sorting and is restricted in its tissue expression and species distribution compared to the conserved CHC17 isoform that mediates endocytosis and several other membrane traffic pathways. Previously, we noted that CHC22 was expressed at elevated levels in regenerating rat muscle. Here we investigate whether the GLUT4 pathway in which CHC22 participates could play a role in muscle regeneration in humans and we test this possibility using CHC22-transgenic mice, which do not normally express CHC22. We observed that GLUT4 expression is elevated in parallel with that of CHC22 in regenerating skeletal muscle fibers from patients with inflammatory and other myopathies. Regenerating human myofibers displayed concurrent increases in expression of VAMP2, another regulator of GLUT4 transport. Regenerating fibers from wild-type mouse skeletal muscle injected with cardiotoxin also showed increased levels of GLUT4 and VAMP2. We previously demonstrated that transgenic mice expressing CHC22 in their muscle over-sequester GLUT4 and VAMP2 and have defective GLUT4 trafficking leading to diabetic symptoms. In this study, we find that muscle regeneration rates in CHC22 mice were delayed compared to wild-type mice, and myoblasts isolated from these mice did not proliferate in response to glucose. Additionally, CHC22-expressing mouse muscle displayed a fiber type switch from oxidative to glycolytic, similar to that observed in type 2 diabetic patients. These observations implicate the pathway for GLUT4 transport in regeneration of both human and mouse skeletal muscle, and demonstrate a role for this pathway in maintenance of muscle fiber type. Extrapolating these findings, CHC22 and GLUT4 can be considered markers of muscle regeneration in humans. PMID:24204966

Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

PubMed Central

López-Mejías, Raquel; Rueda-Gotor, Javier; Miranda-Filloy, José A.; Ubilla, Begoña; Carnero-López, Beatriz; Palmou-Fontana, Natalia; Gómez-Acebo, Inés; Blanco, Ricardo; Pina, Trinitario; Ochoa, Rodrigo; González-Juanatey, Carlos; González-Gay, Miguel A.

2014-01-01

Objective. TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients. PMID:24976690

Characterizing the effects of droplines on target acquisition performance on a 3-D perspective display

NASA Technical Reports Server (NTRS)

Liao, Min-Ju; Johnson, Walter W.

2004-01-01

The present study investigated the effects of droplines on target acquisition performance on a 3-D perspective display in which participants were required to move a cursor into a target cube as quickly as possible. Participants' performance and coordination strategies were characterized using both Fitts' law and acquisition patterns of the 3 viewer-centered target display dimensions (azimuth, elevation, and range). Participants' movement trajectories were recorded and used to determine movement times for acquisitions of the entire target and of each of its display dimensions. The goodness of fit of the data to a modified Fitts function varied widely among participants, and the presence of droplines did not have observable impacts on the goodness of fit. However, droplines helped participants navigate via straighter paths and particularly benefited range dimension acquisition. A general preference for visually overlapping the target with the cursor prior to capturing the target was found. Potential applications of this research include the design of interactive 3-D perspective displays in which fast and accurate selection and manipulation of content residing at multiple ranges may be a challenge.

Poly-silicon TFT AM-OLED on thin flexible metal substrates

NASA Astrophysics Data System (ADS)

Afentakis, Themis; Hatalis, Miltiadis K.; Voutsas, Apostolos T.; Hartzell, John W.

2003-05-01

Thin metal foils present an excellent alternative to polymers for the fabrication of large area, flexible displays. Their main advantage spurs from their ability to withstand higher temperatures during processing; microelectronic fabrication at elevated temperatures offers the ability to utilize a variety of crystallization processes for the active layer of devices and thermally grown gate dielectrics. This can lead to high performance (high mobility, low threshold voltage) low cost and highly reliable thin film transistors. In some cases, the conductive substrate can also be used to provide power to the active devices, thus reducing layout complexity. This paper discusses the first successful attempt to design and fabricate a variety of active matrix organic light emitting diode displays on thin, flexible stainless steel foils. Different pixel architectures, such as two- and four-transistor implementations, and addressing modes, such as voltage- or current-driven schemese are examined. This work clearly demonstrates the advantages associated with the fabrication of OLED displays on thin metal foils, which - through roll-to-roll processing - can potentially result in revolutionizing today's display processing, leading to a new generation of low cost, high performance versatile display systems.

Influence of soil characteristics on rare earth fingerprints in mosses and mushrooms: Example of a pristine temperate rainforest (Slavonia, Croatia).

PubMed

Fiket, Željka; Medunić, Gordana; Furdek Turk, Martina; Ivanić, Maja; Kniewald, Goran

2017-07-01

The present study aims to investigate levels and distribution of rare earth elements (REE) in soils, mosses and mushrooms of a pristine temperate rainforest, a non-polluted natural system, in order to characterise their environmental availability and mobility. The multielement analysis of digested soil, moss and mushroom samples was performed by High Resolution Inductively Coupled Plasma Mass Spectrometry. The distribution of rare earths in mosses and mushrooms was found primarily affected by local pedological setting. Mosses displayed a consistent lithological signature with an almost insignificant REE fractionation compared to soils. Mushrooms showed differences in REE concentrations in certain parts of the fruiting body with regard to their main physiological function and indicated a significant impact of soil organic content on the overall REEs uptake. Results of our work highlight the importance of substrate characteristics on the initial levels of REEs in mosses and mushrooms. Moreover, this study provides baseline data on the rare earth element levels in mosses and mushrooms growing in a pristine forest area characterised by naturally elevated REE levels in the soil. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chromium picolinate inhibits cholesterol-induced stimulation of platelet aggregation in hypercholesterolemic rats.

PubMed

Seif, A A

2015-06-01

Hypercholesterolemia indirectly increases the risk of myocardial infarction by enhancing platelet aggregation. Chromium has been shown to lower plasma lipids. This study was designed to investigate whether chromium inhibits platelet aggregation under hypercholesterolemic conditions. Albino rats were divided into four groups: control rats fed with a normolipemic diet (NLD group), chromium-supplemented rats fed with NLD (NLD + Cr group), rats fed with a high-fat diet (HF group), and chromium-supplemented rats fed with HF (HF + Cr group). After 10 weeks, blood was collected to determine adenosine diphosphate and collagen-induced platelet aggregation and plasma levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B, and thromboxane B2. Low-density lipoprotein cholesterol was calculated by Friedewald formula. High-fat diet animals displayed significant elevation of plasma lipids and platelet aggregation which was normalized to control levels by chromium supplementation. Chromium supplementation in normolipemic (NLD + Cr) rats did not produce significant changes in either plasma lipids or platelet activity. Chromium supplementation to hypercholesterolemic rats improves the lipid profile and returns platelet hyperaggregability to control levels. This normalization is mostly due to a reduction in plasma cholesterol level.

Determination of washout performance of various monochrome displays under simulated flight ambient and solar lighting conditions

NASA Technical Reports Server (NTRS)

Batson, Vernon M.; Robertson, James B.; Parrish, Russell V.

1990-01-01

The aircraft cockpit ambient lighting simulation system (ACALSS) has been developed to study display readability and associated pilot/vehicle performance effects in a part-task simulator cockpit. In the study reported here, the ACALSS was used to determine the illumination levels at which subjects lose the ability to maintain aircraft states when using three display technologies as display media for primary flight displays: a standard monochrome EL (electroluminescent) flat-panel, a laboratory-class monochrome CRT, and an enhanced-brightness EL flat-panel. The multivariate statistical technique of modified profile analysis was used to test for performance differences between display devices as functions of illumination levels. The standard monochrome EL flat-panel display began to washout after the 2500 foot-candle level of illumination. The monochrome CRT began to washout after the 5500 foot-candle level of illumination. No performance decrements by increased illumination up to the 12,000 foot-candle level were found for the enhanced-brightness EL flat-panel display. What was not anticipated was that half the subjects would subjectively prefer the CRT over the enhanced-brightness EL, even though their performance errors would have indicated the opposite.

Spatially homogeneous ferromagnetism below the enhanced Curie temperature in EuO(1-x) thin films.

PubMed

Monteiro, Pedro M S; Baker, Peter J; Ionescu, Adrian; Barnes, Crispin H W; Salman, Zaher; Suter, Andreas; Prokscha, Thomas; Langridge, Sean

2013-05-24

We have used low-energy implanted muons as a volume sensitive probe of the magnetic properties of EuO(1-x) thin films. We find that static and homogeneous magnetic order persists up to the elevated T(C) in the doped samples, and the muon signal displays the double dome feature also observed in the sample magnetization. Our results appear incompatible with either the magnetic phase separation or bound magnetic polaron descriptions previously suggested to explain the elevated T(C), but are compatible with an RKKY-like interaction mediating magnetic interactions above 69 K.

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

PubMed

Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

2017-05-01

Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia.

PubMed

Couch, Yvonne; Anthony, Daniel C; Dolgov, Oleg; Revischin, Alexander; Festoff, Barry; Santos, Ana Isabel; Steinbusch, Harry W; Strekalova, Tatyana

2013-03-01

A chronic stress paradigm comprising exposure to predation, tail suspension and restraint induces a depressive syndrome in C57BL/6J mice that occurs in some, but not all, animals. Here, we sought to extend our behavioural studies to investigate how susceptibility (sucrose preference<65%) or resilience (sucrose preference>65%) to stress-induced anhedonia affects the 5HT system and the expression of inflammation-related genes. All chronically stressed animals, displayed increased level of anxiety, but susceptible mice exhibited an increased propensity to float in the forced swim test and demonstrate hyperactivity under stressful lighting conditions. These changes were not present in resilient or acutely stressed animals. Compared to resilient animals, susceptible mice showed elevated expression of tumour necrosis factor alpha (TNF) and the 5-HT transporter (SERT) in the pre-frontal area. Enhanced expression of 5HT(2A) and COX-1 in the pre-frontal area was observed in all stressed animals. In turn, indoleamine-2,3-dioxygenase (IDO) was significantly unregulated in the raphe of susceptible animals. At the cellular level, increased numbers of Iba-1-positive microglial cells were also present in the prefrontal area of susceptible animals compared to resilient animals. Consequently, the susceptible animals display a unique molecular profile when compared to resilient, but anxious, animals. Unexpectedly, this altered profile provides a rationale for exploring anti-inflammatory, and possibly, TNF-targeted therapy for major depression. Copyright © 2013 Elsevier Inc. All rights reserved.

Interoception drives increased rational decision-making in meditators playing the ultimatum game.

PubMed

Kirk, Ulrich; Downar, Jonathan; Montague, P Read

2011-01-01

Human decision-making is often conceptualized as a competition between cognitive and emotional processes in the brain. Deviations from rational processes are believed to derive from inclusion of emotional factors in decision-making. Here, we investigate whether experienced Buddhist meditators are better equipped to regulate emotional processes compared with controls during economic decision-making in the Ultimatum Game. We show that meditators accept unfair offers on more than half of the trials, whereas controls only accept unfair offers on one-quarter of the trials. By applying fMRI we show that controls recruit the anterior insula during unfair offers. Such responses are powerful predictors of rejecting offers in social interaction. By contrast, meditators display attenuated activity in high-level emotional representations of the anterior insula and increased activity in the low-level interoceptive representations of the posterior insula. In addition we show that a subset of control participants who play rationally (i.e., accepts >85% unfair offers) recruits the dorsolateral prefrontal cortex presumably reflecting increased cognitive demands, whereas rational meditators by contrast display elevated activity in the somatosensory cortex and posterior superior temporal cortex. In summary, when assessing unfairness in the Ultimatum Game, meditators activate a different network of brain areas compared with controls enabling them to uncouple negative emotional reactions from their behavior. These findings highlight the clinically and socially important possibility that sustained training in mindfulness meditation may impact distinct domains of human decision-making.

Improved in vivo gene transfer into tumor tissue by stabilization of pseudodendritic oligoethylenimine-based polyplexes.

PubMed

Russ, Verena; Fröhlich, Thomas; Li, Yunqiu; Halama, Anna; Ogris, Manfred; Wagner, Ernst

2010-02-01

HD O is a low molecular weight pseudodendrimer containing oligoethylenimine and degradable hexanediol diacrylate diesters. DNA polyplexes display encouraging gene transfer efficiency in vitro and in vivo but also a limited stability under physiological conditions. This limitation must be overcome for further development into more sophisticated formulations. HD O polyplexes were laterally stabilized by crosslinking surface amines via bifunctional crosslinkers, bioreducible dithiobis(succimidyl propionate) (DSP) or the nonreducible analog disuccinimidyl suberate (DSS). Optionally, in a subsequent step, the targeting ligand transferrin (Tf) was attached to DSP-linked HD O polyplexes via Schiff base formation between HD O amino groups and Tf aldehyde groups, which were introduced into Tf by periodate oxidation of the glycosylation sites. Crosslinked DNA polyplexes showed an increased stability against exchange reaction by salt or heparin. Disulfide bond containing DSP-linked polyplexes were susceptible to reducing conditions. These polyplexes displayed the highest gene expression levels in vitro and in vivo (upon intratumoral application in mice), and these were significantly elevated and prolonged over standard or DSS-stabilized HD O formulations. DSP-stabilized HD O polyplexes with or without Tf coating were well-tolerated after intravenous application. High gene expression levels were found in tumor tissue, with negligible gene expression in any other organ. Lateral stabilization of HD O polyplexes with DSP crosslinker enhanced gene transfer efficacy and was essential for the incorporation of a ligand (Tf) into a stable particle formulation.

The Chloroplast Protease AMOS1/EGY1 Affects Phosphate Homeostasis under Phosphate Stress1

PubMed Central

Yu, Fang Wei; Zhu, Xiao Fang; Li, Guang Jie; Kronzucker, Herbert J.; Shi, Wei Ming

2016-01-01

Plastid intramembrane proteases in Arabidopsis (Arabidopsis thaliana) are involved in jasmonic acid biosynthesis, chloroplast development, and flower morphology. Here, we show that Ammonium-Overly-Sensitive1 (AMOS1), a member of the family of plastid intramembrane proteases, plays an important role in the maintenance of phosphate (P) homeostasis under P stress. Loss of function of AMOS1 revealed a striking resistance to P starvation. amos1 plants displayed retarded root growth and reduced P accumulation in the root compared to wild type (Col-0) under P-replete control conditions, but remained largely unaffected by P starvation, displaying comparable P accumulation and root and shoot growth under P-deficient conditions. Further analysis revealed that, under P-deficient conditions, the cell wall, especially the pectin fraction of amos1, released more P than that of wild type, accompanied by a reduction of the abscisic acid (ABA) level and an increase in ethylene production. By using an ABA-insensitive mutant, abi4, and applying ABA and ACC exogenously, we found that ABA inhibits cell wall P remobilization while ethylene facilitates P remobilization from the cell wall by increasing the pectin concentration, suggesting ABA can counteract the effect of ethylene. Furthermore, the elevated ABA level and the lower ethylene production also correlated well with the mimicked P deficiency in amos1. Thus, our study uncovers the role of AMOS1 in the maintenance of P homeostasis through ABA-antagonized ethylene signaling. PMID:27516532

An Evaluation of Detect and Avoid (DAA) Displays for Unmanned Aircraft Systems: The Effect of Information Level and Display Location on Pilot Performance

NASA Technical Reports Server (NTRS)

Fern, Lisa; Rorie, R. Conrad; Pack, Jessica S.; Shively, R. Jay; Draper, Mark H.

2015-01-01

A consortium of government, industry and academia is currently working to establish minimum operational performance standards for Detect and Avoid (DAA) and Control and Communications (C2) systems in order to enable broader integration of Unmanned Aircraft Systems (UAS) into the National Airspace System (NAS). One subset of these performance standards will need to address the DAA display requirements that support an acceptable level of pilot performance. From a pilot's perspective, the DAA task is the maintenance of self separation and collision avoidance from other aircraft, utilizing the available information and controls within the Ground Control Station (GCS), including the DAA display. The pilot-in-the-loop DAA task requires the pilot to carry out three major functions: 1) detect a potential threat, 2) determine an appropriate resolution maneuver, and 3) execute that resolution maneuver via the GCS control and navigation interface(s). The purpose of the present study was to examine two main questions with respect to DAA display considerations that could impact pilots' ability to maintain well clear from other aircraft. First, what is the effect of a minimum (or basic) information display compared to an advanced information display on pilot performance? Second, what is the effect of display location on UAS pilot performance? Two levels of information level (basic, advanced) were compared across two levels of display location (standalone, integrated), for a total of four displays. The authors propose an eight-stage pilot-DAA interaction timeline from which several pilot response time metrics can be extracted. These metrics were compared across the four display conditions. The results indicate that the advanced displays had faster overall response times compared to the basic displays, however, there were no significant differences between the standalone and integrated displays. Implications of the findings on understanding pilot performance on the DAA task, the development of DAA display performance standards, as well as the need for future research are discussed.

Application of Raman spectroscopy in type 2 diabetes screening in blood using leucine and isoleucine amino-acids as biomarkers and in comparative anti-diabetic drugs efficacy studies

PubMed Central

Mwangi, Peter Waweru; Bukachi, Fredrick; Mandela, Keith Makori

2017-01-01

Diabetes is an irreversible condition characterized by elevated blood glucose levels. Currently, there are no predictive biomarkers for this disease and the existing ones such as hemoglobin A1c and fasting blood glucose are used only when diabetes symptoms are noticed. The objective of this work was first to explore the potential of leucine and isoleucine amino acids as diabetes type 2 biomarkers using their Raman spectroscopic signatures. Secondly, we wanted to explore whether Raman spectroscopy can be applied in comparative efficacy studies between commercially available anti-diabetic drug pioglitazone and the locally used anti-diabetic herbal extract Momordica spinosa (Gilg.)Chiov. Sprague Dawley (SD) rat’s blood was used and were pipetted onto Raman substrates prepared from conductive silver paste smeared glass slides. Prominent Raman bands associated with glucose (926, 1302, 1125 cm−1), leucine (1106, 1248, 1302, 1395 cm−1) and isolecucine (1108, 1248, 1437 and 1585 cm−1) were observed. The Raman bands centered at 1125 cm−1, 1395 cm−1 and 1437 cm−1 associated respectively to glucose, leucine and isoleucine were chosen as biomarker Raman peaks for diabetes type 2. These Raman bands displayed decreased intensities in blood from diabetic SD rats administered antidiabetic drugs pioglitazone and herbal extract Momordica spinosa (Gilg.)Chiov. The intensity decrease indicated reduced concentration levels of the respective biomarker molecules: glucose (1125 cm−1), leucine (1395 cm−1) and isoleucine (1437 cm−1) in blood. The results displayed the power and potential of Raman spectroscopy in rapid (10 seconds) diabetes and pre-diabetes screening in blood (human or rat’s) with not only glucose acting as a biomarker but also leucine and isoleucine amino-acids where intensities of respectively assigned bands act as references. It also showed that using Raman spectroscopic signatures of the chosen biomarkers, the method can be an alternative for performing comparative efficacy studies between known and new anti-diabetic drugs. Reports on use of Raman spectroscopy in type 2 diabetes mellitus screening with Raman bands associated with leucine and isoleucine molecules acting as reference is rare in literature. The use of Raman spectroscopy in pre-diabetes screening of blood for changes in levels of leucine and isoleucine amino acids is particularly interesting as once elevated levels are noticed, necessary interventions to prevent diabetes development can be initiated. PMID:28926628

Systemic SIRT1 insufficiency results in disruption of energy homeostasis and steroid hormone metabolism upon high-fat-diet feeding

PubMed Central

Purushotham, Aparna; Xu, Qing; Li, Xiaoling

2012-01-01

SIRT1 is a highly-conserved NAD+-dependent protein deacetylase that plays essential roles in the regulation of energy metabolism, genomic stability, and stress response. Although the functions of SIRT1 in many organs have been extensively studied in tissue-specific knockout mouse models, the systemic role of SIRT1 is still largely unknown as a result of severe developmental defects that result from whole-body knockout in mice. Here, we investigated the systemic functions of SIRT1 in metabolic homeostasis by utilizing a whole-body SIRT1 heterozygous mouse model. These mice are phenotypically normal under standard feeding conditions. However, when chronically challenged with a 40% fat diet, they become obese and insulin resistant, display increased serum cytokine levels, and develop hepatomegaly. Hepatic metabolomic analyses revealed that SIRT1 heterozygous mice have elevated gluconeogenesis and oxidative stress. Surprisingly, they are depleted of glycerolipid metabolites and free fatty acids, yet accumulate lysolipids. Moreover, high-fat feeding induces elevation of serum testosterone levels and enlargement of seminal vesicles in SIRT1 heterozygous males. Microarray analysis of liver mRNA indicates that they have altered expression of genes involved in steroid metabolism and glycerolipid metabolism. Taken together, our findings indicate that SIRT1 plays a vital role in the regulation of systemic energy and steroid hormone homeostasis.—Purushotham, A., Xu, Q., Li, X. Systemic SIRT1 insufficiency results in disruption of energy homeostasis and steroid hormone metabolism upon high-fat-diet feeding. PMID:22006157

Transgenic Wuzhishan minipigs designed to express a dominant-negative porcine growth hormone receptor display small stature and a perturbed insulin/IGF-1 pathway.

PubMed

Li, Feida; Li, Yong; Liu, Huan; Zhang, Xingju; Liu, Chuxin; Tian, Kai; Bolund, Lars; Dou, Hongwei; Yang, Wenxian; Yang, Huanming; Staunstrup, Nicklas Heine; Du, Yutao

2015-12-01

Growth hormone (GH) is an anabolic mitogen with widespread influence on cellular growth and differentiation as well as on glucose and lipid metabolism. GH binding to the growth hormone receptor (GHR) on hepatocytes prompts expression of insulin growth factor I (IGF-1) involved in nutritionally induced compensatory hyperplasia of pancreatic β-cell islets and insulin release. A prolonged hyperactivity of the IGF-1/insulin axis in the face of insulinotropic nutrition, on the other hand, can lead to collapse of the pancreatic islets and glucose intolerance. Individuals with Laron syndrome carry mutations in the GHR gene resulting in severe congenital IGF-1 deficiency and elevated GH serum levels leading to short stature as well as perturbed lipid and glucose metabolism. However, these individuals enjoy a reduced prevalence of acne, cancer and possibly diabetes. Minipigs have become important biomedical models for human conditions due to similarities in organ anatomy, physiology, and metabolism relative to humans. The purpose of this study was to generate transgenic Wuzhishan minipigs by handmade cloning with impaired systemic GHR activity and assess their growth profile and glucose metabolism. Transgenic minipigs featuring overexpression of a dominant-negative porcine GHR (GHR(dm)) presented postnatal growth retardation and proportionate dwarfism. Molecular changes included elevated GH serum levels and mild hyperglycemia. We believe that this model may prove valuable in the study of GH functions in relation to cancer, diabetes and longevity.

Syncytin-1, an endogenous retroviral protein, triggers the activation of CRP via TLR3 signal cascade in glial cells.

PubMed

Wang, Xiuling; Liu, Zhongchun; Wang, Peigang; Li, Shan; Zeng, Jie; Tu, Xiaoning; Yan, Qiujin; Xiao, Zheman; Pan, Mengxian; Zhu, Fan

2018-01-01

Schizophrenia is a devastating psychiatric disorder that impacts on social functioning and quality of life, and there is accumulating evidence that inflammation is a potential pathogenic mechanism of schizophrenia. However, the mechanism of inflammation possibly occurred in schizophrenia has not been well understood. The endogenous retroviral protein syncytin-1 and inflammatory marker CRP are both abnormally expressed in schizophrenia patients. CRP is one of the markers of bacterial infection generally. Less clear is whether virus or viral protein can trigger the activation of CRP. Here, we detected a robust increase of the levels of syncytin-1 and CRP in schizophrenia patients, and displayed a positive correlation and marked consistency between expressions of syncytin-1 and CRP in schizophrenia patients. Furthermore, overexpression of syncytin-1 significantly elevated the levels of CRP, TLR3, and IL-6 in both human microglia and astrocytes. TLR3 deficiency impaired the expressions of CRP and IL-6 induced by syncytin-1. Importantly, we observed a cellular co-localization and a direct interaction between syncytin-1 and TLR3. Additionally, knockdown of IL-6 inhibited the syncytin-1-induced CRP expression. Thus, the totality of these results showed that viral protein syncytin-1 could trigger the activation of CRP, which might explain the elevated CRP in sterile inflammation and exhibit a novel mechanism for regulation of inflammation by syncytin-1 in schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Modulation of intracellular Ca(2+) via alpha(1B)-adrenoreceptor signaling molecules, G alpha(h) (transglutaminase II) and phospholipase C-delta 1.

PubMed

Kang, Sung Koo; Kim, Dae Kyong; Damron, Derek S; Baek, Kwang Jin; Im, Mie-Jae

2002-04-26

We characterized the alpha(1B)-adrenoreceptor (alpha(1B)-AR)-mediated intracellular Ca(2+) signaling involving G alpha(h) (transglutaminase II, TGII) and phospholipase C (PLC)-delta 1 using DDT1-MF2 cell. Expression of wild-type TGII and a TGII mutant lacking transglutaminase activity resulted in significant increases in a rapid peak and a sustained level of intracellular Ca(2+) concentration ([Ca(2+)](i)) in response to activation of the alpha(1B)-AR. Expression of a TGII mutant lacking the interaction with the receptor or PLC-delta 1 substantially reduced both the peak and sustained levels of [Ca(2+)](i). Expression of TGII mutants lacking the interaction with PLC-delta 1 resulted in a reduced capacitative Ca(2+) entry. Reduced expression of PLC-delta 1 displayed a transient elevation of [Ca(2+)](i) and a reduction in capacitative Ca(2+) entry. Expression of the C2-domain of PLC-delta 1, which contains the TGII interaction site, resulted in reduction of the alpha(1B)-AR-evoked peak increase in [Ca(2+)](i), while the sustained elevation in [Ca(2+)](i) and capacitative Ca(2+) entry remained unchanged. These findings demonstrate that stimulation of PLC-delta 1 via coupling of the alpha(1B)-AR with TGII evokes both Ca(2+) release and capacitative Ca(2+) entry and that capacitative Ca(2+) entry is mediated by the interaction of TGII with PLC-delta 1.

Light induced intraspecific variability in response to thermal stress in the hard coral Stylophora pistillata

PubMed Central

Wijgerde, Tim; Dini-Andreote, Francisco; Eriksson, Britas Klemens; Salles, Joana Falcão; Pen, Ido; Wild, Christian

2017-01-01

Recent research suggests that prior exposure of several months to elevated irradiance induces enhanced thermal tolerance in scleractinian corals. While this tolerance has been reported at the species level, individual coral colonies may react differently due to individual variability in thermal tolerance. As thermal anomalies are predicted to become common in the upcoming future, intraspecific variation may be key to the survival of coral populations. In order to study light-history based thermal stress responses on individual colonies, we developed a preliminary microcosm experiment where three randomly chosen, aquacultured colonies of the model coral Stylophora pistillata were exposed to two irradiance treatments (200 and 400 μmol photons m−2 s−1) for 31 days, followed by artificially induced heat stress (∼33.4 °C). We found different responses to occur at both the intraspecific and the intracolonial levels, as indicated by either equal, less severe, delayed, and/or even non-necrotic responses of corals previously exposed to the irradiance of 400 compared to 200 μmol photons m−2 s−1. In addition, all individual colonies revealed light-enhanced calcification. Finally, elevated irradiance resulted in a lower chlorophyll a concentration in one colony compared to the control treatment, and the same colony displayed more rapid bleaching compared to the other ones. Taken together, this study highlights the potential importance of intra-individual variability in physiological responses of scleractinian corals and provides recommendations for improving methodological designs for future studies. PMID:29038747

Flowering responses of insect-pollinated plants to elevated CO{sub 2} levels

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

Cushman, J.H.; Koch, G.W.; Chiariello, N.R.

1995-06-01

Elevated atmospheric CO{sub 2} concentrations have been predicted or shown to substantially influence plants, communities and ecosystems in a variety of ways. Here, we examined the effects of elevated CO{sub 2} levels on the timing and magnitude of flowering for two insect-pollinated annual plant species in a serpentine grassland. We focused on Lasthenia californica and Linanthus parviflorus and addressed three questions: (1) Do elevated CO{sub 2} levels influence flowering phenologies and is this species specific? (2) Do elevated CO{sub 2} levels affect flower production and is this due to altered numbers of individuals, flowers per plant, or both? and (3)more » Are effects on flowering due to elevated CO{sub 2} levels per se or changes in environmental conditions associated with methods used to manipulate CO{sub 2} levels? To address these questions, we used the ecosystem experiment at Stanford University`s Jasper Ridge Biological Preserve (San Mateo Co., CA). This system consists of 20 open-topped chambers - half receiving ambient CO{sub 2} (360 ppm) and half receiving elevated CO{sub 2} (720 ppm) - and 10 untreated plots serving as chamber controls. Results from the 1994 season demonstrated that there were species-specific responses to elevated CO{sub 2} levels and the field chambers. For Lasthenia californica, elevated CO{sub 2} per se did not affect relative abundance, inflorescence production, or phenology, but chambers did significantly increase inflorescence production and extend the duration of flowering. For Linanthus parviflorus, elevated CO{sub 2} levels significantly increased relative abundance and flower production, and extended the flowering period slightly, while the chambers significantly decreased flower production early in the season and increased it later in the season.« less

Lidar-enhanced geologic mapping, examples from the Medford and Hood River areas, Oregon

NASA Astrophysics Data System (ADS)

Wiley, T. J.; McClaughry, J. D.

2012-12-01

Lidar-based 3-foot digital elevation models (DEMs) and derivatives (slopeshade, hillshade, contours) were used to help map geology across 1700 km2 (650 mi2) near Hood River and Medford, Oregon. Techniques classically applied to interpret coarse DEMs and small-scale topographic maps were adapted to take advantage of lidar's high resolution. Penetration and discrimination of plant cover by the laser system allowed recognition of fine patterns and textures related to underlying geologic units and associated soils. Surficial geologic maps were improved by the ability to examine tiny variations in elevation and slope. Recognition of low-relief features of all sizes was enhanced where pixel elevation ranges of centimeters to meters, established by knowledge of the site or by trial, were displayed using thousands of sequential colors. Features can also be depicted relative to stream level by preparing a DEM that compensates for gradient. Near Medford, lidar-derived contour maps with 1- to 3-foot intervals revealed incised bajada with young, distal lobes defined by concentric contour lines. Bedrock geologic maps were improved by recognizing geologic features associated with surface textures and patterns or topographic anomalies. In sedimentary and volcanic terrain, structure was revealed by outcrops or horizons lying at one stratigraphic level. Creating a triangulated irregular network (TIN) facet from positions of three or more such points gives strike and dip. Each map area benefited from hundreds of these measurements. A more extensive DEM in the plane of the TIN facet can be subtracted from surface elevation (lidar DEM) to make a DEM with elevation zero where the stratigraphic horizon lies at the surface. The distribution of higher and lower stratigraphic horizons can be shown by highlighting areas similarly higher or lower on the same DEM. Poor fit of contacts or faults projected between field traverses suggest the nature and amount of intervening geologic structure. Intrusive bodies were locally delimited by linear mounds where contact metamorphism hardened soft, fractured country rock. Bedrock faults were revealed where fault traces formed topographic anomalies or where topography associated with stratigraphic horizons or bedding-parallel textural fabrics was offset. This was important for identification of young faults and associated earthquake hazards. Previously unknown Holocene faults southwest of Hood River appear as subtle lineaments redirecting modern drainages or offsetting glacial moraines or glaciated bedrock. West of Medford, the presence young faulting was confirmed by elevation data that showed bedrock in the channel of the Rogue River at higher elevations below Gold Ray dam than in boreholes upstream. Such obscure structural features would have gone unrecognized using traditional topographic analysis or field reconnaissance. Fieldwork verified that lidar techniques improved our early geologic models, resolution of geologic features, and mapping of surficial and bedrock geology between traverses.

Experimental investigation of control/display augmentation effects in a compensatory tracking task

NASA Technical Reports Server (NTRS)

Garg, Sanjay; Schmidt, David K.

1988-01-01

The effects of control/display augmentation on human performance and workload have been investigated for closed-loop, continuous-tracking tasks by a real-time, man-in-the-loop simulation study. The experimental results obtained indicate that only limited improvement in actual tracking performance is obtainable through display augmentation alone; with a very high level of display augmentation, tracking error will actually deteriorate. Tracking performance improves when status information is furnished for reasonable levels of display quickening; again, very high quickening levels lead to tracking error deterioration due to the incompatibility between the status information and the quickened signal.

Wetland Accretion Rate Model of Ecosystem Resilience (WARMER) and its application to habitat sustainability for endangered species in the San Francisco Estuary

USGS Publications Warehouse

Swanson, Kathleen M.; Drexler, Judith Z.; Schoellhamer, David H.; Thorne, Karen M.; Casazza, Michael L.; Overton, Cory T.; Callaway, John C.; Takekawa, John Y.

2014-01-01

Salt marsh faunas are constrained by specific habitat requirements for marsh elevation relative to sea level and tidal range. As sea level rises, changes in relative elevation of the marsh plain will have differing impacts on the availability of habitat for marsh obligate species. The Wetland Accretion Rate Model for Ecosystem Resilience (WARMER) is a 1-D model of elevation that incorporates both biological and physical processes of vertical marsh accretion. Here, we use WARMER to evaluate changes in marsh surface elevation and the impact of these elevation changes on marsh habitat for specific species of concern. Model results were compared to elevation-based habitat criteria developed for marsh vegetation, the endangered California clapper rail (Rallus longirostris obsoletus), and the endangered salt marsh harvest mouse (Reithrodontomys raviventris) to determine the response of marsh habitat for each species to predicted >1-m sea-level rise by 2100. Feedback between vertical accretion mechanisms and elevation reduced the effect of initial elevation in the modeled scenarios. Elevation decreased nonlinearly with larger changes in elevation during the latter half of the century when the rate of sea-level rise increased. Model scenarios indicated that changes in elevation will degrade habitat quality within salt marshes in the San Francisco Estuary, and degradation will accelerate in the latter half of the century as the rate of sea-level rise accelerates. A sensitivity analysis of the model results showed that inorganic sediment accumulation and the rate of sea-level rise had the greatest influence over salt marsh sustainability.

Elevated Blood Lead Levels in Children Associated With the Flint Drinking Water Crisis: A Spatial Analysis of Risk and Public Health Response.

PubMed

Hanna-Attisha, Mona; LaChance, Jenny; Sadler, Richard Casey; Champney Schnepp, Allison

2016-02-01

We analyzed differences in pediatric elevated blood lead level incidence before and after Flint, Michigan, introduced a more corrosive water source into an aging water system without adequate corrosion control. We reviewed blood lead levels for children younger than 5 years before (2013) and after (2015) water source change in Greater Flint, Michigan. We assessed the percentage of elevated blood lead levels in both time periods, and identified geographical locations through spatial analysis. Incidence of elevated blood lead levels increased from 2.4% to 4.9% (P < .05) after water source change, and neighborhoods with the highest water lead levels experienced a 6.6% increase. No significant change was seen outside the city. Geospatial analysis identified disadvantaged neighborhoods as having the greatest elevated blood lead level increases and informed response prioritization during the now-declared public health emergency. The percentage of children with elevated blood lead levels increased after water source change, particularly in socioeconomically disadvantaged neighborhoods. Water is a growing source of childhood lead exposure because of aging infrastructure.

Elevated Blood Lead Levels in Children Associated With the Flint Drinking Water Crisis: A Spatial Analysis of Risk and Public Health Response

PubMed Central

LaChance, Jenny; Sadler, Richard Casey; Champney Schnepp, Allison

2016-01-01

Objectives. We analyzed differences in pediatric elevated blood lead level incidence before and after Flint, Michigan, introduced a more corrosive water source into an aging water system without adequate corrosion control. Methods. We reviewed blood lead levels for children younger than 5 years before (2013) and after (2015) water source change in Greater Flint, Michigan. We assessed the percentage of elevated blood lead levels in both time periods, and identified geographical locations through spatial analysis. Results. Incidence of elevated blood lead levels increased from 2.4% to 4.9% (P < .05) after water source change, and neighborhoods with the highest water lead levels experienced a 6.6% increase. No significant change was seen outside the city. Geospatial analysis identified disadvantaged neighborhoods as having the greatest elevated blood lead level increases and informed response prioritization during the now-declared public health emergency. Conclusions. The percentage of children with elevated blood lead levels increased after water source change, particularly in socioeconomically disadvantaged neighborhoods. Water is a growing source of childhood lead exposure because of aging infrastructure. PMID:26691115

Terrain Portrayal for Head-Down Displays Flight Test

NASA Technical Reports Server (NTRS)

Hughes, Monica F.; Glaab, Louis J.

2003-01-01

The Synthetic Vision Systems General Aviation (SVS-GA) element of NASA's Aviation Safety Program is developing technology to eliminate low visibility induced General Aviation (GA) accidents through the application of synthetic vision techniques. SVS displays present computer generated 3-dimensional imagery of the surrounding terrain to greatly enhance pilot's situation awareness (SA), reducing or eliminating Controlled Flight into Terrain (CFIT), as well as Low-Visibility Loss of Control (LVLOC) accidents. In addition to substantial safety benefits, SVS displays have many potential operational benefits that can lead to flight in instrument meteorological conditions (IMC) resembling those conducted in visual meteorological conditions (VMC). Potential benefits could include lower landing minimums, more approach options, reduced training time, etc. SVS conducted research will develop display concepts providing the pilot with an unobstructed view of the outside terrain, regardless of weather conditions and time of day. A critical component of SVS displays is the appropriate presentation of terrain to the pilot. The relationship between the realism of the terrain presentation and resulting enhancements of pilot SA and pilot performance has been largely undefined. Comprised of coordinated simulation and flight test efforts, the terrain portrayal for head-down displays (TP-HDD) test series examined the effects of two primary elements of terrain portrayal: variations of digital elevation model (DEM) resolution and terrain texturing. Variations in DEM resolution ranged from sparsely spaced (30 arc-sec/2,953ft) to very closely spaced data (1 arc-sec/98 ft). Variations in texture involved three primary methods: constant color, elevation-based generic, and photo-realistic, along with a secondary depth cue enhancer in the form of a fishnet grid overlay. The TP-HDD test series was designed to provide comprehensive data to enable design trades to optimize all SVS applications, as well as develop requirements and recommendations to facilitate the implementation and certification of SVS displays. The TP-HDD flight experiment utilized the NASA LaRC Cessna 206 Stationaire and evaluated eight terrain portrayal concepts in an effort to confirm and extend results from the previously conducted TP-HDD simulation experiment. A total of 15 evaluation pilots, of various qualifications, accumulated over 75 hours of dedicated research flight time at Newport News (PHF) and Roanoke (ROA), VA, airports from August through October, 2002. This report will present results from the portion of testing conducted at Roanoke, VA.

mTORC2 Promotes Tumorigenesis via Lipid Synthesis.

PubMed

Guri, Yakir; Colombi, Marco; Dazert, Eva; Hindupur, Sravanth K; Roszik, Jason; Moes, Suzette; Jenoe, Paul; Heim, Markus H; Riezman, Isabelle; Riezman, Howard; Hall, Michael N

2017-12-11

Dysregulated mammalian target of rapamycin (mTOR) promotes cancer, but underlying mechanisms are poorly understood. We describe an mTOR-driven mouse model that displays hepatosteatosis progressing to hepatocellular carcinoma (HCC). Longitudinal proteomic, lipidomics, and metabolomic analyses revealed that hepatic mTORC2 promotes de novo fatty acid and lipid synthesis, leading to steatosis and tumor development. In particular, mTORC2 stimulated sphingolipid (glucosylceramide) and glycerophospholipid (cardiolipin) synthesis. Inhibition of fatty acid or sphingolipid synthesis prevented tumor development, indicating a causal effect in tumorigenesis. Increased levels of cardiolipin were associated with tubular mitochondria and enhanced oxidative phosphorylation. Furthermore, increased lipogenesis correlated with elevated mTORC2 activity and HCC in human patients. Thus, mTORC2 promotes cancer via formation of lipids essential for growth and energy production. Copyright © 2017 Elsevier Inc. All rights reserved.

Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery.

PubMed

Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

2015-05-01

Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery.

Small-scale topography modulates elevational α-, β- and γ-diversity of Andean leaf beetles.

PubMed

Thormann, Birthe; Ahrens, Dirk; Espinosa, Carlos Iván; Armijos, Diego Marín; Wagner, Thomas; Wägele, Johann W; Peters, Marcell K

2018-05-01

Elevational diversity gradients are typically studied without considering the complex small-scale topography of large mountains, which generates habitats of strongly different environmental conditions within the same elevational zones. Here we analyzed the importance of small-scale topography for elevational diversity patterns of hyperdiverse tropical leaf beetles (Coleoptera: Chrysomelidae). We compared patterns of elevational diversity and species composition of beetles in two types of forests (on mountain ridges and in valleys) and analyzed whether differences in the rate of species turnover among forest habitats lead to shifts in patterns of elevational diversity when scaling up from the local study site to the elevational belt level. We sampled beetle assemblages at 36 sites in the Podocarpus National Park, Ecuador, which were equally distributed over two forest habitats and three elevational levels. DNA barcoding and Poisson tree processes modelling were used to delimitate putative species. On average, local leaf beetle diversity showed a clear hump-shaped pattern. However, only diversity in forests on mountain ridges peaked at mid-elevation, while beetle diversity in valleys was similarly high at low- and mid-elevation and only declined at highest elevations. A higher turnover of species assemblages at lower than at mid-elevations caused a shift from a hump-shaped diversity pattern found at the local level to a low-elevation plateau pattern (with similar species numbers at low and mid-elevation) at the elevational belt level. Our study reveals an important role of small-scale topography and spatial scale for the inference on gradients of elevational species diversity.

Comparison of 3D displays using objective metrics

NASA Astrophysics Data System (ADS)

Havig, Paul; McIntire, John; Dixon, Sharon; Moore, Jason; Reis, George

2008-04-01

Previously, we (Havig, Aleva, Reis, Moore, and McIntire, 2007) presented a taxonomy for the development of three-dimensional (3D) displays. We proposed three levels of metrics: objective (in which physical measurements are made of the display), subjective (Likert-type rating scales to show preferences of the display), and subjective-objective (performance metrics in which one shows how the 3D display may be more or less useful than a 2D display or a different 3D display). We concluded that for each level of metric, drawing practical comparisons among currently disparate 3D displays is difficult. In this paper we attempt to define more clearly the objective metrics for 3D displays. We set out to collect and measure physical attributes of several 3D displays and compare the results. We discuss our findings in terms of both difficulties in making the measurements in the first place, due to the physical set-up of the display, to issues in comparing the results we found and comparing how similar (or dissimilar) two 3D displays may or may not be. We conclude by discussing the next steps in creating objective metrics for three-dimensional displays as well as a proposed way ahead for the other two levels of metrics based on our findings.

Association between involuntary smoking and salivary markers related to periodontitis: a 2-year longitudinal study.

PubMed

Nishida, Nobuko; Yamamoto, Yumiko; Tanaka, Muneo; Kataoka, Kosuke; Kuboniwa, Masae; Nakayama, Kunio; Morimoto, Kanehisa; Shizukuishi, Satoshi

2008-12-01

Insufficient data exist regarding the longitudinal influence of involuntary smoking on periodontitis progression. This study examined the relationship between involuntary smoking and periodontitis progression and the effects of involuntary smoking on salivary inflammatory and microbiologic markers related to periodontitis. Participants were recruited during annual health checkups in 2003 and 2005. In 2005, 200 of 273 (73%) Japanese employees examined at baseline underwent periodontal measurements, including clinical attachment level (CAL) and probing depth (PD). Periodontitis progression was identified when a subject displayed one or more teeth with an increase > or = 2.0 mm in CAL and PD during the 2 years. Salivary marker levels, including cotinine, were determined by enzyme assay, including enzyme-linked immunosorbent assay. The proportions of six periodontal pathogens in saliva were assessed using real-time polymerase chain reaction methodology. Based on receiver-operating characteristic analysis, non-, involuntary, and active smokers were defined as subjects exhibiting salivary cotinine levels of 0, 1 to 7, and > or = 8 ng/ml, respectively. By simple logistic regression analysis, age, alcohol consumption, smoking, breakfast habits, and working hours were related to the risk for significant periodontitis progression. Multiple logistic regression analysis revealed significantly higher periodontitis odds ratios (OR) in involuntary (OR = 2.23; 95% confidence interval [CI]: 1.03 to 4.83) and active (OR = 2.27; 95% CI: 1.02 to 5.04) smokers relative to non-smokers following adjustment for covariates. Levels of salivary markers, including albumin, aspartate aminotransferase, and lactoferrin, were significantly elevated in involuntary smokers relative to non-smokers. In contrast, the percentages of periodontal pathogens did not differ between the smoking groups, with the exception of Prevotella nigrescens, which displayed significantly lower levels in involuntary smokers compared to non-smokers. Involuntary smoking increased the inflammatory response and was associated with a greater risk for periodontitis progression.

Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression.

PubMed

Verdonk, Koen; Saleh, Langeza; Lankhorst, Stephanie; Smilde, J E Ilse; van Ingen, Manon M; Garrelds, Ingrid M; Friesema, Edith C H; Russcher, Henk; van den Meiracker, Anton H; Visser, Willy; Danser, A H Jan

2015-06-01

Women with preeclampsia display low renin-angiotensin-aldosterone system activity and a high antiangiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor levels. To investigate whether renin-angiotensin-aldosterone system suppression in preeclampsia is because of this disturbed angiogenic balance, we measured mean arterial pressure, creatinine, endothelin-1 (ET-1), and renin-angiotensin-aldosterone system components in pregnant women with a high (≥85; n=38) or low (<85; n=65) soluble Fms-like tyrosine kinase-1/placental growth factor ratio. Plasma ET-1 levels were increased in women with a high ratio, whereas their plasma renin activity and plasma concentrations of renin, angiotensinogen, and aldosterone were decreased. Plasma renin activity-aldosterone relationships were identical in both the groups. Multiple regression analysis revealed that plasma renin concentration correlated independently with mean arterial pressure and plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine kinase-1 and negatively with plasma renin concentration, and urinary protein correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma levels of renin and angiotensinogen in the high-ratio group, their urinary levels of these components were elevated. Correction for albumin revealed that this was because of increased glomerular filtration. Subcutaneous arteries obtained from patients with preeclampsia displayed an enhanced, AT2 receptor-mediated response to angiotensin II. In conclusion, a high antiangiogenic state associates with ET-1 activation, which together with the increased mean arterial pressure may underlie the parallel reductions in renin and aldosterone in preeclampsia. Because ET-1 also was a major determinant of urinary protein, our data reveal a key role for ET-1 in the pathogenesis of preeclampsia. Finally, the enhanced angiotensin responsiveness in preeclampsia involves constrictor AT2 receptors. © 2015 American Heart Association, Inc.

Adiposity, Dysmetabolic Traits, and Earlier Onset of Female Puberty in Adolescent Offspring of Women With Gestational Diabetes Mellitus: A Clinical Study Within the Danish National Birth Cohort.

PubMed

Grunnet, Louise G; Hansen, Susanne; Hjort, Line; Madsen, Camilla M; Kampmann, Freja B; Thuesen, Anne Cathrine B; Granstrømi, Charlotta; Strøm, Marin; Maslova, Ekaterina; Frikke-Schmidt, Ruth; Damm, Peter; Chavarro, Jorge E; Hu, Frank B; Olsen, Sjurdur F; Vaag, Allan

2017-12-01

Offspring of pregnancies affected by gestational diabetes mellitus (GDM) are at increased risk of the development of type 2 diabetes. However, the extent to which these dysmetabolic traits may be due to offspring and/or maternal adiposity is unknown. We examined body composition and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring. We measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models. After adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart rate and lower height. Offspring of mothers with GDM had higher total and abdominal fat percentages and lower muscle mass percentages, but these differences disappeared after correction for offspring BMI. The offspring of mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained elevated in the offspring of mothers with GDM after correction for both maternal and offspring BMIs. In summary, adolescent offspring of women with GDM show increased adiposity, an adverse cardiometabolic profile, and earlier onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among the offspring of mothers with GDM may be explained by the programming effects of hyperglycemia in pregnancy. © 2017 by the American Diabetes Association.

Who Engages with Moral Beauty?

ERIC Educational Resources Information Center

Diessner, Rhett; Iyer, Ravi; Smith, Meghan M.; Haidt, Jonathan

2013-01-01

Aristotle considered moral beauty to be the "telos" of the human virtues. Displays of moral beauty have been shown to elicit the moral emotion of elevation and cause a desire to become a better person and to engage in prosocial behavior. Study 1 ("N" = 5380) shows engagement with moral beauty is related to several psychological…

Application of Thermal Infrared Multiband Scanner (TIMS) data to mapping of Plutonic and stratified rock and assemblages in accreted terrains of the Northern Sierra, California

NASA Technical Reports Server (NTRS)

Taranik, James V.; Davis, David; Borengasser, Marcus

1986-01-01

The Thermal Infrared Multispectral Scanner (TIMS) data were acquired over the Donner Pass area in California on September 12, 1985. The higher peaks in the area approach 9,200 feet in elevation, while the canyon of the north fork of the American River is only 3000 feet in elevation. The vegetation is dominated by conifers, although manzanita and other shrubs are present in areas where soils have developed. The data contain noise patterns which cut across scan lines diagonally. The TIMS data were analyzed using both photointerpretative and digital processing techniques. Preliminary image interpretation and field analysis confirmed that TIMS image data displays the chert units and silicic volcanics as bright red. The imagery appears to display zoning in the batholithic and hypabyssal intrusive rocks, although this was not field checked at this time. Rocks which appear to be more dioritic in composition appear purple on the imagery, while rocks more granitic in composition appear shades of red and pink. Areas that have more than 40% vegetative cover appear green on the imagery.

Consolidated ethanol production from Jerusalem artichoke tubers at elevated temperature by Saccharomyces cerevisiae engineered with inulinase expression through cell surface display.

PubMed

Khatun, M Mahfuza; Liu, Chen-Guang; Zhao, Xin-Qing; Yuan, Wen-Jie; Bai, Feng-Wu

2017-02-01

Ethanol fermentation from Jerusalem artichoke tubers was performed at elevated temperatures by the consolidated bioprocessing strategy using Saccharomyces cerevisiae MK01 expressing inulinase through cell surface display. No significant difference was observed in yeast growth when temperature was controlled at 38 and 40 °C, respectively, but inulinase activity with yeast cells was substantially enhanced at 40 °C. As a result, enzymatic hydrolysis of inulin was facilitated and ethanol production was improved with 89.3 g/L ethanol produced within 72 h from 198.2 g/L total inulin sugars consumed. Similar results were also observed in ethanol production from Jerusalem artichoke tubers with 85.2 g/L ethanol produced within 72 h from 185.7 g/L total sugars consumed. On the other hand, capital investment on cooling facilities and energy consumption for running the facilities would be saved, since regular cooling water instead of chill water could be used to cool down the fermentation system.

River stage influences on uranium transport in a hydrologically dynamic groundwater-surface water transition zone

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

Zachara, John M.; Chen, Xingyuan; Murray, Chris

In this study, a well-field within a uranium (U) plume in the groundwater-surface water transition zone was monitored for a 3 year period for water table elevation and dissolved solutes. The plume discharges to the Columbia River, which displays a dramatic spring stage surge resulting from snowmelt. Groundwater exhibits a low hydrologic gradient and chemical differences with river water. River water intrudes the site in spring. Specific aims were to assess the impacts of river intrusion on dissolved uranium (U aq), specific conductance (SpC), and other solutes, and to discriminate between transport, geochemical, and source term heterogeneity effects. Time seriesmore » trends for U aq and SpC were complex and displayed large temporal and well-to-well variability as a result of water table elevation fluctuations, river water intrusion, and changes in groundwater flow directions. The wells were clustered into subsets exhibiting common behaviors resulting from the intrusion dynamics of river water and the location of source terms. Hot-spots in U aq varied in location with increasing water table elevation through the combined effects of advection and source term location. Heuristic reactive transport modeling with PFLOTRAN demonstrated that mobilized U aq was transported between wells and source terms in complex trajectories, and was diluted as river water entered and exited the groundwater system. While U aq time-series concentration trends varied significantly from year-to-year as a result of climate-caused differences in the spring hydrograph, common and partly predictable response patterns were observed that were driven by water table elevation, and the extent and duration of river water intrusion.« less

River stage influences on uranium transport in a hydrologically dynamic groundwater-surface water transition zone: U TRANSPORT IN A GROUNDWATER-SURFACE WATER TRANSITION ZONE

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

Zachara, John M.; Chen, Xingyuan; Murray, Chris

A tightly spaced well-field within a groundwater uranium (U) plume in the groundwater-surface water transition zone was monitored for a three year period for groundwater elevation and dissolved solutes. The plume discharges to the Columbia River, which displays a dramatic spring stage surge resulting from mountain snowmelt. Groundwater exhibits a low hydrologic gradient and chemical differences with river water. River water intrudes the site in spring. Specific aims were to assess the impacts of river intrusion on dissolved uranium (Uaq), specific conductance (SpC), and other solutes, and to discriminate between transport, geochemical, and source term heterogeneity effects. Time series trendsmore » for Uaq and SpC were complex and displayed large temporal well-to well variability as a result of water table elevation fluctuations, river water intrusion, and changes in groundwater flow directions. The wells were clustered into subsets exhibiting common temporal behaviors resulting from the intrusion dynamics of river water and the location of source terms. Concentration hot spots were observed in groundwater that varied in location with increasing water table elevation. Heuristic reactive transport modeling with PFLOTRAN demonstrated that mobilized U was transported between wells and source terms in complex trajectories, and was diluted as river water entered and exited the groundwater system. While uranium time-series concentration trends varied significantly from year to year as a result of climate-caused differences in the spring hydrograph, common and partly predictable response patterns were observed that were driven by water table elevation, and the extent and duration of the river water intrusion event.« less

River stage influences on uranium transport in a hydrologically dynamic groundwater-surface water transition zone

DOE PAGES

Zachara, John M.; Chen, Xingyuan; Murray, Chris; ...

2016-03-04

In this study, a well-field within a uranium (U) plume in the groundwater-surface water transition zone was monitored for a 3 year period for water table elevation and dissolved solutes. The plume discharges to the Columbia River, which displays a dramatic spring stage surge resulting from snowmelt. Groundwater exhibits a low hydrologic gradient and chemical differences with river water. River water intrudes the site in spring. Specific aims were to assess the impacts of river intrusion on dissolved uranium (U aq), specific conductance (SpC), and other solutes, and to discriminate between transport, geochemical, and source term heterogeneity effects. Time seriesmore » trends for U aq and SpC were complex and displayed large temporal and well-to-well variability as a result of water table elevation fluctuations, river water intrusion, and changes in groundwater flow directions. The wells were clustered into subsets exhibiting common behaviors resulting from the intrusion dynamics of river water and the location of source terms. Hot-spots in U aq varied in location with increasing water table elevation through the combined effects of advection and source term location. Heuristic reactive transport modeling with PFLOTRAN demonstrated that mobilized U aq was transported between wells and source terms in complex trajectories, and was diluted as river water entered and exited the groundwater system. While U aq time-series concentration trends varied significantly from year-to-year as a result of climate-caused differences in the spring hydrograph, common and partly predictable response patterns were observed that were driven by water table elevation, and the extent and duration of river water intrusion.« less

Transabdominal ultrasound to assess pelvic floor muscle performance during abdominal curl in exercising women.

PubMed

Barton, Amanda; Serrao, Chloe; Thompson, Judith; Briffa, Kathy

2015-12-01

The aim of this study was to assess pelvic floor muscle (PFM) function using transabdominal ultrasound (TAUS) in women attending group exercise classes. Specific aims were to: (1) identify the ability to perform a correct elevating PFM contraction and (2) assess bladder-base movement during an abdominal curl exercise. Ninety women participating in group exercise were recruited to complete a survey and TAUS assessment performed by two qualified Continence and Women's Health physiotherapists with clinical experience in ultrasound scanning. The assessment comprised three attempts of a PFM contraction and an abdominal curl exercise in crook lying. Bladder-base displacement was measured to determine correct or incorrect activation patterns. Twenty-five percent (n = 23) of women were unable to demonstrate an elevating PFM contraction, and all women displayed bladder-base depression on abdominal curl (range 0.33-31.2 mm). Parous women displayed, on average, significantly more bladder-base depression than did nulliparous women [15.5 (7.3) mm vs 11.4 (5.8) mm, p < 0.009). Sixty percent (n = 54) reported stress urinary incontinence (SUI). There was no association between SUI and the inability to perform an elevating PFM contraction (p = 0.278) or the amount of bladder-base depression with abdominal curl [14.1 (7.6) mm SUI vs 14.2 (6.7) mm non-SUI]. TAUS identified that 25 % of women who participated in group exercise were unable to perform a correctly elevating PFM contraction, and all depressed the bladder-base on abdominal curl. Therefore, exercising women may be at risk of PFM dysfunction when performing abdominal curl activities.

A role for neuropeptide Y in the gender-specific gastrointestinal, corticosterone and feeding responses to stress.

PubMed

Forbes, S; Herzog, H; Cox, H M

2012-08-01

Exposure to an acute stress inhibits gastric emptying and stimulates colonic transit via central neuropeptide Y (NPY) pathways; however, peripheral involvement is uncertain. The anxiogenic phenotype of NPY(-/-) mice is gender-dependent, raising the possibility that stress-induced gastrointestinal (GI) responses are female-dominant through NPY. The aim of this study was to determine GI transit rates, corticosterone levels and food intake after acute restraint (AR) or novel environment (NE) stress in male and female NPY(-/-) and WT mice. Upper gastrointestinal transit (UGIT) (established 30 min after oral gavage) and corticosterone levels were determined under basal or restrained conditions (30 min) and after treatment i.p. with Y(1) antagonist BIBO3304 or Y(2) antagonist BIIE0246. Faecal pellet output (FPO) was established after AR and treatment i.p. with NPY in the NE, as were colonic bead expulsion rates. UGIT and FPO were similar in unrestrained male and female mice. NPY(-/-) females displayed significantly slower UGIT than NPY(-/-) males after AR, but both genders displayed significantly higher FPO and reduced food intake relative to WT counterparts. Peripheral NPY treatment increased bead expulsion time in WT mice. AR male NPY(-/-) mice had higher levels of corticosterone than male WT mice; whilst in AR WT mice, after peripheral Y(1) and Y(2) receptor antagonism in males, and Y(2) antagonism in females, corticosterone was significantly elevated. NPY possesses a role in the gender-dependent susceptibility to stress-induced GI responses. Furthermore, NPY inhibits GI motility through Y(2) receptors and corticosterone release via peripheral Y(1) and Y(2) receptors. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Mice overexpressing chemokine ligand 2 (CCL2) in astrocytes display enhanced nociceptive responses.

PubMed

Menetski, J; Mistry, S; Lu, M; Mudgett, J S; Ransohoff, R M; Demartino, J A; Macintyre, D E; Abbadie, C

2007-11-09

Recent findings demonstrate that chemokines, and more specifically CC chemokine ligand 2 (CCL2 or monocyte chemoattractant protein-1), play a major role in pain processing. In the present study, we assess nociceptive responses of mice that overexpressed CCL2 under control of glial fibrillary acidic protein promoter (CCL2 tg). In models of acute nociception CCL2 tg mice demonstrated significantly enhanced nociceptive behavior relative to wild-type controls in responses to both thermal (hot plate) and chemical (formalin test) stimulus modalities. There were no differences in mechanical allodynia in the partial sciatic nerve ligation model, in terms of either magnitude or duration of the allodynic response; however, both groups responded to the maximal extent measurable. In a model of inflammatory pain, elicited by intraplantar administration of complete Freund's adjuvant (CFA), CCL2 tg mice displayed both greater edema and thermal hyperalgesia compared with control mice. In control mice, edema and hyperalgesia returned to baseline values 5-7 days post CFA. However, in CCL2 tg mice, thermal hyperalgesia was significantly different from baseline up to 3 weeks post CFA. Parallel to these enhanced behavioral responses CCL2 serum levels were significantly greater in CCL2 overexpressing mice and remained elevated 7 days post CFA. Consequently, proinflammatory cytokine mRNA expression (IL-1beta, IL-6, and TNFalpha) levels were greater in skin, dorsal root ganglia (DRG), and spinal cord, whereas the anti-inflammatory cytokine (IL-10) level was lower in skin and DRG in CCL2 overexpressing mice than in control mice. Taken together with data from CCR2-deficient mice, these present data confirm a key role of CCL2/CCR2 axis in pain pathways and suggest that inhibiting this axis may result in novel pain therapies.

Beta-Actin Is Required for Proper Mouse Neural Crest Ontogeny

PubMed Central

Tondeleir, Davina; Noelanders, Rivka; Bakkali, Karima; Ampe, Christophe

2014-01-01

The mouse genome consists of six functional actin genes of which the expression patterns are temporally and spatially regulated during development and in the adult organism. Deletion of beta-actin in mouse is lethal during embryonic development, although there is compensatory expression of other actin isoforms. This suggests different isoform specific functions and, more in particular, an important function for beta-actin during early mammalian development. We here report a role for beta-actin during neural crest ontogeny. Although beta-actin null neural crest cells show expression of neural crest markers, less cells delaminate and their migration arrests shortly after. These phenotypes were associated with elevated apoptosis levels in neural crest cells, whereas proliferation levels were unchanged. Specifically the pre-migratory neural crest cells displayed higher levels of apoptosis, suggesting increased apoptosis in the neural tube accounts for the decreased amount of migrating neural crest cells seen in the beta-actin null embryos. These cells additionally displayed a lack of membrane bound N-cadherin and dramatic decrease in cadherin-11 expression which was more pronounced in the pre-migratory neural crest population, potentially indicating linkage between the cadherin-11 expression and apoptosis. By inhibiting ROCK ex vivo, the knockout neural crest cells regained migratory capacity and cadherin-11 expression was upregulated. We conclude that the presence of beta-actin is vital for survival, specifically of pre-migratory neural crest cells, their proper emigration from the neural tube and their subsequent migration. Furthermore, the absence of beta-actin affects cadherin-11 and N-cadherin function, which could partly be alleviated by ROCK inhibition, situating the Rho-ROCK signaling in a feedback loop with cadherin-11. PMID:24409333

Overexpression of a truncated CTF7 construct leads to pleiotropic defects in reproduction and vegetative growth in Arabidopsis.

PubMed

Liu, Desheng; Makaroff, Christopher A

2015-03-05

Eco1/Ctf7 is essential for the establishment of sister chromatid cohesion during S phase of the cell cycle. Inactivation of Ctf7/Eco1 leads to a lethal phenotype in most organisms. Altering Eco1/Ctf7 levels or point mutations in the gene can lead to alterations in nuclear division as well as a wide range of developmental defects. Inactivation of Arabidopsis CTF7 (AtCTF7) results in severe defects in reproduction and vegetative growth. To further investigate the function(s) of AtCTF7, a tagged version of AtCTF7 and several AtCTF7 deletion constructs were created and transformed into wild type or ctf7 +/- plants. Transgenic plants expressing 35S:NTAP:AtCTF7∆299-345 (AtCTF7∆B) displayed a wide range of phenotypic alterations in reproduction and vegetative growth. Male meiocytes exhibited chromosome fragmentation and uneven chromosome segregation. Mutant ovules contained abnormal megasporocyte-like cells during pre-meiosis, megaspores experienced elongated meiosis and megagametogenesis, and defective megaspores/embryo sacs were produced at various stages. The transgenic plants also exhibited a broad range of vegetative defects, including meristem disruption and dwarfism that were inherited in a non-Mendelian fashion. Transcripts for epigenetically regulated transposable elements (TEs) were elevated in transgenic plants. Transgenic plants expressing 35S:AtCTF7∆B displayed similar vegetative defects, suggesting the defects in 35S:NTAP:AtCTF7∆B plants are caused by high-level expression of AtCTF7∆B. High level expression of AtCTF7∆B disrupts megasporogenesis, megagametogenesis and male meiosis, as well as causing a broad range of vegetative defects, including dwarfism that are inherited in a non-Mendelian fashion.

Monocyte dysregulation and systemic inflammation during pediatric falciparum malaria

PubMed Central

Dobbs, Katherine R.; Embury, Paula; Odada, Peter S.; Rosa, Bruce A.; Mitreva, Makedonka; Kazura, James W.; Dent, Arlene E.

2017-01-01

BACKGROUND. Inflammation and monocytes are thought to be important to human malaria pathogenesis. However, the relationship of inflammation and various monocyte functions to acute malaria, recovery from acute malaria, and asymptomatic parasitemia in endemic populations is poorly understood. METHODS. We evaluated plasma cytokine levels, monocyte subsets, monocyte functional responses, and monocyte inflammatory transcriptional profiles of 1- to 10-year-old Kenyan children at the time of presentation with acute uncomplicated malaria and at recovery 6 weeks later; these results were compared with analogous data from asymptomatic children and adults in the same community. RESULTS. Acute malaria was marked by elevated levels of proinflammatory and regulatory cytokines and expansion of the inflammatory “intermediate” monocyte subset that returned to levels of healthy asymptomatic children 6 weeks later. Monocytes displayed activated phenotypes during acute malaria, with changes in surface expression of markers important to innate and adaptive immunity. Functionally, acute malaria monocytes and monocytes from asymptomatic infected children had impaired phagocytosis of P. falciparum–infected erythrocytes relative to asymptomatic children with no blood-stage infection. Monocytes from both acute malaria and recovery time points displayed strong and equivalent cytokine responsiveness to innate immune agonists that were independent of infection status. Monocyte transcriptional profiles revealed regulated and balanced proinflammatory and antiinflammatory and altered phagocytosis gene expression patterns distinct from malaria-naive monocytes. CONCLUSION. These observations provide insights into monocyte functions and the innate immune response during uncomplicated malaria and suggest that asymptomatic parasitemia in children is not clinically benign. FUNDING. Support for this work was provided by NIH/National Institute of Allergy and Infectious Diseases (R01AI095192-05), the Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene, and the Rainbow Babies & Children’s Foundation. PMID:28931756

Mortality associated with bilirubin levels in insurance applicants.

PubMed

Fulks, Michael; Stout, Robert L; Dolan, Vera F

2009-01-01

Determine the relationship between bilirubin levels with and without other liver function test (LFT) elevations and relative mortality in life insurance applicants. By use of the Social Security Death Master File mortality was determined in 1,905,664 insurance applicants for whom blood samples were submitted to the Clinical Reference Laboratory. There were 50,174 deaths observed in this study population. Results were stratified by 3 age/sex groups: females, age <60; males, age <60; and all, age 60+. The median follow-up was 12 years. Relative mortality increased as bilirubin decreased below bilirubin levels seen for the middle 50% of the population. The known association of smoking with lower bilirubin values explained only part of the additional elevated risk at low bilirubin levels. In the absence of other LFT elevations, relative mortality remained unchanged as bilirubin increased beyond levels seen for the middle 50% of the population. When a bilirubin elevation was combined with other LFT elevations, mortality further increased only at the highest elevations of other LFTs, seen only in <2.5% of applicants. Isolated elevations of bilirubin in this healthy screening population were not associated with excess mortality but values below the midpoint were. Other investigations have suggested a cardiovascular cause may underlie the excess mortality associated with low bilirubin. In association with other LFT elevations, bilirubin elevation further increases the mortality risk only at the highest elevations of other LFTs.

Hsp72 protects against liver injury via attenuation of hepatocellular death, oxidative stress, and JNK signaling.

PubMed

Levada, Kateryna; Guldiken, Nurdan; Zhang, Xiaoji; Vella, Giovanna; Mo, Fa-Rong; James, Laura P; Haybaeck, Johannes; Kessler, Sonja M; Kiemer, Alexandra K; Ott, Thomas; Hartmann, Daniel; Hüser, Norbert; Ziol, Marianne; Trautwein, Christian; Strnad, Pavel

2018-05-01

Heat shock protein (Hsp) 72 is a molecular chaperone that has broad cytoprotective functions and is upregulated in response to stress. To determine its hepatic functions, we studied its expression in human liver disorders and its biological significance in newly generated transgenic animals. Double transgenic mice overexpressing Hsp72 (gene Hspa1a) under the control of a tissue-specific tetracycline-inducible system (Hsp72-LAP mice) were produced. Acute liver injury was induced by a single injection of acetaminophen (APAP). Feeding with either a methionine choline-deficient (MCD; 8 weeks) or a 3,5-diethoxycarbonyl-1,4-dihydrocollidine-supplemented diet (DDC; 12 weeks) was used to induce lipotoxic injury and Mallory-Denk body (MDB) formation, respectively. Primary hepatocytes were treated with palmitic acid. Patients with non-alcoholic steatohepatitis and chronic hepatitis C infection displayed elevated HSP72 levels. These levels increased with the extent of hepatic inflammation and HSP72 expression was induced after treatment with either interleukin (IL)-1β or IL-6. Hsp72-LAP mice exhibited robust, hepatocyte-specific Hsp72 overexpression. Primary hepatocytes from these animals were more resistant to isolation-induced stress and Hsp72-LAP mice displayed lower levels of hepatic injury in vivo. Mice overexpressing Hsp72 had fewer APAP protein adducts and were protected from oxidative stress and APAP-/MCD-induced cell death. Hsp72-LAP mice and/or hepatocytes displayed significantly attenuated Jnk activation. Overexpression of Hsp72 did not affect steatosis or the extent of MDB formation. Our results demonstrate that HSP72 induction occurs in human liver disease, thus, HSP72 represents an attractive therapeutic target owing to its broad hepatoprotective functions. HSP72 constitutes a stress-inducible, protective protein. Our data demonstrate that it is upregulated in patients with chronic hepatitis C and non-alcoholic steatohepatitis. Moreover, Hsp72-overexpressing mice are protected from various forms of liver stress. Copyright © 2018 European Association for the Study of the Liver. All rights reserved.

Serum C-reactive protein (CRP) as a simple and independent prognostic factor in extranodal natural killer/T-cell lymphoma, nasal type.

PubMed

Li, Ya-Jun; Li, Zhi-Ming; Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi

2013-01-01

C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI.

Serum C-Reactive Protein (CRP) as a Simple and Independent Prognostic Factor in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

PubMed Central

Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi

2013-01-01

Background C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). Methods We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Results Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Conclusions Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI. PMID:23724031

Modeling tidal marsh distribution with sea-level rise: evaluating the role of vegetation, sediment, and upland habitat in marsh resiliency.

PubMed

Schile, Lisa M; Callaway, John C; Morris, James T; Stralberg, Diana; Parker, V Thomas; Kelly, Maggi

2014-01-01

Tidal marshes maintain elevation relative to sea level through accumulation of mineral and organic matter, yet this dynamic accumulation feedback mechanism has not been modeled widely in the context of accelerated sea-level rise. Uncertainties exist about tidal marsh resiliency to accelerated sea-level rise, reduced sediment supply, reduced plant productivity under increased inundation, and limited upland habitat for marsh migration. We examined marsh resiliency under these uncertainties using the Marsh Equilibrium Model, a mechanistic, elevation-based soil cohort model, using a rich data set of plant productivity and physical properties from sites across the estuarine salinity gradient. Four tidal marshes were chosen along this gradient: two islands and two with adjacent uplands. Varying century sea-level rise (52, 100, 165, 180 cm) and suspended sediment concentrations (100%, 50%, and 25% of current concentrations), we simulated marsh accretion across vegetated elevations for 100 years, applying the results to high spatial resolution digital elevation models to quantify potential changes in marsh distributions. At low rates of sea-level rise and mid-high sediment concentrations, all marshes maintained vegetated elevations indicative of mid/high marsh habitat. With century sea-level rise at 100 and 165 cm, marshes shifted to low marsh elevations; mid/high marsh elevations were found only in former uplands. At the highest century sea-level rise and lowest sediment concentrations, the island marshes became dominated by mudflat elevations. Under the same sediment concentrations, low salinity brackish marshes containing highly productive vegetation had slower elevation loss compared to more saline sites with lower productivity. A similar trend was documented when comparing against a marsh accretion model that did not model vegetation feedbacks. Elevation predictions using the Marsh Equilibrium Model highlight the importance of including vegetation responses to sea-level rise. These results also emphasize the importance of adjacent uplands for long-term marsh survival and incorporating such areas in conservation planning efforts.

Activation, Impaired Tumor Necrosis Factor-α Production, and Deficiency of Circulating Mucosal-Associated Invariant T Cells in Patients with Scrub Typhus.

PubMed

Kang, Seung-Ji; Jin, Hye-Mi; Won, Eun Jeong; Cho, Young-Nan; Jung, Hyun-Ju; Kwon, Yong-Soo; Kee, Hae Jin; Ju, Jae Kyun; Kim, Jung-Chul; Kim, Uh Jin; Jang, Hee-Chang; Jung, Sook-In; Kee, Seung-Jung; Park, Yong-Wook

2016-07-01

Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. However, little is known about the role of MAIT cells in Orientia tsutsugamushi infection. Hence, the aims of this study were to examine the level and function of MAIT cells in patients with scrub typhus and to evaluate the clinical relevance of MAIT cell levels. Thirty-eight patients with scrub typhus and 53 health control subjects were enrolled in the study. The patients were further divided into subgroups according to disease severity. MAIT cell level and function in the peripheral blood were measured by flow cytometry. Circulating MAIT cell levels were found to be significantly reduced in scrub typhus patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAT cell levels reflect disease severity. MAIT cells in scrub typhus patients displayed impaired tumor necrosis factor (TNF)-α production, which was restored during the remission phase. In addition, the impaired production of TNF-α by MAIT cells was associated with elevated CD69 expression. This study shows that circulating MAIT cells are activated, numerically deficient, and functionally impaired in TNF-α production in patients with scrub typhus. These abnormalities possibly contribute to immune system dysregulation in scrub typhus infection.

Application of Geographic Information System Methods to Identify Areas Yielding Water that will be Replaced by Water from the Colorado River in the Vidal and Chemehuevi Areas, California, and the Mohave Mesa Area, Arizona

USGS Publications Warehouse

Spangler, Lawrence E.; Angeroth, Cory E.; Walton, Sarah J.

2008-01-01

Relations between the elevation of the static water level in wells and the elevation of the accounting surface within the Colorado River aquifer in the vicinity of Vidal, California, the Chemehuevi Indian Reservation, California, and on Mohave Mesa, Arizona, were used to determine which wells outside the flood plain of the Colorado River are presumed to yield water that will be replaced by water from the Colorado River. Wells that have a static water-level elevation equal to or below the elevation of the accounting surface are presumed to yield water that will be replaced by water from the Colorado River. Geographic Information System (GIS) interpolation tools were used to produce maps of areas where water levels are above, below, and near (within ? 0.84 foot) the accounting surface. Calculated water-level elevations and interpolated accounting-surface elevations were determined for 33 wells in the vicinity of Vidal, 16 wells in the Chemehuevi area, and 35 wells on Mohave Mesa. Water-level measurements generally were taken in the last 10 years with steel and electrical tapes accurate to within hundredths of a foot. A Differential Global Positioning System (DGPS) was used to determine land-surface elevations to within an operational accuracy of ? 0.43 foot, resulting in calculated water-level elevations having a 95-percent confidence interval of ? 0.84 foot. In the Vidal area, differences in elevation between the accounting surface and measured water levels range from -2.7 feet below to as much as 17.6 feet above the accounting surface. Relative differences between the elevation of the water level and the elevation of the accounting surface decrease from west to east and from north to south. In the Chemehuevi area, differences in elevation range from -3.7 feet below to as much as 8.7 feet above the accounting surface, which is established at 449.6 feet in the vicinity of Lake Havasu. In all of the Mohave Mesa area, the water-level elevation is near or below the elevation of the accounting surface. Differences in elevation between water levels and the accounting surface range from -0.2 to -11.3 feet, with most values exceeding -7.0 feet. In general, the ArcGIS Triangulated Irregular Network (TIN) Contour and Natural Neighbor tools reasonably represent areas where the elevation of water levels in wells is above, below, and near (within ? 0.84 foot) the elevation of the accounting surface in the Vidal and Chemehuevi study areas and accurately delineate areas around outlying wells and where anomalies exist. The TIN Contour tool provides a strict linear interpolation while the Natural Neighbor tool provides a smoothed interpolation. Using the default options in ArcGIS, the Inverse Distance Weighted (IDW) and Spline tools also reasonably represent areas above, below, and near the accounting surface in the Vidal and Chemehuevi areas. However, spatial extent of and boundaries between areas above, below, and near the accounting surface vary among the GIS methods, which results largely from the fundamentally different mathematical approaches used by these tools. The limited number and spatial distribution of wells in comparison to the size of the areas, and the locations and relative differences in elevation between water levels and the accounting surface of wells with anomalous water levels also influence the contouring by each of these methods. Qualitatively, the Natural Neighbor tool appears to provide the best representation of the difference between water-level and accounting-surface elevations in the study areas, on the basis of available well data.

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China

PubMed Central

Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Background and Objective Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Methods Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels(≥14ng/L) and patients with normal hs-cTnT levels (<14ng/L). Results The final analysis involved 84 patients (31 males; mean age, 61.6±12.2years), of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028), and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Conclusion Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies. PMID:26849554

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China.

PubMed

Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within 1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels (≥14 ng/L) and patients with normal hs-cTnT levels (<14 ng/L). The final analysis involved 84 patients (31 males; mean age, 61.6±12.2 years), of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028), and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies.

High prevalence of elevated blood lead levels in both rural and urban Iowa newborns: Spatial patterns and area-level covariates

PubMed Central

Zahrieh, David; Young, Sean G.; Oleson, Jacob; Ryckman, Kelli K.; Wels, Brian; Simmons, Donald L.; Saftlas, Audrey

2017-01-01

Lead in maternal blood can cross the placenta and result in elevated blood lead levels in newborns, potentially producing negative effects on neurocognitive function, particularly if combined with childhood lead exposure. Little research exists, however, into the burden of elevated blood lead levels in newborns, or the places and populations in which elevated lead levels are observed in newborns, particularly in rural settings. Using ~2300 dried bloods spots collected within 1–3 days of birth among Iowa newborns, linked with the area of mother’s residence at the time of birth, we examine the spatial patterns of elevated (>5 μg/dL) blood lead levels and the ecological-level predictors of elevated blood lead levels. We find that one in five newborns exceed the 5 μg/dL action level set by the US Centers for Disease Control & Prevention (CDC). Bayesian spatial zero inflated regression indicates that elevated blood lead in newborns is associated with areas of increased pre-1940s housing and childbearing-age women with low educational status in both rural and urban settings. No differences in blood lead levels or the proportion of children exceeding 5 μg/dL are observed between urban and rural maternal residence, though a spatial cluster of elevated blood lead is observed in rural counties. These characteristics can guide the recommendation for testing of infants at well-baby appointments in places where risk factors are present, potentially leading to earlier initiation of case management. The findings also suggest that rural populations are at as great of risk of elevated blood lead levels as are urban populations. Analysis of newborn dried blood spots is an important tool for lead poisoning surveillance in newborns and can direct public health efforts towards specific places and populations where lead testing and case management will have the greatest impact. PMID:28520816

Human neuroblastoma SH-SY5Y cells show increased resistance to hyperthermic stress after differentiation, associated with elevated levels of Hsp72.

PubMed

Cheng, Lesley; Smith, Danielle J; Anderson, Robin L; Nagley, Phillip

2011-01-01

Terminally differentiated neurones in the central nervous system need to be protected from stress. We ask here whether differentiation of progenitor cells to neurones is accompanied by up-regulation of Hsp72, with acquisition of enhanced thermotolerance. Human neuroblastoma SH-SY5Y cells were propagated in an undifferentiated form and subsequently differentiated into neurone-like cells. Thermotolerance tests were carried out by exposure of cells to various temperatures, monitoring nuclear morphology as index of cell death. Abundance of Hsp72 was measured in cell lysates by western immunoblotting. The differentiation of SH-SY5Y cells was accompanied by increased expression of Hsp72. Further, in both cell states, exposure to mild hyperthermic stress (43°C for 30 min) increased Hsp72 expression. After differentiation, SH-SY5Y cells were more resistant to hyperthermic stress compared to their undifferentiated state, correlating with levels of Hsp72. Stable exogenous expression of Hsp72 in SH-SY5Y cells (transfected line 5YHSP72.1, containing mildly elevated levels of Hsp72), led to enhanced resistance to hyperthermic stress. Hsp72 was found to be inducible in undifferentiated 5YHSP72.1 cells; such heat-treated cells displayed enhanced thermotolerance. Treatment of cells with KNK437, a suppressor of Hsp72 induction, resulted in acute thermosensitisation of all cell types tested here. Hsp72 has a major role in the enhanced hyperthermic resistance acquired during neuronal differentiation of SH-SY5Y cells. These findings model the requirement in intact organisms for highly differentiated neurones to be specially protected against thermal stress.

Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice.

PubMed

Wieczorek, Lindsay; Fish, Eric W; O'Leary-Moore, Shonagh K; Parnell, Scott E; Sulik, Kathleen K

2015-05-01

The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparing biomarker responses during thermal acclimation: A lethal vs non-lethal approach in a tropical reef clownfish.

PubMed

Madeira, Carolina; Madeira, Diana; Diniz, Mário S; Cabral, Henrique N; Vinagre, Catarina

2017-02-01

Knowledge of thermal stress biology for most tropical fish species in reef ecosystems under climate change is still quite limited. Thus, the objective of this study was to measure the time-course changes of thermal stress biomarkers in the commercially exploited coral reef fish Amphiprion ocellaris, during a laboratory simulated event of increased temperature. Heat shock protein 70kDa (Hsp70) and total ubiquitin (Ub) were determined in the muscle (lethal method) and in the fin (non-lethal alternative method) under two temperature treatments (control - 26°C and elevated temperature - 30°C) throughout one month with weekly samplings. Results suggest that biomarker basal levels are tissue-specific and influence the degree of response under temperature exposure. Responses were highly inducible in the muscle but not in fin tissue, indicating that the latter is not reliable for monitoring purposes. Thermal stress was observed in the muscle after one week of exposure (both biomarkers increased significantly) and Ub levels then decreased, suggesting the animals were able to acclimate by maintaining high levels of Hsp70 and through an effective protein turnover. In addition, the results show that mortality rates did not differ between treatments. This indicates that A. ocellaris is capable of displaying a plastic response to elevated temperature by adjusting the protein quality control system to protect cell functions, without decreasing survival. Thus, this coral reef fish species presents a significant acclimation potential under ocean warming scenarios of +4°C. Monitoring of thermal stress through a non-lethal method, fin-clipping, although desirable proved to be inadequate for this species. Copyright © 2016 Elsevier Inc. All rights reserved.

Greater fear reactivity and psychophysiological hyperactivity among infants with later conduct problems and callous-unemotional traits

PubMed Central

Mills-Koonce, W. Roger; Wagner, Nicholas J.; Willoughby, Michael T.; Stifter, Cynthia; Blair, Clancy; Granger, Douglas A.

2014-01-01

Background Approximately one-third of children who meet criteria for conduct problems (CP) are also characterized by elevated callous-unemotional (CU) traits. This subgroup is at elevated risk for more pervasive and extreme levels of later antisocial behavior and has been characterized by a fearlessness temperament and blunted stress psychophysiology at older ages. The objective of this study is to examine group differences in fear reactivity and stress psychophysiology in infancy among children classified as having CP with CU (CP+CU), CP without CU (CP-only), or no CP in later childhood. Methods A birth cohort study (n = 1,292) was followed longitudinally from birth through 1st grade. Behavioral fear, baseline heart period (HP) and respiratory sinus arrhythmia (RSA), and pre-task, 20-min post-task and 40-min post-task salivary cortisol were assessed at 6 and 15 months of age around a fear challenge task. CP and CU were assessed by maternal report at 1st grade and children were classified into CP and CU groups if they scored in the upper 10th percentile of these ratings. Results No group differences were observed in children at 6 months of age. However, at 15 months of age children with later CP+CU displayed greater high-intensity fear behavior, higher pre-task and overall cortisol levels, and lower levels of HP and RSA compared to children with CP-only and children with no CP. Conclusions The discrepancy between the biobehavioral correlates of conduct problems with callous-unemotional traits in infancy and those reported from studies of older children and adults suggests that the etiology of this behavioral phenotype may be more complex than a simple genetic maturation model. PMID:24992385

Adaptive and Behavioral Changes in Kynurenine 3-Monooxygenase Knockout Mice: Relevance to Psychotic Disorders.

PubMed

Erhardt, Sophie; Pocivavsek, Ana; Repici, Mariaelena; Liu, Xi-Cong; Imbeault, Sophie; Maddison, Daniel C; Thomas, Marian A R; Smalley, Joshua L; Larsson, Markus K; Muchowski, Paul J; Giorgini, Flaviano; Schwarcz, Robert

2017-11-15

Kynurenine 3-monooxygenase converts kynurenine to 3-hydroxykynurenine, and its inhibition shunts the kynurenine pathway-which is implicated as dysfunctional in various psychiatric disorders-toward enhanced synthesis of kynurenic acid, an antagonist of both α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors. Possibly as a result of reduced kynurenine 3-monooxygenase activity, elevated central nervous system levels of kynurenic acid have been found in patients with psychotic disorders, including schizophrenia. In the present study, we investigated adaptive-and possibly regulatory-changes in mice with a targeted deletion of Kmo (Kmo -/- ) and characterized the kynurenine 3-monooxygenase-deficient mice using six behavioral assays relevant for the study of schizophrenia. Genome-wide differential gene expression analyses in the cerebral cortex and cerebellum of these mice identified a network of schizophrenia- and psychosis-related genes, with more pronounced alterations in cerebellar tissue. Kynurenic acid levels were also increased in these brain regions in Kmo -/- mice, with significantly higher levels in the cerebellum than in the cerebrum. Kmo -/- mice exhibited impairments in contextual memory and spent less time than did controls interacting with an unfamiliar mouse in a social interaction paradigm. The mutant animals displayed increased anxiety-like behavior in the elevated plus maze and in a light/dark box. After a D-amphetamine challenge (5 mg/kg, intraperitoneal), Kmo -/- mice showed potentiated horizontal activity in the open field paradigm. Taken together, these results demonstrate that the elimination of Kmo in mice is associated with multiple gene and functional alterations that appear to duplicate aspects of the psychopathology of several neuropsychiatric disorders. Copyright © 2016. Published by Elsevier Inc.

Adaptive and Behavioral Changes in Kynurenine 3-monooxygenase Knockout Mice: Relevance to Psychotic Disorders

PubMed Central

Erhardt, Sophie; Pocivavsek, Ana; Repici, Mariaelena; Liu, Xi-Cong; Imbeault, Sophie; Maddison, Daniel C; Thomas, Marian AR; Smalley, Joshua L; Larsson, Markus K; Muchowski, Paul J; Giorgini, Flaviano; Schwarcz, Robert

2018-01-01

BACKGROUND Kynurenine 3-monooxygenase (KMO) converts kynurenine to 3-hydroxykynurenine, and its inhibition shunts the kynurenine pathway - which is implicated as dysfunctional in various psychiatric disorders - towards enhanced synthesis of kynurenic acid (KYNA), an antagonist of both α7 nicotinic acetylcholine and NMDA receptors. Possibly as a result of reduced KMO activity, elevated central nervous system levels of KYNA have been found in patients with psychotic disorders, including schizophrenia (SZ). METHODS In the present study, we investigated adaptive – and possibly regulatory – changes in mice with a targeted deletion of Kmo (Kmo−/−) and characterized the KMO-deficient mice using six behavioral assays relevant for the study of SZ. RESULTS Genome-wide differential gene expression analyses in the cerebral cortex and cerebellum of these mice identified a network of SZ- and psychosis-related genes, with more pronounced alterations in cerebellar tissue. KYNA levels were also increased in these brain regions in Kmo−/− mice, with significantly higher levels in the cerebellum than in the cerebrum. Kmo−/− mice exhibited impairments in contextual memory and spent less time than controls interacting with an unfamiliar mouse in a social interaction paradigm. The mutant animals displayed increased anxiety-like behavior in the elevated plus maze and in a light-dark box. After a D-amphetamine challenge (5 mg/kg, i.p.), Kmo−/− mice showed potentiated horizontal activity in the open field paradigm. CONCLUSIONS Taken together, these results demonstrate that the elimination of Kmo in mice is associated with multiple gene and functional alterations that appear to duplicate aspects of the psychopathology of several neuropsychiatric disorders. PMID:28187857

Arabidopsis Histone Methylase CAU1/PRMT5/SKB1 Acts as an Epigenetic Suppressor of the Calcium Signaling Gene CAS to Mediate Stomatal Closure in Response to Extracellular Calcium[W

PubMed Central

Fu, Yan-Lei; Zhang, Guo-Bin; Lv, Xin-Fang; Guan, Yuan; Yi, Hong-Ying; Gong, Ji-Ming

2013-01-01

Elevations in extracellular calcium ([Ca2+]o) are known to stimulate cytosolic calcium ([Ca2+]cyt) oscillations to close stomata. However, the underlying mechanisms regulating this process remain largely to be determined. Here, through the functional characterization of the calcium underaccumulation mutant cau1, we report that the epigenetic regulation of CAS, a putative Ca2+ binding protein proposed to be an external Ca2+ sensor, is involved in this process. cau1 mutant plants display increased drought tolerance and stomatal closure. A mutation in CAU1 significantly increased the expression level of the calcium signaling gene CAS, and functional disruption of CAS abolished the enhanced drought tolerance and stomatal [Ca2+]o signaling in cau1. Map-based cloning revealed that CAU1 encodes the H4R3sme2 (for histone H4 Arg 3 with symmetric dimethylation)-type histone methylase protein arginine methytransferase5/Shk1 binding protein1. Chromatin immunoprecipitation assays showed that CAU1 binds to the CAS promoter and modulates the H4R3sme2-type histone methylation of the CAS chromatin. When exposed to elevated [Ca2+]o, the protein levels of CAU1 decreased and less CAU1 bound to the CAS promoter. In addition, the methylation level of H4R3sme2 decreased in the CAS chromatin. Together, these data suggest that in response to increases in [Ca2+]o, fewer CAU1 protein molecules bind to the CAS promoter, leading to decreased H4R3sme2 methylation and consequent derepression of the expression of CAS to mediate stomatal closure and drought tolerance. PMID:23943859

Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells

PubMed Central

Huff, Ryan D.; Hsu, Alan C-Y.; Nichol, Kristy S.; Jones, Bernadette; Knight, Darryl A.; Wark, Peter A. B.; Hansbro, Philip M.

2017-01-01

Introduction The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases. We therefore examined how airway epithelial cells regulate uric acid production. Materials and methods Allergen and cigarette smoke mouse models were performed using house dust mite (HDM) and cigarette smoke exposure, respectively, with outcome measurements of lung uric acid levels. Primary human airway epithelial cells isolated from clinically diagnosed patients with asthma and chronic obstructive pulmonary disease (COPD) were grown in submerged cultures and compared to age-matched healthy controls for uric acid release. HBEC-6KT cells, a human airway epithelial cell line, were grown under submerged monolayer conditions for mechanistic and gene expression studies. Results HDM, but not cigarette smoke exposure, stimulated uric acid production in vivo and in vitro. Primary human airway epithelial cells from asthma, but not COPD patients, displayed elevated levels of extracellular uric acid in culture. In HBEC-6KT, production of uric acid was sensitive to the xanthine dehydrogenase (XDH) inhibitor, allopurinol, and the ATP Binding Cassette C4 (ABCC4) inhibitor, MK-571. Lastly, the pro-inflammatory cytokine combination of TNF-α and IFN-γ elevated extracellular uric acid levels and XDH gene expression in HBEC-6KT cells. Conclusions Our results suggest that the active production of uric acid from human airway epithelial cells may be intrinsically altered in asthma and be further induced by pro-inflammatory cytokines. PMID:28863172

Creatine kinase elevation, lactacidemia, and metabolic myopathy in adult patients with diabetes mellitus.

PubMed

Frank, Marlies; Finsterer, Josef

2012-01-01

To determine the frequency of elevated creatine kinase (CK) levels among patients with diabetes mellitus and to determine how often elevated CK is attributable to primary myopathy. In this prospective study, we investigated how often CK, aspartate amino-transferase, alanine aminotransferase, and resting lactate were elevated among consecutive diabetic patients attending our clinic. Those with elevated CK values were offered a neurologic workup. Ninety-nine patients with diabetes mellitus, aged 19 to 87 years, were assessed between May 2008 and April 2010. Seven patients had type 1 diabetes and 92 patients had type 2 diabetes. CK, aspartate aminotransferase, alanine aminotransferase, and resting lactate were elevated in 19 of 99, 25 of 99, 22 of 99, and 24 of 98 patients, respectively. Eleven of 19 patients with increased CK were self-injecting insulin. Ten of 24 patients with elevated serum lactate took metformin. Seven of 19 patients with elevated CK consented to neurologic workup. Two of the 7 had elevated resting lactate. In all 7 patients, the findings from neurologic investigation were indicative of a metabolic defect and further diagnostic evaluation was recommended. In diabetic patients attending our clinic, elevated CK levels occur in one-fifth and lactacidemia occurs in one-quarter. Elevated CK levels are attributable to a primary metabolic myopathy in most cases. Elevated CK levels in the setting of diabetes mellitus require further neurologic evaluation.

Effects of environmental stress on mRNA expression levels of seven genes related to oxidative stress and growth in Atlantic salmon Salmo salar L. of farmed, hybrid and wild origin.

PubMed

Solberg, Monica F; Kvamme, Bjørn Olav; Nilsen, Frank; Glover, Kevin A

2012-12-05

Ten generations of domestication selection has caused farmed Atlantic salmon Salmo salar L. to deviate from wild salmon in a range of traits. Each year hundreds of thousands of farmed salmon escape into the wild. Thus, interbreeding between farmed escapees and wild conspecifics represents a significant threat to the genetic integrity of wild salmon populations. In a previous study we demonstrated how domestication has inadvertently selected for reduced responsiveness to stress in farmed salmon. To complement that study, we have evaluated the expression of seven stress-related genes in head kidney of salmon of farmed, hybrid and wild origin exposed to environmentally induced stress. In general, the crowding stressor used to induce environmental stress did not have a strong impact on mRNA expression levels of the seven genes, except for insulin-like growth factor-1 (IGF-1) that was downregulated in the stress treatment relative to the control treatment. mRNA expression levels of glutathione reductase (GR), Cu/Zn superoxide dismutase (Cu/Zn SOD), Mn superoxide dismutase (Mn SOD), glutathione peroxidase (GP) and IGF-1 were affected by genetic origin, thus expressed significantly different between the salmon of farmed, hybrid or wild origin. A positive relationship was detected between body size of wild salmon and mRNA expression level of the IGF-1 gene, in both environments. No such relationship was observed for the hybrid or farmed salmon. Farmed salmon in this study displayed significantly elevated mRNA levels of the IGF-1 gene relative to the wild salmon, in both treatments, while hybrids displayed a non additive pattern of inheritance. As IGF-1 mRNA levels are positively correlated to growth rate, the observed positive relationship between body size and IGF-1 mRNA levels detected in the wild but neither in the farmed nor the hybrid salmon, could indicate that growth selection has increased IGF-1 levels in farmed salmon to the extent that they may not be limiting growth rate.

Effects of environmental stress on mRNA expression levels of seven genes related to oxidative stress and growth in Atlantic salmon Salmo salar L. of farmed, hybrid and wild origin

PubMed Central

2012-01-01

Background Ten generations of domestication selection has caused farmed Atlantic salmon Salmo salar L. to deviate from wild salmon in a range of traits. Each year hundreds of thousands of farmed salmon escape into the wild. Thus, interbreeding between farmed escapees and wild conspecifics represents a significant threat to the genetic integrity of wild salmon populations. In a previous study we demonstrated how domestication has inadvertently selected for reduced responsiveness to stress in farmed salmon. To complement that study, we have evaluated the expression of seven stress-related genes in head kidney of salmon of farmed, hybrid and wild origin exposed to environmentally induced stress. Results In general, the crowding stressor used to induce environmental stress did not have a strong impact on mRNA expression levels of the seven genes, except for insulin-like growth factor-1 (IGF-1) that was downregulated in the stress treatment relative to the control treatment. mRNA expression levels of glutathione reductase (GR), Cu/Zn superoxide dismutase (Cu/Zn SOD), Mn superoxide dismutase (Mn SOD), glutathione peroxidase (GP) and IGF-1 were affected by genetic origin, thus expressed significantly different between the salmon of farmed, hybrid or wild origin. A positive relationship was detected between body size of wild salmon and mRNA expression level of the IGF-1 gene, in both environments. No such relationship was observed for the hybrid or farmed salmon. Conclusion Farmed salmon in this study displayed significantly elevated mRNA levels of the IGF-1 gene relative to the wild salmon, in both treatments, while hybrids displayed a non additive pattern of inheritance. As IGF-1 mRNA levels are positively correlated to growth rate, the observed positive relationship between body size and IGF-1 mRNA levels detected in the wild but neither in the farmed nor the hybrid salmon, could indicate that growth selection has increased IGF-1 levels in farmed salmon to the extent that they may not be limiting growth rate. PMID:23217180

Experimental Autoimmune Encephalomyelitis (EAE)-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1): Implications in Multiple Sclerosis (MS)-Induced Neurological Disability and Associated Myelin Damage.

PubMed

Khorshid Ahmad, Tina; Zhou, Ting; AlTaweel, Khaled; Cortes, Claudia; Lillico, Ryan; Lakowski, Ted Martin; Gozda, Kiana; Namaka, Michael Peter

2017-06-12

Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS) over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC) and active control (AC) animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC). The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG). Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC may arise from the elevated MeCP2E1 vs. MeCP2E2 ratio in the SC that creates a more hostile environment thereby preventing local BDNF production. At the level of transcript, we demonstrate that EAE-induces the pathological enhanced expression of MeCP2E1 that contributes to enhanced NDS during the entire disease course. Thus, the pathological induction of the MeCP2E1 isoform contributes to the disruption of the normal homeostatic signaling equilibrium network that exists between cytokines, neurotrophins and chemokines that regulate the myelin repair process by repressing BDNF. Our research suggests that the elevated ratio of MeCP2E1 relative to MeCP2E2 may be a useful diagnostic marker that clinicians can utilize to determine the degree of neurological disability with associated myelin damage. The elevated MeCP2E1 vs. MeCP2E2 ratios (E1/E2) in the SC prevent BDNF from reaching optimal levels required for myelin repair. Thus, the lower E1/E2 ratios in the DRG, allow the DRG to serve as a weak secondary compensatory mechanism for enhanced production and delivery of BDNF to the SC to try to assist in myelin repair.

Experimental Evidence for Hydrogen Tunneling when the Isotopic Arrhenius Prefactor (AH/AD) is Unity

PubMed Central

Sharma, Sudhir C.; Klinman, Judith P.

2009-01-01

The temperature dependence of the kinetic isotope effect (KIE) is one of the major tools used for the investigation of hydrogen tunneling in condensed phase. Hydrogen transfer reactions displaying isotopic Arrhenius prefactor ratios (AH/AD) of unity are generally ascribed to a semi-classical mechanism. Here, we have identified a double mutant of soybean lipoxygenase (SLO-1, an enzyme previously shown to follow quantum mechanical hydrogen tunneling), that displays an AH/AD of unity and highly elevated (non-classical) KIEs. This observation highlights the shortcoming of assigning a hydrogen transfer reaction to a semi-classical model based solely on an Arrhenius prefactor ratio. PMID:19061319

7. Photocopy of photograph (original print in possession of Mary ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. Photocopy of photograph (original print in possession of Mary Lane Knott, 508 Central Avenue, Ridgely MD 21660). Photographer and date unknown, Circa 1900. VIEW EAST, SOUTHWEST FRONT, NORTHWEST SIDE Front and side elevations. Note the duplication of the recessed store front with display windows. Note the break in the original clapboard siding toward the rear on the Northwest side and the new clapboard siding near the buggy. Near the buggy wheel an original brick pier. Note the panelling below the display windows and the penny gumball machine on the wall marked 'Adams Tutti-Frutti'. - 510 Central Avenue (Commercial Building), Ridgely, Caroline County, MD

Shortened estrous cycle length, increased FSH levels, FSH variance, oocyte spindle aberrations, and early declining fertility in aging senescence-accelerated mouse prone-8 (SAMP8) mice: concomitant characteristics of human midlife female reproductive aging.

PubMed

Bernstein, Lori R; Mackenzie, Amelia C L; Kraemer, Duane C; Morley, John E; Farr, Susan; Chaffin, Charles L; Merchenthaler, István

2014-06-01

Women experience a series of specific transitions in their reproductive function with age. Shortening of the menstrual cycle begins in the mid to late 30s and is regarded as the first sign of reproductive aging. Other early changes include elevation and increased variance of serum FSH levels, increased incidences of oocyte spindle aberrations and aneuploidy, and declining fertility. The goal of this study was to investigate whether the mouse strain senescence-accelerated mouse-prone-8 (SAMP8) is a suitable model for the study of these midlife reproductive aging characteristics. Midlife SAMP8 mice aged 6.5-7.85 months (midlife SAMP8) exhibited shortened estrous cycles compared with SAMP8 mice aged 2-3 months (young SAMP8, P = .0040). Midlife SAMP8 mice had high FSH levels compared with young SAMP8 mice, and mice with a single day of high FSH exhibited statistically elevated FSH throughout the cycle, ranging from 1.8- to 3.6-fold elevation on the days of proestrus, estrus, metestrus, and diestrus (P < .05). Midlife SAMP8 mice displayed more variance in FSH than young SAMP8 mice (P = .01). Midlife SAMP8 ovulated fewer oocytes (P = .0155). SAMP8 oocytes stained with fluorescently labeled antitubulin antibodies and scored in fluorescence microscopy exhibited increased incidence of meiotic spindle aberrations with age, from 2/126 (1.59%) in young SAMP8 to 38/139 (27.3%) in midlife SAMP8 (17.2-fold increase, P < .0001). Finally, SAMP8 exhibited declining fertility from 8.9 pups/litter in young SAMP8 to 3.5 pups/litter in midlife SAMP8 mice (P < .0001). The age at which these changes occur is younger than for most mouse strains, and their simultaneous occurrence within a single strain has not been described previously. We propose that SAMP8 mice are a model of midlife human female reproductive aging.

Plasma levels of soluble CD30 in kidney graft recipients as predictors of acute allograft rejection.

PubMed

Ayed, K; Abdallah, T B; Bardi, R; Abderrahim, E; Kheder, A

2006-09-01

In renal transplant recipients elevated soluble serum CD30 levels are associated with increased rejection and graft loss. We sought to determine the sCD30 plasma levels before and after kidney transplantation and to assess whether sCD30 was a predictive factor of immunological risk. sCD30 plasma levels were determined by an enzyme-linked immunosorbent assay assay in 52 kidney graft recipients before as well as 7, 15, and 21 days after transplantation. Eighteen patients developed acute allograft rejection (group I) and 34 patients showed uneventful courses (group II). Before transplantation sCD30 plasma levels were elevated in both groups (mean: 162.6 +/- 89.5 U/mL). After transplantation, group I recipients with acute rejection showed higher relative levels of plasma sCD30 on days 7 and 15 (120.8 +/- 74.6 U/mL and 210.6 +/- 108.7 U/mL respectively) compared with group II patients without rejection (95 +/- 45 U/mL and 59.4 +/- 31.6 U/mL), a difference that was significant for group I (P = .0003) and not significant for group II (P = .09). On day 21, sCD30 decreased in the two groups but remained higher among group I patients (120.6 +/- 92.7 U/mL). HLA antibodies were positive in 18 patients (34.6%) with 9 (50%) experiencing at last one episode of acute rejection. Among 34 patients negative for anti-HLA antibodies, nine displayed acute rejection only (26.4%), a difference that was not significant (P > .05). If we consider 100 U/mL as the minimum predictive level for allograft rejection, our results suggested that levels of sCD30 should be taken into consideration with the presence of HLA-antibodies detectable before and after transplantation, especially in patients with more than three HLA mismatches [RR = 3.20 (0.94 < RR < 10.91)]. These data suggested that measurement of plasma sCD30 is a useful procedure for the recognition of rejection in its earliest stages.

Sea-level Change during Hothouse, Cool Greenhouse, and Icehouse Worlds

NASA Astrophysics Data System (ADS)

Miller, K. G.; Browning, J. V.; Wright, J. D.

2015-12-01

Comparison of sea level and climate proxies shows fundamentally different causes and responses (periods, amplitudes, rates) for Myr scale sea-level changes in Hothouse, Cool Greenhouse, and Icehouse worlds. Peak warmth of the past 100 million years was achieved in the Hothouse intervals of the Cenomanian-Santonian (ca. 100-80 Ma) and early Eocene (56-50 Ma). Hothouse global average sea level falls of ~15 m are associated with d18O increases that reflect primarily high latitude cooling and may reflect the growth of small ice sheets in elevated regions of Antarctica. However, these purported Hothouse ice sheets are at or below the detection level of the d18O proxy (15 m ≤ 0.15‰), and it is possible that changes in groundwater storage ('limnoeustasy') could have caused these falls. Cool greenhouse (Campanian to Paleocene, middle to late Eocene) sea-level changes of 15-25 m were caused by growth and decay of small (25-35% of modern) ice sheets, pacing sea-level change on an apparent 2.4 Myr long eccentricity cycle, likely modulating 405 and 100 kyr cycles. Icehouse (past 33.8 Myr) sea-level and ice-volume changes were paced by the 1.2 Myr tilt cycle, with alternating states of 41 and 100 kyr dominance. Warm periods in the Icehouse displayed different sea-level responses. During the largely unipolar Icehouse of the Oligocene to early Miocene, the East Antarctic Ice Sheet (EAIS) was not permanently developed, with intervals of large-scale (~40-55 m sea level equivalent) growth and collapse. During peak warmth of the Miocene Climate Optimum (MCO; ~17-15 Ma) ice volume changes were small (generally <20 m) and paced by the 100 kyr cycle. A permanent EAIS developed following 3 middle Miocene d18O increases (14.7, 13.8, and 13.2 Ma) that were largely cooling events associated with <40 m sea-level falls; the subsequent late Miocene EAIS displayed lower amplitude (~20-30 m) sea-level variations. Despite only moderate atmospheric CO2 levels (400±50 ppm), during the peak warmth interval of the Pliocene, sea levels were only 22±10 m above present (most likely 12-22 m) requiring loss of Greenland, West Antarctica, and small part of EAIS (likely the Wilkes Basin).

Elevated CO2 levels affects the concentrations of copper and cadmium in crops grown in soil contaminated with heavy metals under fully open-air field conditions.

PubMed

Guo, Hongyan; Zhu, Jianguo; Zhou, Hui; Sun, Yuanyuan; Yin, Ying; Pei, Daping; Ji, Rong; Wu, Jichun; Wang, Xiaorong

2011-08-15

Elevated CO(2) levels and the increase in heavy metals in soils through pollution are serious problems worldwide. Whether elevated CO(2) levels will affect plants grown in heavy-metal-polluted soil and thereby influence food quality and safety is not clear. Using a free-air CO(2) enrichment (FACE) system, we investigated the impacts of elevated atmospheric CO(2) on the concentrations of copper (Cu) or cadmium (Cd) in rice and wheat grown in soil with different concentrations of the metals in the soil. In the two-year study, elevated CO(2) levels led to lower Cu concentrations and higher Cd concentrations in shoots and grain of both rice and wheat grown in the respective contaminated soil. Elevated CO(2) levels slightly but significantly lowered the pH of the soil and led to changes in Cu and Cd fractionation in the soil. Our study indicates that elevated CO(2) alters the distribution of contaminant elements in soil and plants, thereby probably affecting food quality and safety.

Prostate cancer stem-like cells proliferate slowly and resist etoposide-induced cytotoxicity via enhancing DNA damage response

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

Yan, Judy; Father Sean O'Sullivan Research Institute, Hamilton, Ontario, Canada L8N 4A6; The Hamilton Centre for Kidney Research

Despite the development of chemoresistance as a major concern in prostate cancer therapy, the underlying mechanisms remain elusive. In this report, we demonstrate that DU145-derived prostate cancer stem cells (PCSCs) progress slowly with more cells accumulating in the G1 phase in comparison to DU145 non-PCSCs. Consistent with the important role of the AKT pathway in promoting G1 progression, DU145 PCSCs were less sensitive to growth factor-induced activation of AKT in comparison to non-PCSCs. In response to etoposide (one of the most commonly used chemotherapeutic drugs), DU145 PCSCs survived significantly better than non-PCSCs. In addition to etoposide, PCSCs demonstrated increased resistancemore » to docetaxel, a taxane drug that is commonly used to treat castration-resistant prostate cancer. Etoposide produced elevated levels of γH2AX and triggered a robust G2/M arrest along with a coordinated reduction of the G1 population in PCSCs compared to non-PCSCs, suggesting that elevated γH2AX plays a role in the resistance of PCSCs to etoposide-induced cytotoxicity. We have generated xenograft tumors from DU145 PCSCs and non-PCSCs. Consistent with the knowledge that PCSCs produce xenograft tumors with more advanced features, we were able to demonstrate that PCSC-derived xenograft tumors displayed higher levels of γH2AX and p-CHK1 compared to non-PCSC-produced xenograft tumors. Collectively, our research suggests that the elevation of DNA damage response contributes to PCSC-associated resistance to genotoxic reagents. - Highlights: • Increased survival in DU145 PCSCs following etoposide-induced cytotoxicity. • PCSCs exhibit increased sensitivity to etoposide-induced DDR. • Resistance to cytotoxicity may be due to slower proliferation in PCSCs. • Reduced kinetics to growth factor induced activation of AKT in PCSCs.« less

Dysregulated Zn2+ homeostasis impairs cardiac type-2 ryanodine receptor and mitsugumin 23 functions, leading to sarcoplasmic reticulum Ca2+ leakage.

PubMed

Reilly-O'Donnell, Benedict; Robertson, Gavin B; Karumbi, Angela; McIntyre, Connor; Bal, Wojciech; Nishi, Miyuki; Takeshima, Hiroshi; Stewart, Alan J; Pitt, Samantha J

2017-08-11

Aberrant Zn 2+ homeostasis is associated with dysregulated intracellular Ca 2+ release, resulting in chronic heart failure. In the failing heart a small population of cardiac ryanodine receptors (RyR2) displays sub-conductance-state gating leading to Ca 2+ leakage from sarcoplasmic reticulum (SR) stores, which impairs cardiac contractility. Previous evidence suggests contribution of RyR2-independent Ca 2+ leakage through an uncharacterized mechanism. We sought to examine the role of Zn 2+ in shaping intracellular Ca 2+ release in cardiac muscle. Cardiac SR vesicles prepared from sheep or mouse ventricular tissue were incorporated into phospholipid bilayers under voltage-clamp conditions, and the direct action of Zn 2+ on RyR2 channel function was examined. Under diastolic conditions, the addition of pathophysiological concentrations of Zn 2+ (≥2 nm) caused dysregulated RyR2-channel openings. Our data also revealed that RyR2 channels are not the only SR Ca 2+ -permeable channels regulated by Zn 2+ Elevating the cytosolic Zn 2+ concentration to 1 nm increased the activity of the transmembrane protein mitsugumin 23 (MG23). The current amplitude of the MG23 full-open state was consistent with that previously reported for RyR2 sub-conductance gating, suggesting that in heart failure in which Zn 2+ levels are elevated, RyR2 channels do not gate in a sub-conductance state, but rather MG23-gating becomes more apparent. We also show that in H9C2 cells exposed to ischemic conditions, intracellular Zn 2+ levels are elevated, coinciding with increased MG23 expression. In conclusion, these data suggest that dysregulated Zn 2+ homeostasis alters the function of both RyR2 and MG23 and that both ion channels play a key role in diastolic SR Ca 2+ leakage. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of Dietary Iron Loading on Recognition Memory in Growing Rats

PubMed Central

Han, Murui; Kim, Jonghan

2015-01-01

While nutritional and neurobehavioral problems are associated with both iron deficiency during growth and overload in the elderly, the effect of iron loading in growing ages on neurobehavioral performance has not been fully explored. To characterize the role of dietary iron loading in memory function in the young, weanling rats were fed iron-loading diet (10,000 mg iron/kg diet) or iron-adequate control diet (50 mg/kg) for one month, during which a battery of behavioral tests were conducted. Iron-loaded rats displayed elevated non-heme iron levels in serum and liver, indicating a condition of systemic iron overload. In the brain, non-heme iron was elevated in the prefrontal cortex of iron-loaded rats compared with controls, whereas there was no difference in iron content in other brain regions between the two diet groups. While iron loading did not alter motor coordination or anxiety-like behavior, iron-loaded rats exhibited a better recognition memory, as represented by an increased novel object recognition index (22% increase from the reference value) than control rats (12% increase; P=0.047). Western blot analysis showed an up-regulation of dopamine receptor 1 in the prefrontal cortex from iron-loaded rats (142% increase; P=0.002). Furthermore, levels of glutamate receptors (both NMDA and AMPA) and nicotinic acetylcholine receptor (nAChR) were significantly elevated in the prefrontal cortex of iron-loaded rats (62% increase in NR1; 70% increase in Glu1A; 115% increase in nAChR). Dietary iron loading also increased the expression of NMDA receptors and nAChR in the hippocampus. These results support the idea that iron is essential for learning and memory and further reveal that iron supplementation during developmental and rapidly growing periods of life improves memory performance. Our investigation also demonstrates that both cholinergic and glutamatergic neurotransmission pathways are regulated by dietary iron and provides a molecular basis for the role of iron loading in improved memory. PMID:25746420

Cardio-Metabolic Effects of HIV Protease Inhibitors (Lopinavir/Ritonavir)

PubMed Central

Reyskens, Kathleen M. S. E.; Fisher, Tarryn-Lee; Schisler, Jonathan C.; O'Connor, Wendi G.; Rogers, Arlin B.; Willis, Monte S.; Planesse, Cynthia; Boyer, Florence; Rondeau, Philippe; Bourdon, Emmanuel; Essop, M. Faadiel

2013-01-01

Although antiretroviral treatment decreases HIV-AIDS morbidity/mortality, long-term side effects may include the onset of insulin resistance and cardiovascular diseases. However, the underlying molecular mechanisms responsible for highly active antiretroviral therapy (HAART)-induced cardio-metabolic effects are poorly understood. In light of this, we hypothesized that HIV protease inhibitor (PI) treatment (Lopinavir/Ritonavir) elevates myocardial oxidative stress and concomitantly inhibits the ubiquitin proteasome system (UPS), thereby attenuating cardiac function. Lopinavir/Ritonavir was dissolved in 1% ethanol (vehicle) and injected into mini-osmotic pumps that were surgically implanted into Wistar rats for 8 weeks vs. vehicle and sham controls. We subsequently evaluated metabolic parameters, gene/protein markers and heart function (ex vivo Langendorff perfusions). PI-treated rats exhibited increased serum LDL-cholesterol, higher tissue triglycerides (heart, liver), but no evidence of insulin resistance. In parallel, there was upregulation of hepatic gene expression, i.e. acetyl-CoA carboxylase β and 3-hydroxy-3-methylglutaryl-CoA-reductase, key regulators of fatty acid oxidation and cholesterol synthesis, respectively. PI-treated hearts displayed impaired cardiac contractile function together with attenuated UPS activity. However, there was no significant remodeling of hearts exposed to PIs, i.e. lack of ultrastructural changes, fibrosis, cardiac hypertrophic response, and oxidative stress. Western blot analysis of PI-treated hearts revealed that perturbed calcium handling may contribute to the PI-mediated contractile dysfunction. Here chronic PI administration led to elevated myocardial calcineurin, nuclear factor of activated T-cells 3 (NFAT3), connexin 43, and phosphorylated phospholamban, together with decreased calmodulin expression levels. This study demonstrates that early changes triggered by PI treatment include increased serum LDL-cholesterol levels together with attenuated cardiac function. Furthermore, PI exposure inhibits the myocardial UPS and leads to elevated calcineurin and connexin 43 expression that may be associated with the future onset of cardiac contractile dysfunction. PMID:24098634

Experimental Studies of Intent Information on Cockpit Traffic Displays

NASA Technical Reports Server (NTRS)

Barhydt, Richard; Hansman, R. John, Jr.

1997-01-01

Intent information provides knowledge of another aircraft's current and future trajectory states. Prototype traffic displays were designed for four different levels of intent: No Intent, Rate, Commanded State, and Flight Management System (FMS)-Path. The TCAS Display was used as a baseline and represents the No Intent Level. The Rate, Commanded State, and FMS-Path Displays show increasing levels of intent information using TCAS-like symbology in addition to incorporating a conflict probe and profile view display. An experiment was run on the MIT Part Task Flight Simulator in which eight airline pilots flew five traffic scenarios with each of the four displays. Results show that pilots had fewer separation violations and maneuvered earlier with the three intent displays. Separation violations were reduced when pilots maneuvered earlier. A second experiment was run to compare performance between displaying intent information directly and incorporating it into a conflict probe. A different set of eight airline pilots flew four traffic scenarios with the TCAS and Commanded State Displays with and without the conflict probe. Conflict probes with two minute and long range look-ahead times were tested. Displaying conflict bands or showing intent information directly both led to fewer separation violations and earlier avoidance maneuvers than the base TCAS Display. Performance was similar between the two minute and long range look-ahead conflict probes. Pilots preferred all intent displays over the TCAS Display.

Elevation trends and shrink-swell response of wetland soils to flooding and drying

USGS Publications Warehouse

Cahoon, Donald R.; Perez, Brian C.; Segura, Bradley D.; Lynch, James C.

2011-01-01

Given the potential for a projected acceleration in sea-level rise to impact wetland sustainability over the next century, a better understanding is needed of climate-related drivers that influence the processes controlling wetland elevation. Changes in local hydrology and groundwater conditions can cause short-term perturbations to marsh elevation trends through shrink—swell of marsh soils. To better understand the magnitude of these perturbations and their impacts on marsh elevation trends, we measured vertical accretion and elevation dynamics in microtidal marshes in Texas and Louisiana during and after the extreme drought conditions that existed there from 1998 to 2000. In a Louisiana marsh, elevation was controlled by subsurface hydrologic fluxes occurring below the root zone but above the 4 m depth (i.e., the base of the surface elevation table benchmark) that were related to regional drought and local meteorological conditions, with marsh elevation tracking water level variations closely. In Texas, a rapid decline in marsh elevation was related to severe drought conditions, which lowered local groundwater levels. Unfragmented marshes experienced smaller water level drawdowns and more rapid marsh elevation recovery than fragmented marshes. It appears that extended drawdowns lead to increased substrate consolidation making it less resilient to respond to future favorable conditions. Overall, changes in water storage lead to rapid and large short-term impacts on marsh elevation that are as much as five times greater than the long-term elevation trend, indicating the importance of long-term, high-resolution elevation data sets to understand the prolonged effects of water deficits on marsh elevation change.

A Complex Genomic Rearrangement Involving the Endothelin 3 Locus Causes Dermal Hyperpigmentation in the Chicken

PubMed Central

Dorshorst, Ben; Molin, Anna-Maja; Rubin, Carl-Johan; Johansson, Anna M.; Strömstedt, Lina; Pham, Manh-Hung; Chen, Chih-Feng; Hallböök, Finn; Ashwell, Chris; Andersson, Leif

2011-01-01

Dermal hyperpigmentation or Fibromelanosis (FM) is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the dominant FM allele results in extensive pigmentation of the dermal layer of skin and the majority of internal connective tissue. Here we identify the causal mutation of FM as an inverted duplication and junction of two genomic regions separated by more than 400 kb in wild-type individuals. One of these duplicated regions contains endothelin 3 (EDN3), a gene with a known role in promoting melanoblast proliferation. We show that EDN3 expression is increased in the developing Silkie embryo during the time in which melanoblasts are migrating, and elevated levels of expression are maintained in the adult skin tissue. We have examined four different chicken breeds from both Asia and Europe displaying dermal hyperpigmentation and conclude that the same structural variant underlies this phenotype in all chicken breeds. This complex genomic rearrangement causing a specific monogenic trait in the chicken illustrates how novel mutations with major phenotypic effects have been reused during breed formation in domestic animals. PMID:22216010

Leukocyte Bim deficiency does not impact atherogenesis in ldlr -/- mice, despite a pronounced induction of autoimmune inflammation.

PubMed

Temmerman, Lieve; Westra, Marijke M; Bot, Ilze; van Vlijmen, Bart J M; van Bree, Niek; Bot, Martine; Habets, Kim L L; Keulers, Tom G H; van der Vlag, Johan; Cotter, Thomas G; van Berkel, Theo J C; Biessen, Erik A L

2017-06-08

Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. As atherosclerosis is a chronic inflammatory process with features of autoimmune disease, we investigated the impact of hematopoietic Bim deficiency on plaque formation and parameters of plaque stability. Bim -/- or wild type bone marrow transplanted ldlr -/- mice were fed a Western type diet (WTD) for 5 or 10 weeks, after which they were immunophenotyped and atherosclerotic lesions were analyzed. Bim -/- transplanted mice displayed splenomegaly and overt lymphocytosis. CD4 + and CD8 + T cells were more activated (increased CD69 and CD71 expression, increased interferon gamma production). B cells were elevated by 147%, with a shift towards the pro-atherogenic IgG-producing B2 cell phenotype, resulting in a doubling of anti-oxLDL IgG1 antibody titers in serum of bim -/- mice. Bim -/- mice displayed massive intraplaque accumulation of Ig complexes and of lesional T cells, although this did not translate in changes in plaque size or stability features (apoptotic cell and macrophage content). The surprising lack in plaque phenotype despite the profound pro-atherogenic immune effects may be attributable to the sharp reduction of serum cholesterol levels in WTD fed bim -/- mice.

Role for the satiety factor Oleoylethanolamide in alcoholism

PubMed Central

Bilbao, Ainhoa; Serrano, Antonia; Cippitelli, Andrea; Pavón, Francisco J.; Giuffrida, Andrea; Suárez, Juan; García-Marchena, Nuria; Baixeras, Elena; de Heras, Raquel Gomez; Ciccocioppo, Roberto; Cravatt, Benjamin F.; Parsons, Loren H.; Piomelli, Daniele; de Fonseca, Fernando Rodríguez

2015-01-01

Oleoylethanolamide (OEA) is a satiety factor released by the gut that controls motivational responses for caloric foods. Here, using both, rat and mice models, we determined that the administration of alcohol releases OEA that, by engaging peroxisome proliferator-activated receptor alpha (PPARα), reduces alcohol consumption. Animals lacking FAAH, the enzyme that degrades OEA, accumulates this lipid in response to ethanol and displayed reduced alcohol preference. Pharmacological administration of OEA reduced operant alcohol self-administration via a peripheral mechanism, since this effect was abrogated by chemical deafferentation with capsaicin. Intracerebral injection of PPARα agonists did not affect alcohol self-administration. OEA also abolished both, cue-induced reinstatement of alcohol self-administration and the enhancement of alcohol consumption induced by a period of alcohol deprivation, suggesting a role for OEA on alcohol relapse. In addition, animals fed with a liquid diet containing 10% alcohol displayed elevated plasma levels of OEA that decreases upon removal of alcohol in the diet. This decrease paralleled the onset of alcohol withdrawal (AWD) symptoms and the administration of OEA reduced the severity of AWD. Finally, OEA, by inhibiting the expression of lipogenic enzymes, reduces chronic alcohol-induced liver steatosis, an effect not observed in PPARα-deficient mice. These results link OEA to the homeostatic adaption to alcohol and opens new opportunities for the treatment of alcoholism. PMID:26037332

Integrin beta 1 inhibition alleviates the chronic hyperproliferative dermatitis phenotype of SHARPIN-deficient mice.

PubMed

Peuhu, Emilia; Salomaa, Siiri I; De Franceschi, Nicola; Potter, Christopher S; Sundberg, John P; Pouwels, Jeroen

2017-01-01

SHARPIN (Shank-Associated RH Domain-Interacting Protein) is a component of the linear ubiquitin chain assembly complex (LUBAC), which enhances TNF-induced NF-κB activity. SHARPIN-deficient (Sharpincpdm/cpdm) mice display multi-organ inflammation and chronic proliferative dermatitis (cpdm) due to TNF-induced keratinocyte apoptosis. In cells, SHARPIN also inhibits integrins independently of LUBAC, but it has remained enigmatic whether elevated integrin activity levels in the dermis of Sharpincpdm/cpdm mice is due to increased integrin activity or is secondary to inflammation. In addition, the functional contribution of increased integrin activation to the Sharpincpdm/cpdm phenotype has not been investigated. Here, we find increased integrin activity in keratinocytes from Tnfr1-/- Sharpincpdm/cpdm double knockout mice, which do not display chronic inflammation or proliferative dermatitis, thus suggesting that SHARPIN indeed acts as an integrin inhibitor in vivo. In addition, we present evidence for a functional contribution of integrin activity to the Sharpincpdm/cpdm skin phenotype. Treatment with an integrin beta 1 function blocking antibody reduced epidermal hyperproliferation and epidermal thickness in Sharpincpdm/cpdm mice. Our data indicate that, while TNF-induced cell death triggers the chronic inflammation and proliferative dermatitis, absence of SHARPIN-dependent integrin inhibition exacerbates the epidermal hyperproliferation in Sharpincpdm/cpdm mice.

[Prevalence of Elevated Lipoprotein (a) Levels in Patients < 60 Years of Age with Retinal Vein Occlusion].

PubMed

Kuhli-Hattenbach, C; Hellstern, P; Miesbach, W; Kohnen, T; Hattenbach, L-O

2018-01-01

The potential impact of elevated Lipoprotein (a) [Lp(a)] levels on retinal venous occlusive (RVO) diseases with regard to age and various risk factors has not been studied extensively. In a retrospective case-control study, thrombophilia data of 106 young patients (< 60 years at the time of the RVO or a previous thromboembolic event) with RVO and 76 healthy subjects were evaluated. Elevated Lp(a) plasma levels were significantly more prevalent among RVO patients (29.2 %) than among controls (9.2 %; p = 0.0009). Lp(a) levels were found to be significantly (p = 0.012) different between patients and controls. Moreover, we found that an unusual personal or family history of thromboembolism was a strong predictor of elevated Lp(a) (p = 0.03). We observed a significant correlation between elevated Lp(a) and other coagulation disorders (p = 0.005). Multivariate analysis showed that elevated lipoprotein(a) levels (OR: 3.5; p = 0.003) were an independent risk factor for the development of RVO. Elevated plasma levels of Lp(a) are associated with the development of RVO. Selective screening of young patients and subjects with a personal or family history of thromboembolism may be helpful in identifying RVO patients with elevated Lp(a). Georg Thieme Verlag KG Stuttgart · New York.

The Effect of Chronic Arsenic Exposure in Zebrafish

PubMed Central

Hallauer, Janell; Geng, Xiangrong; Yang, Hung-Chi; Shen, Jian; Tsai, Kan-Jen

2016-01-01

Abstract Arsenic is a prevalent environmental toxin and a Group one human carcinogenic agent. Chronic arsenic exposure has been associated with many human diseases. The aim of this study is to evaluate zebrafish as an animal model to assess arsenic toxicity in elevated long-term arsenic exposure. With prolonged exposure (6 months) to various concentrations of arsenic from 50 ppb to 300 ppb, effects of arsenic accumulation in zebrafish tissues, and phenotypes were investigated. Results showed that there are no significant changes of arsenic retention in zebrafish tissues, and zebrafish did not exhibit any visible tumor formation under arsenic exposure conditions. However, the zebrafish demonstrate a dysfunction in their neurological system, which is reflected by a reduction of locomotive activity. Moreover, elevated levels of the superoxide dismutase (SOD2) protein were detected in the eye and liver, suggesting increased oxidative stress. In addition, the progenies of arsenic-treated parents displayed a smaller biomass (four-fold reduction in body weight) compared with those from their parental controls. This result indicates that arsenic may induce genetic or epigenetic changes that are then passed on to the next generation. Overall, this study demonstrates that zebrafish is a convenient vertebrate model with advantages in the evaluation of arsenic-associated neurological disorders as well as its influences on the offspring. PMID:27140519

SUMO1 Affects Synaptic Function, Spine Density and Memory

PubMed Central

Matsuzaki, Shinsuke; Lee, Linda; Knock, Erin; Srikumar, Tharan; Sakurai, Mikako; Hazrati, Lili-Naz; Katayama, Taiichi; Staniszewski, Agnieszka; Raught, Brian; Arancio, Ottavio; Fraser, Paul E.

2015-01-01

Small ubiquitin-like modifier-1 (SUMO1) plays a number of roles in cellular events and recent evidence has given momentum for its contributions to neuronal development and function. Here, we have generated a SUMO1 transgenic mouse model with exclusive overexpression in neurons in an effort to identify in vivo conjugation targets and the functional consequences of their SUMOylation. A high-expressing line was examined which displayed elevated levels of mono-SUMO1 and increased high molecular weight conjugates in all brain regions. Immunoprecipitation of SUMOylated proteins from total brain extract and proteomic analysis revealed ~95 candidate proteins from a variety of functional classes, including a number of synaptic and cytoskeletal proteins. SUMO1 modification of synaptotagmin-1 was found to be elevated as compared to non-transgenic mice. This observation was associated with an age-dependent reduction in basal synaptic transmission and impaired presynaptic function as shown by altered paired pulse facilitation, as well as a decrease in spine density. The changes in neuronal function and morphology were also associated with a specific impairment in learning and memory while other behavioral features remained unchanged. These findings point to a significant contribution of SUMO1 modification on neuronal function which may have implications for mechanisms involved in mental retardation and neurodegeneration. PMID:26022678

A latent profile analysis of childhood trauma in women with bulimia nervosa: Associations with borderline personality disorder psychopathology.

PubMed

Utzinger, Linsey M; Haukebo, Justine E; Simonich, Heather; Wonderlich, Stephen A; Cao, Li; Lavender, Jason M; Mitchell, James E; Engel, Scott G; Crosby, Ross D

2016-07-01

The aim of this study was to empirically examine naturally occurring groups of individuals with bulimia nervosa (BN) based on their childhood trauma (CT) histories and to compare these groups on a clinically relevant external validator, borderline personality disorder (BPD) psychopathology. This study examined the relationship between CT and BPD psychopathology among 133 women with BN using latent profile analysis (LPA) to classify participants based on histories of CT. Participants completed the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P), the Diagnostic Interview for Borderlines-Revised (DIB-R), and the Childhood Trauma Questionnaire (CTQ). The LPA revealed four trauma profiles: low/no trauma, emotional trauma, sexual trauma, and polytrauma. Results indicated that the sexual and polytrauma profiles displayed significantly elevated scores on the DIB-R and that the low/no and emotional trauma profiles did not differ significantly on the DIB-R. Secondary analyses revealed elevated levels of a composite CT score among those with both BN and BPD psychopathology compared to those with BN only. These findings suggest that both childhood sexual abuse and the additive effects of childhood polytrauma may be linked to BPD psychopathology in BN. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:689-694). © 2016 Wiley Periodicals, Inc.

Selenium and mercury have a synergistic negative effect on fish reproduction.

PubMed

Penglase, S; Hamre, K; Ellingsen, S

2014-04-01

Selenium (Se) can reduce the negative impacts of mercury (Hg) toxicity on growth and survival, but little is known about how these two elements interact in reproduction. In the following study we explored the effects of organic Hg and Se on the growth, survival and reproduction of female zebrafish (Danio rerio). Fish were fed one of four diets from 73 until 226 dpf in a 2 × 2 factorial design, using selenomethionine (SeMet) and methylmercury (MeHg) as the Se and Hg sources, respectively. Each diet contained Se at either requirement (0.7 mg Se/kg DM) or elevated levels (10 mg Se/kgDM), and Hg at either low (0.05 mg Hg/kg DM) or elevated (12 mg Hg/kg DM) levels. Between 151 and 206 dpf the female fish were pairwise crossed against untreated male fish and the mating success, fecundity, embryo survival, and subsequent overall reproductive success were measured. Elevated dietary Se reduced Hg levels in both the adult fish and their eggs. Elevated dietary Hg and Se increased egg Se levels to a greater extent than when dietary Se was elevated alone. At elevated maternal intake levels, egg concentrations of Se and Hg reflected the maternal dietary levels and not the body burdens of the adult fish. Elevated dietary Hg reduced the growth and survival of female fish, but these effects were largely prevented with elevated dietary Se. Elevated dietary Se alone did not affect fish growth or survival. Compared to other treatments, elevated dietary Hg alone increased both mating and overall reproductive success with <100 days of exposure, but decreased these parameters with >100 days exposure. Elevated dietary Se decreased fecundity, embryo survival, and overall reproductive success. The combination of elevated Se and Hg had a synergistic negative effect on all aspects of fish reproduction compared to those groups fed elevated levels of either Se or Hg. Overall the data demonstrate that while increased dietary Se may reduce adverse effects of Hg on the growth and survival in adult fish, it can negatively affect fish reproductive potential, and the effect on reproduction is enhanced in the presence of elevated Hg. Copyright © 2014 Elsevier B.V. All rights reserved.

Serum biochemical markers in lung cancer.

PubMed Central

Burt, R. W.; Ratcliffe, J. G.; Stack, B. H.; Cuthbert, J.; Kennedy, R. S.; Corker, C. S.; Franchimont, P.; Spilg, W. G.; Stimson, W. H.

1978-01-01

The prevalence of elevated serum levels of 5 potential tumour-associated antigens was determined in patients with lung cancer sampled at the time of initial presentation, using age- and sex-matched patients with benign lung disease as controls. Elevated levels (greater than upper 95th centile of controls) were found as follows: carcinoembryonic antigen (CEA), 17%; pregnancy-associated alpha-macroglobulin (PAM), 16%; casein 14%; human chorionic gonadotrophin (HCG) 6%; alpha-foetoprotein (AFP), 1.5%. The prevalence of elevated CEA levels (but not other markers) was higher in patients with evidence of extra-thoracic tumour spread (23%) mainly due to anaplastic tumours and adenocarcinomas. A degree of concordance of elevated marker levels occurred with CEA, HCG, casein and AFP, but there was a striking discordance of elevated CEA and PAM levels. Simultaneous assays of CEA and PAM will detect the majority of patients with elevations of any of the markers studied, and are likely to be the most useful biochemical markers in following the response of lung tumours to therapy. PMID:77672

14 CFR 23.1311 - Electronic display instrument systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Electronic display instrument systems. 23... Equipment Instruments: Installation § 23.1311 Electronic display instrument systems. (a) Electronic display..., considering the expected electronic display brightness level at the end of an electronic display indictor's...

14 CFR 23.1311 - Electronic display instrument systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Electronic display instrument systems. 23... Equipment Instruments: Installation § 23.1311 Electronic display instrument systems. (a) Electronic display..., considering the expected electronic display brightness level at the end of an electronic display indictor's...

14 CFR 23.1311 - Electronic display instrument systems.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Electronic display instrument systems. 23... Equipment Instruments: Installation § 23.1311 Electronic display instrument systems. (a) Electronic display..., considering the expected electronic display brightness level at the end of an electronic display indictor's...

Willing and Able: The Coordination between Sexual Displays and Fertility.

PubMed

Aranha, Márcia M; Vasconcelos, Maria Luísa

2016-06-15

In insects, the role of reproductive hormones in coordinating fertility with mating activity is unclear. In this issue of Neuron, Lin et al. (2016) describe a mechanism in which juvenile hormone regulates courtship advantage of older Drosophila males by elevating the pheromone sensitivity of Or47b olfactory circuitry. Copyright © 2016. Published by Elsevier Inc.

Assessment of Refueling Hose Visibility

DTIC Science & Technology

2012-10-01

shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number...10 7 Basic Model of Contrast Loss through Aircraft Windscreen Due To Haze ..................... 10 8...known as a bidirectional (azimuth and elevation) reflectance distribution function or BRDF . This is extremely time-consuming and impractical. In

The floor effect: impoverished spatial memory for elevator buttons.

PubMed

Vendetti, Michael; Castel, Alan D; Holyoak, Keith J

2013-05-01

People typically remember objects to which they have frequently been exposed, suggesting that memory is a by-product of perception. However, prior research has shown that people have exceptionally poor memory for the features of some objects (e.g., coins) to which they have been exposed over the course of many years. Here, we examined how people remember the spatial layout of the buttons on a frequently used elevator panel, to determine whether physical interaction (rather than simple exposure) would ensure the incidental encoding of spatial information. Participants who worked in an eight-story office building displayed very poor recall for the elevator panel but above-chance performance on a recognition test. Performance was related to how often and how recently the person had used the elevator. In contrast to their poor memory for the spatial layout of the elevator buttons, most people readily recalled small distinctive graffiti on the elevator walls. In a more implicit test, the majority were able to locate their office floor and the eighth floor button when asked to point toward these buttons when in the actual elevator, with the button labels covered. However, identification was very poor for other floors (including the first floor), suggesting that even frequent interaction with information does not always lead to accurate spatial memory. These findings have implications for understanding the complex relationships among attention, expertise, and memory.

Change in plasma acylation stimulating protein during euglycaemic-hyperinsulinaemic clamp in overweight and obese postmenopausal women: a MONET study.

PubMed

St-Pierre, David H; Cianflone, Katherine; Smith, Jessica; Coderre, Lise; Karelis, Antony D; Imbeault, Pascal; Lavoie, Jean-Marc; Rabasa-Lhoret, Rémi

2009-04-01

Acylation-stimulating protein (ASP) has been shown to positively stimulate fatty acid esterification and glucose uptake in adipocytes. In vitro studies demonstrate that insulin stimulates ASP secretion from adipocytes. Individuals with obesity and/or metabolic disturbances (insulin resistance and type 2 diabetes) have increased plasma ASP. The present study was designed to evaluate whether ASP levels are influenced by the metabolic profiles of overweight and obese postmenopausal women during a euglycaemic/hyperinsulinaemic clamp (EHC). Patients The study population consisted of 76 overweight and obese sedentary postmenopausal women. We evaluated insulin sensitivity, plasma ASP levels, body composition including visceral adipose tissue area, blood lipid profiles, liver enzymes, peak aerobic capacity, resting metabolic rate (RMR) and total energy expenditure (TEE). We observed wide interindividual variations of ASP levels during the EHC. Therefore, subjects were divided into three groups based on ASP changes. Negative ASP Responders (NAR; n = 24) showed a -20% or greater decrease in ASP levels while Positive ASP Responders (PAR; n = 42) displayed ASP fluctuations superior to +20%. Ten subjects had little or no ASP change and were considered as Zero ASP responders (ZAR). PAR women displayed a worse metabolic profile than NAR women, including higher BMI, visceral adipose tissue, fasting insulin levels, lean body mass, and alanine aminotransferase (ALT), a marker of impaired liver function. After adjustment for BMI, only ALT remained significantly different, while lean body mass (P = 0.08) and visceral adipose tissue (P = 0.07) remained marginally higher. Correlation analysis of all subjects demonstrated that fasting ASP levels correlated positively with albumin and VO(2 peak) and this association remained significant after adjustments for the effect of BMI. In addition, the percentage maximal change in ASP levels during the EHC was positively associated with BMI, lean body mass, visceral adipose tissue, fasting insulin, HOMA, TEE, RMR, ALT and AST. Overall these results suggest that an elevated ASP response during the EHC is associated with metabolic disturbances in overweight and obese postmenopausal women.

Beneficial effects of apple peel polyphenols on vascular endothelial dysfunction and liver injury in high choline-fed mice.

PubMed

Jia, Mengfan; Ren, Daoyuan; Nie, Yan; Yang, Xingbin

2017-03-22

This study was designed to investigate the preventive effects of Red Fuji apple peel polyphenolic extract (APP) on vascular endothelial dysfunction and liver injury in mice fed a high choline diet. The mice were fed 3% dietary choline in drinking water for 8 weeks and displayed vascular dysfunction and liver damage (p < 0.01). The administration of APP at 600 and 900 mg per kg bw significantly elevated serum NO, HDL and 6-Keto-PGF1a levels and lowered serum TC, TG, LDL, ET-1 and TXB2 levels in the HC-fed mice. Besides, APP also caused the reduction of AST, ALT activities and MDA, CRP, TNF-α levels, and increased the hepatic GSH-Px and SOD activities of the HC-fed mice. Furthermore, the histopathology of the liver by conventional H&E and oil red O staining confirmed the liver steatosis induced by a choline diet and the hepatoprotective effect of APP. The experiment results indicated that the polyphenolic extract from apple peel might be regarded as a preventive and therapeutic product for the amelioration of HC diet-induced vascular dysfunction and hepatic injury.

Predicting success in an online parenting intervention: the role of child, parent, and family factors.

PubMed

Dittman, Cassandra K; Farruggia, Susan P; Palmer, Melanie L; Sanders, Matthew R; Keown, Louise J

2014-04-01

The present study involved an examination of the extent to which a wide range of child, parent, family, and program-related factors predicted child behavior and parenting outcomes after participation in an 8-session online version of the Triple P-Positive Parenting Program. Participants were mothers and fathers of 97 children aged between 3 and 8 years displaying elevated levels of disruptive behavior problems. For both mothers and fathers, poorer child behavior outcomes at postintervention were predicted by the number of sessions of the intervention completed by the family. For mothers, postintervention child behavior was also predicted by the quality of the mother-child relationship at baseline; for fathers, baseline child behavior severity was an additional predictor. Mothers' postintervention ineffective parenting was predicted by session completion and preintervention levels of ineffective parenting, whereas the only predictor of fathers' ineffective parenting at postintervention was preintervention levels of ineffective parenting. Socioeconomic risk, parental adjustment, and father participation in the intervention were not significant predictors of mother- or father-reported treatment outcomes. The implications of the findings for the provision of online parenting support are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

High-Intensity Targeted Screening for Elevated Blood Lead Levels Among Children in 2 Inner-City Chicago Communities

PubMed Central

Dignam, Timothy A.; Evens, Anne; Eduardo, Eduard; Ramirez, Shokufeh M.; Caldwell, Kathleen L.; Kilpatrick, Nikki; Noonan, Gary P.; Flanders, W. Dana; Meyer, Pamela A.; McGeehin, Michael A.

2004-01-01

Objectives. We assessed the prevalence of elevated blood lead levels (≥ 10 micrograms of lead per deciliter of blood), risk factors, and previous blood lead testing among children in 2 high-risk Chicago, Ill, communities. Methods. Through high-intensity targeted screening, blood lead levels were tested and risks were assessed among a representative sample of children aged 1 to 5 years who were at risk for lead exposure. Results. Of the 539 children who were tested, 27% had elevated blood lead levels, and 61% had never been tested previously. Elevated blood lead levels were associated with chipped exterior house paint. Conclusions. Most of the children who lived in these communities—where the prevalence for elevated blood lead levels among children was 12 times higher than the national prevalence—were not tested for lead poisoning. Our findings highlight the need for targeted community outreach that includes testing blood lead levels in accordance with the American Academy of Pediatrics’ recommendations. PMID:15514235

Thermal dependence of sprint performance in the lizard Psammodromus algirus along a 2200-meter elevational gradient: Cold-habitat lizards do not perform better at low temperatures.

PubMed

Zamora-Camacho, Francisco Javier; Rubiño-Hispán, María Virtudes; Reguera, Senda; Moreno-Rueda, Gregorio

2015-08-01

Sprint speed has a capital relevance in most animals' fitness, mainly for fleeing from predators. Sprint performance is maximal within a certain range of body temperatures in ectotherms, whose thermal upkeep relies on exogenous thermal sources. Ectotherms can respond to diverse thermal environments either by shifting their thermal preferences or maintaining them through different adaptive mechanisms. Here, we tested whether maximum sprint speed of a lizard that shows conservative thermal ecology along a 2200-meter elevational gradient differs with body temperature in lizards from different elevations. Lizards ran faster at optimum than at suboptimum body temperature. Notably, high-elevation lizards were not faster than mid- and low-elevation lizards at suboptimum body temperature, despite their low-quality thermal environment. This result suggests that both preferred body temperature and thermal dependence of speed performance are co-adapted along the elevational gradient. High-elevation lizards display a number of thermoregulatory strategies that allow them to achieve high optimum body temperatures in a low thermal-quality habitat and thus maximize speed performance. As for reproductive condition, we did not find any effect of it on sprint speed, or any significant interaction with elevation or body temperature. However, strikingly, gravid females were significantly slower than males and non-gravid females at suboptimum temperature, but performed similarly well at optimal temperature. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of muscarinic, alpha-adrenergic, and substance P agonists and ionomycin on ion transport mechanisms in the rat parotid acinar cell. The dependence of ion transport on intracellular calcium

PubMed Central

1989-01-01

The relationship between receptor-mediated increases in the intracellular free calcium concentration [( Ca]i) and the stimulation of ion fluxes involved in fluid secretion was examined in the rat parotid acinar cell. Agonist-induced increases in [Ca]i caused the rapid net loss of up to 50-60% of the total content of intracellular chloride (Cli) and potassium (Ki), which is consistent with the activation of calcium-sensitive chloride and potassium channels. These ion movements were accompanied by a 25% reduction in the intracellular volume. The relative magnitudes of the losses of Ki and the net potassium fluxes promoted by carbachol (a muscarinic agonist), phenylephrine (an alpha-adrenergic agonist), and substance P were very similar to their characteristic effects on elevating [Ca]i. Carbachol stimulated the loss of Ki through multiple efflux pathways, including the large-conductance Ca-activated K channel. Carbachol and substance P increased the levels of intracellular sodium (Nai) to more than 2.5 times the normal level by stimulating the net uptake of sodium through multiple pathways; Na-K-2Cl cotransport accounted for greater than 50% of the influx, and approximately 20% was via Na-H exchange, which led to a net alkalinization of the cells. Ionomycin stimulated similar fluxes through these two pathways, but also promoted sodium influx through an additional pathway which was nearly equivalent in magnitude to the combined uptake through the other two pathways. The carbachol- induced increase in Nai and decrease in Ki stimulated the activity of the sodium pump, measured by the ouabain-sensitive rate of oxygen consumption, to nearly maximal levels. In the absence of extracellular calcium or in cells loaded with the calcium chelator BAPTA (bis[o- aminophenoxy]ethane-N,N,N',N'-tetraacetic acid) the magnitudes of agonist- or ionomycin-stimulated ion fluxes were greatly reduced. The parotid cells displayed a marked desensitization to substance P; within 10 min the elevation of [Ca]i and alterations in Ki, Nai, and cell volume spontaneously returned to near baseline levels. In addition to quantitating the activation of various ion flux pathways in the rat parotid acinar cell, these results demonstrate that the activation of ion transport systems responsible for fluid secretion in this tissue is closely linked to the elevation of [Ca]i. PMID:2467962

NUCB2/nesfatin-1 Is Associated with Elevated Levels of Anxiety in Anorexia Nervosa.

PubMed

Hofmann, Tobias; Ahnis, Anne; Elbelt, Ulf; Rose, Matthias; Klapp, Burghard F; Stengel, Andreas

2015-01-01

NUCB2/nesfatin-1 is an anorexigenic hormone with elevated levels in obese and decreased levels in anorexia nervosa (AN) patients. Moreover, a role in the regulation of stress and emotions was suggested by several rodent and preliminary human studies. Since anxiety and depression are common comorbidities in AN, we investigated the association of NUCB2/nesfatin-1 with anxiety, depression and perceived stress in AN. We analyzed circulating NUCB2/nesfatin-1 levels in 64 female inpatients diagnosed with anorexia nervosa (body mass index, BMI; mean±SD, 14.7±2.3 kg/m2). At the same time anxiety (GAD-7), depression (PHQ-9), stress (PSQ-20) and disordered eating (EDI-2) were measured psychometrically. No correlation was observed between NUCB2/nesfatin-1 and BMI (r = 0.06, p = 0.70). The study population was divided in patients with low anxiety (n = 32, GAD-7 scores, mean±SD, 7.5±3.3) and high anxiety (n = 32, 16.0±3.0, p<0.001). Patients with high anxiety scores displayed 65% higher NUCB2/nesfatin-1 levels (p = 0.04). This was reflected by a positive correlation of GAD-7 and NUCB2/nesfatin-1-levels (r = 0.32, p = 0.04). Scores of PSQ-20 (73.3±14.3 vs. 48.6±17.2) and PHQ-9 (18.8±5.0 vs. 10.3±5.1) were higher in the high anxiety group (p<0.001) but did not correlate with NUCB2/nesfatin-1 (p>0.05). EDI-2 total score was also higher in the high anxiety group (52.3±14.1 vs. 40.2±16.0, p = 0.02), while no correlations of EDI-2-scores with plasma NUCB2/nesfatin-1 were observed (p>0.05). Circulating NUCB2/nesfatin-1 levels correlated positively with perceived anxiety, whereas no association with BMI or eating disorder symptoms was observed. NUCB2/nesfatin-1 might be primarily involved in the modulation of anxiety and subsequently in the regulation of eating habits and body weight in AN.

NUCB2/nesfatin-1 Is Associated with Elevated Levels of Anxiety in Anorexia Nervosa

PubMed Central

Hofmann, Tobias; Ahnis, Anne; Elbelt, Ulf; Rose, Matthias; Klapp, Burghard F.; Stengel, Andreas

2015-01-01

Objective NUCB2/nesfatin-1 is an anorexigenic hormone with elevated levels in obese and decreased levels in anorexia nervosa (AN) patients. Moreover, a role in the regulation of stress and emotions was suggested by several rodent and preliminary human studies. Since anxiety and depression are common comorbidities in AN, we investigated the association of NUCB2/nesfatin-1 with anxiety, depression and perceived stress in AN. Methods We analyzed circulating NUCB2/nesfatin-1 levels in 64 female inpatients diagnosed with anorexia nervosa (body mass index, BMI; mean±SD, 14.7±2.3 kg/m2). At the same time anxiety (GAD-7), depression (PHQ-9), stress (PSQ-20) and disordered eating (EDI-2) were measured psychometrically. Results No correlation was observed between NUCB2/nesfatin-1 and BMI (r = 0.06, p = 0.70). The study population was divided in patients with low anxiety (n = 32, GAD-7 scores, mean±SD, 7.5±3.3) and high anxiety (n = 32, 16.0±3.0, p<0.001). Patients with high anxiety scores displayed 65% higher NUCB2/nesfatin-1 levels (p = 0.04). This was reflected by a positive correlation of GAD-7 and NUCB2/nesfatin-1-levels (r = 0.32, p = 0.04). Scores of PSQ-20 (73.3±14.3 vs. 48.6±17.2) and PHQ-9 (18.8±5.0 vs. 10.3±5.1) were higher in the high anxiety group (p<0.001) but did not correlate with NUCB2/nesfatin-1 (p>0.05). EDI-2 total score was also higher in the high anxiety group (52.3±14.1 vs. 40.2±16.0, p = 0.02), while no correlations of EDI-2-scores with plasma NUCB2/nesfatin-1 were observed (p>0.05). Conclusions Circulating NUCB2/nesfatin-1 levels correlated positively with perceived anxiety, whereas no association with BMI or eating disorder symptoms was observed. NUCB2/nesfatin-1 might be primarily involved in the modulation of anxiety and subsequently in the regulation of eating habits and body weight in AN. PMID:26162003

Effects of Elevated CO2 on Levels of Primary Metabolites and Transcripts of Genes Encoding Respiratory Enzymes and Their Diurnal Patterns in Arabidopsis thaliana: Possible Relationships with Respiratory Rates

PubMed Central

Watanabe, Chihiro K.; Sato, Shigeru; Yanagisawa, Shuichi; Uesono, Yukifumi; Terashima, Ichiro; Noguchi, Ko

2014-01-01

Elevated CO2 affects plant growth and photosynthesis, which results in changes in plant respiration. However, the mechanisms underlying the responses of plant respiration to elevated CO2 are poorly understood. In this study, we measured diurnal changes in the transcript levels of genes encoding respiratory enzymes, the maximal activities of the enzymes and primary metabolite levels in shoots of Arabidopsis thaliana grown under moderate or elevated CO2 conditions (390 or 780 parts per million by volume CO2, respectively). We examined the relationships between these changes and respiratory rates. Under elevated CO2, the transcript levels of several genes encoding respiratory enzymes increased at the end of the light period, but these increases did not result in changes in the maximal activities of the corresponding enzymes. The levels of some primary metabolites such as starch and sugar phosphates increased under elevated CO2, particularly at the end of the light period. The O2 uptake rate at the end of the dark period was higher under elevated CO2 than under moderate CO2, but higher under moderate CO2 than under elevated CO2 at the end of the light period. These results indicate that the changes in O2 uptake rates are not directly related to changes in maximal enzyme activities and primary metabolite levels. Instead, elevated CO2 may affect anabolic processes that consume respiratory ATP, thereby affecting O2 uptake rates. PMID:24319073

A comparison of bat activity at low and high elevations in the Black Hills of western Washington

USGS Publications Warehouse

Erickson, J.; Adams, Michael J.

2003-01-01

We examined the differences in activity patterns and community structure of bats between low (<150 m) and high ( ! 575 m) elevation sites in two habitats of the Capitol State Forest, Washington. Total bat activity averaged four times higher at low elevation sites than at high elevation sites. Feeding activity was almost 20 times higher at low elevation sites. However, the non-myotis group had similar activity levels at high and low elevation, whereas myotis group activity decreased at higher elevations. Different levels of activity between elevations could be the result of differences in insect availability, climatic conditions, and morphology of the bat species.

Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity.

PubMed

Kwon, Yong-Soo; Cho, Young-Nan; Kim, Moon-Ju; Jin, Hye-Mi; Jung, Hyun-Ju; Kang, Jeong-Hwa; Park, Ki-Jeong; Kim, Tae-Jong; Kee, Hae Jin; Kim, Nacksung; Kee, Seung-Jung; Park, Yong-Wook

2015-05-01

Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. The aims of this study were to examine the levels of MAIT cells in pulmonary tuberculosis (TB) and nontuberculous mycobacteria (NTM) lung disease patients, to evaluate the clinical relevance of MAIT cell levels, and to investigate the functions of MAIT cells. Patients with pulmonary TB (n = 35), NTM (n = 29), and healthy controls (n = 75) were enrolled in the study. MAIT cell levels and functions were measured by flow cytometry. Circluating MAIT cell levels were found to be reduced in TB and NTM patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAIT cell numbers were significantly correlated with sputum AFB positivity, extent of disease, hemoglobin levels, lymphocyte counts, CRP and ESR levels. MAIT cells in TB patients failed to produce interferon-γ irrespective of the mode of stimulation, whereas NTM patients displayed a defect in MR1-dependent signaling pathway. Notably, an elevated expression of programmed death-1 was also associated with MAIT cell deficiency in TB. This study shows that MAIT cells are numerically and functionally deficient in TB and NTM patients and these deficiencies could contribute to immune system dysreguation in mycobacterial infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Experimental Studies of the Effect of Intent Information on Cockpit Traffic Displays

NASA Technical Reports Server (NTRS)

Barhydt, Richard; Hansman, R. John

1997-01-01

Intent information provides knowledge of another aircraft's current and future trajectory states. Prototype traffic displays were designed for four different levels of intent: Position, Rate, Commanded State, and FMS (Flight Management System)-Path. The current TCAS (traffic collision avoidance systems) Display, which shows altitude rate in addition to current position and altitude, was used as a baseline and represents the lowest level of intent. The Rate, Commanded State, and FMS-Path Displays show increasing levels of intent information using TCAS-like symbology in addition to incorporating a conflict probe and profile view display. An initial experiment was run on the MIT (Massachusetts Institute of Technology) Part Task Flight Simulator in which eight airline pilots flew five traffic scenarios with each of the four displays. Results show that pilots had fewer separation violations and maneuvered earlier with the three intent displays. Separation violations were reduced when pilots maneuvered earlier. A second experiment was run to compare performance between displaying intent information directly and incorporating it into a conflict probe. A different set of eight airline pilots flew four traffic scenarios with the TCAS and Commanded State Displays with and without the conflict probe. Conflict probes with two minute and long range look-ahead times were tested. Displaying conflict bands or showing intent information directly both led to fewer separation violations and earlier avoidance maneuvers than the base TCAS Display. Performance was similar between the two minute and long range look-ahead conflict probes. Pilots preferred all intent displays over the TCAS Display.