Heterogeneity of Depressive Symptom Trajectories through Adolescence: Predicting Outcomes in Young Adulthood.

PubMed

Chaiton, Michael; Contreras, Gisèle; Brunet, Jennifer; Sabiston, Catherine M; O'Loughlin, Erin; Low, Nancy C P; Karp, Igor; Barnett, Tracie A; O'Loughlin, Jennifer

2013-05-01

This study describes developmental trajectories of depressive symptoms in adolescents and examines the association between trajectory group and mental health outcomes in young adulthood. Depressive symptoms were self-reported every three months from grade seven through grade 11 by 1293 adolescents in the Nicotine Dependence in Teens (NDIT) study and followed in young adulthood (average age 20.4, SD=0.7, n=865). Semi-parametric growth modeling was used to identify sex-specific trajectories of depressive symptoms. THREE DISTINCT TRAJECTORY GROUPS WERE IDENTIFIED: 50% of boys and 29% of girls exhibited low, decreasing levels of depressive symptoms; 14% of boys and 28% of girls exhibited high and increasing levels; and 36% of boys and 43% of girls exhibited moderate levels with linear increase. Trajectory group was a statistically significant independent predictor of depression, stress, and self-rated mental health in young adulthood in boys and girls. Boys, but not girls, in the high trajectory group had a statistically significant increase in the likelihood of seeking psychiatric care. Substantial heterogeneity in changes in depressive symptoms over time was found. Because early depressive symptoms predict mental health problems in young adulthood, monitoring adolescents for depressive symptoms may help identify those most at risk and in need of intervention.

Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

PubMed

Woodman, Andrew G; Mah, Richard; Keddie, Danae; Noble, Ronan M N; Panahi, Sareh; Gragasin, Ferrante S; Lemieux, Hélène; Bourque, Stephane L

2018-06-01

Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

The effect of dietary betaine on intestinal and plasma levels of betaine in uninfected and coccidia-infected broiler chicks.

PubMed

Fetterer, R H; Augustine, P C; Allen, P C; Barfield, R C

2003-07-01

Chicks fed betaine supplemented diets and infected with Eimeria acervulina and Eimeria maxima had markedly higher levels of betaine in the duodenum and mid-gut than unsupplemented, infected chicks. Uninfected chicks fed betaine exhibited almost twice the levels of betaine in the gut as infected chicks. Plasma betaine levels were lower in E. maxima-infected chicks than in E. acervulina-or Eimeria tenella-infected chicks. Betaine supplementation reversed the decrease in weight gain in E. maxima- infected chicks but had no effect on the decrease in weight gains in E acervulina- and E. tenella-infected chicks. Coccidia-infected birds on normal diets regularly exhibit increases in plasma NO(2)(+)NO(3). This increase was abolished in E.tenella-infected birds on betaine supplement. Betaine feeding did not alter this effect in E. acervulina- and E. maxima-infected birds. Results indicate that betaine supplementation has a positive effect on gut betaine levels in birds infected with E. acervulina and E. maxima. In all treatment groups, infection lowered the levels of betaine.

Alcohol Attenuates Load-related Activation During a Working Memory Task: Relation to Level of Response to Alcohol

PubMed Central

Paulus, Martin P.; Tapert, Susan F.; Pulido, Carmen; Schuckit, Marc A.

2008-01-01

Background A low level of response to alcohol is a major risk factor for the development of alcohol dependence, but neural correlates of this marker are unclear. Method Ten healthy volunteers were classified by median split on level of response to alcohol and underwent 2 sessions of functional magnetic resonance imaging following ingestion of a moderate dose of alcohol and a placebo. The blood oxygen level–dependent activation to an event-related visual working memory test was examined. Results The subjects exhibited longer response latencies and more errors as a function of increasing working memory load and showed a load-dependent increase in activation in dorsolateral prefrontal cortex, posterior parietal cortex, and visual cortex. Alcohol did not affect performance (errors or response latency), but attenuated the working memory load–dependent activation in the dorsolateral prefrontal cortex. During the placebo condition, individuals with a low level of response to alcohol showed greater activation in dorsolateral prefrontal cortex and posterior parietal cortex than those with a high level of response to alcohol. During the alcohol condition, groups showed similar attenuation of load-dependent brain activation in these regions. Conclusion Low-level responders relative to high-level responders exhibited an increased working memory load–dependent activation in dorsolateral prefrontal cortex and posterior parietal cortex when not exposed to alcohol. This increase in brain response was attenuated in low-level responders after ingesting a moderate dose of alcohol. PMID:16899039

Improvement of multi-level resistive switching characteristics in solution-processed AlO x -based non-volatile resistive memory using microwave irradiation

NASA Astrophysics Data System (ADS)

Kim, Seung-Tae; Cho, Won-Ju

2018-01-01

We fabricated a resistive random access memory (ReRAM) device on a Ti/AlO x /Pt structure with solution-processed AlO x switching layer using microwave irradiation (MWI), and demonstrated multi-level cell (MLC) operation. To investigate the effect of MWI power on the MLC characteristics, post-deposition annealing was performed at 600-3000 W after AlO x switching layer deposition, and the MLC operation was compared with as-deposited (as-dep) and conventional thermally annealing (CTA) treated devices. All solution-processed AlO x -based ReRAM devices exhibited bipolar resistive switching (BRS) behavior. We found that these devices have four-resistance states (2 bits) of MLC operation according to the modulation of the high-resistance state (HRSs) through reset voltage control. Particularly, compared to the as-dep and CTA ReRAM devices, the MWI-treated ReRAM devices showed a significant increase in the memory window and stable endurance for multi-level operation. Moreover, as the MWI power increased, excellent MLC characteristics were exhibited because the resistance ratio between each resistance state was increased. In addition, it exhibited reliable retention characteristics without deterioration at 25 °C and 85 °C for 10 000 s. Finally, the relationship between the chemical characteristics of the solution-processed AlO x switching layer and BRS-based multi-level operation according to the annealing method and MWI power was investigated using x-ray photoelectron spectroscopy.

Thyroid hormone regulation of Sirtuin 1 expression and implications to integrated responses in fasted mice.

PubMed

Cordeiro, Aline; de Souza, Luana Lopes; Oliveira, Lorraine Soares; Faustino, Larissa Costa; Santiago, Letícia Aragão; Bloise, Flavia Fonseca; Ortiga-Carvalho, Tania Maria; Almeida, Norma Aparecida Dos Santos; Pazos-Moura, Carmen Cabanelas

2013-02-01

Sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylase, has been connected to beneficial effects elicited by calorie restriction. Physiological adaptation to starvation requires higher activity of SIRT1 and also the suppression of thyroid hormone (TH) action to achieve energy conservation. Here, we tested the hypothesis that those two events are correlated and that TH may be a regulator of SIRT1 expression. Forty-eight-hour fasting mice exhibited reduced serum TH and increased SIRT1 protein content in liver and brown adipose tissue (BAT), and physiological thyroxine replacement prevented or attenuated the increment of SIRT1 in liver and BAT of fasted mice. Hypothyroid mice exhibited increased liver SIRT1 protein, while hyperthyroid ones showed decreased SIRT1 in liver and BAT. In the liver, decreased protein is accompanied by reduced SIRT1 activity and no alteration in its mRNA. Hyperthyroid and hypothyroid mice exhibited increases and decreases in food intake and body weight gain respectively. Food-restricted hyperthyroid animals (pair-fed to euthyroid group) exhibited liver and BAT SIRT1 protein levels intermediary between euthyroid and hyperthyroid mice fed ad libitum. Mice with TH resistance at the liver presented increased hepatic SIRT1 protein and activity, with no alteration in Sirt1 mRNA. These results suggest that TH decreases SIRT1 protein, directly and indirectly, via food ingestion control and, in the liver, this reduction involves TRβ. The SIRT1 reduction induced by TH has important implication to integrated metabolic responses to fasting, as the increase in SIRT1 protein requires the fasting-associated suppression of TH serum levels.

High-Density Lipoprotein Maintains Skeletal Muscle Function by Modulating Cellular Respiration in Mice

PubMed Central

Lehti, Maarit; Donelan, Elizabeth; Abplanalp, William; Al-Massadi, Omar; Habegger, Kirk; Weber, Jon; Ress, Chandler; Mansfeld, Johannes; Somvanshi, Sonal; Trivedi, Chitrang; Keuper, Michaela; Ograjsek, Teja; Striese, Cynthia; Cucuruz, Sebastian; Pfluger, Paul T.; Krishna, Radhakrishna; Gordon, Scott M.; Silva, R. A. Gangani D.; Luquet, Serge; Castel, Julien; Martinez, Sarah; D'Alessio, David; Davidson, W. Sean; Hofmann, Susanna M.

2014-01-01

Background Abnormal glucose metabolism is a central feature of disorders with increased rates of cardio-vascular disease (CVD). Low levels of high density lipoprotein (HDL) are a key predictor for CVD. We used genetic mouse models with increased HDL levels (apoA-I tg) and reduced HDL levels (apoA-I ko) to investigate whether HDL modulates mitochondrial bioenergetics in skeletal muscle. Methods and Results ApoA-I ko mice exhibited fasting hyperglycemia and impaired glucose tolerance test (GTT) compared to wild type (wt) mice. Mitochondria isolated from gastrocnemius muscle of apoA-I ko mice displayed markedly blunted ATP synthesis. Endurance capacity (EC) during exercise exhaustion test was impaired in apoA-I ko mice. HDL directly enhanced glucose oxidation by increasing glycolysis and mitochondrial respiration rate (OCR) in C2C12 muscle cells. ApoA-I tg mice exhibited lower fasting glucose levels, improved GTT, increased lactate levels, reduced fat mass, associated with protection against age-induced decline of EC compared to wt mice. Circulating levels of fibroblast growth factor 21 (FGF21), a novel biomarker for mitochondrial respiratory chain deficiencies and inhibitor of white adipose lipolysis, were significantly reduced in apoA-I tg mice. Consistent with an increase in glucose utilization of skeletal muscle, genetically increased HDL and apoA-I levels in mice prevented high fat diet-induced impairment of glucose homeostasis. Conclusions In view of impaired mitochondrial function and decreased HDL levels in T2D, our findings indicate that HDL-raising therapies may preserve muscle mitochondrial function and address key aspects of T2D beyond CVD. PMID:24170386

Anxiety response and restraint-induced stress differentially affect ethanol intake in female adolescent rats.

PubMed

Acevedo, María Belén; Fabio, Maria Carolina; Fernández, Macarena Soledad; Pautassi, Ricardo Marcos

2016-10-15

Anxiety disorders are more likely to occur in women than in men, usually emerge during adolescence and exhibit high comorbidity with alcohol use disorders (AUD). Adolescents with high levels of anxiety or heightened reactivity to stress may be at-risk for developing AUD. An approach to analyze if high levels of inborn anxiety predict greater ethanol drinking is to assess the latter variable in subjects classified as high- or low-anxiety responders. The present study assessed ethanol drinking in adolescent, female Wistar, rats classified as high-, low- or average-anxiety responders and exposed or not to restraint stress (RS, Exp. 1). Classification was made through a multivariate index derived from testing anxiety responses in an elevated plus maze and a light-dark box tests. RS was applied after animals had been initiated to ethanol drinking. Intake of sweetened ethanol was unaffected by level of anxiety response. Adolescents with high levels of inborn anxiety exhibited significantly higher intake of unsweetened ethanol than counterparts with standard levels of anxiety, yet this effect was inhibited by RS exposure. Experiment 2 assessed FOS immunoreactivity after RS. Stress induced a significant increase in FOS immunoreactivity at the paraventricular nucleus, yet this effect was unaffected by level of anxiety response. Female adolescents with high levels of basal anxiety may be at-risk for exhibiting increased predisposition for ethanol intake and preference. The study also indicates that stress may exert differential effects on adolescent ethanol intake as a function of the level of anxiety response. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

An electrophysiological investigation of emotional abnormalities in groups at risk for schizophrenia-spectrum personality disorders.

PubMed

Martin, Elizabeth A; Karcher, Nicole R; Bartholow, Bruce D; Siegle, Greg J; Kerns, John G

2017-03-01

Both extreme levels of social anhedonia (SocAnh) and perceptual aberration/magical ideation (PerMag) are associated with risk for schizophrenia-spectrum disorders and with emotional abnormalities. Yet, the nature of any psychophysiological-measured affective abnormality, including the role of automatic/controlled processes, is unclear. We examined the late positive potential (LPP) during passive viewing (to assess automatic processing) and during cognitive reappraisal (to assess controlled processing) in three groups: SocAnh, PerMag, and controls. The SocAnh group exhibited an increased LPP when viewing negative images. Further, SocAnh exhibited greater reductions in the LPP for negative images when told to use strategies to alter negative emotion. Similar to SocAnh, PerMag exhibited an increased LPP when viewing negative images. However, PerMag also exhibited an increased LPP when viewing positive images as well as an atypical decreased LPP when increasing positive emotion. Overall, these results suggest that at-risk groups are associated with shared and unique automatic and controlled abnormalities. Copyright © 2017 Elsevier B.V. All rights reserved.

Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration

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

Sheard, Michael A., E-mail: msheard@chla.usc.edu; Ghent, Matthew V., E-mail: mattghent@gmail.com; Cabral, Daniel J., E-mail: dcabral14@gmail.com

2015-05-15

Cancer cells typically exhibit increased glycolysis and decreased mitochondrial oxidative phosphorylation, and they continue to exhibit some elevation in glycolysis even under aerobic conditions. However, it is unclear whether cancer cell lines employ a high level of glycolysis comparable to that of the original cancers from which they were derived, even if their culture conditions are changed to physiologically relevant oxygen concentrations. From three childhood acute lymphoblastic leukemia (ALL) patients we established three new pairs of cell lines in both atmospheric (20%) and physiologic (bone marrow level, 5%) oxygen concentrations. Cell lines established in 20% oxygen exhibited lower proliferation, survival,more » expression of glycolysis genes, glucose consumption, and lactate production. Interestingly, the effects of oxygen concentration used during cell line initiation were only partially reversible when established cell cultures were switched from one oxygen concentration to another for eight weeks. These observations indicate that ALL cell lines established at atmospheric oxygen concentration can exhibit relatively low levels of glycolysis and these levels are semi-permanent, suggesting that physiologic oxygen concentrations may be needed from the time of cell line initiation to preserve the high level of glycolysis commonly exhibited by leukemias in vivo. - Highlights: • Establishing new ALL cell lines in 5% oxygen resulted in higher glycolytic expression and function. • Establishing new ALL cell lines in 5% oxygen resulted in higher proliferation and lower cell death. • The divergent metabolic phenotypes selected in 5% and 20% oxygen are semi-permanent.« less

Alcohol Preferring P Rats Exhibit Elevated Motor Impulsivity Concomitant with Operant Responding and Self-Administration of Alcohol

PubMed Central

Beckwith, Steven Wesley; Czachowski, Cristine Lynn

2016-01-01

Background Increased levels of impulsivity are associated with increased illicit drug use and alcoholism. Previous research in our lab has shown that increased levels of delay discounting (a decision-making form of impulsivity) are related to appetitive processes governing alcohol self-administration as opposed to purely consummatory processes. Specifically, the high seeking/high drinking alcohol preferring P rats showed increased delay discounting compared to nonselected Long Evans rats (LE) whereas the high drinking/moderate seeking HAD2 rats did not (Beckwith & Czachowski, 2014). The P rats also displayed a perseverative pattern of behavior such that during operant alcohol self-administration they exhibited greater resistance to extinction. Methods One explanation for the previous findings is that P rats have a deficit in response inhibition. The current study followed up on this possibility by utilizing a countermanding paradigm [stop signal reaction time (SSRT) task] followed by operant self-administration of alcohol across increasing fixed ratio requirements (FR; 1, 2, 5, 10 & 15 responses). In separate animals, 24hr access 2-bottle choice (10% EtOH vs. water) drinking was assessed. Results In the SSRT task, P rats exhibited an increased SSRT compared to both LE and HAD2 rats indicating a decrease in behavioral inhibition in the P rats. Also, P rats showed increased operant self-administration across all FRs and the greatest increase in responding with increasing FR requirements. Conversely, the HAD2 and LE had shorter SSRT, and lower levels of operant alcohol self-administration. However, for 2 bottle choice drinking HAD2s and P rats consumed more EtOH as well as had a greater preference for EtOH compared to LE. Conclusions These data extend previous findings showing the P rats to have increased delay discounting (decision-making impulsivity) and suggest that P rats also have a lack of behavioral inhibition (motor impulsivity). This supports the notion that P rats are a highly impulsive as well as “high seeking” model of alcoholism, and that the HAD2s elevated levels of alcohol consumption are not mediated via appetitive processes or impulsivity. PMID:27028842

Protection from experimental asthma by an endogenous bronchodilator.

PubMed

Que, Loretta G; Liu, Limin; Yan, Yun; Whitehead, Gregory S; Gavett, Stephen H; Schwartz, David A; Stamler, Jonathan S

2005-06-10

Mechanisms that protect against asthma remain poorly understood. S-nitrosoglutathione (GSNO), an endogenous bronchodilator, is depleted from asthmatic airways, suggesting a protective role. We report that, following allergen challenge, wild-type mice exhibiting airway hyperresponsivity have increased airway levels of the enzyme GSNO reductase (GSNOR) and are depleted of lung S-nitrosothiols (SNOs). In contrast, mice with genetic deletion of GSNOR exhibit increases in lung SNOs and are protected from airway hyperresponsivity. Our results indicate that endogenous SNOs, governed by GSNOR, are critical regulators of airway responsivity and may provide new therapeutic approaches to asthma.

Activity in the ferret: oestradiol effects and circadian rhythms

NASA Technical Reports Server (NTRS)

Stockman, E. R.; Albers, H. E.; Baum, M. J.; Wurtman, R. J. (Principal Investigator)

1985-01-01

The present study was conducted to determine whether oestradiol increases activity in the European ferret (Mustela furo), whether this effect is sexually dimorphic, and whether a 24-h rhythm is present in the ferret's daily activity. The activity of male and female adult, postpubertally gonadectomized ferrets was monitored while they were maintained singly on a 13:11 light-dark cycle, before and after implantation with oestradiol-17 beta. Gonadectomized male and female ferrets exhibited equal levels of activity, and neither sex exhibited a significant change in activity following oestradiol implantation. None of the ferrets exhibited a strong circadian rhythm, although weak 24-h rhythms and shorter harmonic rhythms were present. Golden hamsters (Mesocricetus auratus), monitored in an identical manner, exhibited strong circadian rhythms. It was concluded that oestradiol administration may not cause an increase in activity in the ferret, and that this species lacks a strong circadian activity rhythm.

Taking the "Physical" out of Physical Education

ERIC Educational Resources Information Center

Usher, Wayne; Keegan, Richard; Edwards, Allan

2016-01-01

Australian youth (5-17) are exhibiting the most alarming statistics surrounding poor physical activity (PA) levels and increasing correlating chronic disease trends (i.e. obesity). With schools well positioned to address such concerns, this study aimed to determine the type, frequency and intensity levels of PA being undertaken by children during…

Exposure of Pregnant Mice to Perfluorobutanesulfonate Causes Hypothyroxinemia and Developmental Abnormalities in Female Offspring.

PubMed

Feng, Xuejiao; Cao, Xinyuan; Zhao, Shasha; Wang, Xiaoli; Hua, Xu; Chen, Lin; Chen, Ling

2017-02-01

Perfluorobutanesulfonate (PFBS) is widely used in many industrial products. We evaluated the influence of prenatal PFBS exposure on perinatal growth and development, pubertal onset, and reproductive and thyroid endocrine system in female mice. Here, we show that when PFBS (200 and 500 mg/kg/day) was orally administered to pregnant mice (PFBS-dams) on days 1-20 of gestation; their female offspring (PFBS-offspring) exhibited decreased perinatal body weight and delayed eye opening compared with control offspring. Vaginal opening and first estrus were also significantly delayed in PFBS-offspring, and diestrus was prolonged. Ovarian and uterine size, as well as follicle and corpus luteum numbers, were reduced in adult PFBS-offspring. Furthermore, pubertal and adult PFBS-offspring exhibited decreases in serum estrogen (E2) and progesterone (P4) levels with the elevation of luteinizing hormone levels. Notably, decreases in serum total thyroxine (T4) and 3,3', 5-triiodothyronine (T3) levels were observed in fetal, pubertal, and adult PFBS-offspring in conjunction with slight increases in thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone levels. In addition, PFBS-dams exhibited significant decreases in total T4 and T3 levels and free T4 levels and increases in TSH levels, but no changes in E2 and P4 levels. These results indicate that prenatal PFBS exposure (≥200 mg/kg/day) causes permanent hypothyroxinemia accompanied by deficits in perinatal growth, pubertal onset, and reproductive organ development in female mice. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hepatectomy-Related Hypophosphatemia: A Novel Phosphaturic Factor in the Liver-Kidney Axis

PubMed Central

Nomura, Kengo; Miyagawa, Atsumi; Shiozaki, Yuji; Sasaki, Shohei; Kaneko, Ichiro; Ito, Mikiko; Kido, Shinsuke; Segawa, Hiroko; Sano, Mitsue; Fukuwatari, Tsutomu; Shibata, Katsumi

2014-01-01

Marked hypophosphatemia is common after major hepatic resection, but the pathophysiologic mechanism remains unknown. We used a partial hepatectomy (PH) rat model to investigate the molecular basis of hypophosphatemia. PH rats exhibited hypophosphatemia and hyperphosphaturia. In renal and intestinal brush-border membrane vesicles isolated from PH rats, Na+-dependent phosphate (Pi) uptake decreased by 50%–60%. PH rats also exhibited significantly decreased levels of renal and intestinal Na+-dependent Pi transporter proteins (NaPi-IIa [NaPi-4], NaPi-IIb, and NaPi-IIc). Parathyroid hormone was elevated at 6 hours after PH. Hyperphosphaturia persisted, however, even after thyroparathyroidectomy in PH rats. Moreover, DNA microarray data revealed elevated levels of nicotinamide phosphoribosyltransferase (Nampt) mRNA in the kidney after PH, and Nampt protein levels and total NAD concentration increased significantly in the proximal tubules. PH rats also exhibited markedly increased levels of the Nampt substrate, urinary nicotinamide (NAM), and NAM catabolites. In vitro analyses using opossum kidney cells revealed that NAM alone did not affect endogenous NaPi-4 levels. However, in cells overexpressing Nampt, the addition of NAM led to a marked decrease in cell surface expression of NaPi-4 that was blocked by treatment with FK866, a specific Nampt inhibitor. Furthermore, FK866-treated mice showed elevated renal Pi reabsorption and hypophosphaturia. These findings indicate that hepatectomy-induced hypophosphatemia is due to abnormal NAM metabolism, including Nampt activation in renal proximal tubular cells. PMID:24262791

Racial/Ethnic and Gender Differences in the Relationship between Uric Acid and Metabolic Syndrome in Adolescents: An Analysis of NHANES 1999–2006

PubMed Central

DeBoer, Mark D.; Dong, Lili; Gurka, Matthew J.

2011-01-01

Background Among adolescents uric acid is associated with insulin resistance, hypertension and the metabolic syndrome (MetS) and in adults high uric acid levels are an independent risk factor for cardiovascular disease and diabetes. Objective Determine whether the relationship of uric acid with MetS varies in adolescents by race/ethnicity and gender. Methods We used linear regression to evaluate associations between uric acid and other MetS-associated clinical and laboratory measures among 3,296 non-Hispanic-white, non-Hispanic-black and Hispanic adolescents age 12–19y participating in the National Health and Nutrition Evaluation Survey (1999–2006). Results Overall, non-Hispanic-white males and females had the highest uric acid levels among the three racial/ethnic groups. In each racial/ethnic group there were higher uric acid levels for those adolescents with vs. without MetS. However, the extent of the MetS-related increase in uric acid level varied by race and gender. Among males, MetS was associated with the greatest increases in uric acid among non-Hispanic whites. However, among females, the MetS-related increase in uric acid was greatest among non-whites. Non-Hispanic-white females exhibited the lowest degrees of correlation between levels of uric acid and MetS-associated variables. Uric acid levels did not correlate with insulin levels in non-Hispanic-white females. Conclusions These data suggest the relationship between uric acid and MetS varies by race/ethnicity and gender. In particular, non-Hispanic-white males exhibit a strong relationship and non-Hispanic-white females exhibit a relatively poor correlation between uric acid and MetS-related factors. These data may have implications for the use of uric acid as a marker of future risk among adolescents. PMID:22000606

Phenotypic plasticity of sun and shade ecotypes of Stellaria longipes in response to light quality signaling, gibberellins and auxin.

PubMed

Kurepin, Leonid V; Pharis, Richard P; Neil Emery, R J; Reid, David M; Chinnappa, C C

2015-09-01

Stellaria longipes plant communities (ecotypes) occur in several environmentally distinct habitats along the eastern slopes of southern Alberta's Rocky Mountains. One ecotype occurs in a prairie habitat at ∼1000 m elevation where Stellaria plants grow in an environment in which the light is filtered by taller neighbouring vegetation, i.e. sunlight with a low red to far-red (R/FR) ratio. This ecotype exhibits a high degree of phenotypic plasticity by increasing stem elongation in response to the low R/FR ratio light signal. Another Stellaria ecotype occurs nearby at ∼2400 m elevation in a much cooler alpine habitat, one where plants rarely experience low R/FR ratio shade light. Stem elongation of plants is largely regulated by gibberellins (GAs) and auxin, indole-3-acetic acid (IAA). Shoots of the prairie ecotype plants show increased IAA levels under low R/FR ratio light and they also increase their stem growth in response to applied IAA. The alpine ecotype plants show neither response. Plants from both ecotypes produce high levels of growth-active GA1 under low R/FR ratio light, though they differ appreciably in their catabolism of GA1. The alpine ecotype plants exhibit very high levels of GA8, the inactive product of GA1 metabolism, under both normal and low R/FR ratio light. Alpine origin plants may de-activate GA1 by conversion to GA8 via a constitutively high level of expression of the GA2ox gene, thereby maintaining their dwarf phenotype and exhibiting a reduced phenotypic plasticity in terms of shoot elongation. In contrast, prairie plants exhibit a high degree of phenotypic plasticity, using low R/FR ratio light-mediated changes in GA and IAA concentrations to increase shoot elongation, thereby accessing direct sunlight to optimize photosynthesis. There thus appear to be complex adaptation strategies for the two ecotypes, ones which involve modifications in the homeostasis of endogenous hormones. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Genetic Transformation and Hairy Root Induction Enhance the Antioxidant Potential of Lactuca serriola L.

PubMed

El-Esawi, Mohamed A; Elkelish, Amr; Elansary, Hosam O; Ali, Hayssam M; Elshikh, Mohamed; Witczak, Jacques; Ahmad, Margaret

2017-01-01

Lactuca serriola L. is a herbaceous species, used for human nutrition and medicinal purposes. The high antioxidant capacity of L. serriola indicates the possibility of enhancing its edible and health potential by increasing the flavonoid and phenolic contents. The present study aimed at enhancing the production of phenolics and flavonoids by hairy root cultures in Lactuca serriola transformed with Agrobacterium rhizogenes strain AR15834 harbouring the rolB gene. The genetic transformation of rolB in transformed roots was validated, and rolB expression level was evaluated using real-time qPCR analysis. Expression levels of flavonoid biosynthesis genes (CHI, PAL, FLS, and CHS) were assessed in the hairy and nontransformed roots. Results showed higher expression levels in the transgenic roots than in the nontransformed ones ( p < 0.01). Transgenic hairy roots exhibited a 54.8-96.7% increase in the total phenolic content, 38.1-76.2% increase in the total flavonoid content, and 56.7-96.7% increase in the total reducing power when compared with the nontransgenic roots ( p < 0.01). DPPH results also revealed that the transgenic hairy roots exhibited a 31.6-50% increase in antioxidant potential, when compared to normal roots. This study addressed the enhancement of secondary metabolite biosynthesis by hairy root induction in L. serriola .

Resistant starch alters gut microbiome and metabolomics profiles concurrent with amelioration of chronic kidney disease in rats

USDA-ARS?s Scientific Manuscript database

Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xeno-metabolites). The fermentable dietary fiber—high amylose maize...

Increasing Student Achievement through Brain-Based Strategies

ERIC Educational Resources Information Center

Pociask, Amanda; Settles, Jeri

2007-01-01

The students targeted were third and fourth grade students with learning-disabilities and seventh-eighth grade science students who exhibited poor test scores, motivation, and behaviors that negatively impacted their learning. The objective of this study was to change the level of student engagement in order to increase their academic achievement…

T cells expanded in presence of IL-15 exhibit increased antioxidant capacity and innate effector molecules

PubMed Central

Kaur, Navtej; Naga, Osama S.; Norell, Håkan; Al-Khami, Amir A.; Scheffel, Matthew J.; Chakraborty, Nitya G.; Voelkel-Johnson, Christina; Mukherji, Bijay; Mehrotra, Shikhar

2011-01-01

Persistence of effector cytotoxic T lymphocytes (CTLs) during an immunological response is critical for successfully controlling a viral infection or tumor growth. Various cytokines are known to play an important part in regulating the immune response. The IL-2 family of cytokines that includes IL-2 and IL-15 are known to function as growth and survival factors for antigen-experienced T cells. IL-2 and IL-15 possess similar properties, including the ability to induce T cell proliferation. Whereas long term IL-2 exposure has been shown to promote apoptosis and limit CD8+ memory T cell survival and proliferation, it is widely believed that IL-15 can inhibit apoptosis and helps maintain a memory CD8+ T-cell population. However, mechanisms for superior outcomes for IL-15 as compared to IL-2 are still under investigation. Our data shows that human T cells cultured in the presence of IL-15 exhibit increased expression of anti-oxidant molecules Glutathione reductase (GSR), Thioredoxin reductase 1 (TXNDR1), Peroxiredoxin (PRDX), Superoxide dismutase (SOD). An increased expression of cell-surface thiols, intracellular glutathione, and thioredoxins was also noted in IL-15 cultured T cells. Additionally, IL-15 cultured T cells also showed an increase in cytolytic effector molecules. Apart from increased level of Granzyme A and Granzyme B, IL-15 cultured T cells exhibit increased accumulation of reactive oxygen (ROS) and reactive nitrogen (RNS) species as compared to IL-2 cultured T cells. Overall, this study suggests that T cells cultured in IL-15 show increase persistence not only due to increased anti-apoptotic proteins but also due to increased anti-oxidant levels, which is further complimented by increased cytolytic effector functions. PMID:21602054

Expression of a Heterologous S-Adenosylmethionine Decarboxylase cDNA in Plants Demonstrates That Changes in S-Adenosyl-l-Methionine Decarboxylase Activity Determine Levels of the Higher Polyamines Spermidine and Spermine1

PubMed Central

Thu-Hang, Pham; Bassie, Ludovic; Safwat, Gehan; Trung-Nghia, Pham; Christou, Paul; Capell, Teresa

2002-01-01

We posed the question of whether steady-state levels of the higher polyamines spermidine and spermine in plants can be influenced by overexpression of a heterologous cDNA involved in the later steps of the pathway, in the absence of any further manipulation of the two synthases that are also involved in their biosynthesis. Transgenic rice (Oryza sativa) plants engineered with the heterologous Datura stramonium S-adenosylmethionine decarboxylase (samdc) cDNA exhibited accumulation of the transgene steady-state mRNA. Transgene expression did not affect expression of the orthologous samdc gene. Significant increases in SAMDC activity translated to a direct increase in the level of spermidine, but not spermine, in leaves. Seeds recovered from a number of plants exhibited significant increases in spermidine and spermine levels. We demonstrate that overexpression of the D. stramonium samdc cDNA in transgenic rice is sufficient for accumulation of spermidine in leaves and spermidine and spermine in seeds. These findings suggest that increases in enzyme activity in one of the two components of the later parts of the pathway leading to the higher polyamines is sufficient to alter their levels mostly in seeds and, to some extent, in vegetative tissue such as leaves. Implications of our results on the design of rational approaches for the modulation of the polyamine pathway in plants are discussed in the general framework of metabolic pathway engineering. PMID:12177487

Pigeonpea Hybrid-Proline-Rich Protein (CcHyPRP) Confers Biotic and Abiotic Stress Tolerance in Transgenic Rice

PubMed Central

Mellacheruvu, Sunitha; Tamirisa, Srinath; Vudem, Dashavantha Reddy; Khareedu, Venkateswara Rao

2016-01-01

In this study, we report the overexpression of Cajanus cajan hybrid-proline-rich protein encoding gene (CcHyPRP) in rice which resulted in increased tolerance to both abiotic and biotic stresses. Compared to the control plants, the transgenic rice lines, expressing CcHyPRP, exhibited high-level tolerance against major abiotic stresses, viz., drought, salinity, and heat, as evidenced by increased biomass, chlorophyll content, survival rate, root, and shoot growth. Further, transgenic rice lines showed increased panicle size and grain number compared to the control plants under different stress conditions. The CcHyPRP transgenics, as compared to the control, revealed enhanced activities of catalase and superoxide dismutase (SOD) enzymes and reduced malondialdehyde (MDA) levels. Expression pattern of CcHyPRP::GFP fusion-protein confirmed its predominant localization in cell walls. Moreover, the CcHyPRP transgenics, as compared to the control, exhibited increased resistance to the fungal pathogen Magnaporthe grisea which causes blast disease in rice. Higher levels of bZIP and endochitinase transcripts as well as endochitinase activity were observed in transgenic rice compared to the control plants. The overall results demonstrate the intrinsic role of CcHyPRP in conferring multiple stress tolerance at the whole-plant level. The multipotent CcHyPRP seems promising as a prime candidate gene to fortify crop plants for enhanced tolerance/resistance to different stress factors. PMID:26834756

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.

Cooking quality properties and free and bound phenolics content of brown, black, and red rice grains stored at different temperatures for six months.

PubMed

Ziegler, Valmor; Ferreira, Cristiano Dietrich; Hoffmann, Jessica Fernanda; Chaves, Fábio Clasen; Vanier, Nathan Levien; de Oliveira, Maurício; Elias, Moacir Cardoso

2018-03-01

The changes in cooking quality and phenolic composition of whole black and red rice grains stored during six months at different temperatures were evaluated. Brown rice with known cooking quality properties and low phenolic levels was used for purposes comparison. All rice genotypes were stored at 13% moisture content at temperatures of 16, 24, 32, and 40°C. Cooking time, hardness, free and bound phenolics, anthocyanins, proanthocyanidins, and free radical scavenging capacity were analysed. The traditional rice with brown pericarp exhibited an increase in cooking time and free phenolics content, while rice with black pericarp exhibited a reduction in cooking time after six months of storage at the highest studied temperature of 40°C. There as increases in ferulic acid levels occurred as a function of storage temperature. Red pericarp rice grains showed decreased antioxidant capacity against ABTS radical for the soluble phenolic fraction with increased time and storage temperature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression

PubMed Central

Podda, Maria Vittoria; Cocco, Sara; Mastrodonato, Alessia; Fusco, Salvatore; Leone, Lucia; Barbati, Saviana Antonella; Colussi, Claudia; Ripoli, Cristian; Grassi, Claudio

2016-01-01

The effects of transcranial direct current stimulation (tDCS) on brain functions and the underlying molecular mechanisms are yet largely unknown. Here we report that mice subjected to 20-min anodal tDCS exhibited one-week lasting increases in hippocampal LTP, learning and memory. These effects were associated with enhanced: i) acetylation of brain-derived neurotrophic factor (Bdnf) promoter I; ii) expression of Bdnf exons I and IX; iii) Bdnf protein levels. The hippocampi of stimulated mice also exhibited enhanced CREB phosphorylation, pCREB binding to Bdnf promoter I and recruitment of CBP on the same regulatory sequence. Inhibition of acetylation and blockade of TrkB receptors hindered tDCS effects at molecular, electrophysiological and behavioral levels. Collectively, our findings suggest that anodal tDCS increases hippocampal LTP and memory via chromatin remodeling of Bdnf regulatory sequences leading to increased expression of this gene, and support the therapeutic potential of tDCS for brain diseases associated with impaired neuroplasticity. PMID:26908001

Membrane-bound (MUC1) and secretory (MUC2, MUC3, and MUC4) mucin gene expression in human lung cancer.

PubMed

Nguyen, P L; Niehans, G A; Cherwitz, D L; Kim, Y S; Ho, S B

1996-01-01

Abnormalities of mucin-type glycoproteins have been described in lung cancers, but their molecular basis is unknown. In this study, mucin-core-peptide-specific antibodies and cDNA probes were used to determine the relative expression of mucin genes corresponding to one membrane-bound mucin (MUC1), two intestinal mucins (MUC2 and MUC3), and one tracheobronchial mucin (MUC4) in normal (nonneoplastic) lung, and in lung neoplasms. Normal lung tissues exhibited a distinct pattern of mucin gene expression, with high levels of MUC1 and MUC4 mRNA and low to absent levels of MUC2 and MUC3 mucin immunoreactivity and mRNA. In contrast, lung adenocarcinomas, especially well-differentiated cancers, exhibited increased MUC1, MUC3, and MUC4 mRNA levels. Lung squamous-cell, adenosquamous, and large-cell carcinomas were characterized by increased levels of MUC4 mucin only. We conclude that the expression of one membrane-bound and several secretory-type mucins is independently regulated and markedly altered in lung neoplasms. The frequent occurrence of increased MUC4 transcripts in a variety of non-small-cell lung cancers indicates the potential importance of this type of mucin in lung cancer biology.

Mechanosensory based orienting behaviors in fluvial and lacustrine populations of mottled sculpin (Cottus bairdi)

Treesearch

Sheryl Coombs; Gary D. Grossman

2006-01-01

We compared prey-orienting and rheotactic behaviors in a fluvial (Coweeta Creek) and lacustrine (Lake Michigan) population of mottled sculpin. Blinded sculpin from both populations exhibited unconditioned, mechanosensory based rheotaxis to low velocity flows. Whereas Lake Michigan sculpin generally showed increasing levels of positive rheotaxis to increasing velocities...

Increased susceptibility to metabolic dysregulation in a mouse model of Alzheimer’s disease is associated with impaired hypothalamic insulin signaling and elevated BCAA levels

PubMed Central

Ruiz, Henry H.; Chi, Tiffany; Shin, Andrew C.; Lindtner, Claudia; Hsieh, Wilson; Ehrlich, Michelle; Gandy, Sam; Buettner, Christoph

2016-01-01

Introduction Epidemiologic studies have demonstrated an association between diabetes and dementia. Insulin signaling within the brain, in particular within the hypothalamus regulates carbohydrate, lipid, and branched chain amino acid (BCAA) metabolism in peripheral organs such as the liver and adipose tissue. We hypothesized that cerebral amyloidosis impairs central nervous system control of metabolism through disruption of insulin signaling in the hypothalamus, which dysregulates glucose and BCAA homeostasis resulting in increased susceptibility to diabetes. Methods We examined whether APP/PS1 mice exhibit increased susceptibility to aging or high-fat diet (HFD)-induced metabolic impairment using metabolic phenotyping and insulin-signaling studies. Results APP/PS1 mice were more susceptible to high-fat feeding and aging-induced metabolic dysregulation including disrupted BCAA homeostasis and exhibited impaired hypothalamic insulin signaling. Discussion Our data suggest that AD pathology increases susceptibility to diabetes due to impaired hypothalamic insulin signaling, and that plasma BCAA levels could serve as a biomarker of hypothalamic insulin action in patients with AD. PMID:26928090

Increased susceptibility to metabolic dysregulation in a mouse model of Alzheimer's disease is associated with impaired hypothalamic insulin signaling and elevated BCAA levels.

PubMed

Ruiz, Henry H; Chi, Tiffany; Shin, Andrew C; Lindtner, Claudia; Hsieh, Wilson; Ehrlich, Michelle; Gandy, Sam; Buettner, Christoph

2016-08-01

Epidemiologic studies have demonstrated an association between diabetes and dementia. Insulin signaling within the brain, in particular within the hypothalamus regulates carbohydrate, lipid, and branched chain amino acid (BCAA) metabolism in peripheral organs such as the liver and adipose tissue. We hypothesized that cerebral amyloidosis impairs central nervous system control of metabolism through disruption of insulin signaling in the hypothalamus, which dysregulates glucose and BCAA homeostasis resulting in increased susceptibility to diabetes. We examined whether APP/PS1 mice exhibit increased susceptibility to aging or high-fat diet (HFD)-induced metabolic impairment using metabolic phenotyping and insulin-signaling studies. APP/PS1 mice were more susceptible to high-fat feeding and aging-induced metabolic dysregulation including disrupted BCAA homeostasis and exhibited impaired hypothalamic insulin signaling. Our data suggest that AD pathology increases susceptibility to diabetes due to impaired hypothalamic insulin signaling, and that plasma BCAA levels could serve as a biomarker of hypothalamic insulin action in patients with AD. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Over-expression of LeNCED1 in tomato (Solanum lycopersicum L.) with the rbcS3C promoter allows recovery of lines that accumulate very high levels of abscisic acid and exhibit severe phenotypes.

PubMed

Tung, Swee Ang; Smeeton, Rachel; White, Charlotte A; Black, Colin R; Taylor, Ian B; Hilton, Howard W; Thompson, Andrew J

2008-07-01

Previous work where 9-cis-epoxycarotenoid dioxygenase (NCED) was over-expressed using the constitutive Gelvin Superpromoter resulted in mild increases in abscisic acid (ABA) accumulation, accompanied by stomatal closure and increased water-use efficiency (WUE), but with apparently little impact on long-term biomass production. However, one of the negative effects of the over-expression of NCED using constitutive promoters in tomato was increased seed dormancy. Here we report the use of the rbcS3C promoter, from a gene encoding the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), to drive LeNCED1 transgene expression in tomato in a light-responsive and circadian manner. In comparison to the constitutive promoter, the rbcS3C promoter allowed the generation of transgenic plants with much higher levels of ABA accumulation in leaves and sap, but the effect on seed dormancy was diminished. These plants displayed the expected reductions in stomatal conductance and CO(2) assimilation, but they also exhibited a severe set of symptoms that included perturbed cotyledon release from the testa, increased photobleaching in young seedlings, substantially reduced chlorophyll and carotenoid content, interveinal leaf flooding, and greatly reduced growth. These symptoms illustrate adverse consequences of long-term, very high ABA accumulation. Only more moderate increases in ABA biosynthesis are likely to be useful in the context of agriculture. Implications are discussed for the design of transgenic 'high ABA' plants that exhibit increased WUE but have minimal negative phenotypic effects.

Beyond Auditory Sensory Processing Deficits: Lexical Tone Perception Deficits in Chinese Children with Developmental Dyslexia

ERIC Educational Resources Information Center

Tong, Xiuhong; Tong, Xiuli; King Yiu, Fung

2018-01-01

Increasing evidence suggests that children with developmental dyslexia exhibit a deficit not only at the segmental level of phonological processing but also, by extension, at the suprasegmental level. However, it remains unclear whether such a suprasegmental phonological processing deficit is due to a difficulty in processing acoustic cues of…

Single Parents and the Work Setting: The Impact of Multiple Job and Homelife Responsibilities.

ERIC Educational Resources Information Center

Burden, Dianne S.

1986-01-01

Examines the impact of combined work/family responsibilities on single-parent employees. Results indicated that parent employees, but particularly single female parents, were at risk for high job-family role strain and reduced levels of well-being. In spite of increased strain, however, single parents exhibited high levels of job satisfaction and…

Micro-abrasion-corrosion behaviour of a biomedical Ti-25Nb-3Mo-3Zr-2Sn alloy in simulated physiological fluid.

PubMed

Wang, Zhenguo; Li, Yan; Huang, Weijiu; Chen, Xiaoli; He, Haoran

2016-10-01

The micro-abrasion-corrosion behaviour of the biomedical Ti-25Nb-3Mo-3Zr-2Sn alloy in Hank׳s solution with protein has been investigated using electrochemical measurements, tribological tests and scanning electron microscope (SEM) observations. The potentiodynamic polarization tests showed that the corrosion potential (Ecorr) exhibits the maximum value at the abrasive concentration of 0.05gcm(-3) despite of the load level. The tribological results indicated that the total material loss of the Ti-25Nb-3Mo-3Zr-2Sn alloy during micro-abrasion increased with the increasing abrasive concentration at a certain applied load. When the abrasive concentration is no more than 0.15gcm(-3), the total material loss increases with increasing load, while the total material loss exhibits the maximum value at a moderate load in case of higher abrasive concentration levels. This was ascribed to the three-body or two-body micro-abrasion-corrosion at different abrasive concentration levels. The wastage map, abrasion mode map and synergy map associated with the applied load and the abrasive concentration were constructed to evaluate the micro-abrasion-corrosion behaviour of the Ti-25Nb-3Mo-3Zr-2Sn alloy in potential biomedical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Engrailed-2 (En2) deletion produces multiple neurodevelopmental defects in monoamine systems, forebrain structures and neurogenesis and behavior

PubMed Central

Genestine, Matthieu; Lin, Lulu; Durens, Madel; Yan, Yan; Jiang, Yiqin; Prem, Smrithi; Bailoor, Kunal; Kelly, Brian; Sonsalla, Patricia K.; Matteson, Paul G.; Silverman, Jill; Crawley, Jacqueline N.; Millonig, James H.; DiCicco-Bloom, Emanuel

2015-01-01

Many genes involved in brain development have been associated with human neurodevelopmental disorders, but underlying pathophysiological mechanisms remain undefined. Human genetic and mouse behavioral analyses suggest that ENGRAILED-2 (EN2) contributes to neurodevelopmental disorders, especially autism spectrum disorder. In mouse, En2 exhibits dynamic spatiotemporal expression in embryonic mid-hindbrain regions where monoamine neurons emerge. Considering their importance in neuropsychiatric disorders, we characterized monoamine systems in relation to forebrain neurogenesis in En2-knockout (En2-KO) mice. Transmitter levels of serotonin, dopamine and norepinephrine (NE) were dysregulated from Postnatal day 7 (P7) to P21 in En2-KO, though NE exhibited the greatest abnormalities. While NE levels were reduced ∼35% in forebrain, they were increased 40–75% in hindbrain and cerebellum, and these patterns paralleled changes in locus coeruleus (LC) fiber innervation, respectively. Although En2 promoter was active in Embryonic day 14.5–15.5 LC neurons, expression diminished thereafter and gene deletion did not alter brainstem NE neuron numbers. Significantly, in parallel with reduced NE levels, En2-KO forebrain regions exhibited reduced growth, particularly hippocampus, where P21 dentate gyrus granule neurons were decreased 16%, suggesting abnormal neurogenesis. Indeed, hippocampal neurogenic regions showed increased cell death (+77%) and unexpectedly, increased proliferation. Excess proliferation was restricted to early Sox2/Tbr2 progenitors whereas increased apoptosis occurred in differentiating (Dcx) neuroblasts, accompanied by reduced newborn neuron survival. Abnormal neurogenesis may reflect NE deficits because intra-hippocampal injections of β-adrenergic agonists reversed cell death. These studies suggest that disruption of hindbrain patterning genes can alter monoamine system development and thereby produce forebrain defects that are relevant to human neurodevelopmental disorders. PMID:26220976

The bidirectional effects of hypothyroidism and hyperthyroidism on anxiety- and depression-like behaviors in rats.

PubMed

Yu, Dafu; Zhou, Heng; Yang, Yuan; Jiang, Yong; Wang, Tianchao; Lv, Liang; Zhou, Qixin; Yang, Yuexiong; Dong, Xuexian; He, Jianfeng; Huang, Xiaoyan; Chen, Jijun; Wu, Kunhua; Xu, Lin; Mao, Rongrong

2015-03-01

Thyroid hormone disorders have long been linked to depression, but the causal relationship between them remains controversial. To address this question, we established rat models of hypothyroidism using (131)iodine ((131)I) and hyperthyroidism using levothyroxine (LT4). Serum free thyroxine (FT4) and triiodothyronine (FT3) significantly decreased in the hypothyroid of rats with single injections of (131)I (5mCi/kg). These rats exhibited decreased depression-like behaviors in forced swimming test and sucrose preference tests, as well as decreased anxiety-like behaviors in an elevated plus maze. Diminished levels of brain serotonin (5-HT) and increased levels of hippocampal brain-derived neurotrophic factor (BDNF) were found in the hypothyroid rats compared to the control saline-vehicle administered rats. LT4 treatment reversed the decrease in thyroid hormones and depression-like behaviors. In contrast, hyperthyroidism induced by weekly injections of LT4 (15μg/kg) caused a greater than 10-fold increase in serum FT4 and FT3 levels. The hyperthyroid rats exhibited higher anxiety- and depression-like behaviors, higher brain 5-HT level, and lower hippocampal BDNF levels than the controls. Treatment with the antidepressant imipramine (15mg/kg) diminished serum FT4 levels as well as anxiety- and depression-like behaviors in the hyperthyroid rats but led to a further increase in brain 5-HT levels, compared with the controls or the hypothyroid rats. Together, our results suggest that hypothyroidism and hyperthyroidism have bidirectional effects on anxiety- and depression-like behaviors in rats, possibly by modulating hippocampal BDNF levels. Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical and toxicological evaluation of methanol extract of Cuscuta reflexa Roxb. stem and Corchorus olitorius Linn. seed on hematological parameters and hepatorenal functions in mice.

PubMed

Mazumder, Upal Kanti; Gupta, Malaya; Pal, Dilipkumar; Bhattacharya, Shiladitya

2003-01-01

Methanol extract of Cuscuta reflexa Roxb. stem (MECR) contain flavonoids (0.2%) and Corchorus olitorius Linn. seed (MECO) was found to contain steroids and cardenolide glycosides. Effects of multiple weekly dose of MECR (25, 50, 75 mg/kg, i.p.) and MECO (15, 20, 25 mg/kg, i.p.) on liver and kidney functions and hematological parameters in mice were studied. No significant alteration of RBC count and hemoglobin content was observed in all dose level of treatment in MECR and MECO treated mice whereas significant increase of clotting time was seen in moderate and high doses in both case. MECR and MECO both caused significant increase in WBC count only in high dose level of treatment. Both the extracts in medium and high dose level increased SGOT, SGPT, NPN and plasma cholesterol significantly. Serum alkaline phosphatase and total bilirubin were also increased by both moderate and high dose level of treatments in MECR and MECO treated mice respectively. Low dose of both the extract did not exhibit any significant change of creatinine and serum protein level. But high dose level of MECR and MECO significantly increased creatinine level. Increase in plasma cholesterol may be due to decrease in cholesterol catabolism owing to liver dysfunction of due to the intake of MECO itself as it was found to be steroid in nature. Elevated level of SGOT, SGPT and serum alkaline phosphatase activity in moderate and high dose level of weekly treated mice may be due to improper liver function following the treatment. Increased urea, non protein nitrogen and creatinine content in blood have been observed with impaired renal function. The slightly higher toxicity in case of MECO treated mice may be due to the presence of cardenolide glycosides in the ME of C. olitorius seed. However, low doses of MECR and MECO (25 and 15 mg/kg, i.p. respectively) did not exhibit any remarkable change on liver and kidney functions and hematological parameters.

Regional sea level projections with observed gauge, altimeter and reconstructed data along China coast

NASA Astrophysics Data System (ADS)

Du, L.; Shi, H.; Zhang, S.

2017-12-01

Acting as the typical shelf seas in northwest Pacific Ocean, regional sea level along China coasts exhibits complicated and multiscale spatial-temporal characteristics under circumstance of global change. In this paper, sea level variability is investigated with tide gauges records, satellite altimetry data, reconstructed sea surface height, and CMIP simulation fields. Sea level exhibits the interannual variability imposing on a remarkable sea level rising in the China seas and coastal region, although its seasonal signals are significant as the results of global ocean. Sea level exhibits faster rising rate during the satellite altimetry era, nearly twice to the rate during the last sixty years. AVISO data and reconstructed sea surface heights illustrate good correlation coefficient, more than 0.8. Interannual sea level variation is mainly modulated by the low-frequency variability of wind fields over northern Pacific Ocean by local and remote processes. Meanwhile sea level varies obviously by the transport fluctuation and bimodality path of Kuroshio. Its variability possibly linked to internal variability of the ocean-atmosphere system influenced by ENSO oscillation. China Sea level have been rising during the 20th century, and are projected to continue to rise during this century. Sea level can reach the highest extreme level in latter half of 21st century. Modeled sea level including regional sea level projection combined with the IPCC climate scenarios play a significant role on coastal storm surge evolution. The vulnerable regions along the ECS coast will suffer from the increasing storm damage with sea level variations.

Reproduction in shark-attacked sea turtles is supported by stress-reduction mechanisms.

PubMed Central

Jessop, Tim; Sumner, Joanna; Lance, Val; Limpus, Col

2004-01-01

Vertebrates exhibit varied behavioural and physiological tactics to promote reproductive success. We examined mechanisms that could enable female loggerhead turtles to undertake nesting activities and maintain seasonal reproduction despite recent shark injuries of varying severity. We proposed that endocrinal mechanisms that regulate both a turtle's stress response and reproductive ability are modified to promote successful and continued reproduction. Irrespective of the degree of injury, females did not exhibit increased levels of the stress hormone corticosterone, nor decreased levels of the reproductive steroid testosterone; hormone responses consistent with stress. When exposed to a capture stressor, females with shark injury did not exhibit any greater corticosterone response than controls. In addition, breeding females showed a reduced corticosterone stress response compared to non-breeding females. Reduced endocrinal responses following shark injury, and during breeding in general may, in part, enable females to maintain behavioural and physiological commitment to reproduction. PMID:15101429

Insulin-like growth factor binding protein-1 levels are increased in patients with IgA nephropathy

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

Tokunaga, Koki; Uto, Hirofumi, E-mail: hirouto@m2.kufm.kagoshima-u.ac.jp; Takami, Yoichiro

2010-08-20

Research highlights: {yields} IGFBP-1 mRNA over express in kidneys obtained from mice model of IgA nephropathy. {yields} Serum IGFBP-1 levels are high in patients with IgA nephropathy. {yields} Serum IGFBP-1 levels correlate with renal function and the severity of renal injury. -- Abstract: The mechanisms underlying the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) are not well understood. In this study, we examined gene expression profiles in kidneys obtained from mice with high serum IgA levels (HIGA mice), which exhibit features of human IgAN. Female inbred HIGA, established from the ddY line, were used in these experiments. Serum IgA levels,more » renal IgA deposition, mesangial proliferation, and glomerulosclerosis were increased in 32-week-old HIGA mice in comparison to ddY animals. By microarray analysis, five genes were observed to be increased by more than 2.5-fold in 32-week-old HIGA in comparison to 16-week-old HIGA; these same five genes were decreased more than 2.5-fold in 32-week-old ddY in comparison to 16-week-old ddY mice. Of these five genes, insulin-like growth factor (IGF) binding protein (IGFBP)-1 exhibited differential expression between these mouse lines, as confirmed by quantitative RT-PCR. In addition, serum IGFBP-1 levels were significantly higher in patients with IgAN than in healthy controls. In patients with IgAN, these levels correlated with measures of renal function, such as estimated glomerular filtration rate (eGFR), but not with sex, age, serum IgA, C3 levels, or IGF-1 levels. Pathologically, serum IGFBP-1 levels were significantly associated with the severity of renal injury, as assessed by mesangial cell proliferation and interstitial fibrosis. These results suggest that increased IGFBP-1 levels are associated with the severity of renal pathology in patients with IgAN.« less

Transgenic alfalfa (Medicago sativa) with increased sucrose phosphate synthase activity shows enhanced growth when grown under N2-fixing conditions.

PubMed

Gebril, Sayed; Seger, Mark; Villanueva, Fabiola Muro; Ortega, Jose Luis; Bagga, Suman; Sengupta-Gopalan, Champa

2015-10-01

Overexpression of SPS in alfalfa is accompanied by early flowering, increased plant growth and an increase in elemental N and protein content when grown under N2-fixing conditions. Sucrose phosphate synthase (SPS; EC 2.3.1.14) is the key enzyme in the synthesis of sucrose in plants. The outcome of overexpression of SPS in different plants using transgenic approaches has been quite varied, but the general consensus is that increased SPS activity is associated with the production of new sinks and increased sink strength. In legumes, the root nodule is a strong C sink and in this study our objective was to see how increasing SPS activity in a legume would affect nodule number and function. Here we have transformed alfalfa (Medicago sativa, cv. Regen SY), with a maize SPS gene driven by the constitutive CaMV35S promoter. Our results showed that overexpression of SPS in alfalfa, is accompanied by an increase in nodule number and mass and an overall increase in nitrogenase activity at the whole plant level. The nodules exhibited an increase in the level of key enzymes contributing to N assimilation including glutamine synthetase and asparagine synthetase. Moreover, the stems of the transformants showed higher level of the transport amino acids, Asx, indicating increased export of N from the nodules. The transformants exhibited a dramatic increase in growth both of the shoots and roots, and earlier flowering time, leading to increased yields. Moreover, the transformants showed an increase in elemental N and protein content. The overall conclusion is that increased SPS activity improves the N status and plant performance, suggesting that the availability of more C in the form of sucrose enhances N acquisition and assimilation in the nodules.

Genetic Transformation and Hairy Root Induction Enhance the Antioxidant Potential of Lactuca serriola L.

PubMed Central

Elkelish, Amr; Elansary, Hosam O.; Ali, Hayssam M.; Elshikh, Mohamed; Witczak, Jacques; Ahmad, Margaret

2017-01-01

Lactuca serriola L. is a herbaceous species, used for human nutrition and medicinal purposes. The high antioxidant capacity of L. serriola indicates the possibility of enhancing its edible and health potential by increasing the flavonoid and phenolic contents. The present study aimed at enhancing the production of phenolics and flavonoids by hairy root cultures in Lactuca serriola transformed with Agrobacterium rhizogenes strain AR15834 harbouring the rolB gene. The genetic transformation of rolB in transformed roots was validated, and rolB expression level was evaluated using real-time qPCR analysis. Expression levels of flavonoid biosynthesis genes (CHI, PAL, FLS, and CHS) were assessed in the hairy and nontransformed roots. Results showed higher expression levels in the transgenic roots than in the nontransformed ones (p < 0.01). Transgenic hairy roots exhibited a 54.8–96.7% increase in the total phenolic content, 38.1–76.2% increase in the total flavonoid content, and 56.7–96.7% increase in the total reducing power when compared with the nontransgenic roots (p < 0.01). DPPH results also revealed that the transgenic hairy roots exhibited a 31.6–50% increase in antioxidant potential, when compared to normal roots. This study addressed the enhancement of secondary metabolite biosynthesis by hairy root induction in L. serriola. PMID:28835782

Increasing Student Physical Fitness through Increased Choice of Fitness Activities and Student Designed Fitness Activities for Ninth through Twelfth Graders in Physical Education Class

ERIC Educational Resources Information Center

Jacob, Margo A.

2011-01-01

This action research project report began when the teacher researcher determined that students exhibited physical fitness levels below that of the state and national norms, and also displayed negative attitudes about physical education. The purpose of this action research project was to increase physical fitness and fitness attitudes through…

Pain Behavior in Rheumatoid Arthritis Patients: Identification of Pain Behavior Subgroups

PubMed Central

Waters, Sandra J.; Riordan, Paul A.; Keefe, Francis J.; Lefebvre, John C.

2008-01-01

This study used Ward’s minimum variance hierarchical cluster analysis to identify homogeneous subgroups of rheumatoid arthritis patients suffering from chronic pain who exhibited similar pain behavior patterns during a videotaped behavior sample. Ninety-two rheumatoid arthritis patients were divided into two samples. Six motor pain behaviors were examined: guarding, bracing, active rubbing, rigidity, grimacing, and sighing. The cluster analysis procedure identified four similar subgroups in Sample 1 and Sample 2. The first subgroup exhibited low levels of all pain behaviors. The second subgroup exhibited a high level of guarding and low levels of other pain behaviors. The third subgroup exhibited high levels of guarding and rigidity and low levels of other pain behaviors. The fourth subgroup exhibited high levels of guarding and active rubbing and low levels of other pain behaviors. Sample 1 contained a fifth subgroup that exhibited a high level of active rubbing and low levels of other pain measures. The results of this study suggest that there are homogeneous subgroups within rheumatoid arthritis patient populations who differ in the motor pain behaviors they exhibit. PMID:18358682

Estradiol selectively enhances auditory function in avian forebrain neurons

PubMed Central

Caras, Melissa L.; O’Brien, Matthew; Brenowitz, Eliot A.; Rubel, Edwin W

2012-01-01

Sex steroids modulate vertebrate sensory processing, but the impact of circulating hormone levels on forebrain function remains unclear. We tested the hypothesis that circulating sex steroids modulate single-unit responses in the avian telencephalic auditory nucleus, field L. We mimicked breeding or non-breeding conditions by manipulating plasma 17β-estradiol levels in wild-caught female Gambel’s white-crowned sparrows (Zonotrichia leucophrys gambelii). Extracellular responses of single neurons to tones and conspecific songs presented over a range of intensities revealed that estradiol selectively enhanced auditory function in cells that exhibited monotonic rate-level functions to pure tones. In these cells, estradiol treatment increased spontaneous and maximum evoked firing rates, increased pure tone response strengths and sensitivity, and expanded the range of intensities over which conspecific song stimuli elicited significant responses. Estradiol did not significantly alter the sensitivity or dynamic ranges of cells that exhibited non-monotonic rate-level functions. Notably, there was a robust correlation between plasma estradiol concentrations in individual birds and physiological response properties in monotonic, but not non-monotonic neurons. These findings demonstrate that functionally distinct classes of anatomically overlapping forebrain neurons are differentially regulated by sex steroid hormones in a dose-dependent manner. PMID:23223283

Birge-Sponer Estimation of the C-H Bond Dissociation Energy in Chloroform Using Infrared, Near-Infrared, and Visible Absorption Spectroscopy: An Experiment in Physical Chemistry

ERIC Educational Resources Information Center

Myrick, M. L.; Greer, A. E.; Nieuwland, A. A.; Priore, R. J.; Scaffidi, J.; Andreatta, Danielle; Colavita, Paula

2008-01-01

The fundamental and overtone vibrational absorption spectroscopy of the C-H unit in CHCl[subscript 3] is measured for transitions from the v = 0 energy level to v = 1 through v = 5 energy levels. The energies of the transitions exhibit a linearly-decreasing spacing between adjacent vibrational levels as the vibrational quantum number increases.…

Hydrophytes lack potential to exhibit cadmium stress induced enhancement in lipid peroxidation and accumulation of proline.

PubMed

Dhir, Bhupinder; Sharmila, P; Saradhi, P Pardha

2004-02-10

Investigations were carried out to evaluate if hydrophytes (viz. Ceratophyllum, Wolffia, and Hydrilla) can be used as markers to assess the level of heavy metal pollution in aquatic bodies. The potential of these hydrophytes for lipid peroxidation and accumulation of proline in response to cadmium (Cd2+) pollution was studied. Hydrophytes were raised in artificial pond water (APW) supplemented with various levels of Cd2+. Interestingly, unlike mesophytes none of the hydrophytes showed ability to accumulate proline. Infact, in response to Cd2+ pollution hydrophytes exhibited a decline in proline levels in comparison to controls but mesophytes (viz. Brassica juncea, Vigna radiata and Triticum aestivum) showed progressive increase in the level of proline with increase in the extent of Cd2+ pollution. Mesophytes showed six to nine-fold increase in the level of proline in response to 1 mM Cd2+. The potential of the above hydrophytes for lipid peroxidation was also low under Cd2+ stress. In contrast, as expected a significant enhancement in the lipid peroxidation was observed in all three mesophytes in response to their exposure to Cd2+. About two-fold increase in production of malondialdehyde (a cytotoxic product of lipid peroxidation) was recorded in mesophytes exposed to 1 mM Cd2+. However, a decline in chlorophyll (Chl a and Chl b) levels was recorded in response to Cd2+pollution both in hydrophytes as well as mesophytes. In summary, hydrophytes neither have potential to accumulate proline nor have ability to accelerate lipid peroxidation under heavy metal stress. This suggests that the adaptive mechanism(s) existing in hydrophytes to tackle heavy metal stress is distinct from that in mesophytes.

Dynamics of DDT in the terrestrial snail Otala lactea (Stylommatophora:Helicidae)

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

Wurzinger, K.H.; Dindal, D.L.

1975-01-01

Seventy specimens of Otala lactea (Mueller) were fed 40 ..mu..g radiolabelled DDT.gram/sup -1/ body weight and analyzed by liquid scintillation spectrometry to determine the body distribution and dynamics of the DDT within the snail's tissues. More than 50% of the pesticide fed to the animals was excreted in the feces after 1 to 2 days. Residues in the body accumulated mostly in the hepatopancreas. All tissues assayed contained measureable quantities of DDT. Five patterns of residue distribution/time were apparent. Pattern I, exhibited by the buccal mass, esophagus, crop, stomach and intestine, showed a general decrease in residue concentrations over themore » 14 day test period. Pattern II, exhibited by the hepatopancreas, kidney, ovotestis, sperm-oviduct, albumen gland and mucous gland, showed a general increase in residue concentrations. Pattern III, exhibited by the salivary gland, spermatheca, circumesophageal nerve ring, lung, collar (mantle edge), foot and vagina + dart sack, showed a fairly constant level of residues. Pattern IV, exhibited by the retractor muscles, epidermis and heart, showed a cyclical distribution of residue levels. Pattern V, exhibited by the penis, showed a cyclical distribution of residue levels that were different from Pattern IV. A double compartment scheme was utilized to explain those trends. Period A, corresponding to the fast compartment, is due to the initial ingestionof insecticide. Periods B and C, corresponding to the slow compartment, are due to the redistribution of residues within the organism.« less

Effects of tree height on branch hydraulics, leaf structure and gas exchange in California redwoods.

PubMed

Ambrose, Anthony R; Sillett, Stephen C; Dawson, Todd E

2009-07-01

We examined changes in branch hydraulic, leaf structure and gas exchange properties in coast redwood (Sequoia sempervirens) and giant sequoia (Sequoiadendron giganteum) trees of different sizes. Leaf-specific hydraulic conductivity (k(L)) increased with height in S. sempervirens but not in S. giganteum, while xylem cavitation resistance increased with height in both species. Despite hydraulic adjustments, leaf mass per unit area (LMA) and leaf carbon isotope ratios (delta(13)C) increased, and maximum mass-based stomatal conductance (g(mass)) and photosynthesis (A(mass)) decreased with height in both species. As a result, both A(mass) and g(mass) were negatively correlated with branch hydraulic properties in S. sempervirens and uncorrelated in S. giganteum. In addition, A(mass) and g(mass) were negatively correlated with LMA in both species, which we attributed to the effects of decreasing leaf internal CO(2) conductance (g(i)). Species-level differences in wood density, LMA and area-based gas exchange capacity constrained other structural and physiological properties, with S. sempervirens exhibiting increased branch water transport efficiency and S. giganteum exhibiting increased leaf-level water-use efficiency with increasing height. Our results reveal different adaptive strategies for the two redwoods that help them compensate for constraints associated with growing taller, and reflect contrasting environmental conditions each species faces in its native habitat.

The glutathione defense system in the pathogenesis of rheumatoid arthritis.

PubMed

Hassan, M Q; Hadi, R A; Al-Rawi, Z S; Padron, V A; Stohs, S J

2001-01-01

In order to assess a possible role of the natural glutathione defense system in the pathogenesis of rheumatoid arthritis (RA), serum reduced glutathione levels (GSH), glutathione reductase (GSR), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px) and alkaline phosphatase (ALP) activities, lipid peroxidation (MDA content) and indexes of inflammation were evaluated in 58 rheumatic patients. Rheumatoid athritis was associated with significant depletion (ca. 50%) in GSH levels compared with normal control subjects. Serum levels of the detoxifying enzymes GSR and GSH-Px decreased by ca. 50% and 45%, respectively, whereas a threefold increase in the activity of GST was observed. A 1.2-fold increase in ALP was observed in patients with RA. These effects were accompanied by a 3.1-fold increase in serum MDA content. The MDA content was higher in RA patients who were seropositive for rheumatoid factor as well as positive for C-reactive proteins. The erythrocyte sedimentation rate for all patients with RA was approximately 13.8-fold higher than for the control group, and was higher among RA patients who were positive for C-reactive proteins and exhibited seropositivity for rheumatoid factor. Patients with RA receiving gold therapy exhibited significantly lower MDA levels whereas all other factors that were measured were not effected. The results support a hypothesis that defense mechanisms against reactive oxygen species are impaired in RA. Copyright 2001 John Wiley & Sons, Ltd.

Sex-dependent alterations in motor and anxiety-like behavior of aged bacterial peptidoglycan sensing molecule 2 knockout mice.

PubMed

Arentsen, Tim; Khalid, Roksana; Qian, Yu; Diaz Heijtz, Rochellys

2018-01-01

Peptidoglycan recognition proteins (PGRPs) are key sensing-molecules of the innate immune system that specifically detect bacterial peptidoglycan (PGN) and its derivates. PGRPs have recently emerged as potential key regulators of normal brain development and behavior. To test the hypothesis that PGRPs play a role in motor control and anxiety-like behavior in later life, we used 15-month old male and female peptidoglycan recognition protein 2 (Pglyrp2) knockout (KO) mice. Pglyrp2 is an N-acetylmuramyl-l-alanine amidase that hydrolyzes PGN between the sugar backbone and the peptide chain (which is unique among the mammalian PGRPs). Using a battery of behavioral tests, we demonstrate that Pglyrp2 KO male mice display decreased levels of anxiety-like behavior compared with wild type (WT) males. In contrast, Pglyrp2 KO female mice show reduced rearing activity and increased anxiety-like behavior compared to WT females. In the accelerated rotarod test, however, Pglyrp2 KO female mice performed better compared to WT females (i.e., they had longer latency to fall off the rotarod). Further, Pglyrp2 KO male mice exhibited decreased expression levels of synaptophysin, gephyrin, and brain-derived neurotrophic factor in the frontal cortex, but not in the amygdala. Pglyrp2 KO female mice exhibited increased expression levels of spinophilin and alpha-synuclein in the frontal cortex, while exhibiting decreased expression levels of synaptophysin, gephyrin and spinophilin in the amygdala. Our findings suggest a novel role for Pglyrp2asa key regulator of motor and anxiety-like behavior in late life. Copyright © 2017. Published by Elsevier Inc.

Impact of ultraviolet radiation treatments on the quality of freshly prepared tomato (Solanum lycopersicum) juice.

PubMed

Bhat, Rajeev

2016-12-15

Impact of ultraviolet (UV-C) radiation treatments (0, 15, 30 and 60min) on freshly extracted tomato juice quality (physicochemical properties, antioxidant activity and microbial load) was evaluated. On exposure to UV-C, level of water activity, total soluble solids, and titratable acidity exhibited non-significant increase up to 30min of exposure time. Regarding colour analysis, L∗ value significantly increased with subsequent decrease in a∗ and b∗ values post UV-C treatments. Clarity, DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity and total phenolics content significantly increased, whereas ascorbic acid level significantly reduced at 60min of UV-C exposure time. So also, lycopene content exhibited a non-significant decrease after UV-C treatment. Microbial studies showed reduction in total plate count and total mould counts post UV-C treatment. Overall, UV-C treatment being a physical, non-thermal method of food preservation holds the ability to improve or preserve vital quality parameters in freshly prepared tomato juices, and henceforth possesses high scope for commercial exploration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hepatic FGF21 expression is induced at birth via PPARalpha in response to milk intake and contributes to thermogenic activation of neonatal brown fat.

PubMed

Hondares, Elayne; Rosell, Meritxell; Gonzalez, Frank J; Giralt, Marta; Iglesias, Roser; Villarroya, Francesc

2010-03-03

Plasma FGF21 levels and hepatic FGF21 gene expression increase dramatically after birth in mice. This induction is initiated by suckling, requires lipid intake, is impaired in PPARalpha null neonates, and is mimicked by treatment with the PPARalpha activator, Wy14,643. Neonates exhibit reduced FGF21 expression in response to fasting, in contrast to the upregulation occurring in adults. Changes in FGF21 expression due to suckling or nutritional manipulations were associated with circulating free fatty acid and ketone body levels. We mimicked the FGF21 postnatal rise by injecting FGF21 into fasting neonates, and found that this enhanced the expression of genes involved in thermogenesis within brown fat, and increased body temperature. Brown adipocytes treated with FGF21 exhibited increased expression of thermogenic genes, higher total and uncoupled respiration, and enhanced glucose oxidation. We propose that the induction of FGF21 production by the liver mediates direct activation of brown fat thermogenesis during the fetal-to-neonatal transition. 2010 Elsevier Inc. All rights reserved.

Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans.

PubMed

Butler, Andrew A; St-Onge, Marie-Pierre; Siebert, Emily A; Medici, Valentina; Stanhope, Kimber L; Havel, Peter J

2015-10-05

Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations.

Investigation of bandgap modulation, field emission and dielectric properties of cadmium doped CaCu3 Ti4O12

NASA Astrophysics Data System (ADS)

Maitra, S.; Mitra, R.; Bera, K. P.; Nath, T. K.

2017-05-01

We have prepared cadmium doped CCTO (Ca1-xCdxCu3Ti4O12 where x = 0.01, 0.02, 0.03, 0.04, 0.05) by Molten Salt Synthesis technique. It has exhibited high level of crystallinity and a well defined micrometre sized grains with uniform cubic morphology, as confirmed by a combination of X-ray diffraction and field emission scanning electron microscopy. Thereby we have found the modulation of its semiconducting bandgap as a function of doping from recorded UV-Vis reflectance spectra using Kubelka Munk (KM) method where with increasing Cadmium doping content the bandgap is found to increase. We have also carried out investigation on the field emission properties of CCTO crystals and it has exhibited poor field emission characteristics. Finally, we have investigated the dielectric properties of CCTO as a function of temperature. It has exhibited a giant dielectric property with low loss over a considerable temperature regime (50-300°C) and is found to exhibit Maxwell Wagner type dielectric relaxation.

Do serum BDNF levels vary in self-harm behavior among adolescents and are they correlated with traumatic experiences?

PubMed

Kavurma, Canem; Varol Tas, Fatma; Serim Demirgoren, Burcu; Demirci, Ferhat; Akan, Pınar; Eyuboglu, Damla; Guvenir, Taner

2017-12-01

The aim of this study was to compare serum brain-derived neurotrophic factor (BDNF) levels between adolescents that harm themselves, those that receive psychiatric treatment but do not harm themselves, healthy adolescents, and childhood traumas and to investigate the relationship between traumatic experiences and serum BDNF levels. The cases were divided into two groups of 40 adolescents exhibiting self-harm behavior (self-harm/diagnosed group) and 30 adolescents receiving psychiatric treatment but not exhibiting self-harm behaviors (non self-harm/diagnosed group). The control group (healthy control group) consisted of 35 healthy adolescents with no psychiatric disorders or self-harm behaviors. The adolescents were asked to fill in the Inventory of Statements About Self Injury (ISAS) and Childhood Trauma Questionnaire (CTQ). For BDNF measurement, blood samples were taken from the cases and controls. The serum BDNF level of self-harming adolescents who used the self-cutting method was significantly lower than that of other groups, and serum BDNF levels decreased with the increase in the emotional neglect and abuse severity of self-harming adolescents during childhood. In our study, serum BDNF levels decreased with the increase in emotional abuse in self-harming adolescents. This finding may indicate that neuroplasticity can be affected by a negative emotional environment during the early period. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of Excessive Monoamine Oxidase A/B Activity Protects Against Stress-induced Neuronal Death in Huntington Disease.

PubMed

Ooi, Jolene; Hayden, Michael R; Pouladi, Mahmoud A

2015-12-01

Monoamine oxidases (MAO) are important components of the homeostatic machinery that maintains the levels of monoamine neurotransmitters, including dopamine, in balance. Given the imbalance in dopamine levels observed in Huntington disease (HD), the aim of this study was to examine MAO activity in a mouse striatal cell model of HD and in human neural cells differentiated from control and HD patient-derived induced pluripotent stem cell (hiPSC) lines. We show that mouse striatal neural cells expressing mutant huntingtin (HTT) exhibit increased MAO expression and activity. We demonstrate using luciferase promoter assays that the increased MAO expression reflects enhanced epigenetic activation in striatal neural cells expressing mutant HTT. Using cellular stress paradigms, we further demonstrate that the increase in MAO activity in mutant striatal neural cells is accompanied by enhanced susceptibility to oxidative stress and impaired viability. Treatment of mutant striatal neural cells with MAO inhibitors ameliorated oxidative stress and improved cellular viability. Finally, we demonstrate that human HD neural cells exhibit increased MAO-A and MAO-B expression and activity. Altogether, this study demonstrates abnormal MAO expression and activity and suggests a potential use for MAO inhibitors in HD.

Do as We Say, Not as We Do: Teaching Ethics in the Modern College Classroom

ERIC Educational Resources Information Center

Amlie, Thomas T.

2010-01-01

In the past decade, there has been an increasing level of distress over the perceived lack of ethics exhibited by members of the accounting profession. This distress has resulted in a call for a greater emphasis on ethics coverage as part of a college-level accounting education. However, one could argue that the various organizations that are…

The Effect of an Integrative Parent Education Program on Quality of Life for Families of Children with an Autism Spectrum Disorder

ERIC Educational Resources Information Center

White, Caroline Jane

2010-01-01

Families of children with an Autism Spectrum Disorder (ASD) exhibit decreases in cohesion and adaptability, increased social isolation (Higgins et al., 2005), higher levels of marital dissatisfaction (Hastings et al., 2005), and overall disruption to daily life (Bristol et al., 1988). Research has provided evidence of higher levels of stress,…

Mechanisms of copper stress alleviation in Citrus trees after metal uptake by leaves or roots.

PubMed

Hippler, Franz Walter Rieger; Petená, Guilherme; Boaretto, Rodrigo Marcelli; Quaggio, José Antônio; Azevedo, Ricardo Antunes; Mattos-Jr, Dirceu

2018-05-01

Nutritional disorders caused by copper (Cu) have affected citrus orchards. Since Cu is foliar sprayed as a pesticide to control citrus diseases, this metal accumulates in the soil. Thereby, we evaluated the effects of Cu leaf absorption after spray of different metal sources, as well as roots absorption on growth, nutritional status, and oxidative stress of young sweet orange trees. Two experiments were carried out under greenhouse conditions. The first experiment was set up with varying Cu levels to the soil (nil Cu, 0.5, 2.0, 4.0 and 8.0 g of Cu per plant as CuSO 4 .5H 2 O), whereas the second experiment with Cu application via foliar sprays (0.5 and 2.0 g of Cu per plant) and comparing two metal sources (CuSO 4 .5H 2 O or Cu(OH) 2 ). Copper was mainly accumulated in roots with soil supply, but an increase of oxidative stress levels was observed in leaves. On the other hand, Cu concentrations were higher in leaves that received foliar sprays, mainly as Cu(OH) 2 . However, when sulfate was foliar sprayed, plants exhibited more symptoms of injuries in the canopy with decreased chlorophyll contents and increased hydrogen peroxide and lipid peroxidation levels. Copper toxicity was characterized by sap leakage from the trunk and twigs, which is the first report of this specific Cu excess symptom in woody trees. Despite plants with 8.0 g of Cu soil-applied exhibiting the sap leakage, growth of new plant parts was more vigorous with lower oxidative stress levels and injuries compared to those with 4.0 g of Cu soil-applied (without sap leakage). With the highest level of Cu applied via foliar as sulfate, Cu was eliminated by plant roots, increasing the rhizospheric soil metal levels. Despite citrus likely exhibiting different mechanisms to reduce the damages caused by metal toxicity, such as responsive enzymatic antioxidant system, metal accumulation in the roots, and metal exclusion by roots, excess Cu resulted in damages on plant growth and metabolism when the metal was taken up either by roots or leaves.

Bit-1 is an essential regulator of myogenic differentiation

PubMed Central

Griffiths, Genevieve S.; Doe, Jinger; Jijiwa, Mayumi; Van Ry, Pam; Cruz, Vivian; de la Vega, Michelle; Ramos, Joe W.; Burkin, Dean J.; Matter, Michelle L.

2015-01-01

Muscle differentiation requires a complex signaling cascade that leads to the production of multinucleated myofibers. Genes regulating the intrinsic mitochondrial apoptotic pathway also function in controlling cell differentiation. How such signaling pathways are regulated during differentiation is not fully understood. Bit-1 (also known as PTRH2) mutations in humans cause infantile-onset multisystem disease with muscle weakness. We demonstrate here that Bit-1 controls skeletal myogenesis through a caspase-mediated signaling pathway. Bit-1-null mice exhibit a myopathy with hypotrophic myofibers. Bit-1-null myoblasts prematurely express muscle-specific proteins. Similarly, knockdown of Bit-1 expression in C2C12 myoblasts promotes early differentiation, whereas overexpression delays differentiation. In wild-type mice, Bit-1 levels increase during differentiation. Bit-1-null myoblasts exhibited increased levels of caspase 9 and caspase 3 without increased apoptosis. Bit-1 re-expression partially rescued differentiation. In Bit-1-null muscle, Bcl-2 levels are reduced, suggesting that Bcl-2-mediated inhibition of caspase 9 and caspase 3 is decreased. Bcl-2 re-expression rescued Bit-1-mediated early differentiation in Bit-1-null myoblasts and C2C12 cells with knockdown of Bit-1 expression. These results support an unanticipated yet essential role for Bit-1 in controlling myogenesis through regulation of Bcl-2. PMID:25770104

Room temperature degradation of YBa2Cu3O(7-x) superconductors in varying relative humidity environments

NASA Technical Reports Server (NTRS)

Hooker, M. W.; Wise, S. A.; Carlberg, I. A.; Stephens, R. M.; Simchick, R. T.; Farjami, A.

1993-01-01

An aging study was performed to determine the stability of YBa2Cu3O(7-x) ceramics in humid environments at 20 C. In this study, fired ceramic specimens were exposed to humidity levels ranging from 30.5 to 100 percent for 2-, 4-, and 6-week time intervals. After storage under these conditions, the specimens were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and electrical resistance measurements. At every storage condition evaluated, the fired ceramics were found to interact with H2O present in the surrounding environment, resulting in the decomposition of the YBa2Cu3O(7-x) phase. XRD data showed that BaCO3, CuO, and Y2BaCuO5 were present after aging and that the peak intensities of these impurity phases increased both with increasing humidity level and with increasing time of exposure. Additionally, SEM analyses of the ceramic microstructures after aging revealed the development of needle-like crystallites along the surface of the test specimens after aging. Furthermore, the superconducting transition temperature T(sub c) was found to decrease both with increasing humidity level and with increasing time of exposure. All the specimens aged at 30.5, 66, and 81 percent relative humidity exhibited superconducting transitions above 80 K, although these values were reduced by the exposure to the test conditions. Conversely, the specimens stored in direct contact with water (100 percent relative humidity) exhibited no superconducting transitions.

Physiological correlates of symbiont migration during bleaching of two octocoral species.

PubMed

Netherton, Sarah E; Scheer, Daniele M; Morrison, Patrick R; Parrin, Austin P; Blackstone, Neil W

2014-05-01

Perturbed colonies of Phenganax parrini and Sarcothelia sp. exhibit migration of symbionts of Symbiodinium spp. into the stolons. Densitometry and visual inspection indicated that polyps bleached while stolons did not. When migration was triggered by temperature, light and confinement, colonies of Sarcothelia sp. decreased rates of oxygen formation in the light (due to the effects of perturbation on photosynthesis and respiration) and increased rates of oxygen uptake in the dark (due to the effects of perturbation on respiration alone). Colonies of P. parrini, by contrast, showed no significant changes in either aspect of oxygen metabolism. When migration was triggered by light and confinement, colonies of Sarcothelia sp. showed decreased rates of oxygen formation in the light and increased rates of oxygen uptake in the dark, while colonies of P. parrini maintained the former and increased the latter. During symbiont migration into their stolons, colonies of both species showed dramatic increases in reactive oxygen species (ROS), as visualized with a fluorescent probe, with stolons of Sarcothelia sp. exhibiting a nearly immediate increase of ROS. Differences in symbiont type may explain the greater sensitivity of colonies of Sarcothelia sp. Using fluorescent probes, direct measurements of migrating symbionts in the stolons of Sarcothelia sp. showed higher levels of reactive nitrogen species and lower levels of ROS than the surrounding host tissue. As measured by native fluorescence, levels of NAD(P)H in the stolons were unaffected by perturbation. Symbiont migration thus correlates with dramatic physiological changes and may serve as a marker for coral condition.

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.

Estrogenic environmental contaminants alter the mRNA abundance profiles of genes involved in gonadal differentiation of the American bullfrog

PubMed Central

Wolff, Stephanie E.; Veldhoen, Nik; Helbing, Caren C.; Ramirez, Claire A.; Malpas, Janae M.; Propper, Catherine R.

2015-01-01

Wildlife and human populations are exposed to anthropogenic mixtures of chemicals in the environment that may adversely influence normal reproductive function and development. We determined the effects of exposure to estrogenic chemicals and wastewater effluent (WWE) on developing gonads of the American bullfrog, Rana (Lithobates) catesbeiana, a species whose widespread distribution make it an ideal model for environmental monitoring for endocrine effects of chemical contaminants. Premetamorphic bullfrog tadpoles were exposed to treatment vehicle, 17β-estradiol (E2; 10−9 M) or 4-tert-octylphenol (OP; 10−9 M, 10−8 M, and 10−7 M). Additionally, gonadal differentiation was evaluated in bullfrog tadpoles from a WWE-containing site versus those from a reference location receiving no WWE. In both studies, phenotypic sex, steroidogenic factor-1 (nr5a1), and aromatase (cyp19a1) mRNA levels using quantitative real-time PCR were determined. Exposure to E2 or OP did not alter sex ratios. In controls, both nr5a1 and cyp19a1 transcript levels exhibited sexual dimorphism, with males demonstrating higher levels of nr5a1 and females greater abundance of cyp19a1. However, E2 exposure increased cyp19a1 mRNA abundance in testes and decreased levels in ovaries, eliminating the sexual dimorphism observed in controls. E2-exposed males exhibited increased nr5a1 transcript levels in the testes compared to controls, while females demonstrated no E2 effect. OP treatment had no effect on female cyp19a1 mRNA abundance, but exposure to 10−7 M OP increased testicular transcript levels. Treatment with 10−9 and 10−8 M OP, but not 10−7 M, resulted in decreased abundance of nr5a1 transcript in both ovaries and testes. Animals from the field had sexually dimorphic gonadal levels of cyp19a1, but both sexes from the WWE site exhibited elevated cyp19a1 transcript abundance compared to the reference location. Individual chemical compounds and anthropogenic wastewater effluent dispersed within the environment influence the levels of gonadal mRNA encoding key proteins involved in gonadal differentiation. PMID:25863316

The Campylobacter jejuni MarR-like transcriptional regulators RrpA and RrpB both influence bacterial responses to oxidative and aerobic stresses.

PubMed

Gundogdu, Ozan; da Silva, Daiani T; Mohammad, Banaz; Elmi, Abdi; Mills, Dominic C; Wren, Brendan W; Dorrell, Nick

2015-01-01

The ability of the human intestinal pathogen Campylobacter jejuni to respond to oxidative stress is central to bacterial survival both in vivo during infection and in the environment. Re-annotation of the C. jejuni NCTC11168 genome revealed the presence of two MarR-type transcriptional regulators Cj1546 and Cj1556, originally annotated as hypothetical proteins, which we have designated RrpA and RrpB (regulator of response to peroxide) respectively. Previously we demonstrated a role for RrpB in both oxidative and aerobic (O2) stress and that RrpB was a DNA binding protein with auto-regulatory activity, typical of MarR-type transcriptional regulators. In this study, we show that RrpA is also a DNA binding protein and that a rrpA mutant in strain 11168H exhibits increased sensitivity to hydrogen peroxide oxidative stress. Mutation of either rrpA or rrpB reduces catalase (KatA) expression. However, a rrpAB double mutant exhibits higher levels of resistance to hydrogen peroxide oxidative stress, with levels of KatA expression similar to the wild-type strain. Mutation of either rrpA or rrpB also results in a reduction in the level of katA expression, but this reduction was not observed in the rrpAB double mutant. Neither the rrpA nor rrpB mutant exhibits any significant difference in sensitivity to either cumene hydroperoxide or menadione oxidative stresses, but both mutants exhibit a reduced ability to survive aerobic (O2) stress, enhanced biofilm formation and reduced virulence in the Galleria mellonella infection model. The rrpAB double mutant exhibits wild-type levels of biofilm formation and wild-type levels of virulence in the G mellonella infection model. Together these data indicate a role for both RrpA and RrpB in the C. jejuni peroxide oxidative and aerobic (O2) stress responses, enhancing bacterial survival in vivo and in the environment.

A systematic review and meta-analysis of lower limb neuromuscular alterations associated with knee osteoarthritis during level walking.

PubMed

Mills, Kathryn; Hunt, Michael A; Leigh, Ryan; Ferber, Reed

2013-08-01

Neuromuscular alterations are increasingly reported in individuals with knee osteoarthritis (KOA) during level walking. We aimed to determine which neuromuscular alterations are consistent in KOA individuals and how these may be influenced by osteoarthritis severity, varus alignment and/or joint laxity. Electronic databases were searched up to July 2012. Cross-sectional observational studies comparing lower-limb neuromuscular activity in individuals with KOA, healthy controls or with different KOA cohorts were included. Two reviewers assessed methodological quality. Effect sizes were used to quantify the magnitude of observed differences. Where studies were homogenous, effect sizes were pooled using a fixed-effects model. Fourteen studies examining neuromuscular alterations in indices of co-contraction, muscle amplitude and muscle activity duration were included. Data pooling revealed that moderate KOA individuals exhibit increased co-contraction of lateral knee muscles (ES 0.64 [0.3 to 0.97]) and moderately increased rectus femoris (ES 0.73 [0.23 to 1.22]), vastus lateralis (ES 0.77 [0.27 to 1.27]) and biceps femoris (ES 1.18 [0.67 to 1.7]) mean amplitude. Non-pooled data indicated prolonged activity of these muscles. Increased medial knee neuromuscular activity was prevalent for those exhibiting varus alignment and medial knee joint laxity. Interpretation Individuals with KOA exhibited increased co-contraction, amplitude and duration of lateral knee muscles regardless of disease severity, limb alignment or medial joint laxity. Individuals with severe disease, varus alignment and medial joint laxity demonstrate up-regulation of medial knee muscles. Future research investigating the efficacy of neuromuscular rehabilitation programs should consider the effect of simultaneous up-regulation of medial and lateral knee muscles on disease progression. © 2013.

Lion, ungulate, and visitor reactions to playbacks of lion roars at Zoo Atlanta.

PubMed

Kelling, Angela S; Allard, Stephanie M; Kelling, Nicholas J; Sandhaus, Estelle A; Maple, Terry L

2012-01-01

Felids in captivity are often inactive and elusive in zoos, leading to a frustrating visitor experience. Eight roars were recorded from an adult male lion and played back over speakers as auditory enrichment to benefit the lions while simultaneously enhancing the zoo visitor experience. In addition, ungulates in an adjacent exhibit were observed to ensure that the novel location and increased frequency of roars did not lead to a stress or fear response. The male lion in this study roared more in the playback phase than in the baseline phases while not increasing any behaviors that would indicate compromised welfare. In addition, zoo visitors remained at the lion exhibit longer during playback. The nearby ungulates never exhibited any reactions stronger than orienting to playbacks, identical to their reactions to live roars. Therefore, naturalistic playbacks of lion roars are a potential form of auditory enrichment that leads to more instances of live lion roars and enhances the visitor experience without increasing the stress levels of nearby ungulates or the lion themselves, who might interpret the roar as that of an intruder.

Piracetam Facilitates the Anti-Amnesic but not Anti-Diabetic Activity of Metformin in Experimentally Induced Type-2 Diabetic Encephalopathic Rats.

PubMed

Pandey, Shruti; Garabadu, Debapriya

2017-07-01

Piracetam exhibits anti-amnesic activity in several animal models of dementia. However, its anti-amnesic potential has yet to be evaluated in type-2 diabetes mellitus (T2DM)-induced encephalopathy. Therefore, in the present study, piracetam (25, 50 and 100 mg/kg) was screened for anti-amnesic and anti-diabetic activity in T2DM-induced encephalopathic male rats. Subsequently, anti-amnesic and anti-diabetic activities were evaluated for piracetam, metformin and their combination in T2DM-induced encephalopathic animals. Rats received streptozotocin (45 mg/kg) and nicotinamide (110 mg/kg) injections on day-1 (D-1) of the experimental schedule and were kept undisturbed for 35 days to exhibit T2DM-induced encephalopathy. All drug treatments were continued from D-7 to D-35 in both experiments. Piracetam (100 mg/kg) attenuated loss in learning and memory in terms of increase in escape latency on D-4 (D-34) and decrease in time spent in the target quadrant on D-5 (D-35) of Morris water maze test protocol, and spatial memory in terms of reduced spontaneous alternation behavior in Y-maze test of encephalopathic rats. Additionally, piracetam attenuated altered levels of fasting plasma glucose and insulin, HOMA-IR and HOMA-B in encephalopathic animals, comparatively lesser than metformin. In the next experiment, combination of piracetam and metformin exhibited better anti-amnesic but not anti-diabetic activity than respective monotherapies in encephalopathic rats. Further, the combination attenuated reduced acetylcholine level and increased acetylcholinesterase activity, increased glycogen synthase kinase-3β level and decreased brain-derived neurotropic factor level in hippocampus and pre-frontal cortex of encephalopathic animals. Thus, piracetam could be used as an adjuvant to metformin in the management of dementia in T2DM-induced encephalopathy.

Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

NASA Technical Reports Server (NTRS)

Goepfert, T. M.; McCarthy, M.; Kittrell, F. S.; Stephens, C.; Ullrich, R. L.; Brinkley, B. R.; Medina, D.

2000-01-01

Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

Effect of Canning and Freezing on the Nutritional Content of Apricots.

PubMed

Adkison, Erin Claire; Biasi, William B; Bikoba, Veronique; Holstege, Dirk M; Mitcham, Elizabeth J

2018-05-22

The effect of commercial canning and freezing on the nutritional content of fresh apricots was investigated. Processed samples were analyzed post-processing and after 3 months of storage and compared directly to fresh apricots from the same source. Vitamin C, beta-carotene, total phenols, and antioxidants were quantified. Compared to fresh, canned apricots initially exhibited similar levels of antioxidants, a 17% increase in beta-carotene, and a 48% increase in phenols, while vitamin C was reduced by 37%. After 3 months of storage, antioxidant levels were 47% higher than fresh. Vitamin C did not change significantly following storage and beta-carotene decreased by 15%. The canned apricot fruit packed in light syrup did not have higher total soluble solids (TSS) levels indicating no increase in fruit sugar content. Frozen apricots exhibited large increases in antioxidants (529%), beta-carotene (35%), vitamin C (3,370%), and phenols (406%) compared to fresh. After 3 months of storage, frozen apricots decreased in vitamin C (29%) and phenols (17%), but remained 2,375% and 318% higher than fresh, respectively. Beta-carotene increased during storage, reaching levels 56% higher than fresh while antioxidant activity was unchanged. This study demonstrates that key nutrients in canned and frozen apricots are retained or amplified upon processing, with the exception of vitamin C in canned apricots. The routine addition of citric and ascorbic acid to fruit prior to freezing resulted in significantly higher antioxidants, vitamin C, and phenols. Consumers eating canned or frozen apricots can feel confident of similar or superior nutritional content as compared to fresh apricots. The apricot industry is limited by the short shelf life of the fruit and consumer belief that processed produce is not as nutritious as fresh. Assessing the nutritional content of canned and frozen apricots and determining that processed apricots can deliver nearly comparable nutrient levels to fresh apricots provides the evidence needed to dispel these misconceptions and potentially increase demand for processed apricots among consumers. © 2018 Institute of Food Technologists®.

Transgenic Alfalfa Plants Expressing the Sweetpotato Orange Gene Exhibit Enhanced Abiotic Stress Tolerance

PubMed Central

Wang, Zhi; Ke, Qingbo; Kim, Myoung Duck; Kim, Sun Ha; Ji, Chang Yoon; Jeong, Jae Cheol; Lee, Haeng-Soon; Park, Woo Sung; Ahn, Mi-Jeong; Li, Hongbing; Xu, Bingcheng; Deng, Xiping; Lee, Sang-Hoon; Lim, Yong Pyo; Kwak, Sang-Soo

2015-01-01

Alfalfa (Medicago sativa L.), a perennial forage crop with high nutritional content, is widely distributed in various environments worldwide. We recently demonstrated that the sweetpotato Orange gene (IbOr) is involved in increasing carotenoid accumulation and enhancing resistance to multiple abiotic stresses. In this study, in an effort to improve the nutritional quality and environmental stress tolerance of alfalfa, we transferred the IbOr gene into alfalfa (cv. Xinjiang Daye) under the control of an oxidative stress-inducible peroxidase (SWPA2) promoter through Agrobacterium tumefaciens-mediated transformation. Among the 11 transgenic alfalfa lines (referred to as SOR plants), three lines (SOR2, SOR3, and SOR8) selected based on their IbOr transcript levels were examined for their tolerance to methyl viologen (MV)-induced oxidative stress in a leaf disc assay. The SOR plants exhibited less damage in response to MV-mediated oxidative stress and salt stress than non-transgenic plants. The SOR plants also exhibited enhanced tolerance to drought stress, along with higher total carotenoid levels. The results suggest that SOR alfalfa plants would be useful as forage crops with improved nutritional value and increased tolerance to multiple abiotic stresses, which would enhance the development of sustainable agriculture on marginal lands. PMID:25946429

Transgenic alfalfa plants expressing the sweetpotato Orange gene exhibit enhanced abiotic stress tolerance.

PubMed

Wang, Zhi; Ke, Qingbo; Kim, Myoung Duck; Kim, Sun Ha; Ji, Chang Yoon; Jeong, Jae Cheol; Lee, Haeng-Soon; Park, Woo Sung; Ahn, Mi-Jeong; Li, Hongbing; Xu, Bingcheng; Deng, Xiping; Lee, Sang-Hoon; Lim, Yong Pyo; Kwak, Sang-Soo

2015-01-01

Alfalfa (Medicago sativa L.), a perennial forage crop with high nutritional content, is widely distributed in various environments worldwide. We recently demonstrated that the sweetpotato Orange gene (IbOr) is involved in increasing carotenoid accumulation and enhancing resistance to multiple abiotic stresses. In this study, in an effort to improve the nutritional quality and environmental stress tolerance of alfalfa, we transferred the IbOr gene into alfalfa (cv. Xinjiang Daye) under the control of an oxidative stress-inducible peroxidase (SWPA2) promoter through Agrobacterium tumefaciens-mediated transformation. Among the 11 transgenic alfalfa lines (referred to as SOR plants), three lines (SOR2, SOR3, and SOR8) selected based on their IbOr transcript levels were examined for their tolerance to methyl viologen (MV)-induced oxidative stress in a leaf disc assay. The SOR plants exhibited less damage in response to MV-mediated oxidative stress and salt stress than non-transgenic plants. The SOR plants also exhibited enhanced tolerance to drought stress, along with higher total carotenoid levels. The results suggest that SOR alfalfa plants would be useful as forage crops with improved nutritional value and increased tolerance to multiple abiotic stresses, which would enhance the development of sustainable agriculture on marginal lands.

In situ gene expression profiling of the thermoacidophilic alga Cyanidioschyzon in relation to visible and ultraviolet irradiance.

PubMed

Skorupa, Dana J; Castenholz, Richard W; Mazurie, Aurélien; Carey, Charles; Rosenzweig, Frank; McDermott, Timothy R

2014-06-01

Ultraviolet and high-intensity visible radiation generate reactive intermediates that damage phototrophic microorganisms. In Yellowstone National Park, the thermoacidophilic alga Cyanidioschyzon exhibits an annual seasonal biomass fluctuation referred to as 'mat decline', where algal viability decreases as ultraviolet and visible irradiances increase during summer. We examined the role irradiance might play in mat decline using irradiance filters that uncouple ultraviolet and visible effects along with custom microarrays to study gene expression in situ. Of the 6507 genes, 88% showed no response to ultraviolet or visible, implying that at the biomolecular level, these algae inhabit a chemostat-like environment and is consistent with the near constant aqueous chemistry measured. The remaining genes exhibited expression changes linked to ultraviolet exposure, to increased visible radiation, or to the apparent combined effects of ultraviolet and visible. Expression of DNA repetitive elements was synchronized, being repressed by visible but also influenced by ultraviolet. At highest irradiance levels, these algae reduced transcription of genes encoding functions involved with DNA replication, photosynthesis and cell cycle progression but exhibited an uptick in activities related to repairing DNA damage. This corroborates known physiological responses to ultraviolet and visible radiation, and leads us to provisionally conclude that mat decline is linked to photoinhibition. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Tachycardia, reduced vagal capacity, and age-dependent ventricular dysfunction arising from diminished expression of the presynaptic choline transporter.

PubMed

English, Brett A; Appalsamy, Martin; Diedrich, Andre; Ruggiero, Alicia M; Lund, David; Wright, Jane; Keller, Nancy R; Louderback, Katherine M; Robertson, David; Blakely, Randy D

2010-09-01

Healthy cardiovascular function relies on a balanced and responsive integration of noradrenergic and cholinergic innervation of the heart. High-affinity choline uptake by cholinergic terminals is pivotal for efficient ACh production and release. To date, the cardiovascular impact of diminished choline transporter (CHT) expression has not been directly examined, largely due to the transporter's inaccessibility in vivo. Here, we describe findings from cardiovascular experiments using transgenic mice that bear a CHT genetic deficiency. Whereas CHT knockout (CHT(-/-)) mice exhibit early postnatal lethality, CHT heterozygous (CHT(+/-)) mice survive, grow, and reproduce normally and exhibit normal spontaneous behaviors. However, the CHT(+/-) mouse heart displays significantly reduced levels of high-affinity choline uptake accompanied by significantly reduced levels of ACh. Telemeterized recordings of cardiovascular function in these mice revealed tachycardia and hypertension at rest. After treadmill exercise, CHT(+/-) mice exhibited slower heart rate recovery, consistent with a diminished cholinergic reserve, a contention validated through direct vagal nerve stimulation. Echocardiographic and histological experiments revealed an age-dependent decrease in fractional shortening, increased left ventricular dimensions, and increased ventricular fibrosis, consistent with ventricular dysfunction. These cardiovascular phenotypes of CHT(+/-) mice encourage an evaluation of humans bearing reduced CHT expression for their resiliency in maintaining proper heart function as well as risk for cardiovascular disease.

Intraindividual change and variability in daily stress processes: Findings from two measurement-burst diary studies

PubMed Central

Sliwinski, Martin J.; Almeida, David M.; Smyth, Joshua; Stawski, Robert S.

2010-01-01

There is little longitudinal information on aging-related changes in emotional responses to negative events. The present manuscript examined intraindividual change and variability in the within-person coupling of daily stress and negative affect (NA) using data from two-measurement burst daily diary studies. Three main findings emerged. First, average reactivity to daily stress increased longitudinally, and this increase was evident across most the adult lifespan. Second, individual differences in emotional reactivity to daily stress exhibited long-term temporal stability, but this stability was greatest in midlife and decreased in old age. And third, reactivity to daily stress varied reliably within-persons (across-time), with individual exhibiting higher levels of reactivity during times when reporting high levels of global subject stress in previous month. Taken together, the present results emphasize the importance of modeling dynamic psychosocial and aging processes that operate across different time scales for understanding age-related changes in daily stress processes. PMID:20025399

Size-mediated response to public cues of predation risk in a tropical stream fish.

PubMed

Elvidge, C K; Ramnarine, I W; Godin, J-G J; Brown, G E

2010-11-01

In order to investigate any size-dependent differences between behavioural patterns, wild-caught Hart's rivulus Rivulus hartii of varying sizes were exposed to chemical alarm cues extracted from the skin of conspecifics or heterospecific Poecilia reticulata, or a tank water control, in a series of laboratory trials. In response to conspecific alarm cues, R. hartii subjects of the range of body sizes tested exhibited consistent, size-independent antipredator behaviours that were characterized by decreased locomotory activity and foraging levels and increased refuging behaviour. Conversely, focal R. hartii demonstrated significant size-dependent trends in response to heterospecific alarm cues, with smaller individuals exhibiting antipredator responses and larger individuals shifting their behaviour to increased levels of activity consistent with a foraging, or predatory, response. These results show that the behavioural responses of individual R. hartii to publicly available chemical alarm cues from heterospecifics are mediated by the size of the receiver. © 2010 The Authors. Journal of Fish Biology © 2010 The Fisheries Society of the British Isles.

Physiological and morphological responses of pine and willow saplings to post-fire salvage logging

NASA Astrophysics Data System (ADS)

Millions, E. L.; Letts, M. G.; Harvey, T.; Rood, S. B.

2015-12-01

With global warming, forest fires may be increasing in frequency, and post-fire salvage logging may become more common. The ecophysiological impacts of this practice on tree saplings remain poorly understood. In this study, we examined the physiological and morphological impacts of increased light intensity, due to post-fire salvage logging, on the conifer Pinus contorta (pine) and deciduous broadleaf Salix lucida (willow) tree and shrub species in the Crowsnest Pass region of southern Alberta. Photosynthetic gas-exchange and plant morphological measurements were taken throughout the summer of 2013 on approximately ten year-old saplings of both species. Neither species exhibited photoinhibition, but different strategies were observed to acclimate to increased light availability. Willow saplings were able to slightly elevate their light-saturated rate of net photosynthesis (Amax) when exposed to higher photosynthetic photon flux density (PPFD), thus increasing their growth rate. Willow also exhibited increased leaf inclination angles and leaf mass per unit area (LMA), to decrease light interception in the salvage-logged plot. By contrast, pine, which exhibited lower Amax and transpiration (E), but higher water-use efficiency (WUE = Amax/E) than willow, increased the rate at which electrons were moved through and away from the photosynthetic apparatus in order to avoid photoinhibition. Acclimation indices were higher in willow saplings, consistent with the hypothesis that species with short-lived foliage exhibit greater acclimation. LMA was higher in pine saplings growing in the logged plot, but whole-plant and branch-level morphological acclimation was limited and more consistent with a response to decreased competition in the logged plot, which had much lower stand density.

Arginase 2 deletion leads to enhanced M1 macrophage activation and upregulated polyamine metabolism in response to Helicobacter pylori infection

PubMed Central

Hardbower, Dana M.; Asim, Mohammad; Murray-Stewart, Tracy; Casero, Robert A.; Verriere, Thomas; Lewis, Nuruddeen D.; Chaturvedi, Rupesh; Piazuelo, M. Blanca; Wilson, Keith T.

2016-01-01

We reported that arginase 2 (ARG2) deletion results in increased gastritis and decreased bacterial burden during Helicobacter pylori infection in mice. Our studies implicated a potential role for inducible nitric oxide (NO) synthase (NOS2), as Arg2−/− mice exhibited increased NOS2 levels in gastric macrophages, and NO can kill H. pylori. We now bred Arg2−/− to Nos2−/− mice, and infected them with H. pylori. Compared to wild-type mice, both Arg2−/− and Arg2−/−;Nos2−/− mice exhibited increased gastritis and decreased colonization, the latter indicating that the effect of ARG2 deletion on bacterial burden was not mediated by NO. While Arg2−/− mice demonstrated enhanced M1 macrophage activation, Nos2−/− and Arg2−/−;Nos2−/− mice did not demonstrate these changes, but exhibited increased CXCL1 and CXCL2 responses. There was an increased expression of the Th1/ Th17 cytokines, interferon gamma and interleukin 17, in gastric tissues and splenic T-cells from Arg2−/−, but not Nos2−/− or Arg2−/−;Nos2−/− mice. Gastric tissues from infected Arg2−/− mice demonstrated increased expression of arginase 1, ornithine decarboxylase, adenosylmethionine decarboxylase 1, spermidine/spermine N1-acetyltransferase 1, and spermine oxidase, along with increased spermine levels. These data indicate that ARG2 deletion results in compensatory upregulation of gastric polyamine synthesis and catabolism during H. pylori infection, which may contribute to increased gastric inflammation and associated decreased bacterial load. Overall, the finding of this study is that ARG2 contributes to the immune evasion of H. pylori by restricting M1 macrophage activation and polyamine metabolism. PMID:27074721

Irreversibly increased nitrogen fixation in Trichodesmium experimentally adapted to elevated carbon dioxide

PubMed Central

Hutchins, David A.; Walworth, Nathan G.; Webb, Eric A.; Saito, Mak A.; Moran, Dawn; McIlvin, Matthew R.; Gale, Jasmine; Fu, Fei-Xue

2015-01-01

Nitrogen fixation rates of the globally distributed, biogeochemically important marine cyanobacterium Trichodesmium increase under high carbon dioxide (CO2) levels in short-term studies due to physiological plasticity. However, its long-term adaptive responses to ongoing anthropogenic CO2 increases are unknown. Here we show that experimental evolution under extended selection at projected future elevated CO2 levels results in irreversible, large increases in nitrogen fixation and growth rates, even after being moved back to lower present day CO2 levels for hundreds of generations. This represents an unprecedented microbial evolutionary response, as reproductive fitness increases acquired in the selection environment are maintained after returning to the ancestral environment. Constitutive rate increases are accompanied by irreversible shifts in diel nitrogen fixation patterns, and increased activity of a potentially regulatory DNA methyltransferase enzyme. High CO2-selected cell lines also exhibit increased phosphorus-limited growth rates, suggesting a potential advantage for this keystone organism in a more nutrient-limited, acidified future ocean. PMID:26327191

Irreversibly increased nitrogen fixation in Trichodesmium experimentally adapted to elevated carbon dioxide

NASA Astrophysics Data System (ADS)

Hutchins, David A.; Walworth, Nathan G.; Webb, Eric A.; Saito, Mak A.; Moran, Dawn; McIlvin, Matthew R.; Gale, Jasmine; Fu, Fei-Xue

2015-09-01

Nitrogen fixation rates of the globally distributed, biogeochemically important marine cyanobacterium Trichodesmium increase under high carbon dioxide (CO2) levels in short-term studies due to physiological plasticity. However, its long-term adaptive responses to ongoing anthropogenic CO2 increases are unknown. Here we show that experimental evolution under extended selection at projected future elevated CO2 levels results in irreversible, large increases in nitrogen fixation and growth rates, even after being moved back to lower present day CO2 levels for hundreds of generations. This represents an unprecedented microbial evolutionary response, as reproductive fitness increases acquired in the selection environment are maintained after returning to the ancestral environment. Constitutive rate increases are accompanied by irreversible shifts in diel nitrogen fixation patterns, and increased activity of a potentially regulatory DNA methyltransferase enzyme. High CO2-selected cell lines also exhibit increased phosphorus-limited growth rates, suggesting a potential advantage for this keystone organism in a more nutrient-limited, acidified future ocean.

Identification of a Novel Hypocholesterolemic Protein, Major Royal Jelly Protein 1, Derived from Royal Jelly

PubMed Central

Asai, Saori; Kusada, Mio; Watanabe, Suzuyo; Kawashima, Takuji; Nakamura, Tadashi; Shimada, Masaya; Goto, Tsuyoshi; Nagaoka, Satoshi

2014-01-01

Royal jelly (RJ) intake lowers serum cholesterol levels in animals and humans, but the active component in RJ that lowers serum cholesterol level and its molecular mechanism are unclear. In this study, we set out to identify the bile acid-binding protein contained in RJ, because dietary bile acid-binding proteins including soybean protein and its peptide are effective in ameliorating hypercholesterolemia. Using a cholic acid-conjugated column, we separated some bile acid-binding proteins from RJ and identified the major RJ protein 1 (MRJP1), MRJP2, and MRJP3 as novel bile acid-binding proteins from RJ, based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Purified MRJP1, which is the most abundant protein of the bile acid-binding proteins in RJ, exhibited taurocholate-binding activity in vitro. The micellar solubility of cholesterol was significantly decreased in the presence of MRJP1 compared with casein in vitro. Liver bile acids levels were significantly increased, and cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein tended to increase by MRJP1 feeding compared with the control. CYP7A1 mRNA and protein levels were significantly increased by MRJP1 tryptic hydrolysate treatment compared with that of casein tryptic hydrolysate in hepatocytes. MRJP1 hypocholesterolemic effect has been investigated in rats. The cholesterol-lowering action induced by MRJP1 occurs because MRJP1 interacts with bile acids induces a significant increase in fecal bile acids excretion and a tendency to increase in fecal cholesterol excretion and also enhances the hepatic cholesterol catabolism. We have identified, for the first time, a novel hypocholesterolemic protein, MRJP1, in RJ. Interestingly, MRJP1 exhibits greater hypocholesterolemic activity than the medicine β-sitosterol in rats. PMID:25144734

Congenital juvenile granulosa cell tumor of the testis in newborns.

PubMed

Zugor, Vahudin; Labanaris, Apostolos P; Witt, Jörn; Seidler, Alexander; Weingärtner, Karl; Schott, Günter E

2010-05-01

Granulosa cell tumor of the testis is a rare intermediate stromal cell tumor that can be distinguished in the adult and juvenile type. The juvenile type is the most common reason for scrotal swelling in newborns under the age of six months. Less than fifty cases of this disease entity have been reported in the literature. In the following article, two newborn patients with scrotal swelling and a histological confirmation of juvenile granulosa cell tumor of the testis will be presented. Case 1: A newborn patient presented with massive scrotal swelling. Sonography of the testicle exhibited a multiple septic and cystic enlargement of the testicle without distinction of the testicular parenchyma being possible. The laboratory findings demonstrated normal testosterone levels, beta-HCG and inhibin-B levels as well as an increased alpha-fetoprotein level of 35.350 ng/dl. Due to clinical and sonographic findings, an inguinal exploration and later, due to the impossibility of distinction of the testicular parenchyma, an inguinal orchiectomy of the right testicle was performed. Case 2: The clinical and sonographic examination of a newborn patient demonstrated a suspicious process of the left testicle. Sonography exhibited an enlarged testicle with cystic formations with the distinction of the testicular parenchyma not being possible. The laboratory findings demonstrated normal testosterone levels, beta-HCG and inhibin-B levels as well as an increased alpha-fetoprotein level of 9.038 ng/dl and LDH of 768 U/I. An inguinal orchiectomy of the left testicle was performed. In both cases, a histological diagnosis of juvenile granulosa cell tumor of the testis was made. These two aforementioned cases demonstrate that juvenile granulosa cell tumor of the testis is a benign disease encountered in newborns, which exhibits an excellent prognosis. Inguinal orchiectomy is the therapy of choice. After surgical removal of the involved testicle is performed no further management is required.

Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice

PubMed Central

Liu, Xiaojun; Jiang, Shuguang; Fang, Chongyun; Yang, Shiyu; Olalere, Devvora; Pequignot, Edward C.; Cogdill, Alexandria P.; Li, Na; Ramones, Melissa; Granda, Brian; Zhou, Li; Loew, Andreas; Young, Regina M.; June, Carl H.; Zhao, Yangbing

2015-01-01

Target-mediated toxicity is a major limitation in the development of chimeric antigen T cell receptors (CAR) for adoptive cell therapy of solid tumors. In this study, we developed a strategy to adjust the affinities of the scFv component of CAR to discriminate tumors overexpressing the target from normal tissues which express it at physiologic levels. A CAR-expressing T cell panel was generated with target antigen affinities varying over three orders of magnitude. High-affinity cells recognized target expressed at any level, including at levels in normal cells that were undetectable by flow cytometry. Affinity-tuned cells exhibited robust antitumor efficacy similar to high-affinity cells, but spared normal cells expressing physiologic target levels. The use of affinity-tuned scFvs offers a strategy to empower wider use of CAR T cells against validated targets widely overexpressed on solid tumors, including those considered undruggable by this approach. PMID:26330166

Physiologic and anti-G suit performance data from YF-16 flight tests

NASA Technical Reports Server (NTRS)

Gillingham, K. K.; Winter, W. R.

1976-01-01

Biomedical data were collected during high-G portions of 11 YF-16 test flights. Test pilots monitored revealed increased respiratory rate and volume, decreased tidal volume, and increased heart rate at higher G levels, with one pilot exhibiting various cardiac arrhythmias. Anti-G suit inflation and pressurization lags varied inversely with G-onset rate, and suit pressurization slope was near the design value.

Increased sorbitol levels in the hypertrophic ligamentum flavum of diabetic patients with lumbar spinal canal stenosis.

PubMed

Luo, Jiaquan; Huang, Lu; Chen, Zhuo; Zeng, Zhaoxun; Miyamoto, Takeshi; Wu, Hao; Zhang, Zhongzu; Pan, Zhimin; Fujita, Nobuyuki; Hikata, Tomohiro; Iwanami, Akio; Tsuji, Takashi; Ishii, Ken; Nakamura, Masaya; Matsumoto, Morio; Watanabe, Kota; Cao, Kai

2017-05-01

The pathomechanism of the ligamentum flavum (LF) hypertrophy in diabetic patients with lumbar spinal canal stenosis (LSCS) remains unclear. A cross-sectional study was undertaken to investigate the mechanism of LF hypertrophy in these patients. Twenty-four diabetic and 20 normoglycemic patients with LSCS were enrolled in the study. The structure of the LF in the study subjects was evaluated using histological and immunohistochemical methods, and the levels of sorbitol, pro-inflammatory cytokines, and the fibrogenic factor, TGF-β1, in the LF were analyzed. In vitro experiments were performed using NIH3T3 fibroblasts to evaluate the effect of high-glucose conditions and an aldose reductase inhibitor on the cellular production of sorbitol, pro-inflammatory factors, and TGF-β1. We found that the LF of diabetic patients exhibited significantly higher levels of sorbitol and pro-inflammatory cytokines, TGF-β1 and of CD68-positive staining than that of the normoglycemic subjects. The diabetic LF was significantly thicker than that of the controls, and showed evidence of degeneration. The high glucose-cultured fibroblasts exhibited significantly higher levels of sorbitol, pro-inflammatory factors, and TGF-β1 compared to the low glucose-cultured cells, and these levels were dose-dependently reduced by treatment with the aldose reductase inhibitor. Taken together, our data suggests that increased sorbitol levels in the LF of diabetic patients results in increased production of pro-inflammatory and fibrogenic factor, which contribute to LF hypertrophy, and could increase the susceptibility of diabetic patients to LSCS. Furthermore, aldose reductase inhibition effectively reduced the levels of sorbitol and sorbitol-induced pro-inflammatory factor expression in high glucose-cultured fibroblasts. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1058-1066, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Aspartame-fed zebrafish exhibit acute deaths with swimming defects and saccharin-fed zebrafish have elevation of cholesteryl ester transfer protein activity in hypercholesterolemia.

PubMed

Kim, Jae-Yong; Seo, Juyi; Cho, Kyung-Hyun

2011-11-01

Although many artificial sweeteners (AS) have safety issues, the AS have been widely used in industry. To determine the physiologic effect of AS in the presence of hyperlipidemia, zebrafish were fed aspartame or saccharin with a high-cholesterol diet (HCD). After 12 days, 30% of zebrafish, which consumed aspartame and HCD, died with exhibiting swimming defects. The aspartame group had 65% survivability, while the control and saccharin groups had 100% survivability. Under HCD, the saccharin-fed groups had the highest increase in the serum cholesterol level (599 mg/dL). Aspartame-fed group showed a remarkable increase in serum glucose (up to 125 mg/dL), which was 58% greater than the increase in the HCD alone group. The saccharin and HCD groups had the highest cholesteryl ester transfer protein (CETP) activity (52% CE-transfer), while the HCD alone group had 42% CE-transfer. Histologic analysis revealed that the aspartame and HCD groups showed more infiltration of inflammatory cells in the brain and liver sections. Conclusively, under presence of hyperlipidemia, aspartame-fed zebrafish exhibited acute swimming defects with an increase in brain inflammation. Saccharin-fed zebrafish had an increased atherogenic serum lipid profile with elevation of CETP activity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Uridine Affects Liver Protein Glycosylation, Insulin Signaling, and Heme Biosynthesis

PubMed Central

Urasaki, Yasuyo; Pizzorno, Giuseppe; Le, Thuc T.

2014-01-01

Purines and pyrimidines are complementary bases of the genetic code. The roles of purines and their derivatives in cellular signal transduction and energy metabolism are well-known. In contrast, the roles of pyrimidines and their derivatives in cellular function remain poorly understood. In this study, the roles of uridine, a pyrimidine nucleoside, in liver metabolism are examined in mice. We report that short-term uridine administration in C57BL/6J mice increases liver protein glycosylation profiles, reduces phosphorylation level of insulin signaling proteins, and activates the HRI-eIF-2α-ATF4 heme-deficiency stress response pathway. Short-term uridine administration is also associated with reduced liver hemin level and reduced ability for insulin-stimulated blood glucose removal during an insulin tolerance test. Some of the short-term effects of exogenous uridine in C57BL/6J mice are conserved in transgenic UPase1 −/− mice with long-term elevation of endogenous uridine level. UPase1 −/− mice exhibit activation of the liver HRI-eIF-2α-ATF4 heme-deficiency stress response pathway. UPase1 −/− mice also exhibit impaired ability for insulin-stimulated blood glucose removal. However, other short-term effects of exogenous uridine in C57BL/6J mice are not conserved in UPase1 −/− mice. UPase1 −/− mice exhibit normal phosphorylation level of liver insulin signaling proteins and increased liver hemin concentration compared to untreated control C57BL/6J mice. Contrasting short-term and long-term consequences of uridine on liver metabolism suggest that uridine exerts transient effects and elicits adaptive responses. Taken together, our data support potential roles of pyrimidines and their derivatives in the regulation of liver metabolism. PMID:24918436

Distribution pattern of urine albumin creatinine ratio and the prevalence of high-normal levels in untreated asymptomatic non-diabetic hypertensive patients.

PubMed

Ohmaru, Natsuki; Nakatsu, Takaaki; Izumi, Reishi; Mashima, Keiichi; Toki, Misako; Kobayashi, Asako; Ogawa, Hiroko; Hirohata, Satoshi; Ikeda, Satoru; Kusachi, Shozo

2011-01-01

Even high-normal albuminuria is reportedly associated with cardiovascular events. We determined the urine albumin creatinine ratio (UACR) in spot urine samples and analyzed the UACR distribution and the prevalence of high-normal levels. The UACR was determined using immunoturbidimetry in 332 untreated asymptomatic non-diabetic Japanese patients with hypertension and in 69 control subjects. The microalbuminuria and macroalbuminuria levels were defined as a UCAR ≥30 and <300 µg/mg·creatinine and a UCAR ≥300 µg/mg·creatinine, respectively. The distribution patterns showed a highly skewed distribution for the lower levels, and a common logarithmic transformation produced a close fit to a Gaussian distribution with median, 25th and 75th percentile values of 22.6, 13.5 and 48.2 µg/mg·creatinine, respectively. When a high-normal UACR was set at >20 to <30 µg/mg·creatinine, 19.9% (66/332) of the hypertensive patients exhibited a high-normal UACR. Microalbuminuria and macroalbuminuria were observed in 36.1% (120/336) and 2.1% (7/332) of the patients, respectively. UACR was significantly correlated with the systolic and diastolic blood pressures and the pulse pressure. A stepwise multivariate analysis revealed that these pressures as well as age were independent factors that increased UACR. The UACR distribution exhibited a highly skewed pattern, with approximately 60% of untreated, non-diabetic hypertensive patients exhibiting a high-normal or larger UACR. Both hypertension and age are independent risk factors that increase the UACR. The present study indicated that a considerable percentage of patients require anti-hypertensive drugs with antiproteinuric effects at the start of treatment.

Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 1. Peptides to Proteins

NASA Astrophysics Data System (ADS)

Donohoe, Gregory C.; Khakinejad, Mahdiar; Valentine, Stephen J.

2015-04-01

Ion mobility spectrometry (IMS) coupled with hydrogen deuterium exchange (HDX)-mass spectrometry (MS) has been used to study the conformations of negatively-charged peptide and protein ions. Results are presented for ion conformers of angiotensin 1, a synthetic peptide (SP), bovine insulin, ubiquitin, and equine cytochrome c. In general, the SP ion conformers demonstrate a greater level of HDX efficiency as a greater proportion of the sites undergo HDX. Additionally, these ions exhibit the fastest rates of exchange. Comparatively, the angiotensin 1 ions exhibit a lower rate of exchange and HDX level presumably because of decreased accessibility of exchange sites by charge sites. The latter are likely confined to the peptide termini. Insulin ions show dramatically reduced HDX levels and exchange rates, which can be attributed to decreased conformational flexibility resulting from the disulfide bonds. For the larger ubiquitin and protein ions, increased HDX is observed for larger ions of higher charge state. For ubiquitin, a conformational transition from compact to more elongated species (from lower to higher charge states) is reflected by an increase in HDX levels. These results can be explained by a combination of interior site protection by compact conformers as well as decreased access by charge sites. The elongated cytochrome c ions provide the largest HDX levels where higher values correlate with charge state. These results are consistent with increased exchange site accessibility by additional charge sites. The data from these enhanced IMS-HDX experiments are described in terms of charge site location, conformer rigidity, and interior site protection.

Basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and psychological distress in recreational ecstasy polydrug users.

PubMed

Wetherell, Mark A; Montgomery, Catharine

2014-04-01

Ecstasy (MDMA) is a psychostimulant drug which is increasingly associated with psychobiological dysfunction. While some recent studies suggest acute changes in neuroendocrine function, less is known about long-term changes in HPA functionality in recreational users. The current study is the first to explore the effects of ecstasy-polydrug use on psychological distress and basal functioning of the HPA axis through assessing the secretion of cortisol across the diurnal period. Seventy-six participants (21 nonusers, 29 light ecstasy-polydrug users, 26 heavy ecstasy-polydrug users) completed a substance use inventory and measures of psychological distress at baseline, then two consecutive days of cortisol sampling (on awakening, 30 min post awakening, between 1400 and 1600 hours and pre bedtime). On day 2, participants also attended the laboratory to complete a 20-min multitasking stressor. Both user groups exhibited significantly greater levels of anxiety and depression than nonusers. On day 1, all participants exhibited a typical cortisol profile, though light users had significantly elevated levels pre-bed. On day 2, heavy users demonstrated elevated levels upon awakening and all ecstasy-polydrug users demonstrated elevated pre-bed levels compared to non-users. Significant between group differences were also observed in afternoon cortisol levels and in overall cortisol secretion across the day. The increases in anxiety and depression are in line with previous observations in recreational ecstasy-polydrug users. Dysregulated diurnal cortisol may be indicative of inappropriate anticipation of forthcoming demands and hypersecretion may lead to the increased psychological and physical morbidity associated with heavy recreational use of ecstasy.

Inundation Effects on Growth and Decomposition of Two Tidal Marsh Plant Species, Spartina Alterniflora and Typha Angustifolia

EPA Science Inventory

Tidal marshes of southern New England have exhibited substantial changes over the past century: multiple anthropogenic stressors, such as enhanced rates of sea level rise, hydrological modifications, the introduction of invasive species, and increased nutrient loading have result...

Alcohol Consumption and Prehypertension: An Investigation of University Youth

ERIC Educational Resources Information Center

Jorgensen, Randall S.; Maisto, Stephen A.

2008-01-01

Prehypertension and heavy alcohol consumption increase the risk for primary hypertension (PH), a major predictor of cardiovascular-related morbidity and mortality. Although undergraduate college students have exhibited prehypertensive blood pressure (BP) levels and more than 40% of undergraduates drink heavily, few researchers have examined both…

Overweight female rats selectively breed for low aerobic capacity exhibit increased myocardial fibrosis and diastolic dysfunction

PubMed Central

Johnson, Megan S.; Ma, Lixin; Pulakat, Lakshmi; Mugerfeld, Irina; Hayden, Melvin R.; Garro, Mona; Knight, William; Britton, Steven L.; Koch, Lauren G.; Sowers, James R.

2012-01-01

The statistical association between endurance exercise capacity and cardiovascular disease suggests that impaired aerobic metabolism underlies the cardiovascular disease risk in men and women. To explore this connection, we applied divergent artificial selection in rats to develop low-capacity runner (LCR) and high-capacity runner (HCR) rats and found that disease risks segregated strongly with low running capacity. Here, we tested if inborn low aerobic capacity promotes differential sex-related cardiovascular effects. Compared with HCR males (HCR-M), LCR males (LCR-M) were overweight by 34% and had heavier retroperitoneal, epididymal, and omental fat pads; LCR females (LCR-F) were 20% heavier than HCR females (HCR-F), and their retroperitoneal, but not perireproductive or omental, fat pads were heavier as well. Unlike HCR-M, blood pressure was elevated in LCR-M, and this was accompanied by left ventricular (LV) hypertrophy. Like HCR-F, LCR-F exhibited normal blood pressure and LV weight as well as increased spontaneous cage activity compared with males. Despite normal blood pressures, LCR-F exhibited increased myocardial interstitial fibrosis and diastolic dysfunction, as indicated by increased LV stiffness, a decrease in the initial filling rate, and an increase in diastolic relaxation time. Although females exhibited increased arterial stiffness, ejection fraction was normal. Increased interstitial fibrosis and diastolic dysfunction in LCR-F was accompanied by the lowest protein levels of phosphorylated AMP-actived protein kinase [phospho-AMPK (Thr172)] and silent information regulator 1. Thus, the combination of risk factors, including female sex, intrinsic low aerobic capacity, and overweightness, promote myocardial stiffness/fibrosis sufficient to induce diastolic dysfunction in the absence of hypertension and LV hypertrophy. PMID:22345570

Mechanisms to account for maintenance of the soluble methionine pool in transgenic Arabidopsis plants expressing antisense cystathionine gamma-synthase cDNA.

PubMed

Gakière, B; Ravanel, S; Droux, M; Douce, R; Job, D

2000-10-01

To investigate the role of cystathionine gamma-synthase (CGS) in the regulation of methionine synthesis Arabidopsis plants were transformed with a full-length antisense CGS cDNA and transformants analysed. Plants that were heterozygous for the transgene showed a 20-fold reduction of CGS activity that was accompanied by severe growth retardation and morphological abnormalities, from germination to flowering. Application of exogenous methionine to the transgenic lines restored normal growth. Surprisingly, transformed Arabidopsis plants exhibited a modest decrease in methionine content (35% reduction of the wild-type level) but a seven-fold decrease in the soluble pool of S-methylmethionine (SMM), a compound that plays a major role in storage and transport of reduced sulphur and labile methyl moieties. Several mechanisms can account for the maintenance of the soluble pool of methionine. First, the observed 20-fold increase in O-phosphohomoserine, a substrate of CGS, could compensate for the depressed level of CGS polypeptide by increasing the net rate of catalysis supported by the remaining enzyme. Second, the transgenic plants exhibited a two-fold increased level of cystathionine beta-lyase, the second enzyme in the methionine biosynthetic pathway. This indicates that enzymes other than CGS are subjected to a regulatory control by methionine or one of its metabolites. In addition to these mechanisms affecting de novo methionine synthesis, the recruitment of SMM to produce methionine may account for the small change of methionine levels in transgenic lines.

Niemann-pick type C1 (NPC1) overexpression alters cellular cholesterol homeostasis.

PubMed

Millard, E E; Srivastava, K; Traub, L M; Schaffer, J E; Ory, D S

2000-12-08

The Niemann-Pick type C1 (NPC1) protein is a key participant in intracellular trafficking of low density lipoprotein cholesterol, but its role in regulation of sterol homeostasis is not well understood. To characterize further the function of NPC1, we generated stable Chinese hamster ovary (CHO) cell lines overexpressing the human NPC1 protein (CHO/NPC1). NPC1 overexpression increases the rate of trafficking of low density lipoprotein cholesterol to the endoplasmic reticulum and the rate of delivery of endosomal cholesterol to the plasma membrane (PM). CHO/NPC1 cells exhibit a 1.5-fold increase in total cellular cholesterol and up to a 2.9-fold increase in PM cholesterol. This increase in PM cholesterol is closely paralleled by a 3-fold increase in de novo cholesterol synthesis. Inhibition of cholesterol synthesis results in marked redistribution of PM cholesterol to intracellular sites, suggesting an unsuspected role for NPC1 in internalization of PM cholesterol. Despite elevated total cellular cholesterol, CHO/NPC1 cells exhibit increased cholesterol synthesis, which may be attributable to both resistance to oxysterol suppression of sterol-regulated gene expression and to reduced endoplasmic reticulum cholesterol levels under basal conditions. Taken together, these studies provide important new insights into the role of NPC1 in the determination of the levels and distribution of cellular cholesterol.

Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice

PubMed Central

Ai, Ding; Chen, Chiyuan; Han, Seongah; Ganda, Anjali; Murphy, Andrew J.; Haeusler, Rebecca; Thorp, Edward; Accili, Domenico; Horton, Jay D.; Tall, Alan R.

2012-01-01

Individuals with type 2 diabetes have an increased risk of atherosclerosis. One factor underlying this is dyslipidemia, which in hyperinsulinemic subjects with early type 2 diabetes is typically characterized by increased VLDL secretion but normal LDL cholesterol levels, possibly reflecting enhanced catabolism of LDL via hepatic LDLRs. Recent studies have also suggested that hepatic insulin signaling sustains LDLR levels. We therefore sought to elucidate the mechanisms linking hepatic insulin signaling to regulation of LDLR levels. In WT mice, insulin receptor knockdown by shRNA resulted in decreased hepatic mTORC1 signaling and LDLR protein levels. It also led to increased expression of PCSK9, a known post-transcriptional regulator of LDLR expression. Administration of the mTORC1 inhibitor rapamycin caused increased expression of PCSK9, decreased levels of hepatic LDLR protein, and increased levels of VLDL/LDL cholesterol in WT but not Pcsk9–/– mice. Conversely, mice with increased hepatic mTORC1 activity exhibited decreased expression of PCSK9 and increased levels of hepatic LDLR protein levels. Pcsk9 is regulated by the transcription factor HNF1α, and our further detailed analyses suggest that increased mTORC1 activity leads to activation of PKCδ, reduced activity of HNF4α and HNF1α, decreased PCSK9 expression, and ultimately increased hepatic LDLR protein levels, which result in decreased circulating LDL levels. We therefore suggest that PCSK9 inhibition could be an effective way to reduce the adverse side effect of increased LDL levels that is observed in transplant patients taking rapamycin as immunosuppressive therapy. PMID:22426206

Overexpression of porcine lipoprotein-associated phospholipase A2 in swine.

PubMed

Tang, Xiaochun; Wang, Gangqi; Liu, Xingxing; Han, Xiaolei; Li, Zhuang; Ran, Guangyao; Li, Zhanjun; Song, Qi; Ji, Yuan; Wang, Haijun; Wang, Yuhui; Ouyang, Hongsheng; Pang, Daxin

2015-09-25

Lipoprotein-associated phospholipase A 2 (Lp-PLA2) is associated with the risk of vascular disease. It circulates in human blood predominantly in association with low-density lipoprotein cholesterol (LDL-C) and hydrolyses oxidized phospholipids into pro-inflammatory products. However, in the mouse circulation, it predominantly binds to high-density lipoprotein cholesterol (HDL-C) and exhibits anti-inflammatory properties. To further investigate the effects of Lp-PLA2 in the circulation, we generated over-expressed Lp-PLA2 transgenic swine. The eukaryotic expression plasmid of porcine Lp-PLA2 which driven by EF1α promoter was constructed and generate transgenic swine via SCNT. The expression and activity of Lp-PLA2 in transgenic swine were evaluated, and the total cholesterol (TC), HDL-C, LDL-C and triglyceride (TG) levels in the fasting and fed states were also assessed. Compared with wild-type swine controls, the transgenic swine exhibited elevated Lp-PLA2 mRNA levels and activities, and the activity did not depend on the feeding state. The TC, HDL-C and LDL-C levels were not significantly increased. There was no change in the TG levels in the fasting state between transgenic and control pigs. However, in the fed state, the TG levels of transgenic swine were slightly increased compared with the control pigs and were significantly elevated compared with the fasting state. In addition, inflammatory gene (interleukin [IL]-6, monocyte chemotactic protein [MCP]-1 and tumor necrosis factor [TNF]-α) mRNA levels in peripheral blood mononuclear cells (PBMCs) were significantly increased. The results demonstrated that Lp-PLA2 is associated with triglycerides which may be helpful for understanding the relationship of this protein with cardiovascular disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Alteration in plasma corticosterone levels following long term oral administration of lead produces depression like symptoms in rats.

PubMed

Haider, Saida; Saleem, Sadia; Tabassum, Saiqa; Khaliq, Saima; Shamim, Saima; Batool, Zehra; Parveen, Tahira; Inam, Qurat-ul-ain; Haleem, Darakhshan J

2013-03-01

Lead toxicity is known to induce a broad range of physiological, biochemical and behavioral dysfunctions that may result in adverse effects on several organs, including the central nervous system. Long-term exposure to low levels of lead (Pb(2+)) has been shown to produce behavioral deficits in rodents and humans by affecting hypothalamic-pituitary-adrenal (HPA) axis. These deficits are thought to be associated with altered brain monoamine neurotransmission and due to changes in glucocorticoids levels. This study was designed to investigate the effects of Pb(2+)exposure on growth rate, locomotor activity, anxiety, depression, plasma corticosterone and brain serotonin (5-HT) levels in rats. Rats were exposed to lead in drinking water (500 ppm; lead acetate) for 5 weeks. The assessment of depression was done using the forced swimming test (FST). Estimation of brain 5-HT was determined by high-performance liquid chromatography with electrochemical detection. Plasma corticosterone was determined by spectrofluorimetric method. The present study showed that long term exposure to Pb(2+) significantly decreased the food intake followed by the decrease in growth rate in Pb(2+)exposed rats as compared to control group. No significant changes in open field activity were observed following Pb(2+)exposure while significant increase in anxiogenic effect was observed. Increased plasma corticosterone and decreased 5-HT levels were exhibited by Pb(2+)exposed rats as compared to controls. A significant increase in depressive like symptoms was exhibited by Pb(2+)exposed rats as compared to control rats. The results are discussed in the context of Pb(2+) inducing a stress-like response in rats leading to changes in plasma corticosterone and brain 5-HT levels via altering tryptophan pyrrolase activity.

Death qualification and prejudice: the effect of implicit racism, sexism, and homophobia on capital defendants' right to due process.

PubMed

Butler, Brooke

2007-01-01

Two hundred venirepersons from the 12th Judicial Circuit in Bradenton, Florida completed the following measures: (1) one question that measured their level of support for the death penalty; (2) one question that categorized their death-qualification status; (3) 23 questions that measured their attitudes toward the death penalty (ATDP); (4) 22 questions that assessed their attitudes toward women (ATW); (5) 25 questions that measured their level of homophobia (H); (6) seven questions that assessed their level of modern racism (MR); (7) eight questions that measured their level of modern sexism (MS); and (8) standard demographic questions. Results indicated that as death-penalty support increased participants exhibited more positive attitudes toward the death penalty, more negative attitudes toward women, and higher levels of homophobia, modern racism, and modern sexism. Findings also suggested that death-qualified venirepersons exhibited more positive attitudes toward the death penalty and higher levels of homophobia, modern racism, and modern sexism. Finally, more positive attitudes toward the death penalty were correlated with more negative attitudes toward women and higher levels of homophobia, modern racism, and modern sexism. Legal implications are discussed. Copyright (c) 2007 John Wiley & Sons, Ltd.

[Evaluation of various biochemical parameters in the urine and blood of painters in the carpentry business].

PubMed

Sołtys, M; Jakubowska, W; Lenart, E; Nagadowska, H; Lisiecka, M; Ziemer, I; Koćmierkska-Grodzka, D

1986-01-01

The work has been aimed at investigating the effects of organic solvent-toluene-upon the painters of the Building Joinery Factory. Studies carried out during 1978-1980 showed an increased level of toluene metabolite (hippuric acid) in painters' urine, as compared to the environmental control group. The highest level of hippuric acid in painters' urine was found in the first period (first six months) of their job. This was not related to an increase in toluene vapours at the workplace. In painters' blood some irregular and rather small modifications of enzymatic activity were exhibited.

Personality and attention: Levels of neuroticism and extraversion can predict attentional performance during a change detection task.

PubMed

Hahn, Sowon; Buttaccio, Daniel R; Hahn, Jungwon; Lee, Taehun

2015-01-01

The present study demonstrates that levels of extraversion and neuroticism can predict attentional performance during a change detection task. After completing a change detection task built on the flicker paradigm, participants were assessed for personality traits using the Revised Eysenck Personality Questionnaire (EPQ-R). Multiple regression analyses revealed that higher levels of extraversion predict increased change detection accuracies, while higher levels of neuroticism predict decreased change detection accuracies. In addition, neurotic individuals exhibited decreased sensitivity A' and increased fixation dwell times. Hierarchical regression analyses further revealed that eye movement measures mediate the relationship between neuroticism and change detection accuracies. Based on the current results, we propose that neuroticism is associated with decreased attentional control over the visual field, presumably due to decreased attentional disengagement. Extraversion can predict increased attentional performance, but the effect is smaller than the relationship between neuroticism and attention.

The Arabidopsis cax1 Mutant Exhibits Impaired Ion Homeostasis, Development, and Hormonal Responses and Reveals Interplay among Vacuolar Transporters

PubMed Central

Cheng, Ning-Hui; Pittman, Jon K.; Barkla, Bronwyn J.; Shigaki, Toshiro; Hirschi, Kendal D.

2003-01-01

The Arabidopsis Ca2+/H+ transporter CAX1 (Cation Exchanger1) may be an important regulator of intracellular Ca2+ levels. Here, we describe the preliminary localization of CAX1 to the tonoplast and the molecular and biochemical characterization of cax1 mutants. We show that these mutants exhibit a 50% reduction in tonoplast Ca2+/H+ antiport activity, a 40% reduction in tonoplast V-type H+-translocating ATPase activity, a 36% increase in tonoplast Ca2+-ATPase activity, and increased expression of the putative vacuolar Ca2+/H+ antiporters CAX3 and CAX4. Enhanced growth was displayed by the cax1 lines under Mn2+ and Mg2+ stress conditions. The mutants exhibited altered plant development, perturbed hormone sensitivities, and altered expression of an auxin-regulated promoter-reporter gene fusion. We propose that CAX1 regulates myriad plant processes and discuss the observed phenotypes with regard to the compensatory alterations in other transporters. PMID:12566577

The Arabidopsis cax1 mutant exhibits impaired ion homeostasis, development, and hormonal responses and reveals interplay among vacuolar transporters.

PubMed

Cheng, Ning-Hui; Pittman, Jon K; Barkla, Bronwyn J; Shigaki, Toshiro; Hirschi, Kendal D

2003-02-01

The Arabidopsis Ca(2+)/H(+) transporter CAX1 (Cation Exchanger1) may be an important regulator of intracellular Ca(2+) levels. Here, we describe the preliminary localization of CAX1 to the tonoplast and the molecular and biochemical characterization of cax1 mutants. We show that these mutants exhibit a 50% reduction in tonoplast Ca(2+)/H(+) antiport activity, a 40% reduction in tonoplast V-type H(+)-translocating ATPase activity, a 36% increase in tonoplast Ca(2+)-ATPase activity, and increased expression of the putative vacuolar Ca(2+)/H(+) antiporters CAX3 and CAX4. Enhanced growth was displayed by the cax1 lines under Mn(2+) and Mg(2+) stress conditions. The mutants exhibited altered plant development, perturbed hormone sensitivities, and altered expression of an auxin-regulated promoter-reporter gene fusion. We propose that CAX1 regulates myriad plant processes and discuss the observed phenotypes with regard to the compensatory alterations in other transporters.

Tracking How Science Resources Result in Educator- and Community-Level Outcomes

NASA Astrophysics Data System (ADS)

Dusenbery, P.; Harold, J. B.; Fitzhugh, G.; LaConte, K.; Holland, A.

2017-12-01

Learners frequently need to access increasingly complex information to help them understand our changing world. More and more libraries are transforming themselves into places where learners not only access STEM information, but interact with professionals and undertake hands-on learning. Libraries are beginning to position themselves as part of learning ecosystems that contribute to a collective impact on the community. Traveling STEM exhibits are catalyzing these partnerships and engaging students, families, and adults in repeat visits through an accessible venue: their public library. This talk will explore impacts from two STAR Library Network's (STAR_Net) exhibitions (Discover Earth and Discover Tech) on partnerships, the circulation of STEM resources, and the engagement of learners. The STAR_Net project's summative evaluation utilized mixed methods to investigate project implementation and its outcomes. Methods included pre- and post-exhibit surveys administered to staff from each library that hosted the exhibits; interviews with staff from host libraries; patron surveys; exhibit-related circulation records; web metrics regarding the online STAR_Net community of practice; and site visits. The latter provides a more complete view of impacts on the community, including underserved audiences. NASA@ My Library is a new STAR_Net initiative, which provides STEM facilitation kits, training, and other resources to 75 libraries nationwide. Initial results will be presented that show high levels of engagement by librarians and strong response rate from patrons on surveys.

Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up

PubMed Central

Kadara, H; Choi, M; Zhang, J; Parra, E R; Rodriguez-Canales, J; Gaffney, S G; Zhao, Z; Behrens, C; Fujimoto, J; Chow, C; Yoo, Y; Kalhor, N; Moran, C; Rimm, D; Swisher, S; Gibbons, D L; Heymach, J; Kaftan, E; Townsend, J P; Lynch, T J; Schlessinger, J; Lee, J; Lifton, R P; Wistuba, I I; Herbst, R S

2017-01-01

Abstract Background Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable to lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses of a unique set of clinically annotated early-stage LUADs to better understand the pathogenesis of this disease and identify clinically relevant molecular markers. Methods We performed WES of 108 paired stage I-III LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B) were profiled by imaging-based immunohistochemistry (IHC) in a subset of LUADs (n = 92). Associations among mutations, immune markers and clinicopathological variables were analyzed using ANOVA and Fisher’s exact test. Cox proportional hazards regression models were used for multivariate analysis of clinical outcome. Results LUADs in this cohort exhibited an average of 243 coding mutations. We identified 28 genes with significant enrichment for mutation. SETD2-mutated LUADs exhibited relatively poor recurrence- free survival (RFS) and mutations in STK11 and ATM were associated with poor RFS among KRAS-mutant tumors. EGFR, KEAP1 and PIK3CA mutations were predictive of poor response to adjuvant therapy. Immune marker analysis revealed that LUADs in smokers and with relatively high mutation burdens exhibited increased levels of immune markers. Analysis of immunophenotypes revealed that LUADs with STK11 mutations exhibited relatively low levels of infiltrating CD4+/CD8+ T-cells indicative of a muted immune response. Tumoral PD-L1 was significantly elevated in TP53 mutant LUADs whereas PIK3CA mutant LUADs exhibited markedly down-regulated PD-L1 expression. LUADs with TP53 or KEAP1 mutations displayed relatively increased CD57 and Granzyme B levels indicative of augmented natural killer (NK) cell infiltration. Conclusion(s) Our study highlights molecular and immune phenotypes that warrant further analysis for their roles in clinical outcomes and personalized immune-based therapy of LUAD. PMID:27687306

Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up.

PubMed

Kadara, H; Choi, M; Zhang, J; Parra, E R; Rodriguez-Canales, J; Gaffney, S G; Zhao, Z; Behrens, C; Fujimoto, J; Chow, C; Yoo, Y; Kalhor, N; Moran, C; Rimm, D; Swisher, S; Gibbons, D L; Heymach, J; Kaftan, E; Townsend, J P; Lynch, T J; Schlessinger, J; Lee, J; Lifton, R P; Wistuba, I I; Herbst, R S

2017-01-01

Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable to lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses of a unique set of clinically annotated early-stage LUADs to better understand the pathogenesis of this disease and identify clinically relevant molecular markers. We performed WES of 108 paired stage I-III LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B) were profiled by imaging-based immunohistochemistry (IHC) in a subset of LUADs (n = 92). Associations among mutations, immune markers and clinicopathological variables were analyzed using ANOVA and Fisher's exact test. Cox proportional hazards regression models were used for multivariate analysis of clinical outcome. LUADs in this cohort exhibited an average of 243 coding mutations. We identified 28 genes with significant enrichment for mutation. SETD2-mutated LUADs exhibited relatively poor recurrence- free survival (RFS) and mutations in STK11 and ATM were associated with poor RFS among KRAS-mutant tumors. EGFR, KEAP1 and PIK3CA mutations were predictive of poor response to adjuvant therapy. Immune marker analysis revealed that LUADs in smokers and with relatively high mutation burdens exhibited increased levels of immune markers. Analysis of immunophenotypes revealed that LUADs with STK11 mutations exhibited relatively low levels of infiltrating CD4+/CD8+ T-cells indicative of a muted immune response. Tumoral PD-L1 was significantly elevated in TP53 mutant LUADs whereas PIK3CA mutant LUADs exhibited markedly down-regulated PD-L1 expression. LUADs with TP53 or KEAP1 mutations displayed relatively increased CD57 and Granzyme B levels indicative of augmented natural killer (NK) cell infiltration. Our study highlights molecular and immune phenotypes that warrant further analysis for their roles in clinical outcomes and personalized immune-based therapy of LUAD. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Bilingual Storybook Apps: An Interactive Reading Experience for Children

ERIC Educational Resources Information Center

Herzig, Melissa; Malzkuhn, Melissa

2015-01-01

In recent years, researchers have turned their attention to the cognitive impact of bilingualism, and the benefits of using two languages have become increasingly apparent. Children raised in bilingual families exhibit stronger awareness of the style and tone of language, stronger cognitive development, and higher levels of reading skill than…

Training Students with Behavioral Problems to Recruit Teacher Praise

ERIC Educational Resources Information Center

Markelz, Andrew; Riden, Benjamin; Rizzo, Karen

2018-01-01

Students with emotional and behavioral disorders exhibit high levels of inappropriate behaviors. Although many teachers are aware of the benefits of teacher praise, its use in classrooms remains low. Training students to recruit praise is a method to counter suppressing contingencies and increase praise rates for desired classroom behaviors. With…

Sensitivity of the vitellogenin assay: ability to discriminate among exposure concentrations in adult fathead minnow

EPA Science Inventory

Vitellogenin is often used to infer exposure of an organism to estrogenic substances. Vitellogenin gene induction and protein levels increase, up to a point, with concentration of estrogen and duration of exposure. A biomarker such as vitellogenin should exhibit sufficient sens...

Ratoon rice generated from primed parent plants exhibit enhanced herbivore resistance

USDA-ARS?s Scientific Manuscript database

Rice (Oryza sativa) plants have the ability to regenerate new panicle-bearing tillers post-harvest, and for this reason ratooning represents a practical approach for achieving increased production levels with limited labor input for this crop. Here we report that attack by insect herbivores, or trea...

Developmental Changes in Cognitive and Behavioural Functioning of Adolescents with Fragile-X Syndrome

ERIC Educational Resources Information Center

Frolli, A.; Piscopo, S.; Conson, M.

2015-01-01

Background: Individuals with fragile-X syndrome exhibit developmental delay, hyperexcitation and social anxiety; they also show lack of attention and hyperactivity. Few studies have investigated whether levels of functioning change with increasing age. Here, we explored developmental changes across adolescence in the cognitive and behavioural…

Elevated Levels of Somatic Mutation as a Biomarker of Environmental Effects Contributing to Breast Carcinogenesis

DTIC Science & Technology

2001-07-01

and hepatocellular carcinoma patients have been shown to exhibit elevated somatic mutation frequencies with the GPA assay (Okada et al., 1997...T, Kyogoku A, Yoshimori M (1997) Evidence for increased somatic cell mutations in patients with hepatocellular carcinoma . Carcinogenesis 18: 445-449...significant increase in mutation at the GPA locus has been reported for a population of hepatocellular carcinoma patients (Okada et al., 1997

HIF-1α regulates Cx40-dependent vasodilatation following hemorrhagic shock in rats

PubMed Central

Duan, Chenyang; Chen, Ken; Yang, Guangming; Li, Tao; Liu, Liangming

2017-01-01

HIF-1α plays an essential role in hemorrhagic shock-induced vasoconstriction. However, the underlying mechanisms remain poorly understood. Here, we studied both the role of HIF-1α in regulating vasodilatation, and the involvement of Cx40 in this process. We found that endothelium-dependent vasodilatation exhibited an overall decline after hemorrhagic shock: at the beginning of shock vasodilatation reactivity significantly decreased, followed by a slight increase from 0.5 h to 2 h after shock. After 2 h vasodilatation dropped again. Throughout this process, protein levels of HIF-1α gradually increased. In the late period of shock, vasodilatation reactivity was enhanced by oligomycin, an HIF-1α inhibitor, suggesting that HIF-1α may promote vasoconstriction. Moreover, in the late period of shock Cx40 levels gradually increased and exhibited a negative correlation with endothelium-dependent vasoconstriction reactivity. Furthermore, Cx40 AODN significantly improved vasoconstriction reactivity and could be regulated by either an HIF-1α inhibitor or an agonist. Together, these data suggest that HIF-1α may inhibit endothelium-dependent vasodilatation reactivity following hemorrhagic shock by up-regulating Cx40, especially in the late period of shock. PMID:28386353

Effects of 60-Hz electric fields on serotonin metabolism in the rat pineal gland

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

Anderson, L.E.; Hilton, D.I.; Phillips, R.D.

Serotonin and two of its metabolites, melatonin and 5-methoxytryptophol, exhibit circadian rhythmicity in the pineal gland. We recently reported a marked reduction in the normal night-time increase in melatonin concentration in the pineal glands of rats exposed to 60-Hz electric fields. Concomitant with the apparent abolition of melatonin rhythmicity, serotonin-N-acetyl transferase (SNAT) activity was suppressed. We have now conducted studies to determine if abolition of the rhythm in melatonin production in electric-field-exposed rats arises solely from interference in SNAT activity, or if the availability of pineal serotonin is a factor that is affected by exposure. Pineal serotonin concentrations were comparedmore » in rats that were either exposed or sham exposed to 65 kV/m for 30 days. Sham-exposed animals exhibited normal diurnal rhythmicity for pineal concentrations of both melatonin and serotonin; melatonin levels increased markedly during the dark phase with a concurrent decrease in serotonin levels. In the exposed animals, however, normal serotonin rhythmicity was abolished; serotonin levels in these animals did not increase during the light period. The conclusion that electric field exposure results in a biochemical alteration in SNAT enzyme activity can be inferred from the loss of both serotonin and melatonin rhythmicity, as well as by direct measurement of SNAT activity itself. 35 references, 3 figures, 1 table.« less

Mouse model for deficiency of methionine synthase reductase exhibits short-term memory impairment and disturbances in brain choline metabolism.

PubMed

Jadavji, Nafisa M; Bahous, Renata H; Deng, Liyuan; Malysheva, Olga; Grand'maison, Marilyn; Bedell, Barry J; Caudill, Marie A; Rozen, Rima

2014-07-15

Hyperhomocysteinaemia can contribute to cognitive impairment and brain atrophy. MTRR (methionine synthase reductase) activates methionine synthase, which catalyses homocysteine remethylation to methionine. Severe MTRR deficiency results in homocystinuria with cognitive and motor impairments. An MTRR polymorphism may influence homocysteine levels and reproductive outcomes. The goal of the present study was to determine whether mild hyperhomocysteinaemia affects neurological function in a mouse model with Mtrr deficiency. Mtrr+/+, Mtrr+/gt and Mtrrgt/gt mice (3 months old) were assessed for short-term memory, brain volumes and hippocampal morphology. We also measured DNA methylation, apoptosis, neurogenesis, choline metabolites and expression of ChAT (choline acetyltransferase) and AChE (acetylcholinesterase) in the hippocampus. Mtrrgt/gt mice exhibited short-term memory impairment on two tasks. They had global DNA hypomethylation and decreased choline, betaine and acetylcholine levels. Expression of ChAT and AChE was increased and decreased respectively. At 3 weeks of age, they showed increased neurogenesis. In the cerebellum, mutant mice had DNA hypomethylation, decreased choline and increased expression of ChAT. Our work demonstrates that mild hyperhomocysteinaemia is associated with memory impairment. We propose a mechanism whereby a deficiency in methionine synthesis leads to hypomethylation and compensatory disturbances in choline metabolism in the hippocampus. This disturbance affects the levels of acetylcholine, a critical neurotransmitter in learning and memory.

Nisin ZP, a Bacteriocin and Food Preservative, Inhibits Head and Neck Cancer Tumorigenesis and Prolongs Survival

PubMed Central

Kamarajan, Pachiyappan; Hayami, Takayuki; Matte, Bibiana; Liu, Yang; Danciu, Theodora; Ramamoorthy, Ayyalusamy; Worden, Francis; Kapila, Sunil; Kapila, Yvonne

2015-01-01

The use of small antimicrobial peptides or bacteriocins, like nisin, to treat cancer is a new approach that holds great promise. Nisin exemplifies this new approach because it has been used safely in humans for many years as a food preservative, and recent laboratory studies support its anti-tumor potential in head and neck cancer. Previously, we showed that nisin (2.5%, low content) has antitumor potential in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. The current studies explored a naturally occurring variant of nisin (nisin ZP; 95%, high content) for its antitumor effects in vitro and in vivo. Nisin ZP induced the greatest level of apoptosis in HNSCC cells compared to low content nisin. HNSCC cells treated with increasing concentrations of nisin ZP exhibited increasing levels of apoptosis and decreasing levels of cell proliferation, clonogenic capacity, and sphere formation. Nisin ZP induced apoptosis through a calpain-dependent pathway in HNSCC cells but not in human oral keratinocytes. Nisin ZP also induced apoptosis dose-dependently in human umbilical vein endothelial cells (HUVEC) with concomitant decreases in vascular sprout formation in vitro and reduced intratumoral microvessel density in vivo. Nisin ZP reduced tumorigenesis in vivo and long-term treatment with nisin ZP extended survival. In addition, nisin treated mice exhibited normal organ histology with no evidence of inflammation, fibrosis or necrosis. In summary, nisin ZP exhibits greater antitumor effects than low content nisin, and thus has the potential to serve as a novel therapeutic for HNSCC. PMID:26132406

The role of gibberellins in improving the resistance of tebuconazole-coated maize seeds to chilling stress by microencapsulation

NASA Astrophysics Data System (ADS)

Yang, Lijuan; Yang, Daibin; Yan, Xiaojing; Cui, Li; Wang, Zhenying; Yuan, Huizhu

2016-11-01

Chilling stress during germination often causes severe injury. In the present study, maize seed germination and shoot growth under chilling stress were negatively correlated with the dose of tebuconazole in an exponential manner as predicted by the model Y = A + B × e(-x/k). Microencapsulation was an effective means of eliminating potential phytotoxic risk. The gibberellins (GAs) contents were higher after microencapsulation treatment than after conventional treatment when the dose of tebuconazole was higher than 0.12 g AI (active ingredient) kg-1 seed. Further analysis indicated that microencapsulation can stimulate ent-kaurene oxidase (KO) activity to some extent, whereas GA 3-oxidase (GA3ox) and GA 2-oxidase (GA2ox) activities remained similar to those in the control. Genes encoding GA metabolic enzymes exhibited different expression patterns. Transcript levels of ZmKO1 increased in the microcapsule treatments compared to the control. Even when incorporated into microcapsules, tebuconazole led to the upregulation of ZmGA3ox1 at doses of less than 0.12 g AI kg-1 seed and to the upregulation of ZmGA3ox2 when the dose was higher than 0.12 g AI kg-1 seed. With increasing doses of microencapsulated tebuconazole, the transcript levels of ZmGA2ox4, ZmGA2ox5 and ZmGA2ox6 exhibited upward trends, whereas the transcript levels of ZmGA2ox7 exhibited a downward trend.

Differential sensitivity of duckweeds (Lemnaceae) to sulfite: I. Carbon assimilation and frond replication rate as factors influencing sulfite phytotoxicity

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

Takemoto, B.K.; Noble, R.D.

1986-01-01

The thiol content and hydrogen sulfide emission responses of duckweeds (Lemnaceae) differentially sensitive to sulfite enrichment were studied, at two levels of irradiance. The objectives were to examine the relationship of selected parameters of sulfite metabolism to sulfite sensitivity, and the role of light level on modifying sulfite metabolic responses and duckweed sulfite sensitivity. Under low light, thiol contents were increased 30 to 40% by sulfite in all three duckweeds examined. Hydrogen sulfide was emitted by all three species, and emission rates were up to four times higher in the sulfite tolerant duckweed Lemna valdiviana. Under high light, sulfite increasedmore » thiol contents by an average of 40% in L. valdiviana and Spirodela oligorhiza, but only 20% in Lemna gibba. The greater light enhancement of thiol content exhibited by L. valdiviana and S. oligorhiza may be indicative of larger or more numerous sulfur sinks. Hydrogen sulfide emission rates were also enhanced under high light, and L. gibba exhibited a 17% increase relative to its low light rate. In comparison, L. valdiviana and S. oligorhiza exhibited 55% and 60% increases, respectively. The ability to form elevated internal thiols and hydrogen sulfide were found to be important to sulfite tolerance in duckweeds. Enhancement of both processes under high light may contribute to increased tolerance of sulfite in L. gibba and S. oligorhiza. It is hypothesized that thiol production and hydrogen sulfide emission are important sulfite detoxification processes in duckweeds, and enhancement of sulfite detoxification is fundamental to the modification of duckweed sulfite sensitivity by the photoenvironment. 25 refs., 3 tabs.« less

Use of modern contraception by the poor is falling behind.

PubMed

Gakidou, Emmanuela; Vayena, Effy

2007-02-01

The widespread increase in the use of contraception, due to multiple factors including improved access to modern contraception, is one of the most dramatic social transformations of the past fifty years. This study explores whether the global progress in the use of modern contraceptives has also benefited the poorest. Demographic and Health Surveys from 55 developing countries were analyzed using wealth indices that allow the identification of the absolute poor within each country. This article explores the macro level determinants of the differences in the use of modern contraceptives between the poor and the national averages of several countries. Despite increases in national averages, use of modern contraception by the absolute poor remains low. South and Southeast Asia have relatively high rates of modern contraception in the absolute poor, on average 17% higher than in Latin America. Over time the gaps in use persist and are increasing. Latin America exhibits significantly larger gaps in use between the poor and the averages, while gaps in sub-Saharan Africa are on average smaller by 15.8% and in Southeast Asia by 11.6%. The secular trend of increasing rates of modern contraceptive use has not resulted in a decrease of the gap in use for those living in absolute poverty. Countries with large economic inequalities also exhibit large inequalities in modern contraceptive use. In addition to macro level factors that influence contraceptive use, such as economic development and provision of reproductive health services, there are strong regional variations, with sub-Saharan Africa exhibiting the lowest national rates of use, South and Southeast Asia the highest use among the poor, and Latin America the largest inequalities in use.

The stress response to environmental change in captive cheetahs (Acinonyx jubatus).

PubMed

Wells, Amy; Terio, Karen A; Ziccardi, Michael H; Munson, Linda

2004-03-01

The captive North American cheetah (Acinonyx jubatus) population is not self-sustaining because of high prevalences of unusual diseases and poor reproductive success. Cheetahs are commonly moved between zoos for breeding purposes to maintain genetic diversity within the captive population, and movement may exacerbate infertility and disease. Fecal corticoids were analyzed by radioimmunoassay to measure the stress response of cheetahs to movement between facilities. Fecal samples were collected from 15 cheetahs for 14 days before movement and for at least 30 days after movement. For each cheetah, premovement fecal corticoid concentrations were used to determine baseline and then compared with trends in postmovement concentrations. In general, postmovement corticoid concentrations either increased (n = 8), did not change (n = 2), or decreased (n = 5). Although individual animal differences occurred, corticoid concentrations increased for most animals moved on-exhibit and decreased in animals moved off-exhibit. Animals moving on-exhibit had an 18-times greater risk of having corticoids elevated more than two standard deviations above baseline for 30 days after movement compared with animals that moved off-exhibit. In addition, greater day-to-day variation in corticoids occurred in animals moved on-exhibit. In general, animals with initially low baseline corticoid concentrations had a greater postmovement corticoid response than cheetahs with initially high baseline levels. These results indicate that some cheetahs have a prolonged stress response when moved between facilities, and the magnitude and character of this response is influenced by the exhibit environment.

Toll-like receptor 4 knockout ameliorates neuroinflammation due to lung-brain interaction in mechanically ventilated mice.

PubMed

Chen, Ting; Chen, Chang; Zhang, Zongze; Zou, Yufeng; Peng, Mian; Wang, Yanlin

2016-08-01

Toll-like receptor 4 (TLR4) is a crucial receptor in the innate immune system, and increasing evidence supports its role in inflammation, stress, and tissue injury, including injury to the lung and brain. We aimed to investigate the effects of TLR4 on neuroinflammation due to the lung-brain interaction in mechanically ventilated mice. Male wild-type (WT) C57BL/6 and TLR4 knockout (TLR4 KO) mice were divided into three groups: (1) control group (C): spontaneous breathing; (2) anesthesia group (A): spontaneous breathing under anesthesia; and (3) mechanical ventilation group (MV): 6h of MV under anesthesia. The behavioral responses of mice were tested with fear conditioning tests. The histological changes in the lung and brain were assessed using hematoxylin-eosin (HE) staining. The level of TLR4 mRNA in tissue was measured using reverse transcription-polymerase chain reaction (RT-PCR). The levels of inflammatory cytokines were measured with an enzyme-linked immunosorbent assay (ELISA). Microgliosis, astrocytosis, and the TLR4 immunoreactivity in the hippocampus were measured by double immunofluorescence. MV mice exhibited impaired cognition, and this impairment was less severe in TLR4 KO mice than in WT mice. In WT mice, MV increased TLR4 mRNA expression in the lung and brain. MV induced mild lung injury, which was prevented in TLR4 KO mice. MV mice exhibited increased levels of inflammatory cytokines, increased microglia and astrocyte activation. Microgliosis was alleviated in TLR4 KO mice. MV mice exhibited increased TLR4 immunoreactivity, which was expressed in microglia and astrocytes. These results demonstrate that TLR4 is involved in neuroinflammation due to the lung-brain interaction and that TLR4 KO ameliorates neuroinflammation due to lung-brain interaction after prolonged MV. In addition, Administration of a TLR4 antagonist (100μg/mice) to WT mice also significantly attenuated neuroinflammation of lung-brain interaction due to prolonged MV. TLR4 antagonism may be a new and novel approach for the treatment and management of neuroinflammation in long-term mechanically ventilated patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxidative stress upregulates zinc uptake activity via Zrt/Irt-like protein 1 (ZIP1) in cultured mouse astrocytes.

PubMed

Furuta, Takahiro; Ohshima, Chiaki; Matsumura, Mayu; Takebayashi, Naoto; Hirota, Emi; Mawaribuchi, Toshiki; Nishida, Kentaro; Nagasawa, Kazuki

2016-04-15

Zinc released from glutamatergic boutons and astrocytes acts as neuro- and glio-transmitters, and thus its extracellular level has to be strictly regulated. We previously revealed that uptake of zinc by astrocytes plays a critical role in its clearance, and zinc transporter Zrt/Irt-like protein 1 (ZIP1) is the molecule responsible for the uptake. However, it is unknown whether or not the functionality of the zinc clearance system is altered under oxidative stress-loaded conditions. Here, we characterized zinc uptake by oxidative stress-loaded astrocytes. Cultured mouse astrocytes were treated with hydrogen peroxide (H2O2) to load oxidative stress. Functional expression of ZIP1 in astrocytes was evaluated by means of (65)Zn uptake, Western blotting and immunocytochemical analysis. Treatment of astrocytes with 0.4mM H2O2 for 24h increased the expression levels of glial fibrillary acidic protein and 4-hydroxynonenal without significant decreases in their viability, indicating that induction of oxidative stress in astrocytes. Under oxidative stress-loaded conditions, astrocytes exhibited increased (65)Zn uptake activity, and the maximum uptake velocity for the uptake was significantly increased compared to that in the control group, while there was no change in the Michaelis constants, which were almost identical to that of mouse ZIP1. In the H2O2-treated astrocytes, the expression levels of ZIP1 were significantly increased in the cellular and plasma membrane fractions. It appears that under oxidative stress-loaded conditions, astrocytes exhibit increased zinc clearance activity and this is due, at least in part, to increased ZIP1 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Unique sex- and age-dependent effects in protective pathways in acute kidney injury.

PubMed

Boddu, Ravindra; Fan, Chunlan; Rangarajan, Sunil; Sunil, Bhuvana; Bolisetty, Subhashini; Curtis, Lisa M

2017-09-01

Sex and age influence susceptibility to acute kidney injury (AKI), with young females exhibiting lowest incidence. In these studies, we investigated mechanisms which may underlie the sex/age-based dissimilarities. Cisplatin (Cp)-induced AKI resulted in morphological evidence of injury in all groups. A minimal rise in plasma creatinine (PCr) was seen in Young Females, whereas in Aged Females, PCr rose precipitously. Relative to Young Males, Aged Males showed significantly, but temporally, comparably elevated PCr. Notably, Aged Females showed significantly greater mortality, whereas Young Females exhibited none. Tissue KIM-1 and plasma NGAL were significantly lower in Young Females than all others. IGFBP7 levels were modestly increased in both Young groups. IGFBP7 levels in Aged Females were significantly elevated at baseline relative to Aged Males, and increased linearly through day 3 , when these levels were comparable in both Aged groups. Plasma cytokine levels similarly showed a pattern of protective effects preferentially in Young Females. Expression of the drug transporter MATE2 did not explain the sex/age distinctions. Heme oxygenase-1 (HO-1) levels (~28-kDa species) showed elevation at day 1 in all groups with highest levels seen in Young Males. Exclusively in Young Females, these levels returned to baseline on day 3 , suggestive of a more efficient recovery. In aggregate, we demonstrate, for the first time, a distinctive pattern of response to AKI in Young Females relative to males which appears to be significantly altered in aging. These distinctions may offer novel targets to exploit therapeutically in both females and males in the treatment of AKI.

A link between FTO, ghrelin, and impaired brain food-cue responsivity

PubMed Central

Karra, Efthimia; O’Daly, Owen G.; Choudhury, Agharul I.; Yousseif, Ahmed; Millership, Steven; Neary, Marianne T.; Scott, William R.; Chandarana, Keval; Manning, Sean; Hess, Martin E.; Iwakura, Hiroshi; Akamizu, Takashi; Millet, Queensta; Gelegen, Cigdem; Drew, Megan E.; Rahman, Sofia; Emmanuel, Julian J.; Williams, Steven C.R.; Rüther, Ulrich U.; Brüning, Jens C.; Withers, Dominic J.; Zelaya, Fernando O.; Batterham, Rachel L.

2013-01-01

Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO “obesity-risk” rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans. PMID:23867619

A link between FTO, ghrelin, and impaired brain food-cue responsivity.

PubMed

Karra, Efthimia; O'Daly, Owen G; Choudhury, Agharul I; Yousseif, Ahmed; Millership, Steven; Neary, Marianne T; Scott, William R; Chandarana, Keval; Manning, Sean; Hess, Martin E; Iwakura, Hiroshi; Akamizu, Takashi; Millet, Queensta; Gelegen, Cigdem; Drew, Megan E; Rahman, Sofia; Emmanuel, Julian J; Williams, Steven C R; Rüther, Ulrich U; Brüning, Jens C; Withers, Dominic J; Zelaya, Fernando O; Batterham, Rachel L

2013-08-01

Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO "obesity-risk" rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans.

Temporal increase in organic mercury in an endangered pelagic seabird assessed by century-old museum specimens

PubMed Central

Vo, Anh-Thu E.; Bank, Michael S.; Shine, James P.; Edwards, Scott V.

2011-01-01

Methylmercury cycling in the Pacific Ocean has garnered significant attention in recent years, especially with regard to rising mercury emissions from Asia. Uncertainty exists concerning whether increases in anthropogenic emissions over time may have caused increased mercury bioaccumulation in the biota. To address this, we measured total mercury and, for a subset of samples, methylmercury (the bioaccumulated form of mercury) in museum feathers from an endangered seabird, the black-footed albatross (Phoebastria nigripes), spanning a 120-y period. We analyzed stable isotopes of nitrogen (δ15N) and carbon (δ13C) to control for temporal changes in trophic structure and diet. In post-1940 and -1990 feathers, we detected significantly higher mean methylmercury concentrations and higher proportions of samples exhibiting above deleterious threshold levels (∼40,000 ng·g−1) of methylmercury relative to prior time points, suggesting that mercury toxicity may undermine reproductive effort in the species. We also found higher levels of (presumably curator-mediated) inorganic mercury in older specimens of albatross as well as two nonpelagic species lacking historical exposure to bioavailable mercury, patterns suggesting that studies on bioaccumulation should measure methylmercury rather than total mercury when using museum collections. δ15N contributed substantially to models explaining the observed methylmercury variation. After simultaneously controlling for significant trends in δ13C over time and δ15N with methylmercury exposure, year remained a significant independent covariate with feather methylmercury levels among the albatrosses. These data show that remote seabird colonies in the Pacific basin exhibit temporal changes in methylmercury levels consistent with historical global and recent regional increases in anthropogenic emissions. PMID:21502496

The Role of Grain Size on Neutron Irradiation Response of Nanocrystalline Copper

PubMed Central

Mohamed, Walid; Miller, Brandon; Porter, Douglas; Murty, Korukonda

2016-01-01

The role of grain size on the developed microstructure and mechanical properties of neutron irradiated nanocrystalline copper was investigated by comparing the radiation response of material to the conventional micrograined counterpart. Nanocrystalline (nc) and micrograined (MG) copper samples were subjected to a range of neutron exposure levels from 0.0034 to 2 dpa. At all damage levels, the response of MG-copper was governed by radiation hardening manifested by an increase in strength with accompanying ductility loss. Conversely, the response of nc-copper to neutron irradiation exhibited a dependence on the damage level. At low damage levels, grain growth was the primary response, with radiation hardening and embrittlement becoming the dominant responses with increasing damage levels. Annealing experiments revealed that grain growth in nc-copper is composed of both thermally-activated and irradiation-induced components. Tensile tests revealed minimal change in the source hardening component of the yield stress in MG-copper, while the source hardening component was found to decrease with increasing radiation exposure in nc-copper. PMID:28773270

Biomimetic fabrication of a three-level hierarchical calcium phosphate/collagen/hydroxyapatite scaffold for bone tissue engineering.

PubMed

Zhou, Changchun; Ye, Xingjiang; Fan, Yujiang; Ma, Liang; Tan, Yanfei; Qing, Fangzu; Zhang, Xingdong

2014-09-01

A three-level hierarchical calcium phosphate/collagen/hydroxyapatite (CaP/Col/HAp) scaffold for bone tissue engineering was developed using biomimetic synthesis. Porous CaP ceramics were first prepared as substrate materials to mimic the porous bone structure. A second-level Col network was then composited into porous CaP ceramics by vacuum infusion. Finally, a third-level HAp layer was achieved by biomimetic mineralization. The three-level hierarchical biomimetic scaffold was characterized using scanning electron microscopy, energy-dispersive x-ray spectra, x-ray diffraction and Fourier transform infrared spectroscopy, and the mechanical properties of the scaffold were evaluated using dynamic mechanical analysis. The results show that this scaffold exhibits a similar structure and composition to natural bone tissues. Furthermore, this three-level hierarchical biomimetic scaffold showed enhanced mechanical strength compared with pure porous CaP scaffolds. The biocompatibility and osteoinductivity of the biomimetic scaffolds were evaluated using in vitro and in vivo tests. Cell culture results indicated the good biocompatibility of this biomimetic scaffold. Faster and increased bone formation was observed in these scaffolds following a six-month implantation in the dorsal muscles of rabbits, indicating that this biomimetic scaffold exhibits better osteoinductivity than common CaP scaffolds.

Intermittent fasting attenuates increases in neurogenesis after ischemia and reperfusion and improves recovery.

PubMed

Manzanero, Silvia; Erion, Joanna R; Santro, Tomislav; Steyn, Frederik J; Chen, Chen; Arumugam, Thiruma V; Stranahan, Alexis M

2014-05-01

Intermittent fasting (IF) is neuroprotective across a range of insults, but the question of whether extending the interval between meals alters neurogenesis after ischemia remains unexplored. We therefore measured cell proliferation, cell death, and neurogenesis after transient middle cerebral artery occlusion (MCAO) or sham surgery (SHAM) in mice fed ad libitum (AL) or maintained on IF for 3 months. IF was associated with twofold reductions in circulating levels of the adipocyte cytokine leptin in intact mice, but also prevented further reductions in leptin after MCAO. IF/MCAO mice also exhibit infarct volumes that were less than half those of AL/MCAO mice. We observed a 30% increase in basal cell proliferation in the hippocampus and subventricular zone (SVZ) in IF/SHAM, relative to AL/SHAM mice. However, cell proliferation after MCAO was limited in IF mice, which showed twofold increases in cell proliferation relative to IF/SHAM, whereas AL/MCAO mice exhibit fivefold increases relative to AL/SHAM. Attenuation of stroke-induced neurogenesis was correlated with reductions in cell death, with AL/MCAO mice exhibiting twice the number of dying cells relative to IF/MCAO mice. These observations indicate that IF protects against neurological damage in ischemic stroke, with circulating leptin as one possible mediator.

Intermittent fasting attenuates increases in neurogenesis after ischemia and reperfusion and improves recovery

PubMed Central

Manzanero, Silvia; Erion, Joanna R; Santro, Tomislav; Steyn, Frederik J; Chen, Chen; Arumugam, Thiruma V; Stranahan, Alexis M

2014-01-01

Intermittent fasting (IF) is neuroprotective across a range of insults, but the question of whether extending the interval between meals alters neurogenesis after ischemia remains unexplored. We therefore measured cell proliferation, cell death, and neurogenesis after transient middle cerebral artery occlusion (MCAO) or sham surgery (SHAM) in mice fed ad libitum (AL) or maintained on IF for 3 months. IF was associated with twofold reductions in circulating levels of the adipocyte cytokine leptin in intact mice, but also prevented further reductions in leptin after MCAO. IF/MCAO mice also exhibit infarct volumes that were less than half those of AL/MCAO mice. We observed a 30% increase in basal cell proliferation in the hippocampus and subventricular zone (SVZ) in IF/SHAM, relative to AL/SHAM mice. However, cell proliferation after MCAO was limited in IF mice, which showed twofold increases in cell proliferation relative to IF/SHAM, whereas AL/MCAO mice exhibit fivefold increases relative to AL/SHAM. Attenuation of stroke-induced neurogenesis was correlated with reductions in cell death, with AL/MCAO mice exhibiting twice the number of dying cells relative to IF/MCAO mice. These observations indicate that IF protects against neurological damage in ischemic stroke, with circulating leptin as one possible mediator. PMID:24549184

The MADS-box gene SlMBP11 regulates plant architecture and affects reproductive development in tomato plants.

PubMed

Guo, Xuhu; Chen, Guoping; Naeem, Muhammad; Yu, Xiaohu; Tang, Boyan; Li, Anzhou; Hu, Zongli

2017-05-01

MADS-domain proteins are important transcription factors that are involved in many biological processes of plants. In the present study, SlMBP11, a member of the AGL15 subfamily, was cloned in tomato plants (Solanum lycopersicon M.). SlMBP11 is ubiquitously expressed in all of the tissues we examined, whereas the SlMBP11 transcription levels were significantly higher in reproductive tissues than in vegetative tissues. Plants exhibiting increased SlMBP11 levels displayed reduced plant height, leaf size, and internode length as well as a loss of dominance in young seedlings, highly branched growth from each leaf axil, and increased number of nodes and leaves. Moreover, overexpression lines also exhibited reproductive phenotypes, such as those having a shorter style and split ovary, leading to polycarpous fruits, while the wild type showed normal floral organization. In addition, delayed perianth senescence was observed in transgenic tomatoes. These phenotypes were further confirmed by analyzing the morphological, anatomical and molecular features of lines exhibiting overexpression. These results suggest that SlMBP11 plays an important role in regulating plant architecture and reproductive development in tomato plants. These findings add a new class of transcription factors to the group of genes controlling axillary bud growth and illuminate a previously uncharacterized function of MADS-box genes in tomato plants. Copyright © 2017 Elsevier B.V. All rights reserved.

Tachycardia, reduced vagal capacity, and age-dependent ventricular dysfunction arising from diminished expression of the presynaptic choline transporter

PubMed Central

English, Brett A.; Appalsamy, Martin; Diedrich, Andre; Ruggiero, Alicia M.; Lund, David; Wright, Jane; Keller, Nancy R.; Louderback, Katherine M.; Robertson, David

2010-01-01

Healthy cardiovascular function relies on a balanced and responsive integration of noradrenergic and cholinergic innervation of the heart. High-affinity choline uptake by cholinergic terminals is pivotal for efficient ACh production and release. To date, the cardiovascular impact of diminished choline transporter (CHT) expression has not been directly examined, largely due to the transporter's inaccessibility in vivo. Here, we describe findings from cardiovascular experiments using transgenic mice that bear a CHT genetic deficiency. Whereas CHT knockout (CHT−/−) mice exhibit early postnatal lethality, CHT heterozygous (CHT+/−) mice survive, grow, and reproduce normally and exhibit normal spontaneous behaviors. However, the CHT+/− mouse heart displays significantly reduced levels of high-affinity choline uptake accompanied by significantly reduced levels of ACh. Telemeterized recordings of cardiovascular function in these mice revealed tachycardia and hypertension at rest. After treadmill exercise, CHT+/− mice exhibited slower heart rate recovery, consistent with a diminished cholinergic reserve, a contention validated through direct vagal nerve stimulation. Echocardiographic and histological experiments revealed an age-dependent decrease in fractional shortening, increased left ventricular dimensions, and increased ventricular fibrosis, consistent with ventricular dysfunction. These cardiovascular phenotypes of CHT+/− mice encourage an evaluation of humans bearing reduced CHT expression for their resiliency in maintaining proper heart function as well as risk for cardiovascular disease. PMID:20601463

Preliminary Study of Neurodevelopmental Outcomes and Parenting Stress in Pediatric Mitochondrial Disease.

PubMed

Eom, Soyong; Lee, Young-Mock

2017-06-01

Little is known regarding the neuropsychological profiles of pediatric patients with mitochondrial diseases or their parents, information that is crucial for improving the quality of life (QOL) for both patients and parents. We aimed to delineate neurodevelopment and psychological comorbidity in children with mitochondrial diseases in the preliminary investigation of adequate intervention methods, better prognoses, and improved QOL for both patients and parents. Seventy children diagnosed with mitochondrial diseases were neuropsychologically evaluated. Neurocognitive (development, intelligence) and psychological (behavior, daily living function, maternal depression, parenting stress) functions were analyzed. Clinical variables, including the first symptom, epileptic classification, organ involvement, lactic acidosis, brain magnetic resonance imaging findings, muscle pathology, biochemical enzyme assay results, and syndromic diagnosis of mitochondrial diseases, were also reviewed. Prediagnostic assessments indicated that cognitive and psychomotor developments were significantly delayed. Group mean full scale intelligence quotient (IQ) scores indicated mild levels of intellectual disability, borderline levels of verbal IQ impairment, and mild levels of intellectual disability on performance IQ. Many children exhibited clinically significant levels of behavioral problems, whereas mothers of children with mitochondrial diseases exhibited significant increases in parenting stress relative to mothers of healthy children. Furthermore, 65% of mothers exhibited significant levels of depression. Early onset of the first symptoms, diffuse brain atrophy, and drug-resistant epilepsy negatively influenced neurodevelopmental and adaptive functions. Better understanding of the functional levels and profiles of neurodevelopment and psychological comorbidity in children with mitochondrial diseases in the prediagnostic period is essential for adequate support and QOL of children with mitochondrial diseases and their parents. Copyright © 2017 Elsevier Inc. All rights reserved.

Biochemical and nutritional evaluation of patients with visceral leishmaniasis before and after treatment with leishmanicidal drugs.

PubMed

Gatto, Mariana; de Abreu, Mariana Miziara; Tasca, Karen Ingrid; Simão, José Cláudio; Fortaleza, Carlos Magno Castelo Branco; Pereira, Paulo Câmara Marques; Calvi, Sueli Aparecida

2013-01-01

Visceral leishmaniasis (VL) is caused by the intracellular protozoan Leishmania donovani complex. VL may be asymptomatic or progressive and is characterized by fever, anemia, weight loss and the enlargement of the spleen and liver. The nutritional status of the patients with VL is a major determinant of the progression, severity and mortality of the disease, as it affects the clinical progression of the disease. Changes in lipoproteins and plasma proteins may have major impacts in the host during infection. Thus, our goal was evaluate the serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, glucose, albumin, globulin and total protein levels, as well as the body composition, of VL patients before and after treatment. Nutritional evaluation was performed using the bioelectrical impedance analysis (BIA) to assess body composition. Biochemical data on the serum total cholesterol, HDL, LDL, triglycerides, glucose, albumin, globulin and total protein were collected from the medical charts of the patients. BIA indicated that both pre-treatment and post-treatment patients exhibited decreased phase angles compared to the controls, which is indicative of disease. Prior to treatment, the patients exhibited lower levels of total body water compared to the controls. Regarding the biochemical evaluation, patients with active VL exhibited lower levels of total cholesterol, HDL, LDL and albumin and higher triglyceride levels compared to patients after treatment and the controls. Treatment increased the levels of albumin and lipoproteins and decreased the triglyceride levels. Our results suggest that patients with active VL present biochemical and nutritional changes that are reversed by treatment.

Large-Strain Transparent Magnetoactive Polymer Nanocomposites

NASA Technical Reports Server (NTRS)

Meador, Michael A.

2012-01-01

A document discusses polymer nano - composite superparamagnetic actuators that were prepared by the addition of organically modified superparamagnetic nanoparticles to the polymer matrix. The nanocomposite films exhibited large deformations under a magnetostatic field with a low loading level of 0.1 wt% in a thermoplastic polyurethane elastomer (TPU) matrix. The maximum actuation deformation of the nanocomposite films increased exponentially with increasing nanoparticle concentration. The cyclic deformation actuation of a high-loading magnetic nanocomposite film was examined in a low magnetic field, and it exhibited excellent reproducibility and controllability. Low-loading TPU nanocomposite films (0.1-2 wt%) were transparent to semitransparent in the visible wavelength range, owing to good dispersion of the magnetic nanoparticles. Magnetoactuation phenomena were also demonstrated in a high-modulus, high-temperature polyimide resin with less mechanical deformation.

Thermodynamic Approach to Enhanced Dispersion and Physical Properties in a Carbon Nanotube/Polypeptide Nanocomposite

NASA Technical Reports Server (NTRS)

Lovell, Conrad S.; Wise, Kristopher E.; Kim, Jae-Woo; Lillehei, Peter T.; Harrison, Joycelyn S.; Park, Cheol

2009-01-01

A high molecular weight synthetic polypeptide has been designed which exhibits favorable interactions with single wall carbon nanotubes (SWCNTs). The enthalpic and entropic penalties of mixing between these two molecules are reduced due to the polypeptide's aromatic sidechains and helical secondary structure, respectively. These enhanced interactions result in a well dispersed SWCNT/Poly (L-Leucine-ran-L-Phenylalanine) nanocomposite with enhanced mechanical and electrical properties using only shear mixing and sonication. At 0.5 wt% loading of SWCNT filler, the nanocomposite exhibits simultaneous increases in the Young's modulus, failure strain, and toughness of 8%, 120%, and 144%, respectively. At one kHz, the same nanotube loading level also enhances the dielectric constant from 2.95 to 22.81, while increasing the conductivity by four orders of magnitude.

Peer review and competition in the Art Exhibition Game.

PubMed

Balietti, Stefano; Goldstone, Robert L; Helbing, Dirk

2016-07-26

To investigate the effect of competitive incentives under peer review, we designed a novel experimental setup called the Art Exhibition Game. We present experimental evidence of how competition introduces both positive and negative effects when creative artifacts are evaluated and selected by peer review. Competition proved to be a double-edged sword: on the one hand, it fosters innovation and product diversity, but on the other hand, it also leads to more unfair reviews and to a lower level of agreement between reviewers. Moreover, an external validation of the quality of peer reviews during the laboratory experiment, based on 23,627 online evaluations on Amazon Mechanical Turk, shows that competition does not significantly increase the level of creativity. Furthermore, the higher rejection rate under competitive conditions does not improve the average quality of published contributions, because more high-quality work is also rejected. Overall, our results could explain why many ground-breaking studies in science end up in lower-tier journals. Differences and similarities between the Art Exhibition Game and scholarly peer review are discussed and the implications for the design of new incentive systems for scientists are explained.

Choline kinase β mutant mice exhibit reduced phosphocholine, elevated osteoclast activity, and low bone mass.

PubMed

Kular, Jasreen; Tickner, Jennifer C; Pavlos, Nathan J; Viola, Helena M; Abel, Tamara; Lim, Bay Sie; Yang, Xiaohong; Chen, Honghui; Cook, Robert; Hool, Livia C; Zheng, Ming Hao; Xu, Jiake

2015-01-16

The maintenance of bone homeostasis requires tight coupling between bone-forming osteoblasts and bone-resorbing osteoclasts. However, the precise molecular mechanism(s) underlying the differentiation and activities of these specialized cells are still largely unknown. Here, we identify choline kinase β (CHKB), a kinase involved in the biosynthesis of phosphatidylcholine, as a novel regulator of bone homeostasis. Choline kinase β mutant mice (flp/flp) exhibit a systemic low bone mass phenotype. Consistently, osteoclast numbers and activity are elevated in flp/flp mice. Interestingly, osteoclasts derived from flp/flp mice exhibit reduced sensitivity to excessive levels of extracellular calcium, which could account for the increased bone resorption. Conversely, supplementation of cytidine 5'-diphosphocholine in vivo and in vitro, a regimen that bypasses CHKB deficiency, restores osteoclast numbers to physiological levels. Finally, we demonstrate that, in addition to modulating osteoclast formation and function, loss of CHKB corresponds with a reduction in bone formation by osteoblasts. Taken together, these data posit CHKB as a new modulator of bone homeostasis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Fragile X mental retardation protein levels increase following complex environment exposure in rat brain regions undergoing active synaptogenesis.

PubMed

Irwin, Scott A; Christmon, Chariya A; Grossman, Aaron W; Galvez, Roberto; Kim, Soong Ho; DeGrush, Brian J; Weiler, Ivan Jeanne; Greenough, William T

2005-05-01

Fragile X mental retardation protein (FMRP), which is absent in fragile X syndrome, is synthesized in vitro in response to neurotransmitter activation. Humans and mice lacking FMRP exhibit abnormal dendritic spine development, suggesting that this protein plays an important role in synaptic plasticity. Previously, our laboratory demonstrated increased FMRP immunoreactivity in visual cortex of rats exposed to complex environments (EC) and in motor cortex of rats trained on motor-skill tasks compared with animals reared individually in standard laboratory housing (IC). Here, we use immunohistochemistry to extend those findings by investigating FMRP levels in visual cortex and hippocampal dentate gyrus of animals exposed to EC or IC. Rats exposed to EC for 20 days exhibited increased FMRP immunoreactivity in visual cortex compared with animals housed in standard laboratory caging. In the dentate gyrus, animals exposed to EC for 20 days had higher FMRP levels than animals exposed to EC for 5 or 10 days. In light of possible antibody crossreactivity with closely related proteins FXR1P and FXR2P, FMRP immunoreactivity in the posterior-dorsal one-third of cerebral cortex was also examined by Western blotting following 20 days of EC exposure. FMRP levels were greater in EC animals, whereas levels of FXR1P and FXR2P were unaffected by experience. These results provide further evidence for behaviorally induced alteration of FMRP expression in contrast to its homologues, extend previous findings suggesting regulation of its expression by synaptic activity, and support the theories associating FMRP expression with alteration of synaptic structure both in development and later in the life-cycle.

HLA-G is expressed in intestinal samples of ulcerative colitis and Crohn's disease patients and HLA-G5 expression is differentially correlated with TNF and IL-10 cytokine expression.

PubMed

Gomes, Renan Garcia; Brito, Carlos Alexandre Antunes de; Martinelli, Valéria Ferreira; Santos, Rossana Nascimento Dos; Gomes, Fabiana Oliveira Dos Santos; Peixoto, Christina Alves; Crispim, Janaína Oliveira; Diniz, George Tadeu Nunes; Donadi, Eduardo Antônio; Lucena-Silva, Norma

2018-06-01

HLA-G is an immunomodulatory molecule that can be produced by epithelial cells. Considering that TNF and IL-10 participate in bowel inflammatory disorders and that both cytokines modulate HLA-G, we evaluated HLA-G, TNF and IL-10 mRNA expression by qPCR and HLA-G protein levels by immunohistochemistry in two intestinal samples exhibiting different degree of inflammation within a patient suffering from Crohn's disease (CD) or ulcerative colitis (UC). Tissue HLA-G5 (P < 0.0001), TNF (P = 0.0004) and IL-10 (P = 0.0169) mRNA expression levels were higher in intestinal areas exhibiting intense inflammation compared to areas of low inflammation, and HLA-G protein levels were not associated with degree of mucosal inflammation. In CD, the expression of TNF was correlated with IL-10 in low inflamed areas, exhibiting a TNF:IL-10 ratio = 3, but in inflamed areas the ratio increased to 9-folds. In UC, the expression of TNF was correlated to IL-10, irrespective of the inflammation grade, with little variation of the TNF:IL-10 ratio in the various inflamed areas. TNF and IL-10 expression was correlated with HLA-G5 expression in mild inflamed areas. Both CD and UC samples exhibited gene and protein expression of HLA-G; and the HLA-G5 expression is differentially correlated with TNF and IL-10 levels depending on the type of the underlying inflammatory bowel disorder. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Cooperative Adaptive Responses in Gene Regulatory Networks with Many Degrees of Freedom

PubMed Central

Inoue, Masayo; Kaneko, Kunihiko

2013-01-01

Cells generally adapt to environmental changes by first exhibiting an immediate response and then gradually returning to their original state to achieve homeostasis. Although simple network motifs consisting of a few genes have been shown to exhibit such adaptive dynamics, they do not reflect the complexity of real cells, where the expression of a large number of genes activates or represses other genes, permitting adaptive behaviors. Here, we investigated the responses of gene regulatory networks containing many genes that have undergone numerical evolution to achieve high fitness due to the adaptive response of only a single target gene; this single target gene responds to changes in external inputs and later returns to basal levels. Despite setting a single target, most genes showed adaptive responses after evolution. Such adaptive dynamics were not due to common motifs within a few genes; even without such motifs, almost all genes showed adaptation, albeit sometimes partial adaptation, in the sense that expression levels did not always return to original levels. The genes split into two groups: genes in the first group exhibited an initial increase in expression and then returned to basal levels, while genes in the second group exhibited the opposite changes in expression. From this model, genes in the first group received positive input from other genes within the first group, but negative input from genes in the second group, and vice versa. Thus, the adaptation dynamics of genes from both groups were consolidated. This cooperative adaptive behavior was commonly observed if the number of genes involved was larger than the order of ten. These results have implications in the collective responses of gene expression networks in microarray measurements of yeast Saccharomyces cerevisiae and the significance to the biological homeostasis of systems with many components. PMID:23592959

Poverty, inequality, and increased consumption of high calorie food: Experimental evidence for a causal link.

PubMed

Bratanova, Boyka; Loughnan, Steve; Klein, Olivier; Claassen, Almudena; Wood, Robert

2016-05-01

Rising obesity represents a serious, global problem. It is now well established that obesity is associated with poverty and wealth inequality, suggesting that these factors may promote caloric intake. Whereas previous work has examined these links from an epidemiological perspective, the current paper examined them experimentally. In Study 1 we found that people experimentally induced to view themselves as poor (v. wealthy) exhibited increased calorie intake. In Study 2, participants who believed that they were poorer or wealthier than their interaction partners exhibited higher levels of anxiety compared to those in an equal partners condition; this anxiety in turn led to increased calorie consumption for people who had a strong need to belong. The findings provide causal evidence for the poverty-intake and inequality-intake links. Further, we identify social anxiety and a strong need to belong as important social psychological factors linking inequality to increased calorie intake. Copyright © 2016. Published by Elsevier Ltd.

The effects of automated scatter feeders on captive grizzly bear activity budgets.

PubMed

Andrews, Nathan L P; Ha, James C

2014-01-01

Although captive bears are popular zoo attractions, they are known to exhibit high levels of repetitive behaviors (RBs). These behaviors have also made them particularly popular subjects for welfare research. To date, most research on ursid welfare has focused on various feeding methods that seek to increase time spent searching for, extracting, or consuming food. Prior research indicates an average of a 50% reduction in RBs when attempts are successful and, roughly, a 50% success rate across studies. This research focused on decreasing time spent in an RB while increasing the time spent active by increasing time spent searching for, extracting, and consuming food. The utility of timed, automated scatter feeders was examined for use with captive grizzly bears (Ursis arctos horribilis). Findings include a significant decrease in time spent in RB and a significant increase in time spent active while the feeders were in use. Further, the bears exhibited a wider range of behaviors and a greater use of their enclosure.

Short Communication: Lack of Immune Response in Rapid Progressor Morphine-Dependent and SIV/SHIV-Infected Rhesus Macaques Is Correlated with Downregulation of TH1 Cytokines

PubMed Central

Kumar, Rakesh; Noel, Richard J.; Garcia, Yashira; Rodriguez, Idia V.; Martinez, Melween; Sariol, Carlos A.; Kraiselburd, Edmundo; Iszard, Marcus; Mukherji, Mridul; Kumar, Santosh; Giavedoni, Luis D.; Kumar, Anil

2010-01-01

Abstract Our previous studies have shown two distinct disease patterns (rapid and normal onset of clinical symptoms) in morphine-dependent SHIV/SIV-inoculated rhesus macaques. We have also shown that control as well as 50% of morphine-dependent macaques (normal progressor) developed humoral and cellular immune responses whereas the other half of the morphine-dependent macaques (rapid progressor) did not develop antiviral immune responses after infection with SIV/SHIV. In the present study, we analyzed the association between cytokine production, immune response, and disease progression. To study the immunological effects of morphine at cytokine levels in the context of a lentiviral infection, we inoculated rhesus macaques with a mixture of SHIVKU−18, SHIV89.6P, and SIV/17E-Fr. These animals were followed for a period of 56 weeks for cytokine level production in plasma. Drug-dependent rapid disease progressors exhibited an increase in IL-18 and IL-1Ra and a decrease in IL-12 levels in the plasma. Morphine-dependent normal progressors and control macaques exhibited an increase in both IL-18 and IL-12, whereas IL-Ra levels remained constant throughout the observation period. These results suggest that rapid disease progression in relation to morphine dependency may be the result of an altered cytokine profile. PMID:20672973

The microgeographical patterns of morphological and molecular variation of a mixed ploidy population in the species complex Actinidia chinensis.

PubMed

Liu, Yifei; Li, Dawei; Yan, Ling; Huang, Hongwen

2015-01-01

Polyploidy and hybridization are thought to have significant impacts on both the evolution and diversification of the genus Actinidia, but the structure and patterns of morphology and molecular diversity relating to ploidy variation of wild Actinidia plants remain much less understood. Here, we examine the distribution of morphological variation and ploidy levels along geographic and environmental variables of a large mixed-ploidy population of the A. chinensis species complex. We then characterize the extent of both genetic and epigenetic diversity and differentiation exhibited between individuals of different ploidy levels. Our results showed that while there are three ploidy levels in this population, hexaploids were constituted the majority (70.3%). Individuals with different ploidy levels were microgeographically structured in relation to elevation and extent of niche disturbance. The morphological characters examined revealed clear difference between diploids and hexaploids, however tetraploids exhibited intermediate forms. Both genetic and epigenetic diversity were high but the differentiation among cytotypes was weak, suggesting extensive gene flow and/or shared ancestral variation occurred in this population even across ploidy levels. Epigenetic variation was clearly correlated with changes in altitudes, a trend of continuous genetic variation and gradual increase of epigenomic heterogeneities of individuals was also observed. Our results show that complex interactions between the locally microgeographical environment, ploidy and gene flow impact A. chinensis genetic and epigenetic variation. We posit that an increase in ploidy does not broaden the species habitat range, but rather permits A. chinensis adaptation to specific niches.

Peripubertal exposure to low doses of tributyltin chloride affects the homeostasis of serum T, E2, LH, and body weight of male mice.

PubMed

Si, Jiliang; Wu, Xuesen; Wan, Chengen; Zeng, Tao; Zhang, Miao; Xie, Keqin; Li, Jie

2011-06-01

Previous studies have shown that tributyltin could act as an endocrine disruptor in mammals. However, the data on the low-dose effect of tributyltin in animals are still lacking. The objective of this study was to demonstrate the endocrine disruption induced by low levels of tributyltin chloride (TBTCl) in male KM mice. The animals were treated with 0.05 or 0.5 mg TBTCl/kg body weight/3 days from postnatal days (PNDs) 24 to 45, and killed on PNDs 49 and 84, respectively. Mice treated with 0.5 mg TBTCl/kg exhibited decreased serum and intratesticular testosterone (T) levels on PND 49 and then followed by an obvious recovery on PND 84. Furthermore, mice treated with 0.05 mg TBTCl/kg showed reduced serum 17β-estradiol (E2) levels on PND 49. However, treatments with TBTCl resulted in a dose-dependent increase in serum E2 concentration of the mice on PND 84. Administration of TBTCl also decreased levels of serum luteinizing hormone and intratesticular E2 on PND 84. In addition, mice exposed to 0.05 mg/kg TBTCl exhibited an increase in body weight in the late stage of the experiment. These results indicate that treatment with low doses of TBTCl could disturb hormone homeostasis and body weight gain in rodents, and exposure to different levels of TBTCl might have different effects on changing some physiologic parameters. Copyright © 2010 Wiley Periodicals, Inc.

Linear response of field-aligned currents to the interplanetary electric field

NASA Astrophysics Data System (ADS)

Weimer, D. R.; Edwards, T. R.; Olsen, Nils

2017-08-01

Many studies that have shown that the ionospheric, polar cap electric potentials (PCEPs) exhibit a "saturation" behavior in response to the level of the driving by the solar wind. As the magnitudes of the interplanetary magnetic field (IMF) and electric field (IEF) increase, the PCEP response is linear at low driving levels, followed with a rollover to a more constant level. While there are several different theoretical explanations for this behavior, so far, no direct observational evidence has existed to confirm any particular model. In most models of this saturation, the interaction of the field-aligned currents (FACs) with the solar wind/magnetosphere/ionosphere system has a role. As the FACs are more difficult to measure, their behavior in response to the level of the IEF has not been investigated as thoroughly. In order to resolve the question of whether or not the FAC also exhibit saturation, we have processed the magnetic field measurements from the Ørsted, CHAMP, and Swarm missions, spanning more than a decade. As the amount of current in each region needs to be known, a new technique is used to separate and sum the current by region, widely known as R0, R1, and R2. These totals are found separately for the dawnside and duskside. Results indicate that the total FAC has a response to the IEF that is highly linear, continuing to increase well beyond the level at which the electric potentials saturate. The currents within each region have similar behavior.

The growth of small corrosion fatigue cracks in alloy 2024

NASA Technical Reports Server (NTRS)

Piascik, Robert S.; Willard, Scott A.

1993-01-01

The corrosion fatigue crack growth characteristics of small surface and corner cracks in aluminum alloy 2024 is established. The damaging effect of salt water on the early stages of small crack growth is characterized by crack initiation at constituent particle pits, intergranular microcracking for a less than 100 micrometers, and transgranular small crack growth for a micrometer. In aqueous 1 percent NaCl and at a constant anodic potential of -700 mV(sub SCE), small cracks exhibit a factor of three increase in fatigue crack growth rates compared to laboratory air. Small cracks exhibit accelerated corrosion fatigue crack growth rates at low levels of delta-K (less than 1 MPa square root of m) below long crack delta-K (sub th). When exposed to Paris regime levels of crack tip stress intensity, small corrosion fatigue cracks exhibit growth rates similar to that observed for long cracks. Results suggest that crack closure effects influence the corrosion fatigue crack growth rates of small cracks (a less than or equal to 100 micrometers). This is evidenced by similar small and long crack growth behavior at various levels of R. Contrary to the corrosion fatigue characteristics of small cracks in high strength steels, no pronounced chemical crack length effect is observed for Al by 2024 exposed to salt water.

Salmonella DNA Adenine Methylase Mutants Confer Cross-Protective Immunity

PubMed Central

Heithoff, Douglas M.; Enioutina, Elena Y.; Daynes, Raymond A.; Sinsheimer, Robert L.; Low, David A.; Mahan, Michael J.

2001-01-01

Salmonella isolates that lack or overproduce DNA adenine methylase (Dam) elicited a cross-protective immune response to different Salmonella serovars. The protection afforded by the Salmonella enterica serovar Typhimurium Dam vaccine was greater than that elicited in mice that survived a virulent infection. S. enterica serovar Typhimurium Dam mutant strains exhibited enhanced sensitivity to mediators of innate immunity such as antimicrobial peptides, bile salts, and hydrogen peroxide. Also, S. enterica serovar Typhimurium Dam− vaccines were not immunosuppressive; unlike wild-type vaccines, they failed to induce increased nitric oxide levels and permitted a subsequent robust humoral response to diptheria toxoid antigen in infected mice. Dam mutant strains exhibited a low-grade persistence which, coupled with the nonimmunosuppression and the ectopic protein expression caused by altered levels of Dam, may provide an expanded source of potential antigens in vaccinated hosts. PMID:11598044

Acculturation and plasma fatty acid concentrations in Hispanic and Chinese-American adults: The Multi-Ethnic Study of Atherosclerosis

USDA-ARS?s Scientific Manuscript database

Acculturation to the U.S. is associated with increased risk of cardiovascular disease, but the etiologic pathways are not fully understood. Plasma fatty acid levels exhibit ethnic differences and are emerging as biomarkers and predictors of cardiovascular disease risk. Thus, plasma fatty acids may...

Low, medium and high heat tolerant strains of Listeria monocytogenes and increased heat stress resistance after exposure to sublethal heat

USDA-ARS?s Scientific Manuscript database

Listeria monocytogenes exhibits sophisticated adaptive mechanisms to counteract higher levels of lethal acid, heat, salt or oxidative stresses after pre-exposure to sublethal concentrations of homogenous stress. A group of 37 strains representing all 13 serotypes of Listeria monocytogenes with initi...

Regulatory Fit and Systematic Exploration in a Dynamic Decision-Making Environment

ERIC Educational Resources Information Center

Otto, A. Ross; Markman, Arthur B.; Gureckis, Todd M.; Love, Bradley C.

2010-01-01

This work explores the influence of motivation on choice behavior in a dynamic decision-making environment, where the payoffs from each choice depend on one's recent choice history. Previous research reveals that participants in a regulatory fit exhibit increased levels of exploratory choice and flexible use of multiple strategies over the course…

A study of the influence of Hg(6(3)P2) population in a low-pressure discharge on mercury ion emission at 194.2 nm

NASA Technical Reports Server (NTRS)

Maleki, L.; Blasenheim, B. J.; Janik, G. R.

1990-01-01

A low-pressure mercury-argon discharge, similar to the type existing in the mercury lamp for the trapped-ion standard, is probed with a new technique of laser spectroscopy to determine the influence of the Hg(6 3P(sub 2)) population on discharge emission. The discharge is excited with inductively coupled rf power. Variations in the intensity of emission lines in the discharge were examined as lambda = 546.1 nm light from a continuous wave (CW) laser excited the Hg(6 3P(sub 2)) to (7 3S (sub 1)) transition. The spectrum of the discharge viewed in the region of laser irradiation showed increased emission in lambda = 546.1, 435.8, 404.7, 253.7, and 194.2 nm lines. Other lines in Hg I exhibited a decrease in emission. When the discharge was viewed outside the region of laser irradiation, all lines exhibited an increased emission. Based on these results, it is concluded that the dominant mechanism for the excitation of higher lying levels of mercury is the the electron-impact excitation via the 3P(sub 2) level. The depopulation of this metastable is also responsible for the observed increase in the electron temperature when the laser irradiates the discharge. It is also concluded that the 3P(sub 2) metastable level of mercury does not play a significant role in the excitation of the 3P(sub 1/2) level of mercury ion.

Effects of cigarette smoking and nicotine metabolite ratio on leukocyte telomere length.

PubMed

Verde, Zoraida; Reinoso-Barbero, Luis; Chicharro, Luis; Garatachea, Nuria; Resano, Pilar; Sánchez-Hernández, Ignacio; Rodríguez González-Moro, Jose Miguel; Bandrés, Fernando; Santiago, Catalina; Gómez-Gallego, Félix

2015-07-01

Studies of the effects of smoking on leukocyte telomere length (LTL) using cigarettes smoked per day or pack years smoked (PYS) present limitations. Reported high levels of smoking may not increase toxin exposure levels proportionally. Nicotine metabolism ratio (NMR) predicts total cigarette puff volume and overall exposure based on total N-nitrosamines, is highly reproducible and independent of time since the last cigarette. We hypothesized that smokers with higher NMRs will exhibit increased total puff volume, reflecting efforts to extract more nicotine from their cigarettes and increasing toxin exposure. In addition, higher levels of smoking could cause a gross damage in LTL. The urinary cotinine, 3-OH cotinine and nicotine levels of 147 smokers were analyzed using a LC/MS system Triple-Q6410. LTL and CYP2A6 genotype was determined by PCR in blood samples. We found a significant association between NMR and CYP2A6 genotype. Reduction in LTL was seen in relation to accumulated tobacco consumption and years smoking when we adjusted for age and gender. However, there were no significant differences between NMR values and LTL. In our study the higher exposure was associated with lower number of PYS. Smokers with reduced cigarette consumption may exhibit compensatory smoking behavior that results in no reduced tobacco toxin exposure. Our results suggest that lifetime accumulated smoking exposure could cause a gross damage in LTL rather than NMR or PYS. Nevertheless, a combination of smoking topography (NMR) and consumption (PYS) measures may provide useful information about smoking effects on health outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

Heat shock protein defenses in the neo- and allocortex of the telencephalon

PubMed Central

Posimo, Jessica M.; Weilnau, Justin N.; Gleixner, Amanda M.; Broeren, Matthew T.; Weiland, Nicole L.; Brodsky, Jeffrey L.; Wipf, Peter; Leak, Rehana K.

2015-01-01

The telencephalic allocortex develops protein inclusions before the neocortex in many age-related proteinopathies. One major defense mechanism against proteinopathic stress is the heat shock protein (Hsp) network. We therefore contrasted Hsp defenses in stressed primary neo- and allocortical cells. Neocortical neurons were more resistant to the proteasome inhibitor MG132 than neurons from three allocortical subregions: entorhinal cortex, piriform cortex, and hippocampus. However, allocortical neurons exhibited higher MG132-induced increases in Hsp70 and Hsc70. MG132-treated allocortical neurons also exhibited greater levels of protein ubiquitination. Inhibition of Hsp70/Hsc70 activity synergistically exacerbated MG132 toxicity in allocortical neurons more than neocortical neurons, suggesting that the allocortex is more reliant on these Hsp defenses. In contrast, astrocytes harvested from neo- or allocortex did not differ in their response to Hsp70/Hsc70 inhibition. Consistent with the idea that chaperones are maximally engaged in allocortical neurons, an increase in Hsp70/Hsc70 activity was protective only in neocortical neurons. Finally, the levels of select Hsps were altered in neocortex and allocortex in vivo with aging. PMID:25771395

MONOAMINE OXIDASE: From Genes to Behavior

PubMed Central

Shih, J. C.; Chen, K.; Ridd, M. J.

2010-01-01

Cloning of MAO (monoamine oxidase) A and B has demonstrated unequivocally that these enzymes are made up of different polypeptides, and our understanding of MAO structure, regulation, and function has been significantly advanced by studies using their cDNA. MAO A and B genes are located on the X-chromosome (Xp11.23) and comprise 15 exons with identical intron-exon organization, which suggests that they are derived from the same ancestral gene. MAO A and B knockout mice exhibit distinct differences in neurotransmitter metabolism and behavior. MAO A knock-out mice have elevated brain levels of serotonin, norephinephrine, and dopamine and manifest aggressive behavior similar to human males with a deletion of MAO A. In contrast, MAO B knock-out mice do not exhibit aggression and only levels of phenylethylamine are increased. Mice lacking MAO B are resistant to the Parkinsongenic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine. Both MAO A and B knock-out mice show increased reactivity to stress. These knock-out mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders. PMID:10202537

Analysis of high-frequency energy in long-term average spectra of singing, speech, and voiceless fricatives.

PubMed

Monson, Brian B; Lotto, Andrew J; Story, Brad H

2012-09-01

The human singing and speech spectrum includes energy above 5 kHz. To begin an in-depth exploration of this high-frequency energy (HFE), a database of anechoic high-fidelity recordings of singers and talkers was created and analyzed. Third-octave band analysis from the long-term average spectra showed that production level (soft vs normal vs loud), production mode (singing vs speech), and phoneme (for voiceless fricatives) all significantly affected HFE characteristics. Specifically, increased production level caused an increase in absolute HFE level, but a decrease in relative HFE level. Singing exhibited higher levels of HFE than speech in the soft and normal conditions, but not in the loud condition. Third-octave band levels distinguished phoneme class of voiceless fricatives. Female HFE levels were significantly greater than male levels only above 11 kHz. This information is pertinent to various areas of acoustics, including vocal tract modeling, voice synthesis, augmentative hearing technology (hearing aids and cochlear implants), and training/therapy for singing and speech.

Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats.

PubMed

Cheng, Chen; Lin, Jia-zhen; Li, Li; Yang, Jun-ling; Jia, Wei-wei; Huang, Yu-hong; Du, Fei-fei; Wang, Feng-qing; Li, Mei-juan; Li, Yan-fen; Xu, Fang; Zhang, Na-ting; Olaleye, Olajide E; Sun, Yan; Li, Jian; Sun, Chang-hai; Zhang, Gui-ping; Li, Chuan

2016-04-01

Monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. This study was designed to characterize the pharmacokinetics and disposition of monoterpene glycosides. Systemic exposure to Chishao monoterpene glycosides was assessed in human subjects receiving an intravenous infusion and multiple infusions of XueBiJing injection, followed by assessment of the pharmacokinetics of the major circulating compounds. Supportive rat studies were also performed. Membrane permeability and plasma-protein binding were assessed in vitro. A total of 18 monoterpene glycosides were detected in XueBiJing injection (content levels, 0.001-2.47 mmol/L), and paeoniflorin accounted for 85.5% of the total dose of monoterpene glycosides detected. In human subjects, unchanged paeoniflorin exhibited considerable levels of systemic exposure with elimination half-lives of 1.2-1.3 h; no significant metabolite was detected. Oxypaeoniflorin and albiflorin exhibited low exposure levels, and the remaining minor monoterpene glycosides were negligible or undetected. Glomerular-filtration-based renal excretion was the major elimination pathway of paeoniflorin, which was poorly bound to plasma protein. In rats, the systemic exposure level of paeoniflorin increased proportionally as the dose was increased. Rat lung, heart, and liver exposure levels of paeoniflorin were lower than the plasma level, with the exception of the kidney level, which was 4.3-fold greater than the plasma level; brain penetration was limited by the poor membrane permeability. Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance.

Isolated effect of geometry on mitral valve function for in silico model development.

PubMed

Siefert, Andrew William; Rabbah, Jean-Pierre Michel; Saikrishnan, Neelakantan; Kunzelman, Karyn Susanne; Yoganathan, Ajit Prithivaraj

2015-01-01

Computational models for the heart's mitral valve (MV) exhibit several uncertainties that may be reduced by further developing these models using ground-truth data-sets. This study generated a ground-truth data-set by quantifying the effects of isolated mitral annular flattening, symmetric annular dilatation, symmetric papillary muscle (PM) displacement and asymmetric PM displacement on leaflet coaptation, mitral regurgitation (MR) and anterior leaflet strain. MVs were mounted in an in vitro left heart simulator and tested under pulsatile haemodynamics. Mitral leaflet coaptation length, coaptation depth, tenting area, MR volume, MR jet direction and anterior leaflet strain in the radial and circumferential directions were successfully quantified at increasing levels of geometric distortion. From these data, increase in the levels of isolated PM displacement resulted in the greatest mean change in coaptation depth (70% increase), tenting area (150% increase) and radial leaflet strain (37% increase) while annular dilatation resulted in the largest mean change in coaptation length (50% decrease) and regurgitation volume (134% increase). Regurgitant jets were centrally located for symmetric annular dilatation and symmetric PM displacement. Asymmetric PM displacement resulted in asymmetrically directed jets. Peak changes in anterior leaflet strain in the circumferential direction were smaller and exhibited non-significant differences across the tested conditions. When used together, this ground-truth data-set may be used to parametrically evaluate and develop modelling assumptions for both the MV leaflets and subvalvular apparatus. This novel data may improve MV computational models and provide a platform for the development of future surgical planning tools.

MK-801 increases locomotor activity in a context-dependent manner in zebrafish.

PubMed

Tran, Steven; Muraleetharan, Arrujyan; Fulcher, Niveen; Chatterjee, Diptendu; Gerlai, Robert

2016-01-01

Zebrafish have become a popular animal model for behavioral neuroscience with an increasing number of studies examining the effects of pharmacological compounds targeting the brain. Exposure to MK-801, a non-competitive N-methyl-d-aspartate receptor antagonist has been shown to increase locomotor activity in zebrafish. However, others have failed to replicate this finding as several contradicting studies report no changes in locomotor activity following exposure to similar doses. In the current study we reconcile these behavioral reports by demonstrating that zebrafish do not exhibit changes in locomotor activity during exposure to non-sedative doses of MK-801. Interestingly, zebrafish do exhibit significant increases in locomotion if pre-treated with MK-801 followed by subsequent testing in a novel environment, which suggests the effects of MK-801 are context-dependent. In addition, we examine the potential role of the dopaminergic system in mediating MK-801's locomotor stimulant effect by quantifying the levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the brains of zebrafish following a 30 min exposure to 10 μM of MK-801 (the dose found to induce the largest increase in locomotor activity). Our findings indicate that the MK-801-induced increase in locomotor activity is not accompanied by changes in whole-brain levels of dopamine or DOPAC. Overall, our results suggest that MK-801's context-dependent locomotor stimulant effect may be independent of whole-brain dopaminergic activation. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Insight into litter decomposition driven by nutrient demands of symbiosis system through the hypha bridge of arbuscular mycorrhizal fungi.

PubMed

Kong, Xiangshi; Jia, Yanyan; Song, Fuqiang; Tian, Kai; Lin, Hong; Bei, Zhanlin; Jia, Xiuqin; Yao, Bei; Guo, Peng; Tian, Xingjun

2018-02-01

Arbuscular mycorrhizal fungi (AMF) play an important role in litter decomposition. This study investigated how soil nutrient level affected the process. Results showed that AMF colonization had no significant effect on litter decomposition under normal soil nutrient conditions. However, litter decomposition was accelerated significantly under lower nutrient conditions. Soil microbial biomass in decomposition system was significantly increased. Especially, in moderate lower nutrient treatment (condition of half-normal soil nutrient), litters exhibited the highest decomposition rate, AMF hypha revealed the greatest density, and enzymes (especially nitrate reductase) showed the highest activities as well. Meanwhile, the immobilization of nitrogen (N) in the decomposing litter remarkably decreased. Our results suggested that the roles AMF played in ecosystem were largely affected by soil nutrient levels. At normal soil nutrient level, AMF exhibited limited effects in promoting decomposition. When soil nutrient level decreased, the promoting effect of AMF on litter decomposition began to appear, especially on N mobilization. However, under extremely low nutrient conditions, AMF showed less influence on decomposition and may even compete with decomposer microorganisms for nutrients.

Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

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

Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu; Pratheeshkumar, Poyil; Budhraja, Amit

Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROSmore » levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The present study has also shown that the arsenic-transformed cells acquired apoptosis resistance. The inhibition of catalase to increase ROS level restored apoptosis capability of arsenic-transformed BEAS-2B cells, further showing that ROS levels are low in these cells. The apoptosis resistance due to the low ROS levels may increase cells proliferation, providing a favorable environment for tumorigenesis of arsenic-transformed cells.« less

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.

Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans

PubMed Central

Butler, Andrew A.; St-Onge, Marie-Pierre; Siebert, Emily A.; Medici, Valentina; Stanhope, Kimber L.; Havel, Peter J.

2015-01-01

Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations. PMID:26435060

Toxicity study of a rubber antioxidant, mixture of 2-mercaptomethylbenzimidazoles, by repeated oral administration to rats.

PubMed

Saitoh, M; Umemura, T; Kawasaki, Y; Momma, J; Matsushima, Y; Sakemi, K; Isama, K; Kitajima, S; Ogawa, Y; Hasegawa, R; Suzuki, T; Hayashi, M; Inoue, T; Ohno, Y; Sofuni, T; Kurokawa, Y; Tsuda, M

1999-07-01

2-Mercaptobenzimidazole (2-MBI), a rubber antioxidant, is known to exhibit potent antithyroid toxicity in rats and is a candidate as an environmental endocrine disrupter. 2-Mercaptomethylbenzimidazoles (a 1:1 mixture of 4-methyl and 5-methyl isomers, MMBIs), are also employed industrially as rubber antioxidants and are suspected to exert antithyroid toxicity such as 2-MBI. In this investigation, acute and subacute oral toxicity studies of MMBIs in Wistar rats were conducted. The clinical signs of acute oral toxicity were observed including decreased spontaneous movement, a paralytic gait, salivation and lacrimation, and adoption of prone and lateral positions. The LD50 was estimated to be 330 mg/kg. In the subacute oral toxicity study, male and female rats were treated with MMBIs by gavage at doses of 0 (corn oil), 4, 20 and 100 mg/kg for 28 consecutive days followed by a 2-week recovery period for the control and highest dose groups. Body weight and food consumption, clinical signs, organ weights, clinical biochemistry and haematological parameters including clotting times and micronuclei induction in bone marrow erythropoeitic cells, and histopathology were examined. Relative organ weights of lung, liver and kidney, and serum cholesterol and phospholipid significantly increased in male rats treated with MMBIs at doses of 20 and 100 mg/kg. Male rats administered 100 mg/kg MMBIs exhibited a 1.8-fold increase in thyroid weight associated with histopathological changes but not altered serum thyroid hormone levels. Female rats administered 100 mg MMBIs/kg exhibited significant increases of liver and kidney but not thyroid weights, and serum cholesterol level. The antithyroid toxicity of MMBIs in rats was estimated to be one-tenth that of 2-MBI. No-observed-effect levels for male and female rats were found to be 4 and 20 mg/kg, respectively, in this subacute oral toxicity study.

Disuse atrophy, plasma corticosterone, and muscle glucocorticoid receptor levels

NASA Technical Reports Server (NTRS)

Steffen, J. M.; Musacchia, X. J.

1987-01-01

The effect of whole-body suspension on the time course and the extent of plasma corticosterone changes and the tissue sensitivity to glucocorticoids were investigated in rats subjected to seven days of whole-body suspension. Plasma corticosterone increased significantly on the first and the third days of suspension, but returned to control levels by day seven. Muscle glucocorticoid receptors exhibited a characteristic hormonal specificity (evaluated in competitive-displacement experiments). In controls, receptor site concentration in the slow-twitch soleus was comparable to that in the fast-twitch gastrocnemius and plantaris, but was significantly less than in the extensor; seven days of suspension resulted in significant differential effects on muscle receptor levels. The largest increase in receptor concentration was observed in the soleus in which it remained elevated after the receptor levels in other muscles returned to normal.

Identification and functional characterization of the pepper CaDRT1 gene involved in the ABA-mediated drought stress response.

PubMed

Baek, Woonhee; Lim, Sohee; Lee, Sung Chul

2016-05-01

Plants are constantly challenged by various environmental stresses, including high salinity and drought, and they have evolved defense mechanisms to counteract the deleterious effects of these stresses. The plant hormone abscisic acid (ABA) regulates plant growth and developmental processes and mediates abiotic stress responses. Here, we identified the Capsicum annuum DRought Tolerance 1 (CaDRT1) gene from pepper leaves treated with ABA. CaDRT1 was strongly expressed in pepper leaves in response to environmental stresses and after ABA treatment, suggesting that the CaDRT1 protein functions in the abiotic stress response. Knockdown expression of CaDRT1 via virus-induced gene silencing resulted in a high level of drought susceptibility, and this was characterized by increased transpirational water loss via decreased stomatal closure. CaDRT1-overexpressing (OX) Arabidopsis plants exhibited an ABA-hypersensitive phenotype during the germinative, seedling, and adult stages. Additionally, these CaDRT1-OX plants exhibited a drought-tolerant phenotype characterized by low levels of transpirational water loss, high leaf temperatures, increased stomatal closure, and enhanced expression levels of drought-responsive genes. Taken together, our results suggest that CaDRT1 is a positive regulator of the ABA-mediated drought stress response.

Individuals with Asperger's disorder exhibit difficulty in switching attention from a local level to a global level.

PubMed

Katagiri, Masatoshi; Kasai, Tetsuko; Kamio, Yoko; Murohashi, Harumitsu

2013-02-01

The purpose of the present study was to determine whether individuals with Asperger's disorder exhibit difficulty in switching attention from a local level to a global level. Eleven participants with Asperger's disorder and 11 age- and gender-matched healthy controls performed a level-repetition switching task using Navon-type hierarchical stimuli. In both groups, level-repetition was beneficial at both levels. Furthermore, individuals with Asperger's disorder exhibited difficulty in switching attention from a local level to a global level compared to control individuals. These findings suggested that there is a problem with the inhibitory mechanism that influences the output of enhanced local visual processing in Asperger's disorder.

Skin conductance level reactivity moderates the association between harsh parenting and growth in child externalizing behavior.

PubMed

Erath, Stephen A; El-Sheikh, Mona; Hinnant, J Benjamin; Cummings, E Mark

2011-05-01

Skin conductance level reactivity (SCLR) was examined as a moderator of the association between harsh parenting at age 8 years and growth in child externalizing behavior from age 8 to age 10 (N = 251). Mothers and fathers provided reports of harsh parenting and their children's externalizing behavior; children also provided reports of harsh parenting. SCLR was assessed in response to a socioemotional stress task and a problem-solving challenge task. Latent growth modeling revealed that boys with higher harsh parenting in conjunction with lower SCLR exhibited relatively high and stable levels of externalizing behavior during late childhood. Boys with higher harsh parenting and higher SCLR exhibited relatively low to moderate levels of externalizing behavior at age 8, but some results suggested that their externalizing behavior increased over time, approaching the same levels as boys with higher harsh parenting and lower SCLR by age 10. For the most part, girls and boys with lower harsh parenting were given relatively low and stable ratings of externalizing behavior throughout late childhood. Results are discussed from a developmental psychopathology perspective with reference to models of antisocial behavior in childhood. (c) 2011 APA, all rights reserved.

Skin Conductance Level Reactivity Moderates the Association Between Harsh Parenting and Growth in Child Externalizing Behavior

PubMed Central

Erath, Stephen A.; El-Sheikh, Mona; Hinnant, J. Benjamin; Cummings, E. Mark

2011-01-01

Skin conductance level reactivity (SCLR) was examined as a moderator of the association between harsh parenting at age 8 years and growth in child externalizing behavior from age 8 to age 10 (N = 251). Mothers and fathers provided reports of harsh parenting and their children’s externalizing behavior; children also provided reports of harsh parenting. SCLR was assessed in response to a socioemotional stress task and a problem-solving challenge task. Latent growth modeling revealed that boys with higher harsh parenting in conjunction with lower SCLR exhibited relatively high and stable levels of externalizing behavior during late childhood. Boys with higher harsh parenting and higher SCLR exhibited relatively low to moderate levels of externalizing behavior at age 8, but some results suggested that their externalizing behavior increased over time, approaching the same levels as boys with higher harsh parenting and lower SCLR by age 10. For the most part, girls and boys with lower harsh parenting were given relatively low and stable ratings of externalizing behavior throughout late childhood. Results are discussed from a developmental psychopathology perspective with reference to models of antisocial behavior in childhood. PMID:21142369

Monitoring Intracellular Oxygen Concentration: Implications for Hypoxia Studies and Real-Time Oxygen Monitoring.

PubMed

Potter, Michelle; Badder, Luned; Hoade, Yvette; Johnston, Iain G; Morten, Karl J

2016-01-01

The metabolic properties of cancer cells have been widely accepted as a hallmark of cancer for a number of years and have shown to be of critical importance in tumour development. It is generally accepted that tumour cells exhibit a more glycolytic phenotype than normal cells. In this study, we investigate the bioenergetic phenotype of two widely used cancer cell lines, RD and U87MG, by monitoring intracellular oxygen concentrations using phosphorescent Pt-porphyrin based intracellular probes. Our study demonstrates that cancer cell lines do not always exhibit an exclusively glycolytic phenotype. RD demonstrates a reliance on oxidative phosphorylation whilst U87MG display a more glycolytic phenotype. Using the intracellular oxygen sensing probe we generate an immediate readout of intracellular oxygen levels, with the glycolytic lines reflecting the oxygen concentration of the environment, and cells with an oxidative phenotype having significantly lower levels of intracellular oxygen. Inhibition of oxygen consumption in lines with high oxygen consumption increases intracellular oxygen levels towards environmental levels. We conclude that the use of intracellular oxygen probes provides a quantitative assessment of intracellular oxygen levels, allowing the manipulation of cellular bioenergetics to be studied in real time.

An Enantiomer of an Oral Small-Molecule TSH Receptor Agonist Exhibits Improved Pharmacologic Properties.

PubMed

Neumann, Susanne; Padia, Umesh; Cullen, Mary Jane; Eliseeva, Elena; Nir, Eshel A; Place, Robert F; Morgan, Sarah J; Gershengorn, Marvin C

2016-01-01

We are developing an orally available small-molecule, allosteric TSH receptor (TSHR) agonist for follow-up diagnostics of patients with thyroid cancer. The agonist C2 (NCGC00161870) that we have studied so far is a racemic mixture containing equal amounts of two enantiomers, E1 and E2. As enantiomers of many drugs exhibit different pharmacologic properties, we assessed the properties of E1 and E2. We separated the two enantiomers by chiral chromatography and determined E2 as the (S)-(+) isomer via crystal structure analysis. E1 and E2 were shown to bind differently to a homology model of the transmembrane domain of TSHR in which E2 was calculated to exhibit lower binding energy than E1 and was, therefore, predicted to be more potent than E1. In HEK293 cells expressing human TSHRs, C2, E1, and E2 were equally efficacious in stimulating cAMP production, but their potencies were different. E2 was more potent (EC50 = 18 nM) than C2 (EC50 = 46 nM), which was more potent than E1 (EC50 = 217 nM). In primary cultures of human thyrocytes, C2, E1, and E2 stimulated increases in thyroperoxidase mRNA of 92-, 55-, and 137-fold and in sodium-iodide symporter mRNA of 20-, 4-, and 121-fold above basal levels, respectively. In mice, C2 stimulated an increase in radioactive iodine uptake of 1.5-fold and E2 of 2.8-fold above basal level, whereas E1 did not have an effect. C2 stimulated an increase in serum T4 of 2.4-fold, E1 of 1.9-fold, and E2 of 5.6-fold above basal levels, and a 5-day oral dosing regimen of E2 increased serum T4 levels comparable to recombinant human TSH (rhTSH, Thyrogen(®)). Thus, E2 is more effective than either C2 or E1 in stimulating thyroid function and as efficacious as rhTSH in vivo. E2 represents the next step toward developing an oral drug for patients with thyroid cancer.

Lyso-GM2 ganglioside: a possible biomarker of Tay-Sachs disease and Sandhoff disease.

PubMed

Kodama, Takashi; Togawa, Tadayasu; Tsukimura, Takahiro; Kawashima, Ikuo; Matsuoka, Kazuhiko; Kitakaze, Keisuke; Tsuji, Daisuke; Itoh, Kohji; Ishida, Yo-Ichi; Suzuki, Minoru; Suzuki, Toshihiro; Sakuraba, Hitoshi

2011-01-01

To find a new biomarker of Tay-Sachs disease and Sandhoff disease. The lyso-GM2 ganglioside (lyso-GM2) levels in the brain and plasma in Sandhoff mice were measured by means of high performance liquid chromatography and the effect of a modified hexosaminidase (Hex) B exhibiting Hex A-like activity was examined. Then, the lyso-GM2 concentrations in human plasma samples were determined. The lyso-GM2 levels in the brain and plasma in Sandhoff mice were apparently increased compared with those in wild-type mice, and they decreased on intracerebroventricular administration of the modified Hex B. The lyso-GM2 levels in plasma of patients with Tay-Sachs disease and Sandhoff disease were increased, and the increase in lyso-GM2 was associated with a decrease in Hex A activity. Lyso-GM2 is expected to be a potential biomarker of Tay-Sachs disease and Sandhoff disease.

Lyso-GM2 Ganglioside: A Possible Biomarker of Tay-Sachs Disease and Sandhoff Disease

PubMed Central

Kodama, Takashi; Togawa, Tadayasu; Tsukimura, Takahiro; Kawashima, Ikuo; Matsuoka, Kazuhiko; Kitakaze, Keisuke; Tsuji, Daisuke; Itoh, Kohji; Ishida, Yo-ichi; Suzuki, Minoru; Suzuki, Toshihiro; Sakuraba, Hitoshi

2011-01-01

To find a new biomarker of Tay-Sachs disease and Sandhoff disease. The lyso-GM2 ganglioside (lyso-GM2) levels in the brain and plasma in Sandhoff mice were measured by means of high performance liquid chromatography and the effect of a modified hexosaminidase (Hex) B exhibiting Hex A-like activity was examined. Then, the lyso-GM2 concentrations in human plasma samples were determined. The lyso-GM2 levels in the brain and plasma in Sandhoff mice were apparently increased compared with those in wild-type mice, and they decreased on intracerebroventricular administration of the modified Hex B. The lyso-GM2 levels in plasma of patients with Tay-Sachs disease and Sandhoff disease were increased, and the increase in lyso-GM2 was associated with a decrease in Hex A activity. Lyso-GM2 is expected to be a potential biomarker of Tay-Sachs disease and Sandhoff disease. PMID:22205997

Exercise recommendations for individuals with spinal cord injury.

PubMed

Jacobs, Patrick L; Nash, Mark S

2004-01-01

Persons with spinal cord injury (SCI) exhibit deficits in volitional motor control and sensation that limit not only the performance of daily tasks but also the overall activity level of these persons. This population has been characterised as extremely sedentary with an increased incidence of secondary complications including diabetes mellitus, hypertension and atherogenic lipid profiles. As the daily lifestyle of the average person with SCI is without adequate stress for conditioning purposes, structured exercise activities must be added to the regular schedule if the individual is to reduce the likelihood of secondary complications and/or to enhance their physical capacity. The acute exercise responses and the capacity for exercise conditioning are directly related to the level and completeness of the spinal lesion. Appropriate exercise testing and training of persons with SCI should be based on the individual's exercise capacity as determined by accurate assessment of the spinal lesion. The standard means of classification of SCI is by application of the International Standards for Classification of Spinal Cord Injury, written by the Neurological Standards Committee of the American Spinal Injury Association. Individuals with complete spinal injuries at or above the fourth thoracic level generally exhibit dramatically diminished cardiac acceleration with maximal heart rates less than 130 beats/min. The work capacity of these persons will be limited by reductions in cardiac output and circulation to the exercising musculature. Persons with complete spinal lesions below the T(10) level will generally display injuries to the lower motor neurons within the lower extremities and, therefore, will not retain the capacity for neuromuscular activation by means of electrical stimulation. Persons with paraplegia also exhibit reduced exercise capacity and increased heart rate responses (compared with the non-disabled), which have been associated with circulatory limitations within the paralysed tissues. The recommendations for endurance and strength training in persons with SCI do not vary dramatically from the advice offered to the general population. Systems of functional electrical stimulation activate muscular contractions within the paralysed muscles of some persons with SCI. Coordinated patterns of stimulation allows purposeful exercise movements including recumbent cycling, rowing and upright ambulation. Exercise activity in persons with SCI is not without risks, with increased risks related to systemic dysfunction following the spinal injury. These individuals may exhibit an autonomic dysreflexia, significantly reduced bone density below the spinal lesion, joint contractures and/or thermal dysregulation. Persons with SCI can benefit greatly by participation in exercise activities, but those benefits can be enhanced and the relative risks may be reduced with accurate classification of the spinal injury.

Effects of Kaolin Clay on the Mechanical Properties of Asphaltic Concrete AC14

NASA Astrophysics Data System (ADS)

Abdullah, M. E.; Ramadhansyah, P. J.; Rafsanjani, M. H.; Norhidayah, A. H.; Yaacob, H.; Hainin, M. R.; Warid, M. N. Mohd; Satar, M. K. I. Mohd; Aziz, Md Maniruzzaman A.; Mashros, N.

2018-04-01

This study investigated the effect of kaolin clay on the mechanical properties of asphaltic concrete AC14 through Marshall Stability, resilient modulus, and dynamic creep tests. Four replacement levels of kaolin clay (2%, 4%, 6%, and 8% by weight of the binder) were considered. Kaolin clay functioned as an effective filler replacement material to increase the mechanical properties of asphalt mixtures. Asphaltic concrete with 2% to 4% kaolin clay replacement level exhibited excellent performance with good stability, resilient modulus, and creep stiffness.

Maintenance of tumor initiating cells of defined genetic composition by nucleostemin.

PubMed

Okamoto, Naoko; Yasukawa, Mami; Nguyen, Christine; Kasim, Vivi; Maida, Yoshiko; Possemato, Richard; Shibata, Tatsuhiro; Ligon, Keith L; Fukami, Kiyoko; Hahn, William C; Masutomi, Kenkichi

2011-12-20

Recent work has identified a subset of cells resident in tumors that exhibit properties similar to those found in normal stem cells. Such cells are highly tumorigenic and may be involved in resistance to treatment. However, the genes that regulate the tumor initiating cell (TIC) state are unknown. Here, we show that overexpression of either of the nucleolar GTP-binding proteins nucleostemin (NS) or GNL3L drives the fraction of genetically defined tumor cells that exhibit markers and tumorigenic properties of TICs. Specifically, cells that constitutively express elevated levels of NS or GNL3L exhibit increased TWIST expression, phosphorylation of STAT3, expression of genes that induce pluripotent stem cells, and enhanced radioresistance; in addition, they form tumors even when small numbers of cells are implanted and exhibit an increased propensity to metastasize. GNL3L/NS forms a complex with the telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] and the SWItch-Sucrose NonFermentable (SWI-SNF) complex protein brahma-related gene 1 (BRG1), and the expression of each of these components is necessary to facilitate the cancer stem cell state. Together, these observations define a complex composed of TERT, BRG1, and NS/GNL3L that maintains the function of TICs.

Microstructural changes in memory and reticular formation neural pathway after simple concussion☆

PubMed Central

Ouyang, Lin; Shi, Rongyue; Xiao, Yuhui; Meng, Jiarong; Guo, Yihe; Lu, Guangming

2012-01-01

Patients with concussion often present with temporary disturbance of consciousness. The microstructural and functional changes in the brain associated with concussion, as well as the relationship with transient cognitive disorders, are currently unclear. In the present study, a rabbit model of simple concussion was established. Magnetic resonance-diffusion tensor imaging results revealed that the corona radiata and midbrain exhibited significantly decreased fractional anisotropy values in the neural pathways associated with memory and the reticular formation. In addition, the apparent diffusion coefficient values were significantly increased following injury compared with those before injury. Following a 1-hour period of quiet rest, the fractional anisotropy values significantly increased, and apparent diffusion coefficient values significantly decreased, returning to normal pre-injury levels. In contrast, the fractional anisotropy values and apparent diffusion coefficient values in the corpus callosum, thalamus and hippocampus showed no statistical significant alterations following injury. These findings indicate that the neural pathways associated with memory and the reticular formation pathway exhibit reversible microstructural white matter changes when concussion occurs, and these changes are exhibited to a different extent in different regions. PMID:25538741

Microstructural changes in memory and reticular formation neural pathway after simple concussion.

PubMed

Ouyang, Lin; Shi, Rongyue; Xiao, Yuhui; Meng, Jiarong; Guo, Yihe; Lu, Guangming

2012-10-05

Patients with concussion often present with temporary disturbance of consciousness. The microstructural and functional changes in the brain associated with concussion, as well as the relationship with transient cognitive disorders, are currently unclear. In the present study, a rabbit model of simple concussion was established. Magnetic resonance-diffusion tensor imaging results revealed that the corona radiata and midbrain exhibited significantly decreased fractional anisotropy values in the neural pathways associated with memory and the reticular formation. In addition, the apparent diffusion coefficient values were significantly increased following injury compared with those before injury. Following a 1-hour period of quiet rest, the fractional anisotropy values significantly increased, and apparent diffusion coefficient values significantly decreased, returning to normal pre-injury levels. In contrast, the fractional anisotropy values and apparent diffusion coefficient values in the corpus callosum, thalamus and hippocampus showed no statistical significant alterations following injury. These findings indicate that the neural pathways associated with memory and the reticular formation pathway exhibit reversible microstructural white matter changes when concussion occurs, and these changes are exhibited to a different extent in different regions.

Analysis of Protein Kinase C Delta (PKCδ) Expression in Endometrial Tumors

PubMed Central

Reno, Elaine M.; Haughian, James M.; Dimitrova, Irina K.; Jackson, Twila A.; Shroyer, Kenneth R; Bradford., Andrew P.

2007-01-01

Endometrial cancer is the most common gynecological malignancy in the US, however, its underlying molecular mechanisms are poorly understood and few prognostic indicators have been identified. The Protein Kinase C (PKC) family have been shown to regulate pathways critical to malignant transformation, and in endometrial tumors, changes in PKC expression and activity have been linked to a more aggressive phenotype and poor prognosis. We have recently shown that PKCδ is a critical regulator of apoptosis and cell survival in endometrial cancer cells; however, PKCδ levels in endometrial tumors had not been determined. We used immunohistochemistry to examine PKCδ protein levels in normal endometrium and endometrioid carcinomas of increasing grade. Normal endometrium exhibited abundant nuclear and cytoplasmic staining of PKCδ, confined to glandular epithelium. In endometrial tumors, decreased PKCδ expression, both in intensity and fraction of epithelial cells stained, was observed with increasing tumor grade, with PKCδ being preferentially lost from the nucleus. Consistent with these observations, endometrial cancer cell lines derived from poorly differentiated tumors exhibited reduced PKCδ levels relative to well-differentiated lines. Treatment of endometrial cancer cells with etoposide resulted in a translocation of PKCδ from cytoplasm to nucleus concomitant with induction of apoptosis. Decreased PKCδ expression, particularly in the nucleus, may compromise the ability of cells to undergo apoptosis, perhaps conferring resistance to chemotherapy. Our results indicate that loss of PKCδ is an indicator of endometrial malignancy and increasing grade of cancer. Thus, PKCδ may function as a tumor suppressor in endometrial cancer. PMID:17959229

Developmental programming of appetite/satiety.

PubMed

Ross, Michael G; Desai, Mina

2014-01-01

Obesity is often attributed to a Western lifestyle, a high-fat diet and decreased activity. While these factors certainly contribute to adult obesity, compelling data from our laboratory and others indicate that this explanation is oversimplified. Recent studies strongly argue that maternal/fetal under- or overnutrition predisposes the offspring to become hyperphagic and increases the risk of later obesity. Both infants small for gestational age (SGA) or infants born to obese mothers who consume a high-fat diet are at a markedly increased risk of adult obesity. Specific alterations in the fetal metabolic/energy environment directly influence the development of appetite regulatory pathways. Specifically, SGA infants demonstrate (1) impaired satiety and anorexigenic cell signaling, (2) enhanced cellular orexigenic responses, (3) programmed dysfunction of neuroprogenitor cell proliferation/differentiation, and (4) increased expression of appetite (NPY) versus satiety (POMC) neurons. In both hypothalamic tissue and ex vivo culture, SGA newborns exhibit increased levels of the nutrient sensor SIRT1, signifying reduced energy, whereas maternal high-fat-exposed newborns exhibit reduced levels of pAMPK, signifying energy excess. Via downstream regulation of bHLH neuroproliferation (Hes1) and neurodifferentiation factors (Mash1, Ngn3), neurogenesis is biased toward orexigenic and away from anorexigenic neurons, resulting in excess appetite, reduced satiety and development of obesity. Despite the developmental programming of appetite neurogenesis, the potential for neuronal remodeling raises the opportunity for novel interventions.

Heavy metal accumulation and growth of seedlings of five forest species as influenced by soil cadmium level

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

Kelly, J.M.; Parker, G.R.; McFee, W.W.

1979-07-01

White pine (Pinus strobus L.), loblolly pine (P. taeda L.), yellow poplar (Liriodendron tulipifera L.), yellow birch (Betula alleghaniensis Britt.), and choke cherry (Prunus virginiana L.) were grown from seeds in the greenhouse for 17 weeks. Plainfield fine sand, with pretreatment cadmium, lead, copper, and zinc concentrations of 0.6, 11.4, 2.0, and 20.6 ppM, respectively, was used as the growth medium. This soil was amended with CdCl/sub 2/ to produce cadmium addition levels of 0, 15, and 100 ppM. Shoot elongation and root and shoot dry weights were reduced with increasing levels of soil cadmium. All species exhibited increased cadmiummore » content in roots and shoots in response to increased soil cadmium levels; however, content varied according to species. Root and shoot accumulations of lead, copper, and zinc also varied with species as well as cadmium concentration in the soil.« less

Overexpression of bone sialoprotein leads to an uncoupling of bone formation and bone resorption in mice.

PubMed

Valverde, Paloma; Zhang, Jin; Fix, Amanda; Zhu, Ji; Ma, Wenli; Tu, Qisheng; Chen, Jake

2008-11-01

The purpose of this study was to determine the effects of bone sialoprotein (BSP) overexpression in bone metabolism in vivo by using a homozygous transgenic mouse line that constitutively overexpresses mouse BSP cDNA driven by the cytomegalovirus (CMV) promoter. CMV-BSP transgenic (TG) mice and wildtype mice were weighed, and their length, BMD, and trabecular bone volume were measured. Serum levels of RANKL, osteocalcin, osteoprotegerin (OPG), TRACP5b, and PTH were determined. Bone histomorphometry, von Kossa staining, RT-PCR analysis, Western blot, MTS assay, in vitro mineralization assay, and TRACP staining were also performed to delineate phenotypes of this transgenic mouse line. Compared with wildtype mice, adult TG mice exhibit mild dwarfism, lower values of BMD, and lower trabecular bone volume. TG mice serum contained increased calcium levels and decreased PTH levels, whereas the levels of phosphorus and magnesium were within normal limits. TG mice serum also exhibited lower levels of osteoblast differentiation markers and higher levels of markers, indicating osteoclastic activity and bone resorption. H&E staining, TRACP staining, and bone histomorphometry showed that adult TG bones were thinner and the number of giant osteoclasts in TG mice was higher, whereas there were no significant alterations in osteoblast numbers between TG mice and WT mice. Furthermore, the vertical length of the hypertrophic zone in TG mice was slightly enlarged. Moreover, ex vivo experiments indicated that overexpression of BSP decreased osteoblast population and increased osteoclastic activity. Partly because of its effects in enhancing osteoclastic activity and decreasing osteoblast population, BSP overexpression leads to an uncoupling of bone formation and resorption, which in turn results in osteopenia and mild dwarfism in mice. These findings are expected to help the development of therapies to metabolic bone diseases characterized by high serum level of BSP.

A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats.

PubMed

Stanimirovic, Julijana; Obradovic, Milan; Jovanovic, Aleksandra; Sudar-Milovanovic, Emina; Zafirovic, Sonja; Pitt, Samantha J; Stewart, Alan J; Isenovic, Esma R

2016-04-01

Men and women differ substantially with regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR. Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed. The levels of inducible nitric oxide (NO) synthase (iNOS), p65 subunit of NFκB, total and phosphorylated forms of Akt, mTOR and PDK-1 in lysates, and the levels of glucose transporter 2 (Glut-2) and fatty acid translocase/cluster of differentiation 36 (FAT/CD36) in plasma membrane fractions of liver were assessed. HF-fed male rats exhibited a significant increase in plasma nitrite/nitrate, and hepatic FFA and FAT/CD36 levels compared with controls. They also displayed a relative decrease in iNOS and Glut-2 levels in the liver. Phosphorylation of Akt (at Ser(473) and Thr(308)), mTOR and PDK-1 was also reduced. HF-fed female rats exhibited increased levels of NFκB-p65 in liver compared with controls, while levels of Glut-2, FAT/CD36 and Akt phosphorylation at Thr(308) and PDK-1 were decreased. Our results reveal that altered lipid and glucose metabolism in obesity, lead to altered iNOS expression and nitrite/nitrate production. It is likely that this mechanism contributes to sex-specific differences in the development of IR. Copyright © 2016 Elsevier Inc. All rights reserved.

Phenotypic and genotypic characterization of influenza virus mutants selected with the sialidase fusion protein DAS181

PubMed Central

Triana-Baltzer, Gallen B.; Sanders, Rebecca L.; Hedlund, Maria; Jensen, Kellie A.; Aschenbrenner, Laura M.; Larson, Jeffrey L.; Fang, Fang

2011-01-01

Background Influenza viruses (IFVs) frequently achieve resistance to antiviral drugs, necessitating the development of compounds with novel mechanisms of action. DAS181 (Fludase®), a sialidase fusion protein, may have a reduced potential for generating drug resistance due to its novel host-targeting mechanism of action. Methods IFV strains B/Maryland/1/59 and A/Victoria/3/75 (H3N2) were subjected to >30 passages under increasing selective pressure with DAS181. The DAS181-selected IFV isolates were characterized in vitro and in mice. Results Despite extensive passaging, DAS181-selected viruses exhibited a very low level of resistance to DAS181, which ranged between 3- and 18-fold increase in EC50. DAS181-selected viruses displayed an attenuated phenotype in vitro, as exhibited by slower growth, smaller plaque size and increased particle to pfu ratios relative to wild-type virus. Further, the DAS181 resistance phenotype was unstable and was substantially reversed over time upon DAS181 withdrawal. In mice, the DAS181-selected viruses exhibited no greater virulence than their wild-type counterparts. Genotypic and phenotypic analysis of DAS181-selected viruses revealed mutations in the haemagglutinin (HA) and neuraminidase (NA) molecules and also changes in HA and NA function. Conclusions Results indicate that resistance to DAS181 is minimal and unstable. The DAS181-selected IFV isolates exhibit reduced fitness in vitro, likely due to altered HA and NA functions. PMID:21097900

Effects of dehydration on plasma osmolality, thirst-related behavior, and plasma and brain angiotensin concentrations in Couch's spadefoot toad, Scaphiopus couchii.

PubMed

Johnson, W E; Propper, C R

2000-05-01

Under dehydrating conditions, many terrestrial vertebrates species exhibit increases in plasma osmolality and their drinking behavior. Under some circumstances, this behavioral change is accompanied by changes in plasma and central angiotensin concentrations, and it has been proposed that these changes in angiotensin levels induce the thirst-related behaviors. In response to dehydration, the spadefoot toad, Scaphiopus couchii, exhibits thirst-related behavior in the form of cutaneous drinking. This behavior has been termed water absorption response (WR) behavior. Spadefoot toads live in harsh desert environments and are subject annually to dehydrating conditions that may induce thirst-related behavior. We tested the hypothesis that an increase in WR behavior is associated with both an increase in plasma osmolality and an increase in plasma and brain angiotensin concentrations. First, we determined the degree of dehydration that was necessary to initiate WR behavior. Animals dehydrated to 85% of their standard bladder-empty weight via deprivation of water exhibited WR behavior more frequently than control toads left in home containers with water available. Next, using the same dehydration methods, we determined the plasma osmolality and sodium concentrations of dehydrated toads. Toads dehydrated to 85% standard weight also had a significant increase in plasma osmolality, but exhibited no overall change in plasma sodium concentrations, indicating that while an overall increase in plasma osmolality appears to be associated with WR behavior in S. couchii, changes in sodium concentrations alone are not sufficient to induce the behavior. Finally, plasma and brain angiotensin concentrations were measured in control toads and toads dehydrated to 85% standard weight. Plasma and brain angiotensin concentrations did not increase in dehydrated toads, indicating that dehydration-induced WR behavior that is associated with changes in plasma osmolality may not be induced by changes in endogenous angiotensin concentrations in S. couchii.

Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae).

PubMed

Schelegle, E S; Gershwin, L J; Miller, L A; Fanucchi, M V; Van Winkle, L S; Gerriets, J P; Walby, W F; Omlor, A M; Buckpitt, A R; Tarkington, B K; Wong, V J; Joad, J P; Pinkerton, K B; Wu, R; Evans, M J; Hyde, D M; Plopper, C G

2001-01-01

To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.

Allergic Asthma Induced in Rhesus Monkeys by House Dust Mite (Dermatophagoides farinae)

PubMed Central

Schelegle, Edward S.; Gershwin, Laurel J.; Miller, Lisa A.; Fanucchi, Michelle V.; Van Winkle, Laura S.; Gerriets, Joan P.; Walby, William F.; Omlor, Amanda M.; Buckpitt, Alan R.; Tarkington, Brian K.; Wong, Viviana J.; Joad, Jesse P.; Pinkerton, Kent B.; Wu, Reen; Evans, Michael J.; Hyde, Dallas M.; Plopper, Charles G.

2001-01-01

To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4+ lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA. PMID:11141508

Confidence and the stock market: an agent-based approach.

PubMed

Bertella, Mario A; Pires, Felipe R; Feng, Ling; Stanley, Harry Eugene

2014-01-01

Using a behavioral finance approach we study the impact of behavioral bias. We construct an artificial market consisting of fundamentalists and chartists to model the decision-making process of various agents. The agents differ in their strategies for evaluating stock prices, and exhibit differing memory lengths and confidence levels. When we increase the heterogeneity of the strategies used by the agents, in particular the memory lengths, we observe excess volatility and kurtosis, in agreement with real market fluctuations--indicating that agents in real-world financial markets exhibit widely differing memory lengths. We incorporate the behavioral traits of adaptive confidence and observe a positive correlation between average confidence and return rate, indicating that market sentiment is an important driver in price fluctuations. The introduction of market confidence increases price volatility, reflecting the negative effect of irrationality in market behavior.

Confidence and the Stock Market: An Agent-Based Approach

PubMed Central

Bertella, Mario A.; Pires, Felipe R.; Feng, Ling; Stanley, Harry Eugene

2014-01-01

Using a behavioral finance approach we study the impact of behavioral bias. We construct an artificial market consisting of fundamentalists and chartists to model the decision-making process of various agents. The agents differ in their strategies for evaluating stock prices, and exhibit differing memory lengths and confidence levels. When we increase the heterogeneity of the strategies used by the agents, in particular the memory lengths, we observe excess volatility and kurtosis, in agreement with real market fluctuations—indicating that agents in real-world financial markets exhibit widely differing memory lengths. We incorporate the behavioral traits of adaptive confidence and observe a positive correlation between average confidence and return rate, indicating that market sentiment is an important driver in price fluctuations. The introduction of market confidence increases price volatility, reflecting the negative effect of irrationality in market behavior. PMID:24421888

Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

PubMed Central

Niu, Ying-Mei; Zhu, Xiao-Li; Chang, Bing; Tong, Zhao-Hui; Cao, Wen; Qiao, Pei-Huan; Zhang, Lin-Yuan; Zhao, Jing; Song, Yu-Guo

2016-01-01

We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n = 60). Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P < 0.05) at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P < 0.05) 24 hr. after exposure. The levels of blood ALT and LDH in exposed groups were found to be significantly increased (P < 0.05) 24 hr. following exposure. The exposed groups exhibited various degrees of pleural effusion and pericardial effusion. Our findings indicated respiratory exposure to polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity. PMID:26981538

Selection for intrinsic endurance modifies endocrine stress responsiveness

PubMed Central

Waters, R Parrish; Renner, Kenneth J; Summers, Cliff H; Watt, Michael L; Forster, Gina L; Koch, Lauren G; Britton, Steven L; Swallow, John G

2010-01-01

Physical exercise dampens an individual’s stress response and decreases symptoms of anxiety and depression disorders. While the extrinsic relationship of exercise and psychological state are established, their intrinsic relationship is unresolved. We investigated the potential intrinsic relationship of exercise with stress responsiveness using NIH rats bidirectionally selected for intrinsic endurance capacity. Selection resulted in two populations, one with high intrinsic endurance (high capacity runners; HCR) and one with low intrinsic endurance (low capacity runners; LCR). Animals from these populations were subjected to the elevated plus maze (EPM) and novel environment to assess levels of anxiety-like behavior, and to restraint stress to determine stress responsiveness. Pre-test plasma corticosterone levels and the response of plasma corticosterone to exposure to the EPM and restraint were analyzed using ELISA. A dexamethasone suppression test was performed to assess negative feedback tone of corticosterone release. Pre-test plasma corticosterone levels were similar between LCR and HCR, and these populations had similar behavioral and corticosterone responses to the EPM. Following restraint, HCR animals exhibited more anxiotypic behavior than LCR animals on the EPM, and exhibited an increase in plasma corticosterone following EPM and restraint that was not observed in LCR animals. HCR animals also exhibited more anxiotypic behavior in the novel environment compared to LCR animals. Plasma corticosterone levels were equally reduced in both populations following dexamethasone administration. Overall, our data suggest a positive genetic relationship between exercise endurance and stress responsiveness, which is at odds with the established extrinsic relationship of these traits. PMID:20682296

Drug Use and Cognitions about Drug Use amongst Students: Changes over the University Career.

ERIC Educational Resources Information Center

McMillan, Brian; Conner, Mark

2002-01-01

Studied the hypothesis that students would exhibit changes in their levels of, and cognitions about, drug use throughout their university careers. Responses from a sample of 380 undergraduates (response rate, 63%) show no evidence of an increase in the percentage of undergraduates using drugs over their university careers, but there was a…

A Short-Term Longitudinal Study of Memorial Development during Early Grade School.

ERIC Educational Resources Information Center

Kunzinger, Edward L., III

1985-01-01

Overt rehearsal and free recall performance was analyzed longitudinally in two experimental testing sessions at 7 and later at 9 years of age. Measures of short- and long-term memory recall, and two measures of input processing were obtained. Significant increases between age levels were exhibited by all variables except short-term memory.…

Revisiting Data Related to the Age of Onset and Developmental Course of Female Conduct Problems

ERIC Educational Resources Information Center

Brennan, Lauretta M.; Shaw, Daniel S.

2013-01-01

Children who exhibit persistently elevated levels of conduct problems (CP) from early childhood, so-called early-starters, are known to be at increased risk for continued CP throughout middle childhood, adolescence, and adulthood. Theoretical and empirical work has focused on this subgroup of children characterized by similar risk factors, an…

A Novel in Vitro Analog Expressing Learning-Induced Cellular Correlates in Distinct Neural Circuits

ERIC Educational Resources Information Center

Weisz, Harris A.; Wainwright, Marcy L.; Mozzachiodi, Riccardo

2017-01-01

When presented with noxious stimuli, "Aplysia" exhibits concurrent sensitization of defensive responses, such as the tail-induced siphon withdrawal reflex (TSWR) and suppression of feeding. At the cellular level, sensitization of the TSWR is accompanied by an increase in the excitability of the tail sensory neurons (TSNs) that elicit the…

Impact of Climate Change on Food Security in Kenya

NASA Astrophysics Data System (ADS)

Yator, J. J.

2016-12-01

This study sought to address the existing gap on the impact of climate change on food security in support of policy measures to avert famine catastrophes. Fixed and random effects regressions for crop food security were estimated. The study simulated the expected impact of future climate change on food insecurity based on the Representative Concentration Pathways scenario (RCPs). The study makes use of county-level yields estimates (beans, maize, millet and sorghum) and daily climate data (1971 to 2010). Climate variability affects food security irrespective of how food security is defined. Rainfall during October-November-December (OND), as well as during March-April-May (MAM) exhibit an inverted U-shaped relationship with most food crops; the effects are most pronounced for maize and sorghum. Beans and Millet are found to be largely unresponsive to climate variability and also to time-invariant factors. OND rains and fall and summer temperature exhibit a U-shaped relationship with yields for most crops, while MAM rains temperature exhibits an inverted U-shaped relationship. However, winter temperatures exhibit a hill-shaped relationship with most crops. Project future climate change scenarios on crop productivity show that climate change will adversely affect food security, with up to 69% decline in yields by the year 2100. Climate variables have a non-linear relationship with food insecurity. Temperature exhibits an inverted U-shaped relationship with food insecurity, suggesting that increased temperatures will increase crop food insecurity. However, maize and millet, benefit from increased summer and winter temperatures. The simulated effects of different climate change scenarios on food insecurity suggest that adverse climate change will increase food insecurity in Kenya. The largest increases in food insecurity are predicted for the RCP 8.5Wm2, compared to RCP 4.5Wm2. Climate change is likely to have the greatest effects on maize insecurity, which is likely to increase by between 8.56% and 21% by the year 2100. There exists a need for policies that safeguard agriculture against the adverse effects of climate change to alleviate food insecurity in Kenya. Therefore, it is important that climate change mitigation is given much more priority in policy planning and also implementation.

The relationship between phenolics and flavonoids production with total non structural carbohydrate and photosynthetic rate in Labisia pumila Benth. under high CO2 and nitrogen fertilization.

PubMed

Ibrahim, Mohd Hafiz; Jaafar, Hawa Z E; Rahmat, Asmah; Rahman, Zaharah Abdul

2010-12-29

A factorial split plot 4 × 3 experiment was designed to examine and characterize the relationship among production of secondary metabolites (total phenolics, TP; total flavonoids, TF), carbohydrate content and photosynthesis of three varieties of the Malaysian medicinal herb Labisia pumila Benth. namely the varieties alata, pumila and lanceolata under CO(2) enrichment (1,200 µmol mol(-1)) combined with four levels of nitrogen fertilization (0, 90, 180 and 270 kg N ha(-1)). No varietal differences were observed, however, as the levels of nitrogen increased from 0 to 270 kg N ha(-1), the production of TP and TF decreased in the order leaves>roots>stems. The production of TP and TF was related to increased total non structural carbohydrate (TNC), where the increase in starch content was larger than that in sugar concentration. Nevertheless, the regression analysis exhibited a higher influence of soluble sugar concentration (r(2) = 0.88) than starch on TP and TF biosynthesis. Photosynthesis, on the other hand, displayed a significant negative relationship with TP and TF production (r(2) = -0.87). A decrease in photosynthetic rate with increasing secondary metabolites might be due to an increase in the shikimic acid pathway that results in enhanced production of TP and TF. Chlorophyll content exhibited very significant negative relationships with total soluble sugar, starch and total non structural carbohydrate.

Ethylene Regulates Energy-Dependent Non-Photochemical Quenching in Arabidopsis through Repression of the Xanthophyll Cycle.

PubMed

Chen, Zhong; Gallie, Daniel R

2015-01-01

Energy-dependent (qE) non-photochemical quenching (NPQ) thermally dissipates excess absorbed light energy as a protective mechanism to prevent the over reduction of photosystem II and the generation of reactive oxygen species (ROS). The xanthophyll cycle, induced when the level of absorbed light energy exceeds the capacity of photochemistry, contributes to qE. In this work, we show that ethylene regulates the xanthophyll cycle in Arabidopsis. Analysis of eto1-1, exhibiting increased ethylene production, and ctr1-3, exhibiting constitutive ethylene response, revealed defects in NPQ resulting from impaired de-epoxidation of violaxanthin by violaxanthin de-epoxidase (VDE) encoded by NPQ1. Elevated ethylene signaling reduced the level of active VDE through decreased NPQ1 promoter activity and impaired VDE activation resulting from a lower transthylakoid membrane pH gradient. Increasing the concentration of CO2 partially corrected the ethylene-mediated defects in NPQ and photosynthesis, indicating that changes in ethylene signaling affect stromal CO2 solubility. Increasing VDE expression in eto1-1 and ctr1-3 restored light-activated de-epoxidation and qE, reduced superoxide production and reduced photoinhibition. Restoring VDE activity significantly reversed the small growth phenotype of eto1-1 and ctr1-3 without altering ethylene production or ethylene responses. Our results demonstrate that ethylene increases ROS production and photosensitivity in response to high light and the associated reduced plant stature is partially reversed by increasing VDE activity.

Ethylene Regulates Energy-Dependent Non-Photochemical Quenching in Arabidopsis through Repression of the Xanthophyll Cycle

PubMed Central

Chen, Zhong; Gallie, Daniel R.

2015-01-01

Energy-dependent (qE) non-photochemical quenching (NPQ) thermally dissipates excess absorbed light energy as a protective mechanism to prevent the over reduction of photosystem II and the generation of reactive oxygen species (ROS). The xanthophyll cycle, induced when the level of absorbed light energy exceeds the capacity of photochemistry, contributes to qE. In this work, we show that ethylene regulates the xanthophyll cycle in Arabidopsis. Analysis of eto1-1, exhibiting increased ethylene production, and ctr1-3, exhibiting constitutive ethylene response, revealed defects in NPQ resulting from impaired de-epoxidation of violaxanthin by violaxanthin de-epoxidase (VDE) encoded by NPQ1. Elevated ethylene signaling reduced the level of active VDE through decreased NPQ1 promoter activity and impaired VDE activation resulting from a lower transthylakoid membrane pH gradient. Increasing the concentration of CO2 partially corrected the ethylene-mediated defects in NPQ and photosynthesis, indicating that changes in ethylene signaling affect stromal CO2 solubility. Increasing VDE expression in eto1-1 and ctr1-3 restored light-activated de-epoxidation and qE, reduced superoxide production and reduced photoinhibition. Restoring VDE activity significantly reversed the small growth phenotype of eto1-1 and ctr1-3 without altering ethylene production or ethylene responses. Our results demonstrate that ethylene increases ROS production and photosensitivity in response to high light and the associated reduced plant stature is partially reversed by increasing VDE activity. PMID:26630486

The physiological and biochemical effects of salicylic acid on sunflowers (Helianthus annuus) exposed to flurochloridone.

PubMed

Kaya, Armagan; Yigit, Emel

2014-08-01

In this study, we comparatively evaluated the effects of the flurochloridone as well as flurochloridone and exogenously applied salicylic acid (SA) on Helianthus annuus L. to find out herbicide-induced toxicity reducing influence of SA. We examined and compared the physiological and biochemical effects of different concentrations of flurochloridone (11, 32 and 72 mM) in both the SA pre-treated and non-treated plants. The plants treated with flurochloridone exhibited reduced total chlorophyll, carotenoid, and relative water content compared to the control group, whereas the plants that were pre-treated with SA exhibited relatively higher values for the same physiological parameters. In the SA non-treated plants, the superoxide dismutase, glutathione reductase and glutathione S-transferase activities were increased in the treatment groups compared to the control group. In the treatment groups, these enzyme activities were decreased in the SA-pre-treated plants compared to the non-treated plants. Ascorbate peroxidase and catalase activities decreased in the flurochloridone-treated plants compared to the control plants. The ascorbate peroxidase activity increased in the control groups but decreased in the treatment groups in the SA pre-treated plants compared to the non-treated plants. However, SA treatment decreased the activity of catalase in the control and treatment groups compared to the plants that were not treated with SA. Flurochloridone treatment increased the malondialdehyde content in the treated groups compared to the control groups, whereas SA-pretreatment decreased malondialdehyde content compared to plants that were not treated with SA. Flurochloridone treatment increased endogenous SA content compared to the control. Although the residual levels of herbicide in the plants increased proportionately with increasing herbicide concentrations, the SA-pre-treated plants exhibited reduced residual herbicide levels compared to the plants that were not treated with SA. These results indicate that the flurochloridone induces various physiological and biochemical responses in non-target plants and that treatment with exogenous SA can increase stress resistance by altering these responses. Copyright © 2014 Elsevier Inc. All rights reserved.

Fish proteins as targets of ferrous-catalyzed oxidation: identification of protein carbonyls by fluorescent labeling on two-dimensional gels and MALDI-TOF/TOF mass spectrometry.

PubMed

Pazos, Manuel; da Rocha, Angela Pereira; Roepstorff, Peter; Rogowska-Wrzesinska, Adelina

2011-07-27

Protein oxidation in fish meat is considered to affect negatively the muscle texture. An important source of free radicals taking part in this process is Fenton's reaction dependent on ferrous ions present in the tissue. The aim of this study was to investigate the susceptibility of cod muscle proteins in sarcoplasmic and myofibril fractions to in vitro metal-catalyzed oxidation and to point out protein candidates that might play a major role in the deterioration of fish quality. Extracted control proteins and proteins subjected to free radicals generated by Fe(II)/ascorbate mixture were labeled with fluorescein-5-thiosemicarbazide (FTSC) to tag carbonyl groups and separated by two-dimensional gel electrophoresis. Consecutive visualization of protein carbonyl levels by capturing the FTSC signal and total protein levels by capturing the SyproRuby staining signal allowed us to quantify the relative change in protein carbonyl levels corrected for changes in protein content. Proteins were identified using MALDI-TOF/TOF mass spectrometry and homology-based searches. The results show that freshly extracted cod muscle proteins exhibit a detectable carbonylation background and that the incubation with Fe(II)/ascorbate triggers a further oxidation of both sarcoplasmic and myofibril proteins. Different proteins exhibited various degrees of sensitivity to oxidation processes. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), nucleoside diphosphate kinase B (NDK), triosephosphate isomerase, phosphoglycerate mutase, lactate dehydrogenase, creatine kinase, and enolase were the sarcoplasmic proteins most vulnerable to ferrous-catalyzed oxidation. Moreover, NDK, phosphoglycerate mutase, and GAPDH were identified in several spots differing by their pI, and those forms showed different susceptibilities to metal-catalyzed oxidation, indicating that post-translational modifications may change the resistance of proteins to oxidative damage. The Fe(II)/ascorbate treatment significantly increased carbonylation of important structural proteins in fish muscle, mainly actin and myosin, and degradation products of those proteins were observed, some of them exhibiting increased carbonylation levels.

The influence of duckweed species diversity on ecophysiological tolerance to copper exposure.

PubMed

Zhao, Zhao; Shi, Huijuan; Duan, Dongzhu; Li, Hongmei; Lei, Tingwen; Wang, Maolin; Zhao, Hai; Zhao, Yun

2015-07-01

In excess, copper is toxic to plants. In the plants, Landoltia punctata and Lemna minor grown in mixed and monoculture, the effects of exposure to varying concentrations of copper (0.01, 0.1, 0.5 and 1mgL(-1) Cu) for seven days were assessed by measuring changes in the chlorophyll, protein and malondialdehyde (MDA) content, catalase (CAT), superoxide dismutase (SOD) and ascorbate peroxidase (APX) activity. According to results, Cu levels in plants increased with increasing Cu concentration. The level of photosynthetic pigments and crude proteins decreased only upon exposure to high Cu concentrations. However, the starch and malondialdehyde (MDA) content increased. These results suggested a stress alleviation that was possibly the result of antioxidants such as CAT and SOD, the activities of which increased with increasing Cu levels. APX activity increased in L. punctata, but decreased in L. minor, under monoculture or mixed culture conditions. In addition, the duckweed in mixed culture exhibited increased antioxidant enzyme activities which provide increased resistance to copper in moderate copper concentrations. As the copper concentration increased, the duckweed in the mixed culture limited the uptake of copper to avoid toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis, photophysical, and electrochemical properties of wide band gap tetraphenylsilane-carbazole derivatives: Effect of the substitution position and naphthalene side chain

NASA Astrophysics Data System (ADS)

Ho, Kar Wei; Ariffin, A.

2016-12-01

Four tetraphenylsilane-carbazole derivatives with wide bandgaps (3.38-3.55 eV) were synthesized. The effects of the substitution position and of the presence of naphthalene groups on the photophysical, electrochemical and thermal properties were investigated. The derivatives exhibited maximum absorption peaks ranging from 293 to 304 nm and maximum emission peaks ranging from 347 to 386 nm. Changing the carbazole substitution position on the tetraphenylsilane did not significantly change the photophysical and electrochemical properties. However, p-substituted compounds exhibited higher glass transition temperatures than m-substituted compounds. Naphthalene groups with bulky structures had extended the conjugation lengths that red-shifted both the absorption and emission spectra. The LUMO level was decreased, which reduced the optical bandgap and triplet energy level. However, the naphthalene groups significantly improved the thermal stability by increasing the glass transition temperature of the compounds.

Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice.

PubMed

Yamamoto, Kenta; Wang, Yunyue; Jiang, Wenxia; Liu, Xiangyu; Dubois, Richard L; Lin, Chyuan-Sheng; Ludwig, Thomas; Bakkenist, Christopher J; Zha, Shan

2012-08-06

Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic acid (DNA) damage responses by phosphorylating numerous substrates implicated in DNA repair and cell cycle checkpoint activation. A-T patients and mouse models that express no ATM protein undergo normal embryonic development but exhibit pleiotropic DNA repair defects. In this paper, we report that mice carrying homozygous kinase-dead mutations in Atm (Atm(KD/KD)) died during early embryonic development. Atm(KD/-) cells exhibited proliferation defects and genomic instability, especially chromatid breaks, at levels higher than Atm(-/-) cells. Despite this increased genomic instability, Atm(KD/-) lymphocytes progressed through variable, diversity, and joining recombination and immunoglobulin class switch recombination, two events requiring nonhomologous end joining, at levels comparable to Atm(-/-) lymphocytes. Together, these results reveal an essential function of ATM during embryogenesis and an important function of catalytically inactive ATM protein in DNA repair.

Seed-specific overexpression of an endogenous Arabidopsis phytoene synthase gene results in delayed germination and increased levels of carotenoids, chlorophyll, and abscisic acid.

PubMed

Lindgren, L Ove; Stålberg, Kjell G; Höglund, Anna-Stina

2003-06-01

Phytoene synthase catalyzes the dimerization of two molecules of geranylgeranyl pyrophosphate to phytoene and has been shown to be rate limiting for the synthesis of carotenoids. To elucidate if the capacity to produce phytoene is limiting also in the seed of Arabidopsis (Wassilewskija), a gene coding for an endogenous phytoene synthase was cloned and coupled to a seed-specific promoter, and the effects of the overexpression were examined. The resulting transgenic plants produced darker seeds, and extracts from the seed of five overexpressing plants had a 43-fold average increase of beta-carotene and a total average amount of beta-carotene of approximately 260 microg g-1 fresh weight. Lutein, violaxanthin, and chlorophyll were significantly increased, whereas the levels of zeaxanthin only increased by a factor 1.1. In addition, substantial levels of lycopene and alpha-carotene were produced in the seeds, whereas only trace amounts were found in the control plants. Seeds from the transgenic plants exhibited delayed germination, and the degree of delay was positively correlated with the increased levels of carotenoids. The abscisic acid levels followed the increase of the carotenoids, and plants having the highest carotenoid levels also had the highest abscisic acid content. Addition of gibberellic acid to the growth medium only partly restored germination of the transgenic seeds.

Human Mesenchymal Stem Cell Spheroids in Fibrin Hydrogels Exhibit Improved Cell Survival and Potential for Bone Healing

PubMed Central

Murphy, Kaitlin C.; Fang, Sophia Y.; Leach, J. Kent

2014-01-01

Mesenchymal stem cells (MSC) have great therapeutic potential for the repair of nonhealing bone defects due to their proliferative capacity, multilineage potential, trophic factor secretion, and lack of immunogenicity. However, a major barrier to the translation of cell-based therapies into clinical practice is ensuring their survival and function upon implantation into the defect site. We hypothesized that forming MSC into more physiologic 3-dimensional spheroids, rather than employing dissociated cells from 2-dimensional monolayer culture, would enhance their survival when exposed to a harsh microenvironment while maintaining their osteogenic potential. MSC spheroids were formed using the hanging drop method with increasing cell numbers. Compared to larger spheroids, the smallest spheroids which contained 15,000 cells exhibited increased metabolic activity, reduced apoptosis, and the most uniform distribution of proliferating cells. Spheroids were then entrapped in fibrin gels and cultured in serum-free media and 1% oxygen. Compared to identical numbers of dissociated MSC in fibrin gels, spheroids exhibited significantly reduced apoptosis and secreted up to 100-fold more VEGF. We also observed that fibrin gels containing spheroids and those containing an equivalent number of dissociated cells exhibited similar expression levels of early and late markers of osteogenic differentiation. These data demonstrate that MSC spheroids exhibit greater resistance to apoptosis and enhanced proangiogenic potential, while maintaining similar osteogenic potential to dissociated MSC entrapped in a clinically relevant biomaterial, supporting the use of MSC spheroids in cell-based approaches to bone repair. PMID:24781147

Quantitative proteomics reveals that peroxidases play key roles in post-flooding recovery in soybean roots.

PubMed

Khan, Mudassar Nawaz; Sakata, Katsumi; Hiraga, Susumu; Komatsu, Setsuko

2014-12-05

Soybean is an important legume crop that exhibits markedly reduced growth and yields under flooding conditions. To unravel the mechanisms involved in recovery after flooding in soybean root, gel-free proteomic analysis was performed. Morphological analysis revealed that growth suppression was more severe with increased flooding duration. Out of a total of 1645 and 1707 identified proteins, 73 and 21 proteins were changed significantly during the recovery stage following 2 and 4 days flooding, respectively. Based on the proteomic, clustering, and in silico protein-protein interaction analyses, six key enzymes were analyzed at the mRNA level. Lipoxygenase 1, which was increased at the protein level during the recovery period, was steadily down-regulated at the mRNA level. The peroxidase superfamily protein continuously increased in abundance during the course of recovery and was up-regulated at the mRNA level. HAD acid phosphatase was decreased at the protein level and down-regulated at the transcript level, while isoflavone reductase and an unknown protein were increased at both the protein and mRNA levels. Consistent with these findings, the enzymatic activity of peroxidase was decreased under flooding stress but increased significantly during the recovery sage. These results suggest that peroxidases might play key roles in post-flooding recovery in soybean roots through the scavenging of toxic radicals.

Patients with IgA nephropathy exhibit high systemic PDGF-DD levels.

PubMed

Boor, Peter; Eitner, Frank; Cohen, Clemens D; Lindenmeyer, Maja T; Mertens, Peter R; Ostendorf, Tammo; Floege, Jürgen

2009-09-01

Platelet-derived growth factor (PDGF) is a central mediator of mesangioproliferative glomerulonephritis (GN). In experimental mesangioproliferative GN, PDGF-DD serum levels, unlike PDGF-BB, increased up to 1000-fold. We assessed disease activity in 72 patients with GN, established a novel PDGF-D ELISA and then determined their PDGF-DD levels. In parallel, we studied renal PDGF-DD mRNA expression by RT-PCR. PDGF-DD serum levels in patients with IgA nephropathy (IgAN) were significantly higher (1.67 +/- 0.45 ng/ml) and in patients with lupus nephritis significantly lower (0.66 +/- 0.86 ng/ml) compared to healthy controls (1.17 +/- 0.46 ng/ml), while patients with focal segmental glomerulosclerosis, membranous GN and ANCA-positive vasculitis did not differ from controls. The subgroup of IgAN patients with elevated PDGF-DD levels (27% of samples) did not differ in their clinical features from those with normal PDGF-DD levels. In IgAN patients with repetitive PDGF-DD determinations, most exhibited only minor fluctuations of serum levels over time. Intrarenal PDGF-DD mRNA expression did not differ between controls and patients, suggesting an extrarenal source of the elevated PDGF-DD in IgAN. Serum PDGF-DD levels were specifically elevated in patients with IgAN, in particular in those with early disease, i.e. preserved renal function. Our data support the rationale for anti-PDGF-DD therapy in mesangioproliferative GN.

Sound Environments Surrounding Preterm Infants Within an Occupied Closed Incubator.

PubMed

Shimizu, Aya; Matsuo, Hiroya

2016-01-01

Preterm infants often exhibit functional disorders due to the stressful environment in the neonatal intensive care unit (NICU). The sound pressure level (SPL) in the NICU is often much higher than the levels recommended by the American Academy of Pediatrics. Our study aims to describe the SPL and sound frequency levels surrounding preterm infants within closed incubators that utilize high frequency oscillation (HFO) or nasal directional positive airway pressure (nasal-DPAP) respiratory settings. This is a descriptive research study of eight preterm infants (corrected age<33 weeks) exposed to the equipment when placed in an incubator. The actual noise levels were observed and the results were compared to the recommendations made by neonatal experts. Increased noise levels, which have reported to affect neonates' ability to self-regulate, could increase the risk of developing attention deficit disorder, and may result in tachycardia, bradycardia, increased intracranial pressure, and hypoxia. The care provider should closely assess for adverse effects of higher sound levels generated by different modes of respiratory support and take measures to ensure that preterm infants are protected from exposure to noise exceeding the optimal safe levels. Copyright © 2016 Elsevier Inc. All rights reserved.

Implications of multi-scale sea level and climate variability for coastal resources

USGS Publications Warehouse

Karamperidou, Christina; Engel, Victor; Lall, Upmanu; Stabenau, Erik; Smith, Thomas J.

2013-01-01

While secular changes in regional sea levels and their implications for coastal zone management have been studied extensively, less attention is being paid to natural fluctuations in sea levels, whose interaction with a higher mean level could have significant impacts on low-lying areas, such as wetlands. Here, the long record of sea level at Key West, FL is studied in terms of both the secular trend and the multi-scale sea level variations. This analysis is then used to explore implications for the Everglades National Park (ENP), which is recognized internationally for its ecological significance, and is the site of the largest wetland restoration project in the world. Very shallow topographic gradients (3–6 cm per km) make the region susceptible to small changes in sea level. Observations of surface water levels from a monitoring network within ENP exhibit both the long-term trends and the interannual-to-(multi)decadal variability that are observed in the Key West record. Water levels recorded at four long-term monitoring stations within ENP exhibit increasing trends approximately equal to or larger than the long-term trend at Key West. Time- and frequency-domain analyses highlight the potential influence of climate mechanisms, such as the El Niño/Southern Oscillation and the North Atlantic Oscillation (NAO), on Key West sea levels and marsh water levels, and the potential modulation of their influence by the background state of the North Atlantic Sea Surface Temperatures. In particular, the Key West sea levels are found to be positively correlated with the NAO index, while the two series exhibit high spectral power during the transition to a cold Atlantic Multidecadal Oscillation (AMO). The correlation between the Key West sea levels and the NINO3 Index reverses its sign in coincidence with a reversal of the AMO phase. Water levels in ENP are also influenced by precipitation and freshwater releases from the northern boundary of the Park. The analysis of both climate variability and climate change in such wetlands is needed to inform management practices in coastal wetland zones around the world.

Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells.

PubMed

Abraham, Nader G; Quan, Shuo; Mieyal, Paul A; Yang, Liming; Burke-Wolin, Theresa; Mingone, Christopher J; Goodman, Alvin I; Nasjletti, Alberto; Wolin, Michael S

2002-11-01

Carbon monoxide (CO) stimulates guanylate cyclase (GC) and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels. We transfected rat-lung pulmonary endothelial cells with a retrovirus-mediated human heme oxygenase (hHO)-1 gene. Pulmonary cells that expressed hHO-1 exhibited a fourfold increase in HO activity associated with decreases in the steady-state levels of heme and cGMP without changes in soluble GC (sGC) and endothelial nitric oxide synthase (NOS) proteins or basal nitrite production. Heme elicited significant increases in CO production and intracellular cGMP levels in both pulmonary endothelial and pulmonary hHO-1-expressing cells. N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly decreased cGMP levels in heme-treated pulmonary endothelial cells but not heme-treated hHO-1-expressing cells. In the presence of exogenous heme, CO and cGMP levels in hHO-1-expressing cells exceeded the corresponding levels in pulmonary endothelial cells. Acute exposure of endothelial cells to SnCl2, which is an inducer of HO-1, increased cGMP levels, whereas chronic exposure decreased heme and cGMP levels. These results indicate that prolonged overexpression of HO-1 ultimately decreases sGC activity by limiting the availability of cellular heme. Heme activates sGC and enhances cGMP levels via a mechanism that is largely insensitive to NOS inhibition.

Air-Sea Interaction in the Gulf of Tehuantepec

NASA Astrophysics Data System (ADS)

Khelif, D.; Friehe, C. A.; Melville, W. K.

2007-05-01

Measurements of meteorological fields and turbulence were made during gap wind events in the Gulf of Tehuantepec using the NSF C-130 aircraft. The flight patterns started at the shore and progressed to approximately 300km offshore with low-level (30m) tracks, stacks and soundings. Parameterizations of the wind stress, sensible and latent heat fluxes were obtained from approximately 700 5 km low-level tracks. Structure of the marine boundary layer as it evolved off-shore was obtained with stack patterns, aircraft soundings and deployment of dropsondes. The air-sea fluxes approximately follow previous parameterizations with some evidence of the drag coefficient leveling out at about 20 meters/sec with the latent heat flux slightly increasing. The boundary layer starts at shore as a gap wind low-level jet, thins as the jet expands out over the gulf, exhibits a hydraulic jump, and then increases due to turbulent mixing.

Osmoregulation in wild and captive West Indian manatees (Trichechus manatus).

PubMed

Ortiz, R M; Worthy, G A; MacKenzie, D S

1998-01-01

The ability of West Indian manatees (Trichechus manatus latirostris and Trichechus manatus manatus) to inhabit both freshwater and marine habitats presents an interesting model to study osmoregulation in sirenians. Blood samples were analyzed from manatees held in fresh- and saltwater and from wild animals captured in fresh-, brackish, and saltwater for concentrations of aldosterone, arginine vasopressin, plasma renin activity, Na+, K+, Cl-, and osmolality. Two separate experiments were also conducted on captive animals to evaluate osmoregulatory responses to acute saltwater exposure and freshwater deprivation. Spurious differences were observed in plasma electrolyte and osmolality among the captive and wild groups. Wild brackish water animals exhibited the highest vasopressin concentrations, while wild freshwater manatees had the highest aldosterone levels. A significant correlation between mean vasopressin and osmolality was demonstrated for captive and wild animals. When freshwater animals were acutely exposed to saltwater, osmolality, Na+, and Cl- increased 5.5%, 8.0%, and 14%, respectively, while aldosterone decreased 82.6%. Saltwater animals deprived of freshwater exhibited an almost twofold increase in aldosterone during the deprivation period and a fourfold decrease when freshwater was again provided. Within this group, osmolality increased significantly by 3.4% over the course of the study; however, electrolytes did not change. The lack of consistent differences in electrolyte and osmolality among wild and captive groups suggests that manatees are good osmoregulators regardless of the environment. The high aldosterone levels in wild freshwater animals may indicate a need to conserve Na+, while the high vasopressin levels in wild brackish-water manatees suggest an antidiuretic state to conserve water. Vasopressin levels appear to be osmotically mediated in manatees as in other mammals.

Transiently enhanced LPS-induced fever following hyperthermic stress in rabbits

NASA Astrophysics Data System (ADS)

Shibata, Masaaki; Uno, Tadashi; Riedel, Walter; Nishimaki, Michiyo; Watanabe, Kaori

2005-11-01

Hyperthermia has been shown to induce an enhanced febrile response to the bacterial-derived endotoxin lipopolysaccharide (LPS). The aim of the present study was to test the hypothesis that the enhanced LPS-induced fever seen in heat stressed (HS) animals is caused by leakage of intestinal bacterial LPS into the circulation. Male rabbits were rendered transiently hyperthermic (a maximum rectal temperature of 43°C) and divided into three groups. They were then allowed to recover in a room at 24°C for 1, 2 or 3 days post-HS. One day after injection with LPS, the post-HS rabbits exhibited significantly higher fevers than the controls, though this was not seen in rabbits at either 2 or 3 days post-HS. The plasma levels of endogenous LPS were significantly increased during the HS as compared to those seen in normothermic rabbits prior to HS. LPS fevers were not induced in these animals. One day post-HS, rabbits that had been pretreated with oral antibiotics exhibited significantly attenuated LPS levels. When challenged with human recombinant interleukin-1β instead of LPS, the 1-day post-HS rabbits did not respond with enhanced fevers. The plasma levels of TNFα increased similarly during LPS-induced fevers in both the control and 1-day post-HS rabbits, while the plasma levels of corticosterone and the osmolality of the 1-day post-HS rabbits showed no significant differences to those seen prior to the HS. These results suggest that the enhanced fever in the 1-day post-HS rabbits is LPS specific, and may be caused by increased leakage of intestinal endotoxin into blood circulation.

A NAP-AAO3 Regulatory Module Promotes Chlorophyll Degradation via ABA Biosynthesis in Arabidopsis Leaves[W][OPEN

PubMed Central

Yang, Jiading; Worley, Eric

2014-01-01

Chlorophyll degradation is an important part of leaf senescence, but the underlying regulatory mechanisms are largely unknown. Excised leaves of an Arabidopsis thaliana NAC-LIKE, ACTIVATED BY AP3/PI (NAP) transcription factor mutant (nap) exhibited lower transcript levels of known chlorophyll degradation genes, STAY-GREEN1 (SGR1), NON-YELLOW COLORING1 (NYC1), PHEOPHYTINASE (PPH), and PHEIDE a OXYGENASE (PaO), and higher chlorophyll retention than the wild type during dark-induced senescence. Transcriptome coexpression analysis revealed that abscisic acid (ABA) metabolism/signaling genes were disproportionately represented among those positively correlated with NAP expression. ABA levels were abnormally low in nap leaves during extended darkness. The ABA biosynthetic genes 9-CIS-EPOXYCAROTENOID DIOXYGENASE2, ABA DEFICIENT3, and ABSCISIC ALDEHYDE OXIDASE3 (AAO3) exhibited abnormally low transcript levels in dark-treated nap leaves. NAP transactivated the promoter of AAO3 in mesophyll cell protoplasts, and electrophoretic mobility shift assays showed that NAP can bind directly to a segment (−196 to −162 relative to the ATG start codon) of the AAO3 promoter. Exogenous application of ABA increased the transcript levels of SGR1, NYC1, PPH, and PaO and suppressed the stay-green phenotype of nap leaves during extended darkness. Overexpression of AAO3 in nap leaves also suppressed the stay-green phenotype under extended darkness. Collectively, the results show that NAP promotes chlorophyll degradation by enhancing transcription of AAO3, which leads to increased levels of the senescence-inducing hormone ABA. PMID:25516602

Effects of nitrate on metamorphosis, thyroid and iodothyronine deiodinases expression in Bufo gargarizans larvae.

PubMed

Wang, Ming; Chai, Lihong; Zhao, Hongfeng; Wu, Minyao; Wang, Hongyuan

2015-11-01

Chinese toad (Bufo gargarizans) tadpoles were exposed to nitrate (10, 50 and 100mg/L NO3-N) from the beginning of the larval period through metamorphic climax. We examined the effects of chronic nitrate exposure on metamorphosis, mortality, body size and thyroid gland. In addition, thyroid hormone (TH) levels, type II iodothyronine deiodinase (Dio2) and type III iodothyronine deiodinase (Dio3) mRNA levels were also measured to assess disruption of TH synthesis. Results showed that significant metamorphic delay and mortality increased were caused in larvae exposed to 100mg/L NO3-N. The larvae exposed to 100mg/L NO3-N clearly exhibited a greater reduction in thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels. Moreover, treatment with NO3-N induced down-regulation of Dio2 mRNA levels and up-regulation of Dio3 mRNA levels, reflecting the disruption of thyroid endocrine. It seems that increased mass and body size may be correlated with prolonged metamorphosis. Interestingly, we observed an exception that exposure to 100mg/L NO3-N did not exhibit remarkable alterations of thyroid gland size. Compared with control groups, 100mg/L NO3-N caused partial colloid depletion in the thyroid gland follicles. These results suggest that nitrate can act as a chemical stressor inducing retardation in development and metamorphosis. Therefore, we concluded that the presence of high concentrations nitrate can influence the growth, decline the survival, impair TH synthesis and induce metamorphosis retardation of B. gargarizans larvae. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neural correlates of stress- and food cue-induced food craving in obesity: association with insulin levels.

PubMed

Jastreboff, Ania M; Sinha, Rajita; Lacadie, Cheryl; Small, Dana M; Sherwin, Robert S; Potenza, Marc N

2013-02-01

Obesity is associated with alterations in corticolimbic-striatal brain regions involved in food motivation and reward. Stress and the presence of food cues may each motivate eating and engage corticolimibic-striatal neurocircuitry. It is unknown how these factors interact to influence brain responses and whether these interactions are influenced by obesity, insulin levels, and insulin sensitivity. We hypothesized that obese individuals would show greater responses in corticolimbic-striatal neurocircuitry after exposure to stress and food cues and that brain activations would correlate with subjective food craving, insulin levels, and HOMA-IR. Fasting insulin levels were assessed in obese and lean subjects who were exposed to individualized stress and favorite-food cues during functional MRI. Obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food and stress cues. In obese but not lean individuals, food craving, insulin, and HOMA-IR levels correlated positively with neural activity in corticolimbic-striatal brain regions during favorite-food and stress cues. The relationship between insulin resistance and food craving in obese individuals was mediated by activity in motivation-reward regions including the striatum, insula, and thalamus. These findings demonstrate that obese, but not lean, individuals exhibit increased corticolimbic-striatal activation in response to favorite-food and stress cues and that these brain responses mediate the relationship between HOMA-IR and food craving. Improving insulin sensitivity and in turn reducing corticolimbic-striatal reactivity to food cues and stress may diminish food craving and affect eating behavior in obesity.

Flame Structure and Emissions of Strongly-Pulsed Turbulent Diffusion Flames with Swirl

NASA Astrophysics Data System (ADS)

Liao, Ying-Hao

This work studies the turbulent flame structure, the reaction-zone structure and the exhaust emissions of strongly-pulsed, non-premixed flames with co-flow swirl. The fuel injection is controlled by strongly-pulsing the fuel flow by a fast-response solenoid valve such that the fuel flow is completely shut off between pulses. This control strategy allows the fuel injection to be controlled over a wide range of operating conditions, allowing the flame structure to range from isolated fully-modulated puffs to interacting puffs to steady flames. The swirl level is controlled by varying the ratio of the volumetric flow rate of the tangential air to that of the axial air. For strongly-pulsed flames, both with and without swirl, the flame geometry is strongly impacted by the injection time. Flames appear to exhibit compact, puff-like structures for short injection times, while elongated flames, similar in behaviors to steady flames, occur for long injection times. The flames with swirl are found to be shorter for the same fuel injection conditions. The separation/interaction level between flame puffs in these flames is essentially governed by the jet-off time. The separation between flame puffs decreases as swirl is imposed, consistent with the decrease in flame puff celerity due to swirl. The decreased flame length and flame puff celerity are consistent with an increased rate of air entrainment due to swirl. The highest levels of CO emissions are generally found for compact, isolated flame puffs, consistent with the rapid quenching due to rapid dilution with excess air. The imposition of swirl generally results in a decrease in CO levels, suggesting more rapid and complete fuel/air mixing by imposing swirl in the co-flow stream. The levels of NO emissions for most cases are generally below the steady-flame value. The NO levels become comparable to the steady-flame value for sufficiently short jet-off time. The swirled co-flow air can, in some cases, increase the NO emissions. The elevated NO emissions are due to a longer combustion residence time due to the flow recirculation within the swirl-induced recirculation zone. The reaction zone structure, based on OH planar laser-induced fluorescence (PLIF) is broadly consistent with the observation of luminous flame structure for these types of flames. In many cases, the reaction zone exhibits discontinuities at the instantaneous flame tip in the early period of fuel injection. These discontinuities in the reaction zone likely result from the non-ignition of injected fuel, due to a relatively slower reaction rate in comparison with the mixing rate. The discontinuity in the OH zone is generally seen to diminish with increased swirl level. Statistics generated from the OH PLIF signals show that the reaction zone area generally increases with increased swirl level, consistent with a broader and more convoluted OH-zone structure for flames with swirl. The reaction zone area for swirled flames generally exhibits a higher degree of fluctuation, suggesting a relatively stronger impact of flow turbulence on the flame structure for flames with swirl.

Levels of BDNF Impact Oligodendrocyte Lineage Cells Following a Cuprizone Lesion

PubMed Central

VonDran, Melissa W.; Singh, Harmandeep; Honeywell, Jean Z.; Dreyfus, Cheryl F.

2011-01-01

Previous work in culture has shown that basal forebrain (BF) oligodendrocyte (OLG) lineage cells respond to BDNF by increasing DNA synthesis and differentiation. Further, in the BF in vivo, reduced levels of BDNF as seen in BDNF +/− mice result in reduced numbers of NG2+ cells and deficits in myelin proteins throughout development and in the adult, suggesting that BDNF impacts the proliferating population of OLGs as well as differentiation in vivo. In this study, to investigate roles BDNF may play in the repair of a demyelinating lesion, the cuprizone model was used and the corpus callosum was examined. BDNF protein levels were reduced after cuprizone, suggesting that the demyelinating lesion, itself, elicits a decrease in BDNF. To analyze effects of a further reduction of BDNF on OLG lineage cells following cuprizone, BDNF +/− mice were evaluated. These mice exhibited a blunted increase in the NG2 response at 4 and 5 weeks of cuprizone. In addition, BDNF +/− mice exhibited decreased levels of myelin proteins during the demyelination and remyelination processes with no change in the total number of OLGs. These effects appear to be relatively specific to OLG lineage cells as comparable changes in CD11b+ microglia, GFAP+ astrocytes, and SMI32+ injured axons were not observed. These data indicate that BDNF may play a role following a demyelinating lesion, by regulating numbers of progenitors and the abilities of demyelinating and differentiating cells to express myelin proteins. PMID:21976503

Is there a signal of sea-level rise in Chesapeake Bay salinity?

NASA Astrophysics Data System (ADS)

Hilton, T. W.; Najjar, R. G.; Zhong, L.; Li, M.

2008-09-01

We evaluate the hypothesis that sea-level rise over the second half of the 20th century has led to detectable increases in Chesapeake Bay salinity. We exploit a simple, statistical model that predicts monthly mean salinity as a function of Susquehanna River flow in 23 segments of the main stem Chesapeake Bay. The residual (observed minus modeled) salinity exhibits statistically significant linear (p < 0.05) trends between 1949 and 2006 in 13 of the 23 segments of the bay. The salinity change estimated from the trend line over this period varies from -2.0 to 2.2, with 10 of the 13 cells showing positive changes. The mean and median salinity changes over all 23 cells are 0.47 and 0.72; over the 13 cells with significant trends they are 0.71 and 1.1. We ran a hydrodynamic model of the bay under present-day and reduced sea level conditions and found a bay-average salinity increase of about 0.5, which supports the hypothesis that the salinity residual trends have a significant component due to sea-level rise. Uncertainties remain, however, due to the spatial and temporal extent of historical salinity data and the infilling of the bay due to sedimentation. The salinity residuals also exhibit interannual variability, with peaks occurring at intervals of roughly 7 to 9 years, which are partially explained by Atlantic Shelf salinity, Potomac River flow and the meridional component of wind stress.

Inherent variations in CO-H2S-mediated carotid body O2 sensing mediate hypertension and pulmonary edema

PubMed Central

Peng, Ying-Jie; Makarenko, Vladislav V.; Nanduri, Jayasri; Vasavda, Chirag; Raghuraman, Gayatri; Yuan, Guoxiang; Gadalla, Moataz M.; Kumar, Ganesh K.; Snyder, Solomon H.; Prabhakar, Nanduri R.

2014-01-01

Oxygen (O2) sensing by the carotid body and its chemosensory reflex is critical for homeostatic regulation of breathing and blood pressure. Humans and animals exhibit substantial interindividual variation in this chemosensory reflex response, with profound effects on cardiorespiratory functions. However, the underlying mechanisms are not known. Here, we report that inherent variations in carotid body O2 sensing by carbon monoxide (CO)-sensitive hydrogen sulfide (H2S) signaling contribute to reflex variation in three genetically distinct rat strains. Compared with Sprague-Dawley (SD) rats, Brown-Norway (BN) rats exhibit impaired carotid body O2 sensing and develop pulmonary edema as a consequence of poor ventilatory adaptation to hypobaric hypoxia. Spontaneous Hypertensive (SH) rat carotid bodies display inherent hypersensitivity to hypoxia and develop hypertension. BN rat carotid bodies have naturally higher CO and lower H2S levels than SD rat, whereas SH carotid bodies have reduced CO and greater H2S generation. Higher CO levels in BN rats were associated with higher substrate affinity of the enzyme heme oxygenase 2, whereas SH rats present lower substrate affinity and, thus, reduced CO generation. Reducing CO levels in BN rat carotid bodies increased H2S generation, restoring O2 sensing and preventing hypoxia-induced pulmonary edema. Increasing CO levels in SH carotid bodies reduced H2S generation, preventing hypersensitivity to hypoxia and controlling hypertension in SH rats. PMID:24395806

Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats.

PubMed

Zaitone, Sawsan A; Abo-Elmatty, Dina M; Elshazly, Shimaa M

2012-01-01

To evaluate the neuroprotective effect of the nootropic drugs, piracetam (PIR) and vinpocetine (VIN), in rotenone-induced Parkinsonism in rats. Sixty male rats were divided into 6 groups of 10 rats each. The groups were administered vehicle, control (rotenone, 1.5 mg/kg/48 h/6 doses, s.c.), PIR (100 and 200 mg/kg/day, p.o.) and VIN (3 and 6 mg/kg/day, p.o.). The motor performance of the rats was evaluated by the open field and pole test. Striatal dopamine level, malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor-α (TNF-α) were assayed. Histopathological study of the substantia nigra was also done. Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field test. In addition, GSH level was decreased whereas MDA and TNF-α increased in striata of rotenone-treated rats as compared to vehicle-treated rats. Marked degeneration of the substantia nigra pars compacta (SNpc) neurons and depletion of striatal dopamine was also observed in the rotenone-treated rats. Treatment with PIR or VIN significantly reversed the locomotor deficits and increased striatal dopamine level. Treatment with VIN significantly (P<0.05) reduced the striatal level of MDA and GSH in comparison to rotenone group whereas TNF-α production was found to be significantly decreased in PIR group (P<0.05). VIN and PIR exhibit neuroprotective activity in rotenone-induced Parkinsonism. Hence, these nootropic agents may be considered as possible candidates in the treatment of Parkinson's disease.

Change in Maternal Criticism and Behavior Problems in Adolescents and Adults with Autism Across a Seven-Year Period

PubMed Central

Baker, Jason K.; Smith, Leann E.; Greenberg, Jan S.; Seltzer, Marsha Mailick; Taylor, Julie Lounds

2010-01-01

In a previous study from our laboratory, high levels of maternal criticism predicted increased behavior problems in adolescents and adults with autism spectrum disorders (ASD) over an 18-month period (Greenberg, Seltzer, Hong, & Orsmond, 2006). The current investigation followed these families over a period of seven years to examine the longitudinal course of criticism and behavior problems, to assess the association between their trajectories, and to determine the degree to which change in each of these factors predicted levels of criticism and behavior problems at the end of the study period. A sample of 118 mothers co-residing with their adolescents and adults with ASD provided open-ended narratives about their children and reported on the children's behavior problems at four waves. Maternal criticism was derived from expressed emotion ratings of the narratives. Criticism exhibited low but significant stability over the seven year period and behavior problems exhibited high stability. Using latent growth curve modeling, (a) criticism was found to have increased over time, but only for the group of families in which the sons or daughters transitioned from high school services during the study period, (b) individual changes in criticism and behavior problems were positively correlated over the seven-year period, and (c) changes in criticism predicted levels of behavior problems at the conclusion of the study. Changes in behavior problems were not predictive of end levels of criticism. Implications for intervention and prevention efforts are discussed. PMID:21319925

Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels.

PubMed Central

Rubin, B S; Murray, M K; Damassa, D A; King, J C; Soto, A M

2001-01-01

The nonsteroidal estrogenic compound bisphenol A (BPA) is a monomer used in the manufacture of polycarbonate plastics and resins. BPA may be ingested by humans as it reportedly leaches from the lining of tin cans into foods, from dental sealants into saliva, and from polycarbonate bottles into their contents. Because BPA is weakly estrogenic--approximately 10,000-fold less potent than 17beta-estradiol--current environmental exposure levels have been considered orders of magnitude below the dose required for adverse effects on health. Herein we demonstrate measurable effects on the offspring of Sprague-Dawley female rats that were exposed, via their drinking water, to approximately 0.1 mg BPA/kg body weight (bw)/day (low dose) or 1.2 mg BPA/kg bw/day (high dose) from day 6 of pregnancy through the period of lactation. Offspring exposed to BPA exhibited an increase in body weight that was apparent soon after birth and continued into adulthood. In addition, female offspring exposed perinatally to the high dose of BPA exhibited altered patterns of estrous cyclicity and decreased levels of plasma luteinizing hormone (LH) in adulthood. Administration of neither the doses of BPA that caused effects during perinatal exposure nor a 10-fold higher dose was able to evoke a uterotropic response in ovariectomized postpubertal females. These data indicate an increased sensitivity to BPA during the perinatal period and suggest the need for careful evaluation of the current levels of exposure to this compound. PMID:11485865

Glucose ingestion stimulates atherothrombotic inflammation in polycystic ovary syndrome

PubMed Central

Kirwan, John P.; Rote, Neal S.; Minium, Judi

2013-01-01

Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation that can increase the risk of atherothrombosis. We performed a cross-sectional study to examine the effect of glucose ingestion on markers of atherothrombotic inflammation in mononuclear cells (MNC) of 16 women with PCOS (8 lean, 8 obese) and 16 weight-matched controls. Activator protein-1 (AP-1) activation and the protein content of early growth response-1 (EGR-1), matrix matalloproteinases-2 (MMP2), and tissue factor (TF) were quantified from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Plasma MMP9 and C-reactive protein (CRP) were measured from fasting blood samples. Truncal fat was determined by DEXA. Lean women with PCOS exhibited greater AP-1 activation and MMP2 protein content after glucose ingestion and higher plasma MMP9 and CRP levels than lean controls. Obese women with PCOS exhibited greater EGR-1 and TF protein content after glucose ingestion, and plasma CRP levels were even higher compared with lean subjects regardless of PCOS status. Truncal fat correlated with MMP9 and CRP levels and glucose-stimulated increases in AP-1 activation and EGR-1 and TF protein content. Testosterone correlated with glucose-stimulated AP-1 activation, and androstenedione correlated with MMP9 and CRP levels and glucose-stimulated AP-1 activation. Thus, both PCOS and obesity contribute to an atherothrombotic state in which excess abdominal adiposity and hyperandrogenism may be specific risk factors for developing atherothrombosis. PMID:23249695

Mutation of the Glucosinolate Biosynthesis Enzyme Cytochrome P450 83A1 Monooxygenase Increases Camalexin Accumulation and Powdery Mildew Resistance.

PubMed

Liu, Simu; Bartnikas, Lisa M; Volko, Sigrid M; Ausubel, Frederick M; Tang, Dingzhong

2016-01-01

Small secondary metabolites, including glucosinolates and the major phytoalexin camalexin, play important roles in immunity in Arabidopsis thaliana. We isolated an Arabidopsis mutant with increased resistance to the powdery mildew fungus Golovinomyces cichoracearum and identified a mutation in the gene encoding cytochrome P450 83A1 monooxygenase (CYP83A1), which functions in glucosinolate biosynthesis. The cyp83a1-3 mutant exhibited enhanced defense responses to G. cichoracearum and double mutant analysis showed that this enhanced resistance requires NPR1, EDS1, and PAD4, but not SID2 or EDS5. In cyp83a1-3 mutants, the expression of genes related to camalexin synthesis increased upon G. cichoracearum infection. Significantly, the cyp83a1-3 mutant also accumulated higher levels of camalexin. Decreasing camalexin levels by mutation of the camalexin synthetase gene PAD3 or the camalexin synthesis regulator AtWRKY33 compromised the powdery mildew resistance in these mutants. Consistent with these observations, overexpression of PAD3 increased camalexin levels and enhanced resistance to G. cichoracearum. Taken together, our data indicate that accumulation of higher levels of camalexin contributes to increased resistance to powdery mildew.

Mutation of the Glucosinolate Biosynthesis Enzyme Cytochrome P450 83A1 Monooxygenase Increases Camalexin Accumulation and Powdery Mildew Resistance

PubMed Central

Liu, Simu; Bartnikas, Lisa M.; Volko, Sigrid M.; Ausubel, Frederick M.; Tang, Dingzhong

2016-01-01

Small secondary metabolites, including glucosinolates and the major phytoalexin camalexin, play important roles in immunity in Arabidopsis thaliana. We isolated an Arabidopsis mutant with increased resistance to the powdery mildew fungus Golovinomyces cichoracearum and identified a mutation in the gene encoding cytochrome P450 83A1 monooxygenase (CYP83A1), which functions in glucosinolate biosynthesis. The cyp83a1-3 mutant exhibited enhanced defense responses to G. cichoracearum and double mutant analysis showed that this enhanced resistance requires NPR1, EDS1, and PAD4, but not SID2 or EDS5. In cyp83a1-3 mutants, the expression of genes related to camalexin synthesis increased upon G. cichoracearum infection. Significantly, the cyp83a1-3 mutant also accumulated higher levels of camalexin. Decreasing camalexin levels by mutation of the camalexin synthetase gene PAD3 or the camalexin synthesis regulator AtWRKY33 compromised the powdery mildew resistance in these mutants. Consistent with these observations, overexpression of PAD3 increased camalexin levels and enhanced resistance to G. cichoracearum. Taken together, our data indicate that accumulation of higher levels of camalexin contributes to increased resistance to powdery mildew. PMID:26973671

Prolonged whole body immersion in cold water: hormonal and metabolic changes.

PubMed

Smith, D J; Deuster, P A; Ryan, C J; Doubt, T J

1990-03-01

To characterize metabolic and hormonal responses during prolonged whole body immersion, 16 divers wearing dry suits completed four immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 meters of sea water. One immersion began in the AM (1000 h) and one began in the PM (2200 h) to evaluate diurnal variations. Venous blood samples were obtained before and after completion of each immersion. Cortisol and ACTH levels demonstrated diurnal variation, with larger increases occurring after PM immersions. A greater than three-fold postimmersion increase occurred in norepinephrine (NE). There were significant increases in triiodothyronine (T3) uptake and epinephrine, but no change in T3, thyroxine, thyrotrophic hormone, and dopamine. Postimmersion free fatty acid levels increased 409% from preimmersion levels; glucose levels declined, and lactate increased significantly. Only changes in NE correlated significantly with changes in rectal temperature. In summary, when subjects are immersed in cold water for prolonged periods, with a slow rate of body cooling afforded by thermal protection and intermittent exercise, hormonal and metabolic changes occur that are similar in direction and magnitude to short-duration unprotected exposures. Except for cortisol and ACTH, none of the other measured variables exhibited diurnal alterations.

CD8+ recent thymic emigrants exhibit increased responses to low affinity ligands and improved access to peripheral sites of inflammation

PubMed Central

Berkley, Amy M.; Fink, Pamela J.

2014-01-01

To explore the TCR sensitivity of recent thymic emigrants (RTEs), we triggered T cells with altered peptide ligands (APLs). Upon peptide stimulation in vitro, RTEs exhibited increased TCR signal transduction, and following infection in vivo with APL-expressing bacteria, CD8 RTEs expanded to a greater extent in response to low affinity antigens than their mature T cell counterparts. RTEs skewed to short-lived effector cells in response to all APLs but were also characterized by diminished cytokine production. RTEs responding to infection expressed increased levels of VLA-4, with consequent improved entry into inflamed tissue and pathogen clearance. These positive outcomes were offset by the capacity of RTEs to elicit autoimmunity. Overall, salient features of CD8 RTE biology should inform strategies to improve neonatal vaccination and therapies for cancer and HIV, as RTEs make up a large proportion of the T cells in lymphodepleted environments. PMID:25172492

Cutting edge: CD8+ recent thymic emigrants exhibit increased responses to low-affinity ligands and improved access to peripheral sites of inflammation.

PubMed

Berkley, Amy M; Fink, Pamela J

2014-10-01

To explore the TCR sensitivity of recent thymic emigrants (RTEs), we triggered T cells with altered peptide ligands (APLs). Upon peptide stimulation in vitro, RTEs exhibited increased TCR signal transduction, and following infection in vivo with APL-expressing bacteria, CD8 RTEs expanded to a greater extent in response to low-affinity Ags than did their mature T cell counterparts. RTEs skewed to short-lived effector cells in response to all APLs but also were characterized by diminished cytokine production. RTEs responding to infection expressed increased levels of VLA-4, with consequent improved entry into inflamed tissue and pathogen clearance. These positive outcomes were offset by the capacity of RTEs to elicit autoimmunity. Overall, salient features of CD8 RTE biology should inform strategies to improve neonatal vaccination and therapies for cancer and HIV, because RTEs make up a large proportion of the T cells in lymphodepleted environments. Copyright © 2014 by The American Association of Immunologists, Inc.

Cybersickness without the wobble: Experimental results speak against postural instability theory.

PubMed

Dennison, Mark Stephen; D'Zmura, Michael

2017-01-01

It has been suggested that postural instability is necessary for cybersickness to occur. Seated and standing subjects used a head-mounted display to view a virtual tunnel that rotated about their line of sight. We found that the offset direction of perceived vertical settings matched the direction of the tunnel's rotation, so replicating earlier findings. Increasing rotation speed caused cybersickness to increase, but had no significant impact on perceived vertical settings. Postural sway during rotation was similar to postural sway during rest. While a minority of subjects exhibited postural sway in response to the onset of tunnel rotation, the majority did not. Furthermore, cybersickness increased with rotation speed similarly for the seated and standing conditions. Finally, subjects with greater levels of cybersickness exhibited less variation in postural sway. These results lead us to conclude that the link between postural instability and cybersickness is a weak one in the present experiment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Isolated Effect of Geometry on Mitral Valve Function for In-Silico Model Development

PubMed Central

Siefert, Andrew William; Rabbah, Jean-Pierre Michel; Saikrishnan, Neelakantan; Kunzelman, Karyn Susanne; Yoganathan, Ajit Prithivaraj

2013-01-01

Computational models for the heart’s mitral valve (MV) exhibit several uncertainties which may be reduced by further developing these models using ground-truth data sets. The present study generated a ground-truth data set by quantifying the effects of isolated mitral annular flattening, symmetric annular dilatation, symmetric papillary muscle displacement, and asymmetric papillary muscle displacement on leaflet coaptation, mitral regurgitation (MR), and anterior leaflet strain. MVs were mounted in an in vitro left heart simulator and tested under pulsatile hemodynamics. Mitral leaflet coaptation length, coaptation depth, tenting area, MR volume, MR jet direction, and anterior leaflet strain in the radial and circumferential directions were successfully quantified for increasing levels of geometric distortion. From these data, increasing levels of isolated papillary muscle displacement resulted in the greatest mean change in coaptation depth (70% increase), tenting area (150% increase), and radial leaflet strain (37% increase) while annular dilatation resulted in the largest mean change in coaptation length (50% decrease) and regurgitation volume (134% increase). Regurgitant jets were centrally located for symmetric annular dilatation and symmetric papillary muscle displacement. Asymmetric papillary muscle displacement resulted in asymmetrically directed jets. Peak changes in anterior leaflet strain in the circumferential direction were smaller and exhibited non-significant differences across the tested conditions. When used together, this ground-truth data may be used to parametrically evaluate and develop modeling assumptions for both the MV leaflets and subvalvular apparatus. This novel data may improve MV computational models and provide a platform for the development of future surgical planning tools. PMID:24059354

Delayed expression of SAGs correlates with longevity in CMS wheat plants compared to its fertile plants.

PubMed

Semwal, Vimal Kumar; Singh, Bhupinder; Khanna-Chopra, Renu

2014-04-01

Reproductive sinks regulate monocarpic senescence in crop plants. Monocarpic senescence was studied in wheat fertile (cv. HW 2041) and its isonuclear cytoplasmic male sterile (CMS) line. CMS plants exhibited slower rate of senescence accompanied by longer green leaf area duration and slower deceleration in chlorophyll, protein content, PN and rubisco content coupled with lower protease activities than fertile (F) plants. CMS plants also exhibited lower ROS levels and less membrane damage than F plants. CMS plants maintained better antioxidant defense, less oxidative damage in chloroplast and higher transcript levels of both rbcL and rbcS genes during senescence than F plants. F plants exhibited early induction and higher expression of SAGs like serine and cysteine proteases, glutamine synthetases GS1 and GS2, WRKY53 transcription factor and decline in transcript levels of CAT1 and CAT2 genes than CMS plants. Hence, using genetically fertile and its CMS line of wheat it is confirmed that delayed senescence in the absence of reproductive sinks is linked with slower protein oxidation, rubisco degradation and delayed activation of SAGs. Better antioxidant defense in chloroplasts at later stages of senescence was able to mitigate the deleterious effects of ROS in CMS plants. We propose that delayed increase in ROS in cytoplasmic male sterile wheat plants resulted in delayed activation of WRKY53, SAGs and the associated biochemical changes than fertile plants.

Peer review and competition in the Art Exhibition Game

PubMed Central

Goldstone, Robert L.; Helbing, Dirk

2016-01-01

To investigate the effect of competitive incentives under peer review, we designed a novel experimental setup called the Art Exhibition Game. We present experimental evidence of how competition introduces both positive and negative effects when creative artifacts are evaluated and selected by peer review. Competition proved to be a double-edged sword: on the one hand, it fosters innovation and product diversity, but on the other hand, it also leads to more unfair reviews and to a lower level of agreement between reviewers. Moreover, an external validation of the quality of peer reviews during the laboratory experiment, based on 23,627 online evaluations on Amazon Mechanical Turk, shows that competition does not significantly increase the level of creativity. Furthermore, the higher rejection rate under competitive conditions does not improve the average quality of published contributions, because more high-quality work is also rejected. Overall, our results could explain why many ground-breaking studies in science end up in lower-tier journals. Differences and similarities between the Art Exhibition Game and scholarly peer review are discussed and the implications for the design of new incentive systems for scientists are explained. PMID:27402744

Pleiotropic effects of interleukin-6 in a "two-hit" murine model of acute respiratory distress syndrome.

PubMed

Goldman, Julia L; Sammani, Saad; Kempf, Carrie; Saadat, Laleh; Letsiou, Eleftheria; Wang, Ting; Moreno-Vinasco, Liliana; Rizzo, Alicia N; Fortman, Jeffrey D; Garcia, Joe G N

2014-06-01

Patients with acute respiratory distress syndrome (ARDS) exhibit elevated levels of interleukin-6 (IL-6), which correlate with increased morbidity and mortality. The exact role of IL-6 in ARDS has proven difficult to study because it exhibits either pro- or anti-inflammatory actions in mouse models of lung injury, depending on the model utilized. In order to improve understanding of the role of this complex cytokine in ARDS, we evaluated IL-6 using the clinically relevant combination of lipopolysaccharide (LPS) and ventilator-induced lung injury (VILI) in IL-6(-/-) mice. Bronchoalveolar lavage fluid (BAL), whole-lung tissue, and histology were evaluated for inflammatory markers of injury. Transendothelial electrical resistance was used to evaluate the action of IL-6 on endothelial cells in vitro. In wild-type mice, the combination model showed a significant increase in lung injury compared to either LPS or VILI alone. IL-6(-/-) mice exhibited a statistically significant decrease in BAL cellular inflammation as well as lower histologic scores for lung injury, changes observed only in the combination model. A paradoxical increase in BAL total protein was observed in IL-6(-/-) mice exposed to LPS, suggesting that IL-6 provides protection from vascular leakage. However, in vitro data showed that IL-6, when combined with its soluble receptor, actually caused a significant increase in endothelial cell permeability, suggesting that the protection seen in vivo was likely due to complex interactions of IL-6 and other inflammatory mediators rather than to direct effects of IL-6. These studies suggest that a dual-injury model exhibits utility in evaluating the pleiotropic effects of IL-6 in ARDS on inflammatory cells and lung endothelium.

Individuals with Asperger's Disorder Exhibit Difficulty in Switching Attention from a Local Level to a Global Level

ERIC Educational Resources Information Center

Katagiri, Masatoshi; Kasai, Tetsuko; Kamio, Yoko; Murohashi, Harumitsu

2013-01-01

The purpose of the present study was to determine whether individuals with Asperger's disorder exhibit difficulty in switching attention from a local level to a global level. Eleven participants with Asperger's disorder and 11 age- and gender-matched healthy controls performed a level-repetition switching task using Navon-type hierarchical…

Increased serum bicarbonate in critically ill patients: a retrospective analysis.

PubMed

Libório, Alexandre Braga; Noritomi, Danilo Teixeira; Leite, Tacyano Tavares; de Melo Bezerra, Candice Torres; de Faria, Evandro Rodrigues; Kellum, John A

2015-03-01

Although metabolic alkalosis is a common occurrence, no study has evaluated its prevalence, associated factors or outcomes in critically ill patients. This is a retrospective study from the Multiparameter Intelligent Monitoring in Intensive Care II database. From 23,529 adult patient records, 18,982 patients met the inclusion criteria. Serum bicarbonate levels demonstrated a U-shaped association with mortality with knots at 25 and 30 mEq/l. Of the total included patients, 5,565 (29.3 %) had at least one serum bicarbonate level measurement >30 mEq/l. The majority were exposed to multiple factors that are classically associated with metabolic alkalosis (mainly diuretic use, hypernatremia, hypokalemia and high gastric output). Patients with increased serum bicarbonate exhibited increased ICU LOS, more days on mechanical ventilation and higher hospital mortality. After multivariate adjustment, each 5-mEq/l increment in the serum bicarbonate level above 30 mEq/l was associated with an odds ratio of 1.21 for hospital mortality. The association between increased serum bicarbonate levels and mortality occurs independently of its possible etiologies. An increased serum bicarbonate level is common in critically ill patients; this can be attributed to multiple factors in the majority of cases, and its presence and duration negatively influence patient outcomes.

Promotion of chloroplast proliferation upon enhanced post-mitotic cell expansion in leaves.

PubMed

Kawade, Kensuke; Horiguchi, Gorou; Ishikawa, Naoko; Hirai, Masami Yokota; Tsukaya, Hirokazu

2013-09-28

Leaves are determinate organs; hence, precise control of cell proliferation and post-mitotic cell expansion is essential for their growth. A defect in cell proliferation often triggers enhanced post-mitotic cell expansion in leaves. This phenomenon is referred to as 'compensation'. Several lines of evidence from studies on compensation have shown that cell proliferation and post-mitotic cell expansion are coordinately regulated during leaf development. Therefore, compensation has attracted much attention to the mechanisms for leaf growth. However, our understanding of compensation at the subcellular level remains limited because studies of compensation have focused mainly on cellular-level phenotypes. Proper leaf growth requires quantitative control of subcellular components in association with cellular-level changes. To gain insight into the subcellular aspect of compensation, we investigated the well-known relationship between cell area and chloroplast number per cell in compensation-exhibiting lines, and asked whether chloroplast proliferation is modulated in response to the induction of compensation. We first established a convenient and reliable method for observation of chloroplasts in situ. Using this method, we analyzed Arabidopsis thaliana mutants fugu5 and angustifolia3 (an3), and a transgenic line KIP-RELATED PROTEIN2 overexpressor (KRP2 OE), which are known to exhibit typical features of compensation. We here showed that chloroplast number per cell increased in the subepidermal palisade tissue of these lines. We analyzed tetraploidized wild type, fugu5, an3 and KRP2 OE, and found that cell area itself, but not nuclear ploidy, is a key parameter that determines the activity of chloroplast proliferation. In particular, in the case of an3, we uncovered that promotion of chloroplast proliferation depends on the enhanced post-mitotic cell expansion. The expression levels of chloroplast proliferation-related genes are similar to or lower than that in the wild type during this process. This study demonstrates that chloroplast proliferation is promoted in compensation-exhibiting lines. This promotion of chloroplast proliferation takes place in response to cell-area increase in post-mitotic phase in an3. The expression of chloroplast proliferation-related genes were not promoted in compensation-exhibiting lines including an3, arguing that an as-yet-unknown mechanism is responsible for modulation of chloroplast proliferation in these lines.

Promotion of chloroplast proliferation upon enhanced post-mitotic cell expansion in leaves

PubMed Central

2013-01-01

Background Leaves are determinate organs; hence, precise control of cell proliferation and post-mitotic cell expansion is essential for their growth. A defect in cell proliferation often triggers enhanced post-mitotic cell expansion in leaves. This phenomenon is referred to as ‘compensation’. Several lines of evidence from studies on compensation have shown that cell proliferation and post-mitotic cell expansion are coordinately regulated during leaf development. Therefore, compensation has attracted much attention to the mechanisms for leaf growth. However, our understanding of compensation at the subcellular level remains limited because studies of compensation have focused mainly on cellular-level phenotypes. Proper leaf growth requires quantitative control of subcellular components in association with cellular-level changes. To gain insight into the subcellular aspect of compensation, we investigated the well-known relationship between cell area and chloroplast number per cell in compensation-exhibiting lines, and asked whether chloroplast proliferation is modulated in response to the induction of compensation. Results We first established a convenient and reliable method for observation of chloroplasts in situ. Using this method, we analyzed Arabidopsis thaliana mutants fugu5 and angustifolia3 (an3), and a transgenic line KIP-RELATED PROTEIN2 overexpressor (KRP2 OE), which are known to exhibit typical features of compensation. We here showed that chloroplast number per cell increased in the subepidermal palisade tissue of these lines. We analyzed tetraploidized wild type, fugu5, an3 and KRP2 OE, and found that cell area itself, but not nuclear ploidy, is a key parameter that determines the activity of chloroplast proliferation. In particular, in the case of an3, we uncovered that promotion of chloroplast proliferation depends on the enhanced post-mitotic cell expansion. The expression levels of chloroplast proliferation-related genes are similar to or lower than that in the wild type during this process. Conclusions This study demonstrates that chloroplast proliferation is promoted in compensation-exhibiting lines. This promotion of chloroplast proliferation takes place in response to cell-area increase in post-mitotic phase in an3. The expression of chloroplast proliferation-related genes were not promoted in compensation-exhibiting lines including an3, arguing that an as-yet-unknown mechanism is responsible for modulation of chloroplast proliferation in these lines. PMID:24074400

Hormetic efficacy of rutin to promote longevity in Drosophila melanogaster.

PubMed

Chattopadhyay, Debarati; Chitnis, Atith; Talekar, Aishwarya; Mulay, Prajakta; Makkar, Manyata; James, Joel; Thirumurugan, Kavitha

2017-06-01

Hormetins are compounds that mediate hormesis by being beneficial at low doses but detrimental at high doses. Recent studies have highlighted that many compounds that extended lifespan in model organisms did so by mediating hormesis. Rutin is a glycosylate conjugate of quercetin and rutinose and is abundant in citrus fruits and buckwheat seeds. Rutin possess ROS scavenging, anti-cancer, cardio-protective, skin-regenerative and neuro-protective properties. Drosophila melanogaster is an attractive model organism for longevity studies owing to its homology of organ and cellular-pathways with mammals. In this study, we aimed to understand the effect of rutin on extending longevity in Drosophila melanogaster. Male and female flies were administered with a range of rutin doses (100-800 µM) to analyse whether rutin mediated lifespan-extension by hormesis. Effect of rutin on physiological parameters like food intake, fecundity, climbing activity, development and resistance to various stresses was also studied. Lifespan assays showed that rutin at 200 and 400 µM significantly extended median lifespan in both male and female flies beyond which flies exhibited drastically reduced longevity. Increase in survival at 400 µM was associated with reduced food intake and fecundity. Flies exhibited improved climbing capability with both 200 and 400 µM rutin. Flies fed with 100 and 200 µM rutin exhibited enhanced survival upon exposure to oxidative stress with 400 µM rutin exhibiting no improvement in median lifespan following oxidative stress. Analysis of endogenous peroxide upon treatment with rutin (100-400 µM) with or without 5% H 2 O 2 showed elevated levels of endogenous peroxide with 400 µM rutin whereas no increase in hydrogen peroxide level was observed with rutin at 100 and 200 µM. Finally, gene expression studies in male flies revealed that rutin treatment at 200 and/or 400 µM elevated transcript levels of dFoxO, MnSod, Cat, dTsc1, dTsc2, Thor, dAtg1, dAtg5 and dAtg7 and reduced transcript levels of dTor. Collectively, rutin at 200 and 400 µM improved longevity in flies; 200 µM rutin acted as a mild stressor to prolong lifespan in flies by mediating hormesis whereas 400 µM, being a high dose for best positive effects.

Decreased Prostaglandin D2 Levels in Major Depressive Disorder Are Associated with Depression-Like Behaviors.

PubMed

Chu, Cuilin; Wei, Hui; Zhu, Wanwan; Shen, Yan; Xu, Qi

2017-09-01

Prostaglandin (PG) D2 is the most abundant prostaglandin in the mammalian brain. The physiological and pharmacological actions of PGD2 in the central nervous system seem to be associated with some of the symptoms exhibited by patients with major depressive disorder. Previous studies have found that PGD2 synthase was decreased in the cerebrospinal fluid of major depressive disorder patients. We speculated that there may be a dysregulation of PGD2 levels in major depressive disorder. Ultra-performance liquid chromatography-tandem mass spectrometry coupled with a stable isotopic-labeled internal standard was used to determine PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice. A total of 32 drug-free major depressive disorder patients and 30 healthy controls were recruited. An animal model of depression was constructed by exposing mice to 5 weeks of chronic unpredictable mild stress. To explore the role of PGD2 in major depressive disorder, selenium tetrachloride was administered to simulate the change in PGD2 levels in mice. Mice exposed to chronic unpredictable mild stress exhibited depression-like behaviors, as indicated by reduced sucrose preference and increased immobility time in the forced swimming test. PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice were both decreased compared with their corresponding controls. Further inhibiting PGD2 production in mice resulted in an increased immobility time in the forced swimming test that could be reversed by imipramine. Decreased PGD2 levels in major depressive disorder are associated with depression-like behaviors. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Resting cortisol level, self-concept, and putative familial environment in adolescents at ultra high-risk for psychotic disorders

PubMed Central

Carol, Emily E.; Mittal, Vijay A.

2015-01-01

Summary A growing body of evidence suggests that resting cortisol levels are elevated in patients with schizophrenia and closely tied to symptom severity. However, there is limited research on the biological stress system during the ultra high-risk (UHR) period immediately preceding the onset of psychosis, and cortisol has not been examined in relation to individual characteristics such as self-concept or potential stressors such as putative familial environment in this critical population. In the present study, salivary cortisol samples were collected on 37 UHR and 42 matched control adolescents, and these individuals were assessed with clinical interviews as well as a measure of self-concept. For a subsection of the sample (23 UHR and 20 control adolescents), a participating relative/caretaker was also assessed with an expressed emotion interview designed to gauge psychosocial environment. Consistent with previous studies, UHR participants exhibited elevated resting cortisol levels when compared with controls. In addition, UHR adolescents exhibited increased negative self-concept and their relatives/caretakers endorsed significantly fewer initial positive statements about the participant. Interestingly, a strong trend in the UHR group suggests that higher cortisol levels are associated with higher rates of critical statements from relatives/caretakers. Furthermore, elevated cortisol levels in the participants were associated with increased negative self-concept as well as fewer initial positive comments from relatives/caretakers. Results suggest that hypothalamic-pituitary-adrenal axis (HPA) dysfunction is closely associated with both individual and environmental-level characteristics. Taken together, these findings support a neural diathesis-stress model of psychosis and future studies, designed to examine causal relationships, stand to inform both our understanding of pathogenic processes in the high-risk period as well as early intervention efforts. PMID:25880698

Decreased Prostaglandin D2 Levels in Major Depressive Disorder Are Associated with Depression-Like Behaviors

PubMed Central

Chu, Cuilin; Wei, Hui; Zhu, Wanwan; Shen, Yan

2017-01-01

Abstract Background Prostaglandin (PG) D2 is the most abundant prostaglandin in the mammalian brain. The physiological and pharmacological actions of PGD2 in the central nervous system seem to be associated with some of the symptoms exhibited by patients with major depressive disorder. Previous studies have found that PGD2 synthase was decreased in the cerebrospinal fluid of major depressive disorder patients. We speculated that there may be a dysregulation of PGD2 levels in major depressive disorder. Methods Ultra-performance liquid chromatography-tandem mass spectrometry coupled with a stable isotopic-labeled internal standard was used to determine PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice. A total of 32 drug-free major depressive disorder patients and 30 healthy controls were recruited. An animal model of depression was constructed by exposing mice to 5 weeks of chronic unpredictable mild stress. To explore the role of PGD2 in major depressive disorder, selenium tetrachloride was administered to simulate the change in PGD2 levels in mice. Results Mice exposed to chronic unpredictable mild stress exhibited depression-like behaviors, as indicated by reduced sucrose preference and increased immobility time in the forced swimming test. PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice were both decreased compared with their corresponding controls. Further inhibiting PGD2 production in mice resulted in an increased immobility time in the forced swimming test that could be reversed by imipramine. Conclusion Decreased PGD2 levels in major depressive disorder are associated with depression-like behaviors. PMID:28582515

Expression and function of Kv1.1 potassium channels in human atria from patients with atrial fibrillation.

PubMed

Glasscock, Edward; Voigt, Niels; McCauley, Mark D; Sun, Qiang; Li, Na; Chiang, David Y; Zhou, Xiao-Bo; Molina, Cristina E; Thomas, Dierk; Schmidt, Constanze; Skapura, Darlene G; Noebels, Jeffrey L; Dobrev, Dobromir; Wehrens, Xander H T

2015-09-01

Voltage-gated Kv1.1 channels encoded by the Kcna1 gene are traditionally regarded as being neural-specific with no known expression or intrinsic functional role in the heart. However, recent studies in mice reveal low-level Kv1.1 expression in heart and cardiac abnormalities associated with Kv1.1-deficiency suggesting that the channel may have a previously unrecognized cardiac role. Therefore, this study tests the hypothesis that Kv1.1 channels are associated with arrhythmogenesis and contribute to intrinsic cardiac function. In intra-atrial burst pacing experiments, Kcna1-null mice exhibited increased susceptibility to atrial fibrillation (AF). The atria of Kcna1-null mice showed minimal Kv1 family ion channel remodeling and fibrosis as measured by qRT-PCR and Masson's trichrome histology, respectively. Using RT-PCR, immunocytochemistry, and immunoblotting, KCNA1 mRNA and protein were detected in isolated mouse cardiomyocytes and human atria for the first time. Patients with chronic AF (cAF) showed no changes in KCNA1 mRNA levels relative to controls; however, they exhibited increases in atrial Kv1.1 protein levels, not seen in paroxysmal AF patients. Patch-clamp recordings of isolated human atrial myocytes revealed significant dendrotoxin-K (DTX-K)-sensitive outward current components that were significantly increased in cAF patients, reflecting a contribution by Kv1.1 channels. The concomitant increases in Kv1.1 protein and DTX-K-sensitive currents in atria of cAF patients suggest that the channel contributes to the pathological mechanisms of persistent AF. These findings provide evidence of an intrinsic cardiac role of Kv1.1 channels and indicate that they may contribute to atrial repolarization and AF susceptibility.

Expression and function of Kv1.1 potassium channels in human atria from patients with atrial fibrillation

PubMed Central

Glasscock, Edward; Voigt, Niels; McCauley, Mark D.; Sun, Qiang; Li, Na; Chiang, David Y.; Zhou, Xiao-Bo; Molina, Cristina E.; Thomas, Dierk; Schmidt, Constanze; Skapura, Darlene G.; Noebels, Jeffrey L.; Dobrev, Dobromir; Wehrens, Xander H. T.

2016-01-01

Voltage-gated Kv1.1 channels encoded by the Kcna1 gene are traditionally regarded as being neural-specific with no known expression or intrinsic functional role in the heart. However, recent studies in mice reveal low-level Kv1.1 expression in heart and cardiac abnormalities associated with Kv1.1-deficiency suggesting that the channel may have a previously unrecognized cardiac role. Therefore, this study tests the hypothesis that Kv1.1 channels are associated with arrhythmogenesis and contribute to intrinsic cardiac function. In intra-atrial burst pacing experiments, Kcna1-null mice exhibited increased susceptibility to atrial fibrillation (AF). The atria of Kcna1-null mice showed minimal Kv1 family ion channel remodeling and fibrosis as measured by qRT-PCR and Masson’s trichrome histology, respectively. Using RT-PCR, immunocytochemistry, and immunoblotting, KCNA1 mRNA and protein were detected in isolated mouse cardiomyocytes and human atria for the first time. Patients with chronic AF (cAF) showed no changes in KCNA1 mRNA levels relative to controls; however, they exhibited increases in atrial Kv1.1 protein levels, not seen in paroxysmal AF patients. Patch-clamp recordings of isolated human atrial myocytes revealed significant dendrotoxin-K (DTX-K)-sensitive outward current components that were significantly increased in cAF patients, reflecting a contribution by Kv1.1 channels. The concomitant increases in Kv1.1 protein and DTX-K-sensitive currents in atria of cAF patients suggest that the channel contributes to the pathological mechanisms of persistent AF. These findings provide evidence of an intrinsic cardiac role of Kv1.1 channels and indicate that they may contribute to atrial repolarization and AF susceptibility. PMID:26162324

Analysis of surface EMG spike shape across different levels of isometric force.

PubMed

Gabriel, David A; Lester, Steven M; Lenhardt, Sean A; Cambridge, Edward D J

2007-01-15

This research evaluated changes in surface electromyographic (SEMG) spike shape across different levels of isometric force. Ninety-six subjects generated three 5-s isometric step contractions of the elbow flexors at 40, 60, 80, and 100% of maximal voluntary contraction (MVC). Force and bipolar SEMG activity were monitored concurrently. The mean spike amplitude (MSA) exhibited a linear increase across the four levels of force. The mean spike frequency (MSF) remained stable from 40 to 80% of MVC; it then decreased from 80 to 100% of MVC. There was a concomitant increase in mean spike slope (MSS) that indicates that the biceps brachii (BB) relied on the recruitment of higher threshold motor units (MUs) from 40 to 80% of MVC. However, there progressive decrease in the mean number of peaks per spike (MNPPS) that suggests that MU synchronization was additionally required to increase force from 80 to 100% of MVC. The spike shape measures, taken together, indicate that the decrease in frequency content of the signal was due to synchronization, not an increased probability of temporal overlap due an increase in rate-coding.

Cyclic fluctuations of water level as a basis for determining aquifer transmissibility

USGS Publications Warehouse

Ferris, John G.

1952-01-01

In coastal areas, wells near bodies of tidal water frequently exhibit sinusoidal fluctuations of water level, in response to periodic changes of tidewater stage.  Inland, the regulation of a surface reservoir often produces correlative changes of ground-water stage in wells adjacent either to the reservoir or to its attendant stream.  As the stage of the surface water rises, the head upon the subaqueous outcrop of the aquifer increases and thereby either increases the rate of inflow to the aquifer or reduces the rate of outflow therefrom.  The increase in recharge or reduction in discharge results in a general recovery of water level in the aquifer. On the subsequent falling stage this pattern is reversed.  When the stage of the surface body fluctuates as a simple harmonic motion a train of sinusoidal waves is propagated shoreward through the sub-outcrop of the aquifer.  With increasing distance from the sub-outcrop, the amplitude of the transmitted wave decreases and the time lag of a given maximum or minimum increases.

Analysis of high-frequency energy in long-term average spectra of singing, speech, and voiceless fricatives

PubMed Central

Monson, Brian B.; Lotto, Andrew J.; Story, Brad H.

2012-01-01

The human singing and speech spectrum includes energy above 5 kHz. To begin an in-depth exploration of this high-frequency energy (HFE), a database of anechoic high-fidelity recordings of singers and talkers was created and analyzed. Third-octave band analysis from the long-term average spectra showed that production level (soft vs normal vs loud), production mode (singing vs speech), and phoneme (for voiceless fricatives) all significantly affected HFE characteristics. Specifically, increased production level caused an increase in absolute HFE level, but a decrease in relative HFE level. Singing exhibited higher levels of HFE than speech in the soft and normal conditions, but not in the loud condition. Third-octave band levels distinguished phoneme class of voiceless fricatives. Female HFE levels were significantly greater than male levels only above 11 kHz. This information is pertinent to various areas of acoustics, including vocal tract modeling, voice synthesis, augmentative hearing technology (hearing aids and cochlear implants), and training/therapy for singing and speech. PMID:22978902

Delineation of gravel-bed clusters via factorial kriging

NASA Astrophysics Data System (ADS)

Wu, Fu-Chun; Wang, Chi-Kuei; Huang, Guo-Hao

2018-05-01

Gravel-bed clusters are the most prevalent microforms that affect local flows and sediment transport. A growing consensus is that the practice of cluster delineation should be based primarily on bed topography rather than grain sizes. Here we present a novel approach for cluster delineation using patch-scale high-resolution digital elevation models (DEMs). We use a geostatistical interpolation method, i.e., factorial kriging, to decompose the short- and long-range (grain- and microform-scale) DEMs. The required parameters are determined directly from the scales of the nested variograms. The short-range DEM exhibits a flat bed topography, yet individual grains are sharply outlined, making the short-range DEM a useful aid for grain segmentation. The long-range DEM exhibits a smoother topography than the original full DEM, yet groupings of particles emerge as small-scale bedforms, making the contour percentile levels of the long-range DEM a useful tool for cluster identification. Individual clusters are delineated using the segmented grains and identified clusters via a range of contour percentile levels. Our results reveal that the density and total area of delineated clusters decrease with increasing contour percentile level, while the mean grain size of clusters and average size of anchor clast (i.e., the largest particle in a cluster) increase with the contour percentile level. These results support the interpretation that larger particles group as clusters and protrude higher above the bed than other smaller grains. A striking feature of the delineated clusters is that anchor clasts are invariably greater than the D90 of the grain sizes even though a threshold anchor size was not adopted herein. The average areal fractal dimensions (Hausdorff-Besicovich dimensions of the projected areas) of individual clusters, however, demonstrate that clusters delineated with different contour percentile levels exhibit similar planform morphologies. Comparisons with a compilation of existing field data show consistency with the cluster properties documented in a wide variety of settings. This study thus points toward a promising, alternative DEM-based approach to characterizing sediment structures in gravel-bed rivers.

4-containing GABA receptors at the hippocampal CA1 spines is a biomarker for resilience to food restriction-evoked excessive exercise and weight loss of adolescent female rats

PubMed Central

Aoki, Chiye; Wable, Gauri; Chowdhury, Tara G.; Sabaliauskas, Nicole A.; Laurino, Kevin; Barbarich-Marsteller, Nicole C.

2014-01-01

Anorexia nervosa (AN) is a psychiatric illness characterized by restricted eating and an intense fear of gaining weight. Most individuals with AN are females, diagnosed first during adolescence, 40% to 80% of whom exhibit excessive exercise, and an equally high number with a history of anxiety disorder. We sought to determine the cellular basis for individual differences in AN vulnerability by using an animal model, activity-based anorexia (ABA), that is induced by combining food restriction (FR) with access to a running wheel that allows voluntary exercise. Previously, we showed that by the 4th day of FR, the ABA group of adolescent female rats exhibit > 500% greater levels of non-synaptic α4βδ−GABAARs at the plasma membrane of hippocampal CA1 pyramidal cell spines, relative to the levels found in age-matched controls that are not FR and without wheel access. Here, we show that the ABA group exhibits individual differences in body weight loss, with some losing nearly 30%, while others lose only 15%. The individual differences in weight loss are ascribable to individual differences in wheel activity that both precedes and concurs with days of FR. Moreover, the increase in activity during FR correlates strongly and negatively with α4βδ−GABAAR levels (R= - 0.9, p<0.01). This negative correlation is evident within 2 days of FR, before body weight loss approaches life-threatening levels for any individual. These findings suggest that increased shunting inhibition by α4βδ−GABAARs in spines of CA1 pyramidal neurons may participate in the protection against the ABA-inducing environmental factors of severe weight loss by suppressing excitability of the CA1 pyramidal neurons which, in turn, is related indirectly to suppression of excessive exercise. The data also indicate that, although exercise has many health benefits, it can be maladaptive to individuals with low levels of α4βδ−GABAARs in the CA1, particularly when combined with FR. PMID:24444828

Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels

PubMed Central

Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B.; Dong, Xiao; Wang, Hongjun

2015-01-01

Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

Original Research: Potential of urinary nephrin as a biomarker reflecting podocyte dysfunction in various kidney disease models

PubMed Central

Wada, Yusuke; Moritani, Hiroshi; Mitori, Hikaru; Kondo, Mitsuhiro; Tanaka-Amino, Keiko; Eguchi, Megumi; Imasato, Akira; Inoki, Yutaka; Kajiyama, Hiroshi; Mimura, Toshihide; Tomura, Yuichi

2016-01-01

Urinary nephrin is a potential non-invasive biomarker of disease. To date, however, most studies of urinary nephrin have been conducted in animal models of diabetic nephropathy, and correlations between urinary nephrin-to-creatinine ratio and other parameters have yet to be evaluated in animal models or patients of kidney disease with podocyte dysfunction. We hypothesized that urinary nephrin-to-creatinine ratio can be up-regulated and is negatively correlated with renal nephrin mRNA levels in animal models of kidney disease, and that increased urinary nephrin-to-creatinine ratio levels are attenuated following administration of glucocorticoids. In the present study, renal nephrin mRNA, urinary nephrin-to-creatinine ratio, urinary protein-to-creatinine ratio, and creatinine clearance ratio were measured in animal models of adriamycin nephropathy, puromycin aminonucleoside nephropathy, anti-glomerular basement membrane glomerulonephritis, and 5/6 nephrectomy. The effects of prednisolone on urinary nephrin-to-creatinine ratio and other parameters in puromycin aminonucleoside (single injection) nephropathy rats were also investigated. In all models tested, urinary nephrin-to-creatinine ratio and urinary protein-to-creatinine ratio increased, while renal nephrin mRNA and creatinine clearance ratio decreased. Urinary nephrin-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA in almost all models, as well as a significant positive correlation with urinary protein-to-creatinine ratio and a significant negative correlation with creatinine clearance ratio. Urinary protein-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA. Following the administration of prednisolone to puromycin aminonucleoside (single injection) nephropathy rats, urinary nephrin-to-creatinine ratio was significantly suppressed and exhibited a significant positive correlation with urinary protein-to-creatinine ratio. In addition, the decrease in number of glomerular Wilms tumor antigen-1-positive cells was attenuated, and urinary nephrin-to-creatinine ratio exhibited a significant negative correlation in these cells. In conclusion, these results suggest that urinary nephrin-to-creatinine ratio level is a useful and reliable biomarker for predicting the amelioration of podocyte dysfunction by candidate drugs in various kidney disease models with podocyte dysfunction. This suggestion will also be validated in a clinical setting in future studies. PMID:27216597

Getting the Balance Right: The Challenge of Balancing Praise and Correction for Early School Years Children Who Exhibit Oppositional and Defiant Behaviour

ERIC Educational Resources Information Center

Fields, Barry

2012-01-01

Increasingly, early childhood practitioners are faced with children who present with significant levels of oppositional and defiant behaviour. The management of this behaviour is often difficult and stressful. Efforts to minimise disruptive behaviour and to encourage more prosocial behaviour have very much revolved around the teaching of…

Contrasting neural effects of aging on proactive and reactive response inhibition.

PubMed

Bloemendaal, Mirjam; Zandbelt, Bram; Wegman, Joost; van de Rest, Ondine; Cools, Roshan; Aarts, Esther

2016-10-01

Two distinct forms of response inhibition may underlie observed deficits in response inhibition in aging. We assessed whether age-related neurocognitive impairments in response inhibition reflect deficient reactive inhibition (outright stopping) or also deficient proactive inhibition (anticipatory response slowing), which might be particularly evident with high information load. We used functional magnetic resonance imaging in young (n = 25, age range 18-32) and older adults (n = 23, 61-74) with a stop-signal task. Relative to young adults, older adults exhibited impaired reactive inhibition (i.e., longer stop-signal reaction time) and increased blood oxygen level-dependent (BOLD) signal for successful versus unsuccessful inhibition in the left frontal cortex and cerebellum. Furthermore, older adults also exhibited impaired proactive slowing, but only as a function of information load. This load-dependent behavioral deficit was accompanied by a failure to increase blood oxygen level-dependent (BOLD) signal under high information load in lateral frontal cortex, presupplementary motor area and striatum. Our findings suggest that inhibitory deficits in older adults are caused both by reduced stopping abilities and by diminished preparation capacity during information overload. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of obesity on acute hemostatic responses to live-fire training drills.

PubMed

Smith, Denise L; Horn, Gavin P; Petruzzello, Steven J; Freund, Gregory G; Woods, Jeffrey A; Cook, Marc D; Goldstein, Eric; Fernhall, Bo

2014-12-01

The objective of this study was to evaluate the impact of obesity and firefighting activities on coagulation and fibrinolytic activity in relatively young, apparently healthy firefighters. Firefighters performed simulated firefighting activities for 18 minutes in a live-fire training structure. Blood samples were obtained at baseline, before firefighting, and within a few minutes of completing the activity. Nearly all markers of coagulation and fibrinolytic activity increased immediately after firefighting with an overall shift toward a procoagulatory profile. Obese firefighters exhibited lower levels of tissue plasminogen activator activity (0.98 vs 0.63 IU/ml) and higher levels of plasminogen activator inhibitor-1 activity (2.2 vs 4.5 ng/ml) at baseline compared with normal-weight firefighters, suggesting that fibrinolytic activity was lower in obese firefighters. There were few interactions between body mass index and firefighting activity, thus our findings suggest that obese firefighters did not exhibit a greater procoagulatory response to live firefighting compared with normal-weight firefighters. Acute live firefighting produced increases in both fibrinolytic and coagulatory responses; although obesity was associated with a reduced fibrinolytic profile at baseline, the changes produced by acute firefighting were similar in obese and nonobese firefighters. Copyright © 2014 Elsevier Inc. All rights reserved.

Interleukin-33 modulates inflammation in endometriosis.

PubMed

Miller, Jessica E; Monsanto, Stephany P; Ahn, Soo Hyun; Khalaj, Kasra; Fazleabas, Asgerally T; Young, Steven L; Lessey, Bruce A; Koti, Madhuri; Tayade, Chandrakant

2017-12-20

Endometriosis is a debilitating condition that is categorized by the abnormal growth of endometrial tissue outside the uterus. Although the pathogenesis of this disease remains unknown, it is well established that endometriosis patients exhibit immune dysfunction. Interleukin (IL)-33 is a danger signal that is a critical regulator of chronic inflammation. Although plasma and peritoneal fluid levels of IL-33 have been associated with deep infiltrating endometriosis, its contribution to the disease pathophysiology is unknown. We investigated the role of IL-33 in the pathology of endometriosis using patient samples, cell lines and a syngeneic mouse model. We found that endometriotic lesions produce significantly higher levels of IL-33 compared to the endometrium of healthy, fertile controls. In vitro stimulation of endometrial epithelial, endothelial and endometriotic epithelial cells with IL-33 led to the production of pro-inflammatory and angiogenic cytokines. In a syngeneic mouse model of endometriosis, IL-33 injections caused systemic inflammation, which manifested as an increase in plasma pro-inflammatory cytokines compared to control mice. Furthermore, endometriotic lesions from IL-33 treated mice were highly vascularized and exhibited increased proliferation. Collectively, we provide convincing evidence that IL-33 perpetuates inflammation, angiogenesis and lesion proliferation, which are critical events in the lesion survival and progression of endometriosis.

Modeling and Simulation of Linear and Nonlinear MEMS Scale Electromagnetic Energy Harvesters for Random Vibration Environments

PubMed Central

Sassani, Farrokh

2014-01-01

The simulation results for electromagnetic energy harvesters (EMEHs) under broad band stationary Gaussian random excitations indicate the importance of both a high transformation factor and a high mechanical quality factor to achieve favourable mean power, mean square load voltage, and output spectral density. The optimum load is different for random vibrations and for sinusoidal vibration. Reducing the total damping ratio under band-limited random excitation yields a higher mean square load voltage. Reduced bandwidth resulting from decreased mechanical damping can be compensated by increasing the electrical damping (transformation factor) leading to a higher mean square load voltage and power. Nonlinear EMEHs with a Duffing spring and with linear plus cubic damping are modeled using the method of statistical linearization. These nonlinear EMEHs exhibit approximately linear behaviour under low levels of broadband stationary Gaussian random vibration; however, at higher levels of such excitation the central (resonant) frequency of the spectral density of the output voltage shifts due to the increased nonlinear stiffness and the bandwidth broadens slightly. Nonlinear EMEHs exhibit lower maximum output voltage and central frequency of the spectral density with nonlinear damping compared to linear damping. Stronger nonlinear damping yields broader bandwidths at stable resonant frequency. PMID:24605063

FABP4 attenuates PPARγ and adipogenesis and is inversely correlated with PPARγ in adipose tissues.

PubMed

Garin-Shkolnik, Tali; Rudich, Assaf; Hotamisligil, Gökhan S; Rubinstein, Menachem

2014-03-01

Fatty acid binding protein 4 (FABP4, also known as aP2) is a cytoplasmic fatty acid chaperone expressed primarily in adipocytes and myeloid cells and implicated in the development of insulin resistance and atherosclerosis. Here we demonstrate that FABP4 triggers the ubiquitination and subsequent proteasomal degradation of peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis and insulin responsiveness. Importantly, FABP4-null mouse preadipocytes as well as macrophages exhibited increased expression of PPARγ, and complementation of FABP4 in the macrophages reversed the increase in FABP4 expression. The FABP4-null preadipocytes exhibited a remarkably enhanced adipogenesis compared with wild-type cells, indicating that FABP4 regulates adipogenesis by downregulating PPARγ. We found that the FABP4 level was higher and PPARγ level was lower in human visceral fat and mouse epididymal fat compared with their subcutaneous fat. Furthermore, FABP4 was higher in the adipose tissues of obese diabetic individuals compared with healthy ones. Suppression of PPARγ by FABP4 in visceral fat may explain the reported role of FABP4 in the development of obesity-related morbidities, including insulin resistance, diabetes, and atherosclerosis.

PPARγ and MyoD are differentially regulated by myostatin in adipose-derived stem cells and muscle satellite cells

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

Zhang, Feng; Deng, Bing; Wen, Jianghui

2015-03-06

Myostatin (MSTN) is a secreted protein belonging to the transforming growth factor-β (TGF-β) family that is primarily expressed in skeletal muscle and also functions in adipocyte maturation. Studies have shown that MSTN can inhibit adipogenesis in muscle satellite cells (MSCs) but not in adipose-derived stem cells (ADSCs). However, the mechanism by which MSTN differently regulates adipogenesis in these two cell types remains unknown. Peroxisome proliferator-activated receptor-γ (PPARγ) and myogenic differentiation factor (MyoD) are two key transcription factors in fat and muscle cell development that influence adipogenesis. To investigate whether MSTN differentially regulates PPARγ and MyoD, we analyzed PPARγ and MyoDmore » expression by assessing mRNA, protein and methylation levels in ADSCs and MSCs after treatment with 100 ng/mL MSTN for 0, 24, and 48 h. PPARγ mRNA levels were downregulated after 24 h and upregulated after 48 h of treatment in ADSCs, whereas in MSCs, PPARγ levels were downregulated at both time points. MyoD expression was significantly increased in ADSCs and decreased in MSCs. PPARγ and MyoD protein levels were upregulated in ADSCs and downregulated in MSCs. The CpG methylation levels of the PPARγ and MyoD promoters were decreased in ADSCs and increased in MSCs. Therefore, this study demonstrated that the different regulatory adipogenic roles of MSTN in ADSCs and MSCs act by differentially regulating PPARγ and MyoD expression. - Highlights: • PPARγ and MyoD mRNA and protein levels are upregulated by myostatin in ADSCs. • PPARγ and MyoD mRNA and protein levels are downregulated by myostatin in MSCs. • PPARγ exhibited different methylation levels in myostatin-treated ADSCs and MSCs. • MyoD exhibited different methylation levels in myostatin-treated ADSCs and MSCs. • PPARγ and MyoD are differentially regulated by myostatin in ADSCs and MSCs.« less

p21{sup WAF1/CIP1} deficiency induces mitochondrial dysfunction in HCT116 colon cancer cells

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

Kim, Ae Jeong; Jee, Hye Jin; Song, Naree

2013-01-11

Highlights: Black-Right-Pointing-Pointer p21{sup -/-} HCT116 cells exhibited an increase in mitochondrial mass. Black-Right-Pointing-Pointer The expression levels of PGC-1{alpha} and AMPK were upregulated in p21{sup -/-} HCT116 cells. Black-Right-Pointing-Pointer The proliferation of p21{sup -/-} HCT116 cells in galactose medium was significantly impaired. Black-Right-Pointing-Pointer p21 may play a role in maintaining proper mitochondrial mass and respiratory function. -- Abstract: p21{sup WAF1/CIP1} is a critical regulator of cell cycle progression. However, the role of p21 in mitochondrial function remains poorly understood. In this study, we examined the effect of p21 deficiency on mitochondrial function in HCT116 human colon cancer cells. We found thatmore » there was a significant increase in the mitochondrial mass of p21{sup -/-} HCT116 cells, as measured by 10-N-nonyl-acridine orange staining, as well as an increase in the mitochondrial DNA content. In contrast, p53{sup -/-} cells had a mitochondrial mass comparable to that of wild-type HCT116 cells. In addition, the expression levels of the mitochondrial biogenesis regulators PGC-1{alpha} and TFAM and AMPK activity were also elevated in p21{sup -/-} cells, indicating that p21 deficiency induces the rate of mitochondrial biogenesis through the AMPK-PGC-1{alpha} axis. However, the increase in mitochondrial biogenesis in p21{sup -/-} cells did not accompany an increase in the cellular steady-state level of ATP. Furthermore, p21{sup -/-} cells exhibited significant proliferation impairment in galactose medium, suggesting that p21 deficiency induces a defect in the mitochondrial respiratory chain in HCT116 cells. Taken together, our results suggest that the loss of p21 results in an aberrant increase in the mitochondrial mass and in mitochondrial dysfunction in HCT116 cells, indicating that p21 is required to maintain proper mitochondrial mass and respiratory function.« less

Early-Life Social Isolation Stress Increases Kappa Opioid Receptor Responsiveness and Downregulates the Dopamine System

PubMed Central

Karkhanis, Anushree N; Rose, Jamie H; Weiner, Jeffrey L; Jones, Sara R

2016-01-01

Chronic early-life stress increases vulnerability to alcoholism and anxiety disorders during adulthood. Similarly, rats reared in social isolation (SI) during adolescence exhibit augmented ethanol intake and anxiety-like behaviors compared with group housed (GH) rats. Prior studies suggest that disruption of dopamine (DA) signaling contributes to SI-associated behaviors, although the mechanisms underlying these alterations are not fully understood. Kappa opioid receptors (KORs) have an important role in regulating mesolimbic DA signaling, and other kinds of stressors have been shown to augment KOR function. Therefore, we tested the hypothesis that SI-induced increases in KOR function contribute to the dysregulation of NAc DA and the escalation in ethanol intake associated with SI. Our ex vivo voltammetry experiments showed that the inhibitory effects of the kappa agonist U50,488 on DA release were significantly enhanced in the NAc core and shell of SI rats. Dynorphin levels in NAc tissue were observed to be lower in SI rats. Microdialysis in freely moving rats revealed that SI was also associated with reduced baseline DA levels, and pretreatment with the KOR antagonist nor-binaltorphimine (nor-BNI) increased DA levels selectively in SI subjects. Acute ethanol elevated DA in SI and GH rats and nor-BNI pretreatment augmented this effect in SI subjects, while having no effect on ethanol-stimulated DA release in GH rats. Together, these data suggest that KORs may have increased responsiveness following SI, which could lead to hypodopaminergia and contribute to an increased drive to consume ethanol. Indeed, SI rats exhibited greater ethanol intake and preference and KOR blockade selectively attenuated ethanol intake in SI rats. Collectively, the findings that nor-BNI reversed SI-mediated hypodopaminergic state and escalated ethanol intake suggest that KOR antagonists may represent a promising therapeutic strategy for the treatment of alcohol use disorders, particularly in cases linked to chronic early-life stress. PMID:26860203

Size dictated thermal conductivity of GaN

NASA Astrophysics Data System (ADS)

Beechem, Thomas E.; McDonald, Anthony E.; Fuller, Elliot J.; Talin, A. Alec; Rost, Christina M.; Maria, Jon-Paul; Gaskins, John T.; Hopkins, Patrick E.; Allerman, Andrew A.

2016-09-01

The thermal conductivity of n- and p-type doped gallium nitride (GaN) epilayers having thicknesses of 3-4 μm was investigated using time domain thermoreflectance. Despite possessing carrier concentrations ranging across 3 decades (1015-1018 cm-3), n-type layers exhibit a nearly constant thermal conductivity of 180 W/mK. The thermal conductivity of p-type epilayers, in contrast, reduces from 160 to 110 W/mK with increased doping. These trends—and their overall reduction relative to bulk—are explained leveraging established scattering models where it is shown that, while the decrease in p-type layers is partly due to the increased impurity levels evolving from its doping, size effects play a primary role in limiting the thermal conductivity of GaN layers tens of microns thick. Device layers, even of pristine quality, will therefore exhibit thermal conductivities less than the bulk value of 240 W/mK owing to their finite thickness.

Power Electronic Semiconductor Materials for Automotive and Energy Saving Applications - SiC, GaN, Ga2O3, and Diamond.

PubMed

Wellmann, Peter J

2017-11-17

Power electronics belongs to the future key technologies in order to increase system efficiency as well as performance in automotive and energy saving applications. Silicon is the major material for electronic switches since decades. Advanced fabrication processes and sophisticated electronic device designs have optimized the silicon electronic device performance almost to their theoretical limit. Therefore, to increase the system performance, new materials that exhibit physical and chemical properties beyond silicon need to be explored. A number of wide bandgap semiconductors like silicon carbide, gallium nitride, gallium oxide, and diamond exhibit outstanding characteristics that may pave the way to new performance levels. The review will introduce these materials by (i) highlighting their properties, (ii) introducing the challenges in materials growth, and (iii) outlining limits that need innovation steps in materials processing to outperform current technologies.

Power Electronic Semiconductor Materials for Automotive and Energy Saving Applications – SiC, GaN, Ga2O3, and Diamond

PubMed Central

2017-01-01

Power electronics belongs to the future key technologies in order to increase system efficiency as well as performance in automotive and energy saving applications. Silicon is the major material for electronic switches since decades. Advanced fabrication processes and sophisticated electronic device designs have optimized the silicon electronic device performance almost to their theoretical limit. Therefore, to increase the system performance, new materials that exhibit physical and chemical properties beyond silicon need to be explored. A number of wide bandgap semiconductors like silicon carbide, gallium nitride, gallium oxide, and diamond exhibit outstanding characteristics that may pave the way to new performance levels. The review will introduce these materials by (i) highlighting their properties, (ii) introducing the challenges in materials growth, and (iii) outlining limits that need innovation steps in materials processing to outperform current technologies. PMID:29200530

Photocontrol of the expression of genes encoding chlorophyll a/b binding proteins and small subunit of ribulose-1,5-bisphosphate carboxylase in etiolated seedlings of Lycopersicon esculentum (L. ) and Nicotiana tabacum (L. )

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

Wehmeyer, B.; Cashmore, A.R.; Schaefer, E.

Phytochrome and the blue ultraviolet-A photoreceptor control light-induced expression of genes encoding the chlorophyll a/b binding protein of photosystem II and photosystem I and the genes for the small subunit of the ribulose-1,5-bisphosphate carboxylase in etiolated seedlings of Lycopersicon esculentum (tomato) and Nicotiana tabacum (tobacco). A high irradiance response also controls the induction of these genes. Genes encoding photosystem II- and I-associated chlorophyll a/b binding proteins both exhibit a transient rapid increase in expression in response to light pulse or to continuous irradiation. In contrast, genes encoding the small subunit exhibit a continuous increase in expression in response to light.more » These distinct expression characteristics are shown to reflect differences at the level of transcription.« less

Role of Vascular Endothelial Cells in Disseminated Intravascular Coagulation Induced by Seawater Immersion in a Rat Trauma Model

PubMed Central

Zhang, Dajin; Qu, Jia; Xiong, Ming; Qiao, Yuanyuan; Wang, Dapeng; Liu, Fengjiao; Li, Dandan; Hu, Ming; Zhang, Jiashu

2017-01-01

Trauma complicated by seawater immersion is a complex pathophysiological process with higher mortality than trauma occurring on land. This study investigated the role of vascular endothelial cells (VECs) in trauma development in a seawater environment. An open abdominal injury rat model was used. The rat core temperatures in the seawater (SW, 22°C) group and normal sodium (NS, 22°C) group declined equivalently. No rats died within 12 hours in the control and NS groups. However, the median lethal time of the rats in the SW group was only 260 minutes. Among the 84 genes involved in rat VEC biology, the genes exhibiting the high expression changes (84.62%, 11/13) on a qPCR array were associated with thrombin activity. The plasma activated partial thromboplastin time and fibrinogen and vWF levels decreased, whereas the prothrombin time and TFPI levels increased, indicating intrinsic and extrinsic coagulation pathway activation and inhibition, respectively. The plasma plasminogen, FDP, and D-dimer levels were elevated after 2 hours, and those of uPA, tPA, and PAI-1 exhibited marked changes, indicating disseminated intravascular coagulation (DIC). Additionally, multiorgan haemorrhagia was observed. It indicated that seawater immersion during trauma may increase DIC, elevating mortality. VECs injury might play an essential role in this process. PMID:28744465

Rice pectin methylesterase inhibitor28 (OsPMEI28) encodes a functional PMEI and its overexpression results in a dwarf phenotype through increased pectin methylesterification levels.

PubMed

Nguyen, Hong Phuong; Jeong, Ho Young; Jeon, Seung Ho; Kim, Donghyuk; Lee, Chanhui

2017-01-01

Pectin methylesterases (PMEs, EC 3.1.1.11) belonging to carbohydrate esterase family 8 cleave the ester bond between a galacturonic acid and an methyl group and the resulting change in methylesterification level plays an important role during the growth and development of plants. Optimal pectin methylesterification status in each cell type is determined by the balance between PME activity and post-translational PME inhibition by PME inhibitors (PMEIs). Rice contains 49 PMEIs and none of them are functionally characterized. Genomic sequence analysis led to the identification of rice PMEI28 (OsPMEI28). Recombinant OsPMEI28 exhibited inhibitory activity against commercial PME protein with the highest activities detected at pH 8.5. Overexpression of OsPMEI28 in rice resulted in an increased level of cell wall bound methylester groups and differential changes in the composition of cell wall neutral monosaccharides and lignin content in culm tissues. Consequently, transgenic plants overexpressing OsPMEI28 exhibited dwarf phenotypes and reduced culm diameter. Our data indicate that OsPMEI28 functions as a critical structural modulator by regulating the degree of pectin methylesterification and that an impaired status of pectin methylesterification affects physiochemical properties of the cell wall components and causes abnormal cell extensibility in rice culm tissues. Copyright © 2016 Elsevier GmbH. All rights reserved.

System controls on the aqueous distribution of mercury in the northern Florida Everglades

USGS Publications Warehouse

Hurley, J.P.; Krabbenhoft, D.P.; Cleckner, L.B.; Olson, M.L.; Aiken, G.R.; Rawlik, P.S.

1998-01-01

The forms and partitioning of aqueous mercury species in the canals and marshes of the Northern Florida Everglades exhibit strong spatial and temporal variability. In canals feeding Water Conservation Area (WCA) 2A, unfiltered total Hg (HgT(U)) is less than 3 ng L-1 and relatively constant. In contrast, methyl mercury (MeHg) exhibited a strong seasonal pattern, with highest levels entering WCA-2A marshes during July. Stagnation and reduced flows also lead to particle enrichment of MeHg. In the marshes of WCA-2A, 2B and 3A, HgT(U) is usually <5 ng L-1 with no consistent north-south patterns. However, for individual dates, aqueous unfiltered MeHg (MeHg(U)) levels increase from north to south with generally lowest levels in the eutrophied regions of northern WCA-2A. A strong relationship between filtered Hg species and dissolved organic carbon (DOC), evident for rivers draining wetlands in Wisconsin, was not apparent in the Everglades, suggesting either differences in the binding sites of DOC between the two regions, or non-organic Hg complexation in the Everglades.

Effects of Impurity Content on the Sintering Characteristics of Plasma-Sprayed Zirconia

NASA Astrophysics Data System (ADS)

Paul, S.; Cipitria, A.; Golosnoy, I. O.; Xie, L.; Dorfman, M. R.; Clyne, T. W.

2007-12-01

Yttria-stabilized zirconia powders, containing different levels of SiO2 and Al2O3, have been plasma sprayed onto metallic substrates. The coatings were detached from their substrates and a dilatometer was used to monitor the dimensional changes they exhibited during prolonged heat treatments. It was found that specimens containing higher levels of silica and alumina exhibited higher rates of linear contraction, in both in-plane and through-thickness directions. The in-plane stiffness and the through-thickness thermal conductivity were also measured after different heat treatments and these were found to increase at a greater rate for specimens with higher impurity (silica and alumina) levels. Changes in the pore architecture during heat treatments were studied using Mercury Intrusion Porosimetry (MIP). Fine scale porosity (< ˜50 nm) was found to be sharply reduced even by relatively short heat treatments. This is correlated with improvements in inter-splat bonding and partial healing of intra-splat microcracks, which are responsible for the observed changes in stiffness and conductivity, as well as the dimensional changes.

Sex and age differences in the impact of the forced swimming test on the levels of steroid hormones.

PubMed

Martínez-Mota, Lucía; Ulloa, Rosa-Elena; Herrera-Pérez, Jaime; Chavira, Roberto; Fernández-Guasti, Alonso

2011-10-24

Compared with the adult disorder, depression in children exhibits differences in its neurobiology, particularly in the HPA axis regulation. The bases of such differences can be evaluated in animal models of depression. The objective of the present study was to determine age and sex differences of Wistar rats in the forced swimming test (FST). The influence of sex and age on corticosterone, estrogens and testosterone serum levels was also determined. Prepubertal rats showed immobility, swimming and climbing behaviors during the pre-test and test sessions. In addition, in the prepubertal animals, no sex differences were found during the pre-test and test sessions. Age comparisons indicated no differences in the female groups, however adult males exhibited more immobility and less swimming than young males, in both FST sessions. The young and female rats showed less immobility behavior and increased levels of estrogens after the FST. The present results indicate that the FST is an animal model suitable to evaluate depressive-like behaviors in prepubertal subjects and to explore behavioral changes related to neurodevelopment. Copyright © 2011 Elsevier Inc. All rights reserved.

Partial Tmem106b reduction does not correct abnormalities due to progranulin haploinsufficiency.

PubMed

Arrant, Andrew E; Nicholson, Alexandra M; Zhou, Xiaolai; Rademakers, Rosa; Roberson, Erik D

2018-06-22

Loss of function mutations in progranulin (GRN) are a major cause of frontotemporal dementia (FTD). Progranulin is a secreted glycoprotein that localizes to lysosomes and is critical for proper lysosomal function. Heterozygous GRN mutation carriers develop FTD with TDP-43 pathology and exhibit signs of lysosomal dysfunction in the brain, with increased levels of lysosomal proteins and lipofuscin accumulation. Homozygous GRN mutation carriers develop neuronal ceroid lipofuscinosis (NCL), an earlier-onset lysosomal storage disorder caused by severe lysosomal dysfunction. Multiple genome-wide association studies have shown that risk of FTD in GRN mutation carriers is modified by polymorphisms in TMEM106B, which encodes a lysosomal membrane protein. Risk alleles of TMEM106B may increase TMEM106B levels through a variety of mechanisms. Brains from FTD patients with GRN mutations exhibit increased TMEM106B expression, and protective TMEM106B polymorphisms are associated with decreased TMEM106B expression. Together, these data raise the possibility that reduction of TMEM106B levels may protect against the pathogenic effects of progranulin haploinsufficiency. We crossed Tmem106b +/- mice with Grn +/- mice, which model the progranulin haploinsufficiency of GRN mutation carriers and develop age-dependent social deficits and lysosomal abnormalities in the brain. We tested whether partial Tmem106b reduction could normalize the social deficits and lysosomal abnormalities of Grn +/- mice. Partial reduction of Tmem106b levels did not correct the social deficits of Grn +/- mice. Tmem106b reduction also failed to normalize most lysosomal abnormalities of Grn +/- mice, except for β-glucuronidase activity, which was suppressed by Tmem106b reduction and increased by progranulin insufficiency. These data do not support the hypothesis that Tmem106b reduction protects against the pathogenic effects of progranulin haploinsufficiency, but do show that Tmem106b reduction normalizes some lysosomal phenotypes in Grn +/- mice.

Sex-dependent influence of chronic mild stress (CMS) on voluntary alcohol consumption; study of neurobiological consequences.

PubMed

Marco, Eva M; Ballesta, Javier Antonio; Irala, Carlos; Hernández, María-Donina; Serrano, María Elisa; Mela, Virginia; López-Gallardo, Meritxell; Viveros, María-Paz

2017-01-01

Alcohol use disorder and depression are highly comorbid, and both conditions exhibit important sexual dimorphisms. Here, we aimed to investigate voluntary alcohol consumption after 6weeks of chronic mild stress (CMS) in Wistar rats - employed as an animal model of depression. Male and female rats were investigated, and changes in several molecular markers were analysed in frontal cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like responses in the forced swimming test - increased immobility time - in male and female animals, without affecting anhedonia (sucrose preference test) nor motor activity (holeboard); body weight gain and food intake were diminished only among CMS males. Voluntary alcohol consumption was evaluated in a two-bottle choice paradigm (ethanol 20% versus tap water) for 4 consecutive days; females exhibited a higher preference for alcohol compared to male animals. In particular, alcohol consumption was significantly higher among CMS females compared to CMS male animals. Remarkably, similar changes in both male and female animals exposed to CMS were observed regarding the expression levels of NCAM-140KDa (decrease), GFAP and CB1R expression (increase) within the FCx as well as for HF PSD-95 levels (increase). However, contrasting effects in males and females were reported in relation to synaptophysin (SYN) protein levels within the FCx, HF CB1R expression (a decrease among male animals but an increase in females); while the opposite pattern was observed for NCAM-140KDa protein levels in the HF. A decrease in CB2R expression was only observed in the HF of CMS-females. The present study suggests that male and female animals might be differentially affected by CMS regarding later voluntary alcohol consumption. In this initial approach, cortical SYN, and NCAM-140KDa, CB1R and CB2R expression within the HF have arisen as potential candidates to explain such sex differences in behaviour. However, the depression-alcoholism relationship still deserves further investigation. Copyright © 2016. Published by Elsevier Inc.

Quantitative analysis of lentiviral transgene expression in mice over seven generations.

PubMed

Wang, Yong; Song, Yong-tao; Liu, Qin; Liu, Cang'e; Wang, Lu-lu; Liu, Yu; Zhou, Xiao-yang; Wu, Jun; Wei, Hong

2010-10-01

Lentiviral transgenesis is now recognized as an extremely efficient and cost-effective method to produce transgenic animals. Transgenes delivered by lentiviral vectors exhibited inheritable expression in many species including those which are refractory to genetic modification such as non-human primates. However, epigenetic modification was frequently observed in lentiviral integrants, and transgene expression found to be inversely correlated with methylation density. Recent data showed that about one-third lentiviral integrants exhibited hypermethylation and low expression, but did not demonstrate whether those integrants with high expression could remain constant expression and hypomethylated during long term germline transmission. In this study, using lentiviral eGFP transgenic mice as the experimental animals, lentiviral eGFP expression levels and its integrant numbers in genome were quantitatively analyzed by fluorescent quantitative polymerase-chain reaction (FQ-PCR), using the house-keeping gene ribosomal protein S18 (Rps18) and the single copy gene fatty acid binding protein of the intestine (Fabpi) as the internal controls respectively. The methylation densities of the integrants were quantitatively analyzed by bisulfite sequencing. We found that the lentiviral integrants with high expression exhibited a relative constant expression level per integrant over at least seven generations. Besides, the individuals containing these integrants exhibited eGFP expression levels which were positively and almost linearly correlated with the integrant numbers in their genomes, suggesting that no remarkable position effect on transgene expression of the integrants analyzed was observed. In addition, over seven generations the methylation density of these integrants did not increase, but rather decreased remarkably, indicating that these high expressing integrants were not subjected to de novo methylation during at least seven generations of germline transmission. Taken together, these data suggested that transgenic lines with long term stable expression and no position effect can be established by lentiviral transgenesis.

Cancer Stem-Like Cells Enriched in Panc-1 Spheres Possess Increased Migration Ability and Resistance to Gemcitabine

PubMed Central

Yin, Tao; Wei, Hongji; Gou, Shanmiao; Shi, Pengfei; Yang, Zhiyong; Zhao, Gang; Wang, Chunyou

2011-01-01

Pancreatic cancer is one of the most lethal malignancies with poor prognosis. Previously, we found that a subpopulation of cancer stem cells (CSCs) in the Panc-1 pancreatic cancer cell line could propagate to form spheres. Here we characterized the malignant phenotypes of the pancreatic cancer stem CD44+/CD24+ cells, which were enriched under sphere forming conditions as analyzed by flow cytometry. These cells demonstrated increased resistance to gemcitabine and increased migration ability. Moreover, these cells exhibited epithelial to mesenchymal transition characterized by a decreased level of the epithelial marker E-cadherin and an increased level of the mesenchymal marker vimentin. Notably, abnormal expression of Bmi-1, ABCG2, Cyclin D1 and p16 were found in Panc-1 CSCs. Our results suggest that targeted inhibition of CSCs represents a novel therapeutic approach to overcome chemoresistance and metastasis of pancreatic cancer. PMID:21673909

Quaternary ammonium salt N-(dodecyloxycarboxymethyl)-N,N,N-trimethyl ammonium chloride induced alterations in Saccharomyces cerevisiae physiology.

PubMed

Oblak, Ewa; Piecuch, Agata; Maciaszczyk-Dziubinska, Ewa; Wawrzycka, Donata

2016-12-01

We investigated the influence of the quaternary ammonium salt (QAS) called IM (N-(dodecyloxycarboxymethyl)- N,N,N-trimethyl ammonium chloride) on yeast cells of the parental strain and the IM-resistant mutant (EO25 IMR) growth. The phenotype of this mutant was pleiotropic. The IMR mutant exhibited resistance to ethanol, osmotic shock and oxidative stress, as well as increased sensitivity to UV. Moreover, it was noted that mutant EO25 appears to have an increased resistance to clotrimazole, ketoconazole, fluconazole, nystatin and cycloheximide. It also tolerated growth in the presence of crystal violet, DTT and metals (selenium, tin, arsenic). It was shown that the presence of IM decreased ergosterol level in mutant plasma membrane and increased its unsaturation. These results indicate changes in the cell lipid composition. Western blot analysis showed the induction of Pma1 level by IM. RT-PCR revealed an increased PMA1 expression after IM treatment.

In vivo regeneration of red cell 2,3-diphosphoglycerate following transfusion of DPG-depleted AS-1, AS-3 and CPDA-1 red cells.

PubMed

Heaton, A; Keegan, T; Holme, S

1989-01-01

Regeneration of 2,3-diphosphoglycerate (DPG) was determined following transfusion of DPG-depleted group O red cells into group A recipients. Blood from five donors was stored in the adenine-containing solutions CPDA-1, AS-1 or AS-3 for 35 d at 4 degrees C. Post-transfusion red cell DPG and ATP were measured in separated group O red cells over a 7 d period. The studies confirmed rapid in vivo DPG regeneration with greater than or equal to 50% of the maximum level being achieved within 7 h. An average of 95% of the recipients' pre-transfusion DPG level was achieved by 72 h and by 7 d mean (+/- SEM) DPG levels relative to recipient's pre-transfusion DPG averaged 84% (+/- 13%), 92% (+/- 17%) and 84% (+/- 21%) for CPDA-1, AS-1 and AS-3 red cells, respectively. Results were comparable to those previously reported for blood stored in ACD for 15-20 d (Valeri & Hirsch, 1969; Beutler & Wood, 1969). The immediate regeneration rate, V, closely approximated first order regeneration kinetics with AS-3 red cells exhibiting double the rate of CPDA-1 red cells (P less than 0.001). AS-1 red cells exhibited an intermediate rate of regeneration which was not significantly different compared to either CPDA-1 or AS-3 (P greater than 0.05). V exhibited a significant (P less than 0.05) positive correlation with ATP levels 5-7 h post-infusion. ATP regeneration of the infused cells was rapid with a mean increase of 1.2 mumol/g Hb above post-storage levels being achieved 1 h following transfusion.

Formononetin exhibits anti-hyperglycemic activity in alloxan-induced type 1 diabetic mice.

PubMed

Qiu, Guizhen; Tian, Wei; Huan, Mei; Chen, Jinlong; Fu, Haitao

2017-01-01

The aim of this study was to investigate the anti-hyperglycemic activity and mechanism of formononetin in alloxan-induced type 1 diabetic mice by determining its effect on some diabetes-related indices as described below. Body weight, fasting blood glucose, hepatic glycogen, serum insulin, and serum glucagon were determined by electronic scales, glucometer, and ELISA kits. Fas, Caspase-3, pancreatic and duodenal homeobox-1 , insulin receptor substrate 2, glucokinase and glucose transporter 2, mRNA and proteins levels in pancreas tissue, and glucokinase and glucose-6-phosphatase mRNA, and proteins levels in liver tissue were detected by fluorogenic quantitative-polymerase chain reaction and Western blot assays. The results indicated that formononetin (5, 10, and 20 mg/kg; oral administration) reversed the alloxan-induced increase of some indices (fasting blood glucose level and Fas and Caspase-3 mRNA and proteins levels in pancreas tissue) and reduction of some indices (body weight gain, oral glucose tolerance, insulin activity, hepatic glycogen level, pancreatic and duodenal homeobox-1, insulin receptor substrate 2, glucokinase and glucose transporter 2, mRNA and proteins levels in pancreas tissue, and glucokinase mRNA and protein levels in liver tissue). The glucagon level and glucose-6-phosphatase mRNA and protein levels in liver tissue were not affected by the drugs administration. In conclusion, formononetin exhibited anti-hyperglycemic activity in alloxan-induced type 1 diabetic mice by inhibiting islet B cell apoptosis and promoting islet B cell regeneration, insulin secretion, hepatic glycogen synthesis, and hepatic glycolysis.

A monostable piezoelectric energy harvester for broadband low-level excitations

NASA Astrophysics Data System (ADS)

Fan, Kangqi; Tan, Qinxue; Zhang, Yiwei; Liu, Shaohua; Cai, Meiling; Zhu, Yingmin

2018-03-01

This letter presents a monostable piezoelectric energy harvester (PEH) for achieving enhanced energy extraction from low-level excitations. The proposed PEH is realized by introducing symmetric magnetic attraction to a piezoelectric cantilever beam and a pair of stoppers to confine the maximum deflection of the beam. The lumped parameter model of such a system is presented and experimentally validated. Theoretical simulations and experimental measurements demonstrate that the proposed design can bring about a wider operating bandwidth and higher output voltage than the linear PEH. Under a sinusoidal vibration with an amplitude of 3 m/s2, a 54% increase in the operating bandwidth and a 253% increase in the magnitude of output power are achieved compared to its linear counterpart. Moreover, the proposed PEH exhibits rich dynamic features, including the tunable operating bandwidth, adjustable voltage and power levels, and softening hysteresis.

Serum copper concentration as an index of clinical lung injury

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

Molteni, A.; Ward, W.F.; Kim, Y.T.

1989-01-01

The purpose of this ongoing study is to determine whether thoracic radiotherapy for lung cancer produces an early increase in serum copper (Cu) concentration, an increase which might predict clinical outcome. Copper and iron concentrations were measured in serum obtained from nonsmall cell lung cancer patients at 0, 1, 2, 4, and 6 weeks after the start of radiotherapy. Control groups included patients irradiated for breast cancer (low dose of radiation to the lung), for endometrial, cervical or prostatic cancer, and patients with congestive heart failure, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and cutaneous burns with or without smokemore » inhalation. Serum Cu concentration increased at least 10 micrograms/dl from the pretreatment level in approximately 75% of the adenocarcinoma and squamous cell lung cancer patients, but in only 1 of 4 undifferentiated lung cancer cases. In virtually all of these responders, serum Cu increased to a maximum at 2 weeks after the start of therapy, then plateaued or decreased slightly despite continuing irradiation. Within the subset of squamous cell lung cancers, there was a direct correlation between the degree of histologic differentiation and both baseline serum Cu concentration and the probability of an early increase therein. In contrast, only 33% of breast cancer patients and 15% of endometrial, cervical and prostate cancer patients exhibited an increase in serum Cu concentration at 2 weeks after the start of radiotherapy. Serum Cu concentration was within normal limits in virtually all patients with congestive heart failure, pulmonary hypertension, and COPD. Burn patients exhibited a significant reduction in serum Cu, although concomitant smoke inhalation increased serum Cu back to low-normal levels. Serum iron concentration did not change significantly in any category of patients.« less

Effect of exposure to solid wastes in relation to employment duration on some important markers of health and disease in waste management workers of Ogun State in southwest Nigeria.

PubMed

Odewabi, Adesina O; Ogundahunsi, Omobola A; Ekor, Martins

2013-12-01

Waste management workers (WMWs) around the world are at risk of work-related health disorders. The influence of employment duration on individuals occupationally exposed to solid waste was investigated in this study. The study comprised (n = 280) 180 WMWs and 100 controls. Employment duration was obtained from questionnaire survey and categorized into three groups: group I (0.5-2 years), group II (>2-4 years) and group III (>4-6 years). Blood sample (10 ml) was collected from the antecubital vein of subjects for analysis. WMWs exhibited significantly (p < 0.001) elevated inflammatory markers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and ceruloplasmin (Cp)) relative to control. While Cp increased, ESR and CRP decreased with increasing WMWs' employment duration. Alteration in oxidant/antioxidant markers was characterized by significant (p < 0.001) decrease in ferric-reducing ability of plasma (FRAP) and catalase activity together with marked (p < 0.01) elevation of thiobarbituric acid reactive substances (TBARS) and uric acid (UA). TBARS, UA and FRAP increased while catalase decreased with WMWs' employment duration. In addition, WMWs exhibited significantly (p < 0.01) elevated immunoglobulin A (IgA) and IgG, which also increased and decreased, respectively, with job duration. The significantly (p < 0.01) decreased haemoglobin and haematocrit levels as well as the significantly (p < 0.001) elevated total leukocytes in WMWs increased with employment duration. Alanine aminotransferase increased and albumin decreased significantly (p < 0.05) in WMWs, and these changes also increased and decreased, respectively, with job duration. Data suggest that levels of alteration of important systemic markers of health/disease are related to WMWs' employment or exposure duration.

Dietary Tocotrienol/γ-Cyclodextrin Complex Increases Mitochondrial Membrane Potential and ATP Concentrations in the Brains of Aged Mice

PubMed Central

Schloesser, Anke; Esatbeyoglu, Tuba; Piegholdt, Stefanie; Dose, Janina; Ikuta, Naoko; Okamoto, Hinako; Ishida, Yoshiyuki; Terao, Keiji; Matsugo, Seiichi; Rimbach, Gerald

2015-01-01

Brain aging is accompanied by a decrease in mitochondrial function. In vitro studies suggest that tocotrienols, including γ- and δ-tocotrienol (T3), may exhibit neuroprotective properties. However, little is known about the effect of dietary T3 on mitochondrial function in vivo. In this study, we monitored the effect of a dietary T3/γ-cyclodextrin complex (T3CD) on mitochondrial membrane potential and ATP levels in the brain of 21-month-old mice. Mice were fed either a control diet or a diet enriched with T3CD providing 100 mg T3 per kg diet for 6 months. Dietary T3CD significantly increased mitochondrial membrane potential and ATP levels compared to those of controls. The increase in MMP and ATP due to dietary T3CD was accompanied by an increase in the protein levels of the mitochondrial transcription factor A (TFAM). Furthermore, dietary T3CD slightly increased the mRNA levels of superoxide dismutase, γ-glutamyl cysteinyl synthetase, and heme oxygenase 1 in the brain. Overall, the present data suggest that T3CD increases TFAM, mitochondrial membrane potential, and ATP synthesis in the brains of aged mice. PMID:26301044

Mediation of a corticosterone-induced reproductive conflict.

PubMed

Love, Oliver P; Breuner, Creagh W; Vézina, François; Williams, Tony D

2004-06-01

Current research in birds suggests that a conflict should exist during reproduction for the role of the glucocorticoid corticosterone (CORT). While elevated levels have been correlated with the increased energetic demand of raising offspring, elevated CORT levels have traditionally been implicated in reproductive abandonment. We examined the relationship between CORT and nest desertion in breeding wild female European starlings (Sturnus vulgaris) incorporating analyses of both total circulating levels and 'free', unbound CORT through analysis of corticosteroid-binding globulin (CBG). Free baseline CORT levels of nest-abandoning birds were significantly higher than nonabandoning birds within each stage, with chick-rearing birds exhibiting the highest free baseline CORT levels, while concurrently remaining the most resistant stage to nest desertion. Elevated free baseline CORT levels in chick-rearing birds were not due to increased total CORT secretion, but rather to a decrease in CBG levels. Overall, our results suggest that CORT and CBG interact to play a role in mediating the increased energetic demand of offspring, while minimizing the chances of nest desertion, thereby alleviating any potential behavioral conflict for CORT during reproduction. Furthermore, these results demonstrate that the traditional view of the role of CORT during reproduction is much more complex than previously appreciated. Together with mounting evidence, we suggest that elevated corticosteroid levels are an inherent and necessary part of reproduction in nonmammalian tetrapods.

Pyridoxine and its relation to lipids. Studies with pyridoxineless mutants of Aspergillus nidulans.

PubMed

Mohana, K; Shanmugasundaram, E R

1978-01-01

The effect of pyridoxine deficiency on fat metabolism was studied using mutant strains of Aspergillus nidulans requiring pyridoxine for growth. Under pyridoxine deficiency the mutants exhibited increased levels of total lipid, sterols, phospholipids, and triacylglycerols. Total fatty acids were found to decrease with pyridoxine deficiency. An increase in saturated fatty acids and decrease in unsaturated fatty acids were seen with deficiency. Pyridoxine deficiency also increased lower carbon chain fatty acids. A possible involvement of pyridoxine in the elongation of fatty acid chain and in the desaturation of fatty acids in Aspergillus nidulans is suggested.

Increased radiation resistance in lithium-counterdoped silicon solar cells

NASA Technical Reports Server (NTRS)

Weinberg, I.; Swartz, C. K.; Mehta, S.

1984-01-01

Lithium-counterdoped n(+)p silicon solar cells are found to exhibit significantly increased radiation resistance to 1-MeV electron irradiation when compared to boron-doped n(+)p silicon solar cells. In addition to improved radiation resistance, considerable damage recovery by annealing is observed in the counterdoped cells at T less than or equal to 100 C. Deep level transient spectroscopy measurements are used to identify the defect whose removal results in the low-temperature aneal. It is suggested that the increased radiation resistance of the counterdoped cells is primarily due to interaction of the lithium with interstitial oxygen.

Testosterone is protective against impaired glucose metabolism in male intrauterine growth-restricted offspring

PubMed Central

Dasinger, John Henry; Fahling, Joel M.; Backstrom, Miles A.; Alexander, Barbara T.

2017-01-01

Placental insufficiency alters the intrauterine environment leading to increased risk for chronic disease including impaired glucose metabolism in low birth weight infants. Using a rat model of low birth weight, we previously reported that placental insufficiency induces a significant increase in circulating testosterone in male intrauterine growth-restricted offspring (mIUGR) in early adulthood that is lost by 12 months of age. Numerous studies indicate testosterone has a positive effect on glucose metabolism in men. Female growth-restricted littermates exhibit glucose intolerance at 6 months of age. Thus, the aim of this paper was to determine whether mIUGR develop impaired glucose metabolism, and whether a decrease in elevated testosterone levels plays a role in its onset. Male growth-restricted offspring were studied at 6 and 12 months of age. No impairment in glucose tolerance was observed at 6 months of age when mIUGR exhibited a 2-fold higher testosterone level compared to age-matched control. Fasting blood glucose was significantly higher and glucose tolerance was impaired with a significant decrease in circulating testosterone in mIUGR at 12 compared with 6 months of age. Castration did not additionally impair fasting blood glucose or glucose tolerance in mIUGR at 12 months of age, but fasting blood glucose was significantly elevated in castrated controls. Restoration of elevated testosterone levels significantly reduced fasting blood glucose and improved glucose tolerance in mIUGR. Thus, our findings suggest that the endogenous increase in circulating testosterone in mIUGR is protective against impaired glucose homeostasis. PMID:29145418

Maternal Caloric Restriction Implemented during the Preconceptional and Pregnancy Period Alters Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Overweight and Increased Adiposity at Adulthood in Male Rat Offspring

PubMed Central

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

2016-01-01

Exposure to inadequate nutritional conditions in critical windows of development has been associated to disturbances on metabolism and behavior in the offspring later in life. The role of the endocannabinoid system, a known regulator of energy expenditure and adaptive behaviors, in the modulation of these processes is unknown. In the present study, we investigated the impact of exposing rat dams to diet restriction (20% less calories than standard diet) during pre-gestational and gestational periods on: (a) neonatal outcomes; (b) endocannabinoid content in hypothalamus, hippocampus and olfactory bulb at birth; (c) metabolism-related parameters; and (d) behavior in adult male offspring. We found that calorie-restricted dams tended to have a reduced litter size, although the offspring showed normal weight at birth. Pups from calorie-restricted dams also exhibited a strong decrease in the levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), arachidonic acid (AA) and palmitoylethanolamide (PEA) in the hypothalamus at birth. Additionally, pups from diet-restricted dams displayed reduced levels of AEA in the hippocampus without significant differences in the olfactory bulb. Moreover, offspring exhibited increased weight gain, body weight and adiposity in adulthood as well as increased anxiety-related responses. We propose that endocannabinoid signaling is altered by a maternal caloric restriction implemented during the preconceptional and pregnancy periods, which might lead to modifications of the hypothalamic and hippocampal circuits, potentially contributing to the long-term effects found in the adult offspring. PMID:27847471

Glutathione-deficient Plasmodium berghei parasites exhibit growth delay and nuclear DNA damage.

PubMed

Padín-Irizarry, Vivian; Colón-Lorenzo, Emilee E; Vega-Rodríguez, Joel; Castro, María Del R; González-Méndez, Ricardo; Ayala-Peña, Sylvette; Serrano, Adelfa E

2016-06-01

Plasmodium parasites are exposed to endogenous and exogenous oxidative stress during their complex life cycle. To minimize oxidative damage, the parasites use glutathione (GSH) and thioredoxin (Trx) as primary antioxidants. We previously showed that disruption of the Plasmodium berghei gamma-glutamylcysteine synthetase (pbggcs-ko) or the glutathione reductase (pbgr-ko) genes resulted in a significant reduction of GSH in intraerythrocytic stages, and a defect in growth in the pbggcs-ko parasites. In this report, time course experiments of parasite intraerythrocytic development and morphological studies showed a growth delay during the ring to schizont progression. Morphological analysis shows a significant reduction in size (diameter) of trophozoites and schizonts with increased number of cytoplasmic vacuoles in the pbggcs-ko parasites in comparison to the wild type (WT). Furthermore, the pbggcs-ko mutants exhibited an impaired response to oxidative stress and increased levels of nuclear DNA (nDNA) damage. Reduced GSH levels did not result in mitochondrial DNA (mtDNA) damage or protein carbonylations in neither pbggcs-ko nor pbgr-ko parasites. In addition, the pbggcs-ko mutant parasites showed an increase in mRNA expression of genes involved in oxidative stress detoxification and DNA synthesis, suggesting a potential compensatory mechanism to allow for parasite proliferation. These results reveal that low GSH levels affect parasite development through the impairment of oxidative stress reduction systems and damage to the nDNA. Our studies provide new insights into the role of the GSH antioxidant system in the intraerythrocytic development of Plasmodium parasites, with potential translation into novel pharmacological interventions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Transient anhedonia phenotype and altered circadian timing of behaviour during night-time dim light exposure in Per3-/- mice, but not wildtype mice.

PubMed

Martynhak, Bruno Jacson; Hogben, Alexandra L; Zanos, Panos; Georgiou, Polymnia; Andreatini, Roberto; Kitchen, Ian; Archer, Simon N; von Schantz, Malcolm; Bailey, Alexis; van der Veen, Daan R

2017-01-10

Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are 'direct' effects of light on affect, an 'indirect' pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3 -/- mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3 -/- ) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2-3 of dim light at night, whereas WT mice did not. Per3 -/- mice also exhibited a significantly smaller delay in behavioural timing than WT mice during weeks 1, 2 and 4 of dim light at night exposure. When treated with imipramine, neither Per3 -/- nor WT mice exhibited an anhedonia-like phenotype, and neither genotypes exhibited a delay in behavioural timing in responses to dLAN. While the association between both Per3 -/- phenotypes remains unclear, both are alleviated by imipramine treatment during dim night-time light.

Glyoxal administration induces formation of high molecular weight aggregates of hemoglobin exhibiting amyloidal nature in experimental rats: An in vivo study.

PubMed

Banerjee, Sauradipta; Chakraborti, Abhay Sankar

2016-12-01

Glyoxal, a highly reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs). In the present study, we have investigated the effect of glyoxal on experimental rat hemoglobin in vivo after external administration of the α-dicarbonyl compound in animals. Gel electrophoretic profile of hemolysate collected from glyoxal-treated rats (32mg/kg body wt. dose) after one week exhibited the presence of some high molecular weight protein bands that were found to be absent for control, untreated rats. Mass spectrometric and absorption studies indicated that the bands represented hemoglobin. Further studies revealed that the fraction exhibited the presence of intermolecular cross β-sheet structure. Thus glyoxal administration induces formation of high molecular weight aggregates of hemoglobin with amyloid characteristics in rats. Aggregated hemoglobin fraction was found to exhibit higher stability compared to glyoxal-untreated hemoglobin. As evident from mass spectrometric studies, glyoxal was found to modify Arg-30β and Arg-31α of rat hemoglobin to hydroimidazolone adducts. The modifications thus appear to induce amyloid-like aggregation of hemoglobin in rats. Considering the increased level of glyoxal in diabetes mellitus as well as its high reactivity, the above findings may be physiologically significant. Copyright © 2016 Elsevier B.V. All rights reserved.

Sex-dimorphic psychomotor activation after perinatal exposure to (-)-delta 9-tetrahydrocannabinol. An ontogenic study in Wistar rats.

PubMed

Navarro, M; Rubio, P; Rodríguez de Fonseca, F

1994-12-01

The ontogeny and the adult expression of motor behaviors were studied in male and female rats born from mothers exposed to delta 9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. Perinatal exposure to THC increased both rearing and locomotor activities in males and females at immature preweanling ages (P-15 and P-20). These effects disappeared after ceasing THC exposure (postweaning ages), but they were observed again in adult (P-70) females. The effects appeared as persistently high motor activity in familiar environments, disappearing the characteristic habituation profile in locomotor and exploratory behaviors. In novel environment condition tests, adult (P-70) THC-exposed females, but not males, exhibited lower locomotor activity in the socio-sexual approach test, and an increase in the emergence latency in the dark-light emergence test. Additionally, animals of both sexes exposed to THC showed a increase in the time spent grooming measured in novelty conditions. These findings suggest that perinatal exposure to THC affects both the development and the adult expression of motor behaviors and it resulted in a sex-dimorphic psychomotor activation very similar to that observed after perinatal exposure to other drugs of abuse. A possible role of THC-induced pituitary-adrenal (PA) axis activation was also evaluated by measuring plasma corticosterone levels in adult animals perinatally exposed: THC-exposed females exhibit a clear increase of this adrenal hormone, whereas THC-exposed males displayed lower levels of this hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional history does not modulate hepatic oxidative status of European sea bass (Dicentrarchus labrax) submitted to handling stress.

PubMed

Castro, Carolina; Peréz-Jiménez, Amalia; Coutinho, Filipe; Corraze, Geneviève; Panserat, Stéphane; Peres, Helena; Teles, Aires Oliva; Enes, Paula

2018-06-01

The aim of the present study was to assess the impact of an acute handling stress on hepatic oxidative status of European sea bass (Dicentrarchus labrax) juveniles fed diets differing in lipid so urce and carbohydrate content. For that purpose, four diets were formulated with fish oil (FO) and vegetable oils (VO) as lipid source and with 20 or 0% gelatinized starch as carbohydrate source. Triplicate groups of fish with 74 g were fed each diet during 13 weeks and then subjected to an acute handling stress. Stress exposure decreased hematocrit (Ht) and hemoglobin (Hb) levels. Independent of dietary treatment, stress exposure increased hepatic lipid peroxidation (LPO). Stressed fish exhibited lower glucose 6-phosphate dehydrogenase (G6PD), catalase (CAT), and superoxide dismutase (SOD) activities, independent of previous nutritional history. In the VO groups, stress exposure increased glutathione peroxidase (GPX) activity. Diet composition had no effect on Ht and Hb levels. In contrast, dietary carbohydrate decreased hepatic LPO and CAT activity and increased glutathione reductase (GR) and G6PD activities. Dietary lipids had no effect on LPO. Fish fed the VO diets exhibited higher G6PD activity than fish fed the FO diets. In conclusion, dietary carbohydrates contributed to the reduction of oxidative stress in fish. However, under the imposed handling stress conditions, liver enzymatic antioxidant mechanisms were not enhanced, which may explain the overall increased oxidative stress.

Effects of intraoral aging on surface properties of coated nickel-titanium archwires.

PubMed

Rongo, Roberto; Ametrano, Gianluca; Gloria, Antonio; Spagnuolo, Gianrico; Galeotti, Angela; Paduano, Sergio; Valletta, Rosa; D'Antò, Vincenzo

2014-07-01

To evaluate the effects of intraoral aging on surface properties of esthetic and conventional nickel-titanium (NiTi) archwires. Five NiTi wires were considered for this study (Sentalloy, Sentalloy High Aesthetic, Superelastic Titanium Memory Wire, Esthetic Superelastic Titanium Memory Wire, and EverWhite). For each type of wire, four samples were analyzed as received and after 1 month of clinical use by an atomic force microscope (AFM) and a scanning electronic microscope (SEM). To evaluate sliding resistance, two stainless steel plates with three metallic or three monocrystalline brackets, bonded in passive configuration, were manufactured; four as-received and retrieved samples for every wire were pulled five times at 5 mm/min for 1 minute by means of an Instron 5566, recording the greatest friction value (N). Data were analyzed by one-way analysis of variance and by Student's t-test. After clinical use, surface roughness increased considerably. The SEM images showed homogeneity for the as-received control wires; however, after clinical use esthetic wires exhibited a heterogeneous surface with craters and bumps. The lowest levels of friction were observed with the as-received Superelastic Titanium Memory Wire on metallic brackets. When tested on ceramic brackets, all the wires exhibited an increase in friction (t-test; P < .05). Furthermore, all the wires, except Sentalloy, showed a statistically significant increase in friction between the as-received and retrieved groups (t-test; P < .05). Clinical use of the orthodontic wires increases their surface roughness and the level of friction.

Radiation-hardened nano-particles-based Erbium-doped fiber for space environment

NASA Astrophysics Data System (ADS)

Thomas, Jérémie; Myara, Mikhaël.; Signoret, Philippe; Burov, Ekaterina; Pastouret, Alain; Melin, Gilles; Boivin, David; Gilard, Olivier; Sotom, Michel

2017-11-01

We demonstrate for the first time a radiationresistant Erbium-Doped Fiber exhibiting performances that can fill the requirements of Erbium-Doped Fiber Amplifiers for space applications. This is based on an Aluminum co-doping atom reduction enabled by Nanoparticules Doping-Process. For this purpose, we developed several fibers containing very different erbium and aluminum concentrations, and tested them in the same optical amplifier configuration. This work allows to bring to the fore a highly radiation resistant Erbium-doped pure silica optical fiber exhibiting a low quenching level. This result is an important step as the EDFA is increasingly recognized as an enabling technology for the extensive use of photonic sub-systems in future satellites.

Influence of levels of information as presented by different technologies on students' understanding of acid, base, and ph concepts

NASA Astrophysics Data System (ADS)

Nakhleh, Mary B.; Krajcik, Joseph S.

We investigated how different levels of information presented by various technologies affected secondary students' understanding of acid, base, and pH concepts. Secondary students who were selected for the study had just completed their study of acid-base chemistry. No attempt was made to provide further instruction. We analyzed changes in the understanding of individual students by constructing concept maps from the propositions that the students used in interviews conducted before and after a series of acid-base titrations. After the initial interview, students were divided into three groups. Within each group, students individually performed the same set of titrations using different technologies: chemical indicators, pH meters, and microcomputer-based laboratories (MBL). After the titrations were completed, all students were interviewed again. We found that students using MBL exhibited a larger positive shift in their concept map scores, which indicates a greater differentiation and integration of their knowledge of acids and bases. The chemical indicator students exhibited a more moderate positive shift in their concept map scores, and the pH meter students exhibited a smaller positive shift. We also found that the MBL students constructed more inappropriate links in their concept maps than the chemical indicator or pH meter students. However, we speculate that this increased number of inappropriate links indicates a high level of involvement with the technology. We therefore argue that the level of information offered by the technology affected students' understanding of the chemical concepts.Received: 24 February 1993; Revised: 21 February 1994;

The relationship between visitor characteristics and learning-associated behaviors in a science museum discovery space

NASA Astrophysics Data System (ADS)

Lozowski Boisvert, Dorothy; Jochums Slez, Brenda

As informal educational institutions, science museums must do more than entertain and amaze visitors. Museum educators must design exhibits that attract and hold the attention of visitors long enough so that the visitors become engaged with the exhibits and learn from them. In order for museum educators to develop such exhibits, more information is needed about the variables associated with learning in museums. This study contributes to the growing body of knowledge on informal education by examining the relationship between visitor characteristics and attraction, holding power, and visitor engagement.One hundred fifty-four visitors to a science museum discovery space were observed as they interacted freely with the exhibits. Trained volunteers recorded the subjects' movements including the exhibits at which they stopped (attraction), the amount of time spent at each exhibit (holding power), and behaviors indicative of subjects' engagement levels with the exhibits. Data indicated significant differences between age group and the holding power of exhibits. Though not significant statistically, a similar trend was noted between age group and attraction and visitor engagement level. No significant differences were found between gender or social grouping and attraction, holding power, or engagement levels.

The intervention effect of zuogui pill on chronic kidney disease-mineral and bone disorder regulatory factor.

PubMed

Ma, Xiaohong; He, Liqun

2018-06-24

Chronic kidney disease-mineral and bone disorder (CKD-MBD) play a critical role in the pathogenesis of cardiovascular complications in patients with chronic kidney disease (CKD). Zuogui pill as a traditional Chinese herbal drug has been used for nourish kidney essence improve bone malnutrition of renal bone disease by regulating the metabolism of calcium and phosphorus and participating in osteoblast metabolism. In the present study, 5/6 nephrectomy rat model was used to reveal the mechanism of zuogui pill in treatment of CKD-MBD. Compared with sham rats, the levels of serum phosphorus, PTH, iPTH and creatinine were significantly decreased, while the serum calcium level was significantly increased, and the Cbfa1 protein level was significantly decreased and FGF23 protein level was significantly increased by Zuogui pill treatment. Compared with model rats, the BMD of rat was significantly increased by Zuogui pill treatment. Histological analysis revealed that the kidney injury of rats with CKD was significantly reduced by zuogui pill treatment. Compared with model rats, the CYP27B1 mRNA level was significantly increased, and the PTH mRNA level and NaPiIIa protein level were significantly decreased in the kidney by zuogui pill treatment. We inferred that zuogui pill exhibited potential therapeutic effects on CKD-MBD in the rats by regulating bone metabolism and nourish kidney. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

NASA Astrophysics Data System (ADS)

Ke, Zhang-Hong; Pan, Jie-Xue; Jin, Lu-Yang; Xu, Hai-Yan; Yu, Tian-Tian; Ullah, Kamran; Rahman, Tanzil Ur; Ren, Jun; Cheng, Yi; Dong, Xin-Yan; Sheng, Jian-Zhong; Huang, He-Feng

2016-08-01

Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns.

Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

PubMed Central

Ke, Zhang-Hong; Pan, Jie-Xue; Jin, Lu-Yang; Xu, Hai-Yan; Yu, Tian-Tian; Ullah, Kamran; Rahman, Tanzil Ur; Ren, Jun; Cheng, Yi; Dong, Xin-Yan; Sheng, Jian-Zhong; Huang, He-Feng

2016-01-01

Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns. PMID:27502578

A Virulent Strain of Deformed Wing Virus (DWV) of Honeybees (Apis mellifera) Prevails after Varroa destructor-Mediated, or In Vitro, Transmission

PubMed Central

Ryabov, Eugene V.; Wood, Graham R.; Fannon, Jessica M.; Moore, Jonathan D.; Bull, James C.; Chandler, Dave; Mead, Andrew; Burroughs, Nigel; Evans, David J.

2014-01-01

The globally distributed ectoparasite Varroa destructor is a vector for viral pathogens of the Western honeybee (Apis mellifera), in particular the Iflavirus Deformed Wing Virus (DWV). In the absence of Varroa low levels DWV occur, generally causing asymptomatic infections. Conversely, Varroa-infested colonies show markedly elevated virus levels, increased overwintering colony losses, with impairment of pupal development and symptomatic workers. To determine whether changes in the virus population were due Varroa amplifying and introducing virulent virus strains and/or suppressing the host immune responses, we exposed Varroa-naïve larvae to oral and Varroa-transmitted DWV. We monitored virus levels and diversity in developing pupae and associated Varroa, the resulting RNAi response and transcriptome changes in the host. Exposed pupae were stratified by Varroa association (presence/absence) and virus levels (low/high) into three groups. Varroa-free pupae all exhibited low levels of a highly diverse DWV population, with those exposed per os (group NV) exhibiting changes in the population composition. Varroa-associated pupae exhibited either low levels of a diverse DWV population (group VL) or high levels of a near-clonal virulent variant of DWV (group VH). These groups and unexposed controls (C) could be also discriminated by principal component analysis of the transcriptome changes observed, which included several genes involved in development and the immune response. All Varroa tested contained a diverse replicating DWV population implying the virulent variant present in group VH, and predominating in RNA-seq analysis of temporally and geographically separate Varroa-infested colonies, was selected upon transmission from Varroa, a conclusion supported by direct injection of pupae in vitro with mixed virus populations. Identification of a virulent variant of DWV, the role of Varroa in its transmission and the resulting host transcriptome changes furthers our understanding of this important viral pathogen of honeybees. PMID:24968198

Toxicity of nalidixic acid on candida albicans, Saccharomyces cerevisiae, and Kluyveromyces lactis.

PubMed

Sobieski, R J; Brewer, A R

1976-03-01

The antibacterial drug nalidixic acid (Nal) can suppress the growth of Candida albicans at levels of the drug normally found in urine. Growth suppression increases as drug levels are increased, and Nal also causes a similar proportional inhibition of the synthesis of all cellular macromolecules. However, growth temperature (25 versus 37 C) and the divalent cations Mg(2+) and Mn(2+) can increase C. albicans resistance to Nal. Also, nitrogen depletion of Candida shows that Nal-treated and untreated cells exhibit no difference in leucine uptake during readaptation to nitrogen. In Nal-treated, nitrogen-starved cells, ribonucleic acid and deoxyribonucleic acid (DNA) biosynthesis are less affected than in unstarved Nal-treated cells, but of the two nucleic acids DNA synthesis is the most affected. Nal-resistant strains of C. albicans exhibit a slight toxicity for macromolecular synthesis. Nal treatment of a synchronized population of Saccharomyces cerevisiae results in an increase in the culture mean doubling time of, at most, 20%, but Nal causes the loss of synchronous cell division. With a synchronized population of Kluyveromyces lactis, Nal causes an increase in the mean doubling time of upwards of 300%, with synchrony of cell division being maintained. It is known that S. cerevisiae asynchronously synthesizes mitochondrial DNA during the cell cycle, whereas with K. lactis it is synchronous. Thus, with C. albicans Nal toxicity is dependent both on the dose and the physiological state of the cell. Furthermore, Nal inhibits growth of yeast with synchronous mitochondrial DNA synthesis more adversely than yeast with asynchronous mitochondrial DNA synthesis.

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.

Revealing the transport properties of the spin-polarized β‧-Tb2(MoO4)3: DFT+U

NASA Astrophysics Data System (ADS)

Reshak, A. H.

2017-11-01

The thermoelectric properties of the spin-polarized β‧-Tb2(MoO4)3 phase are calculated using first-principles and second-principles methods to solve the semi-classical Bloch-Boltzmann transport equations. It is interesting to highlight that the calculated electronic band structure reveals that the β‧-Tb2(MoO4)3 has parabolic bands in the vicinity of the Fermi level (EF); therefore, the carriers exhibit low effective mass and hence high mobility. The existence of strong covalent bonds between Mo and O in the MoO4 tetrahedrons is more favorable for the transport of the carriers than the ionic bond. It has been found that the carrier concentration of spin-up (↑) and spin-down (↓) increases linearly with increasing the temperature and exhibits a maximum carrier concentration at EF. The calculations reveal that the β‧-Tb2(MoO4)3 exhibits maximum electrical conductivity, minimum electronic thermal conductivity, a large Seebeck coefficient and a high power factor at EF for (↑) and (↓). Therefore, the vicinity of EF is the area where the β‧-Tb2(MoO4)3 is expected to show maximum efficiency.

Glucose Uptake and Triacylglycerol Synthesis Are Increased in Barth Syndrome Lymphoblasts.

PubMed

Mejia, Edgard M; Zinko, James C; Hauff, Kristin D; Xu, Fred Y; Ravandi, Amir; Hatch, Grant M

2017-02-01

Barth syndrome (BTHS) is an X-linked genetic disease resulting in loss of cardiolipin (Ptd 2 Gro). Patients may be predisposed to hypoglycemia and exhibit increases in whole-body glucose disposal rates and a higher fat mass percentage. We examined the reasons for this in BTHS lymphoblasts. BTHS lymphoblasts exhibited a 60% increase (p < 0.004) in 2-[1,2- 3 H(N)]deoxy-D-glucose uptake, a 40% increase (p < 0.01) in glucose transporter-3 protein expression, an increase in phosphorylated-adenosine monophosphate kinase (AMPK) and a 58% increase (p < 0.001) in the phosphorylated-AMPK/AMPK ratio compared to controls. In addition, BTHS lymphoblasts exhibited a 90% (p < 0.001) increase in D-[U- 14 C]glucose incorporated into 1,2,3-triacyl-sn-glycerol (TAG) and a 29% increase (p < 0.025) in 1,2-diacyl-sn-glycerol acyltransferase-2 activity compared to controls. Thus, BTHS lymphoblasts exhibit increased glucose transport and increased glucose utilization for TAG synthesis. These results may, in part, explain why BTHS patients exhibit an increase in whole-body glucose disposal rates, may be predisposed to hypoglycemia and exhibit a higher fat mass percentage.

Wear behavior of austenite containing plate steels

NASA Astrophysics Data System (ADS)

Hensley, Christina E.

As a follow up to Wolfram's Master of Science thesis, samples from the prior work were further investigated. Samples from four steel alloys were selected for investigation, namely AR400F, 9260, Hadfield, and 301 Stainless steels. AR400F is martensitic while the Hadfield and 301 stainless steels are austenitic. The 9260 exhibited a variety of hardness levels and retained austenite contents, achieved by heat treatments, including quench and tempering (Q&T) and quench and partitioning (Q&P). Samples worn by three wear tests, namely Dry Sand/Rubber Wheel (DSRW), impeller tumbler impact abrasion, and Bond abrasion, were examined by optical profilometry. The wear behaviors observed in topography maps were compared to the same in scanning electron microscopy micrographs and both were used to characterize the wear surfaces. Optical profilometry showed that the scratching abrasion present on the wear surface transitioned to gouging abrasion as impact conditions increased (i.e. from DSRW to impeller to Bond abrasion). Optical profilometry roughness measurements were also compared to sample hardness as well as normalized volume loss (NVL) results for each of the three wear tests. The steels displayed a relationship between roughness measurements and observed wear rates for all three categories of wear testing. Nanoindentation was used to investigate local hardness changes adjacent to the wear surface. DSRW samples generally did not exhibit significant work hardening. The austenitic materials exhibited significant hardening under the high impact conditions of the Bond abrasion wear test. Hardening in the Q&P materials was less pronounced. The Q&T microstructures also demonstrated some hardening. Scratch testing was performed on samples at three different loads, as a more systematic approach to determining the scratching abrasion behavior. Wear rates and scratch hardness were calculated from scratch testing results. Certain similarities between wear behavior in scratch testing and DSRW samples were observed. Different microstructures exhibited different scratching behaviors. Martensitic microstructures exhibited chipping and cracking, whereas Q&P microstructures exhibited limited or no chipping. The Q&P samples exhibited more deformation at greater loads and hardness levels than the martensitic microstructures. Austenitic microstructures exhibited significant deformation adjacent to the scratches.

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

Cadmium induced pathophysiology: prophylactic role of edible jute (Corchorus olitorius) leaves with special emphasis on oxidative stress and mitochondrial involvement.

PubMed

Dewanjee, Saikat; Gangopadhyay, Moumita; Sahu, Ranabir; Karmakar, Sarmila

2013-10-01

The present study was undertaken to evaluate the protective effect of aqueous extract of Corchorus olitorius leaves (AECO) against CdCl₂ intoxication. In vitro bioassay on isolated mice hepatocytes confirmed dose dependent cytoprotective effect of AECO. The CdCl₂ (30 μM) exhibited a significantly increased levels of lipid peroxidation, protein carbonylation along with the reduction of antioxidant enzymes and reduced glutathione levels in hepatocytes. AECO (200 and 400 μg/ml) + CdCl₂ (30 μM) could significantly restore the aforementioned oxidation parameters in hepatocytes. Beside this, AECO could significantly reduce Cd-induced increase in Bad/Bcl-2 ratio and the over-expression of NF-κB, caspase 3 and caspase 9. In in vivo assay, CdCl₂ (4 mg/kg body weight, for 6 days) treated rats exhibited a significantly increased intracellular Cd accumulation, oxidative stress and DNA fragmentation in the organs. In addition, the haematological parameters were significantly altered in the CdCl₂ treated rats. Simultaneous administration of AECO (50 and 100 mg/kg body weight), could significantly restore the biochemical, antioxidant and haematological parameters near to the normal status. Histological studies of the organs supported the protective role of jute leaves. Presence of substantial quantity of phenolic compounds and flavonoids in extract may be responsible for overall protective effect. Copyright © 2013 Elsevier Ltd. All rights reserved.

Nitric oxide measurements in hTERT-RPE cells and subcellular fractions exposed to low levels of red light

NASA Astrophysics Data System (ADS)

Wigle, Jeffrey C.; Castellanos, Cherry C.; Denton, Michael L.; Holwitt, Eric A.

2014-02-01

Cells in a tissue culture model for laser eye injury exhibit increased resistance to a lethal pulse of 2.0-μm laser radiation if the cells are first exposed to 2.88 J/cm2 of red light 24 hr prior to the lethal laser exposure. Changes in expression of various genes associated with apoptosis have been observed, but the biochemical link between light absorption and gene expression remains unknown. Cytochome c oxidase (CCOX), in the electron transport chain, is the currentlyhypothesized absorber. Absorption of the red light by CCOX is thought to facilitate displacement of nitric oxide (NO) by O2 in the active site, increasing cellular respiration and intracellular ATP. However, NO is also an important regulator and mediator of numerous physiological processes in a variety of cell and tissue types that is synthesized from l-arginine by NO synthases. In an effort to determine the relative NO contributions from these competing pathways, we measured NO levels in whole cells and subcellular fractions, with and without exposure to red light, using DAF-FM, a fluorescent dye that stoichiometrically reacts with NO. Red light induced a small, but consistently reproducible, increase in fluorescence intensity in whole cells and some subcellular fractions. Whole cells exhibited the highest overall fluorescence intensity followed by (in order) cytosolic proteins, microsomes, then nuclei and mitochondria.

[CAM in Tillandsia usneoides: Studies on the pathway of carbon and the dependency of CO2-exchange on light intensity, temperature and water content of the plant].

PubMed

Kluge, M; Lange, O L; Eichmann, M V; Schmid, R

1973-12-01

Tillandsia usneoides, in the common sense a non-succulent plant, exhibits CO2 exchange characterized by net CO2 dark fixation during the night and depression of CO2 exchange during the day. Malate has been demonstrated to accumulate during CO2 dark fixation and to be converted to carbohydrates in light. Thus, T. usneoides exhibits CAM like typical succulents.Net CO2 uptake during the day is increased with net CO2 output being suppressed in duration of time and extent when light intensity increases. Furthermore, a slight increase in CO2 fixation during the following night can be observed if the plants were treated with high light intensity during the previous day.Curves of CO2 exchange typical for CAM are obtained if T. usneoides is kept at 15°C and 20°C. Lower temperature tend to increase CO2 uptake during the day and to inhibit CO2 dark fixation. Temperatures higher than 20°C favour loss of CO2 by respiration, which becomes apparent during the whole day and night at 30°C and higher temperatures. Thus, T. usneoides gains carbon only at temperatures well below 25°C.Net CO2 uptake during the day occurs only in moist plant material and is inhibited in plants cept under water stress conditions. However, CO2 uptake during the night is clearly favoured if the plants dry out. Therefore dry plants gain more carbon than moist ones.Curves of CO2 exchange typical for CAM were also obtained with 13 other species of the genus Tillandsia.The exhibition of CAM by the non-succulent T. usneoides calls for a new definition of the term "succulence" if it is to remain useful in characterizing this metabolic pathway. Because CO2-fixing cells of T. usneoides possess relatively large vacuoles and are relatively poor in chloroplasts, they resembles the assimilatory cells of typical CAM-exhibiting succulents. Therefore, if "succulence" only means the capacity of big vacuoles to store malate, the assimilatory cells in T. usneoides are succulent. It seems to be useful to investigate parameters which would allow a definition of the term "succulence" on the level of the cell rather than on the level of the whole plant or plant organs.

Changes in Triglyceride Levels Over Time and Risk of Type 2 Diabetes in Young Men

PubMed Central

Tirosh, Amir; Shai, Iris; Bitzur, Rafael; Kochba, Ilan; Tekes-Manova, Dorit; Israeli, Eran; Shochat, Tzippora; Rudich, Assaf

2008-01-01

OBJECTIVE—The association between changes in triglyceride concentrations over time and diabetes is unknown. We assessed whether two triglyceride determinations obtained 5 years apart can predict incident type 2 diabetes. RESEARCH DESIGN AND METHODS—Triglyceride levels at baseline (time 1) and 5 years later (time 2), followed by subsequent follow-up of 5.5 years, were measured in 13,953 apparently healthy men (age 26–45 years) with triglycerides <300 mg/dl (<3.39 mmol/l). RESULTS—During 76,742 person-years, 322 cases of diabetes occurred. A multivariate model adjusted for age, BMI, total cholesterol–to–HDL cholesterol ratio, family history of diabetes, fasting glucose, blood pressure, physical activity, and smoking status revealed a continuous independent rise in incident diabetes with increasing time 1 triglyceride levels (Ptrend < 0.001). Men in the lowest tertile of time 1 triglyceride levels who progressed to the highest tertile over follow-up (low-high) exhibited a hazard ratio (HR) of 12.62 (95% CI 3.52–31.34) compared with those remaining in the lowest tertile at both time points (reference group: low-low). Whereas men who were at the top triglyceride level tertile throughout follow-up (high-high) had a HR for diabetes of 7.08 (2.52–14.45), those whose triglyceride level decreased to the lowest tertile (high-low) exhibited a HR of 1.97 (0.67–6.13). Alterations in triglyceride levels during follow-up were associated with changes in BMI, physical activity, and eating breakfast habit (P < 0.05), but remained an independent modifier of diabetes risk even after adjustment for such changes. CONCLUSIONS—Two measurements of fasting triglyceride levels obtained 5 years apart can assist in identifying apparently healthy young men at increased risk for diabetes, independent of traditional risk factors and of associated changes in BMI and lifestyle parameters. PMID:18591400

Changes in triglyceride levels over time and risk of type 2 diabetes in young men.

PubMed

Tirosh, Amir; Shai, Iris; Bitzur, Rafael; Kochba, Ilan; Tekes-Manova, Dorit; Israeli, Eran; Shochat, Tzippora; Rudich, Assaf

2008-10-01

The association between changes in triglyceride concentrations over time and diabetes is unknown. We assessed whether two triglyceride determinations obtained 5 years apart can predict incident type 2 diabetes. Triglyceride levels at baseline (time 1) and 5 years later (time 2), followed by subsequent follow-up of 5.5 years, were measured in 13,953 apparently healthy men (age 26-45 years) with triglycerides <300 mg/dl (<3.39 mmol/l). During 76,742 person-years, 322 cases of diabetes occurred. A multivariate model adjusted for age, BMI, total cholesterol-to-HDL cholesterol ratio, family history of diabetes, fasting glucose, blood pressure, physical activity, and smoking status revealed a continuous independent rise in incident diabetes with increasing time 1 triglyceride levels (P(trend) < 0.001). Men in the lowest tertile of time 1 triglyceride levels who progressed to the highest tertile over follow-up (low-high) exhibited a hazard ratio (HR) of 12.62 (95% CI 3.52-31.34) compared with those remaining in the lowest tertile at both time points (reference group: low-low). Whereas men who were at the top triglyceride level tertile throughout follow-up (high-high) had a HR for diabetes of 7.08 (2.52-14.45), those whose triglyceride level decreased to the lowest tertile (high-low) exhibited a HR of 1.97 (0.67-6.13). Alterations in triglyceride levels during follow-up were associated with changes in BMI, physical activity, and eating breakfast habit (P < 0.05), but remained an independent modifier of diabetes risk even after adjustment for such changes. Two measurements of fasting triglyceride levels obtained 5 years apart can assist in identifying apparently healthy young men at increased risk for diabetes, independent of traditional risk factors and of associated changes in BMI and lifestyle parameters.

Nicotinamide extends replicative lifespan of human cells.

PubMed

Kang, Hyun Tae; Lee, Hyung Il; Hwang, Eun Seong

2006-10-01

We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.

Impact of male obesity on infertility: a critical review of the current literature.

PubMed

Hammoud, Ahmad O; Gibson, Mark; Peterson, C Matthew; Meikle, A Wayne; Carrell, Douglas T

2008-10-01

To evaluate the current understanding of the effects and potential mechanisms of obesity on male fertility. Literature review of articles pertaining to obesity and male infertility. Recent population-based studies suggest an elevated risk for subfertility among couples in which the male partner is obese and an increased likelihood of abnormal semen parameters among heavier men. Male factor infertility is associated with a higher incidence of obesity in the male partner. Obese men exhibit reduced androgen and SHBG levels accompanied by elevated estrogen levels. Reduced inhibin B levels correlate with degree of obesity and are not accompanied by compensatory increases in FSH. This complexly altered reproductive hormonal profile suggests that endocrine dysregulation in obese men may explain the increased risk of altered semen parameters and infertility. Additional features of male obesity that may contribute to an increased risk for infertility are altered retention and metabolism of environmental toxins, altered lifestyle factors, and increased risks for sexual dysfunction. Neither reversibility of obesity-associated male infertility with weight loss nor effective therapeutic interventions have been studied yet. The increasing prevalence of obesity calls for greater clinician awareness of its effects on fertility, better understanding of underlying mechanisms, and eventually avenues for mitigation or treatment.

Transcriptional bursting explains the noise–versus–mean relationship in mRNA and protein levels

DOE PAGES

Dar, Roy; Shaffer, Sydney M.; Singh, Abhyudai; ...

2016-07-28

Recent analysis demonstrates that the HIV-1 Long Terminal Repeat (HIV LTR) promoter exhibits a range of possible transcriptional burst sizes and frequencies for any mean-expression level. However, these results have also been interpreted as demonstrating that cell-tocell expression variability (noise) and mean are uncorrelated, a significant deviation from previous results. Here, we re-examine the available mRNA and protein abundance data for the HIV LTR and find that noise in mRNA and protein expression scales inversely with the mean along analytically predicted transcriptional burst-size manifolds. We then experimentally perturb transcriptional activity to test a prediction of the multiple burst-size model: thatmore » increasing burst frequency will cause mRNA noise to decrease along given burst-size lines as mRNA levels increase. In conclusion, the data show that mRNA and protein noise decrease as mean expression increases, supporting the canonical inverse correlation between noise and mean.« less

How is adaptation, resilience, and vulnerability research engaging with gender?

NASA Astrophysics Data System (ADS)

Bunce, A.; Ford, J.

2015-12-01

The gendered dimensions of climate change have received increasing interest in climate change adaptation, resilience, and vulnerability (ARV) research. Yet concerns have been expressed that engagement with ‘gender’ in this work has been tokenistic. In this context, we ask: how is climate change ARV research engaging with gender? To answer this question, we develop an assessment framework capturing key attributes of engagement and use it to evaluate peer reviewed ARV articles with a focus on gender published since 2006 (n = 123). Results indicate an increase in ARV studies with a gender focus over this period, with the level of gender engagement also increasing. There are a relatively equal numbers of studies categorized as engaging gender at a high, medium, and low level, with studies from Sub-Saharan Africa consistently exhibiting high levels of gender engagement. Gender focused ARV has a strong focus on examining female experiences, with few studies explicitly focusing on men, and no work accounting for those identifying outside the gender binary.

Hajdu Cheney Mouse Mutants Exhibit Osteopenia, Increased Osteoclastogenesis, and Bone Resorption.

PubMed

Canalis, Ernesto; Schilling, Lauren; Yee, Siu-Pok; Lee, Sun-Kyeong; Zanotti, Stefano

2016-01-22

Notch receptors are determinants of cell fate and function and play a central role in skeletal development and bone remodeling. Hajdu Cheney syndrome, a disease characterized by osteoporosis and fractures, is associated with NOTCH2 mutations resulting in a truncated stable protein and gain-of-function. We created a mouse model reproducing the Hajdu Cheney syndrome by introducing a 6955C→T mutation in the Notch2 locus leading to a Q2319X change at the amino acid level. Notch2(Q2319X) heterozygous mutants were smaller and had shorter femurs than controls; and at 1 month of age they exhibited cancellous and cortical bone osteopenia. As the mice matured, cancellous bone volume was restored partially in male but not female mice, whereas cortical osteopenia persisted in both sexes. Cancellous bone histomorphometry revealed an increased number of osteoclasts and bone resorption, without a decrease in osteoblast number or bone formation. Osteoblast differentiation and function were not affected in Notch2(Q2319X) cells. The pre-osteoclast cell pool, osteoclast differentiation, and bone resorption in response to receptor activator of nuclear factor κB ligand in vitro were increased in Notch2(Q2319X) mutants. These effects were suppressed by the γ-secretase inhibitor LY450139. In conclusion, Notch2(Q2319X) mice exhibit cancellous and cortical bone osteopenia, enhanced osteoclastogenesis, and increased bone resorption. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Antisense RNA Strategies for Metabolic Engineering of Clostridium acetobutylicum

PubMed Central

Desai, Ruchir P.; Papoutsakis, Eleftherios T.

1999-01-01

We examined the effectiveness of antisense RNA (as RNA) strategies for metabolic engineering of Clostridium acetobutylicum. Strain ATCC 824(pRD4) was developed to produce a 102-nucleotide asRNA with 87% complementarity to the butyrate kinase (BK) gene. Strain ATCC 824(pRD4) exhibited 85 to 90% lower BK and acetate kinase specific activities than the control strain. Strain ATCC 824(pRD4) also exhibited 45 to 50% lower phosphotransbutyrylase (PTB) and phosphotransacetylase specific activities than the control strain. This strain exhibited earlier induction of solventogenesis, which resulted in 50 and 35% higher final concentrations of acetone and butanol, respectively, than the concentrations in the control. Strain ATCC 824(pRD1) was developed to putatively produce a 698-nucleotide asRNA with 96% complementarity to the PTB gene. Strain ATCC 824(pRD1) exhibited 70 and 80% lower PTB and BK activities, respectively, than the control exhibited. It also exhibited 300% higher levels of a lactate dehydrogenase activity than the control exhibited. The growth yields of ATCC 824(pRD1) were 28% less than the growth yields of the control. While the levels of acids were not affected in ATCC 824(pRD1) fermentations, the acetone and butanol concentrations were 96 and 75% lower, respectively, than the concentrations in the control fermentations. The lower level of solvent production by ATCC 824(pRD1) was compensated for by ∼100-fold higher levels of lactate production. The lack of any significant impact on butyrate formation fluxes by the lower PTB and BK levels suggests that butyrate formation fluxes are not controlled by the levels of the butyrate formation enzymes. PMID:10049845

Antisense RNA strategies for metabolic engineering of Clostridium acetobutylicum.

PubMed

Desai, R P; Papoutsakis, E T

1999-03-01

We examined the effectiveness of antisense RNA (as RNA) strategies for metabolic engineering of Clostridium acetobutylicum. Strain ATCC 824(pRD4) was developed to produce a 102-nucleotide asRNA with 87% complementarity to the butyrate kinase (BK) gene. Strain ATCC 824(pRD4) exhibited 85 to 90% lower BK and acetate kinase specific activities than the control strain. Strain ATCC 824(pRD4) also exhibited 45 to 50% lower phosphotransbutyrylase (PTB) and phosphotransacetylase specific activities than the control strain. This strain exhibited earlier induction of solventogenesis, which resulted in 50 and 35% higher final concentrations of acetone and butanol, respectively, than the concentrations in the control. Strain ATCC 824(pRD1) was developed to putatively produce a 698-nucleotide asRNA with 96% complementarity to the PTB gene. Strain ATCC 824(pRD1) exhibited 70 and 80% lower PTB and BK activities, respectively, than the control exhibited. It also exhibited 300% higher levels of a lactate dehydrogenase activity than the control exhibited. The growth yields of ATCC 824(pRD1) were 28% less than the growth yields of the control. While the levels of acids were not affected in ATCC 824(pRD1) fermentations, the acetone and butanol concentrations were 96 and 75% lower, respectively, than the concentrations in the control fermentations. The lower level of solvent production by ATCC 824(pRD1) was compensated for by approximately 100-fold higher levels of lactate production. The lack of any significant impact on butyrate formation fluxes by the lower PTB and BK levels suggests that butyrate formation fluxes are not controlled by the levels of the butyrate formation enzymes.

Cytokinins: Their Impact on Molecular and Growth Responses to Drought Stress and Recovery in Arabidopsis

PubMed Central

Prerostova, Sylva; Dobrev, Petre I.; Gaudinova, Alena; Knirsch, Vojtech; Körber, Niklas; Pieruschka, Roland; Fiorani, Fabio; Brzobohatý, Břetislav; černý, Martin; Spichal, Lukas; Humplik, Jan; Vanek, Tomas; Schurr, Ulrich; Vankova, Radomira

2018-01-01

Our phenotyping and hormonal study has characterized the role of cytokinins (CK) in the drought and recovery responses of Arabidopsis thaliana. CK down-regulation was achieved by overexpression of the gene for CK deactivating enzyme cytokinin oxidase/dehydrogenase (CKX): constitutive (35S:CKX) or at the stress onset using a dexamethasone-inducible pOp/LhGR promoter (DEX:CKX). The 35S:CKX plants exhibited slow ontogenesis and higher expression levels of stress-associated genes, e.g., AtP5CS1, already at well-watered conditions. CK down-regulation resulted during drought in higher stress tolerance (indicated by relatively low up-regulation of the expression of drought stress marker gene AtRD29B) accompanied with lower leaf water loss. Nevertheless, these plants exhibited slow and delayed recovery after re-watering. CK levels were increased at the stress onset by stimulation of the expression of CK biosynthetic gene isopentenyl transferase (ipt) (DEX:IPT) or by application of exogenous CK meta-topolin. After water withdrawal, long-term CK elevation resulted in higher water loss in comparison with CKX transformants as well as with plants overexpressing ipt driven by senescence-inducible SAG12 promoter (SAG:IPT), which gradually enhanced CKs during the stress progression. In all cases, CK up-regulation resulted in fast and more vigorous recovery. All drought-stressed plants exhibited growth suppression associated with elevation of abscisic acid and decrease of auxins and active CKs (with the exception of SAG:IPT plants). Apart from the ipt overexpressers, also increase of jasmonic and salicylic acid was found. PMID:29872444

The transport systems of Ventricaria ventricosa: hypotonic and hypertonic turgor regulation.

PubMed

Bisson, M A; Beilby, M J

2002-11-01

The time course of hypertonic and hypotonic turgor regulation was studied in Ventricaria (Valonia) using pressure probe and I/V(current-voltage) analysis. Of 11 cells, 9 exhibited hypertonic turgor regulation, ranging from 100% regulation in 150 min to 14% regulation (14% recovery of the decrease in turgor) in 314 min. Some cells began regulating immediately, others took up to 90 min to begin. The resting PD (potential difference) became more positive in most cells. The I/V characteristics became more nonlinear with high resistance between -150 and -20 mV and negative conductance region near -70 mV. Prolonged (16 sec) voltage clamps to negative levels (-100 to -150 mV) showed progressively more rapid current turn-off, but subsequent I/V characteristics were not affected. Clamping to +150 mV, however, abolished the high conductance between -50 and +100 mV to yield a uniform high resistance I/V characteristic, similar to that in high [K+]o. Decreasing illumination from 2.02 micromol sec(-1) m(-2) to 0.5 micromol sec(-1)1 m(-2) had a similar effect. Two out of a total of three cells exhibited hypotonic turgor regulation. Both cells started regulating within minutes and achieved near 50% regulation within 50 min. The PD became more negative. The I/V curves exhibited high resistance between +50 and +150 mV. The characteristics were similar to those in cells exposed to low [K+]o. Prolonged voltage clamps to both negative and positive levels showed slow current increase. Decreased illumination increased the membrane resistance.

High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents.

PubMed

Kaniowski, Damian; Ebenryter-Olbińska, Katarzyna; Sobczak, Milena; Wojtczak, Błażej; Janczak, Sławomir; Leśnikowski, Zbigniew J; Nawrot, Barbara

2017-08-23

Boron cluster-modified therapeutic nucleic acids with improved properties are of interest in gene therapy and in cancer boron neutron capture therapy (BNCT). High metallacarborane-loaded antisense oligonucleotides (ASOs) targeting epidermal growth factor receptor (EGFR) were synthesized through post-synthetic Cu (I)-assisted "click" conjugation of alkyne-modified DNA-oligonucleotides with a boron cluster alkyl azide component. The obtained oligomers exhibited increased lipophilicity compared to their non-modified precursors, while their binding affinity to complementary DNA and RNA strands was slightly decreased. Multiple metallacarborane residues present in the oligonucleotide chain, each containing 18 B-H groups, enabled the use of IR spectroscopy as a convenient analytical method for these oligomers based on the diagnostic B-H signal at 2400-2650 cm -1 . The silencing activity of boron cluster-modified ASOs used at higher concentrations was similar to that of unmodified oligonucleotides. The screened ASOs, when used in low concentrations (up to 50 μM), exhibited pro-oxidative properties by inducing ROS production and an increase in mitochondrial activities in HeLa cells. In contrast, when used at higher concentrations, the ASOs exhibited anti-oxidative properties by lowering ROS species levels. In the HeLa cells (tested in the MTT assay) treated (without lipofectamine) or transfected with the screened compounds, the mitochondrial activity remained equal to the control level or only slightly changed (±30%). These findings may be useful in the design of dual-action boron cluster-modified therapeutic nucleic acids with combined antisense and anti-oxidant properties.

Breast tumor DNA methylation patterns associated with smoking in the Carolina Breast Cancer Study.

PubMed

Conway, Kathleen; Edmiston, Sharon N; Parrish, Eloise; Bryant, Christopher; Tse, Chiu-Kit; Swift-Scanlan, Theresa; McCullough, Lauren E; Kuan, Pei Fen

2017-06-01

Tobacco smoking is a risk factor in several cancers, yet its roles as a putative etiologic exposure or poor prognostic factor in breast cancer are less clear. Altered DNA methylation contributes to breast cancer development and may provide a mechanistic link between smoking and gene expression changes leading to cancer development or progression. Using a cancer-focused array, we examined methylation at 933 CpGs in 517 invasive breast tumors in the Carolina Breast Cancer Study to determine whether methylation patterns differ by exposure to tobacco smoke. Multivariable generalized linear regression models were used to compare tumor methylation profiles between smokers and never smokers, overall, or stratified on hormone receptor (HR) status. Modest differences in CpG methylation were detected at p < 0.05 in breast tumors from current or ever smokers compared with never smokers. In stratified analyses, HR- tumors from smokers exhibited primarily hypomethylation compared with tumors from never smokers; hypomethylation was similarly detected within the more homogeneous basal-like subtype. Most current smoking-associated CpG loci exhibited methylation levels in former smokers that were intermediate between those in current and never smokers and exhibited progressive changes in methylation with increasing duration of smoking. Among former smokers, restoration of methylation toward baseline (never smoking) levels was observed with increasing time since quitting. Moreover, smoking-related hypermethylation was stronger in HR+ breast tumors from blacks than in whites. Our results suggest that breast tumor methylation patterns differ with tobacco smoke exposure; however, additional studies are needed to confirm these findings.

Diet-induced obesity, energy metabolism and gut microbiota in C57BL/6J mice fed Western diets based on lean seafood or lean meat mixtures.

PubMed

Holm, Jacob Bak; Rønnevik, Alexander; Tastesen, Hanne Sørup; Fjære, Even; Fauske, Kristin Røen; Liisberg, Ulrike; Madsen, Lise; Kristiansen, Karsten; Liaset, Bjørn

2016-05-01

High protein diets may protect against diet-induced obesity, but little is known regarding the effects of different protein sources consumed at standard levels. We investigated how a mixture of lean seafood or lean meat in a Western background diet modulated diet-induced obesity, energy metabolism and gut microbiota. Male C57BL/6J mice fed a Western diet (WD) containing a mixture of lean seafood (seafood WD) for 12weeks accumulated less fat mass than mice fed a WD containing a mixture of lean meat (meat WD). Meat WD-fed mice exhibited increased fasting blood glucose, impaired glucose clearance, elevated fasting plasma insulin and increased plasma and liver lipid levels. We observed no first choice preference for either of the WDs, but over time, mice fed the seafood WD consumed less energy than mice fed the meat WD. Mice fed the seafood WD exhibited higher spontaneous locomotor activity and a lower respiratory exchange ratio (RER) than mice fed the meat WD. Thus, higher activity together with the decreased energy intake contributed to the different phenotypes observed in mice fed the seafood WD compared to mice fed the meat WD. Comparison of the gut microbiomes of mice fed the two WDs revealed significant differences in the relative abundance of operational taxonomic units (OTUs) belonging to the orders Bacteroidales and Clostridiales, with genes involved in metabolism of aromatic amino acids exhibiting higher relative abundance in the microbiomes of mice fed the seafood WD. Copyright © 2016 Elsevier Inc. All rights reserved.

Variation and significance of secretory immunoglobulin A, interleukin 6 and dendritic cells in oral cancer.

PubMed

Zhang, Suxin; Zhang, Xin; Yin, Ke; Li, Tianke; Bao, Yang; Chen, Zhong

2017-04-01

The present study aimed to determine changes in the concentration of secretory immunoglobulin A (SIgA) and interleukin 6 (IL-6) in the saliva of patients with oral cancer, to evaluate the abnormal expression of cluster of differentiation (CD) 1a, CD83, CD80 and CD86 on dendritic cells (DCs) of oral cancer tissues and to discuss the interaction between SIgA, IL-6 and DCs in oral cancer. A total of 40 patients between 27 and 70 years of age, median age 52 years, with primary oral cancer were enrolled in the present study, and a group of 20 healthy male and female volunteers was used as the control group. The concentration of SIgA and IL-6 in the saliva of the preoperative patients was determined by ELISA. The expression levels of CD1a, CD83, CD80 and CD86 were detected by immunohistochemistry and flow cytometry, which was performed on histopathological sections from paraffin-embedded tumor and corresponding adjacent control tissues. The specimens were assessed using the semi-quantitative immunoreactive score (IRS). The concentration of SIgA in the saliva from patients with oral cancer decreased, whereas the IL-6 level significantly increased compared with the control subjects (P<0.05). In addition, the decrease of SIgA level and increase of IL-6 level exhibited a negative correlation (r=-0.543, P<0.05). According to the IRS score, the expression levels of CD1a, CD83, CD80 and CD86 in the cancer tissue were lower than the expression levels of the control group (P<0.05). Furthermore, the expression of CD80 and CD86 exhibited no correlation with histological grade or pathological type (P>0.05), but exhibited a negative correlation with clinical stage and lymph node metastasis (P<0.05). The concentration of SIgA and IL-6 in saliva may be used as an auxiliary diagnostic indicator for oral cancer. The detection of CD80 and CD86 expressed on DCs in oral cancer tissue may be useful for the diagnosis and evaluation of the prognosis of tumors. The present study hypothesized that the use of SIgA vaccines or IL-6 inhibitors may be useful for reversing the immune deficiency associated with DCs in oral cancer.

Increased serum and testicular androgen levels in F1 rats with lifetime exposure to soy isoflavones.

PubMed

McVey, Mark J; Cooke, Gerard M; Curran, Ivan H A

2004-07-01

The consequences of dietary soy isoflavones on serum and testicular androgen levels were examined in F1 male rats from a multigeneration study investigating the effects of diets varying in isoflavone content. Rats were fed either a soy-free casein based diet (AIN93G) or a diet in which alcohol-washed soy protein replaced casein as the protein source and to which increasing amounts of Novasoy, a commercially available isoflavone supplement were added. Analysis of these diets showed that the isoflavone content in each diet was 0 (diet 1; casein based control), 31.7 (diet 2; alcohol-washed soy-based diet control), 36.1 (diet 3), 74.5 (diet 4), 235.6 (diet 5) and 1046.6 (diet 6) mg total isoflavones/kg pelleted diet. The levels of isoflavones in diet 1 would represent a daily intake level of 0 mg isoflavones, diets 2 and 3 estimate a low soy-containing human diet (e.g. North American), diet 4 would correspond to Asian diets (e.g. Japanese) or adult humans taking isoflavone supplements, diet 5 approximates the isoflavone intake by babies fed soy based infant formula and diet 6 approximates fivefold the intake levels by babies or 10-fold the intake levels of adults consuming high isoflavone containing diets. Serum testosterone (T) from F1 male rats sacrificed on postnatal days (PND) 28, 70, 120, 240 and 360 were low at PND 28 (0.4 ng/ml), increased approximately five to sixfold at PND 70 (2.5-3.0 ng/ml) and thereafter declined to a steady state level of approximately 1 ng/ml by PND 120. However, rats on diets 5 and 6 demonstrated altered serum testosterone profiles such that at days 120, testosterone levels remained significantly elevated at approximately 3 ng/ml (P < 0.05). Serum dihydrotestosterone levels exhibited similar profiles and the levels in PND 120 rats on diet 5 or 6 were also significantly elevated (two to threefold, P < 0.05). The intra-testicular testosterone concentration in rats on diet 5 was also elevated at PND 120 compared with diet 1 (P < 0.05). These findings show that F1 male rats continuously exposed to a mixture of dietary soy isoflavones from conception onwards exhibit altered serum and testicular androgen profiles.

Fuel level sensor based on polymer optical fiber Bragg gratings for aircraft applications

NASA Astrophysics Data System (ADS)

Marques, C. A. F.; Pospori, A.; Sáez-Rodríguez, D.; Nielsen, K.; Bang, O.; Webb, D. J.

2016-04-01

Safety in civil aviation is increasingly important due to the increase in flight routes and their more challenging nature. Like other important systems in aircraft, fuel level monitoring is always a technical challenge. The most frequently used level sensors in aircraft fuel systems are based on capacitive, ultrasonic and electric techniques, however they suffer from intrinsic safety concerns in explosive environments combined with issues relating to reliability and maintainability. In the last few years, optical fiber liquid level sensors (OFLLSs) have been reported to be safe and reliable and present many advantages for aircraft fuel measurement. Different OFLLSs have been developed, such as the pressure type, float type, optical radar type, TIR type and side-leaking type. Amongst these, many types of OFLLSs based on fiber gratings have been demonstrated. However, these sensors have not been commercialized because they exhibit some drawbacks: low sensitivity, limited range, long-term instability, or limited resolution. In addition, any sensors that involve direct interaction of the optical field with the fuel (either by launching light into the fuel tank or via the evanescent field of a fiber-guided mode) must be able to cope with the potential build up of contamination - often bacterial - on the optical surface. In this paper, a fuel level sensor based on microstructured polymer optical fiber Bragg gratings (mPOFBGs), including poly (methyl methacrylate) (PMMA) and TOPAS fibers, embedded in diaphragms is investigated in detail. The mPOFBGs are embedded in two different types of diaphragms and their performance is investigated with aviation fuel for the first time, in contrast to our previous works, where water was used. Our new system exhibits a high performance when compared with other previously published in the literature, making it a potentially useful tool for aircraft fuel monitoring.

Low and moderate photosynthetically active radiation affects the flavonol glycosides and hydroxycinnamic acid derivatives in kale (Brassica oleracea var. sabellica) dependent on two low temperatures.

PubMed

Neugart, Susanne; Fiol, Michaela; Schreiner, Monika; Rohn, Sascha; Zrenner, Rita; Kroh, Lothar W; Krumbein, Angelika

2013-11-01

Kale (Brassica oleracea var. sabellica) contains a large number of naturally occurring structurally different non-acylated and acylated flavonol glycosides as well as hydroxycinnamic acid derivatives. The objective of this study was to determine the effect of low and moderate photosynthetic active radiation (PAR) and how these levels interact with low temperature in these phenolic compounds. Juvenile kale plants were treated with PAR levels from 200 to 800 μmol m(-2) s(-1) at 5 and 10 °C under defined conditions in climate chambers. Of the investigated 20 compounds, 11 and 17 compounds were influenced by PAR and temperature, respectively. In addition, an interaction between PAR and temperature was found for eight compounds. The response of the phenolic compounds to PAR was structure-dependent. While quercetin triglycosides increased with higher PAR at 5 and 10 °C, the kaempferol triglycosides exhibited the highest concentrations at 400 μmol m(-2) s(-1). In contrast, kaempferol diglycosides exhibited the highest concentrations at increased PAR levels of 600 and 800 μmol m(-2) s(-1) at 10 °C. However, key genes of flavonol biosynthesis were influenced by temperature but remained unaffected by PAR. Furthermore, there was no interaction between the PAR level and the low temperature in the response of hydroxycinnamic acid derivatives in kale with the exception of caffeoylquinic acid, which decreased with higher PAR levels of 600 and 800 μmol m(-2) s(-1) and at a lower temperature. In conclusion, PAR and its interaction with temperature could be a suitable tool for modifying the profile of phenolic compounds. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Varied immuno-related adverse events induced by immune-check point inhibitors - Nivolumab-associated psoriasiform dermatitis related with increased serum level of interleukin-6.

PubMed

Okiyama, Naoko; Tanaka, Ryota

2017-01-01

Nivolumab is a standard recombinant antibody treatment for patients with malignant melanoma (MM), which functions as an immune checkpoint inhibitor by blocking the programmed cell death-1 (PD-1) pathway in T cells. However, it leads to various immune-related adverse events (irAEs), and also exacerbates underlying autoimmune diseases. Herein we report cases of MM with irAE. Case 1: A 69-year-old woman with MM developed destructive thyroiditis resulting in hypothyroidism after 3 doses of nivolumab, and had been treated with thyroid gland auxiliary therapy. Case 2: A 80-year-old man with MM developed an acute onset of hyperthyroidism after 4 doses of nivolumab. Case 3: A 85-year-old woman with MM developed polyradiculoneuropathy resulting in somatosensory disorder and muscle weakness after 2 doses of nivolumab, and had been treated with intravenous immunoglobulin and oral predonisolone (40 mg/day). Case 4: A 77-year-old man with MM developed psoriasiform dermatitis after local injections of IFN-β and 11 doses of nivolumab. Case 5: Case 2 also developed psoriasiform dermatitis. We analyzed serum levels of inflammatory cytokines in MM patients before/after treatments with nivolumab. All six patients who developed psoriasiform dermatitis with/without anamnesis of psoriasis after treatment with nivolumab, and all seven patients with other irAE exhibited increased serum IL-6 levels after nivolumab treatment, while decreased serum levels of IL-6 were observed in 5 of 7 non-afflicted MM patients. In addition, MM patients who achieved good responses to nivolumab significantly exhibited decreased serum TNF-α levels after nivolumab treatment compared to progressive MM patients.

IGF-1 REGULATES VERTEBRAL BONE AGING THROUGH SEX-SPECIFIC AND TIME-DEPENDENT MECHANISMS

PubMed Central

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L.; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-01-01

Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, while others report that loss of IGF-1 is beneficial as it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igff/f mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan- early in postnatal development (crossing albumin-Cre mice with Igff/f mice), or early adulthood, and late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using microCT and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NFkB-ligand levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2 fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. PMID:26260312

IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

PubMed

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-02-01

Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igf(f/f) mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin-cyclic recombinase [Cre] mice with Igf(f/f) mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro-computed tomography (μCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NF-κB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. © 2015 American Society for Bone and Mineral Research.

Effects of food deprivation on expression of growth hormone receptor and proximate composition in liver of black seabream Acanthopagrus schlegeli.

PubMed

Deng, L; Zhang, W M; Lin, H R; Cheng, Christopher H K

2004-04-01

The effects of food deprivation on the hepatic level growth hormone receptor (GHR) were investigated in black seabream (Acanthopagrus schlegeli) both at the protein level (by radioreceptor assay) and at the mRNA level (by ribonuclease protection assay). Serum levels of growth hormone (GH) and triiodothyronine (T(3)) were also measured. Condition factor and hepatic proximate composition of the fish were also assessed. Significant decrease in hepatic GHR binding was recorded as early as on day 2 of starvation. On day 30 this decrease was even more pronounced, with the level in the starved fish reaching less than 20% the fed control level. A concomitant decrease in the hepatic GHR mRNA content was also noted during this period, with a progressive decrease from day 2 to day 30 of starvation. The extent of decrease in the mRNA content was less pronounced than the decrease in receptor binding, with the hepatic GHR mRNA content in the day 30 starved fish representing approximately 30% of the level in the fed control. In large contrast, serum GH level increased progressively during starvation. After 30 days of starvation, serum GH levels in the starved fish were more than three times the concentration found in the fed control. Serum T(3) levels, on the other hand, decreased during starvation, with the difference reaching significance on day 15 and day 30. After 30 days of starvation, serum T(3) levels in the starved fish were only approximately 40% the concentration found in the fed control. The hepatic lipid content exhibited an increasing trend during starvation. On day 30 the hepatic lipid content of the starved fish had doubled the level found in the fed control. However, the hepatic protein content did not exhibit much change during starvation. There was also a minor decrease in the moisture content of the liver during starvation, but the condition factor of the fish as a whole registered a gradual decrease during the course of food deprivation.

Sodium citrate inhibits the proliferation of human gastric adenocarcinoma epithelia cells

PubMed Central

Xia, Yuan; Zhang, Xulong; Bo, Agula; Sun, Juan; Li, Minhui

2018-01-01

The objective of the present study was to investigate the cytotoxic effects of sodium citrate on human gastric adenocarcinoma epithelia AGS cells. Numerous cytotoxicity-associated sodium citrate-induced effects were assessed, including cell viability and proliferation, cytokine expression and caspase activity. In vitro studies demonstrated that incubation with sodium citrate (>3.125 mM) inhibited AGS cell viability and proliferation in a dose-dependent manner. Incubation with sodium citrate for 24 h revealed that the levels of interleukin-1β (IL-1β), IL-8 and tumor necrosis factor increased with an increasing of dose of sodium citrate, whereas the IL-6 levels exhibited only a slight alteration. In addition, increases in caspase-3 and −9 activities were associated with increased duration of treatment and dosage of sodium citrate. Collectively, the results of the present study demonstrated that treatment with sodium citrate at higher concentrations or for longer durations exerts a cytotoxic effect on AGS cells via the induction of the intrinsic apoptosis pathway and the alteration in the levels of certain cytokines. PMID:29616124

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

Sivakumar Babu, G.L., E-mail: gls@civil.iisc.ernet.in; Lakshmikanthan, P., E-mail: lakshmikanthancp@gmail.com; Santhosh, L.G., E-mail: lgsanthu2006@gmail.com

Highlights: • Shear strength properties of mechanically biologically treated municipal solid waste. • Effect of unit weight and particle size on the shear strength of waste. • Effect of particle size on the strength properties. • Stiffness ratio and the strength ratio of MSW. - Abstract: Strength and stiffness properties of municipal solid waste (MSW) are important in landfill design. This paper presents the results of comprehensive testing of shear strength properties of mechanically biologically treated municipal solid waste (MBT-MSW) in laboratory. Changes in shear strength of MSW as a function of unit weight and particle size were investigated bymore » performing laboratory studies on the MSW collected from Mavallipura landfill site in Bangalore. Direct shear tests, small scale and large scale consolidated undrained and drained triaxial tests were conducted on reconstituted compost reject MSW samples. The triaxial test results showed that the MSW samples exhibited a strain-hardening behaviour and the strength of MSW increased with increase in unit weight. Consolidated drained tests showed that the mobilized shear strength of the MSW increased by 40% for a unit weight increase from 7.3 kN/m{sup 3} to 10.3 kN/m{sup 3} at 20% strain levels. The mobilized cohesion and friction angle ranged from 5 to 9 kPa and 8° to 33° corresponding to a strain level of 20%. The consolidated undrained tests exhibited reduced friction angle values compared to the consolidated drained tests. The friction angle increased with increase in the unit weight from 8° to 55° in the consolidated undrained tests. Minor variations were found in the cohesion values. Relationships for strength and stiffness of MSW in terms of strength and stiffness ratios are developed and discussed. The stiffness ratio and the strength ratio of MSW were found to be 10 and 0.43.« less

Joint trajectories of cognitive functioning and challenging behavior for persons living with dementia in long-term care.

PubMed

Robitaille, Annie; Garcia, Linda; McIntosh, Cameron

2015-09-01

The current study examines the longitudinal relationship between dementia-related challenging behaviors (e.g., vocal disruption, physical aggression, repetitive behaviors, and restlessness) and cognitive functioning in the long-term care (LTC) context. A multivariate latent growth curve model within the structural equation modeling (SEM) framework was applied to data collected from 16,804 older adults upon admission to LTC and every 3 months for a period of 2.5 years. Increases in challenging behaviors were characterized by a significant positive linear and negative quadratic trend (i.e., a subtle leveling off at later assessment times), whereas increases in cognitive impairment were characterized by a positive linear trend. On average, individuals who were more cognitively impaired upon entry into LTC and who exhibited a steeper increase in cognitive impairment also exhibited more challenging behaviors at entry into LTC and a steeper increase in challenging behaviors, respectively. At the within-person level, individuals demonstrating an increase in cognitive impairment at a specific occasion were also more likely to demonstrate an increase in challenging behaviors at that same occasion; however, the magnitude of these effects was very small, suggesting limited practical implications. This study provides novel empirical evidence about the coevolution of cognitive impairment and challenging behaviors, going beyond prior research that has been either cross-sectional in nature, examined longitudinal change in only 1 variable, or simply looked at linear trends without attempting to explore the possibility of nonlinear change. Most importantly, this longitudinal examination of persons with dementia living in LTC has implications for how challenging behaviors can be better managed and for how new strategies can be implemented to prevent challenging behaviors. (c) 2015 APA, all rights reserved).

Shear strength characteristics of mechanically biologically treated municipal solid waste (MBT-MSW) from Bangalore.

PubMed

Sivakumar Babu, G L; Lakshmikanthan, P; Santhosh, L G

2015-05-01

Strength and stiffness properties of municipal solid waste (MSW) are important in landfill design. This paper presents the results of comprehensive testing of shear strength properties of mechanically biologically treated municipal solid waste (MBT-MSW) in laboratory. Changes in shear strength of MSW as a function of unit weight and particle size were investigated by performing laboratory studies on the MSW collected from Mavallipura landfill site in Bangalore. Direct shear tests, small scale and large scale consolidated undrained and drained triaxial tests were conducted on reconstituted compost reject MSW samples. The triaxial test results showed that the MSW samples exhibited a strain-hardening behaviour and the strength of MSW increased with increase in unit weight. Consolidated drained tests showed that the mobilized shear strength of the MSW increased by 40% for a unit weight increase from 7.3kN/m(3) to 10.3kN/m(3) at 20% strain levels. The mobilized cohesion and friction angle ranged from 5 to 9kPa and 8° to 33° corresponding to a strain level of 20%. The consolidated undrained tests exhibited reduced friction angle values compared to the consolidated drained tests. The friction angle increased with increase in the unit weight from 8° to 55° in the consolidated undrained tests. Minor variations were found in the cohesion values. Relationships for strength and stiffness of MSW in terms of strength and stiffness ratios are developed and discussed. The stiffness ratio and the strength ratio of MSW were found to be 10 and 0.43. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adaptive response of rat pancreatic β-cells to insulin resistance induced by monocrotophos: Biochemical evidence.

PubMed

Nagaraju, Raju; Rajini, Padmanabhan Sharda

2016-11-01

Our previous findings clearly suggested the role of duration of exposure to monocrotophos (MCP) in the development of insulin resistance. Rats exposed chronically to MCP developed insulin resistance with hyperinsulinemia without overt diabetes. In continuation of this vital observation, we sought to delineate the biochemical mechanisms that mediate heightened pancreatic β-cell response in the wake of MCP-induced insulin resistance in rats. Adult rats were orally administered (0.9 and 1.8mg/kgb.w/d) MCP for 180days. Terminally, MCP-treated rats exhibited glucose intolerance, hyperinsulinemia, and potentiation of glucose-induced insulin secretion along with elevated levels of circulating IGF1, free fatty acids, corticosterone, and paraoxonase activity. Biochemical analysis of islet extracts revealed increased levels of insulin, malate, pyruvate and ATP with a concomitant increase in activities of cytosolic and mitochondrial enzymes that are known to facilitate insulin secretion and enhanced shuttle activities. Interestingly, islets from MCP-treated rats exhibited increased insulin secretory potential ex vivo compared to those isolated from control rats. Further, MCP-induced islet hypertrophy was associated with increased insulin-positive cells. Our study demonstrates the impact of the biological interaction between MCP and components of metabolic homeostasis on pancreatic beta cell function/s. We speculate that the heightened pancreatic beta cell function evidenced may be mediated by increased IGF1 and paraoxonase activity, which effectively counters insulin resistance induced by chronic exposure to MCP. Our findings emphasize the need for focused research to understand the confounding environmental risk factors which may modulate heightened beta cell functions in the case of organophosphorus insecticide-induced insulin resistance. Such an approach may help us to explain the sharp increase in the prevalence of type II diabetes worldwide. Copyright © 2016 Elsevier B.V. All rights reserved.

Total levels, localization patterns, and proportions of sperm exhibiting phospholipase C zeta are significantly correlated with fertilization rates after intracytoplasmic sperm injection.

PubMed

Yelumalai, Suseela; Yeste, Marc; Jones, Celine; Amdani, Siti N; Kashir, Junaid; Mounce, Ginny; Da Silva, Sarah J Martins; Barratt, Christopher L; McVeigh, Enda; Coward, Kevin

2015-09-01

To study the relationship of total levels, localization patterns, and proportions of sperm exhibiting phospholipase C zeta, with fertilization rates after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Laboratory study; controls vs. patients after IVF (n = 27) or ICSI (n = 17) treatment. Fertility center. A total of 44 semen samples, subjected to either IVF or ICSI treatment. Oocyte collection, ICSI or IVF, determination of sperm concentration and motility, and immunocytochemical analyses of phospholipase C zeta (PLCζ). None. Percentages of sperm exhibiting PLCζ. Significant positive correlation between ICSI fertilization rates and total levels, localization patterns, and the proportion (percentage) of sperm exhibiting PLCζ. Total levels, localization patterns, and the proportion of sperm exhibiting PLCζ are correlated with fertilization rates for ICSI, but not for IVF. Evaluating total levels, localization patterns, and proportions of PLCζ may represent a useful diagnostic tool for clinical purposes in men for whom IVF is not advised or has previously failed. This clinical study further supports the fundamental role of PLCζ in the oocyte activation process. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats

PubMed Central

Zaitone, Sawsan A.; Abo-Elmatty, Dina M.; Elshazly, Shimaa M.

2012-01-01

Objective: To evaluate the neuroprotective effect of the nootropic drugs, piracetam (PIR) and vinpocetine (VIN), in rotenone-induced Parkinsonism in rats. Materials and Methods: Sixty male rats were divided into 6 groups of 10 rats each. The groups were administered vehicle, control (rotenone, 1.5 mg/kg/48 h/6 doses, s.c.), PIR (100 and 200 mg/kg/day, p.o.) and VIN (3 and 6 mg/kg/day, p.o.). The motor performance of the rats was evaluated by the open field and pole test. Striatal dopamine level, malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor-α (TNF-α) were assayed. Histopathological study of the substantia nigra was also done. Results: Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field test. In addition, GSH level was decreased whereas MDA and TNF-α increased in striata of rotenone-treated rats as compared to vehicle-treated rats. Marked degeneration of the substantia nigra pars compacta (SNpc) neurons and depletion of striatal dopamine was also observed in the rotenone-treated rats. Treatment with PIR or VIN significantly reversed the locomotor deficits and increased striatal dopamine level. Treatment with VIN significantly (P < 0.05) reduced the striatal level of MDA and GSH in comparison to rotenone group whereas TNF-α production was found to be significantly decreased in PIR group (P < 0.05). Conclusion: VIN and PIR exhibit neuroprotective activity in rotenone-induced Parkinsonism. Hence, these nootropic agents may be considered as possible candidates in the treatment of Parkinson's disease. PMID:23248410

Social Enrichment during Postnatal Development Induces Transgenerational Effects on Emotional and Reproductive Behavior in Mice

PubMed Central

Curley, James P.; Davidson, Stephanie; Bateson, Patrick; Champagne, Frances A.

2009-01-01

Across species there is evidence that the quality of the early social environment can have a profound impact on neurobiology and behavior. In the present study we explore the effect of communal rearing conditions (three dams with three litters per cage) during the postnatal period on offspring (F1) and grand-offspring (F2) anxiety-like and maternal behavior in Balb/c mice. Females rearing pups in communal nests exhibited increased levels of postpartum maternal care and communal rearing was found to abolish sex-differences in weaning weights. In adulthood, communally reared offspring were observed to display reduced anxiety-like behavior when placed in a novel environment. When rearing their own offspring under standard conditions, communally reared females demonstrated higher levels of motivation to retrieve pups, built higher quality nests, and exhibited higher levels of postpartum care compared to standard reared females. When exposed to an intruder male, communally reared females were more subordinate and less aggressive. F2 offspring of communally reared females were observed to engage in reduced anxiety-like behavior, have larger litter sizes and an increased frequency of nursing on PND 1. Analysis of neuropeptide receptor levels suggest that a communal rearing environment may exert sustained effects on behavior through modification of oxytocin and vasopressin (V1a) receptor densities. Though Balb-C mice are often considered “socially-incompetent” and high in anxiety-like behavior, our findings suggest that through enrichment of the postnatal environment, these behavioral and neuroendocrine deficits may be attenuated both within and across generations. PMID:19826497

Neural Correlates of Stress- and Food Cue–Induced Food Craving in Obesity

PubMed Central

Jastreboff, Ania M.; Sinha, Rajita; Lacadie, Cheryl; Small, Dana M.; Sherwin, Robert S.; Potenza, Marc N.

2013-01-01

OBJECTIVE Obesity is associated with alterations in corticolimbic-striatal brain regions involved in food motivation and reward. Stress and the presence of food cues may each motivate eating and engage corticolimibic-striatal neurocircuitry. It is unknown how these factors interact to influence brain responses and whether these interactions are influenced by obesity, insulin levels, and insulin sensitivity. We hypothesized that obese individuals would show greater responses in corticolimbic-striatal neurocircuitry after exposure to stress and food cues and that brain activations would correlate with subjective food craving, insulin levels, and HOMA-IR. RESEARCH DESIGN AND METHODS Fasting insulin levels were assessed in obese and lean subjects who were exposed to individualized stress and favorite-food cues during functional MRI. RESULTS Obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food and stress cues. In obese but not lean individuals, food craving, insulin, and HOMA-IR levels correlated positively with neural activity in corticolimbic-striatal brain regions during favorite-food and stress cues. The relationship between insulin resistance and food craving in obese individuals was mediated by activity in motivation-reward regions including the striatum, insula, and thalamus. CONCLUSIONS These findings demonstrate that obese, but not lean, individuals exhibit increased corticolimbic-striatal activation in response to favorite-food and stress cues and that these brain responses mediate the relationship between HOMA-IR and food craving. Improving insulin sensitivity and in turn reducing corticolimbic-striatal reactivity to food cues and stress may diminish food craving and affect eating behavior in obesity. PMID:23069840

Dietary capsanthin, the main carotenoid in paprika (Capsicum annuum), alters plasma high-density lipoprotein-cholesterol levels and hepatic gene expression in rats.

PubMed

Aizawa, Koichi; Inakuma, Takahiro

2009-12-01

The effects of dietary capsanthin, the main carotenoid in paprika (Capsicum annuum), on lipid metabolism were examined. Young male Wistar rats were fed diets containing paprika powder, paprika organic solvent extract, residue of paprika extract, and purified capsanthin. Administration of purified capsanthin for 2 weeks resulted in a significant increase in plasma HDL-cholesterol (P < 0.05) without detectable differences in plasma total cholesterol and TAG concentrations. A statistically significant correlation (r 0.567; P < 0.001) was found between dietary capsanthin concentrations and plasma HDL-cholesterol concentrations. Animals receiving diets containing two different capsanthin concentrations exhibited dose-dependent increases in plasma HDL-cholesterol (r 0.597; P < 0.005). While capsanthin was absent in the liver of animals fed the basal diet, it increased markedly in capsanthin-fed animals (P < 0.001). Quantitative analyses of hepatic mRNA levels revealed that capsanthin administration resulted in up-regulation of mRNA for apoA5 and lecithin cholesterol acyltransferase (LCAT), without significant differences in other mRNA levels related to HDL-cholesterol metabolism. These results suggest that capsanthin had an HDL-cholesterol-raising effect on plasma, and the potential to increase cholesterol efflux to HDL particles by increasing apoA5 levels and/or enhancement of LCAT activity.

Protection against cyanide-induced convulsions with alpha-ketoglutarate.

PubMed

Yamamoto, H

1990-04-30

Protection against convulsions induced by cyanide was observed after treatment with alpha-ketoglutarate, either alone or in combination with sodium thiosulfate, a classical antagonist for cyanide intoxication. However, sodium thiosulfate alone did not protect against cyanide (30 mg/kg)-induced convulsions. gamma-Aminobutyric acid (GABA) levels in brain were decreased by 31% in KCN-treated mice exhibiting convulsions. The combined administration of alpha-ketoglutarate and sodium thiosulfate completely abolished the decrease of GABA levels induced by cyanide. Furthermore, sodium thiosulfate alone also completely abolished the decrease of GABA levels. These results suggest that the depletion of brain GABA levels may not directly contribute to the development of convulsions induced by cyanide. On the other hand, cyanide increased calcium levels by 32% in brain crude mitochondrial fractions in mice with convulsions. The increased calcium levels were completely abolished by the combined administration of alpha-ketoglutarate and sodium thiosulfate, but not affected by sodium thiosulfate alone. These findings support the hypothesis proposed by Johnson et al. (Toxicol. Appl. Pharmacol., 84 (1986) 464) and Robinson et al. (Toxicology, 35 (1985) 59) that calcium may play an important role in mediating cyanide neurotoxicity.

Why is bidirectional sex change rare?

PubMed

Yamaguchi, Sachi; Iwasa, Yoh

2018-09-14

Various species of fish living in coral reef communities show sequential hermaphroditism, or sex change. In a typical case, an individual first matures as a female, and later, when it becomes dominant in the mating group, it becomes a male (i.e., protogynous sex change). Many species show only unidirectional changes but some of coral reef fishes exhibit bidirectional sex changes, in which even a dominant male may revert to female when a socially more dominant competitor arrives. However, bidirectional sex change has rarely been observed in natural conditions, even among those species exhibiting it under experimental conditions. Here we explain the rarity of bidirectional sex change by studying dynamics of hormones controlling sex expression. We consider social status factor, S F , which is elevated when the individual becomes more dominant in the mating group. When the S F level is high, the dynamics would culminate with low estradiol expression and high testosterone expression, suggesting a male phenotype. In contrast, when S F level is low, the system converges to an equilibrium with high estradiol expression and low testosterone expression, suggesting a female phenotype. There is a parameter region in which the dynamics exhibit bistability. The model demonstrates hysteresis: as S F increases smoothly, the system undergoes a sudden transition in the levels of sex hormones. The model can explain why species show unidirectional sex change, in that an individual's switch to a new sex is irreversible, even if the individual's social situation returns to the original subdominant status. Copyright © 2018 Elsevier Ltd. All rights reserved.

Deletion of Monoglyceride Lipase in Astrocytes Attenuates Lipopolysaccharide-induced Neuroinflammation*

PubMed Central

Grabner, Gernot F.; Eichmann, Thomas O.; Wagner, Bernhard; Gao, Yuanqing; Farzi, Aitak; Taschler, Ulrike; Radner, Franz P. W.; Schweiger, Martina; Lass, Achim; Holzer, Peter; Zinser, Erwin; Tschöp, Matthias H.; Yi, Chun-Xia; Zimmermann, Robert

2016-01-01

Monoglyceride lipase (MGL) is required for efficient hydrolysis of the endocannabinoid 2-arachidonoylglyerol (2-AG) in the brain generating arachidonic acid (AA) and glycerol. This metabolic function makes MGL an interesting target for the treatment of neuroinflammation, since 2-AG exhibits anti-inflammatory properties and AA is a precursor for pro-inflammatory prostaglandins. Astrocytes are an important source of AA and 2-AG, and highly express MGL. In the present study, we dissected the distinct contribution of MGL in astrocytes on brain 2-AG and AA metabolism by generating a mouse model with genetic deletion of MGL specifically in astrocytes (MKOGFAP). MKOGFAP mice exhibit moderately increased 2-AG and reduced AA levels in brain. Minor accumulation of 2-AG in the brain of MKOGFAP mice does not cause cannabinoid receptor desensitization as previously observed in mice globally lacking MGL. Importantly, MKOGFAP mice exhibit reduced brain prostaglandin E2 and pro-inflammatory cytokine levels upon peripheral lipopolysaccharide (LPS) administration. These observations indicate that MGL-mediated degradation of 2-AG in astrocytes provides AA for prostaglandin synthesis promoting LPS-induced neuroinflammation. The beneficial effect of astrocyte-specific MGL-deficiency is not fully abrogated by the inverse cannabinoid receptor 1 agonist SR141716 (Rimonabant) suggesting that the anti-inflammatory effects are rather caused by reduced prostaglandin synthesis than by activation of cannabinoid receptors. In conclusion, our data demonstrate that MGL in astrocytes is an important regulator of 2-AG levels, AA availability, and neuroinflammation. PMID:26565024

Effects of chemical elements in the trophic levels of natural salt marshes.

PubMed

Kamiński, Piotr; Barczak, Tadeusz; Bennewicz, Janina; Jerzak, Leszek; Bogdzińska, Maria; Aleksandrowicz, Oleg; Koim-Puchowska, Beata; Szady-Grad, Małgorzata; Klawe, Jacek J; Woźniak, Alina

2016-06-01

The relationships between the bioaccumulation of Na, K, Ca, Mg, Fe, Zn, Cu, Mn, Co, Cd, and Pb, acidity (pH), salinity (Ec), and organic matter content within trophic levels (water-soil-plants-invertebrates) were studied in saline environments in Poland. Environments included sodium manufactures, wastes utilization areas, dumping grounds, and agriculture cultivation, where disturbed Ca, Mg, and Fe exist and the impact of Cd and Pb is high. We found Zn, Cu, Mn, Co, and Cd accumulation in the leaves of plants and in invertebrates. Our aim was to determine the selectivity exhibited by soil for nutrients and heavy metals and to estimate whether it is important in elucidating how these metals are available for plant/animal uptake in addition to their mobility and stability within soils. We examined four ecological plant groups: trees, shrubs, minor green plants, and water macrophytes. Among invertebrates, we sampled breastplates Malacostraca, small arachnids Arachnida, diplopods Diplopoda, small insects Insecta, and snails Gastropoda. A higher level of chemical elements was found in saline polluted areas (sodium manufactures and anthropogenic sites). Soil acidity and salinity determined the bioaccumulation of free radicals in the trophic levels measured. A pH decrease caused Zn and Cd to increase in sodium manufactures and an increase in Ca, Zn, Cu, Cd, and Pb in the anthropogenic sites. pH increase also caused Na, Mg, and Fe to increase in sodium manufactures and an increase in Na, Fe, Mn, and Co in the anthropogenic sites. There was a significant correlation between these chemical elements and Ec in soils. We found significant relationships between pH and Ec, which were positive in saline areas of sodium manufactures and negative in the anthropogenic and control sites. These dependencies testify that the measurement of the selectivity of cations and their fluctuation in soils provide essential information on the affinity and binding strength in these environments. The chemical elements accumulated in soils and plants; however, further flow is selective and variable. The selectivity exhibited by soil systems for nutrients and heavy metals is important in elucidating how these metals become available for plant/animal uptake and also their mobility and stability in soils.

The influence of feeding and fasting on plasma metabolites in the dogfish shark (Squalus acanthias).

PubMed

Wood, Chris M; Walsh, Patrick J; Kajimura, Makiko; McClelland, Grant B; Chew, Shit F

2010-04-01

Dogfish sharks are opportunistic predators, eating large meals at irregular intervals. Here we present a synthesis of data from several previous studies on responses in plasma metabolites after natural feeding and during prolonged fasting (up to 56days), together with new data on changes in plasma concentrations of amino acids and non-esterified fatty acids. Post-prandial and long-term fasting responses were compared to control sharks fasted for 7days, a typical inter-meal interval. A feeding frenzy was created in which dogfish were allowed to feed naturally on dead teleosts at two consumed ration levels, 2.6% and 5.5% of body weight. Most responses were more pronounced at the higher ration level. These included increases in urea and TMAO concentrations at 20h, followed by stability through to 56days of fasting. Ammonia levels were low and exhibited little short-term response to feeding, but declined to very low values during the extended fast. Glucose and beta-hydroxybutyrate both fell after feeding, the latter to a greater and more prolonged extent (up to 60h), whereas acetoacetate did not change. During prolonged fasting, glucose concentrations were well regulated, but beta-hydroxybutyrate increased to 2-3-fold control levels. Total plasma amino acid concentrations increased in a biphasic fashion, with peaks at 6-20h, and 48-60h after the meal, followed by homeostasis during the extended fast. Essential and non-essential amino acids generally followed this same pattern, though some exhibited different trends after feeding: taurine, beta-alanine, and glycine (decreases or stability), alanine and glutamine (modest prolonged increases), and threonine, serine, asparagine, and valine (much larger short-term increases). Plasma non-esterified fatty acid concentrations declined markedly through 48h after the 2.6% meal. These data are interpreted in light of companion studies showing elevations in aerobic metabolic rate, urea production, rectal gland function, metabolic base excretion, and activation of ornithine-urea cycle and aerobic enzymes after the meal, and muscle N-depletion but maintenance of osmolality and urea production during long-term fasting.

Secreted Frizzled-related protein 2 as a target in antifibrotic therapeutic intervention.

PubMed

Mastri, Michalis; Shah, Zaeem; Hsieh, Karin; Wang, Xiaowen; Wooldridge, Bailey; Martin, Sean; Suzuki, Gen; Lee, Techung

2014-03-15

Progressive fibrosis is a pathological hallmark of many chronic diseases responsible for organ failure. Although there is currently no therapy on the market that specifically targets fibrosis, the dynamic fibrogenic process is known to be regulated by multiple soluble mediators that may be therapeutically intervened. The failing hamster heart exhibits marked fibrosis and increased expression of secreted Frizzled-related protein 2 (sFRP2) amenable to reversal by mesenchymal stem cell (MSC) therapy. Given the previous demonstration that sFRP2-null mice subjected to myocardial infarction exhibited reduced fibrosis and improved function, we tested whether antibody-based sFRP2 blockade might counteract the fibrogenic pathway and repair cardiac injury. Cardiomyopathic hamsters were injected intraperitoneally twice a week each with 20 μg of sFRP2 antibody. Echocardiography, histology, and biochemical analyses were performed after 1 mo. sFRP2 antibody increased left ventricular ejection fraction from 40 ± 1.2 to 49 ± 6.5%, whereas saline and IgG control exhibited a further decline to 37 ± 0.9 and 31 ± 3.2%, respectively. Functional improvement is associated with a ∼ 50% reduction in myocardial fibrosis, ∼ 65% decrease in apoptosis, and ∼ 75% increase in wall thickness. Consistent with attenuated fibrosis, both MSC therapy and sFRP2 antibody administration significantly increased the activity of myocardial matrix metalloproteinase-2. Gene expression analysis of the hamster heart and cultured fibroblasts identified Axin2 as a downstream target, the expression of which was activated by sFRP2 but inhibited by therapeutic intervention. sFRP2 blockade also increased myocardial levels of VEGF and hepatocyte growth factor (HGF) along with increased angiogenesis. These findings highlight the pathogenic effect of dysregulated sFRP2, which may be specifically targeted for antifibrotic therapy.

Copper deficiency in Tule Elk at Point Reyes, California

USGS Publications Warehouse

Gogan, Peter J.P.; Jessup, David A.; Akeson, Mark

1989-01-01

Tule elk (Cervus elaphus nannodes) reintroduced to Point Reyes, Calif., in 1978 exhibited gross signs of copper deficiency by June 1979. Copper levels in liver (x=5.9 ppm) and serum (0.42 ppm) of elk in Point Reyes were below levels in adult tule elk from other locations in California (liver, x=80 ppm; serum, x=1.4 ppm). These levels were consistent with documented copper deficiencies in wild and domestic ruminants. Copper serum levels increased in response to copper enriched dietary supplements and declined after the elk stopped eating the supplements. Analysis of plant and soil samples showed both are deficient in copper and normal in molybdenum and sulfur-sulfates. Deficiency in plants and soils at Point Reyes are probably due to low copper levels in the underlying granitic parent material.

The development of callous-unemotional traits and antisocial behavior in children: are there shared and/or unique predictors?

PubMed

Pardini, Dustin A; Lochman, John E; Powell, Nicole

2007-01-01

Callous and unemotional (CU) traits have been linked to severe antisocial behavior in youth, but studies examining the etiology of CU traits are lacking. Based on prior research, it was hypothesized that childhood anxiety and parenting practices would interact to predict changes in CU traits over time. Hypotheses were tested using a sample of 120 moderate to highly aggressive fifth graders followed over a 1-year period. Although CU traits displayed moderate temporal stability and predicted increases in antisocial behavior, evidence suggested that these features were not immutable. Children exposed to lower levels of physical punishment showed decreases in CU traits over time, whereas higher levels of child-reported parental warmth and involvement predicted decreases in both CU traits and antisocial behavior over time. Lower levels of anxiety were uniquely related to increased CU traits for children who described their primary caregiver as exhibiting low warmth and involvement.

IL-18 promoter -137G/C polymorphism correlates with chronic hepatitis B and affects the expression of interleukins.

PubMed

Jiang, H; Cao, H; Liu, G; Huang, Q; Li, Y

2014-01-01

The relationship between the interleukin (IL)-18 promoter -137G/C polymorphism and plasma levels of IL-18, IL-12, IL-4, and IFN-γ in chronic hepatitis B (CHB) patients and healthy subjects was investigated. The polymorphism was genotyped by a ligase detection reaction-PCR (LDR-PCR), while the cytokines were assayed by ELISA. Compared with healthy subjects, CHB patients exhibited an increased frequency of the G allele, GG genotype and increased IL-4 levels, but decreased levels of IL-18, IL-12, and IFN-γ. A positive correlation for IL-18 ~ IL-12 ~ IFN-γ and a negative correlation for IL-18 ~ IL-4 were found. We conclude that the IL-18 promoter -137G polymorphisms correlated with CHB infection and influenced the expression of IL-18. The studied interleukins represent an immunomodulatory network that plays important roles in host immune responses to CHB infection.

Comparative transcriptomic profiling of two tomato lines with different ascorbate content in the fruit.

PubMed

Di Matteo, Antonio; Sacco, Adriana; De Stefano, Rosalba; Frusciante, Luigi; Barone, Amalia

2012-12-01

In recent years, interest in tomato breeding for enhanced antioxidant content has increased as medical research has pointed to human health benefits from antioxidant dietary intake. Ascorbate is one of the major antioxidants present in tomato, and little is known about mechanisms governing ascorbate pool size in this fruit. In order to provide further insights into genetic mechanisms controlling ascorbate biosynthesis and accumulation in tomato, we investigated the fruit transcriptome profile of the Solanum pennellii introgression line 10-1 that exhibits a lower fruit ascorbate level than its cultivated parental genotype. Our results showed that this reduced ascorbate level is associated with an increased antioxidant demand arising from an accelerated oxidative metabolism mainly involving mitochondria, peroxisomes, and cytoplasm. Candidate genes for controlling ascorbate level in tomato fruit were identified, highlighting the role of glycolysis, glyoxylate metabolism, and purine breakdown in modulating the ascorbate pool size.

Ecological release and venom evolution of a predatory marine snail at Easter Island.

PubMed

Duda, Thomas F; Lee, Taehwan

2009-05-20

Ecological release is coupled with adaptive radiation and ecological diversification yet little is known about the molecular basis of phenotypic changes associated with this phenomenon. The venomous, predatory marine gastropod Conus miliaris has undergone ecological release and exhibits increased dietary breadth at Easter Island. We examined the extent of genetic differentiation of two genes expressed in the venom of C. miliaris among samples from Easter Island, American Samoa and Guam. The population from Easter Island exhibits unique frequencies of alleles that encode distinct peptides at both loci. Levels of divergence at these loci exceed observed levels of divergence observed at a mitochondrial gene region at Easter Island. Patterns of genetic variation at two genes expressed in the venom of this C. miliaris suggest that selection has operated at these genes and contributed to the divergence of venom composition at Easter Island. These results show that ecological release is associated with strong selection pressures that promote the evolution of new phenotypes.

Immuno-efficacy of DNA vaccines encoding PLP1 and ROP18 against experimental Toxoplasma gondii infection in mice.

PubMed

Chen, Yajun; Yu, Miao; Hemandez, J A; Li, Jiexi; Yuan, Zi-Guo; Yan, Haikuo

2018-05-01

We constructed a new plasmid pIRESneo/ROP18/PLP1 that was injected intramuscularly into Kunming mice to evaluate its immune efficacy. The immunized mice exhibited significantly increased serum IgG2a levels, lymphocyte counts and Th1-type cytokine (IL-2, IL-12 and IFN-γ) levels. Moreover, the immunized mice exhibited longer survival times (44.7 ± 2.1 days for ROP18/PLP1 and 47.2 ± 2.9 days for ROP18/PLP1 + IL-18) and lower brain cyst burden (68.9% for ROP18/PLP1 and 72.4% for ROP18/PLP1 + IL-18) than control mice after T. gondii challenge. Our results demonstrate that the multiple-gene DNA vaccine including both ROP18 and PLP1 elicits greater protection against T. gondii challenge and stronger immunogenicity than single-gene vaccines. Copyright © 2018 Elsevier Inc. All rights reserved.

Can teacher-child relationships alter the effects of early socioeconomic status on achievement in middle childhood?

PubMed

McCormick, Meghan P; O'Connor, Erin E; Parham Horn, E

2017-10-01

Using data from the NICHD SECCYD (N=1053), we used two-level hierarchical linear models with site fixed effects to examine whether teacher-child closeness and conflict moderated associations between two indicators of early socioeconomic status (maternal education and family income) and standardized measures of children's math and reading achievement at 54months, 1st, 3rd, and 5th grades. Children whose mothers had lower levels of education and conflictual relationships with teachers exhibited lower reading achievement, on average, across elementary school. At the same time, children with less educated mothers who experienced increases in teacher-child closeness and decreases in teacher-child conflict exhibited improvements in reading achievement across elementary school. Finally, low teacher-child closeness elevated the risk for poor math achievement posed by low family income. Implications for intervention design and development are discussed. Copyright © 2017 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Aesthetic properties and message customization: navigating the dark side of web recruitment.

PubMed

Dineen, Brian R; Ling, Juan; Ash, Steven R; DelVecchio, Devon

2007-03-01

The authors examined recruitment message viewing time, information recall, and attraction in a Web-based context. In particular, they extended theory related to the cognitive processing of recruitment messages and found that the provision of customized information about likely fit related to increased viewing time and recall when good aesthetics were also present. A 3-way interaction among moderate-to low-fitting individuals further indicated that objective fit was most strongly related to attraction when messages included both good aesthetics and customized information. In particular, given this combination, the poorest fitting individuals exhibited lower attraction levels, whereas more moderately fitting individuals exhibited invariant attraction levels across combinations of aesthetics and customized information. The results suggest that, given good aesthetics, customized information exerts effects mostly by causing poorly fitting individuals to be less attracted, which further suggests a means of averting the "dark side" of Web recruitment that occurs when organizations receive too many applications from poorly fitting applicants. (c) 2007 APA, all rights reserved.

Correlation of serum metal ion levels with pathological changes of ARMD in failed metal-on-metal-hip-resurfacing arthroplasties.

PubMed

Grammatopoulos, George; Munemoto, Mitsuru; Pollalis, Athanasios; Athanasou, Nicholas A

2017-08-01

Metal-on-metal-hip-resurfacing arthroplasties (MoMHRAs) have been associated with an increased failure rates due to an adverse-response-to-metal-debris (ARMD) associated with a spectrum of pathological features. Serum levels of cobalt (Co) and chromium (Cr) are used to assess MoMHRAs, with regard to ARMD, but it is not certain whether ion levels correlate with pathological changes in periprosthetic tissues. Serum Co and Cr levels were correlated with histological findings in 38 revised MoMHRAs (29 pseudotumour cases and 9 non-pseudotumour cases revised for pain). The extent of necrosis and macrophage infiltrate as well as the aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response was assessed semi-quantitatively; the prosthesis linear wear rate (PLWR) was also determined in ten cases. Cr levels were elevated in 82% and Co levels elevated in 53% of cases; the PLWR correlated with Cr level (rho = 0.8, p = 0.006). Tissue necrosis and macrophage infiltration were noted in all, most of which also exhibited significant ALVAL. Although a discrete correlation was not seen between Co and/or Cr ion levels and the extent of necrosis, degree of macrophage infiltration, or ALVAL score, it was noted that cases with acceptable metal ions levels had high ALVAL score. Histological features of both innate and adaptive immune response to metal wear are seen in periprosthetic tissues in cases with both elevated and non-elevated metal ion levels. MoMHRA failures with acceptable ion levels exhibited a pronounced ALVAL response. Although metal ion levels are elevated in most cases of MoMHRA failure due to ARMD, the finding of a normal metal ion level does not exclude this diagnosis.

[Serum sclerostin levels and metabolic bone diseases].

PubMed

Yamauchi, Mika; Sugimoto, Toshitsugu

2013-06-01

Serum sclerostin levels are being investigated in various metabolic bone diseases. Since serum sclerostin levels are decreased in primary hyperparathyroidism and elevated in hypoparathyroidism, parathyroid hormone (PTH) is thought to be a regulatory factor for sclerostin. Serum sclerostin levels exhibit a significant positive correlation with bone mineral density. On the other hand, a couple of studies on postmenopausal women have shown that high serum sclerostin levels are a risk factor for fracture. Although glucocorticoid induced osteoporosis and diabetes are both diseases that reduce bone formation, serum sclerostin levels have been reported to be decreased in the former and elevated in the latter, suggesting differences in the effects of sclerostin in the two diseases. Serum sclerostin levels are correlated with renal function, and increase with reduction in renal function. Serum sclerostin level may be a new index of bone assessment that differs from bone mineral density and bone metabolic markers.

Observations and estimates of wave-driven water level extremes at the Marshall Islands

NASA Astrophysics Data System (ADS)

Merrifield, M. A.; Becker, J. M.; Ford, M.; Yao, Y.

2014-10-01

Wave-driven extreme water levels are examined for coastlines protected by fringing reefs using field observations obtained in the Republic of the Marshall Islands. The 2% exceedence water level near the shoreline due to waves is estimated empirically for the study sites from breaking wave height at the outer reef and by combining separate contributions from setup, sea and swell, and infragravity waves, which are estimated based on breaking wave height and water level over the reef flat. Although each component exhibits a tidal dependence, they sum to yield a 2% exceedence level that does not. A hindcast based on the breaking wave height parameterization is used to assess factors leading to flooding at Roi-Namur caused by an energetic swell event during December 2008. Extreme water levels similar to December 2008 are projected to increase significantly with rising sea level as more wave and tide events combine to exceed inundation threshold levels.

Unravelling Doping Effects on PEDOT at the Molecular Level: From Geometry to Thermoelectric Transport Properties.

PubMed

Shi, Wen; Zhao, Tianqi; Xi, Jinyang; Wang, Dong; Shuai, Zhigang

2015-10-14

Tuning carrier concentration via chemical doping is the most successful strategy to optimize the thermoelectric figure of merit. Nevertheless, how the dopants affect charge transport is not completely understood. Here we unravel the doping effects by explicitly including the scattering of charge carriers with dopants on thermoelectric properties of poly(3,4-ethylenedioxythiophene), PEDOT, which is a p-type thermoelectric material with the highest figure of merit reported. We corroborate that the PEDOT exhibits a distinct transition from the aromatic to quinoid-like structure of backbone, and a semiconductor-to-metal transition with an increase in the level of doping. We identify a close-to-unity charge transfer from PEDOT to the dopant, and find that the ionized impurity scattering dominates over the acoustic phonon scattering in the doped PEDOT. By incorporating both scattering mechanisms, the doped PEDOT exhibits mobility, Seebeck coefficient and power factors in very good agreement with the experimental data, and the lightly doped PEDOT exhibits thermoelectric properties superior to the heavily doped one. We reveal that the thermoelectric transport is highly anisotropic in ordered crystals, and suggest to utilize large power factors in the direction of polymer backbone and low lattice thermal conductivity in the stacking and lamellar directions, which is viable in chain-oriented amorphous nanofibers.

Overexpression of Bone Sialoprotein Leads to an Uncoupling of Bone Formation and Bone Resorption in Mice

PubMed Central

Valverde, Paloma; Zhang, Jin; Fix, Amanda; Zhu, Ji; Ma, Wenli; Tu, Qisheng; Chen, Jake

2008-01-01

The purpose of this study was to determine the effects of bone sialoprotein (BSP) overexpression in bone metabolism in vivo by using a homozygous transgenic mouse line that constitutively overexpresses mouse BSP cDNA driven by the cytomegalovirus (CMV) promoter. CMV-BSP transgenic (TG) mice and wildtype mice were weighed, and their length, BMD, and trabecular bone volume were measured. Serum levels of RANKL, osteocalcin, osteoprotegerin (OPG), TRACP5b, and PTH were determined. Bone histomorphometry, von Kossa staining, RT-PCR analysis, Western blot, MTS assay, in vitro mineralization assay, and TRACP staining were also performed to delineate phenotypes of this transgenic mouse line. Compared with wildtype mice, adult TG mice exhibit mild dwarfism, lower values of BMD, and lower trabecular bone volume. TG mice serum contained increased calcium levels and decreased PTH levels, whereas the levels of phosphorus and magnesium were within normal limits. TG mice serum also exhibited lower levels of osteoblast differentiation markers and higher levels of markers, indicating osteoclastic activity and bone resorption. H&E staining, TRACP staining, and bone histomorphometry showed that adult TG bones were thinner and the number of giant osteoclasts in TG mice was higher, whereas there were no significant alterations in osteoblast numbers between TG mice and WT mice. Furthermore, the vertical length of the hypertrophic zone in TG mice was slightly enlarged. Moreover, ex vivo experiments indicated that overexpression of BSP decreased osteoblast population and increased osteoclastic activity. Partly because of its effects in enhancing osteoclastic activity and decreasing osteoblast population, BSP overexpression leads to an uncoupling of bone formation and resorption, which in turn results in osteopenia and mild dwarfism in mice. These findings are expected to help the development of therapies to metabolic bone diseases characterized by high serum level of BSP. PMID:18597627

Intestine-Specific Mttp Deletion Decreases Mortality and Prevents Sepsis-Induced Intestinal Injury in a Murine Model of Pseudomonas aeruginosa Pneumonia

PubMed Central

Dominguez, Jessica A.; Xie, Yan; Dunne, W. Michael; Yoseph, Benyam P.; Burd, Eileen M.; Coopersmith, Craig M.; Davidson, Nicholas O.

2012-01-01

Background The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the “motor” of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO), which exhibit a block in chylomicron assembly together with lipid malabsorption. Methodology/Principal Findings Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0%) dying compared to 5/17 (29%) control mice (p<0.05). This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL) levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice. Conclusions/Significance These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by metabolic and physiological adaptations in both intestinal and hepatic lipid flux. PMID:23145105

Modulatory influence of sandalwood oil on mouse hepatic glutathione S-transferase activity and acid soluble sulphydryl level.

PubMed

Banerjee, S; Ecavade, A; Rao, A R

1993-02-01

The effect of the oil from the wood of Santalum album on glutathione S-transferase (GST) activity and acid soluble sulphydryl (SH) levels in the liver of adult male Swiss albino mice was investigated. Oral feeding by gavage to mice each day with 5 and 15 microliters sandalwood oil for 10 and 20 days exhibited an increase in GST activity in time- and dose-responsive manners. Feeding a dose of 5 microliters sandalwood oil for 10 and 20 days caused, respectively, a 1.80-fold (P < 0.001) and 1.93-fold (P < 0.001) increase in GST enzyme activity, while feeding a dose of 15 microliters of the oil per day for 10 and 20 days induced, respectively, 4.73-fold (P < 0.001) and 6.10-fold (P < 0.001) increases in the enzyme's activity. In addition, there were 1.59-fold (P < 0.001) and 1.57 (P < 0.001) increases in acid-soluble SH levels in the hepatic tissue of the mice following feeding of the oil at the dose levels of 5 and 15 microliters for 10 days. Furthermore, mice fed on a diet containing 1% 2(3)-butyl-4-hydroxyanisole (positive control) also showed an increase in hepatic GST activity and SH levels. Enhancement of GST activity and acid-soluble SH levels are suggestive of a possible chemopreventive action of sandalwood oil on carcinogenesis through a blocking mechanism.

Effects of voluntary exercise on the viability, proliferation and BDNF levels of bone marrow stromal cells in rat pups born from morphine- dependent mothers during pregnancy.

PubMed

Haydari, Sakineh; Safari, Manouchehr; Zarbakhsh, Sam; Bandegi, Ahmad Reza; Miladi-Gorji, Hossein

2016-11-10

This study was designed to investigate whether free access to a running wheel during pregnancy in morphine-dependent mothers would influence the viability, proliferation and BDNF levels of bone marrow stromal cells in rat pups. Pregnant rats were made dependent by chronic administration of morphine in drinking water simultaneously with free access to a running wheel. Male pups are weaned at 21days of birth and their bones marrows were aspirated from the femurs and tibias and also the bone marrow stromal cells (BMSCs) cultured. MTT assay was used to determine cell viability and proliferation rate. The level of BDNF was measured in the supernant of BMSCs culture by ELISA. The sedentary morphine-dependent mothers' pups showed a significant increase in the percentage cell viability and proliferation rate and also a significant decrease in the BDNF protein levels in BMSCs. The rat pups borne from exercising the control and morphine-dependent mothers exhibited an increase in the percentage viability, proliferation rate and BDNF levels of the BMSCs. This study showed that maternal exercise during pregnancy in morphine-dependent and non-dependent mothers, with increasing of BDNF levels increased the proliferation and viability of BMSCs in the rat pups. Also, chronic administration of morphine during pregnancy was able to increase the proliferation and viability of BMSCs in the rat pups. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Lake seasonality across the Tibetan Plateau and their varying relationship with regional mass changes and local hydrology

NASA Astrophysics Data System (ADS)

Lei, Yanbin; Yao, Tandong; Yang, Kun; Sheng, Yongwei; Kleinherenbrink, Marcel; Yi, Shuang; Bird, Broxton W.; Zhang, Xiaowen; Zhu, La; Zhang, Guoqing

2017-01-01

The recent growth and deepening of inland lakes in the Tibetan Plateau (TP) may be a salient indicator of the consequences of climate change. The seasonal dynamics of these lakes is poorly understood despite this being potentially crucial for disentangling contributions from glacier melt and precipitation, which are all sensitive to climate, to lake water budget. Using in situ observations, satellite altimetry and gravimetry data, we identified two patterns of lake level seasonality. In the central, northern, and northeastern TP, lake levels are characterized by considerable increases during warm seasons and decreases during cold seasons, which is consistent with regional mass changes related to monsoon precipitation and evaporation. In the northwestern TP, however, lake levels exhibit dramatic increases during both warm and cold seasons, which deviate from regional mass changes. This appears to be more connected with high spring snowfall and large summer glacier melt. The variable lake level response to different drivers indicates heterogeneous sensitivity to climate change between the northwestern TP and other regions.

Neural connectivity in Internet gaming disorder and alcohol use disorder: A resting-state EEG coherence study.

PubMed

Park, Su Mi; Lee, Ji Yoon; Kim, Yeon Jin; Lee, Jun-Young; Jung, Hee Yeon; Sohn, Bo Kyung; Kim, Dai Jin; Choi, Jung-Seok

2017-05-02

The present study compared neural connectivity and the level of phasic synchronization between neural populations in patients with Internet gaming disorder (IGD), patients with alcohol use disorder (AUD), and healthy controls (HCs) using resting-state electroencephalography (EEG) coherence analyses. For this study, 92 adult males were categorized into three groups: IGD (n = 30), AUD (n = 30), and HC (n = 32). The IGD group exhibited increased intrahemispheric gamma (30-40 Hz) coherence compared to the AUD and HC groups regardless of psychological features (e.g., depression, anxiety, and impulsivity) and right fronto-central gamma coherence positively predicted the scores of the Internet addiction test in all groups. In contrast, the AUD group showed marginal tendency of increased intrahemispheric theta (4-8 Hz) coherence relative to the HC group and this was dependent on the psychological features. The present findings indicate that patients with IGD and AUD exhibit different neurophysiological patterns of brain connectivity and that an increase in the fast phasic synchrony of gamma coherence might be a core neurophysiological feature of IGD.

Evaluation of toxicological endpoints in female zebrafish after bisphenol A exposure.

PubMed

Molina, Ana M; Abril, Nieves; Morales-Prieto, Noelia; Monterde, José G; Lora, Antonio J; Ayala, Nahúm; Moyano, Rosario

2018-02-01

Given the importance of bisphenol A (BPA) as a xenoestrogen and its potential effects on human and animal health, we evaluated BPA exposure's short-term effects on follicular development, yolk protein vitellogenin (VTG) production and aromatase expression in female zebrafish. Histological modifications were observed along with increased presence of atretic follicles. Whole-body VTG concentration increased with the dose of BPA exposure. In contrast, expression of Cyp19a mRNA in the ovaries of BPA-exposed fish exhibited an apparent non-monotonic response curve, marked by downregulation at 1 μg/L BPA, upregulation at 10 μg/L BPA, and a return to downregulation at 100 μg/L BPA and higher doses. Ovaries only exhibited significant increases in follicular atresia and VTG concentration after exposure to 100 μg/L BPA and higher doses. Ovarian histopathology, aromatase Cyp19a transcript levels and whole-body VTG protein abundance may be good biomarkers for early detection of environmental BPA exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simultaneous Increase in Open-Circuit Voltage and Efficiency of Fullerene-Free Solar Cells through Chlorinated Thieno[3,4-b]thiophene Polymer Donor

DOE PAGES

Wang, Huan; Chao, Pengjie; Chen, Hui; ...

2017-08-01

Here, the chlorinated polymer, PBTCl, have been found to be an efficient donor in non-fullerene PSCs, which showed a blue-shifted absorbance compared to that of its fluorine analog (PTB7-th), and resulted in a more complementary light absorption with non-fullerene acceptor, such as ITIC. Meanwhile, chlorine substitution lowered the HOMO level of PBTCl, which increased the open-circuit voltage of the corresponding polymer-based devices. The 2D GIWAXS analysis illustrated that the PBTCl/ITIC blend film exhibited a “face-on” orientation and scattering features of both PBTCl and ITIC, suggesting that the blend of PBTCl and ITIC was phase separated and formed individual crystalline domainsmore » of the donor and acceptor, which promoted charge transfer in the bi-continuous film and eventually elevated the solar energy conversion efficiency. The PBTCl-based non-fullerene PSC exhibited a maximum PCE of 7.57% with a Voc of 0.91 V, which was an approximately 13% increasing in the PCE compared to the fluorine-analog-based device.« less

Simultaneous Increase in Open-Circuit Voltage and Efficiency of Fullerene-Free Solar Cells through Chlorinated Thieno[3,4- b ]thiophene Polymer Donor

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

Wang, Huan; Chao, Pengjie; Chen, Hui

The chlorinated polymer, PBTCl, has been found to be an efficient donor in nonfullerene polymer solar cells (PSCs), which showed a blue-shifted absorbance compared to that of its fluorine analogue (PTB7-th) and resulted in more complementary light absorption with a nonfullerene acceptor, such as ITIC. Meanwhile, chlorine substitution lowered the HOMO level of PBTCl, which increased the open-circuit voltage of the corresponding polymer-based devices. The 2D GIWAXS analysis illustrated that the PBTCl/ITIC blend film exhibited a “face-on” orientation and scattering features of both PBTCl and ITIC, suggesting that the blend of PBTCl and ITIC was phase-separated and formed individual crystallinemore » domains of the donor and acceptor, which promoted charge transfer in the bicontinuous film and eventually elevated the solar energy conversion efficiency. The PBTCl-based nonfullerene PSC exhibited a maximum PCE of 7.57% with a Voc of 0.91 V, which was an approximately 13% increasing in the PCE compared to that of the fluorine-analogue-based device.« less

Simultaneous Increase in Open-Circuit Voltage and Efficiency of Fullerene-Free Solar Cells through Chlorinated Thieno[3,4-b]thiophene Polymer Donor

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

Wang, Huan; Chao, Pengjie; Chen, Hui

Here, the chlorinated polymer, PBTCl, have been found to be an efficient donor in non-fullerene PSCs, which showed a blue-shifted absorbance compared to that of its fluorine analog (PTB7-th), and resulted in a more complementary light absorption with non-fullerene acceptor, such as ITIC. Meanwhile, chlorine substitution lowered the HOMO level of PBTCl, which increased the open-circuit voltage of the corresponding polymer-based devices. The 2D GIWAXS analysis illustrated that the PBTCl/ITIC blend film exhibited a “face-on” orientation and scattering features of both PBTCl and ITIC, suggesting that the blend of PBTCl and ITIC was phase separated and formed individual crystalline domainsmore » of the donor and acceptor, which promoted charge transfer in the bi-continuous film and eventually elevated the solar energy conversion efficiency. The PBTCl-based non-fullerene PSC exhibited a maximum PCE of 7.57% with a Voc of 0.91 V, which was an approximately 13% increasing in the PCE compared to the fluorine-analog-based device.« less

Formononetin exhibits anti-hyperglycemic activity in alloxan-induced type 1 diabetic mice

PubMed Central

Qiu, Guizhen; Tian, Wei; Huan, Mei; Chen, Jinlong

2016-01-01

The aim of this study was to investigate the anti-hyperglycemic activity and mechanism of formononetin in alloxan-induced type 1 diabetic mice by determining its effect on some diabetes-related indices as described below. Body weight, fasting blood glucose, hepatic glycogen, serum insulin, and serum glucagon were determined by electronic scales, glucometer, and ELISA kits. Fas, Caspase-3, pancreatic and duodenal homeobox-1 , insulin receptor substrate 2, glucokinase and glucose transporter 2, mRNA and proteins levels in pancreas tissue, and glucokinase and glucose-6-phosphatase mRNA, and proteins levels in liver tissue were detected by fluorogenic quantitative-polymerase chain reaction and Western blot assays. The results indicated that formononetin (5, 10, and 20 mg/kg; oral administration) reversed the alloxan-induced increase of some indices (fasting blood glucose level and Fas and Caspase-3 mRNA and proteins levels in pancreas tissue) and reduction of some indices (body weight gain, oral glucose tolerance, insulin activity, hepatic glycogen level, pancreatic and duodenal homeobox-1, insulin receptor substrate 2, glucokinase and glucose transporter 2, mRNA and proteins levels in pancreas tissue, and glucokinase mRNA and protein levels in liver tissue). The glucagon level and glucose-6-phosphatase mRNA and protein levels in liver tissue were not affected by the drugs administration. In conclusion, formononetin exhibited anti-hyperglycemic activity in alloxan-induced type 1 diabetic mice by inhibiting islet B cell apoptosis and promoting islet B cell regeneration, insulin secretion, hepatic glycogen synthesis, and hepatic glycolysis. PMID:27412955

Muscle-Specific SIRT1 Gain-of-Function Increases Slow-Twitch Fibers and Ameliorates Pathophysiology in a Mouse Model of Duchenne Muscular Dystrophy

PubMed Central

Chalkiadaki, Angeliki; Igarashi, Masaki; Nasamu, Armiyaw Sebastian; Knezevic, Jovana; Guarente, Leonard

2014-01-01

SIRT1 is a metabolic sensor and regulator in various mammalian tissues and functions to counteract metabolic and age-related diseases. Here we generated and analyzed mice that express SIRT1 at high levels specifically in skeletal muscle. We show that SIRT1 transgenic muscle exhibits a fiber shift from fast-to-slow twitch, increased levels of PGC-1α, markers of oxidative metabolism and mitochondrial biogenesis, and decreased expression of the atrophy gene program. To examine whether increased activity of SIRT1 protects from muscular dystrophy, a muscle degenerative disease, we crossed SIRT1 muscle transgenic mice to mdx mice, a genetic model of Duchenne muscular dystrophy. SIRT1 overexpression in muscle reverses the phenotype of mdx mice, as determined by histology, creatine kinase release into the blood, and endurance in treadmill exercise. In addition, SIRT1 overexpression also results in increased levels of utrophin, a functional analogue of dystrophin, as well as increased expression of PGC-1α targets and neuromuscular junction genes. Based on these findings, we suggest that pharmacological interventions that activate SIRT1 in skeletal muscle might offer a new approach for treating muscle diseases. PMID:25032964

Nutritional and Metabolic Biomarkers in Autism Spectrum Disorders: An Exploratory Study.

PubMed

Esparham, Anna E; Smith, Teri; Belmont, John M; Haden, Michael; Wagner, Leigh E; Evans, Randall G; Drisko, Jeanne A

2015-04-01

Autism spectrum disorder (ASD) is currently on the rise, now affecting approximately 1 in 68 children in the United States according to a 2010 surveillance summary from the Centers for Disease Control and Prevention (CDC). This figure is an estimated increase of 78% from the figure in 2002. The CDC suggests that more investigation is needed to understand this astounding increase in autism in such a short period. The aim of this pilot study was to determine whether a group of children with ASD exhibited similar variations in a broad array of potential correlates, including medical histories, symptoms, genetics, and multiple nutritional and metabolic biomarkers. This study was a retrospective, descriptive chart review. The study took place at the University of Kansas Medical Center (KUMC). Participants were 7 children with ASD who had sought treatment at the Integrative Medicine Clinic at the medical center. A majority of the children exhibited an elevated copper:zinc ratio and abnormal vitamin D levels. Children also demonstrated abnormal levels of the essential fatty acids: (1) α-linolenic acid (ALA)- C13:3W3, and (2) linoleic acid (LA)-C18:2W6; high levels of docosahexaenoic acid (DHA); and an elevated ω-6:ω-3 ratio. Three of 7 children demonstrated abnormal manganese levels. Children did not demonstrate elevated urine pyruvate or lactate but did have abnormal detoxification markers. Three of 7 patients demonstrated abnormalities in citric acid metabolites, bacterial metabolism, and fatty acid oxidation markers. A majority demonstrated elevated serum immunoglobulin G (IgG) antibodies to casein, egg whites, egg yolks, and peanuts. A majority had absent glutathione S-transferase (GSTM) at the 1p13.3 location, and 3 of 7 children were heterozygous for the glutathione S-transferase I105V (GSTP1). A majority also exhibited genetic polymorphism of the mitochondrial gene superoxide dismutase A16V (SOD2). The findings from this small group of children with ASD points to the existence of nutritional, metabolic, and genetic correlates of ASD. These factors appear to be important potential abnormalities that warrant a case control study to evaluate their reliability and validity as markers of ASD.

Human osteoblast-like cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation

NASA Technical Reports Server (NTRS)

Harter, L. V.; Hruska, K. A.; Duncan, R. L.

1995-01-01

Exposure of osteosarcoma cell lines to chronic intermittent strain increases the activity of mechano-sensitive cation (SA-cat) channels. The impact of mechano-transduction on osteoblast function has not been well studied. We analyzed the expression and production of bone matrix proteins in human osteoblast-like osteosarcoma cells, OHS-4, in response to chronic intermittent mechanical strain. The OHS-4 cells exhibit type I collagen production, 1,25-Dihydroxyvitamin D-inducible osteocalcin, and mineralization of the extracellular matrix. The matrix protein message level was determined from total RNA isolated from cells exposed to 1-4 days of chronic intermittent strain. Northern analysis for type I collagen indicated that strain increased collagen message after 48 h. Immunofluorescent labeling of type I collagen demonstrated that secretion was also enhanced with mechanical strain. Osteopontin message levels were increased several-fold by the application of mechanical load in the absence of vitamin D, and the two stimuli together produced an additive effect. Osteocalcin secretion was also increased with cyclic strain. Osteocalcin levels were not detectable in vitamin D-untreated control cells. However, after 4 days of induced load, significant levels of osteocalcin were observed in the medium. With vitamin D present, osteocalcin levels were 4 times higher in the medium of strained cells compared to nonstrained controls. We conclude that mechanical strain of osteoblast-like cells is sufficient to increase the transcription and secretion of matrix proteins via mechano-transduction without hormonal induction.

Metals-contaminated benthic invertebrates in the Clark Fork River, Montana: Effects on age-0 brown trout and rainbow trout

USGS Publications Warehouse

Woodward, Daniel F.; Farag, Aïda M.; Bergman, Harold L.; Delonay, Aaron J.; Little, Edward E.; Smiths, Charlie E.; Barrows, Frederic T.

1995-01-01

Benthic organisms in the upper Clark Fork River have recently been implicated as a dietary source of metals that may be a chronic problem for young-of-the-year rainbow trout (Oncorhynchus mykiss). In this present study, early life stage brown trout (Salmo trutta) and rainbow trout were exposed for 88 d to simulated Clark Fork River water and a diet of benthic invertebrates collected from the river. These exposures resulted in reduced growth and elevated levels of metals in the whole body of both species. Concentrations of As, Cd, Cu, and Pb increased in whole brown trout; in rainbow trout, As and Cd increased in whole fish, and As also increased in liver. Brown trout on the metals-contaminated diets exhibited constipation, gut impaction, increased cell membrane damage (lipid peroxidation), decreased digestive enzyme production (zymogen), and a sloughing of intestinal mucosal epithelial cells. Rainbow trout fed the contaminated diets exhibited constipation and reduced feeding activity. We believe that the reduced standing crop of trout in the Clark Fork River results partly from chronic effects of metals contamination in benthic invertebrates that are important as food for young-of-the-year fish.

Fascin regulates nuclear actin during Drosophila oogenesis

PubMed Central

Kelpsch, Daniel J.; Groen, Christopher M.; Fagan, Tiffany N.; Sudhir, Sweta; Tootle, Tina L.

2016-01-01

Drosophila oogenesis provides a developmental system with which to study nuclear actin. During Stages 5–9, nuclear actin levels are high in the oocyte and exhibit variation within the nurse cells. Cofilin and Profilin, which regulate the nuclear import and export of actin, also localize to the nuclei. Expression of GFP-tagged Actin results in nuclear actin rod formation. These findings indicate that nuclear actin must be tightly regulated during oogenesis. One factor mediating this regulation is Fascin. Overexpression of Fascin enhances nuclear GFP-Actin rod formation, and Fascin colocalizes with the rods. Loss of Fascin reduces, whereas overexpression of Fascin increases, the frequency of nurse cells with high levels of nuclear actin, but neither alters the overall nuclear level of actin within the ovary. These data suggest that Fascin regulates the ability of specific cells to accumulate nuclear actin. Evidence indicates that Fascin positively regulates nuclear actin through Cofilin. Loss of Fascin results in decreased nuclear Cofilin. In addition, Fascin and Cofilin genetically interact, as double heterozygotes exhibit a reduction in the number of nurse cells with high nuclear actin levels. These findings are likely applicable beyond Drosophila follicle development, as the localization and functions of Fascin and the mechanisms regulating nuclear actin are widely conserved. PMID:27535426

Doping of AlxGa1-xN

NASA Astrophysics Data System (ADS)

Stampfl, C.; Van de Walle, Chris G.

1998-01-01

N-type AlxGa1-xN exhibits a dramatic decrease in the free-carrier concentration for x⩾0.40. Based on first-principles calculations, we propose that two effects are responsible for this behavior: (i) in the case of doping with oxygen (the most common unintentional donor), a DX transition occurs, which converts the shallow donor into a deep level; and (ii) compensation by the cation vacancy (VGa or VAl), a triple acceptor, increases with alloy composition x. For p-type doping, the calculations indicate that the doping efficiency decreases due to compensation by the nitrogen vacancy. In addition, an increase in the acceptor ionization energy is found with increasing x.

Megakaryocyte Polyploidization and Proplatelet Formation in Low-Attachment Conditions.

PubMed

Schlinker, Alaina C; Duncan, Mark T; DeLuca, Teresa A; Whitehead, David C; Miller, William M

2016-07-15

In vitro -derived platelets (PLTs), which could provide an alternative source of PLTs for patient transfusions, are formed from polyploid megakaryocytes (MKs) that extend long cytoplasmic projections, termed proplatelets (proPLTs). In this study, we compared polyploidization and proPLT formation (PPF) of MKs cultured on surfaces that either promote or inhibit protein adsorption and subsequent cell adhesion. A megakaryoblastic cell line exhibited increased polyploidization and arrested PPF on a low-attachment surface. Primary human MKs also showed low levels of PPF on the same surface, but no difference in ploidy. Importantly, both cell types exhibited accelerated PPF after transfer to a surface that supports attachment, suggesting that pre-culture on a non-adhesive surface may facilitate synchronization of PPF and PLT generation in culture.

Tainted visions: the effect of visionary leader behaviors and leader categorization tendencies on the financial performance of ethnically diverse teams.

PubMed

Greer, Lindred L; Homan, Astrid C; De Hoogh, Annebel H B; Den Hartog, Deanne N

2012-01-01

Despite the increasing prevalence of ethnic diversity, findings regarding its effects on team performance remain contradictory. We suggest that past inconsistencies can be reconciled by examining the joint impact of leader behavior and leader categorization tendencies in ethnically diverse teams. We propose that leaders who exhibit high levels of visionary leader behavior and also have the tendency to categorize their team members into in- and out-groups will facilitate a negative effect of ethnic diversity on team communication and financial performance, whereas leaders who exhibit visionary behaviors but do not tend to categorize will lead ethnically diverse teams to positive outcomes. We find support for these ideas in a study of 100 retail outlets.

Levels of prostaglandin E metabolite and leukotriene E(4) are increased in the urine of smokers: evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway.

PubMed

Duffield-Lillico, Anna J; Boyle, Jay O; Zhou, Xi Kathy; Ghosh, Aradhana; Butala, Geera S; Subbaramaiah, Kotha; Newman, Robert A; Morrow, Jason D; Milne, Ginger L; Dannenberg, Andrew J

2009-04-01

Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) play a role in inflammation and carcinogenesis. Biomarkers that reflect tobacco smoke-induced tissue injury are needed. In this study, levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE(4)), biomarkers of the COX and 5-LO pathways, were compared in never smokers, former smokers, and current smokers. The effects of celecoxib, a selective COX-2 inhibitor, on levels of PGE-M and LTE(4) were determined. Baseline levels of PGE-M and LTE(4) were positively associated with smoking status; levels of PGE-M and LTE(4) were higher in current versus never smokers. Treatment with 200 mg celecoxib twice daily for 6 +/- 1 days led to a reduction in urinary PGE-M levels in all groups but exhibited the greatest effect among subjects with high baseline PGE-M levels. Thus, high baseline PGE-M levels in smokers reflected increased COX-2 activity. In individuals with high baseline PGE-M levels, treatment with celecoxib led to a significant increase in levels of urinary LTE(4), an effect that was not found in individuals with low baseline PGE-M levels. In conclusion, increased levels of urinary PGE-M and LTE(4) were found in human smokers, a result that may reflect subclinical lung inflammation. In individuals with high baseline levels of PGE-M (elevated COX-2 activity), celecoxib administration shunted arachidonic acid into the proinflammatory 5-LO pathway. Because 5-LO activity and LTE(4) have been suggested to play a role in cardiovascular disease, these results may help to explain the link between use of COX-2 inhibitors and cardiovascular complications.

Symptoms Moderating the Association Between Recent Suicide Attempts and Trauma Levels: Fan-Shaped Effects.

PubMed

Afzali, Mohammad H; Birmes, Philippe; Vautier, Stéphane

2015-01-01

The present study focuses on variables moderating the incidence of recent suicide attempt in a large community sample (n = 39,617) of French citizens with various levels of trauma. Five trauma levels were established based on posttraumatic stress disorder items of the Mini International Neuropsychiatric Interview. Twenty-three symptoms were examined as potential moderating variables with a fan-shaped pattern. Seven symptoms regarding desire for death, self-harm intention, suicidal ideation, lifetime suicide attempt, depressed mood, loss of interest, and panic attack exhibited the fan-shaped pattern. The absence of these moderating symptoms decreases the incidence of suicide attempt and their presence leads to a gradual increase.

Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential

PubMed Central

ALAM, BADRUL; MAJUMDER, RAJIB; AKTER, SHAHINA; LEE, SANG-HAN

2015-01-01

The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (P<0.05). Hematological and serum biochemical profiles were restored to normal levels in the extract-treated mice compared with the EAC control mice. MPBL and EPBL treatment significantly decreased lipid peroxidation (P<0.05) and restored GSH, SOD and CAT levels towards normal compared with the EAC control. Taken together, the results of the present study demonstrated that Piper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential. PMID:25624910

Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential.

PubMed

Alam, Badrul; Majumder, Rajib; Akter, Shahina; Lee, Sang-Han

2015-02-01

The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (P<0.05). Hematological and serum biochemical profiles were restored to normal levels in the extract-treated mice compared with the EAC control mice. MPBL and EPBL treatment significantly decreased lipid peroxidation (P<0.05) and restored GSH, SOD and CAT levels towards normal compared with the EAC control. Taken together, the results of the present study demonstrated that Piper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential.

Interactions between ecology, demography, capture stress, and profiles of corticosterone and glucose in a free-living population of Australian freshwater crocodiles.

PubMed

Jessop, Tim S; Tucker, Anton D; Limpus, Colin J; Whittier, Joan M

2003-06-01

In this study we examined three aspects pertaining to adrenocortical responsiveness in free-ranging Australian freshwater crocodiles (Crocodylus johnstoni). First, we examined the ability of freshwater crocodiles to produce corticosterone in response to a typical capture-stress protocol. A second objective addressed the relationship between capture stress, plasma glucose and corticosterone. Next we examined if variation in basal and capture-stress-induced levels of plasma corticosterone was linked to ecological or demographic factors for individuals in this free-ranging population. Blood samples obtained on three field trips were taken from a cross-sectional sample of the population. Crocodiles were bled once during four time categories at 0, 0.5, 6, and 10h post-capture. Plasma corticosterone increased significantly with time post-capture. Plasma glucose also significantly increased with duration of capture-stress and exhibited a positive and significant relationship with plasma corticosterone. Significant variation in basal or stress induced levels of corticosterone in crocodiles was not associated with any ecological or demographic factors including sex, age class or the year of capture that the crocodiles were sampled from. However, three immature males had basal levels of plasma corticosterone greater than 2 standard deviations above the mean. While crocodiles exhibited a pronounced adrenocortical and hyperglycaemic response to capture stress, limited variation in adrenocortical responsiveness due to ecological and demographic factors was not evident. This feature could arise in part because this population was sampled during a period of environmental benigness.

Glycemic control and adipokines after periodontal therapy in patients with Type 2 diabetes and chronic periodontitis.

PubMed

Wang, Shunqin; Liu, Jingsong; Zhang, Junfeng; Lin, Jiancheng; Yang, Shuyu; Yao, Jiangwu; Du, Minquan

2017-11-27

The mechanism by which chronic periodontitis (CP) affects type 2 diabetes (T2DM) remains unclear. Therefore, the aim of this study is to evaluate the effects of periodontal therapy (PT) on the glycemic control and adipokines of patients with T2DM and CP with the purpose of elucidating the possible mechanisms by which CP influences T2DM. Forty-four patients with T2DM and CP were randomly divided into two groups according to whether they underwent PT. Periodontal status, blood glucose, and the levels of serum tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), adiponectin (APN), and fibroblast growth factor-21 (FGF-21) were measured at baseline and after 3 months. The results revealed that the probing depth (PD) and attachment loss (AL) were significantly improved, the serum levels of TNF-α and IL-6 were significantly decreased, and APN and FGF-21 exhibited substantial increases in the intervention group after 3 months (p < 0.05), whereas no significant changes were observed in the control group. The glycated hemoglobin (HbA1c) levels in both groups decreased significantly after 3 months compared with baseline (p < 0.05), but the intervention group exhibited a significantly greater change (p < 0.05). In conclusion, PT may relieve periodontal inflammation, which causes a reduction of insulin-antagonizing adipokines and an increase in insulin-sensitizing adipokines, thereby eliciting an improvement in glycemic control.

Developmental alterations in anxiety and cognitive behavior in serotonin transporter mutant mice.

PubMed

Sakakibara, Yasufumi; Kasahara, Yoshiyuki; Hall, F Scott; Lesch, Klaus-Peter; Murphy, Dennis L; Uhl, George R; Sora, Ichiro

2014-10-01

A promoter variant of the serotonin transporter (SERT) gene is known to affect emotional and cognitive regulation. In particular, the "short" allelic variant is implicated in the etiology of multiple neuropsychiatric disorders. Heterozygous (SERT(+/-)) and homozygous (SERT(-/-)) SERT mutant mice are valuable tools for understanding the mechanisms of altered SERT levels. Although these genetic effects are well investigated in adulthood, the developmental trajectory of altered SERT levels for behavior has not been investigated. We assessed anxiety-like and cognitive behaviors in SERT mutant mice in early adolescence and adulthood to examine the developmental consequences of reduced SERT levels. Spine density of pyramidal neurons was also measured in corticolimbic brain regions. Adult SERT(-/-) mice exhibited increased anxiety-like behavior, but these differences were not observed in early adolescent SERT(-/-) mice. Conversely, SERT(+/-) and SERT(-/-) mice did display higher spontaneous alternation during early adolescence and adulthood. SERT(+/-) and SERT(-/-) also exhibited greater neuronal spine densities in the orbitofrontal but not the medial prefrontal cortices. Adult SERT(-/-) mice also showed an increased spine density in the basolateral amygdala. Developmental alterations of the serotonergic system caused by genetic inactivation of SERT can have different influences on anxiety-like and cognitive behaviors through early adolescence into adulthood, which may be associated with changes of spine density in the prefrontal cortex and amygdala. The altered maturation of serotonergic systems may lead to specific age-related vulnerabilities to psychopathologies that develop during adolescence.

Effect of sex on ethanol consumption and conditioned taste aversion in adolescent and adult rats.

PubMed

Schramm-Sapyta, Nicole L; Francis, Reynold; MacDonald, Andrea; Keistler, Colby; O'Neill, Lauren; Kuhn, Cynthia M

2014-04-01

Vulnerability to alcoholism is determined by many factors, including the balance of pleasurable vs. aversive alcohol-induced sensations: pleasurable sensations increase intake, while aversive sensations decrease it. Female sex and adolescent age are associated with lower sensitivity to intake-reducing effects and more rapid development of alcohol abuse. This study assessed voluntary drinking and the aversive effects of alcohol to determine whether these measures are inversely related across the sexes and development. Voluntary drinking of 20 % ethanol in an every-other-day (EOD) availability pattern and the dose-response relationship of ethanol conditioned taste aversion (CTA) were assessed in male and female adolescent and adult rats. CTA was sex specific in adult but not adolescent rats, with adult females exhibiting less aversion. Voluntary ethanol consumption varied according to age and individual differences but was not sex specific. Adolescents initially drank more than adults, exhibited greater day-to-day variation in consumption, were more susceptible to the alcohol deprivation effect, and took longer to establish individual differences in consumption patterns. These results show that the emergence of intake patterns differs between adolescents and adults. Adolescents as a group initiate drinking at high levels but decrease intake as they mature. A subset of adolescents maintained high drinking levels into adulthood. In contrast, most adults consumed at steady, low levels, but a small subset quickly established and maintained high-consumption patterns. Adolescents also showed marked deprivation-induced increases. Sex differences were not observed in EOD drinking during either adolescence or adulthood.

INFLAMMATION IS INCREASED WITH ANXIETY- AND DEPRESSION-LIKE SIGNS IN A RAT MODEL OF SPINAL CORD INJURY

PubMed Central

Maldonado-Bouchard, Sioui; Peters, Kelsey; Woller, Sarah A.; Madahian, Behrouz; Faghihi, Usef; Patel, Shivani; Bake, Shameena; Hook, Michelle A

2015-01-01

Spinal cord injury (SCI) leads to increased anxiety and depression in as many as 60% of patients. Yet, despite extensive clinical research focused on understanding the variables influencing psychological well-being following SCI, risk factors that decrease it remain unclear. We hypothesized that excitation of the immune system, inherent to SCI, may contribute to the decrease in psychological well-being. To test this hypothesis, we used a battery of established behavioral tests to assess depression and anxiety in spinally contused rats. The behavioral tests, and subsequent statistical analyses, revealed three cohorts of subjects that displayed behavioral characteristics of 1) depression, 2) depression and anxiety, or 3) no signs of decreased psychological well-being. Subsequent molecular analyses demonstrated that the psychological cohorts differed not only in behavioral symptoms, but also in peripheral (serum) and central (hippocampi and spinal cord) levels of pro-inflammatory cytokines. Subjects exhibiting a purely depression-like profile showed higher levels of pro-inflammatory cytokines peripherally, whereas subjects exhibiting a depression- and anxiety-like profile showed higher levels of pro-inflammatory cytokines centrally (hippocampi and spinal cord). These changes in inflammation were not associated with injury severity; suggesting that the association between inflammation and the expression of behaviors characteristic of decreased psychological well-being was not confounded by differential impairments in motor ability. These data support the hypothesis that inflammatory changes are associated with decreased psychological well-being following SCI. PMID:26296565

Attenuation of reserpine-induced pain/depression dyad by gentiopicroside through downregulation of GluN2B receptors in the amygdala of mice.

PubMed

Liu, Shui-bing; Zhao, Rong; Li, Xu-sheng; Guo, Hong-ju; Tian, Zhen; Zhang, Nan; Gao, Guo-dong; Zhao, Ming-gao

2014-06-01

Epidemiological studies demonstrate that pain frequently occurs comorbid with depression. Gentiopicroside (Gent) is a secoiridoid compound isolated from Gentiana lutea that exhibits analgesic properties and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cortex of mice. However, the effects of Gent on the reserpine-induced pain/depression dyad and its underlying mechanisms are unclear. Reserpine administration (1 mg/kg subcutaneous daily for 3 days) caused a significant decrease in the nociceptive threshold as evidenced by the reduced paw withdrawal latency in response to a radiant heat source and mechanical allodynia. Behavioral detection indicated a significant increase in immobility time during a forced swim test, as well as decreased time in the central area and total travel distance in an open field test. Furthermore, reserpinized animals exhibited increased oxidative stress. Systemic Gent administration dose-dependently ameliorated the behavioral deficits associated with reserpine-induced pain/depression dyad. At the same time, the decrease in biogenic amine levels (norepinephrine, dopamine, and serotonin) was integrated with the increase in caspase-3 levels and GluN2B-containing NMDA receptors in the amygdala of the reserpine-injected mice. Gent significantly reversed the changes in the levels of biogenic amines, caspase-3, and GluN2B-containing NMDA receptors in amygdala. However, Gent did not affect the expression of GluN2A-containing NMDA receptors. The inhibitory effects of Gent on oxidative stress were occluded by simultaneous treatment of GluN2B receptors antagonist Ro25-6981. Our study provides strong evidence that Gent inhibits reserpine-induced pain/depression dyad by downregulating GluN2B receptors in the amygdala.

Early-life dietary spray-dried plasma influences immunological and intestinal injury responses to later-life Salmonella typhimurium challenge.

PubMed

Boyer, P E; D'Costa, S; Edwards, L L; Milloway, M; Susick, E; Borst, L B; Thakur, S; Campbell, J M; Crenshaw, J D; Polo, J; Moeser, A J

2015-03-14

Increasing evidence supports the concept that early-life environmental influences, including nutrition and stress, have an impact on long-term health outcomes and disease susceptibility. The objective of the present study was to determine whether dietary spray-dried plasma (SDP), fed during the first 2 weeks post-weaning (PW), influences subsequent immunological and intestinal injury responses to Salmonella typhimurium challenge. A total of thirty-two piglets (age 16-17 d) were weaned onto nursery diets containing 0, 2·5 % SDP (fed for 7 d PW) or 5 % SDP (fed for 14 d PW), and were then fed control diets (without SDP), for the remainder of the experiment. At 34 d PW (age 50 d), pigs were challenged with 3 × 10⁹ colony-forming units of S. typhimurium. A control group (non-challenged) that was fed 0 % SDP in the nursery was included. At 2 d post-challenge, the distal ileum was harvested for the measurement of inflammatory, histological and intestinal physiological parameters. S. typhimurium challenge induced elevated ileal histological scores, myeloperoxidase (MPO), IL-8 and TNF, and increased intestinal permeability (indicated by reduced transepithelial voltage (potential difference) and elevated 4 kDa fluorescein isothiocyanate dextran (FD4) flux rates). Compared with S. typhimurium-challenged controls (0 % SDP), pigs fed the 5 % SDP-14 d diet exhibited reduced ileal histological scores, MPO levels, IL-8 levels and FD4 flux rates. Pigs fed the 5 % SDP-14 d nursery diet exhibited increased levels of plasma and ileal TNF-α in response to the challenge, compared with the other treatments. These results indicate that inclusion of SDP in PW diets can have an influence on subsequent immunological and intestinal injury responses induced by later-life S. typhimurium challenge.

pH-responsive, gluconeogenic renal epithelial LLC-PK1-FBPase+cells: a versatile in vitro model to study renal proximal tubule metabolism and function

PubMed Central

Curthoys, Norman P.

2014-01-01

Ammoniagenesis and gluconeogenesis are prominent metabolic features of the renal proximal convoluted tubule that contribute to maintenance of systemic acid-base homeostasis. Molecular analysis of the mechanisms that mediate the coordinate regulation of the two pathways required development of a cell line that recapitulates these features in vitro. By adapting porcine renal epithelial LLC-PK1 cells to essentially glucose-free medium, a gluconeogenic subline, termed LLC-PK1-FBPase+ cells, was isolated. LLC-PK1-FBPase+ cells grow in the absence of hexoses and pentoses and exhibit enhanced oxidative metabolism and increased levels of phosphate-dependent glutaminase. The cells also express significant levels of the key gluconeogenic enzymes, fructose-1,6-bisphosphatase (FBPase) and phosphoenolpyruvate carboxykinase (PEPCK). Thus the altered phenotype of LLC-PK1-FBPase+ cells is pleiotropic. Most importantly, when transferred to medium that mimics a pronounced metabolic acidosis (9 mM HCO3−, pH 6.9), the LLC-PK1-FBPase+ cells exhibit a gradual increase in NH4+ ion production, accompanied by increases in glutaminase and cytosolic PEPCK mRNA levels and proteins. Therefore, the LLC-PK1-FBPase+ cells retained in culture many of the metabolic pathways and pH-responsive adaptations characteristic of renal proximal tubules. The molecular mechanisms that mediate enhanced expression of the glutaminase and PEPCK in LLC-PK1-FBPase+ cells have been extensively reviewed. The present review describes novel properties of this unique cell line and summarizes the molecular mechanisms that have been defined more recently using LLC-PK1-FBPase+ cells to model the renal proximal tubule. It also identifies future studies that could be performed using these cells. PMID:24808535

Roux-en-Y Gastric Bypass Surgery Suppresses Hepatic Gluconeogenesis and Increases Intestinal Gluconeogenesis in a T2DM Rat Model.

PubMed

Yan, Yong; Zhou, Zhou; Kong, Fanzhi; Feng, Suibin; Li, Xuzhong; Sha, Yanhua; Zhang, Guangjun; Liu, Haijun; Zhang, Haiqing; Wang, Shiguang; Hu, Cheng; Zhang, Xueli

2016-11-01

Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and intestinal morphological adaption, as well as hepatic and intestinal gluconeogenesis. Twenty adult male T2DM rats induced by high-fat diet and low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, and serum lipid profiles were assessed to evaluate metabolic changes. Intestinal sections were stained with hematoxylin and eosin (H&E) for light microscopy examination. The messenger RNA (mRNA) and protein expression levels of key regulatory enzymes of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase)] were determined through reverse-transcription PCR (RT-PCR) and Western blotting, respectively. RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum triglyceride (TG) and free fatty acid (FFA) levels. The jejunum and ileum exhibited a marked increase in the length and number of intestinal villi after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK and G6Pase in the liver and upregulated expression of these enzymes in the jejunum and ileum tissues. RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The small intestine shows hyperplasia and hypertrophy after RYGB. Meanwhile, our study demonstrated that the reduced hepatic gluconeogenesis and increased intestinal gluconeogenesis may contribute to improved glucose homeostasis after RYGB.

Future property damage from flooding: sensitivities to economy and climate change

DOE PAGES

Liu, Jing; Hertel, Thomas; Diffenbaugh, Noah; ...

2015-08-09

Using a unique dataset for Indiana counties during the period 1995-2012, we estimate the effects of flood hazard, asset exposure, and social vulnerability on property damage. This relationship then is combined with the expected level of future flood risks to project property damage from flooding in 2030 under various scenarios. We compare these scenario projections to identify which risk management strategy offers the greatest potential to mitigate flooding loss. Results show that by 2030, county level flooding hazard measured by extreme flow volume and frequency will increase by an average of 16.2% and 7.4%, respectively. The total increase in propertymore » damages projected under different model specifications range from 13.3% to 20.8%. Across models future damages consistently exhibit the highest sensitivity to future increases in asset exposure, reinforcing the importance of non-structural measures in managing floodplain development.« less

Spectroscopic Study of Deep Level Emissions from Acceptor Defects in ZnO Thin Films with Oxygen Rich Stoichiometry

NASA Astrophysics Data System (ADS)

Ilyas, Usman; Rawat, R. S.; Tan, T. L.

2013-10-01

This paper reports the tailoring of acceptor defects in oxygen rich ZnO thin films at different post-deposition annealing temperatures (500-800°C) and Mn doping concentrations. The XRD spectra exhibited the nanocrystalline nature of ZnO thin films along with inconsistent variation in lattice parameters suggesting the temperature-dependent activation of structural defects. Photoluminescence emission spectra revealed the temperature dependent variation in deep level emissions (DLE) with the presence of acceptors as dominating defects. The concentration of native defects was estimated to be increased with temperature while a reverse trend was observed for those with increasing doping concentration. A consistent decrease in DLE spectra, with increasing Mn content, revealed the quenching of structural defects in the optical band gap of ZnO favorable for good quality thin films with enhanced optical transparency.

Intermittent Noise Induces Physiological Stress in a Coastal Marine Fish

PubMed Central

Nichols, Tye A.; Anderson, Todd W.; Širović, Ana

2015-01-01

Anthropogenic noise in the ocean has increased substantially in recent decades, and motorized vessels produce what is likely the most common form of underwater noise pollution. Noise has the potential to induce physiological stress in marine fishes, which may have negative ecological consequences. In this study, physiological effects of increased noise (playback of boat noise recorded in the field) on a coastal marine fish (the giant kelpfish, Heterostichus rostratus) were investigated by measuring the stress responses (cortisol concentration) of fish to increased noise of various temporal dynamics and noise levels. Giant kelpfish exhibited acute stress responses when exposed to intermittent noise, but not to continuous noise or control conditions (playback of recorded natural ambient sound). These results suggest that variability in the acoustic environment may be more important than the period of noise exposure for inducing stress in a marine fish, and provide information regarding noise levels at which physiological responses occur. PMID:26402068

Radiation damage and defect behavior in ion-implanted, lithium counterdoped silicon solar cells

NASA Technical Reports Server (NTRS)

Weinberg, I.; Mehta, S.; Swartz, C. K.

1984-01-01

Boron doped silicon n+p solar cells were counterdoped with lithium by ion implantation and the resuitant n+p cells irradiated by 1 MeV electrons. The function of fluence and a Deep Level Transient Spectroscopy (DLTS) was studied to correlate defect behavior with cell performance. It was found that the lithium counterdoped cells exhibited significantly increased radiation resistance when compared to boron doped control cells. It is concluded that the annealing behavior is controlled by dissociation and recombination of defects. The DLTS studies show that counterdoping with lithium eliminates at least three deep level defects and results in three new defects. It is speculated that the increased radiation resistance of the counterdoped cells is due primarily to the interaction of lithium with oxygen, single vacanies and divacancies and that the lithium-oxygen interaction is the most effective in contributing to the increased radiation resistance.

Radiation damage and defect behavior in ion-implanted, lithium counterdoped silicon solar cells

NASA Technical Reports Server (NTRS)

Weinberg, I.; Mehta, S.; Swartz, C. K.

1984-01-01

Boron doped silicon n+p solar cells were counterdoped with lithium by ion implanation and the resultant n+p cells irradiated by 1 MeV electrons. The function of fluence and a Deep Level Transient Spectroscopy (DLTS) was studied to correlate defect behavior with cell performance. It was found that the lithium counterdoped cells exhibited significantly increased radiation resistance when compared to boron doped control cells. It is concluded that the annealing behavior is controlled by dissociation and recombination of defects. The DLTS studies show that counterdoping with lithium eliminates at least three deep level defects and results in three new defects. It is speculated that the increased radiation resistance of the counterdoped cells is due primarily to the interaction of lithium with oxygen, single vacancies and divacancies and that the lithium-oxygen interaction is the most effective in contributing to the increased radiation resistance.

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

Dar, Roy; Shaffer, Sydney M.; Singh, Abhyudai

Recent analysis demonstrates that the HIV-1 Long Terminal Repeat (HIV LTR) promoter exhibits a range of possible transcriptional burst sizes and frequencies for any mean-expression level. However, these results have also been interpreted as demonstrating that cell-tocell expression variability (noise) and mean are uncorrelated, a significant deviation from previous results. Here, we re-examine the available mRNA and protein abundance data for the HIV LTR and find that noise in mRNA and protein expression scales inversely with the mean along analytically predicted transcriptional burst-size manifolds. We then experimentally perturb transcriptional activity to test a prediction of the multiple burst-size model: thatmore » increasing burst frequency will cause mRNA noise to decrease along given burst-size lines as mRNA levels increase. In conclusion, the data show that mRNA and protein noise decrease as mean expression increases, supporting the canonical inverse correlation between noise and mean.« less

Evaluation of Aqueous Leaf Extract of Cardiospermum halicacabum (L.) on Fertility of Male Rats.

PubMed

Peiris, L Dinithi C; Dhanushka, M A T; Jayathilake, T A H D G

2015-01-01

Treatment with 100 mg/kg and 200 mg/kg body weight of aqueous leaf extract (ALE) of Cardiospermum halicacabum for 30 days produced a significant dose dependent increase in the sperm counts and sperm motility in both caput and cauda regions. Further, significant increase in serum testosterone level was evident at all applied doses. However, no significant changes in the weight of sex organs were observed. Aqueous leaf extract also increased the number of females impregnated, number of implantations, and number of viable fetuses while decreasing the total number of resorption sites in the pregnant females. However, the total cholesterol level in the serum remained unchanged and there were no records on renotoxicity; nevertheless ALE exhibited a hepatoprotective effect. It was concluded that aqueous leaf extract of Cardiospermum halicacabum enhanced sperm concentration, motility, and testosterone, leading to positive results in fertility.

Polarization and Piezoelectric Properties of a Nitrile Substituted Polyimide

NASA Technical Reports Server (NTRS)

Simpson, Joycelyn; Ounaies, Zoubeida; Fay, Catharine

1997-01-01

This research focuses on the synthesis and characterization of a piezoelectric (beta-CN)- APB/ODPA polyimide. The remanent polarization and piezoelectric d(sub 31) and g(sub 33) coefficients are reported to assess the effect of synthesis variations. Each of the materials exhibits a level of piezoelectricity which increases with temperature. The remanent polarization is retained at temperatures close to the glass transition temperature of the polyimide.

Total carbon and nitrogen in mineral soil after 26 years of prescribed fire: Long Valley and Fort Valley Experimental Forests

Treesearch

Daniel G. Neary; Sally M. Haase; Steven T. Overby

2008-01-01

Prescribed fire was introduced to high density ponderosa pine stands at Fort Valley and Long Valley Experimental Forests in 1976. This paper reports on mineral soil total carbon (C) and nitrogen (N) at Long Valley. Total soil C and N levels were highly variable and exhibited an increasing, but inconsistent, concentration trend related to burn interval. Total N ranged...

CD44+CD24+ subset of PANC-1 cells exhibits radiation resistance via decreased levels of reactive oxygen species.

PubMed

Wang, Lei; Li, Pengping; Hu, Wei; Xia, Youyou; Hu, Chenxi; Liu, Liang; Jiang, Xiaodong

2017-08-01

Emerging evidence has suggested that pancreatic adenocarcinoma is sustained by pancreatic cancer stem cells. The present study aimed to investigate the expression patterns of the pancreatic cancer stem cell surface markers cluster of differentiation CD44 and CD24 in a pancreatic adenocarcinoma cell line, and to investigate the possible mechanisms for their radiation resistance. Flow cytometry was used to analyze the expression patterns of CD44 and CD24 in the pancreatic adenocarcinoma PANC-1 cell line. In addition, a multi-target click model was used to fit cell survival curves and determine the sensitizer enhancement ratio. The apoptosis and cycle distribution of the four cell subsets was determined using flow cytometry, and the level of reactive oxygen species (ROS) was determined using the 2',7'-dichlorofluorescin diacetate probe. The present results identified that the ratios of CD44 + and CD24 + in the sorted PANC-1 cell line were 92.0 and 4.7%, respectively. Prior to radiation, no statistically significant differences were observed among the four groups. Following treatment with 6 MV of X-rays, the rate of apoptosis was decreased in the CD44 + CD24 + group compared with other subsets. The percentage of G0/G1 cells was highest in the CD44 + CD24 + group compared with the three other groups, which exhibited increased radiosensitivity. In addition, the level of ROS in the CD44 + CD24 + group was reduced compared with the other groups. In summary, the results of the present study indicated that CD44 + CD24 + exhibited stem cell properties. The lower level of ROS and apoptosis in CD44 + CD24 + cells may contribute to their resistance to radiation in pancreatic adenocarcinoma.

Decreased medial prefrontal cortex activation during self-referential processing in bipolar mania.

PubMed

Herold, Dorrit; Usnich, Tatiana; Spengler, Stephanie; Sajonz, Bastian; Bauer, Michael; Bermpohl, Felix

2017-09-01

Patients with bipolar disorder in mania exhibit symptoms pointing towards altered self-referential processing, such as decreased self-focus, flight of ideas and high distractibility. In depression, the opposite pattern of symptoms has been connected to increased activation of medial prefrontal cortex (mPFC) during self-referential processing. In this study, we hypothesized that (1) patients with mania will exhibit decreased activation in the mPFC during self-referential processing and (2) will be more alexithymic and that levels of alexithymia will correlate negatively with mPFC activation. The neural response to standardized pictures was compared in 14 patients with bipolar I disorder in mania to 14 healthy controls using blood oxygen level dependent contrast magnetic resonance imaging. Participants were asked to indicate with button press during the scanning session for each picture whether the pictures personally related to them or not. Toronto alexithymia scale (TAS) scores were recorded from all participants. In the group analysis, patients with mania exhibited decreased activation in a predefined region of interest in the mPFC during self-referential processing compared to healthy controls. Patients with mania showed significantly higher levels of alexithymia, attributable to difficulties in identifying and describing emotions. Activation in the mPFC correlated negatively with levels of alexithymia. Results presented here should be replicated in a larger group, potentially including unmedicated patients. The finding of decreased mPFC activation during self-referential processing in mania may reflect decreased self-focus and high distractibility. Support for this view comes from the negative correlation between higher alexithymia scores and decreased mPFC activation. These findings represent an opposite clinical and neuroimaging pattern to findings in depression. Copyright © 2017. Published by Elsevier B.V.

In vivo neuronal function of the fragile X mental retardation protein is regulated by phosphorylation

PubMed Central

Coffee, R. Lane; Williamson, Ashley J.; Adkins, Christopher M.; Gray, Marisa C.; Page, Terry L.; Broadie, Kendal

2012-01-01

Fragile X syndrome (FXS), caused by loss of the Fragile X Mental Retardation 1 (FMR1) gene product (FMRP), is the most common heritable cause of intellectual disability and autism spectrum disorders. It has been long hypothesized that the phosphorylation of serine 500 (S500) in human FMRP controls its function as an RNA-binding translational repressor. To test this hypothesis in vivo, we employed neuronally targeted expression of three human FMR1 transgenes, including wild-type (hFMR1), dephosphomimetic (S500A-hFMR1) and phosphomimetic (S500D-hFMR1), in the Drosophila FXS disease model to investigate phosphorylation requirements. At the molecular level, dfmr1 null mutants exhibit elevated brain protein levels due to loss of translational repressor activity. This defect is rescued for an individual target protein and across the population of brain proteins by the phosphomimetic, whereas the dephosphomimetic phenocopies the null condition. At the cellular level, dfmr1 null synapse architecture exhibits increased area, branching and bouton number. The phosphomimetic fully rescues these synaptogenesis defects, whereas the dephosphomimetic provides no rescue. The presence of Futsch-positive (microtubule-associated protein 1B) supernumerary microtubule loops is elevated in dfmr1 null synapses. The human phosphomimetic restores normal Futsch loops, whereas the dephosphomimetic provides no activity. At the behavioral level, dfmr1 null mutants exhibit strongly impaired olfactory associative learning. The human phosphomimetic targeted only to the brain-learning center restores normal learning ability, whereas the dephosphomimetic provides absolutely no rescue. We conclude that human FMRP S500 phosphorylation is necessary for its in vivo function as a neuronal translational repressor and regulator of synaptic architecture, and for the manifestation of FMRP-dependent learning behavior. PMID:22080836

Carotenoids buffer the acute phase response on fever, sickness behavior and rapid bill color change in zebra finches.

PubMed

George, Deanna B; Schneider, Brent C; McGraw, Kevin J; Ardia, Daniel R

2017-08-15

Carotenoids are finite resources that animals can allocate to self-maintenance, attractiveness or reproduction. Here we test how carotenoids affect the acute phase response (APR), an intense rapid systemic response characterized by fever, sickness behavior and production of acute phase proteins, which serves to reduce pathogen persistence. We conducted a 2×2 factorial design experiment in captive adult male and female zebra finches ( Taeniopygia guttata ) to determine the effects of carotenoid supplementation on the intensity of the APR. We measured changes in feeding rate, activity level and body temperature of the birds. We found that, relative to unsupplemented controls, carotenoid-supplemented birds exhibited less severe reductions in feeding and activity, smaller increases in body temperature and lower circulating levels of haptoglobin (an acute phase protein) 24 h after inducing an APR. Among supplemented individuals, those with higher blood carotenoid levels exhibited a lower reduction in activity rate after 24 h. Forty-eight hours after APR induction, birds exhibited a significant decrease in plasma carotenoid levels and a decrease in bill hue, with less reduction in hue in carotenoid-supplemented individuals. These results demonstrate that carotenoids can alleviate several important behavioral and physiological effects of an APR and that bill color can change rapidly following induction of the costly APR immune defense. In particular, immune activation may have caused birds to preferentially draw down carotenoids from the bloodstream, ostensibly for use in health. Rapid bill color changes over a 48-h period support growing evidence that bills may serve as short-term signals of health and condition. © 2017. Published by The Company of Biologists Ltd.

Decreased anxiety- and depression-like behaviors and hyperactivity in a type 3 deiodinase-deficient mouse showing brain thyrotoxicosis and peripheral hypothyroidism.

PubMed

Stohn, J Patrizia; Martinez, M Elena; Hernandez, Arturo

2016-12-01

Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 -/- mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 -/- mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 -/- mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decreased Anxiety- and Depression-like Behaviors and Hyperactivity in a Type 3 Deiodinase-Deficient Mouse Showing Brain Thyrotoxicosis and Peripheral Hypothyroidism

PubMed Central

Stohn, J. Patrizia; Martinez, M. Elena; Hernandez, Arturo

2016-01-01

Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 −/− mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 −/− mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 −/− mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. PMID:27580013

Effects of severity of gross motor disability on anticipatory postural adjustments while standing in individuals with bilateral spastic cerebral palsy.

PubMed

Tomita, Hidehito; Fukaya, Yoshiki; Takagi, Yukina; Yokozawa, Asami

2016-10-01

Although individuals with bilateral spastic cerebral palsy (BSCP) exhibit several deficits in anticipatory postural adjustments (APAs) while standing, effects of severity of motor disability on their APAs are unclear. To determine whether individuals with BSCP exhibit severity-dependent deficits in APAs. Seven individuals with level II BSCP (BSCP-II group) and seven with level III BSCP (BSCP-III group) according to the Gross Motor Function Classification System and seven healthy controls lifted a load under two different load conditions. Anticipatory activities of the erector spinae (ES), medial hamstring (MH), and gastrocnemius (GCM) were smaller in the two BSCP groups than in the control group. Although the anticipatory GCM activity was similar between the BSCP groups, the ES and MH activities were larger in the BSCP-II group than in the BSCP-III group. In the BSCP-II group, an increase in anticipatory activity with an increase in load was observed in the MH, but not in the GCM. In the BSCP-III group, load-related modulation was not found in the MH or GCM. The present findings suggest that in individuals with BSCP with severe motor disability, APA deficits extend to more proximal parts of the body. Copyright © 2016 Elsevier Ltd. All rights reserved.

Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine.

PubMed

Schalling, M; Dagerlind, A; Brené, S; Hallman, H; Djurfeldt, M; Persson, H; Terenius, L; Goldstein, M; Schlesinger, D; Hökfelt, T

1988-11-01

Expression and regulation of the catecholamine-synthesizing enzymes phenylethanolamine N-methyltransferase (PNMTase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28) and tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the coexisting neuropeptide tyrosine (NPY) were studied in rat and bovine adrenal medulla. By using both immunohistochemistry and in situ hybridization, PNMTase- and NPY-positive cells exhibited a close overlap in bovine medulla and were preferentially localized in the outer two-thirds of the medulla. Although TyrOHase and its mRNA were observed in virtually all medullary gland cells, TyrOHase mRNA levels were much higher in the PNMTase- and NPY-positive cells. After administration of the catecholamine-depleting drug reserpine to rats, a brief increase, followed by a dramatic decrease, in the level of PNMTase mRNA was observed in the adrenal medulla. In contrast, mRNA for both TyrOHase and NPY only exhibited an increase, whereby the TyrOHase mRNA peak preceded that of NPY mRNA. Different regulatory mechanisms may thus operate for these three compounds coexisting in the adrenal medulla.

Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine.

PubMed Central

Schalling, M; Dagerlind, A; Brené, S; Hallman, H; Djurfeldt, M; Persson, H; Terenius, L; Goldstein, M; Schlesinger, D; Hökfelt, T

1988-01-01

Expression and regulation of the catecholamine-synthesizing enzymes phenylethanolamine N-methyltransferase (PNMTase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28) and tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the coexisting neuropeptide tyrosine (NPY) were studied in rat and bovine adrenal medulla. By using both immunohistochemistry and in situ hybridization, PNMTase- and NPY-positive cells exhibited a close overlap in bovine medulla and were preferentially localized in the outer two-thirds of the medulla. Although TyrOHase and its mRNA were observed in virtually all medullary gland cells, TyrOHase mRNA levels were much higher in the PNMTase- and NPY-positive cells. After administration of the catecholamine-depleting drug reserpine to rats, a brief increase, followed by a dramatic decrease, in the level of PNMTase mRNA was observed in the adrenal medulla. In contrast, mRNA for both TyrOHase and NPY only exhibited an increase, whereby the TyrOHase mRNA peak preceded that of NPY mRNA. Different regulatory mechanisms may thus operate for these three compounds coexisting in the adrenal medulla. Images PMID:2903502

Lombard effect onset times reveal the speed of vocal plasticity in a songbird.

PubMed

Hardman, Samuel I; Zollinger, Sue Anne; Koselj, Klemen; Leitner, Stefan; Marshall, Rupert C; Brumm, Henrik

2017-03-15

Animals that use vocal signals to communicate often compensate for interference and masking from background noise by raising the amplitude of their vocalisations. This response has been termed the Lombard effect. However, despite more than a century of research, little is known how quickly animals can adjust the amplitude of their vocalisations after the onset of noise. The ability to respond quickly to increases in noise levels would allow animals to avoid signal masking and ensure their calls continue to be heard, even if they are interrupted by sudden bursts of high-amplitude noise. We tested how quickly singing male canaries ( Serinus canaria ) exhibit the Lombard effect by exposing them to short playbacks of white noise and measuring the speed of their responses. We show that canaries exhibit the Lombard effect in as little as 300 ms after the onset of noise and are also able to increase the amplitude of their songs mid-song and mid-phrase without pausing. Our results demonstrate high vocal plasticity in this species and suggest that birds are able to adjust the amplitude of their vocalisations very rapidly to ensure they can still be heard even during sudden changes in background noise levels. © 2017. Published by The Company of Biologists Ltd.

Micro-indentation fracture behavior of human enamel.

PubMed

Padmanabhan, Sanosh Kunjalukkal; Balakrishnan, Avinash; Chu, Min-Cheol; Kim, Taik Nam; Cho, Seong Jai

2010-01-01

The purpose of this study was to determine the crack resistance behavior (K(R)) of human enamel in relation to its microstructure. Human molar teeth were precision cut, polished and tested using Vickers micro-indentation at different loads ranging from 0.98 to 9.8 N. Five indentation load levels were considered, 20 indentation cracks for each load level were introduced on the surface of the test specimen (10 indentations per tooth) and their variability was evaluated using Weibull statistics and an empirical model. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to analyze the crack morphology and propagation mechanisms involved. The results showed that enamel exhibited increasing cracking resistance (K(R)) with increasing load. It was found that the crack propagation mainly depended on the location and the microstructure it encountered. SEM showed the formation of crack bridges and crack deflection near the indentation crack tip. The crack mode was of Palmqvist type even at larger loads of 9.8 N. This was mainly attributed to the large process zone created by the interwoven lamellar rod like microstructure exhibited by the enamel surface. This study shows that there are still considerable prospects for improving dental ceramics and for mimicking the enamel structure developed by nature.

Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome.

PubMed

Mizuno, Kei; Tanaka, Masaaki; Tanabe, Hiroki C; Joudoi, Takako; Kawatani, Junko; Shigihara, Yoshihito; Tomoda, Akemi; Miike, Teruhisa; Imai-Matsumura, Kyoko; Sadato, Norihiro; Watanabe, Yasuyoshi

2015-01-01

The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue.

Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome

PubMed Central

Mizuno, Kei; Tanaka, Masaaki; Tanabe, Hiroki C.; Joudoi, Takako; Kawatani, Junko; Shigihara, Yoshihito; Tomoda, Akemi; Miike, Teruhisa; Imai-Matsumura, Kyoko; Sadato, Norihiro; Watanabe, Yasuyoshi

2015-01-01

The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue. PMID:26594619

Zinc in an ultraoligotrophic lake food web.

PubMed

Montañez, Juan Cruz; Arribére, María A; Rizzo, Andrea; Arcagni, Marina; Campbell, Linda; Ribeiro Guevara, Sergio

2018-06-01

Zinc (Zn) bioaccumulation and trophic transfer were analyzed in the food web of Lake Nahuel Huapi, a deep, unpolluted ultraoligotrophic system in North Patagonia. Benthic macroinvertebrates, plankton, and native and introduced fish were collected at three sites. The effect of pyroclastic inputs on Zn levels in lacustrine food webs was assessed by studying the impact of the eruption of Puyehue-Cordón Caulle volcanic complex (PCCVC) in 2011, by performing three sampling campaigns immediately before and after the PCCVC eruption, and after 2 years of recovery of the ecosystem. Zinc trophodynamics in L. Nahuel Huapi food web was assessed using nitrogen stable isotopes (δ 15 N). There was no significant increase of Zn concentrations ([Zn]) in L. Nahuel Huapi biota after the PCCVC eruption, despite the evidence of [Zn] increase in lake water that could be associated with volcanic ash leaching. The organisms studied exhibited [Zn] above the threshold level considered for dietary deficiency, regulating Zn adequately even under a catastrophic situations like PCCVC 2011 eruption. Zinc concentrations exhibited a biodilution pattern in the lake's food web. To the best of our knowledge, present research is the first report of Zn biodilution in lacustrine systems, and the first to study Zn transfer in a freshwater food web including both pelagic and benthic compartments.

A mouse model of fragile X syndrome exhibits heightened arousal and/or emotion following errors or reversal of contingencies.

PubMed

Moon, J; Ota, K T; Driscoll, L L; Levitsky, D A; Strupp, B J

2008-07-01

This study was designed to further assess cognitive and affective functioning in a mouse model of Fragile X syndrome (FXS), the Fmr1(tm1Cgr) or Fmr1 "knockout" (KO) mouse. Male KO mice and wild-type littermate controls were tested on learning set and reversal learning tasks. The KO mice were not impaired in associative learning, transfer of learning, or reversal learning, based on measures of learning rate. Analyses of videotapes of the reversal learning task revealed that both groups of mice exhibited higher levels of activity and wall-climbing during the initial sessions of the task than during the final sessions, a pattern also seen for trials following an error relative to those following a correct response. Notably, the increase in both behavioral measures seen early in the task was significantly more pronounced for the KO mice than for controls, as was the error-induced increase in activity level. This pattern of effects suggests that the KO mice reacted more strongly than controls to the reversal of contingencies and pronounced drop in reinforcement rate, and to errors in general. This pattern of effects is consistent with the heightened emotional reactivity frequently described for humans with FXS. (c) 2008 Wiley Periodicals, Inc.

High-biomass C4 grasses-Filling the yield gap.

PubMed

Mullet, John E

2017-08-01

A significant increase in agricultural productivity will be required by 2050 to meet the needs of an expanding and rapidly developing world population, without allocating more land and water resources to agriculture, and despite slowing rates of grain yield improvement. This review examines the proposition that high-biomass C 4 grasses could help fill the yield gap. High-biomass C 4 grasses exhibit high yield due to C 4 photosynthesis, long growth duration, and efficient capture and utilization of light, water, and nutrients. These C 4 grasses exhibit high levels of drought tolerance during their long vegetative growth phase ideal for crops grown in water-limited regions of agricultural production. The stems of some high-biomass C 4 grasses can accumulate high levels of non-structural carbohydrates that could be engineered to enhance biomass yield and utility as feedstocks for animals and biofuels production. The regulatory pathway that delays flowering of high-biomass C 4 grasses in long days has been elucidated enabling production and deployment of hybrids. Crop and landscape-scale modeling predict that utilization of high-biomass C 4 grass crops on land and in regions where water resources limit grain crop yield could increase agricultural productivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, in Aspergillus fumigatus

PubMed Central

Mulvihill, Eoin D.; Moloney, Nicola M.; Owens, Rebecca A.; Dolan, Stephen K.; Russell, Lauren; Doyle, Sean

2017-01-01

The functionality of many microsome-associated proteins which exhibit altered abundance in response to iron limitation in Aspergillus fumigatus is unknown. Here, we generate and characterize eight gene deletion strains, and of most significance reveal that MirC (AFUA_2G05730) contributes to the maintenance of intracellular siderophore [ferricrocin (FC)] levels, augments conidiation, confers protection against oxidative stress, exhibits an intracellular localization and contributes to fungal virulence in the Galleria mellonella animal model system. FC levels were unaffected following deletion of all other genes encoding microsome-associated proteins. MirC does not appear to play a role in either siderophore export from, or uptake into, A. fumigatus. Label-free quantitative proteomic analysis unexpectedly revealed increased abundance of siderophore biosynthetic enzymes. In addition, increased expression of hapX (7.2 and 13.8-fold at 48 and 72 h, respectively; p < 0.001) was observed in ΔmirC compared to wild-type under iron-replete conditions by qRT-PCR. This was complemented by significantly elevated extracellular triacetylfusarinine C (TAFC; p < 0.01) and fusarinine C (FSC; p < 0.05) siderophore secretion. We conclude that MirC plays an important role in FC biosynthesis and contributes to the maintenance of iron homeostasis in A. fumigatus. PMID:28367141

Influence of patient-related and surgery-related risk factors on cognitive performance, emotional state, and convalescence after cardiac surgery.

PubMed

Ille, Rottraut; Lahousen, Theresa; Schweiger, Stefan; Hofmann, Peter; Kapfhammer, Hans-Peter

2007-01-01

Cardiac surgery may account for complications such as cognitive impairment, depression, and delay of convalescence. This study investigated the influence of different risk factors on cognitive performance, emotional state, and convalescence. We included 83 patients undergoing cardiac surgery who had no indication of postoperative delirium. Psychometric testing was performed 1 day before and 7 days after surgery. Neuron-specific enolase (NSE) levels were measured 1 day before and 36 h after surgery. Depression score increased after surgery, but patients showed no clinically significant depression. Postoperative cognitive performance correlated with postoperative depression level and preoperative cognitive performance. Forty-three percent of patients showed postoperative decline. Older patients exhibited a higher postoperative increase in NSE concentrations. Patients undergoing coronary artery bypass grafts or combined procedures exhibited more medical risk factors than those undergoing valve surgery alone. The number of bypass grafts was associated with time of hospitalization, and the number of patient-related risk factors correlated with stay in intensive care unit. For elderly patients undergoing cardiac surgery, older age, total preexisting medical risk factors, and surgery duration seem to be the most important factors influencing cognitive outcome and convalescence. Results show that, also for patients without postoperative delirium, medical risk factors and intraoperative parameters can result in delay of convalescence.

Meditation-induced changes in high-frequency heart rate variability predict smoking outcomes

PubMed Central

Libby, Daniel J.; Worhunsky, Patrick D.; Pilver, Corey E.; Brewer, Judson A.

2012-01-01

Background: High-frequency heart rate variability (HF-HRV) is a measure of parasympathetic nervous system (PNS) output that has been associated with enhanced self-regulation. Low resting levels of HF-HRV are associated with nicotine dependence and blunted stress-related changes in HF-HRV are associated with decreased ability to resist smoking. Meditation has been shown to increase HF-HRV. However, it is unknown whether tonic levels of HF-HRV or acute changes in HF-HRV during meditation predict treatment responses in addictive behaviors such as smoking cessation. Purpose: To investigate the relationship between HF-HRV and subsequent smoking outcomes. Methods: HF-HRV during resting baseline and during mindfulness meditation was measured within two weeks of completing a 4-week smoking cessation intervention in a sample of 31 community participants. Self-report measures of smoking were obtained at a follow up 17-weeks after the initiation of treatment. Results: Regression analyses indicated that individuals exhibiting acute increases in HF-HRV from resting baseline to meditation smoked fewer cigarettes at follow-up than those who exhibited acute decreases in HF-HRV (b = −4.89, p = 0.008). Conclusion: Acute changes in HF-HRV in response to meditation may be a useful tool to predict smoking cessation treatment response. PMID:22457646

Transient anhedonia phenotype and altered circadian timing of behaviour during night-time dim light exposure in Per3−/− mice, but not wildtype mice

PubMed Central

Martynhak, Bruno Jacson; Hogben, Alexandra L.; Zanos, Panos; Georgiou, Polymnia; Andreatini, Roberto; Kitchen, Ian; Archer, Simon N.; von Schantz, Malcolm; Bailey, Alexis; van der Veen, Daan R.

2017-01-01

Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are ‘direct’ effects of light on affect, an ‘indirect’ pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3−/− mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3−/−) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2–3 of dim light at night, whereas WT mice did not. Per3−/− mice also exhibited a significantly smaller delay in behavioural timing than WT mice during weeks 1, 2 and 4 of dim light at night exposure. When treated with imipramine, neither Per3−/− nor WT mice exhibited an anhedonia-like phenotype, and neither genotypes exhibited a delay in behavioural timing in responses to dLAN. While the association between both Per3−/− phenotypes remains unclear, both are alleviated by imipramine treatment during dim night-time light. PMID:28071711

Variation in Enamel Formation Genes Influences Enamel Demineralization In Vitro in a Streptococcus mutans Biofilm Model

PubMed Central

Pang, Liangyue; Zhi, Qinghui; Zhuang, Peilin; Yu, Lixia; Tao, Ye; Lin, Huancai

2017-01-01

Genetic studies have shown that variations in enamel formation genes are associated with caries susceptibility. The aim of this study was to test in vitro whether variants in these genes are associated with dental enamel demineralization in a Streptococcus mutans biofilm model. DNA and enamel samples were obtained from 213 individuals. DNA was extracted from saliva, and 16 single nucleotide polymorphisms were analyzed. The physical and chemical properties of sound enamel samples and the mineral loss and the lesion depth of the demineralized enamel samples under cariogenic challenge were analyzed. Microhardness, enamel chemicals, mineral loss and demineralization depth were compared between different genotypes at each single nucleotide polymorphism. The GG genotype of TUFT1 (rs17640579) and the GT genotype of MMP20 (rs1612069) exhibited increased microhardness (p = 0.044 and 0.016, respectively). The GG genotype of AMBN (rs7694409) had a higher magnesium level, while the CT genotype of TFIP11 (rs2097470) had a lower magnesium level (p = 0.044 and 0.046, respectively). The GT genotype of MMP20 (rs1612069) had a higher calcium level (p = 0.034). The GG genotype of AMBN (rs13115627), the AG genotype of ENAM (rs12640848) and the AA genotype of MMP20 (rs2292730) had a lower phosphorus level (p = 0.012, 0.006, and 0.023, respectively). The GG genotype of AMBN (rs13115627) was also associated with a higher calcium-phosphorus ratio (p = 0.034). Individuals with the CC genotype of TFIP11 (rs134143) exhibited significantly more mineral loss (p = 0.011) and a deeper lesions (p = 0.042). Individuals with the TT genotype of TFIP11 (rs2097470) had more mineral loss (p = 0.018). Individuals with the GG genotype of TUFT1 (rs17640579) exhibited a shallower demineralization depth (p = 0.047). Individuals with the GT genotype of MMP20 (rs1612069) exhibited a shallower demineralization depth (p = 0.042). Individuals with the GG genotype of ENAM (rs12640848) exhibited less mineral loss (p = 0.01) and a shallower demineralization depth (p = 0.03). Genetic variations in TFIP11, TUFT1, MMP20, and ENAM influenced enamel demineralization in a Streptococcus mutans biofilm model. PMID:29163197

Genetic instability caused by loss of MutS homolog 3 in human colorectal cancer

PubMed Central

Haugen, Astrid C.; Goel, Ajay; Yamada, Kanae; Marra, Giancarlo; Nguyen, Thuy-Phuong; Nagasaka, Takeshi; Kanazawa, Shinsaku; Koike, Junichi; Kikuchi, Yoshinori; Zhong, Xiaoling; Arita, Michitsune; Shibuya, Kazutoshi; Oshimura, Mitsuo; Hemmi, Hiromichi; Boland, Clement Richard; Koi, Minoru

2008-01-01

Microsatellite instability (MSI) is a hallmark of mismatch repair deficiency. High levels of MSI at mono- and dinucleotide repeats in colorectal cancer (CRC) are attributed to inactivation of the mismatch repair genes, hMLH1 and hMSH2. CRC with low levels of MSI (MSI-L) exists; however its molecular basis is unclear. There is another type of MSI - “elevated microsatellite alterations at selected tetranucleotide repeats” - (EMAST) where loci containing [AAAG]n or [ATAG]n repeats are unstable. EMAST is frequent in non-colorectal cancers; however the incidence of EMAST and its cause in CRC is not known. Here, we report that MSH3-knock-down or MSH3-deficient cells exhibit the EMAST phenotype and low levels of mutations at dinucleotide repeats. About 60% of 117 sporadic CRC cases exhibit EMAST. All of the cases defined as MSI-H (16 cases) exhibited high levels of EMAST. Among 101 non-MSI-H cases, all 19 cases of MSI-L and 35 of 82 cases of MSS exhibited EMAST. Although non-MSI-H CRC tissues contained MSH3-negative tumor cells ranging from 2-50% of the total tumor cell population, the tissues exhibiting EMAST contained more MSH3-negative cells (average 31.5%) than did the tissues not exhibiting EMAST (8.4%). Taken together, our results support the idea that MSH3-deficiency causes EMAST or EMAST with low levels of MSI at the loci with dinucleotide repeats in CRC. PMID:18922920

Activity budgets and the relationship between feeding and stereotypic behaviors in Asian elephants (Elephas maximus) in a Zoo.

PubMed

Rees, Paul A

2009-03-01

Activity budgets were studied in eight Asian elephants (Elephas maximus) at Chester Zoo (UK) for 35 days, between January and November 1999. Recordings were made between 10:00 and 16:00 hr (with most behavior frequencies calculated between 10:00 and 14:00 hr). The elephants exhibited variation in activity depending on their age, sex, the time of day and the time of year. Only the five adult cows exhibited stereotypic behavior, with frequencies ranging from 3.9 to 29.4% of all observations. These elephants exhibited individual, diurnal and seasonal variation in stereotypic behavior. This has implications for studies that use short sampling periods and may make comparisons of data collected at different times of the day or year invalid. The six adult elephants spent 27.4-41.4% of the time feeding (between 10:00 and 14:00 hr), 22.9-42.0% standing still, 6.1-19.2% walking and 3.9-9.6% dusting. The hypothesis that the frequency of stereotypic behavior in adult cow elephants was negatively correlated with the frequency of feeding behavior was tested and was found to be true. Stereotypic behavior increased in frequency toward the end of the day-while waiting to return to the elephant house for food--and elephants spent more time stereotyping during the winter months than during the summer months. Elephants were inactive (i.e. exhibited behaviors other than locomotion) for between 70.1 and 93.9% of the time. Creating more opportunities for elephants to exhibit foraging behavior and the introduction of greater unpredictability into management regimes, especially feeding times, may reduce the frequency of stereotypic behavior and increase general activity levels.

Head-space, small-chamber and in-vehicle tests for volatile organic compounds (VOCs) emitted from air fresheners for the Korean market.

PubMed

Jo, Wan-Kuen; Lee, Jong-Hyo; Kim, Mo-Keun

2008-02-01

The present study investigated the emission characteristics of gel-type air fresheners (AFs), using head-space, small-chamber, and in-vehicle tests. Five toxic or hazardous analytes were found in the headspace phase of AFs (toluene, benzene, ethyl benzene, and m,p-xylene) at a frequency of more than 50%. Limonene and linalool, which are known to be unsaturated ozone-reactive VOCs, were detected at a frequency of 58 and 35%, respectively. The empirical model fitted well with the time-series concentrations in the chamber, thereby suggesting that the empirical model was suitable for testing emissions. Limonene exhibited the highest emission rate, followed by m,p-xylene, toluene, ethyl benzene, and benzene. For most target VOCs, higher air change per hour (ACH) levels exhibited increased emission rates. In contrast, higher ACH levels resulted in lower chamber concentrations. The mean concentration of limonene was significantly higher in passenger cars with an AF than without. For other target compounds, there were no significant differences between the two conditions tested. Consequently, it was suggested that unlike limonene, the emission strength for aromatic compounds identified in the chamber tests was not strong enough to elevate in-vehicle levels.

Influences of Reduced Expression of Maternal Bone Morphogenetic Protein 2 on Embryonic Development

PubMed Central

Singh, Ajeet P.; Castranio, Trisha; Scott, Greg; Guo, Dayong; Harris, Marie A.; Ray, Manas; Harris, Stephan E.; Mishina, Yuji

2009-01-01

Bone morphogenetic protein 2 (BMP2) was originally found by its osteoinductive ability, and recent genetic analyses have revealed that it plays critical roles during early embryogenesis, cardiogenesis, decidualization as well as skeletogenesis. During a course of evaluation of the conditional allele for Bmp2, we found that the presence of a neo cassette, a selection marker needed for gene targeting events in embryonic stem cells, in the 3’ untranslated region of exon 3 of Bmp2, reduced the expression levels of Bmp2 both in embryonic and maternal tissues. Some of the embryos that were genotyped as transheterozygous for the floxed allele with the neo cassette over the conventional null allele (fn/−) showed a lethal phenotype including defects in cephalic neural tube closure and ventral abdominal wall closure. Embryos exhibiting these abnormalities were increased when genotypes of the pregnant females were different; when expression levels of Bmp2 in maternal tissues were lower, a larger proportion of fn/− embryos exhibit these abnormalities. These results suggest that the expression levels of Bmp2 together in both in embryonic and maternal tissues influence the normal neural tube closure and body wall closure with different thresholds. PMID:18769073

Quality and readability of English-language internet information for aphasia.

PubMed

Azios, Jamie H; Bellon-Harn, Monica; Dockens, Ashley L; Manchaiah, Vinaya

2017-08-14

Little is known about the quality and readability of treatment information in specific neurogenic disorders, such as aphasia. The purpose of this study was to assess quality and readability of English-language Internet information available for aphasia treatment. Forty-three aphasia treatment websites were aggregated using five different country-specific search engines. Websites were then analysed using quality and readability assessments. Statistical calculations were employed to examine website ratings, differences between website origin and quality and readability scores, and correlations between readability instruments. Websites exhibited low quality with few websites obtaining Health On the Net (HON) certification or clear, thorough information as measured by the DISCERN. Regardless of website origin, readability scores were also poor. Approximate educational levels required to comprehend information on aphasia treatment websites ranged from 13 to 16 years of education. Significant differences were found between website origin and readability measures with higher levels of education required to understand information on websites of non-profit organisations. Current aphasia treatment websites were found to exhibit low levels of quality and readability, creating potential accessibility problems for people with aphasia and significant others. Websites including treatment information for aphasia must be improved in order to increase greater information accessibility.

The concentration of disadvantage and the rise of an urban penalty: urban slum prevalence and the social production of health inequalities in the developing countries.

PubMed

Rice, James; Rice, Julie Steinkopf

2009-01-01

Urban slums are proliferating in the developing countries. A corollary of this structural transformation is the increasing recognition of an urban penalty wherein slum populations exhibit notable inequalities in health relative to non-slum urban residents and even rural populations. The built urban environment, in turn, is a crucial context within which the social production of disproportionate morbidity and mortality is enacted. The authors develop this assertion and use bivariate and partial correlation analysis to highlight the association of urban slum prevalence, or proportion of the total population living in urban slum conditions, with indicators of mortality and gender parity, measured at the national level. Data for 99 developing countries show that greater urban slum prevalence is strongly correlated with higher levels of infant, child, and maternal mortality. Further, urban slum prevalence exhibits strong, deleterious correlations with gender parity (measured by the gender development index) and fertility rate, factors that have a crucial direct impact in shaping variant mortality levels. Future research is warranted on the social inequalities in health and illness derived from the expansion of urban slum conditions in the developing countries.

Carbon cycling at the tipping point: Does ecosystem structure predict resistance to disturbance?

NASA Astrophysics Data System (ADS)

Gough, C. M.; Bond-Lamberty, B. P.; Stuart-Haentjens, E.; Atkins, J.; Haber, L.; Fahey, R. T.

2017-12-01

Ecosystems worldwide are subjected to disturbances that reshape their physical and biological structure and modify biogeochemical processes, including carbon storage and cycling rates. Disturbances, including those from insect pests, pathogens, and extreme weather, span a continuum of severity and, accordingly, may have different effects on carbon cycling processes. Some ecosystems resist biogeochemical changes following disturbance, until a critical threshold of severity is exceeded. The ecosystem properties underlying such functional resistance, and signifying when a tipping point will occur, however, are almost entirely unknown. Here, we present observational and experimental results from forests in the Great Lakes region, showing ecosystem structure is closely coupled with carbon cycling responses to disturbance, with shifts in structure predicting thresholds of and, in some cases, increases in carbon storage. We find, among forests in the region, that carbon storage regularly exhibits a non-linear threshold response to increasing disturbance levels, but the severity at which a threshold is reached varies among disturbed forests. More biologically and structurally complex forest ecosystems sometimes exhibit greater functional resistance than simpler forests, and consequently may have a higher disturbance severity threshold. Counter to model predictions but consistent with some theoretical frameworks, empirical data show moderate levels of disturbance may increase ecosystem complexity to a point, thereby increasing rates of carbon storage. Disturbances that increase complexity therefore may stimulate carbon storage, while severe disturbances at or beyond thresholds may simplify structure, leading to carbon storage declines. We conclude that ecosystem structural attributes are closely coupled with biogeochemical thresholds across disturbance severity gradients, suggesting that improved predictions of disturbance-related changes in the carbon cycle require better representation of ecosystem structure in models.

Aldosterone Activates Transcription Factor Nrf2 in Kidney Cells Both In Vitro and In Vivo

PubMed Central

Oteiza, Patricia I.; Link, Samuel; Hey, Valentin; Stopper, Helga; Schupp, Nicole

2014-01-01

Abstract Aims: An increased kidney cancer risk was found in hypertensive patients, who frequently exhibit hyperaldosteronism, known to contribute to kidney injury, with oxidative stress playing an important role. The capacity of kidney cells to up-regulate transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2), a key regulator of the cellular antioxidative defense, as a prevention of aldosterone-induced oxidative damage was investigated both in vitro and in vivo. Results: Aldosterone activated Nrf2 and increased the expression of enzymes involved in glutathione (GSH) synthesis and detoxification. This activation depended on the mineralocorticoid receptor (MR) and oxidative stress. In vitro, Nrf2 activation, GSH amounts, and target gene levels decreased after 24 h, while oxidant levels remained high. Nrf2 activation could not protect cells against oxidative DNA damage, as aldosterone-induced double-strand breaks and 7,8-dihydro-8-oxo-guanine (8-oxodG) lesions steadily rose. The Nrf2 activator sulforaphane enhanced the Nrf2 response both in vitro and in vivo, thereby preventing aldosterone-induced DNA damage. In vivo, Nrf2 activation further had beneficial effects on the aldosterone-caused blood pressure increase and loss of kidney function. Innovation: This is the first study showing the activation of Nrf2 by aldosterone. Moreover, the results identify sulforaphane as a substance that is capable of preventing aldosterone-induced damage both in vivo and in vitro. Conclusion: Aldosterone-induced Nrf2 adaptive response cannot neutralize oxidative actions of chronically increased aldosterone, which, therefore could be causally involved in the increased cancer incidence of hypertensive individuals. Enhancing the cellular antioxidative defense with sulforaphane might exhibit beneficial effects. Antioxid. Redox Signal. 21, 2126–2142. PMID:24512358

Interaction of 5-HTTLPR and Idiographic Stressors Predicts Prospective Depressive Symptoms Specifically among Youth in a Multi-wave Design

PubMed Central

Hankin, Benjamin L.; Jenness, Jessica; Abela, John R.Z.; Smolen, Andrew

2011-01-01

5-HTTLPR, episodic stressors, depressive and anxious symptoms were assessed prospectively (child and parent report) every 3 months over 1 year (5 waves of data) among community youth ages 9–15 (n = 220). Lagged HLM analyses showed 5-HTTLPR interacted with idiographic stressors (increases relative to the child’s own average level over time), but not nomothetic stressors (higher stress exposure relative to the sample), to predict prospective elevations in depressive, but not anxious, symptoms. Youth with copies of the S or LG alleles of 5-HTTLPR, who experienced more stressors relative to their typical level, exhibited prospective increases in depressive symptoms over time. These findings suggest that 5-HTTLPR confers susceptibility to depression via stress reactivity. PMID:21722029

Metastability of the midgap level EL 2 in GaAs - Relationship with the As antisite defect

NASA Technical Reports Server (NTRS)

Skowronski, M.; Lagowski, J.; Gatos, H. C.

1985-01-01

It is found that the rate of the photoinduced transition of the GaAs midgap level EL 2 to its metastable state increases as its occupation increases. High-resolution optical spectra of this transition exhibit a sharp peak very similar to the no-phonon line of the intracenter absorption of the As antisite defect. These findings show that the transition to the metastable state is initiated from the ground state 1A1, and it is finalized via the excited state 1T2 of the neutral As antisite defect. They thus provide a new basis for the critical assessment of the EL 2 metastability models and further confirmation of the association of EL 2 with the isolated As antisite defect.

Phosphatidylserine Ameliorates Neurodegenerative Symptoms and Enhances Axonal Transport in a Mouse Model of Familial Dysautonomia

PubMed Central

Naftelberg, Shiran; Abramovitch, Ziv; Gluska, Shani; Yannai, Sivan; Joshi, Yuvraj; Donyo, Maya; Ben-Yaakov, Keren; Gradus, Tal; Zonszain, Jonathan; Farhy, Chen; Ashery-Padan, Ruth

2016-01-01

Familial Dysautonomia (FD) is a neurodegenerative disease in which aberrant tissue-specific splicing of IKBKAP exon 20 leads to reduction of IKAP protein levels in neuronal tissues. Here we generated a conditional knockout (CKO) mouse in which exon 20 of IKBKAP is deleted in the nervous system. The CKO FD mice exhibit developmental delays, sensory abnormalities, and less organized dorsal root ganglia (DRGs) with attenuated axons compared to wild-type mice. Furthermore, the CKO FD DRGs show elevated HDAC6 levels, reduced acetylated α-tubulin, unstable microtubules, and impairment of axonal retrograde transport of nerve growth factor (NGF). These abnormalities in DRG properties underlie neuronal degeneration and FD symptoms. Phosphatidylserine treatment decreased HDAC6 levels and thus increased acetylation of α-tubulin. Further PS treatment resulted in recovery of axonal outgrowth and enhanced retrograde axonal transport by decreasing histone deacetylase 6 (HDAC6) levels and thus increasing acetylation of α-tubulin levels. Thus, we have identified the molecular pathway that leads to neurodegeneration in FD and have demonstrated that phosphatidylserine treatment has the potential to slow progression of neurodegeneration. PMID:27997532

Phosphatidylserine Ameliorates Neurodegenerative Symptoms and Enhances Axonal Transport in a Mouse Model of Familial Dysautonomia.

PubMed

Naftelberg, Shiran; Abramovitch, Ziv; Gluska, Shani; Yannai, Sivan; Joshi, Yuvraj; Donyo, Maya; Ben-Yaakov, Keren; Gradus, Tal; Zonszain, Jonathan; Farhy, Chen; Ashery-Padan, Ruth; Perlson, Eran; Ast, Gil

2016-12-01

Familial Dysautonomia (FD) is a neurodegenerative disease in which aberrant tissue-specific splicing of IKBKAP exon 20 leads to reduction of IKAP protein levels in neuronal tissues. Here we generated a conditional knockout (CKO) mouse in which exon 20 of IKBKAP is deleted in the nervous system. The CKO FD mice exhibit developmental delays, sensory abnormalities, and less organized dorsal root ganglia (DRGs) with attenuated axons compared to wild-type mice. Furthermore, the CKO FD DRGs show elevated HDAC6 levels, reduced acetylated α-tubulin, unstable microtubules, and impairment of axonal retrograde transport of nerve growth factor (NGF). These abnormalities in DRG properties underlie neuronal degeneration and FD symptoms. Phosphatidylserine treatment decreased HDAC6 levels and thus increased acetylation of α-tubulin. Further PS treatment resulted in recovery of axonal outgrowth and enhanced retrograde axonal transport by decreasing histone deacetylase 6 (HDAC6) levels and thus increasing acetylation of α-tubulin levels. Thus, we have identified the molecular pathway that leads to neurodegeneration in FD and have demonstrated that phosphatidylserine treatment has the potential to slow progression of neurodegeneration.

CD73 and AMPD3 deficiency enhance metabolic performance via erythrocyte ATP that decreases hemoglobin oxygen affinity.

PubMed

O'Brien, William G; Berka, Vladimir; Tsai, Ah-Lim; Zhao, Zhaoyang; Lee, Cheng Chi

2015-08-07

Erythrocytes are the key target in 5'-AMP induced hypometabolism. To understand how regulation of endogenous erythrocyte AMP levels modulates systemic metabolism, we generated mice deficient in both CD73 and AMPD3, the key catabolic enzymes for extracellular and intra-erythrocyte AMP, respectively. Under physiological conditions, these mice displayed enhanced capacity for physical activity accompanied by significantly higher food and oxygen consumption, compared to wild type mice. Erythrocytes from Ampd3(-/-) mice exhibited higher half-saturation pressure of oxygen (p50) and about 3-fold higher levels of ATP and ADP, while they maintained normal 2,3-bisphosphoglycerate (2,3-BPG), methemoglobin levels and intracellular pH. The affinity of mammalian hemoglobin for oxygen is thought to be regulated primarily by 2,3-BPG levels and pH (the Bohr effect). However, our results show that increased endogenous levels of ATP and ADP, but not AMP, directly increase the p50 value of hemoglobin. Additionally, the rise in erythrocyte p50 directly correlates with an enhanced capability of systemic metabolism.

Developmental effects on ureide levels are mediated by tissue-specific regulation of allantoinase in Phaseolus vulgaris L.

PubMed

Díaz-Leal, Juan Luis; Gálvez-Valdivieso, Gregorio; Fernández, Javier; Pineda, Manuel; Alamillo, Josefa M

2012-06-01

The ureides allantoin and allantoate are key molecules in the transport and storage of nitrogen in ureide legumes. In shoots and leaves from Phaseolus vulgaris plants using symbiotically fixed nitrogen as the sole nitrogen source, ureide levels were roughly equivalent to those of nitrate-supported plants during the whole vegetative stage, but they exhibited a sudden increase at the onset of flowering. This rise in the level of ureides, mainly in the form of allantoate, was accompanied by increases in allantoinase gene expression and enzyme activity, consistent with developmental regulation of ureide levels mainly through the tissue-specific induction of allantoate synthesis catalysed by allantoinase. Moreover, surprisingly high levels of ureides were also found in non-nodulated plants fertilized with nitrate, at both early and late developmental stages. The results suggest that remobilized N from lower leaves is probably involved in the sharp rise in ureides in shoots and leaves during early pod filling in N(2)-fixing plants and in the significant amounts of ureides observed in non-nodulated plants.

Antioxidant effects of melatonin in heart tissue after induction of experimental periodontitis in rats.

PubMed

Özdem, Muhsin; Kırzıoğlu, Fatma Y; Yılmaz, Hacı R; Vural, Hüseyin; Fentoğlu, Özlem; Uz, Efkan; Koçak, Ahmet; Yiğit, Ayşe

2017-01-01

The aim of this study was to evaluate the effects of melatonin on the oxidative stress in heart tissues after induction of experimental periodontitis in rats. Thirty Wistar Albino male rats were divided into four groups as follows: healthy + saline solution (Hs, n = 7), healthy + melatonin (Hm, n = 7), periodontitis + saline solution (Ps, n = 8), and periodontitis + melatonin (Pm, n = 8). Experimental periodontitis was induced using a ligature placed at the gingival margin of the maxillary second molars. Melatonin was applied intraperitoneally (10 mg/kg) every day for 2 weeks. After sacrificing the rats, serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) levels, and melatonin levels were evaluated. The Pm group exhibited lower alveolar bone loss than the Ps group. Melatonin levels increased in the periodontitis groups, and the Pm group had lower MDA levels and higher GSH-Px levels than the Ps group. These findings suggest that melatonin administration reduces MDA and increases GSH-Px levels in heart tissue, and these effects may be due to its antioxidant properties. Further studies are needed to understand the effects of melatonin on the association between periodontitis and cardiovascular disease.

Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque.

PubMed

Bonin, L R; Madden, K; Shera, K; Ihle, J; Matthews, C; Aziz, S; Perez-Reyes, N; McDougall, J K; Conroy, S C

1999-03-01

The study of atherogenesis in humans has been restricted by the limited availability and brief in vitro life span of plaque smooth muscle cells (SMCs). We describe plaque SMC lines with extended life spans generated by the expression of the human papillomavirus (HPV)-16 E6 and E7 genes, which has been shown to extend the life span of normal adult human aortic SMCs. Resulting cell lines (pdSMC1A and 2) demonstrated at least 10-fold increases in life span; pdSMC1A became immortal. The SMC identity of both pdSMC lines was confirmed by SM22 mRNA expression. pdSMC2 were generally diploid but with various structural and numerical alterations; pdSMC1A demonstrated several chromosomal abnormalities, most commonly -Y, +7, -13, anomalies previously reported in both primary pdSMCs and atherosclerotic tissue. Confluent pdSMC2 appeared grossly similar to HPV-16 E6/E7-expressing normal adult aortic SMCs (AASMCs), exhibiting typical SMC morphology/growth patterns; pdSMC1A displayed irregular cell shape/organization with numerous mitotic figures. Dedifferentiation to a synthetic/proliferative phenotype has been hypothesized as a critical step in atherogenesis, because rat neonatal SMCs and adult intimal SMCs exhibit similar gene expression patterns. To confirm that our pdSMC lines likewise express this apparent plaque phenotype, osteopontin, platelet-derived growth factor B, and elastin mRNA levels were determined in pdSMC1A, pdSMC2, and AASMCs. However, no significant increases in osteopontin or platelet-derived growth factor B expression levels were observed in either pdSMC compared with AASMCs. pdSMC2 alone expressed high levels of elastin mRNA. Lower levels of SM22 mRNA in pdSMC1A suggested greater dedifferentiation and/or additional population doublings in pdSMC1A relative to pdSMC2. Both pdSMC lines (particularly 1A) demonstrated high message levels for matrix Gla protein, previously reported to be highly expressed by human neointimal SMCs in vitro. These results describe 2 novel plaque cell lines exhibiting various features of plaque SMC biology; pdSMC2 may represent an earlier plaque SMC phenotype, whereas pdSMC1A may be representative of cells comprising an advanced atherosclerotic lesion.

Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes.

PubMed

Calanna, S; Scicali, R; Di Pino, A; Knop, F K; Piro, S; Rabuazzo, A M; Purrello, F

2014-06-01

We aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia. Ninety-one subjects with prediabetes according to HbA1c, i.e. from 5.7 to 6.4% (39-46 mmol/mol), 50 newly diagnosed patients with HbA1c-defined type 2 diabetes (HbA1c ≥6.5% [≥48 mmol/mol]), and 67 controls with HbA1c lower than 5.7% (<39 mmol/mol), were studied. Fasting blood samples for lipid profiles, fatty liver index (FLI), bioimpedance analysis, ultrasound scan of the liver, and BARD (body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score for evaluation of liver fibrosis, were performed in all subjects. In comparison to controls, subjects with prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure, triglycerides levels and apolipoprotein B/apolipoprotein AI ratio, higher FLI, increased prevalence of and more severe hepatic steatosis, similar BARD score, and higher total body fat mass. In comparison to subjects with diabetes, subjects with prediabetes exhibited: similar blood pressure and apolipoprotein B/apolipoprotein AI ratio, similar FLI, reduced prevalence of and less severe hepatic steatosis, lower BARD score, increased percent fat and lower total body muscle mass. In comparison to controls, subjects with diabetes showed: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure and triglycerides levels, higher FLI, increased prevalence of and more severe hepatic steatosis, higher BARD score, and higher total body muscle mass. Moreover, HbA1c was correlated with BMI, HOMA-IR, triglycerides, HDL cholesterol, AST, and ALT. Subjects with HbA1c-defined prediabetes and type 2 diabetes, respectively, are characterised by abnormalities in lipid profile and liver steatosis, thus exhibiting a severe risk profile for cardiovascular and liver diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

The immunomodulatory activities of licorice polysaccharides (Glycyrrhiza uralensis Fisch.) in CT 26 tumor-bearing mice.

PubMed

Ayeka, Peter Amwoga; Bian, YuHong; Githaiga, Peter Mwitari; Zhao, Ying

2017-12-15

The increasing use of complementary and alternative medicine (CAM) has kindled the need for scientific evaluation of the mechanism of action of CAMs. Although, licorice, a common ingredient in many Traditional Chinese medicine (TCM) has attracted great attention for its antitumor and immunomodulatory activities, the mechanism of action of its polysaccharides is still unclear. Here we report the immunomodulatory activity of licorice polysaccharides in vivo. The differential anticancer activities of licorice polysaccharides by tumorigenesis and immunomodulation was evaluated in vivo. Six weeks old, 120 CT-26 tumor bearing BALB/c mice, weighing 20 ± 2 g were used. They were randomly divided into six groups, three groups receiving high molecular weight (fraction A), low molecular weight (fraction B) polysaccharides and crude extract (fraction C); positive, negative and normal groups receiving cytoxin, saline and normal diet respectively. Weight of mice and tumors was determined and tumorigenicity assay calculated to determine the anticancer effects. Immunomodulatory potential was determined by immune organ indices, immune cell population and serum cytokine levels using immune organ weight and index, flow cytometry and cytokine/chemokine bead panel kit respectively. Licorice polysaccharides exhibited immunomodulatory activities in CT 26 tumor bearing BALB/c mice. The polysaccharides significantly suppressed tumor growth and increased immune organ index. Furthermore, the immunomodulatory effect was evident with activation of CD4 + and CD8 + immune cells population. The polysaccharides also affected the production of various cytokines, by increasing IL 2, IL 6, IL 7 levels and a decreasing TNFα levels. In summary, licorice polysaccharide especially of low molecular weight exhibit anticancer and immunomodulatory activities by suppressing tumor growth and improving general health of mice. They also augment the thymus/spleen index and population of T lymphocytes. Furthermore, the polysaccharides enhance the levels of serum antitumor cytokines, IL 2, IL 6 and IL 7 while decreasing pro-tumor cytokine TNFα.

Decomposition and transformation of cutin and cutan biopolymers in soils: effect on their sorptive capabilities

NASA Astrophysics Data System (ADS)

Shechter, M.; Chefetz, B.

2009-04-01

Plant cuticle materials, especially the highly aliphatic biopolymers cutin and cutan, have been reported as highly efficient natural sorbents. The objective of this study was to examine the effects of decomposition on their sorption behavior with naphthol and phenanthrene. The level of cutin and cutan was reduced by 15 and 27% respectively during the first 3 mo of incubation. From that point, the level of the cutan did not change, while the level of the cutin continued to decrease up to 32% after 20 mo. 13C NMR analysis suggested transformation of cutan mainly within its alkyl-C structure which are assigned as crystalline moieties. Cutin, however, did not exhibit significant structure changes with time. The level of humic-like substances increased due to cutin decomposition but was not influenced in the cutan system after 20 mo of incubation. This indicates that the cutin biopolymer has been decomposed and transformed into humic-like substances, whereas the cutan was less subject to transformation. Decomposition affected sorption properties in similar trends for both cutin and cutan. The Freundlich capacity coefficients (KFOC) of naphthol were much lower than phenanthrene and were less influenced by the decomposition, whereas with phenanthrene KFOC values increased significantly with time. Naphthol exhibited non-linear isotherms; and nonlinearity was decreased with incubation time. In contrast, phenanthrene isotherms were more linear and showed only moderate change with time. The decrease in the linearity of naphthol isotherms might relate to the transformation of the sorption sites due to structural changes in the biopolymers. However, with phenanthrene, these changes did not affect sorption linearity but increased sorption affinities mainly for cutan. This is probably due to decomposition of the rigid alkyl-C moieties in the cutan biopolymer. Our data suggest that both biopolymers were relatively stable in the soil for 20 mo. Cutan is less degradable than cutin and therefore is more likely to accumulate in soils and contribute to the refractory aliphatic components of soil organic matter.

Profiling Coping Strategies in Male and Female Rats: Potential neurobehavioral markers of increased resilience to depressive symptoms

PubMed Central

Kent, Molly; Bardi, Massimo; Hazelgrove, Ashley; Sewell, Kaitlyn; Kirk, Emily; Thompson, Brooke; Trexler, Kristen; Terhune-Cotter, Brennan; Lambert, Kelly

2018-01-01

Coping strategies have been associated with differential stress responsivity, perhaps providing a valuable neurobiological marker for susceptibility to the emergence of depressogenic symptoms or vulnerability to other anxiety-related disorders. Rats profiled with a flexible coping phenotype, for example, exhibit increased neurobiological markers of emotional regulation compared to active and passive copers (Bardi et al., 2012; Lambert et al., 2014). In the current study, responses of male and female rats to prediction errors in a spatial foraging task (dry land maze; DLM) were examined after animals were exposed to chronic unpredictable stress (CUS). Brains were processed following the DLM training/assessment for fos-activation patterns and several measures of neuroplasticity in relevant areas. Behavioral responses observed during both the CUS and DLM phases of testing suggested that males and females employ different means of gathering information such as increased ambulatory exploration in males and rear responses in females. Fecal samples collected during baseline and following CUS swim exposure revealed higher corticosterone (CORT) in active copers, whereas flexible copers had higher dehydroepiandrosterone (DHEA) and DHEA/CORT ratios, both indications of enhanced emotional regulation. Focusing on the neural analysis, flexible copers exhibited fewer fos-immunoreactive cells in the basolateral amygdala and a trend toward lower activation in the insula while encountering the prediction error associated with the DLM probe trial. Coping profiles also differentially influenced markers of neuroplasticity; specifically, flexible copers exhibited higher levels nestin-immunoreactivity (ir). Further, less hippocampal glucocorticoid receptor-ir was observed in the flexible copers than the active and passive copers. In sum, flexible coping rats exhibited evidence of emotional resilience as indicated by several neurobiological measures; however, despite increased rates of depression and related symptoms reported in human females, sex effects weren’t as pervasive as coping strategy profiles in the analysis of neurobiological markers employed in the current study. PMID:28755980

Original Research: Potential of urinary nephrin as a biomarker reflecting podocyte dysfunction in various kidney disease models.

PubMed

Wada, Yusuke; Abe, Masaki; Moritani, Hiroshi; Mitori, Hikaru; Kondo, Mitsuhiro; Tanaka-Amino, Keiko; Eguchi, Megumi; Imasato, Akira; Inoki, Yutaka; Kajiyama, Hiroshi; Mimura, Toshihide; Tomura, Yuichi

2016-10-01

Urinary nephrin is a potential non-invasive biomarker of disease. To date, however, most studies of urinary nephrin have been conducted in animal models of diabetic nephropathy, and correlations between urinary nephrin-to-creatinine ratio and other parameters have yet to be evaluated in animal models or patients of kidney disease with podocyte dysfunction. We hypothesized that urinary nephrin-to-creatinine ratio can be up-regulated and is negatively correlated with renal nephrin mRNA levels in animal models of kidney disease, and that increased urinary nephrin-to-creatinine ratio levels are attenuated following administration of glucocorticoids. In the present study, renal nephrin mRNA, urinary nephrin-to-creatinine ratio, urinary protein-to-creatinine ratio, and creatinine clearance ratio were measured in animal models of adriamycin nephropathy, puromycin aminonucleoside nephropathy, anti-glomerular basement membrane glomerulonephritis, and 5/6 nephrectomy. The effects of prednisolone on urinary nephrin-to-creatinine ratio and other parameters in puromycin aminonucleoside (single injection) nephropathy rats were also investigated. In all models tested, urinary nephrin-to-creatinine ratio and urinary protein-to-creatinine ratio increased, while renal nephrin mRNA and creatinine clearance ratio decreased. Urinary nephrin-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA in almost all models, as well as a significant positive correlation with urinary protein-to-creatinine ratio and a significant negative correlation with creatinine clearance ratio. Urinary protein-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA. Following the administration of prednisolone to puromycin aminonucleoside (single injection) nephropathy rats, urinary nephrin-to-creatinine ratio was significantly suppressed and exhibited a significant positive correlation with urinary protein-to-creatinine ratio. In addition, the decrease in number of glomerular Wilms tumor antigen-1-positive cells was attenuated, and urinary nephrin-to-creatinine ratio exhibited a significant negative correlation in these cells. In conclusion, these results suggest that urinary nephrin-to-creatinine ratio level is a useful and reliable biomarker for predicting the amelioration of podocyte dysfunction by candidate drugs in various kidney disease models with podocyte dysfunction. This suggestion will also be validated in a clinical setting in future studies. © 2016 by the Society for Experimental Biology and Medicine.

High accumulation of anthocyanins via the ectopic expression of AtDFR confers significant salt stress tolerance in Brassica napus L.

PubMed

Kim, Jihye; Lee, Won Je; Vu, Tien Thanh; Jeong, Chan Young; Hong, Suk-Whan; Lee, Hojoung

2017-08-01

The ectopic expression of AtDFR results in increased accumulation of anthocyanins leading to enhanced salinity and drought stress tolerance in B. napus plants. Flavonoids with antioxidant effects confer many additional benefits to plants. Evidence indicates that flavonoids, including anthocyanins, protect tissues against oxidative stress from various abiotic stressors. We determined whether increases in anthocyanins increased abiotic stress tolerance in Brassica napus, because the values of B. napus L. and its cultivation area are increasing worldwide. We overexpressed Arabidopsis dihydroflavonol-4-reductase (DFR) in B. napus. Increased DFR transcript levels for AtDFR-OX B. shoots correlated with higher anthocyanin accumulation. AtDFR-OX Brassica shoots exhibited lower reactive oxygen species (ROS) accumulation than wild-type (WT) shoots under high NaCl and mannitol concentrations. This was corroborated by 3,3-diaminobenzidine staining for ROS scavenging activity in 1,1-diphenyl-2-picryl-hydrazyl assays. Shoots of the AtDFR-OX B. napus lines grown in a high salt medium exhibited enhanced salt tolerance and higher chlorophyll content than similarly grown WT plants. Our observations suggested that the AtDFR gene can be effectively manipulated to modulate salinity and drought stress tolerance by directing to high accumulation of anthocyanins in oilseed plants.

Decreased resting-state brain activity complexity in schizophrenia characterized by both increased regularity and randomness.

PubMed

Yang, Albert C; Hong, Chen-Jee; Liou, Yin-Jay; Huang, Kai-Lin; Huang, Chu-Chung; Liu, Mu-En; Lo, Men-Tzung; Huang, Norden E; Peng, Chung-Kang; Lin, Ching-Po; Tsai, Shih-Jen

2015-06-01

Schizophrenia is characterized by heterogeneous pathophysiology. Using multiscale entropy (MSE) analysis, which enables capturing complex dynamics of time series, we characterized MSE patterns of blood-oxygen-level-dependent (BOLD) signals across different time scales and determined whether BOLD activity in patients with schizophrenia exhibits increased complexity (increased entropy in all time scales), decreased complexity toward regularity (decreased entropy in all time scales), or decreased complexity toward uncorrelated randomness (high entropy in short time scales followed by decayed entropy as the time scale increases). We recruited 105 patients with schizophrenia with an age of onset between 18 and 35 years and 210 age- and sex-matched healthy volunteers. Results showed that MSE of BOLD signals in patients with schizophrenia exhibited two routes of decreased BOLD complexity toward either regular or random patterns. Reduced BOLD complexity toward regular patterns was observed in the cerebellum and temporal, middle, and superior frontal regions, and reduced BOLD complexity toward randomness was observed extensively in the inferior frontal, occipital, and postcentral cortices as well as in the insula and middle cingulum. Furthermore, we determined that the two types of complexity change were associated differently with psychopathology; specifically, the regular type of BOLD complexity change was associated with positive symptoms of schizophrenia, whereas the randomness type of BOLD complexity was associated with negative symptoms of the illness. These results collectively suggested that resting-state dynamics in schizophrenia exhibit two routes of pathologic change toward regular or random patterns, which contribute to the differences in syndrome domains of psychosis in patients with schizophrenia. © 2015 Wiley Periodicals, Inc.

Increase in recombination rate in Arabidopsis thaliana plants sharing gaseous environment with X-ray and UVC-irradiated plants depends on production of radicals.

PubMed

Zemp, Franz J; Sidler, Corinne; Kovalchuk, Igor

2012-07-01

X-ray and UVC are the two physical agents that damage DNA directly, with both agents capable of inducing double-strand breaks. Some of our recent work has demonstrated that local exposure to UVC results in a systemic increase in recombination frequency, suggesting that information about exposure can be passed from damaged to non-damaged tissue. Indeed, we recently showed that plants sharing the same enclosed environment with UVC-irradiated plants exhibit similar increase in homologous recombination frequency as irradiated plants. Here, we further tested whether yet another DNA-damaging agent, X-ray, is capable of increasing recombination rate (RR) in neighboring plants grown in a Petri dish. To test this, we grew plants exposed to X-ray or UVC irradiation in an enclosed environment next to non-exposed plants. We found that both X-ray and UVC-irradiated plants and neighboring plants exhibited comparable increases in the levels of strand breaks and the RR. We further showed that pre-exposure of plants to radical scavenger DMSO substantially alleviates the radiation-induced increase in RR and prevents formation of bystander signal. Our results suggest that the increase in RR in bystander plants can also be triggered by X-ray and that radicals may play some role in initiation or maintenance of this signal.

Increase in recombination rate in Arabidopsis thaliana plants sharing gaseous environment with X-ray and UVC-irradiated plants depends on production of radicals

PubMed Central

Zemp, Franz J.; Sidler, Corinne; Kovalchuk, Igor

2012-01-01

X-ray and UVC are the two physical agents that damage DNA directly, with both agents capable of inducing double-strand breaks. Some of our recent work has demonstrated that local exposure to UVC results in a systemic increase in recombination frequency, suggesting that information about exposure can be passed from damaged to non-damaged tissue. Indeed, we recently showed that plants sharing the same enclosed environment with UVC-irradiated plants exhibit similar increase in homologous recombination frequency as irradiated plants. Here, we further tested whether yet another DNA-damaging agent, X-ray, is capable of increasing recombination rate (RR) in neighboring plants grown in a Petri dish. To test this, we grew plants exposed to X-ray or UVC irradiation in an enclosed environment next to non-exposed plants. We found that both X-ray and UVC-irradiated plants and neighboring plants exhibited comparable increases in the levels of strand breaks and the RR. We further showed that pre-exposure of plants to radical scavenger DMSO substantially alleviates the radiation-induced increase in RR and prevents formation of bystander signal. Our results suggest that the increase in RR in bystander plants can also be triggered by X-ray and that radicals may play some role in initiation or maintenance of this signal. PMID:22751301

Changes in VEGF and nitric oxide after deep dermal injury in the female, red Duroc pig-further similarities between female, Duroc scar and human hypertrophic scar.

PubMed

Zhu, Kathy Q; Engrav, Loren H; Armendariz, Rebecca; Muangman, Pornprom; Klein, Matthew B; Carrougher, Gretchen J; Deubner, Heike; Gibran, Nicole S

2005-02-01

Despite decades of research, our understanding of human hypertrophic scar is limited. A reliable animal model could significantly increase our understanding. We previously confirmed similarities between scarring in the female, red, Duroc pig and human hypertrophic scarring. The purpose of this study was to: (1) measure vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels in wounds on the female Duroc; and (2) to compare the NO levels to those reported for human hypertrophic scar. Shallow and deep wounds were created on four female Durocs. VEGF levels were measured using ELISA and NO levels with the Griess reagent. VEGF and NO levels were increased in deep wounds at 10 days when compared to shallow wounds (p < 0.05). At 15 weeks, VEGF and NO levels had returned to the level of shallow wounds. At 21 weeks, VEGF and NO levels had declined below baseline levels in deep wounds and the NO levels were significantly lower (p < 0.01). We found that VEGF and NO exhibit two distinctly different temporal patterns in shallow and deep wounds on the female Durocs. Furthermore, NO is decreased in female, Duroc scar as it is in human, hypertrophic scar further validating the usefulness of the model.

Selective Deletion of the Brain-Specific Isoform of Renin Causes Neurogenic Hypertension.

PubMed

Shinohara, Keisuke; Liu, Xuebo; Morgan, Donald A; Davis, Deborah R; Sequeira-Lopez, Maria Luisa S; Cassell, Martin D; Grobe, Justin L; Rahmouni, Kamal; Sigmund, Curt D

2016-12-01

The renin-angiotensin system (RAS) in the brain is a critical determinant of blood pressure, but the mechanisms regulating RAS activity in the brain remain unclear. Expression of brain renin (renin-b) occurs from an alternative promoter-first exon. The predicted translation product is a nonsecreted enzymatically active renin whose function is unknown. We generated a unique mouse model by selectively ablating the brain-specific isoform of renin (renin-b) while preserving the expression and function of the classical isoform expressed in the kidney (renin-a). Preservation of renal renin was confirmed by measurements of renin gene expression and immunohistochemistry. Surprisingly, renin-b-deficient mice exhibited hypertension, increased sympathetic nerve activity to the kidney and heart, and impaired baroreflex sensitivity. Whereas these mice displayed decreased circulating RAS activity, there was a paradoxical increase in brain RAS activity. Physiologically, renin-b-deficient mice exhibited an exaggerated depressor response to intracerebroventricular administration of losartan, captopril, or aliskiren. At the molecular level, renin-b-deficient mice exhibited increased expression of angiotensin-II type 1 receptor in the paraventricular nucleus, which correlated with an increased renal sympathetic nerve response to leptin, which was dependent on angiotensin-II type 1 receptor activity. Interestingly, despite an ablation of renin-b expression, expression of renin-a was significantly increased in rostral ventrolateral medulla. These data support a new paradigm for the genetic control of RAS activity in the brain by a coordinated regulation of the renin isoforms, with expression of renin-b tonically inhibiting expression of renin-a under baseline conditions. Impairment of this control mechanism causes neurogenic hypertension. © 2016 American Heart Association, Inc.

Synonymous codon choices in the extremely GC-poor genome of Plasmodium falciparum: compositional constraints and translational selection.

PubMed

Musto, H; Romero, H; Zavala, A; Jabbari, K; Bernardi, G

1999-07-01

We have analyzed the patterns of synonymous codon preferences of the nuclear genes of Plasmodium falciparum, a unicellular parasite characterized by an extremely GC-poor genome. When all genes are considered, codon usage is strongly biased toward A and T in third codon positions, as expected, but multivariate statistical analysis detects a major trend among genes. At one end genes display codon choices determined mainly by the extreme genome composition of this parasite, and very probably their expression level is low. At the other end a few genes exhibit an increased relative usage of a particular subset of codons, many of which are C-ending. Since the majority of these few genes is putatively highly expressed, we postulate that the increased C-ending codons are translationally optimal. In conclusion, while codon usage of the majority of P. falciparum genes is determined mainly by compositional constraints, a small number of genes exhibit translational selection.

p53 downregulates the Fanconi anaemia DNA repair pathway

PubMed Central

Jaber, Sara; Toufektchan, Eléonore; Lejour, Vincent; Bardot, Boris; Toledo, Franck

2016-01-01

Germline mutations affecting telomere maintenance or DNA repair may, respectively, cause dyskeratosis congenita or Fanconi anaemia, two clinically related bone marrow failure syndromes. Mice expressing p53Δ31, a mutant p53 lacking the C terminus, model dyskeratosis congenita. Accordingly, the increased p53 activity in p53Δ31/Δ31 fibroblasts correlated with a decreased expression of 4 genes implicated in telomere syndromes. Here we show that these cells exhibit decreased mRNA levels for additional genes contributing to telomere metabolism, but also, surprisingly, for 12 genes mutated in Fanconi anaemia. Furthermore, p53Δ31/Δ31 fibroblasts exhibit a reduced capacity to repair DNA interstrand crosslinks, a typical feature of Fanconi anaemia cells. Importantly, the p53-dependent downregulation of Fanc genes is largely conserved in human cells. Defective DNA repair is known to activate p53, but our results indicate that, conversely, an increased p53 activity may attenuate the Fanconi anaemia DNA repair pathway, defining a positive regulatory feedback loop. PMID:27033104

p53 downregulates the Fanconi anaemia DNA repair pathway.

PubMed

Jaber, Sara; Toufektchan, Eléonore; Lejour, Vincent; Bardot, Boris; Toledo, Franck

2016-04-01

Germline mutations affecting telomere maintenance or DNA repair may, respectively, cause dyskeratosis congenita or Fanconi anaemia, two clinically related bone marrow failure syndromes. Mice expressing p53(Δ31), a mutant p53 lacking the C terminus, model dyskeratosis congenita. Accordingly, the increased p53 activity in p53(Δ31/Δ31) fibroblasts correlated with a decreased expression of 4 genes implicated in telomere syndromes. Here we show that these cells exhibit decreased mRNA levels for additional genes contributing to telomere metabolism, but also, surprisingly, for 12 genes mutated in Fanconi anaemia. Furthermore, p53(Δ31/Δ31) fibroblasts exhibit a reduced capacity to repair DNA interstrand crosslinks, a typical feature of Fanconi anaemia cells. Importantly, the p53-dependent downregulation of Fanc genes is largely conserved in human cells. Defective DNA repair is known to activate p53, but our results indicate that, conversely, an increased p53 activity may attenuate the Fanconi anaemia DNA repair pathway, defining a positive regulatory feedback loop.

Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models.

PubMed

Jandial, Rahul; Neman, Josh; Lim, Punnajit P; Tamae, Daniel; Kowolik, Claudia M; Wuenschell, Gerald E; Shuck, Sarah C; Ciminera, Alexandra K; De Jesus, Luis R; Ouyang, Ching; Chen, Mike Y; Termini, John

2018-01-30

Cancers that exhibit the Warburg effect may elevate expression of glyoxylase 1 (GLO1) to detoxify the toxic glycolytic byproduct methylglyoxal (MG) and inhibit the formation of pro-apoptotic advanced glycation endproducts (AGEs). Inhibition of GLO1 in cancers that up-regulate glycolysis has been proposed as a therapeutic targeting strategy, but this approach has not been evaluated for glioblastoma multiforme (GBM), the most aggressive and difficult to treat malignancy of the brain. Elevated GLO1 expression in GBM was established in patient tumors and cell lines using bioinformatics tools and biochemical approaches. GLO1 inhibition in GBM cell lines and in an orthotopic xenograft GBM mouse model was examined using both small molecule and short hairpin RNA (shRNA) approaches. Inhibition of GLO1 with S -( p -bromobenzyl) glutathione dicyclopentyl ester ( p- BrBzGSH(Cp)₂) increased levels of the DNA-AGE N ²-1-(carboxyethyl)-2'-deoxyguanosine (CEdG), a surrogate biomarker for nuclear MG exposure; substantially elevated expression of the immunoglobulin-like receptor for AGEs (RAGE); and induced apoptosis in GBM cell lines. Targeting GLO1 with shRNA similarly increased CEdG levels and RAGE expression, and was cytotoxic to glioma cells. Mice bearing orthotopic GBM xenografts treated systemically with p -BrBzGSH(Cp)₂ exhibited tumor regression without significant off-target effects suggesting that GLO1 inhibition may have value in the therapeutic management of these drug-resistant tumors.

Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models

PubMed Central

Jandial, Rahul; Neman, Josh; Tamae, Daniel; Kowolik, Claudia M.; Wuenschell, Gerald E.; Ciminera, Alexandra K.; De Jesus, Luis R.; Ouyang, Ching; Chen, Mike Y.

2018-01-01

Cancers that exhibit the Warburg effect may elevate expression of glyoxylase 1 (GLO1) to detoxify the toxic glycolytic byproduct methylglyoxal (MG) and inhibit the formation of pro-apoptotic advanced glycation endproducts (AGEs). Inhibition of GLO1 in cancers that up-regulate glycolysis has been proposed as a therapeutic targeting strategy, but this approach has not been evaluated for glioblastoma multiforme (GBM), the most aggressive and difficult to treat malignancy of the brain. Elevated GLO1 expression in GBM was established in patient tumors and cell lines using bioinformatics tools and biochemical approaches. GLO1 inhibition in GBM cell lines and in an orthotopic xenograft GBM mouse model was examined using both small molecule and short hairpin RNA (shRNA) approaches. Inhibition of GLO1 with S-(p-bromobenzyl) glutathione dicyclopentyl ester (p-BrBzGSH(Cp)2) increased levels of the DNA-AGE N2-1-(carboxyethyl)-2′-deoxyguanosine (CEdG), a surrogate biomarker for nuclear MG exposure; substantially elevated expression of the immunoglobulin-like receptor for AGEs (RAGE); and induced apoptosis in GBM cell lines. Targeting GLO1 with shRNA similarly increased CEdG levels and RAGE expression, and was cytotoxic to glioma cells. Mice bearing orthotopic GBM xenografts treated systemically with p-BrBzGSH(Cp)2 exhibited tumor regression without significant off-target effects suggesting that GLO1 inhibition may have value in the therapeutic management of these drug-resistant tumors. PMID:29385725

Vibration stimulates vocal mucosa-like matrix expression by hydrogel-encapsulated fibroblasts.

PubMed

Kutty, Jaishankar K; Webb, Ken

2010-01-01

The composition and organization of the vocal fold extracellular matrix (ECM) provide the viscoelastic mechanical properties that are required to sustain high-frequency vibration during voice production. Although vocal injury and pathology are known to produce alterations in matrix physiology, the mechanisms responsible for the development and maintenance of vocal fold ECM are poorly understood. The objective of this study was to investigate the effect of physiologically relevant vibratory stimulation on ECM gene expression and synthesis by fibroblasts encapsulated within hyaluronic acid hydrogels that approximate the viscoelastic properties of vocal mucosa. Relative to static controls, samples exposed to vibration exhibited significant increases in mRNA expression levels of HA synthase 2, decorin, fibromodulin and MMP-1, while collagen and elastin expression were relatively unchanged. Expression levels exhibited a temporal response, with maximum increases observed after 3 and 5 days of vibratory stimulation and significant downregulation observed at 10 days. Quantitative assays of matrix accumulation confirmed significant increases in sulphated glycosaminoglycans and significant decreases in collagen after 5 and 10 days of vibratory culture, relative to static controls. Cellular remodelling and hydrogel viscosity were affected by vibratory stimulation and were influenced by varying the encapsulated cell density. These results indicate that vibration is a critical epigenetic factor regulating vocal fold ECM and suggest that rapid restoration of the phonatory microenvironment may provide a basis for reducing vocal scarring, restoring native matrix composition and improving vocal quality. 2009 John Wiley & Sons, Ltd.

The lemon balm extract ALS-L1023 inhibits obesity and nonalcoholic fatty liver disease in female ovariectomized mice.

PubMed

Kim, Jeongjun; Lee, Hyunghee; Lim, Jonghoon; Lee, Haerim; Yoon, Seolah; Shin, Soon Shik; Yoon, Michung

2017-08-01

Increasing evidence indicates that angiogenesis inhibitors regulate obesity. This study aimed to determine whether the lemon balm extract ALS-L1023 inhibits diet-induced obesity and nonalcoholic fatty liver disease (NAFLD) in female ovariectomized (OVX) mice. OVX mice received a low fat diet (LFD), a high fat diet (HFD) or HFD supplemented with ALS-L1023 (ALS-L1023) for 15 weeks. HFD mice exhibited increases in visceral adipose tissue (VAT) angiogenesis, body weight, VAT mass and VAT inflammation compared with LFD mice. In contrast, all of these effects were reduced in ALS-L1023 mice compared with HFD mice. Serum lipids and liver injury markers were improved in ALS-L1023 mice. Hepatic lipid accumulation, inflammatory cells and collagen levels were lower in ALS-L1023 mice than in HFD mice. ALS-L1023 mice exhibited a tendency to normalize hepatic expression of genes involved in lipid metabolism, inflammation and fibrosis to levels in LFD mice. ALS-L1023 also induced Akt phosphorylation and increased Nrf2 mRNA expression in livers of obese mice. Our results indicate that the angiogenesis inhibitor ALS-L1023 can regulate obesity, hepatic steatosis and fibro-inflammation, in part through improvement of VAT function, in obese OVX mice. These findings suggest that angiogenesis inhibitors may contribute to alleviation of NAFLD in post-menopausal women with obesity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of wound healing, anti-microbial and antioxidant potential of Pongamia pinnata in wistar rats.

PubMed

Dwivedi, Deepak; Dwivedi, Mona; Malviya, Sourabh; Singh, Vinod

2017-01-01

To investigate wound healing, antimicrobial and antioxidant activity of leaf extract of Pongamia Pinnata . Methanolic extracts of P. pinnata leaf were studied for wound healing efficiency, and was assessed by the rate of wound contraction, tensile strength, breaking strength, hydroxyproline and hexosamine content, along with its effect on pro-inflammatory and anti-inflammatory cytokines was assessed using excision and incision model of wound repair in Wistar rats. Antimicrobial activity against ten microorganisms was also assessed. In vivo antioxidant activity was performed to understand the mechanism of wound healing potency. The results indicated that P. pinnata extract has potent wound healing capacity as evident from the wound contraction and increased tensile strength. Hydroxyproline and hexosamine expression were also well correlated with the healing pattern observed. extract exhibited significant antimicrobial activity, Staphylococcus aureus, Staphylococcus pyogenes, Staphylococcus epidermidis, Escherichia coli, Micrococcus luteus, Enterobacter aerogenes, Salmonella typhi, Pseudomonas aeruginosa, Candida albicans, Aspergillus niger also indicate that P. pinnata posses potent antioxidant activity by inhibition lipid peroxidation, reduce glutathione, superoxide dismutase level and increases catalase activity. During early wound healing phase TNF-α and IL-6 level were found to be up-regulated by P. pinnata treatment. Increased wound contraction and tensile strength, augmented hydroxyproline and hexosamine content, antioxidative activity and moderate antimicrobial activity support the early wound healing exhibited by P. pinnata . Induction in cytokine production may be one of the mechanisms in accelerating the wound healing. Results suggest that P. pinnata may be useful in tropical management of wound healing.

Investigations on the structural, morphological, optical and electrical properties of undoped and nanosized Zn-doped CdS thin films prepared by a simplified spray technique

NASA Astrophysics Data System (ADS)

Anbarasi, M.; Nagarethinam, V. S.; Balu, A. R.

2014-12-01

CdS and Zn-doped CdS (CdS:Zn) thin films have been deposited on glass substrates by spray pyrolysis technique using a perfume atomizer. The influence of Zn incorporation on the structural, morphological, optical and electrical properties of the films has been studied. All the films exhibit hexagonal phase with (0 0 2) as preferential orientation. A shift of the (0 0 2) diffraction peak towards higher diffraction angle is observed with increased Zn doping. The optical studies confirmed that the transparency increases as Zn doping level increases and the film coated with 2 at.% Zn doping has the maximum transmittance of about 90 %. The sheet resistance (R sh ) decreases as the Zn-doping level increases and a minimum value of 1.113 × 103 Ω/sq is obtained for the film coated with 8 at.% Zn dopant. The CdS film coated with 8 at.% Zn dopant has the best structural, morphological and electrical properties.

Blunted Hypothalamo-pituitary Adrenal Axis Response to Predator Odor Predicts High Stress Reactivity

PubMed Central

Whitaker, Annie M.; Gilpin, Nicholas W.

2015-01-01

Individuals with trauma- and stress-related disorders exhibit increases in avoidance of trauma-related stimuli, heightened anxiety and altered neuroendocrine stress responses. Our laboratory uses a rodent model of stress that mimics the avoidance symptom cluster associated with stress-related disorders. Animals are classified as ‘Avoiders’ or Non-Avoiders' post-stress based on avoidance of predator-odor paired context. Utilizing this model, we are able to examine subpopulation differences in stress reactivity. Here, we used this predator odor model of stress to examine differences in anxiety-like behavior and hypothalamo-pituitary adrenal (HPA) axis function in animals that avoid a predator-paired context relative to those that do not. Rats were exposed to predator odor stress paired with a context and tested for avoidance (24 hours and 11 days), anxiety-like behavior (48 hours and 5 days) and HPA activation following stress. Control animals were exposed to room air. Predator odor stress produced avoidance in approximately 65% of the animals at 24 hours that persisted 11 days post-stress. Both Avoiders and Non-Avoiders exhibited heightened anxiety-like behavior at 48 hours and 5 days post-stress when compared to unstressed Controls. Non-Avoiders exhibited significant increases in circulating adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations immediately following predator odor stress compared to Controls and this response was significantly attenuated in Avoiders. There was an inverse correlation between circulating ACTH/CORT concentrations and avoidance, indicating that lower levels of ACTH/CORT predicted higher levels of avoidance. These results suggest that stress effects on HPA stress axis activation predict long-term avoidance of stress-paired stimuli, and builds on previous data showing the utility of this model for exploring the neurobiological mechanisms of trauma- and stress-related disorders. PMID:25824191

Reduced expression of the Ca(2+) transporter protein PMCA2 slows Ca(2+) dynamics in mouse cerebellar Purkinje neurones and alters the precision of motor coordination.

PubMed

Empson, Ruth M; Turner, Paul R; Nagaraja, Raghavendra Y; Beesley, Philip W; Knöpfel, Thomas

2010-03-15

Cerebellar Purkinje neurones (PNs) express high levels of the plasma membrane calcium ATPase, PMCA2, a transporter protein critical for the clearance of calcium from excitable cells. Genetic deletion of one PMCA2 encoding gene in heterozygous PMCA2 knock-out (PMCA2(+/-) mice enabled us to determine how PMCA2 influences PN calcium regulation without the complication of the severe morphological changes associated with complete PMCA2 knock-out (PMCA2(-/-) in these cells. The PMCA2(+/-) cerebellum expressed half the normal levels of PMCA2 and this nearly doubled the time taken for PN dendritic calcium transients to recover (mean fast and slow recovery times increased from 70 ms to 110 ms and from 600 ms to 1100 ms). The slower calcium recovery had distinct consequences for PMCA2(+/-) PN physiology. The PNs exhibited weaker climbing fibre responses, prolonged outward Ca(2+)-dependent K(+) current (mean fast and slow recovery times increased from 136 ms to 192 ms and from 595 ms to 1423 ms) and a slower mean frequency of action potential firing (7.4 Hz compared with 15.8 Hz). Our findings were consistent with prolonged calcium accumulation in the cytosol of PMCA2(+/-) Purkinje neurones. Although PMCA2(+/-) mice exhibited outwardly normal behaviour and little change in their gait pattern, when challenged to run on a narrow beam they exhibited clear deficits in hindlimb coordination. Training improved the motor performance of both PMCA2(+/-) and wild-type mice, although PMCA2(+/-) mice were always impaired. We conclude that reduced calcium clearance perturbs calcium dynamics in PN dendrites and that this is sufficient to disrupt the accuracy of cerebellar processing and motor coordination.

Evidence Suggesting that the Cardiomyocyte Circadian Clock Modulates Responsiveness of the Heart to Hypertrophic Stimuli in Mice

PubMed Central

Durgan, David J.; Tsai, Ju-Yun; Grenett, Maximiliano H.; Pat, Betty M.; Ratcliffe, William F.; Villegas-Montoya, Carolina; Garvey, Merissa E.; Nagendran, Jeevan; Dyck, Jason R.B.; Bray, Molly S.; Gamble, Karen L.; Gimble, Jeffrey M.; Young, Martin E.

2011-01-01

Circadian dyssynchrony of an organism (at the whole body level) with its environment, either through light/dark cycle or genetic manipulation of clock genes, augments various cardiometabolic diseases. The cardiomyocyte circadian clock has recently been shown to influence multiple myocardial processes, ranging from transcriptional regulation and energy metabolism, to contractile function. We therefore reasoned that chronic dyssychrony of the cardiomyocyte circadian clock with its environment would precipitate myocardial maladaptation to a circadian challenge (simulated shift work; SSW). To test this hypothesis, 2 and 20 month old wild-type and CCM (Cardiomyocyte Clock Mutant; a model with genetic temporal suspension of the cardiomyocyte circadian clock at the active-to-sleep phase transition) mice were subjected to chronic (16-wks) bi-weekly 12-hr phase shifts in the light/dark cycle (i.e., SSW). Assessment of adaptation/maladaptation at whole body homeostatic, gravimetric, humoral, histological, transcriptional, and cardiac contractile function levels revealed essentially identical responses between wild-type and CCM littermates. However, CCM hearts exhibit increased bi-ventricular weight, cardiomyocyte size, and molecular markers of hypertrophy (anf, mcip1) independent of aging and/or SSW. Similarly, a second genetic model of selective temporal suspension of the cardiomyocyte circadian clock (Cardiomyocyte-specific BMAL1 Knockout [CBK] mice) exhibits increased bi-ventricular weight and mcip1 expression. Wild-type mice exhibit 5-fold greater cardiac hypertrophic growth (and 6-fold greater anf mRNA induction) when challenged with the hypertrophic agonist isoproterenol at the active-to-sleep phase transition, relative to isoproterenol administration at the sleep-to-active phase transition. This diurnal variation was absent in CCM mice. Collectively, these data suggest that the cardiomyocyte circadian clock likely influences responsiveness of the heart to hypertrophic stimuli. PMID:21452915

Blunted hypothalamo-pituitary adrenal axis response to predator odor predicts high stress reactivity.

PubMed

Whitaker, Annie M; Gilpin, Nicholas W

2015-08-01

Individuals with trauma- and stress-related disorders exhibit increases in avoidance of trauma-related stimuli, heightened anxiety and altered neuroendocrine stress responses. Our laboratory uses a rodent model of stress that mimics the avoidance symptom cluster associated with stress-related disorders. Animals are classified as 'Avoiders' or 'Non-Avoiders' post-stress based on avoidance of predator-odor paired context. Utilizing this model, we are able to examine subpopulation differences in stress reactivity. Here, we used this predator odor model of stress to examine differences in anxiety-like behavior and hypothalamo-pituitary adrenal (HPA) axis function in animals that avoid a predator-paired context relative to those that do not. Rats were exposed to predator odor stress paired with a context and tested for avoidance (24h and 11days), anxiety-like behavior (48h and 5days) and HPA activation following stress. Control animals were exposed to room air. Predator odor stress produced avoidance in approximately 65% of the animals at 24h that persisted 11days post-stress. Both Avoiders and Non-Avoiders exhibited a heightened anxiety-like behavior at 48h and 5days post-stress when compared to unstressed Controls. Non-Avoiders exhibited significant increases in circulating adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations immediately following predator odor stress compared to Controls and this response was significantly attenuated in Avoiders. There was an inverse correlation between circulating ACTH/CORT concentrations and avoidance, indicating that lower levels of ACTH/CORT predicted higher levels of avoidance. These results suggest that stress effects on HPA stress axis activation predict long-term avoidance of stress-paired stimuli, and build on previous data showing the utility of this model for exploring the neurobiological mechanisms of trauma- and stress-related disorders. Copyright © 2015. Published by Elsevier Inc.

Attentive processes, blood lactate and CrossFit®.

PubMed

Perciavalle, Valentina; Marchetta, Nunzio Salvatore; Giustiniani, Salvatore; Borbone, Carlo; Perciavalle, Vincenzo; Petralia, Maria Cristina; Buscemi, Andrea; Coco, Marinella

2016-11-01

To analyze the influences of blood lactate produced during a specific session of CrossFit® on intensity and selectivity of attention. The first was evaluated by measuring the reaction time and the second by analyzing divided attention with a dual task. Fifteen male professionals of CrossFit® volunteered in the study. The training session was the Workout Of the Day (WOD) called 15.5, marked as: 27-21-15-9 repetitions (without recovery) in term of calories measured by using a rowing ergometer (e.g. 27 rowed calories) and in term of barbell full squats (raising a weight of 43 kg for men and of 29.5 kg for women). Blood lactate, blood glucose, reaction time, execution time of a dual task, number of errors and number of omissions were measured at rest, at the conclusion of the session and 15 minutes after its end. The levels of the blood lactate before the start of the session were considerably higher than those which normally occur at rest (<2 mmol /L), with a mean value of 4.5 mmol /l (± 1.99 SD). At the end of the workout session the blood lactate exhibited a significant increase, reaching a mean value of 13.8 mmol /l (± 1.18 SD) and then returning to values similar to the initial ones after 15 minutes. Blood glucose did not exhibit any statistically significant differences during the session. Reaction time, execution time, number of errors and number of omissions exhibited a significant worsening concomitantly with the increase in blood lactate. Athletes practicing CrossFit®, with high levels of blood lactate even at rest, should consequently have attentional performances somewhat limited.

The effect of drought on photosynthetic plasticity in Marrubium vulgare plants growing at low and high altitudes.

PubMed

Habibi, Ghader; Ajory, Neda

2015-11-01

Photosynthesis is a biological process most affected by water deficit. Plants have various photosynthetic mechanisms that are matched to specific climatic zones. We studied the photosynthetic plasticity of C3 plants at water deficit using ecotypes of Marrubium vulgare L. from high (2,200 m) and low (1,100 m) elevation sites in the Mishou-Dagh Mountains of Iran. Under experimental drought, high-altitude plants showed more tolerance to water stress based on most of the parameters studied as compared to the low-altitude plants. Increased tolerance in high-altitude plants was achieved by lower levels of daytime stomatal conductance (g s) and reduced damaging effect on maximal quantum yield of photosystem II (PSII) (F v /F m ) coupled with higher levels of carotenoids and non-photochemical quenching (NPQ). High-altitude plants exhibited higher water use efficiency (WUE) than that in low-altitude plants depending on the presence of thick leaves and the reduced daytime stomatal conductance. Additionally, we have studied the oscillation in H(+) content and diel gas exchange patterns to determine the occurrence of C3 or weak CAM (Crassulacean acid metabolism) in M. vulgare through 15 days drought stress. Under water-stressed conditions, low-altitude plants exhibited stomatal conductance and acid fluctuations characteristic of C3 photosynthesis, though high-altitude plants exhibited more pronounced increases in nocturnal acidity and phosphoenolpyruvate carboxylase (PEPC) activity, suggesting photosynthetic flexibility. These results indicated that the regulation of carotenoids, NPQ, stomatal conductance and diel patterns of CO2 exchange presented the larger differences among studied plants at different altitudes and seem to be the protecting mechanisms controlling the photosynthetic performance of M. vulgare plants under drought conditions.

Prolonged fasting increases the response of the renin-angiotensin-aldosterone system, but not vasopressin levels, in postweaned northern elephant seal pups

NASA Technical Reports Server (NTRS)

Ortiz, R. M.; Wade, C. E.; Ortiz, C. L.

2000-01-01

The 8- to 12-week postweaning fast exhibited by northern elephant seal pups (Mirounga angustirostris) occurs without any apparent deleterious effects on fluid and electrolyte homeostasis. However, during the fast the role of vasopressin (AVP) has been shown to be inconclusive and the involvement of the renin-angiotensin-aldosterone system (RAAS) has yet to be examined. To examine the effects of prolonged fasting on these osmoregulatory hormones, 15 postweaned pups were serially blood-sampled during the first 49 days of their fast. Fasting did not induce significant changes in ionic or osmotic concentrations, suggesting electrolyte homeostasis. Total proteins were reduced by day 21 of fasting and remained depressed, suggesting a lack of dehydration. Aldosterone and plasma renin activity exhibited a correlated, linear increase over the first 49 days of the fast, suggesting an active RAAS. Aldosterone exhibited a parabolic trend over the fast with a peak at day 35, suggesting a shift in the sensitivity of the kidney to aldosterone later in the fast. AVP was elevated at day 49 only, but concentrations were relatively low. RAAS was modified during the postweaning fast in pups and appears to play a significant role in the regulation of electrolyte and, most likely, water homeostasis during this period. Copyright 2000 Academic Press.

Of Meat and Men: Sex Differences in Implicit and Explicit Attitudes Toward Meat.

PubMed

Love, Hamish J; Sulikowski, Danielle

2018-01-01

Modern attitudes to meat in both men and women reflect a strong meat-masculinity association. Sex differences in the relationship between meat and masculinity have not been previously explored. In the current study we used two IATs (implicit association tasks), a visual search task, and a questionnaire to measure implicit and explicit attitudes toward meat in men and women. Men exhibited stronger implicit associations between meat and healthiness than did women, but both sexes associated meat more strongly with 'healthy' than 'unhealthy' concepts. As 'healthy' was operationalized in the current study using terms such as "virile" and "powerful," this suggests that a meat-strength/power association may mediate the meat-masculinity link readily observed across western cultures. The sex difference was not related to explicit attitudes to meat, nor was it attributable to a variety of other factors, such as a generally more positive disposition toward meat in men than women. Men also exhibited an attention bias toward meats, compared to non-meat foods, while females exhibited more caution when searching for non-meat foods, compared to meat. These biases were not related to implicit attitudes, but did tend to increase with increasing hunger levels. Potential ultimate explanations for these differences, including sex differences in bio-physiological needs and receptivity to social signals are discussed.

Network Disruption in the Preclinical Stages of Alzheimer's Disease: From Subjective Cognitive Decline to Mild Cognitive Impairment.

PubMed

López-Sanz, David; Garcés, Pilar; Álvarez, Blanca; Delgado-Losada, María Luisa; López-Higes, Ramón; Maestú, Fernando

2017-12-01

Subjective Cognitive Decline (SCD) is a largely unknown state thought to represent a preclinical stage of Alzheimer's Disease (AD) previous to mild cognitive impairment (MCI). However, the course of network disruption in these stages is scarcely characterized. We employed resting state magnetoencephalography in the source space to calculate network smallworldness, clustering, modularity and transitivity. Nodal measures (clustering and node degree) as well as modular partitions were compared between groups. The MCI group exhibited decreased smallworldness, clustering and transitivity and increased modularity in theta and beta bands. SCD showed similar but smaller changes in clustering and transitivity, while exhibiting alterations in the alpha band in opposite direction to those showed by MCI for modularity and transitivity. At the node level, MCI disrupted both clustering and nodal degree while SCD showed minor changes in the latter. Additionally, we observed an increase in modular partition variability in both SCD and MCI in theta and beta bands. SCD elders exhibit a significant network disruption, showing intermediate values between HC and MCI groups in multiple parameters. These results highlight the relevance of cognitive concerns in the clinical setting and suggest that network disorganization in AD could start in the preclinical stages before the onset of cognitive symptoms.

Maternal allergy increases susceptibility to offspring allergy in association with TH2-biased epigenetic alterations in a mouse model of peanut allergy.

PubMed

Song, Ying; Liu, Changda; Hui, Yiqun; Srivastava, Kamal; Zhou, Zhenwen; Chen, Jia; Miller, Rachel L; Finkelman, Fred D; Li, Xiu-Min

2014-12-01

Although maternal atopy is a risk factor for the development of peanut allergy, this phenomenon has not been well characterized experimentally, and the mechanisms underlying offspring risk are unclear. We sought to determine whether offspring of mothers with peanut allergy (O-PAM mice) are more susceptible to peanut allergy than offspring of naive mothers (O-NM mice) in a murine model and, if so, whether the susceptibility is linked to TH2-biased epigenetic alterations. Five-week-old O-PAM and O-NM mice were intragastrically sensitized to and challenged with peanut. Serum peanut-specific IgE levels, plasma histamine levels, anaphylactic reactions, and splenocyte and MLN cell cytokine production were measured. DNA methylation levels of the Il4 gene promoter from splenocytes and MLN cells from sensitized offspring and splenocytes from unsensitized neonatal offspring were determined by means of pyrosequencing. O-PAM mice exhibited 3-fold higher peanut-specific IgE levels after peanut sensitization, as well as 5-fold higher histamine levels and significantly higher anaphylactic symptom scores after challenge than O-NM mice (P < .05-.01). Cultured splenocytes and MLNs from O-PAM mice produced significantly more TH2 cytokines than cells from O-NM mice (P < .05-.01). Cells from O-PAM mice exhibited significantly reduced DNA methylation at CpG sites of the Il4 gene promoter than cells from O-NM mice. DNA methylation levels were inversely correlated with IL-4 and IgE production. O-PAM neonatal splenocyte hypomethylation of the Il4 gene promoter was also present. This study is the first to demonstrate that increased susceptibility to peanut allergy in O-PAM mice is associated with epigenetic alteration of the Il4 gene promoter. This finding might provide insight into preventing the development of early-life allergy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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.

Learning Achieved in Structured Online Debates: Levels of Learning and Types of Postings

ERIC Educational Resources Information Center

Jin, Li; Jeong, Allan

2013-01-01

The purpose of this study was to examine the learning process exhibited in restrained online debates in terms of to what extent each of Bloom's six levels of cognitive learning were exhibited among four types of message (argument, critique, evidence, and explanation). Thirty-three graduate students enrolled in an online entry-level course in…

Evaluation of the role of oxidative stress, inflammation and apoptosis in the pulmonary and the hepatic toxicity induced by cerium oxide nanoparticles following intratracheal instillation in male Sprague-Dawley rats

NASA Astrophysics Data System (ADS)

Nalabotu, Siva Krishna

The field of nanotechnology is rapidly progressing with potential applications in the automobile, healthcare, electronics, cosmetics, textiles, information technology, and environmental sectors. Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. With increased applications of nanotechnology, there are increased chances of exposure to manufactured nanomaterials. Recent reports on the toxicity of engineered nanomaterials have given scientific and regulatory agencies concerns over the safety of nanomaterials. Specifically, the Organization for Economic Co-operation and Development (OECD) has identified fourteen high priority nanomaterials for study. Cerium oxide (CeO2) nanoparticles are one among the high priority group. Recent data suggest that CeO2 nanoparticles may be toxic to lung cell lines in vitro and lung tissues in vivo. Other work has proposed that oxidative stress may play an important role in the toxicity; however, the exact mechanism of the toxicity, has to our knowledge, not been investigated. Similarly, it is not clear whether CeO2 nanoparticles exhibit systemic toxicity. Here, we investigate whether pulmonary exposure to CeO2 nanoparticles is associated with oxidative stress, inflammation and apoptosis in the lungs and liver of adult male Sprague-Dawley rats. Our data suggest that the intratracheal instillation of CeO2 nanoparticles can cause an increased lung weight to body weight ratio. Changes in lung weights were associated with the accumulation of cerium in the lungs, elevations in serum inflammatory markers, an increased Bax to Bcl-2 ratio, elevated caspase-3 protein levels, increased phosphorylation of p38-MAPK and diminished phosphorylation of ERK1/2-MAPK. Our findings from the study evaluating the possible translocation of CeO2 nanoparticles from the lungs to the liver suggest that CeO 2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio and decreased serum triglyceride levels. Consistent with these data, rats exposed to CeO2 nanoparticles also exhibited reductions in liver weight and dose dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation and the accumulation of granular material in the hepatocytes. In a follow-up study, we next examined if CeO2 deposition in the liver is characterized by increased oxidative stress and apoptosis. Our data demonstrate that increased cerium in the liver is associated with increased oxidative stress and apoptosis as assessed from hydroethidium staining, the analysis of lipid peroxidation, and TUNEL staining. In addition, increased cerium concentration in the liver was associated with an increased Bax to Bcl-2 ratio, elevated caspase-9 and elevated caspase-3 protein levels. Taken together, these data suggest that exposure to CeO 2 nanoparticles is associated with increased oxidative stress and cellular apoptosis in the lungs. It is also evident that CeO2 nanoparticles can translocate to liver and induce hepatic damage. The hepatic damage induced by CeO2 nanoparticles is associated with increased oxidative stress and apoptosis in the liver.

Exploring the impact of music concerts in promoting well-being in dementia care.

PubMed

Shibazaki, Kagari; Marshall, Nigel A

2017-05-01

This study explores the specific effects of live music concerts on the clients with dementia, their families and nursing staff/caregivers. Researchers attended 22 concerts in care facilities in England and Japan. Interviews were carried out with clients with dementia, nursing staff and family members. Observations were also carried out before, during and after the concerts. All observations were recorded in field notes. The effect of the concerts in both countries was seen to be beneficial to all clients and nursing staff, whether or not they attended the concert. Interviews with clients with mild to mid-stage dementia noted increased levels of cooperation, interaction and conversation. Those with more advanced forms of dementia exhibited decreased levels of agitation and anti-social behaviour. Staff members reported increased levels of care, cooperation and opportunities for assessment. Family members noted an increase in the levels of well-being in their partner/parent as well as in themselves. The study also suggested that the knowledge of musical components, an awareness of the rules of music and specific musical preferences appear to remain well beyond the time when other cognitive skills and abilities have disappeared. This initial study provided some further indication in terms of the uses of music as a non-pharmacological intervention for those living with all stages of dementia. These included opportunities for assessment of physical abilities as well as facilitating an increasing level of care.

Micro-RNA-126 Reduces the Blood Thrombogenicity in Diabetes Mellitus via Targeting of Tissue Factor.

PubMed

Witkowski, Marco; Weithauser, Alice; Tabaraie, Termeh; Steffens, Daniel; Kränkel, Nicolle; Witkowski, Mario; Stratmann, Bernd; Tschoepe, Diethelm; Landmesser, Ulf; Rauch-Kroehnert, Ursula

2016-06-01

Diabetes mellitus involves vascular inflammatory processes and is a main contributor to cardiovascular mortality. Notably, heightened levels of circulating tissue factor (TF) account for the increased thrombogenicity and put those patients at risk for thromboembolic events. Here, we sought to investigate the role of micro-RNA (miR)-driven TF expression and thrombogenicity in diabetes mellitus. Plasma samples of patients with diabetes mellitus were analyzed for TF protein and activity as well as miR-126 expression before and after optimization of the antidiabetic treatment. We found low miR-126 levels to be associated with markedly increased TF protein and TF-mediated thrombogenicity. Reduced miR-126 expression was accompanied by increased vascular inflammation as evident from the levels of vascular adhesion molecule-1 and fibrinogen, as well as leukocyte counts. With optimization of the antidiabetic treatment miR-126 levels increased and thrombogenicity was reduced. Using a luciferase reporter system, we demonstrated miR-126 to directly bind to the F3-3'-untranslated region, thereby reducing TF expression both on mRNA and on protein levels in human microvascular endothelial cells as well as TF mRNA and activity in monocytes. Circulating miR-126 exhibits antithrombotic properties via regulating post-transcriptional TF expression, thereby impacting the hemostatic balance of the vasculature in diabetes mellitus. © 2016 The Authors.

Streptococcus pneumoniae Phosphotyrosine Phosphatase CpsB and Alterations in Capsule Production Resulting from Changes in Oxygen Availability

PubMed Central

Geno, K. Aaron; Hauser, Jocelyn R.; Gupta, Kanupriya

2014-01-01

Streptococcus pneumoniae produces a protective capsular polysaccharide whose production must be modulated for bacterial survival within various host niches. Capsule production is affected in part by a phosphoregulatory system comprised of CpsB, CpsC, and CpsD. Here, we found that growth of serotype 2 strain D39 under conditions of increased oxygen availability resulted in decreased capsule levels concurrent with an ∼5-fold increase in Cps2B-mediated phosphatase activity. The change in Cps2B phosphatase activity did not result from alterations in the levels of either the cps2B transcript or the Cps2B protein. Recombinant Cps2B expressed in Escherichia coli similarly exhibited increased phosphatase activity under conditions of high-oxygen growth. S. pneumoniae D39 derivatives with defined deletion or point mutations in cps2B demonstrated reduced phosphatase activity with corresponding increases in levels of Cps2D tyrosine phosphorylation. There was, however, no correlation between these phenotypes and the level of capsule production. During growth under reduced-oxygen conditions, the Cps2B protein was essential for parental levels of capsule, but phosphatase activity alone could be eliminated without an effect on capsule. Under increased-oxygen conditions, deletion of cps2B did not affect capsule levels. These results indicate that neither Cps2B phosphatase activity nor Cps2D phosphorylation levels per se are determinants of capsule levels, whereas the Cps2B protein is important for capsule production during growth under conditions of reduced but not enhanced oxygen availability. Roles for factors outside the capsule locus, possible interactions between capsule regulatory proteins, and links to other cellular processes are also suggested by the results described in this study. PMID:24659769

Mechanical properties of a medical β-type titanium alloy with specific microstructural evolution through high-pressure torsion.

PubMed

Yilmazer, H; Niinomi, M; Nakai, M; Cho, K; Hieda, J; Todaka, Y; Miyazaki, T

2013-07-01

The effect of high-pressure torsion (HPT) processing on the microstructure and mechanical biocompatibility includes Young's modulus, tensile strength, ductility, fatigue life, fretting fatigue, wear properties and other functionalities such as super elasticity and shape memory effect, etc. at levels suitable for structural biomaterials used in implants that replace hard tissue in the broad sense (Sumitomo et al., 2008 [4]). In particular, in this study, the mechanical biocompatibility implies a combination of great hardness and high strength with an adequate ductility while keeping low Young's modulus of a novel Ti-29Nb-13Ta-4.6Zr (TNTZ) for biomedical applications at rotation numbers (N) ranging from 1 to 60 under a pressure of 1.25 GPa at room temperature was systematically investigated in order to increase its mechanical strength with maintaining low Young's modulus and an adequate ductility. TNTZ subjected to HPT processing (TNTZHPT) at low N exhibits a heterogeneous microstructure in micro-scale and nano-scale consisting of a matrix and a non-etched band, which has nanosized equiaxed and elongated single β grains, along its cross section. The grains exhibit high dislocation densities, consequently non-equilibrium grain boundaries, and non-uniform subgrains distorted by severe deformation. At high N which is N>20, TNTZHPT has a more homogeneous microstructure in nano-scale with increasing equivalent strain, εeq. Therefore, TNTZHPT at high N exhibits a more homogenous hardness distribution. The tensile strength and 0.2% proof stress of TNTZHPT increase significantly with N over the range of 0≤N≤5, and then become saturated at around 1100 MPa and 800 MPa at N≥10. However, the ductility of TNTZHPT shows a reverse trend and a low-level elongation, at around 7%. And, Young's modulus of TNTZHPT decreases slightly to 60 GPa with increasing N and then becomes saturated at N≥10. These obtained results confirm that the mechanical strength of TNTZ can be improved while maintaining a low Young's modulus in single β grain structures through severe plastic deformation. Copyright © 2013 Elsevier B.V. All rights reserved.