Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus.

PubMed

Chen, Qian; Xiao, De-Sheng

2014-01-30

Adult hippocampus is highly vulnerable to iron-induced oxidative stress. Aerobic exercise has been proposed to reduce oxidative stress but the findings in the hippocampus are conflicting. This study aimed to observe the changes of redox-active iron and concomitant regulation of cellular iron homeostasis in the hippocampus by aerobic exercise, and possible regulatory effect of nitric oxide (NO). A randomized controlled study was designed in the rats with swimming exercise treatment (for 3 months) and/or an unselective inhibitor of NO synthase (NOS) (L-NAME) treatment. The results from the bleomycin-detectable iron assay showed additional redox-active iron in the hippocampus by exercise treatment. The results from nonheme iron content assay, combined with the redox-active iron content, showed increased storage iron content by exercise treatment. NOx (nitrate plus nitrite) assay showed increased NOx content by exercise treatment. The results from the Western blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS. In these effects of exercise treatment, the increased redox-active iron content, storage iron content, IRP1 and IRP2 expressions were completely reversed by L-NAME treatment, and decreased ferroportin expression was in part reversed by L-NAME. L-NAME treatment completely inhibited increased NOx and both eNOS and nNOS expression in the hippocampus. Our findings suggest that aerobic exercise could increase the redox-active iron in the hippocampus, indicating an increase in the capacity to generate hydroxyl radicals through the Fenton reactions, and aerobic exercise-induced iron accumulation in the hippocampus might mainly result from the role of the endogenous NO. Copyright © 2013 Elsevier Inc. All rights reserved.

Antimicrobial and Efflux Inhibitor Activity of Usnic Acid Against Mycobacterium abscessus.

PubMed

Ramis, Ivy B; Vianna, Júlia S; Reis, Ana Júlia; von Groll, Andrea; Ramos, Daniela F; Viveiros, Miguel; da Silva, Pedro E Almeida

2018-06-18

New drugs are needed to treat infections with antimicrobial-resistant Mycobacterium abscessus ; therefore, we evaluated usnic acid as an antimicrobial agent and efflux inhibitor (EI) against M. abscessus . Usnic acid showed antimicrobial activity, and synergistically, the EI verapamil increased this activity. In addition, when we evaluated the interaction of antimicrobials with usnic acid, the increase of their activity was observed. Finally, usnic acid showed an efflux inhibitory effect between the classical EIs verapamil and carbonyl cyanide m-chlorophenylhydrazine. In conclusion, usnic acid showed both antimicrobial and EI activity, indicating that this natural compound may be a promising scaffold for new drugs against this difficult-to-treat microorganism. Georg Thieme Verlag KG Stuttgart · New York.

Carboxylate metabolism in sugar beet plants grown with excess Zn.

PubMed

Sagardoy, R; Morales, F; Rellán-Álvarez, R; Abadía, A; Abadía, J; López-Millán, A F

2011-05-01

The effects of Zn excess on carboxylate metabolism were investigated in sugar beet (Beta vulgaris L.) plants grown hydroponically in a growth chamber. Root extracts of plants grown with 50 or 100μM Zn in the nutrient solution showed increases in several enzymatic activities related to organic acid metabolism, including citrate synthase and phosphoenolpyruvate carboxylase, when compared to activities in control root extracts. Root citric and malic acid concentrations increased in plants grown with 100μM Zn, but not in plants grown with 50μM Zn. In the xylem sap, plants grown with 50 and 100μM Zn showed increases in the concentrations of citrate and malate compared to the controls. Leaves of plants grown with 50 or 100μM Zn showed increases in the concentrations of citric and malic acid and in the activities of citrate synthase and fumarase. Leaf isocitrate dehydrogenase increased only in plants grown with 50μM Zn when compared to the controls. In plants grown with 300μM Zn, the only enzyme showing activity increases in root extracts was citrate synthase, whereas the activities of other enzymes decreased compared to the controls, and root citrate concentrations increased. In the 300μM Zn-grown plants, the xylem concentrations of citric and malic acids were higher than those of controls, whereas in leaf extracts the activity of fumarase increased markedly, and the leaf citric acid concentration was higher than in the controls. Based on our data, a metabolic model of the carboxylate metabolism in sugar beet plants grown under Zn excess is proposed. Copyright © 2010 Elsevier GmbH. All rights reserved.

Oligo-carrageenan kappa-induced reducing redox status and increase in TRR/TRX activities promote activation and reprogramming of terpenoid metabolism in Eucalyptus trees.

PubMed

González, Alberto; Gutiérrez-Cutiño, Marlen; Moenne, Alejandra

2014-06-05

In order to analyze whether the reducing redox status and activation of thioredoxin reductase (TRR)/thioredoxin(TRX) system induced by oligo-carrageenan (OC) kappa in Eucalyptus globulus activate secondary metabolism increasing terpenoid synthesis, trees were sprayed on the leaves with water, with OC kappa, or with inhibitors of NAD(P)H, ascorbate (ASC) and (GSH) synthesis and TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO) and auranofine, respectively, and with OC kappa and cultivated for four months. The main terpenoids in control Eucalyptus trees were eucalyptol (76%), α-pinene (7.4%), aromadendrene (3.6%), silvestrene (2.8%), sabinene (2%) and α-terpineol (0.9%). Treated trees showed a 22% increase in total essential oils as well as a decrease in eucalyptol (65%) and sabinene (0.8%) and an increase in aromadendrene (5%), silvestrene (7.8%) and other ten terpenoids. In addition, treated Eucalyptus showed seven de novo synthesized terpenoids corresponding to carene, α-terpinene, α-fenchene, γ-maaliene, spathulenol and α-camphenolic aldehyde. Most increased and de novo synthesized terpenoids have potential insecticidal and antimicrobial activities. Trees treated with CHS-828, lycorine, BSO and auranofine and with OC kappa showed an inhibition of increased and de novo synthesized terpenoids. Thus, OC kappa-induced reducing redox status and activation of TRR/TRX system enhance secondary metabolism increasing the synthesis of terpenoids and reprogramming of terpenoid metabolism in Eucalyptus trees.

Professional training in creative writing is associated with enhanced fronto-striatal activity in a literary text continuation task.

PubMed

Erhard, K; Kessler, F; Neumann, N; Ortheil, H-J; Lotze, M

2014-10-15

The aim of the present study was to explore brain activities associated with creativity and expertise in literary writing. Using functional magnetic resonance imaging (fMRI), we applied a real-life neuroscientific setting that consisted of different writing phases (brainstorming and creative writing; reading and copying as control conditions) to well-selected expert writers and to an inexperienced control group. During creative writing, experts showed cerebral activation in a predominantly left-hemispheric fronto-parieto-temporal network. When compared to inexperienced writers, experts showed increased left caudate nucleus and left dorsolateral and superior medial prefrontal cortex activation. In contrast, less experienced participants recruited increasingly bilateral visual areas. During creative writing activation in the right cuneus showed positive association with the creativity index in expert writers. High experience in creative writing seems to be associated with a network of prefrontal (mPFC and DLPFC) and basal ganglia (caudate) activation. In addition, our findings suggest that high verbal creativity specific to literary writing increases activation in the right cuneus associated with increased resources obtained for reading processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Injury-induced rapid activation of MAPK signaling in dechorionated eggs and larvae of the silkworm Bombyx mori.

PubMed

Gu, Shi-Hong; Chen, Chien-Hung

2017-04-01

Previous study showed that diapause in Bombyx mori eggs can be terminated by dechorionation and that activation in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) in dechorionated cultured eggs is involved in diapause termination. In the present study, the possible mechanism underlying activation of ERK upon dechorionation was further investigated. Results showed that mechanical injury of diapause eggs without medium incubation also resulted in rapid increase in the phospho-ERK levels and that injury increased the phospho-ERK levels at different stages of both diapause eggs and eggs in which diapause initiation was prevented by HCl. Effects of anaerobiosis on dechorionation-stimulated phospho-ERK levels showed that the mechanical injury itself but not the dramatic increase in oxygen uptake upon injury is involved in a rapid activation of ERK. Chemical anaerobiosis on dechorionation-stimulated phospho-ERK levels and the in vivo effect of anaerobiosis showed that the supply of oxygen also plays a role in ERK signaling. In addition, injury induced the phosphorylation of c-jun N-terminal kinases (JNKs) and p38 kinase, components of two parallel MAPK pathways. A kinase assay showed a dramatic increase in JNK kinase activity in egg lysates upon injury. When newly hatched first instar larvae were injured, an increase in the phospho-ERK levels similar to that in dechorionated eggs was observed. From the results, we hypothesize that the injury-induced rapid activation of MAPK signaling, which serves as a natural signal for embryonic development, is related to diapause termination in dechorionated eggs. © 2015 Institute of Zoology, Chinese Academy of Sciences.

Parks promoting physical activity: synthesis of findings from interventions in seven national parks.

PubMed

Hoehner, Christine M; Brownson, Ross C; Allen, Diana; Gramann, James; Behrens, Timothy K; Floyd, Myron F; Leahy, Jessica; Liddle, Joseph B; Smaldone, David; Spain, Diara D; Tardona, Daniel R; Ruthmann, Nicholas P; Seiler, Rachel L; Yount, Byron W

2010-03-01

We synthesized the results of 7 National Park Service pilot interventions designed to increase awareness of the health benefits from participation in recreation at national parks and to increase physical activity by park visitors. A content analysis was conducted of the final evaluation reports of the 7 participating parks. Pooled data were also analyzed from a standardized trail-intercept survey administered in 3 parks. The theme of new and diverse partnerships was the most common benefit reported across the 7 sites. The 2 parks that focused on youth showed evidence of an increase in awareness of the benefits of physical activity. Many of the other sites found high levels of awareness at baseline (approaching 90%), suggesting little room for improvement. Five of the 7 projects showed evidence of an increase in physical activity that was associated with the intervention activities. Multivariate analyses suggested that the media exposure contributed to a small but significant increase in awareness of the importance of physical activity (6%) and number of active visits (7%). Enhancements and replication of these programs represents a promising opportunity for improving partnerships between public health and recreation to increase physical activity.

Antioxidants from steamed used tea leaves and their reaction behavior.

PubMed

Nomizu, Kayoko; Hashida, Koh; Makino, Rei; Ohara, Seiji

2008-07-01

The most efficient steaming conditions below 200 degrees C for extracting antioxidants from used tea leaves and their reaction behavior during the steaming treatment were investigated. The antioxidative activity of the steamed extracts increased with increasing steaming temperature, and the yield of the ethyl acetate extract fraction from each steamed extract showing the greatest antioxidative activity also increased. Caffeine, (-)-catechin, (-)-epicatechin, (-)-gallocatechin, (-)-epigallocatechin, (-)-catechin gallate, (-)-epicatechin gallate, (-)-gallocatechin gallate, (-)-epigallocatechin gallate and gallic acid were identified from the ethyl acetate extract fraction. Quantitative analyses demonstrated that the catechins with a 2,3-cis configuration decreased with increasing steaming temperature, whereas the corresponding epimers at the C-2 position increased. Each pair of epimers showed similar antioxidative activity to each other, indicating that the epimerization reaction did not contribute to the improved antioxidative activity. It is concluded from these results that the improvement in antioxidative activity at higher steaming temperatures was due to the increased yield of catechins and other antioxidants.

Antioxidant and analgesic activities of turpentine of Pinus nigra Arn. subsp. pallsiana (Lamb.) Holmboe.

PubMed

Gülçin, Ilhami; Büyükokuroglu, M Emin; Oktay, Münir; Küfrevioglu, O Irfan

2003-05-01

The aim of this study is to examine possible antioxidant and analgesic activities of turpentine exudes from Pinus nigra Arn. subsp. pallsiana (Lamb.) Holmboe (TPN). Total antioxidant activity, reducing power, superoxide anion radical scavenging, free radical scavenging, metal chelating, and hydrogen peroxide scavenging activities were studied. The total antioxidant activity increased with the increasing amount of extracts (100, 300, and 500 microg) added to linoleic acid emulsion. All of the doses of TPN showed higher antioxidant activity than alpha-tocopherol. The samples showed 49, 70, and 91% inhibition on peroxidation of linoleic acid emulsion, respectively. On the other hand, the 300 microg of alpha-tocopherol showed 40% inhibition on peroxidation of linoleic acid emulsion. There is correlation between antioxidant activity and the reducing power, superoxide anion radical scavenging, free radical scavenging, metal chelating, and hydrogen peroxide scavenging activities. Like antioxidant activity, the reducing power, superoxide anion radical scavenging, free radical scavenging, metal chelating, and hydrogen peroxide scavenging activities of TPN depending on concentration and increasing with increased concentration of TPN. These properties may be the major reasons for the inhibition of lipid peroxidation. The results obtained in the present study indicate that the TPN has a potential source of natural antioxidant. In addition, analgesic effect of TPN was investigated in present study and TPN had strong analgesic effect. The analgesic effect of TPN compared with metamizol as a standard analgesic compound.

Levels-of-processing effects in first-degree relatives of individuals with schizophrenia.

PubMed

Bonner-Jackson, Aaron; Csernansky, John G; Barch, Deanna M

2007-05-15

First-degree relatives of individuals with schizophrenia show cognitive impairments that are similar to but less severe than their ill relatives. We have shown that memory impairments can be improved and prefrontal cortical (PFC) activity increased in individuals with schizophrenia by providing beneficial encoding strategies. The current study used a similar paradigm to determine whether siblings of individuals with schizophrenia (SIBs) also show increases in brain activity when presented with beneficial encoding strategies. Twenty-one SIBs and 38 siblings of healthy comparison subjects underwent functional magnetic resonance imaging scans while engaged in deep (abstract/concrete judgments) and shallow (orthographic judgments) encoding. Subjects were then given a recognition memory test. The groups did not differ on encoding or recognition accuracy, and the SIBs benefited from deep encoding to a similar degree as control subjects. The SIBs showed deep encoding-related activity in a number of PFC regions typically activated during semantic processing. However, SIBs showed more activity than control subjects in three subregions of PFC (left BA 44 & BA 47 bilaterally). Siblings of individuals with schizophrenia benefit from supportive verbal encoding conditions. Like individuals with schizophrenia, SIBs also show increased task-related activity in a larger number of PFC subregions than control subjects during deep verbal encoding.

Mitochondrial protection by low doses of insulin-like growth factor- I in experimental cirrhosis.

PubMed

Pérez, Raquel; García-Fernández, María; Díaz-Sánchez, Matías; Puche, Juan E; Delgado, Gloria; Conchillo, Marian; Muntané, Jordi; Castilla-Cortázar, Inma

2008-05-07

To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-I (IGF- I) therapy (4 wk) is able to induce beneficial effects on damaged mitochondria leading to cellular protection. Wistar rats were divided into three groups: Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF- I treatment (2 microg/100 g bw/d). Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three experimental groups. Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential (in status 4 and 3); an increase of intramitochondrial reactive oxigen species (ROS) generation and a significant reduction of ATPase activity. IGF- I therapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes I and III was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF- I therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. These results show that IGF- I exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.

Mitochondrial protection by low doses of insulin-like growth factor-Iin experimental cirrhosis

PubMed Central

Pérez, Raquel; García-Fernández, María; Díaz-Sánchez, Matías; Puche, Juan E; Delgado, Gloria; Conchillo, Marian; Muntané, Jordi; Castilla-Cortázar, Inma

2008-01-01

AIM: To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-I(IGF-I) therapy (4 wk) is able to induce beneficial effects on damaged mitochondria leading to cellular protection. METHODS: Wistar rats were divided into three groups: Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF-Itreatment (2 μg/100 g bw/d). Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three experimental groups. RESULTS: Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential (in status 4 and 3); an increase of intramitochondrial reactive oxigen species (ROS) generation and a significant reduction of ATPase activity. IGF-Itherapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes Iand III was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF-Itherapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. CONCLUSION: These results show that IGF-Iexerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production. PMID:18461658

Structure and activity of Bombyx PBAN.

PubMed

Nagasawa, H; Kuniyoshi, H; Arima, R; Kawano, T; Ando, T; Suzuki, A

1994-01-01

Two structurally related molecular species of pheromone biosynthesis activating neuropeptides (PBANs), PBAN-I and -II, were isolated from adult heads of the silkworm, Bombyx mori, and characterized. PBAN-I is a carboxyl-terminally amidated 33-residue peptide. Structure-activity relationship studies revealed that 1) its carboxyl-terminal pentapeptide is the smallest size showing activity, 2) the carboxyl-terminal amide is indispensable for activity, and 3) oxidation of three Met residues in PBAN-I to Met(O) (methionine sulfoxide) caused marked enhancement of activity, and the three Met(O) residues contribute equally to the enhancement of activity. Molecular design of PBAN analogs using a carboxyl-terminal hexapeptide showed that modification of the amino-terminal amino group brought about a dramatic increase in activity. This increase was presumed to be mainly due to the increased stability in hemolymph. PBANs share the common carboxyl-terminal sequence, -Phe-Xaa-Pro-Arg-Leu-NH2, with myotropic peptides isolated from locust and cockroach. Examination of cross-activity of these two groups of peptides revealed that PBAN and its analogs exhibited myotropic activity comparable to myotropic peptides, while myotropic peptides showed extremely high pheromonotropic activity. In B. mori, PBAN activates sex pheromone (bombykol) production presumably by promoting the reduction reaction from acyl to alcohol, which is the last step in the biosynthesis of bombykol.

Spatiotemporal frequency tuning of BOLD and gamma band MEG responses compared in primary visual cortex.

PubMed

Muthukumaraswamy, Suresh D; Singh, Krish D

2008-05-01

In this study, the spatial and temporal frequency tuning characteristics of the MEG gamma (40-60 Hz) rhythm and the BOLD response in primary visual cortex were measured and compared. In an identical MEG/fMRI paradigm, 10 participants viewed reversing square wave gratings at 2 spatial frequencies [0.5 and 3 cycles per degree (cpd)] reversing at 5 temporal frequencies (0, 1 6, 10, 15 Hz). Three-dimensional images of MEG source power were generated with synthetic aperture magnetometry (SAM) and showed a high degree of spatial correspondence with BOLD responses in primary visual cortex with a mean spatial separation of 6.5 mm, but the two modalities showed different tuning characteristics. The gamma rhythm showed a clear increase in induced power for the high spatial frequency stimulus while BOLD showed no difference in activity for the two spatial frequencies used. Both imaging modalities showed a general increase of activity with temporal frequency, however, BOLD plateaued around 6-10 Hz while the MEG generally increased with a dip exhibited at 6 Hz. These results demonstrate that the two modalities may show activation in similar spatial locations but that the functional pattern of these activations may differ in a complex manner, suggesting that they may be tuned to different aspects of neuronal activity.

Effect of steeping temperature on antioxidant and inhibitory activities of green tea extracts against α-amylase, α-glucosidase and intestinal glucose uptake.

PubMed

Liu, Shuyuan; Ai, Zeyi; Qu, Fengfeng; Chen, Yuqiong; Ni, Dejiang

2017-11-01

The objective of the present study was to evaluate the effect of steeping temperature on the biological activities of green tea, including the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging capacity, α-glucosidase and α-amylase inhibitory activities, and glucose uptake inhibitory activity in Caco-2 cells. Results showed that, with increasing extraction temperature, the polyphenol content increased, which contributed to enhance antioxidant activity and inhibitory effects on α-glucosidase and α-amylase. Green tea steeped at 100°C showed the highest DPPH radical-scavenging activity and inhibitory effects on α-glucosidase and α-amylase activities with EC 50 or IC 50 values of 6.15μg/mL, 0.09mg/mL, and 6.31mg/mL, respectively. However, the inhibitory potential on glucose uptake did not show an upward trend with increasing extraction temperature. Green tea steeped at 60°C had significantly stronger glucose uptake inhibitory activity (p<0.05). The integrated data suggested that steeping temperature should be considered when evaluating the biological activities of green tea. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anxiolytic-Like Effects and Increase in Locomotor Activity Induced by Infusions of NMDA into the Ventral Hippocampus in Rat: Interaction with GABAergic System.

PubMed

Bina, Payvand; Rezvanfard, Mehrnaz; Ahmadi, Shamseddin; Zarrindast, Mohammad Reza

2014-10-01

In this study, we investigated the role of N-Methyl-D-Aspartate (NMDA) receptors in the ventral hippocampus (VH) and their possible interactions with GABAA system on anxiety-like behaviors. We used an elevated-plus maze test (EPM) to assess anxiety-like behaviors and locomotor activity in male Wistar rats. The results showed that intra-VH infusions of different doses of NMDA (0.25 and 0.5 μg/rat) increased locomotor activity, and also induced anxiolytic-like behaviors, as revealed by a tendency to increase percentage of open arm time (%OAT), and a significant increase in percentage of open arm entries (%OAE). The results also showed that intra-VH infusions of muscimol (0.5 and 1 μg/rat) or bicuculline (0.5 and 1 μg/rat) did not significantly affect anxiety-like behaviors, but bicuculline at dose of 1 μg/rat increased locomotor activity. Intra-VH co-infusions of muscimol (0.5 μg/rat) along with low doses of NMDA (0.0625 and 0.125 μg/rat) showed a tendency to increase %OAT, %OAE and locomotor activity; however, no interaction was observed between the drugs. Interestingly, intra-VH co-infusions of bicuculline (0.5 μg/rat) along with effective doses of NMDA (0.25 and 0.5 μg/rat) decreased %OAT, %OAE and locomotor activity, and a significant interaction between two drugs was observed. It can be concluded that GABAergic system may mediate the anxiolytic-like effects and increase in locomotor activity induced by NMDA in the VH.

TGF-beta1 expression in EL4 lymphoma cells overexpressing growth hormone.

PubMed

Farmer, John T; Weigent, Douglas A

2006-03-01

Our previous studies show that growth hormone overexpression (GHo) upregulates the expression of the IGF-1R and IGF-2R resulting in the protection of the EL4 lymphoma cell line from apoptosis. In this study, we report that GHo also increases TGF-beta1 protein expression measured by luciferase promoter assay, Western analysis, and ELISA. Further, the data show that antibody to TGF-betaR2 decreases TGF-beta1 promoter activity to the level of vector alone control cells. GHo cells treated with (125)I-rh-latent TGF-beta1 showed increased activation of latent TGF-beta1 as measured by an increase in the active 24kDa, TGF-beta1 compared to vector alone control cells. The ability of endogenous GH to increase TGF-beta1 expression is blocked in EL4 cells by antisense but not sense oligodeoxynucleotides or in cells cultured with antibody to growth hormone (GH). The data suggest that endogenous GH may protect from apoptosis through the IGF-1R receptor while limiting cellular growth through increased expression and activation of TGF-beta1.

Net superoxide levels: steeper increase with activity in cooler female and hotter male lizards.

PubMed

Ballen, Cissy; Healey, Mo; Wilson, Mark; Tobler, Michael; Wapstra, Erik; Olsson, Mats

2012-03-01

Ectotherms increase their body temperature in response to ambient heat, thereby elevating their metabolic rate. An often inferred consequence of this is an overall upregulation of gene expression and energetic expenditure, and a concomitant increased production of reactive oxygen species (e.g. superoxide) and, perhaps, a shortened lifespan. However, recent work shows that this may be a superficial interpretation. For example, sometimes a reduced temperature may in fact trigger up-regulation of gene expression. We studied temperature and associated activity effects in male and female Australian painted dragon lizards (Ctenophorus pictus) by allowing the lizards to bask for 4 h versus 12 h, and scoring their associated activity (inactive versus active basking and foraging). As predicted, long-basking lizards (hereafter 'hot') showed heightened activity in both sexes, with a more pronounced effect in females. We then tested for sex-specific effects of basking treatment and activity levels on the increase in net levels of superoxide. In males, short-baskers (hereafter 'cold') had significantly more rapidly decreasing levels of superoxide per unit increasing activity than hot males. In females, however, superoxide levels increased faster with increasing activity in the cold than in the hot basking treatment, and females earlier in the ovarian cycle had lower superoxide levels than females closer to ovulation. In short, males and females differ in how their levels of reactive oxygen species change with temperature-triggered activity.

In Sickness and in Health: The Co-Regulation of Inflammation and Social Behavior

PubMed Central

Eisenberger, Naomi I; Moieni, Mona; Inagaki, Tristen K; Muscatell, Keely A; Irwin, Michael R

2017-01-01

Although it has commonly been assumed that the immune system and the processes that govern social behavior are separate, non-communicating entities, research over the past several decades suggests otherwise. Considerable evidence now shows that inflammatory processes and social behavior are actually powerful regulators of one another. This review first summarizes evidence that inflammatory processes regulate social behavior, leading to characteristic changes that may help an individual navigate the social environment during times of sickness. Specifically, this review shows that inflammation: (1) increases threat-related neural sensitivity to negative social experiences (eg, rejection, negative social feedback), presumably to enhance sensitivity to threats to well-being or safety in order to avoid them and (2) enhances reward-related neural sensitivity to positive social experiences (eg, viewing close others and receiving positive social feedback), presumably to increase approach-related motivation towards others who might provide support and care during sickness. Next, this review summarizes evidence showing that social behavior also regulates aspects of inflammatory activity, preparing the body for situations in which wounding and infection may be more likely (social isolation). Here, we review research showing: (1) that exposure to social stressors increases proinflammatory activity, (2) that individuals who are more socially isolated (ie, lonely) show increased proinflammatory activity, and (3) that individuals who are more socially isolated show increased proinflammatory activity in response to an inflammatory challenge or social stressor. The implications of the co-regulation of inflammation and social behavior are discussed. PMID:27480575

Direct evidence that genetic variation in glycerol-3-phosphate and malate dehydrogenase genes (Gpdh and Mdh1) affects adult ethanol tolerance in Drosophila melanogaster.

PubMed

Eanes, Walter F; Merritt, Thomas J S; Flowers, Jonathan M; Kumagai, Seiji; Zhu, Chen-Tseh

2009-02-01

Many studies of alcohol adaptation in Drosophila melanogaster have focused on the Adh polymorphism, yet the metabolic elimination of alcohol should involve many enzymes and pathways. Here we evaluate the effects of glycerol-3-phosphate dehydrogenase (Gpdh) and cytosolic malate dehydrogenase (Mdh1) genotype activity on adult tolerance to ethanol. We have created a set of P-element-excision-derived Gpdh, Mdh1, and Adh alleles that generate a range of activity phenotypes from full to zero activity. Comparisons of paired Gpdh genotypes possessing 10 and 60% normal activity and 66 and 100% normal activity show significant effects where higher activity increases tolerance. Mdh1 null allele homozygotes show reductions in tolerance. We use piggyBac FLP-FRT site-specific recombination to create deletions and duplications of Gpdh. Duplications show an increase of 50% in activity and an increase of adult tolerance to ethanol exposure. These studies show that the molecular polymorphism associated with GPDH activity could be maintained in natural populations by selection related to adaptation to alcohols. Finally, we examine the interactions between activity genotypes for Gpdh, Mdh1, and Adh. We find no significant interlocus interactions. Observations on Mdh1 in both Gpdh and Adh backgrounds demonstrate significant increases in ethanol tolerance with partial reductions (50%) in cytosolic MDH activity. This observation strongly suggests the operation of pyruvate-malate and, in particular, pyruvate-citrate cycling in adaptation to alcohol exposure. We propose that an understanding of the evolution of tolerance to alcohols will require a system-level approach, rather than a focus on single enzymes.

Impact of orientation of carbohydrate binding modules family 22 and 6 on the catalytic activity of Thermotoga maritima xylanase XynB.

PubMed

Tajwar, Razia; Shahid, Saher; Zafar, Rehan; Akhtar, Muhammad Waheed

2017-11-01

Xylanase XynB of the hyperthermophile Thermotoga maritima, which belongs to glycoside hydrolase family 10 (GH10), does not have an associated carbohydrate binding module (CBM) in the native state. CBM6 and CBM22 from a thermophile Clostridium thermocellum were fused to the catalytic domain of XynB (XynB-C) to determine the effects on activity and other properties. XynB-B22C and XynB-CB22, produced by fusing CBM22 to the N- and C-terminal of XynB-C, showed 1.7- and 3.24-fold increase in activity against the insoluble birchwood xylan, respectively. Similarly, CBM6 when attached to the C-terminal of XynB-C resulted in 2.0-fold increase in activity, whereas its attachment to the N-terminal did not show any increase of activity. XynB-B22C and XynB-CB22 retained all the activity, whereas XynB-B6C and XynB-CB6 lost 17 and 11% of activity, respectively, at 60°C for 4h. Thermostability data and the secondary structure contents obtained by molecular modelling are in agreement with the data from circular dichroism analysis. Molecular modelling analysis showed that the active site residues of the catalytic domain and the binding residues of CBM6 and CBM22 were located on the surface of molecule, except XynB-B6C, where the binding residues were found somewhat buried. In the case of XynB-CB22, the catalytic and the binding residues seem to be located favorably adjacent to each other, thus showing higher increase in activity. This study shows that the active site residues of the catalytic domain and the binding residues of the CBM are arranged in a unique fashion, not reported before. Copyright © 2017 Elsevier Inc. All rights reserved.

Protective effect of N-acetyl-L-cysteine against disulfiram-induced oxidative stress and apoptosis in V79 cells

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

Grosicka-Maciag, Emilia; Kurpios-Piec, Dagmara; Grzela, Tomasz

2010-11-01

This work investigated the effect of N-acetyl-L-cysteine (NAC) on disulfiram (DSF) induced oxidative stress in Chinese hamster fibroblast cells (V79). An increase in oxidative stress induced by DSF was observed up to a 200 {mu}M concentration. It was evidenced by a statistically significant increase of both GSH{sub t} and GSSG levels, as well as elevated protein carbonyl (PC) content. There was no increase in lipid peroxidation (measured as TBARS). DSF increased CAT activity, but did not change SOD1 and SOD2 activities. Analysis of GSH related enzymes showed that DSF significantly increased GR activity, did not change Se-dependent GPx, but statisticallymore » significantly decreased non-Se-dependent GPx activity. DSF showed also pro-apoptotic activity. NAC alone did not produce any significant changes, besides an increase of GSH{sub t} level, in any of the variables measured. However, pre-treatment of cells with NAC ameliorated DSF-induced changes. NAC pre-treatment restored the viability of DSF-treated cells evaluated by Trypan blue exclusion assay and MTT test, GSSG level, and protein carbonyl content to the control values as well as it reduced pro-apoptotic activity of DSF. The increase of CAT and GR activity was not reversed. Activity of both GPx was significantly increased compared to their values after DSF treatment. In conclusion, oxidative properties are at least partially attributable to the cellular effects of disulfiram and mechanisms induced by NAC pre-treatment may lower or even abolish the observed effects. These observations illustrate the importance of the initial cellular redox state in terms of cell response to disulfiram exposure. -- Research Highlights: {yields}This report explores biological properties of disulfiram under a condition of modulated intra-cellular GSH level. It shows a protective role of N-acetyl-L-cysteine in V79 cells exposed to disulfiram (in GSH metabolism as well as in changes of antioxidant enzyme activity).« less

Palatable Meal Anticipation in Mice

PubMed Central

Hsu, Cynthia T.; Patton, Danica F.; Mistlberger, Ralph E.; Steele, Andrew D.

2010-01-01

The ability to sense time and anticipate events is a critical skill in nature. Most efforts to understand the neural and molecular mechanisms of anticipatory behavior in rodents rely on daily restricted food access, which induces a robust increase of locomotor activity in anticipation of daily meal time. Interestingly, rats also show increased activity in anticipation of a daily palatable meal even when they have an ample food supply, suggesting a role for brain reward systems in anticipatory behavior, and providing an alternate model by which to study the neurobiology of anticipation in species, such as mice, that are less well adapted to “stuff and starve” feeding schedules. To extend this model to mice, and exploit molecular genetic resources available for that species, we tested the ability of wild-type mice to anticipate a daily palatable meal. We observed that mice with free access to regular chow and limited access to highly palatable snacks of chocolate or “Fruit Crunchies” avidly consumed the snack but did not show anticipatory locomotor activity as measured by running wheels or video-based behavioral analysis. However, male mice receiving a snack of high fat chow did show increased food bin entry prior to access time and a modest increase in activity in the two hours preceding the scheduled meal. Interestingly, female mice did not show anticipation of a daily high fat meal but did show increased activity at scheduled mealtime when that meal was withdrawn. These results indicate that anticipation of a scheduled food reward in mice is behavior, diet, and gender specific. PMID:20941366

Transformation of Lactuca sativa L. with rol C gene results in increased antioxidant potential and enhanced analgesic, anti-inflammatory and antidepressant activities in vivo.

PubMed

Ismail, Hammad; Dilshad, Erum; Waheed, Mohammad Tahir; Sajid, Moniba; Kayani, Waqas Khan; Mirza, Bushra

2016-12-01

Lettuce is an important edible crop which possesses various medicinal properties. In this study Lactuca sativa L. (cv Grand Rapids) was transformed by Agrobacterium-mediated transformation with rol C gene. Transgene integration and expression was confirmed through PCR and semiquantitative RT-PCR. The transformed extracts were evaluated for their in vitro antioxidant and in vivo analgesic, anti-inflammatory and antidepressant activities in rats. The transformed plants showed 53-98 % increase in total phenolic and 45-58 % increase in total flavonoid contents compared with untransformed plants. Results of total reducing power and total antioxidant capacity exhibited 90-118 and 61-75 % increase in transformed plants, respectively. In contrast to control, DPPH, lipid peroxidation and DNA protection assay showed up to 37, 20 and 50 % enhancement in transformed plants, respectively. The extracts showed similar but significant enhancement behavior in hot plate analgesic and carrageenan-induced hind paw edema test. The transformed extracts showed 72.1 and 78.5 % increase for analgesic and anti-inflammatory activities, respectively. The transformants of rol C gene exhibited prominent antidepressant activity with 64-73 % increase compared with untransformed plants. In conclusion, the present work suggests that transformation with rol C gene can be used to generate lettuce with enhanced medicinally important properties, such as antioxidant, analgesic, anti-inflammatory and antidepressant potential.

Aging effects on functional auditory and visual processing using fMRI with variable sensory loading.

PubMed

Cliff, Michael; Joyce, Dan W; Lamar, Melissa; Dannhauser, Thomas; Tracy, Derek K; Shergill, Sukhwinder S

2013-05-01

Traditionally, studies investigating the functional implications of age-related structural brain alterations have focused on higher cognitive processes; by increasing stimulus load, these studies assess behavioral and neurophysiological performance. In order to understand age-related changes in these higher cognitive processes, it is crucial to examine changes in visual and auditory processes that are the gateways to higher cognitive functions. This study provides evidence for age-related functional decline in visual and auditory processing, and regional alterations in functional brain processing, using non-invasive neuroimaging. Using functional magnetic resonance imaging (fMRI), younger (n=11; mean age=31) and older (n=10; mean age=68) adults were imaged while observing flashing checkerboard images (passive visual stimuli) and hearing word lists (passive auditory stimuli) across varying stimuli presentation rates. Younger adults showed greater overall levels of temporal and occipital cortical activation than older adults for both auditory and visual stimuli. The relative change in activity as a function of stimulus presentation rate showed differences between young and older participants. In visual cortex, the older group showed a decrease in fMRI blood oxygen level dependent (BOLD) signal magnitude as stimulus frequency increased, whereas the younger group showed a linear increase. In auditory cortex, the younger group showed a relative increase as a function of word presentation rate, while older participants showed a relatively stable magnitude of fMRI BOLD response across all rates. When analyzing participants across all ages, only the auditory cortical activation showed a continuous, monotonically decreasing BOLD signal magnitude as a function of age. Our preliminary findings show an age-related decline in demand-related, passive early sensory processing. As stimulus demand increases, visual and auditory cortex do not show increases in activity in older compared to younger people. This may negatively impact on the fidelity of information available to higher cognitive processing. Such evidence may inform future studies focused on cognitive decline in aging. Copyright © 2012 Elsevier Ltd. All rights reserved.

Oxytocin increases VTA activation to infant and sexual stimuli in nulliparous and postpartum women

PubMed Central

Gregory, Rebecca; Cheng, Hu; Rupp, Heather A.; Sengelaub, Dale R.; Heiman, Julia R.

2015-01-01

After giving birth, women typically experience decreased sexual desire and increased responsiveness to infant stimuli. These postpartum changes may be viewed as a trade-off in reproductive interests, which could be due to alterations in brain activity including areas associated with reward. The goal of this study was to describe the roles of oxytocin and parity on reward area activation in response to reproductive stimuli, specifically infant and sexual images. Because they have been shown to be associated with reward, the ventral tegmental area (VTA) and nucleus accumbens (NAc) were targeted as areas of expected alterations in activity. Oxytocin was chosen as a potential mediator of reproductive trade-offs because of its relationship to both mother–infant interactions, including breastfeeding and bonding, and sexual responses. We predicted that postpartum women would show higher reward area activation to infant stimuli and nulliparous women would show higher activation to sexual stimuli and that oxytocin would increase activation to infant stimuli in nulliparous women. To test this, we measured VTA and NAc activation using fMRI in response to infant photos, sexual photos, and neutral photos in 29 postpartum and 30 nulliparous women. Participants completed the Sexual Inhibition (SIS) and Sexual Excitation (SES) Scales and the Brief Index of Sexual Function for Women (BISF-W), which includes a sexual desire dimension, and received either oxytocin or placebo nasal spray before viewing crying and smiling infant and sexual images in an fMRI scanner. For both groups of women, intranasal oxytocin administration increased VTA activation to both crying infant and sexual images but not to smiling infant images. We found that postpartum women showed lower SES, higher SIS, and lower sexual desire compared to nulliparous women. Across parity groups, SES scores were correlated with VTA activation and subjective arousal ratings to sexual images. In postpartum women, sexual desire was positively correlated with VTA activation to sexual images and with SES. Our findings show that postpartum decreases in sexual desire may in part be mediated by VTA activation, and oxytocin increased activation of the VTA but not NAc in response to sexual and infant stimuli. Oxytocin may contribute to the altered reproductive priorities in postpartum women by increasing VTA activation to salient infant stimuli. PMID:25562711

An RNAi-mediated screen identifies novel targets for next-generation antiepileptic drugs based on increased expression of the homeostatic regulator pumilio.

PubMed

Lin, Wei-Hsiang; He, Miaomiao; Fan, Yuen Ngan; Baines, Richard A

2018-05-02

Despite availability of a diverse range of anti-epileptic drugs (AEDs), only about two-thirds of epilepsy patients respond well to drug treatment. Thus, novel targets are required to catalyse the design of next-generation AEDs. Manipulation of neuron firing-rate homoeostasis, through enhancing Pumilio (Pum) activity, has been shown to be potently anticonvulsant in Drosophila. In this study, we performed a genome-wide RNAi screen in S2R + cells, using a luciferase-based dPum activity reporter and identified 1166 genes involved in dPum regulation. Of these genes, we focused on 699 genes that, on knock-down, potentiate dPum activity/expression. Of this subgroup, 101 genes are activity-dependent based on comparison with genes previously identified as activity-dependent by RNA-sequencing. Functional cluster analysis shows these genes are enriched in pathways involved in DNA damage, regulation of cell cycle and proteasomal protein catabolism. To test for anticonvulsant activity, we utilised an RNA-interference approach in vivo. RNAi-mediated knockdown showed that 57/101 genes (61%) are sufficient to significantly reduce seizure duration in the characterized seizure mutant, para bss . We further show that chemical inhibitors of protein products of some of the genes targeted are similarly anticonvulsant. Finally, to establish whether the anticonvulsant activity of identified compounds results from increased dpum transcription, we performed a luciferase-based assay to monitor dpum promoter activity. Third instar larvae exposed to sodium fluoride, gemcitabine, metformin, bestatin, WP1066 or valproic acid all showed increased dpum promoter activity. Thus, this study validates Pum as a favourable target for AED design and, moreover, identifies a number of lead compounds capable of increasing the expression of this homeostatic regulator.

G protein-coupled estrogen receptor 1 (GPER1)/GPR30 increases ERK1/2 activity through PDZ motif-dependent and -independent mechanisms.

PubMed

Gonzalez de Valdivia, Ernesto; Broselid, Stefan; Kahn, Robin; Olde, Björn; Leeb-Lundberg, L M Fredrik

2017-06-16

G protein-coupled receptor 30 (GPR30), also called G protein-coupled estrogen receptor 1 (GPER1), is thought to play important roles in breast cancer and cardiometabolic regulation, but many questions remain about ligand activation, effector coupling, and subcellular localization. We showed recently that GPR30 interacts through the C-terminal type I PDZ motif with SAP97 and protein kinase A (PKA)-anchoring protein (AKAP) 5, which anchor the receptor in the plasma membrane and mediate an apparently constitutive decrease in cAMP production independently of G i/o Here, we show that GPR30 also constitutively increases ERK1/2 activity. Removing the receptor PDZ motif or knocking down specifically AKAP5 inhibited the increase, showing that this increase also requires the PDZ interaction. However, the increase was inhibited by pertussis toxin as well as by wortmannin but not by AG1478, indicating that G i/o and phosphoinositide 3-kinase (PI3K) mediate the increase independently of epidermal growth factor receptor transactivation. FK506 and okadaic acid also inhibited the increase, implying that a protein phosphatase is involved. The proposed GPR30 agonist G-1 also increased ERK1/2 activity, but this increase was only observed at a level of receptor expression below that required for the constitutive increase. Furthermore, deleting the PDZ motif did not inhibit the G-1-stimulated increase. Based on these results, we propose that GPR30 increases ERK1/2 activity via two G i/o -mediated mechanisms, a PDZ-dependent, apparently constitutive mechanism and a PDZ-independent G-1-stimulated mechanism. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Coronary vasospasm induced in transgenic mouse with increased phospholipase C-δ1 activity.

PubMed

Shibutani, Shuji; Osanai, Tomohiro; Ashitate, Toshihiro; Sagara, Shigeki; Izumiyama, Kei; Yamamoto, Yuko; Hanada, Kenji; Echizen, Takashi; Tomita, Hirofumi; Fujita, Takeshi; Miwa, Takeshi; Matsubara, Hiroaki; Homma, Yoshimi; Okumura, Ken

2012-02-28

We reported that phospholipase C (PLC)-δ1 activity was enhanced 3-fold in patients with coronary spastic angina. We detected variant PLC-δ1 with replacement of arginine 257 by histidine (R257H) showing increased enzymatic activity. We tested the hypothesis that increased PLC-δ1 activity causes enhanced coronary vasomotility. We generated transgenic (TG) mice with human R257H variant PLC-δ1 in vascular smooth muscle cells. PLC enzymatic activity in the coronary artery was increased by 2.57 and 1.89 times, respectively, in homozygous and heterozygous TG compared with wild-type (WT) mice. ST elevation after ergometrine occurred in 17 of 18 homozygous TG, 6 of 20 heterozygous TG, and 3 of 22 WT mice (P<0.01, homozygous TG versus WT; P<0.05, homozygous TG versus heterozygous TG; P=NS, heterozygous TG versus WT). ST elevation was associated with bradyarrhythmias in homozygous TG mice. Focal coronary artery narrowing was documented with the microvascular filling technique in 3 of 5 homozygous TG mice after ergometrine but not in any of 7 WT mice (P<0.05). In the isolated Langendorff hearts, coronary perfusion pressure was increased after ergometrine in homozygous TG mice (P<0.01) but not in heterozygous TG or WT mice. Coronary perfusion pressure increase after prostaglandin F2α was similar among homozygous TG, heterozygous TG, and WT mice. Cultured rat aortic smooth muscle cells transfected with variant PLC-δ1 showed a higher PLC activity than those with WT PLC-δ1 (P<0.05) and furthermore showed greater intracellular Ca2+ response to acetylcholine in variant than in WT PLC-δ1 (P<0.05). Increased PLC-δ1 activity enhances coronary vasomotility such as that seen in patients with coronary spastic angina.

White Light-Activated Antimicrobial Paint using Crystal Violet.

PubMed

Hwang, Gi Byoung; Allan, Elaine; Parkin, Ivan P

2016-06-22

Crystal violet (CV) was incorporated into acrylic latex to produce white-light-activated antimicrobial paint (WLAAP). Measurement of the water contact angle of the WLAAP showed that the water contact angle increased with increasing CV concentration. In a leaching test over 120 h, the amount of CV that leached from the WLAAPs was close to the detection limit (<0.03%). The WLAAPs were used to coat samples of polyurethane, and these showed bactericidal activity against Escherichia coli, which is a key causative agent of healthcare-associated infections (HAIs). A reduction in the numbers of viable bacteria was observed on the painted coated polyurethane after 6 h in the dark, and the bactericidal activity increased with increasing CV concentration (P < 0.1). After 6 h of white light exposure, all of coated polyurethanes demonstrated a potent photobactericidal activity, and it was statistically confirmed that the WLAAP showed better activity in white light than in the dark (P < 0.05). At the highest CV concentration, the numbers of viable bacteria fell below the detection limit (<10(3) CFU/mL) after 6 h of white light exposure. The difference in antimicrobial activity between the materials in the light and dark was 0.48 log at CV 250 ppm, and it increased by 0.43 log at each increment of CV 250 ppm. The difference was the highest (>1.8 log) at the highest CV concentration (1000 ppm). These WLAAPs are promising candidates for use in healthcare facilities to reduce HAIs.

Differential transcriptional regulation by alternatively designed mechanisms: A mathematical modeling approach.

PubMed

Yildirim, Necmettin; Aktas, Mehmet Emin; Ozcan, Seyma Nur; Akbas, Esra; Ay, Ahmet

2017-01-01

Cells maintain cellular homeostasis employing different regulatory mechanisms to respond external stimuli. We study two groups of signal-dependent transcriptional regulatory mechanisms. In the first group, we assume that repressor and activator proteins compete for binding to the same regulatory site on DNA (competitive mechanisms). In the second group, they can bind to different regulatory regions in a noncompetitive fashion (noncompetitive mechanisms). For both competitive and noncompetitive mechanisms, we studied the gene expression dynamics by increasing the repressor or decreasing the activator abundance (inhibition mechanisms), or by decreasing the repressor or increasing the activator abundance (activation mechanisms). We employed delay differential equation models. Our simulation results show that the competitive and noncompetitive inhibition mechanisms exhibit comparable repression effectiveness. However, response time is fastest in the noncompetitive inhibition mechanism due to increased repressor abundance, and slowest in the competitive inhibition mechanism by increased repressor level. The competitive and noncompetitive inhibition mechanisms through decreased activator abundance show comparable and moderate response times, while the competitive and noncompetitive activation mechanisms by increased activator protein level display more effective and faster response. Our study exemplifies the importance of mathematical modeling and computer simulation in the analysis of gene expression dynamics.

Curcumin-docetaxel co-loaded nanosuspension for enhanced anti-breast cancer activity.

PubMed

Sahu, Bhanu P; Hazarika, Hemanga; Bharadwaj, Rituraj; Loying, Pojul; Baishya, Rinku; Dash, Suvakanta; Das, Malay K

2016-08-01

A curcumin-docetaxel co-loaded nanosuspension with increased anti-breast cancer activity was developed. Curcumin is a potential anticancer agent with p-glycoprotein (p-gp) inhibiting activity may be co-administered with docetaxel as a nanosuspension to enhance its anticancer effect by increasing the oral bioavailability and decreasing drug efflux. Nanosuspensions of curcumin and docetaxel were prepared by precipitation-homozenisation technique and evaluated for particle size, polydispersity, zeta potential and drug release. The in vitro MTT assay was conducted using MCF-7 for anti-breast cancer activity. The in vivo biodistribution by radiolabeling and tumor inhibition study was conducted in mice. Homogenous nanosuspensions of 80 ± 20 nm were obtained with increased solubility. The drugs as nanosuspensions showed higher cytotoxicity on MCF-7 cell line compared to their suspensions due to the increased in vitro cellular uptake. Due to this increased solubility, sensitization of tumor cells and inhibition of p-gp the in-vivo results showed greater tumor inhibition rate of up to 70% in MCF-7 treated mice. Histopathological results showed higher apoptotic activity and reduced level of angiogenesis. The in vitro and in vivo study of the nanosuspensions has shown that Co-administration of Curcumin as a p-gp inhibitor with docetaxel may have the potential to increase the anti-breast cancer efficacy of both drugs.

Strong fascin expression promotes metastasis independent of its F-actin bundling activity.

PubMed

Heinz, Lisa S; Muhs, Stefanie; Schiewek, Johanna; Grüb, Saskia; Nalaskowski, Marcus; Lin, Yuan-Na; Wikman, Harriet; Oliveira-Ferrer, Leticia; Lange, Tobias; Wellbrock, Jasmin; Konietzny, Anja; Mikhaylova, Marina; Windhorst, Sabine

2017-12-15

High expression of the actin bundling protein Fascin increases the malignancy of tumor cells. Here we show that fascin expression is up-regulated in more malignant sub-cell lines of MDA-MB-231 cells as compared to parental cells. Since also parental MDA-MB-231 cells exhibit high fascin levels, increased fascin expression was termed as "hyperexpression". To examine the effect of fascin hyperexpression, fascin was hyperexpressed in parental MDA-MB-231 cells and metastasis was analyzed in NOD scid gamma (NSG) mice. In addition, the effect of fascin mutants with inactive or constitutively active actin bundling activity was examined. Unexpectedly, we found that hyperexpression of both, wildtype (wt) and mutant fascin strongly increased metastasis in vivo , showing that the effect of fascin hyperexpression did not depend on its actin bundling activity. Cellular assays revealed that hyperexpression of wt and mutant fascin increased adhesion of MDA-MB-231 cells while transmigration and proliferation were not affected. Since it has been shown that fascin controls adhesion by directly interacting with microtubules ( MTs), we analyzed if fascin hyperexpression affects MT dynamics. We found that at high concentrations fascin significantly increased MT dynamics in cells and in cell-free approaches. In summary our data show that strong expression of fascin in breast cancer cells increases metastasis independent of its actin bundling activity. Thus, it seems that the mechanism of fascin-stimulated metastasis depends on its concentration.

Coagulation parameters in senior athletes practicing endurance sporting activity.

PubMed

Cerneca, E; Simeone, R; Bruno, G; Gombacci, A

2005-12-01

Physical activity is practiced more and more by middle-aged people. We studied the behavior of the coagulation system before and after near-maximum, specific and standardized exercise tests in 2 groups of senior athletes. The subjects of the study were 2 groups of athletes over 40 years of age (ranging 41 to 60 years): 10 rowers and 10 marathon runners. The data were compared with 10 controls (ranging in age from 40 to 71 years) tested on the cycle ergometer. The first group (rowers) was tested on a rowing machine; the second group (marathon runners) performed a maximal exercise on the treadmill. All subjects were tested to a maximal level of cardiovascular and muscular exertion and cardiac and respiratory parameters were monitored. The following coagulation tests were performed before and after maximal exercise: prothrombin time (PT), partial activated thromboplastin time (PTT), fibrinogen (FBG), antithrombin III (ATIII), protein C (PC), protein S (PS), prothrombin fragment 1+2 (F1+2), tissue activator of plasminogen (t-PA) and its inhibitor (PAI). All subjects performed a complete maximal specific test. The results showed all individuals produced a significant increase of FBG, PT and PTT activities and a lowering trend for PC and PS inhibitors after maximal exercise testing. ATIII levels increased significantly in trained subjects. After the test, data regarding fibrinolysis showed higher t-PA levels in athletes as compared with controls. PAI levels indicated a more marked decrease in athletes. The F1+2 showed a moderate but significant increase in the control group. Coagulative tests showed an increase in procoagulant and fibrinolysis parameters in all the groups but the increased fibrinolytic activity in trained athletes indicates a protective factor and greater vascular efficiency. The results demonstrate that sporting activity practiced by middle-aged people accelerates fibrinolytic activity in conditioned subjects. In conclusion, physical activity benefits the coagulation system particularly as regards fibrinolysis.

Vertebrate blood cell volume increases with temperature: implications for aerobic activity.

PubMed

Gillooly, James F; Zenil-Ferguson, Rosana

2014-01-01

Aerobic activity levels increase with body temperature across vertebrates. Differences in these levels, from highly active to sedentary, are reflected in their ecology and behavior. Yet, the changes in the cardiovascular system that allow for greater oxygen supply at higher temperatures, and thus greater aerobic activity, remain unclear. Here we show that the total volume of red blood cells in the body increases exponentially with temperature across vertebrates, after controlling for effects of body size and taxonomy. These changes are accompanied by increases in relative heart mass, an indicator of aerobic activity. The results point to one way vertebrates may increase oxygen supply to meet the demands of greater activity at higher temperatures.

Long-term increases in tropical flowering activity across growth forms in response to rising CO2 and climate change.

PubMed

Pau, Stephanie; Okamoto, Daniel K; Calderón, Osvaldo; Wright, S Joseph

2018-05-01

Mounting evidence suggests that anthropogenic global change is altering plant species composition in tropical forests. Fewer studies, however, have focused on long-term trends in reproductive activity, in part because of the lack of data from tropical sites. Here, we analyze a 28-year record of tropical flower phenology in response to anthropogenic climate and atmospheric change. We show that a multidecadal increase in flower activity is most strongly associated with rising atmospheric CO 2 concentrations using yearly aggregated data. Compared to significant climatic factors, CO 2 had on average an approximately three-, four-, or fivefold stronger effect than rainfall, solar radiation, and the Multivariate ENSO Index, respectively. Peaks in flower activity were associated with greater solar radiation and lower rainfall during El Niño years. The effect of atmospheric CO 2 on flowering has diminished over the most recent decade for lianas and canopy trees, whereas flowering of midstory trees and shrub species continued to increase with rising CO 2 . Increases in flowering were accompanied by a lengthening of flowering duration for canopy and midstory trees. Understory treelets did not show increases in flowering but did show increases in duration. Given that atmospheric CO 2 will likely continue to climb over the next century, a long-term increase in flowering activity may persist in some growth forms until checked by nutrient limitation or by climate change through rising temperatures, increasing drought frequency and/or increasing cloudiness and reduced insolation. © 2017 John Wiley & Sons Ltd.

Brain Responses during the Anticipation of Dyspnea

PubMed Central

Stoeckel, M. Cornelia; Esser, Roland W.; Büchel, Christian

2016-01-01

Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea. PMID:27648309

Brain Responses during the Anticipation of Dyspnea.

PubMed

Stoeckel, M Cornelia; Esser, Roland W; Gamer, Matthias; Büchel, Christian; von Leupoldt, Andreas

2016-01-01

Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea.

Angiotensin I-converting enzyme-inhibitory activity of the Norwegian autochthonous cheeses Gamalost and Norvegia after in vitro human gastrointestinal digestion.

PubMed

Qureshi, T M; Vegarud, G E; Abrahamsen, R K; Skeie, S

2013-02-01

The angiotensin I-converting enzyme (ACE) inhibitory activity of Gamalost cheese, its pH 4.6-soluble fraction, and Norvegia cheese was monitored before and after digestion with human gastric and duodenal juices. Both Gamalost and Norvegia cheeses showed an increased ACE-inhibitory activity during gastrointestinal digestion. However, only Norvegia showed pronounced increased activity after duodenal digestion. More peptides were detected in digested Gamalost compared with digested Norvegia. Most of the peptides in Gamalost were derived from β-casein (CN), some originated from α(s1)-CN, and only a very few originated from α(s2)-CN and κ-CN. In general, the number of peptides increased during gastrointestinal digestion, whereas some peptides were further degraded and disappeared; however, surprisingly, a few peptides remained stable. The aromatic amino acids, such as Tyr, Phe, and Trp; the positively charged amino acids (Arg and Lys); and Leu increased after simulated gastrointestinal digestion of Gamalost and Norvegia. After in vitro gastrointestinal digestion, both Gamalost and Norvegia showed high ACE-inhibitory activity, which may contribute in lowering of mild hypertension. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Radio Imaging Observations of Solar Activity Cycle and Its Anomaly

NASA Astrophysics Data System (ADS)

Shibasaki, K.

2011-12-01

The 24th solar activity cycle has started and relative sunspot numbers are increasing. However, their rate of increase is rather slow compared to previous cycles. Active region sizes are small, lifetime is short, and big (X-class) flares are rare so far. We study this anomalous situation using data from Nobeyama Radioheliograph (NoRH). Radio imaging observations have been done by NoRH since 1992. Nearly 20 years of daily radio images of the Sun at 17 GHz are used to synthesize a radio butterfly diagram. Due to stable operation of the instrument and a robust calibration method, uniform datasets are available covering the whole period of observation. The radio butterfly diagram shows bright features corresponding to active region belts and their migration toward low latitude as the solar cycle progresses. In the present solar activity cycle (24), increase of radio brightness is delayed and slow. There are also bright features around both poles (polar brightening). Their brightness show solar cycle dependence but peaks around solar minimum. Comparison between the last minimum and the previous one shows decrease of its brightness. This corresponds to weakening of polar magnetic field activity between them. In the northern pole, polar brightening is already weakened in 2011, which means it is close to solar maximum in the northern hemisphere. Southern pole does not show such feature yet. Slow rise of activity in active region belt, weakening of polar activity during the minimum, and large north-south asymmetry in polar activity imply that global solar activity and its synchronization are weakening.

Antioxidant and antiproliferative activities of methanolic extract from a neglected agricultural product: corn cobs.

PubMed

Melo-Silveira, Raniere Fagundes; Fidelis, Gabriel Pereira; Viana, Rony Lucas Silva; Soeiro, Vinícius Campelo; Silva, Rodrigo Augusto da; Machado, Daisy; Costa, Leandro Silva; Ferreira, Carmen Veríssima; Oliveira Rocha, Hugo Alexandre

2014-04-24

Neglected agricultural products (NAPs) are defined as discarded material in agricultural production. Corn cobs are a major waste of agriculture maize. Here, a methanolic extract from corn cobs (MEC) was obtained. MEC contains phenolic compounds, protein, carbohydrates (1.4:0.001:0.001). We evaluated the in vitro and in vivo antioxidant potential of MEC. Furthermore, its antiproliferative property against tumor cells was assessed through MTT assays and proteins related to apoptosis in tumor cells were examined by western blot. MEC showed no hydroxyl radical scavenger capacity, but it showed antioxidant activity in Total Antioxidant Capacity and DPPH scavenger ability assays. MEC showed higher Reducing Power than ascorbic acid and exhibited high Superoxide Scavenging activity. In tumor cell culture, MEC increased catalase, metallothionein and superoxide dismutase expression in accordance with the antioxidant tests. In vivo antioxidant test, MEC restored SOD and CAT, decreased malondialdehyde activities and showed high Trolox Equivalent Antioxidant Capacity in animals treated with CCl4. Furthermore, MEC decreased HeLa cells viability by apoptosis due an increase of Bax/Bcl-2 ratio, caspase 3 active. Protein kinase C expression increased was also detected in treated tumor cells. Thus, our findings pointed out the biotechnological potential of corn cobs as a source of molecules with pharmacological activity.

Oxidation of platinum nickel nanowires to improve durability of oxygen-reducing electrocatalysts

DOE PAGES

Alia, Shaun M.; Pylypenko, Svitlana; Dameron, Arrelaine; ...

2016-01-12

In this study, the impact of heat treating platinum-coated nickel (Pt-Ni) nanowires in oxygen is examined to determine the effect on oxygen reduction (ORR) activity and durability. Pt-Ni nanowires exhibit promising ORR mass activities (3 times greater than Pt nanoparticles, 1.5 times greater than U.S. Department of Energy target) both before and after potential cycling for all but the highest annealing temperatures explored. The annealing of Pt-Ni nanowires in oxygen with increasing temperature is found to reduce surface area and ORR activity in comparison to the untreated material, but also reduces activity losses following durability testing. Following potential cycling, unannealedmore » Pt-Ni nanowires show significant losses in surface area (23%) and specific activity (18%) while Pt-Ni nanowires annealed at 200°C show modest increases in surface area (2%) and specific activity (6%) after potential cycling. Increasing annealing temperatures also show a clear trend of decreasing Ni dissolution rates. While oxygen annealing has shown the ability to improve durability of Pt-Ni nanowires, significant Ni dissolution was observed in all samples and suggests oxide passivation while showing promise for improved durability, when employed by itself is insufficient to prevent all contamination concerns involving Ni dissolution.« less

Comparison of the Effects of Walking with and without Nordic Pole on Upper Extremity and Lower Extremity Muscle Activation.

PubMed

Shim, Je-Myung; Kwon, Hae-Yeon; Kim, Ha-Roo; Kim, Bo-In; Jung, Ju-Hyeon

2013-12-01

[Purpose] The aim of this study was to assess the effect of Nordic pole walking on the electromyographic activities of upper extremity and lower extremity muscles. [Subjects and Methods] The subjects were randomly divided into two groups as follows: without Nordic pole walking group (n=13) and with Nordic pole walking group (n=13). The EMG data were collected by measurement while the subjects walking on a treadmill for 30 minutes by measuring from one heel strike to the next. [Results] Both the average values and maximum values of the muscle activity of the upper extremity increased in both the group that used Nordic poles and the group that did not use Nordic poles, and the values showed statistically significant differences. There was an increase in the average value for muscle activity of the latissimus dorsi, but the difference was not statistically significant, although there was a statistically significant increase in its maximum value. The average and maximum values for muscle activity of the lower extremity did not show large differences in either group, and the values did not show any statistically significant differences. [Conclusion] The use of Nordic poles by increased muscle activity of the upper extremity compared with regular walking but did not affect the lower extremity.

Comparison of the Effects of Walking with and without Nordic Pole on Upper Extremity and Lower Extremity Muscle Activation

PubMed Central

Shim, Je-myung; Kwon, Hae-yeon; Kim, Ha-roo; Kim, Bo-in; Jung, Ju-hyeon

2014-01-01

[Purpose] The aim of this study was to assess the effect of Nordic pole walking on the electromyographic activities of upper extremity and lower extremity muscles. [Subjects and Methods] The subjects were randomly divided into two groups as follows: without Nordic pole walking group (n=13) and with Nordic pole walking group (n=13). The EMG data were collected by measurement while the subjects walking on a treadmill for 30 minutes by measuring from one heel strike to the next. [Results] Both the average values and maximum values of the muscle activity of the upper extremity increased in both the group that used Nordic poles and the group that did not use Nordic poles, and the values showed statistically significant differences. There was an increase in the average value for muscle activity of the latissimus dorsi, but the difference was not statistically significant, although there was a statistically significant increase in its maximum value. The average and maximum values for muscle activity of the lower extremity did not show large differences in either group, and the values did not show any statistically significant differences. [Conclusion] The use of Nordic poles by increased muscle activity of the upper extremity compared with regular walking but did not affect the lower extremity. PMID:24409018

Neural activity during interoceptive awareness and its associations with alexithymia—An fMRI study in major depressive disorder and non-psychiatric controls

PubMed Central

Wiebking, Christine; Northoff, Georg

2015-01-01

Objective: Alexithymia relates to difficulties recognizing and describing emotions. It has been linked to subjectively increased interoceptive awareness (IA) and to psychiatric illnesses such as major depressive disorder (MDD) and somatization. MDD in turn is characterized by aberrant emotion processing and IA on the subjective as well as on the neural level. However, a link between neural activity in response to IA and alexithymic traits in health and depression remains unclear. Methods: A well-established fMRI task was used to investigate neural activity during IA (heartbeat counting) and exteroceptive awareness (tone counting) in non-psychiatric controls (NC) and MDD. Firstly, comparing MDD and NC, a linear relationship between IA-related activity and scores of the Toronto Alexithymia Scale (TAS) was investigated through whole-brain regression. Secondly, NC were divided by median-split of TAS scores into groups showing low (NC-low) or high (NC-high) alexithymia. MDD and NC-high showed equally high TAS scores. Subsequently, IA-related neural activity was compared on a whole-brain level between the three independent samples (MDD, NC-low, NC-high). Results: Whole-brain regressions between MDD and NC revealed neural differences during IA as a function of TAS-DD (subscale difficulty describing feelings) in the supragenual anterior cingulate cortex (sACC; BA 24/32), which were due to negative associations between TAS-DD and IA-related activity in NC. Contrasting NC subgroups after median-split on a whole-brain level, high TAS scores were associated with decreased neural activity during IA in the sACC and increased insula activity. Though having equally high alexithymia scores, NC-high showed increased insula activity during IA compared to MDD, whilst both groups showed decreased activity in the sACC. Conclusions: Within the context of decreased sACC activity during IA in alexithymia (NC-high and MDD), increased insula activity might mirror a compensatory mechanism in NC-high, which is disrupted in MDD. PMID:26074827

Neuroimaging of decoding and language comprehension in young very low birth weight (VLBW) adolescents: Indications for compensatory mechanisms.

PubMed

van Ettinger-Veenstra, Helene; Widén, Carin; Engström, Maria; Karlsson, Thomas; Leijon, Ingemar; Nelson, Nina

2017-01-01

In preterm children with very low birth weight (VLBW ≤ 1500 g), reading problems are often observed. Reading comprehension is dependent on word decoding and language comprehension. We investigated neural activation-within brain regions important for reading-related to components of reading comprehension in young VLBW adolescents in direct comparison to normal birth weight (NBW) term-born peers, with the use of functional magnetic resonance imaging (fMRI). We hypothesized that the decoding mechanisms will be affected by VLBW, and expect to see increased neural activity for VLBW which may be modulated by task performance and cognitive ability. The study investigated 13 (11 included in fMRI) young adolescents (ages 12 to 14 years) born preterm with VLBW and in 13 NBW controls (ages 12-14 years) for performance on the Block Design and Vocabulary subtests of the Wechsler Intelligence Scale for Children; and for semantic, orthographic, and phonological processing during an fMRI paradigm. The VLBW group showed increased phonological activation in left inferior frontal gyrus, decreased orthographic activation in right supramarginal gyrus, and decreased semantic activation in left inferior frontal gyrus. Block Design was related to altered right-hemispheric activation, and VLBW showed lower WISC Block Design scores. Left angular gyrus showed activation increase specific for VLBW with high accuracy on the semantic test. Young VLBW adolescents showed no accuracy and reaction time performance differences on our fMRI language tasks, but they did exhibit altered neural activation during these tasks. This altered activation for VLBW was observed as increased activation during phonological decoding, and as mainly decreased activation during orthographic and semantic processing. Correlations of neural activation with accuracy on the semantic fMRI task and with decreased WISC Block Design performance were specific for the VLBW group. Together, results suggest compensatory mechanisms by recruiting additional brain regions upon altered neural development of decoding for VLBW.

Thermal signature analysis of human face during jogging activity using infrared thermography technique

NASA Astrophysics Data System (ADS)

Budiarti, Putria W.; Kusumawardhani, Apriani; Setijono, Heru

2016-11-01

Thermal imaging has been widely used for many applications. Thermal camera is used to measure object's temperature above absolute temperature of 0 Kelvin using infrared radiation emitted by the object. Thermal imaging is color mapping taken using false color that represents temperature. Human body is one of the objects that emits infrared radiation. Human infrared radiations vary according to the activity that is being done. Physical activities such as jogging is among ones that is commonly done. Therefore this experiment will investigate the thermal signature profile of jogging activity in human body, especially in the face parts. The results show that the significant increase is found in periorbital area that is near eyes and forehand by the number of 7.5%. Graphical temperature distributions show that all region, eyes, nose, cheeks, and chin at the temperature of 28.5 - 30.2°C the pixel area tends to be constant since it is the surrounding temperature. At the temperature of 30.2 - 34.7°C the pixel area tends to increase, while at the temperature of 34.7 - 37.1°C the pixel area tends to decrease because pixels at temperature of 34.7 - 37.1°C after jogging activity change into temperature of 30.2 - 34.7°C so that the pixel area increases. The trendline of jogging activity during 10 minutes period also shows the increasing of temperature. The results of each person also show variations due to physiological nature of each person, such as sweat production during physical activities.

Baicalin promotes the bacteriostatic activity of lysozyme on S. aureus in mammary glands and neutrophilic granulocytes in mice

PubMed Central

Zhang, Zecai; Shen, Peng; Yang, Zhengtao; Zhang, Naisheng

2017-01-01

Staphylococcus aureus causes mastitis as a result of community-acquired or nosocomial infections. Lysozyme (LYSO) is an enzyme that is upregulated in many organisms during the innate immune response against infection by bacterial pathogens. Baicalin is a bioactive flavonoid that can bind to enzymes, often to potentiate their effect. Here we tested the effects of baicalin on the activity of LYSO using the S. aureus mastitis mouse model and neutrophilic granulocyte model of S. aureus infection. In our experiments, S. aureus counts decreased with increasing baicalin concentration. Furthermore, qPCR and western blot analyses showed that LYSO expression was unaffected by baicalin, while fluorescence quenching and UV fluorescence spectral analyses showed that baicalin binds to LYSO. To test whether this binding increased LYSO activity, we assessed LYSO-induced bacteriostasis in the presence of baicalin. Our results showed that LYSO-induced S. aureus bacteriostasis increased with increasing concentrations of baicalin, and that baicalin binding to LYSO synergistically increased the antibacterial activity of LYSO. These results demonstrate that baicalin enhances LYSO-induced bacteriostasis during the innate immune response to S. aureus. They suggest baicalin is a potentially useful therapeutic agent for the treatment of bacterial infections. PMID:28184027

Catalytic properties of thermophilic lactate dehydrogenase and halophilic malate dehydrogenase at high temperature and low water activity.

PubMed

Hecht, K; Wrba, A; Jaenicke, R

1989-07-15

Thermophilic lactate dehydrogenases from Thermotoga maritima and Bacillus stearothermophilus are stable up to temperature limits close to the optimum growth temperature of their parent organisms. Their catalytic properties are anomalous in that Km shows a drastic increase with increasing temperature. At low temperatures, the effect levels off. Extreme halophilic malate dehydrogenase from Halobacterium marismortui exhibits a similar anomaly. Increasing salt concentration (NaCl) leads to an optimum curve for Km, oxaloacctate while Km, NADH remains constant. Previous claims that the activity of halophilic malate dehydrogenase shows a maximum at 1.25 M NaCl are caused by limiting substrate concentration; at substrate saturation, specific activity of halophilic malate dehydrogenase reaches a constant value at ionic strengths I greater than or equal to 1 M. Non-halophilic (mitochondrial) malate dehydrogenase shows Km characteristics similar to those observed for the halophilic enzyme. The drastic decrease in specific activity of the mitochondrial enzyme at elevated salt concentrations is caused by the salt-induced increase in rigidity of the enzyme, rather than gross structural changes.

Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment.

PubMed

Tran, Tammy T; Speck, Caroline L; Pisupati, Aparna; Gallagher, Michela; Bakker, Arnold

2017-01-01

Increased fMRI activation in the hippocampus is recognized as a signature characteristic of the amnestic mild cognitive impairment (aMCI) stage of Alzheimer's disease (AD). Previous work has localized this increased activation to the dentate gyrus/CA3 subregion of the hippocampus and showed a correlation with memory impairments in those patients. Increased hippocampal activation has also been reported in carriers of the ApoE-4 allelic variation independently of mild cognitive impairment although these findings were not localized to a hippocampal subregion. To assess the ApoE-4 contribution to increased hippocampal fMRI activation, patients with aMCI genotyped for ApoE-4 status and healthy age-matched control participants completed a high-resolution fMRI scan while performing a memory task designed to tax hippocampal subregion specific functions. Consistent with previous reports, patients with aMCI showed increased hippocampal activation in the left dentate gyrus/CA3 region of the hippocampus as well as memory task errors attributable to this subregion. However, this increased fMRI activation in the hippocampus did not differ between ApoE-4 carriers and ApoE-4 non-carriers and the proportion of memory errors attributable to dentate gyrus/CA3 function did not differ between ApoE-4 carriers and ApoE-4 non-carriers. These results indicate that increased fMRI activation of the hippocampus observed in patients with aMCI is independent of ApoE-4 status and that ApoE-4 does not contribute to the dysfunctional hippocampal activation or the memory errors attributable to this subregion in these patients.

Effects of aging on value-directed modulation of semantic network activity during verbal learning

PubMed Central

Cohen, Michael S.; Rissman, Jesse; Suthana, Nanthia A.; Castel, Alan D.; Knowlton, Barbara J.

2015-01-01

While impairments in memory recall are apparent in aging, older adults show a remarkably preserved ability to selectively remember information deemed valuable. Here, we use fMRI to compare brain activation in healthy older and younger adults during encoding of high and low value words to determine whether there are differences in how older adults achieve value-directed memory selectivity. We find that memory selectivity in older adults is associated with value-related changes in activation during word presentation in left hemisphere regions that are involved in semantic processing, similar to young adults. However, highly selective young adults show a relatively greater increase in semantic network activity during encoding of high-value items, whereas highly selective older adults show relatively diminished activity during encoding of low-value items. Additionally, only younger adults showed value-related increases in activity in semantic and reward processing regions during presentation of the value cue preceding each to-be-remembered word. Young adults therefore respond to cue value more proactively than do older adults, yet the magnitude of value-related differences in cue period brain activity did not predict individual differences in memory selectivity. Thus, our data also show that age-related reductions in prestimulus activity do not always lead to inefficient performance. PMID:26244278

Evolution of microglial activation in ischaemic core and peri-infarct regions after stroke: a PET study with the TSPO molecular imaging biomarker [((11))C]vinpocetine.

PubMed

Gulyás, Balázs; Tóth, Miklós; Schain, Martin; Airaksinen, Anu; Vas, Adám; Kostulas, Konstantinos; Lindström, Per; Hillert, Jan; Halldin, Christer

2012-09-15

Although there is increasing evidence for microglial activation after an ischaemic stroke in the infarct core and the peri-infarct region, the "evolution" of the process in stroke patients is poorly known. Using PET and [((11))C]vinpocetine, we measured the regional changes of TSPO in the brain of nine ischaemic stroke patients up to 14weeks after the insult. Already a week after stroke there was an increased radioligand uptake, indicating the up-regulation of TSPO and the presence of activated microglia, in both the ischaemic core and the peri-infarct zone. This increased activation showed a steady decrease with post stroke time. The proportion between %SUV values in the peri-infarct zone and the ischaemic core increased with time. There were no time-dependent TSPO activity changes in other regions, not affected directly by the stroke. The present observations demonstrate that increased regional microglia activation, as a consequence of stroke, can be visualised with PET, using the TSPO molecular imaging biomarker [((11))C]vinpocetine. The evolution of this microglial activation shows a time dependent decrease the gradient of which is different between the peri-infarct zone and the ischaemic core. The findings indicate an increased microglial activation in the peri-stroke region for several weeks after the insult. Copyright © 2012 Elsevier B.V. All rights reserved.

[Responses of antioxidation system of Cynodon dactylon to recirculated landfill leachate irrigation].

PubMed

Wang, Ruyi; He, Pinjing; Shao, Liming; Zhang, Bin; Li, Guojian

2005-05-01

With pot experiment, this paper studied the membrane lipid peroxidation and the variations of antioxidation system in Cynodon dactylon under recirculated landfill leachate irrigation. The results showed that when irrigated with low dilution ratio (< 25%) leachate, the chlorophyll a/b ratio increased with increasing dilution ratio, membrane permeability and MDA and H2O2 contents were in adverse, and membrane lipid peroxidation was relatively weak. However, with the increasing leachate dilution ratio (> 25%), there existed an obvious negative fect on Cynodon dactylon, i.e., the chlorophyll a/b ratio decreased, while cell membrane permeability and MDA and H2O2 contents increased, which meant that the membrane lipid peroxidation was accelerated. The contents antioxidants AsA, GSH and Car also showed the similar trend, i.e., they increased with increasing leachate dilution ratio when irrigated with low dilution ratio leachate, but decreased under medium or high dilution ratio leachate irrigation. Among three test anti-oxidative enzymes, SOD and POD activities showed a similar change test antioxidants, and POD activity was more sensitive, while CAT activity was on the contrary. The contents test antioxidants and the activities of SOD and POD were negatively and significantly correlated to MDA content, indicating that they might play an important role in preventing Cynodon dactylon from cell membrane lipid peroxdation.

Response-related fMRI of veridical and false recognition of words.

PubMed

Heun, Reinhard; Jessen, Frank; Klose, Uwe; Erb, Michael; Granath, Dirk-Oliver; Grodd, Wolfgang

2004-02-01

Studies on the relation between local cerebral activation and retrieval success usually compared high and low performance conditions, and thus showed performance-related activation of different brain areas. Only a few studies directly compared signal intensities of different response categories during retrieval. During verbal recognition, we recently observed increased parieto-occipital activation related to false alarms. The present study intends to replicate and extend this observation by investigating common and differential activation by veridical and false recognition. Fifteen healthy volunteers performed a verbal recognition paradigm using 160 learned target and 160 new distractor words. The subjects had to indicate whether they had learned the word before or not. Echo-planar MRI of blood-oxygen-level-dependent signal changes was performed during this recognition task. Words were classified post hoc according to the subjects' responses, i.e. hits, false alarms, correct rejections and misses. Response-related fMRI-analysis was used to compare activation associated with the subjects' recognition success, i.e. signal intensities related to the presentation of words were compared by the above-mentioned four response types. During recognition, all word categories showed increased bilateral activation of the inferior frontal gyrus, the inferior temporal gyrus, the occipital lobe and the brainstem in comparison with the control condition. Hits and false alarms activated several areas including the left medial and lateral parieto-occipital cortex in comparison with subjectively unknown items, i.e. correct rejections and misses. Hits showed more pronounced activation in the medial, false alarms in the lateral parts of the left parieto-occipital cortex. Veridical and false recognition show common as well as different areas of cerebral activation in the left parieto-occipital lobe: increased activation of the medial parietal cortex by hits may correspond to true recognition, increased activation of the parieto-occipital cortex by false alarms may correspond to familiarity decisions. Further studies are needed to investigate the reasons for false decisions in healthy subjects and patients with memory problems.

Mycoextraction by Clitocybe maxima combined with metal immobilization by biochar and activated carbon in an aged soil.

PubMed

Wu, Bin; Cheng, Guanglei; Jiao, Kai; Shi, Wenjin; Wang, Can; Xu, Heng

2016-08-15

To develop an eco-friendly and efficient route to remediate soil highly polluted with heavy metals, the idea of mycoextraction combined with metal immobilization by carbonaceous sorbents (biochar and activated carbon) was investigated in this study. Results showed that the application of carbonaceous amendments decreased acid soluble Cd and Cu by 5.13-14.06% and 26.86-49.58%, respectively, whereas the reducible and oxidizable fractions increased significantly as the amount of carbonaceous amendments added increased. The biological activities (microbial biomass, soil enzyme activities) for treatments with carbonaceous sorbents were higher than those of samples without carbonaceous amendments. Clitocybe maxima (C. maxima) simultaneously increased soil enzyme activities and the total number of microbes. Biochar and activated carbon both showed a positive effect on C. maxima growth and metal accumulation. The mycoextraction efficiency of Cd and Cu in treatments with carbonaceous amendments enhanced by 25.64-153.85% and 15.18-107.22%, respectively, in response to that in non-treated soil, which showed positive correlation to the augment of biochar and activated carbon in soil. Therefore, this work suggested the effectiveness of mycoextraction by C. maxima combined the application of biochar and activated carbon in immobilising heavy metal in contaminated soil. Copyright © 2016. Published by Elsevier B.V.

Deletion of creB in Aspergillus oryzae increases secreted hydrolytic enzyme activity.

PubMed

Hunter, A J; Morris, T A; Jin, B; Saint, C P; Kelly, J M

2013-09-01

Aspergillus oryzae has been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of an Aspergillus nidulans strain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show that Aspergillus oryzae contains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in both Aspergillus nidulans and Aspergillus oryzae are mirrored at the transcript level, indicating transcriptional regulation. We report that Aspergillus oryzae DAR3699, originally isolated from soy fermentation, has a similar phenotype to that of a creB deletion mutant of the RIB40 strain, and it contains a mutation in the creB gene. Collectively, the results for Aspergillus oryzae, Aspergillus nidulans, Trichoderma reesei, and Penicillium decumbens show that deletion of creB may be broadly useful in diverse fungi for increasing production of a variety of enzymes.

Deletion of creB in Aspergillus oryzae Increases Secreted Hydrolytic Enzyme Activity

PubMed Central

Hunter, A. J.; Morris, T. A.; Jin, B.; Saint, C. P.

2013-01-01

Aspergillus oryzae has been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of an Aspergillus nidulans strain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show that Aspergillus oryzae contains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in both Aspergillus nidulans and Aspergillus oryzae are mirrored at the transcript level, indicating transcriptional regulation. We report that Aspergillus oryzae DAR3699, originally isolated from soy fermentation, has a similar phenotype to that of a creB deletion mutant of the RIB40 strain, and it contains a mutation in the creB gene. Collectively, the results for Aspergillus oryzae, Aspergillus nidulans, Trichoderma reesei, and Penicillium decumbens show that deletion of creB may be broadly useful in diverse fungi for increasing production of a variety of enzymes. PMID:23835170

Hepatic and renal oxidative stress in acute toxicity of N-nitrosodiethylamine in rats.

PubMed

Bansal, A K; Trivedi, R; Soni, G L; Bhatnagar, D

2000-09-01

Nitrosoamines such as N-nitrosodiethylamine (NDEA) produce oxidative stress due to generation of reactive oxygen species and may alter antioxidant defence system in the tissues. NDEA was administered ip as a single dose to rats in LD50 or in lower amounts and the animals were sacrificed after 0-48 hr of treatment. The results showed that lipid peroxidation in liver increased, however no significant increase in kidney LPO was observed after NDEA administration. Superoxide dismutase (SOD) and glutathione reductase (GSH-R) activity increased in liver, however, catalase (CAT) activity in liver was inhibited in NDEA treated rats. Kidney showed an increase in SOD activity after an initial decrease along with increase in GSH-R activity in NDEA treated rats. However, kidney CAT activity was not significantly altered in NDEA intoxicated rats. Serum transaminases, serum alkaline phosphatase blood urea nitrogen, serum creatinine and scrum proteins were elevated in NDEA treated rats. The results indicate NDEA-induced oxidative stress and alteration in antioxidant enzymes in liver and kidney to neutralise oxidative stress.

Effects of heavy metal Cd pollution on microbial activities in soil.

PubMed

Shi, Weilin; Ma, Xiying

2017-12-23

Heavy metal contamination of soil occurs when heavy metals are introduced to soil through human activities, leading to the gradual deterioration of the ecology and environment. Microorganism activity reflects the intensity of various biochemical reactions in soil, and changes in it reflect the level of heavy metal pollution affecting the soil. The effects were studied of heavy metal Cd on the microbial activity of soil at different concentrations by investigating the respiratory intensity, urease activity, and catalase activity in forest soil and garden soil. The results showed that the respiratory intensity, urease and catalase activities in the garden soil were all higher than in the forest soil. Cd has obvious inhibitory effects on microbial activities. The three parameters exhibited a downward trend with increasing concentrations of Cd. Catalase activity increased when the mass concentration of Cd reached 1.0 mg/kg, indicating that low concentrations of Cd can promote the activity of some microorganisms. Respiratory intensity and urease activity also increased when the concentration reached 10.0 mg/kg, showing that respiratory intensity and urease activity have strong response mechanisms to adverse conditions. The effective state of Cd in soil, as well as inhibition of microbial activity, decreased with incubation time.

Ventromedial hypothalamic melanocortin receptor activation: regulation of activity energy expenditure and skeletal muscle thermogenesis.

PubMed

Gavini, Chaitanya K; Jones, William C; Novak, Colleen M

2016-09-15

The ventromedial hypothalamus (VMH) and the central melanocortin system both play vital roles in regulating energy balance by modulating energy intake and utilization. Recent evidence suggests that activation of the VMH alters skeletal muscle metabolism. We show that intra-VMH melanocortin receptor activation increases energy expenditure and physical activity, switches fuel utilization to fats, and lowers work efficiency such that excess calories are dissipated by skeletal muscle as heat. We also show that intra-VMH melanocortin receptor activation increases sympathetic nervous system outflow to skeletal muscle. Intra-VMH melanocortin receptor activation also induced significant changes in the expression of mediators of energy expenditure in muscle. These results support the role of melanocortin receptors in the VMH in the modulation of skeletal muscle metabolism. The ventromedial hypothalamus (VMH) and the brain melanocortin system both play vital roles in increasing energy expenditure (EE) and physical activity, decreasing appetite and modulating sympathetic nervous system (SNS) outflow. Because of recent evidence showing that VMH activation modulates skeletal muscle metabolism, we propose the existence of an axis between the VMH and skeletal muscle, modulated by brain melanocortins, modelled on the brain control of brown adipose tissue. Activation of melanocortin receptors in the VMH of rats using a non-specific agonist melanotan II (MTII), compared to vehicle, increased oxygen consumption and EE and decreased the respiratory exchange ratio. Intra-VMH MTII enhanced activity-related EE even when activity levels were held constant. MTII treatment increased gastrocnemius muscle heat dissipation during controlled activity, as well as in the home cage. Compared to vehicle-treated rats, rats with intra-VMH melanocortin receptor activation had higher skeletal muscle norepinephrine turnover, indicating an increased SNS drive to muscle. Lastly, intra-VMH MTII induced mRNA expression of muscle energetic mediators, whereas short-term changes at the protein level were primarily limited to phosphorylation events. These results support the hypothesis that melanocortin peptides act in the VMH to increase EE by lowering the economy of activity via the enhanced expression of mediators of EE in the periphery including skeletal muscle. The data are consistent with the role of melanocortins in the VMH in the modulation of skeletal muscle metabolism. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Antioxidant activities of methanol extract of Sambucus ebulus L. flower.

PubMed

Ebrahimzadeh, M A; Nabavi, S F; Nabavi, S M

2009-03-01

In this study antioxidant activity of methanol extract of Sambucus ebulus L. flower was investigated employing various in vitro assay systems, i.e., DPPH and nitric oxide radical scavenging, hydrogen peroxide scavenging, reducing power, iron ion chelating power and linoleic acid. IC50 for DPPH radical-scavenging activity was 228 +/- 12 microg mL(-1). The extract showed very high activity in the reducing power assay that was comparable with positive control, vitamin C. The extract showed good nitric oxide-scavenging activity (IC50 = 309 +/- 14 microg mL(-1). It was found that antioxidant activity was dose dependent i.e., activity was increased with the increase of their concentrations. The extract showed very weak activity in iron ion chelating (IC50 = 1.3 +/- 0.07 mg mL(-1)). It is showed very good activity in scavenging of hydrogen'peroxide. IC50 for scavenging of extract was 59.5 +/- 3.3 mcirog mL(-1). The extracts exhibited no activity in linoleic acid model. The total phenolic content of flower was 56.3 +/- 2.81 mg gallic acid equivalent g(-1) of extract powder and total flavonoid content was 14.5 +/- 0.72 mg quercetin equivalent g(-1) of extract powder by reference to standard curve.

Repression of GSK3 restores NK cell cytotoxicity in AML patients

PubMed Central

Parameswaran, Reshmi; Ramakrishnan, Parameswaran; Moreton, Stephen A.; Xia, Zhiqiang; Hou, Yongchun; Lee, Dean A.; Gupta, Kalpana; deLima, Marcos; Beck, Rose C.; Wald, David N.

2016-01-01

Natural killer cells from acute myeloid leukaemia patients (AML-NK) show a dramatic impairment in cytotoxic activity. The exact reasons for this dysfunction are not fully understood. Here we show that the glycogen synthase kinase beta (GSK3β) expression is elevated in AML-NK cells. Interestingly, GSK3 overexpression in normal NK cells impairs their ability to kill AML cells, while genetic or pharmacological GSK3 inactivation enhances their cytotoxic activity. Mechanistic studies reveal that the increased cytotoxic activity correlates with an increase in AML-NK cell conjugates. GSK3 inhibition promotes the conjugate formation by upregulating LFA expression on NK cells and by inducing ICAM-1 expression on AML cells. The latter is mediated by increased NF-κB activation in response to TNF-α production by NK cells. Finally, GSK3-inhibited NK cells show significant efficacy in human AML mouse models. Overall, our work provides mechanistic insights into the AML-NK dysfunction and a potential NK cell therapy strategy. PMID:27040177

Response of soil physicochemical properties and enzyme activities to long-term reclamation of coastal saline soil, Eastern China.

PubMed

Xie, Xuefeng; Pu, Lijie; Wang, Qiqi; Zhu, Ming; Xu, Yan; Zhang, Meng

2017-12-31

Soil enzyme activity during different years of reclamation and land use patterns could indicate changes in soil quality. The objective of this research is to explore the dynamics of 5 soil enzyme activities (dehydrogenase, amylase, urease, acid phosphatase and alkaline phosphatase) involved in C, N, and P cycling and their responses to changes in soil physicochemical properties resulting from long-term reclamation of coastal saline soil. Soil samples from a total of 55 sites were collected from a coastal reclamation area with different years of reclamation (0, 7, 32, 40, 63a) in this study. The results showed that both long-term reclamation and land use patterns have significant effects on soil physicochemical properties and enzyme activities. Compared with the bare flat, soil water content, soil bulk density, pH and electrical conductivity showed a decreasing trend after reclamation, whereas soil organic carbon, total nitrogen and total phosphorus tended to increase. Dehydrogenase, amylase and acid phosphatase activities initially increased and then decreased with increasing years of reclamation, whereas urease and alkaline phosphatase activities were characterized by an increase-decrease-increase trend. Moreover, urease, acid phosphatase and alkaline phosphatase activities exhibited significant differences between coastal saline soil with 63years of reclamation and bare flat, whereas dehydrogenase and amylase activities remained unchanged. Aquaculture ponds showed higher soil water content, pH and EC but lower soil organic carbon, total nitrogen and total phosphorus than rapeseed, broad bean and wheat fields. Rapeseed, broad bean and wheat fields displayed higher urease and alkaline phosphatase activities and lower dehydrogenase, amylase and acid phosphatase activities compared with aquaculture ponds. Redundancy analysis revealed that the soil physicochemical properties explained 74.5% of the variation in soil enzyme activities and that an obvious relationship existed between soil nutrients and soil enzyme activities. These results will assist governmental evaluation of the quality of reclaimed coastal soil. Copyright © 2017 Elsevier B.V. All rights reserved.

Fungus-mediated synthesis of silver nanoparticles and their activity against pathogenic fungi in combination with fluconazole.

PubMed

Gajbhiye, Monali; Kesharwani, Jayendra; Ingle, Avinash; Gade, Aniket; Rai, Mahendra

2009-12-01

Silver nanoparticles (Ag-NPs) are known to have inhibitory and bactericidal effects. Resistance of fungal infections has emerged in recent years and is a major health problem. Here, we report the extracellular biosynthesis of Ag-NPs using a common fungus, Alternaria alternata. Also in this study, these nanoparticles were evaluated for their part in increasing the antifungal activity of fluconazole against Phoma glomerata, Phoma herbarum, Fusarium semitectum, Trichoderma sp., and Candida albicans. The antifungal activity of fluconazole was enhanced against the test fungi in the presence of Ag-NPs. Fluconazole in combination with Ag-NPs showed the maximum inhibition against C. albicans, which was confirmed from the increase in fold area of inhibition, followed by P. glomerata and Trichoderma sp., which showed less increase in the fold area, whereas no significant enhancement of activity was found against P. herbarum and F. semitectum. The antifungal activity of fluconazole was enhanced in presence of silver nanoparticles against the test fungi. Fluconazole in combination with Ag-NPs showed the maximum inhibition against C. albicans, followed by P. glomerata and Trichoderma sp. No significant enhancement of activity was found against P. herbarum and F. semitectum.

Activity and Safety of Synthetic Lectins Based on Benzoboroxole-Functionalized Polymers for Inhibition of HIV Entry

PubMed Central

Mahalingam, Alamelu; Geonnotti, Anthony R.; Balzarini, Jan; Kiser, Patrick F.

2011-01-01

Lectins derived from plant and microbial sources constitute a vital class of entry inhibitors that target the oligomannose residues on the HIV envelope gp120. Despite their potency and specificity, success of lectin-based entry inhibitors may be impeded by issues in regards to economical production, formulation and potential mitogenicity. Therefore, there exists a gap in the HIV therapeutics pipeline that underscores the need for mass producible, synthetic, broad-spectrum, and biocomptabile inhibitors of HIV entry. Here, we present the development of a polymeric synthetic lectin, based on benzoboroxole (BzB), which exhibits weak affinity (~25 M−1) for non-reducing sugars, similar to those found on the HIV envelope. High molecular weight BzB-functionalized polymers demonstrated antiviral activity that increased with an increase in ligand density and molecular weight of the polymer construct; revealing that polyvalency improves activity. Polymers showed significant increase in activity from 25 to 75 mol% BzB functionalization with EC50 of 15 μM and 15 nM, respectively. A further increase in mole functionalization to 90% resulted in an increase of the EC50 (59 ± 5 nM), likely due to the elongated rigid structure of the polymer chain compelled by electrostatic repulsion between the boronic acid groups. An increase in molecular weight of the polymer at 50 mol% BzB functionalization showed a gradual but significant increase in antiviral activity, with the highest activity seen with the 382 kDa polymer (EC50 of 1.1 ± 0.5 nM in CEM cells and 11 ± 3 nM in TZM-bl cells). Supplementing the polymer backbone with 10 mol% sulfonic acid not only increased the aqueous solubility of the polymers by at least 50-fold, but also demonstrated a synergistic increase in anti-HIV activity (4.0 ± 1.5 nM in TZM-bl cells), possibly due to electrostatic interactions between the negatively charged polymer backbone and the positively charged V3-loop in the gp120. The benzoboroxole-sulfonic acid copolymers showed no decrease in activity in the presence of a seminal concentration of fructose (p > 0.05). Additionally, the co-polymers exhibit minimal, if any effect on the cellular viability, barrier properties, or cytokine levels in human reconstructed ecto-cervical tissue after 3 days of repeated exposure and did not show pronounced activity against a variety of other RNA and DNA viruses. PMID:21879735

Age-related increase in brain activity during task-related and -negative networks and numerical inductive reasoning.

PubMed

Sun, Li; Liang, Peipeng; Jia, Xiuqin; Qi, Zhigang; Li, Kuncheng

2014-01-01

Recent neuroimaging studies have shown that elderly adults exhibit increased and decreased activation on various cognitive tasks, yet little is known about age-related changes in inductive reasoning. To investigate the neural basis for the aging effect on inductive reasoning, 15 young and 15 elderly subjects performed numerical inductive reasoning while in a magnetic resonance (MR) scanner. Functional magnetic resonance imaging (fMRI) analysis revealed that numerical inductive reasoning, relative to rest, yielded multiple frontal, temporal, parietal, and some subcortical area activations for both age groups. In addition, the younger participants showed significant regions of task-induced deactivation, while no deactivation occurred in the elderly adults. Direct group comparisons showed that elderly adults exhibited greater activity in regions of task-related activation and areas showing task-induced deactivation (TID) in the younger group. Our findings suggest an age-related deficiency in neural function and resource allocation during inductive reasoning.

Recall versus familiarity when recall fails for words and scenes: The differential roles of the hippocampus, perirhinal cortex, and category-specific cortical regions☆

PubMed Central

Ryals, Anthony J.; Cleary, Anne M.; Seger, Carol A.

2013-01-01

This fMRI study examined recall and familiarity for words and scenes using the novel recognition without cued recall (RWCR) paradigm. Subjects performed a cued recall task in which half of the test cues resembled studied items (and thus were familiar) and half did not. Subjects also judged the familiarity of the cue itself. RWCR is the finding that, among cues for which recall fails, subjects generally rate cues that resemble studied items as more familiar than cues that do not. For words, left and right hippocampal activity increased when recall succeeded relative to when it failed. When recall failed, right hippocampal activity was decreased for familiar relative to unfamiliar cues. In contrast, right Prc activity increased for familiar cues for which recall failed relative to both familiar cues for which recall succeeded and to unfamiliar cues. For scenes, left hippocampal activity increased when recall succeeded relative to when it failed but did not differentiate familiar from unfamiliar cues when recall failed. In contrast, right Prc activity increased for familiar relative to unfamiliar cues when recall failed. Category-specific cortical regions showed effects unique to their respective stimulus types: The visual word form area (VWFA) showed effects for recall vs. familiarity specific to words, and the parahippocampal place area (PPA) showed effects for recall vs. familiarity specific to scenes. In both cases, these effects were such that there was increased activity occurring during recall relative to when recall failed, and decreased activity occurring for familiar relative to unfamiliar cues when recall failed. PMID:23142268

Effects of a tryptophan supplemented diet and U.V. radiation on the rat lens.

PubMed

Mathur, R L; Sahai, P

1990-01-01

Rats maintained on a tryptophan supplemented diet and exposed to U.V. radiation showed decreased concentration of ascorbic acid in serum. In the lens, a small increase in the urea-mercaptoethanol soluble fraction was observed suggesting some oxidation of P-SH groups. The decreased concentrations of lens glutathione and ascorbic acid were accompanied with increased concentration of malondialdehyde suggesting increased oxidative stress. The activities of glutathione peroxidase decreased by about 40%. Though the activity of glutathione reductase decreased by about 58%, addition of FAD in the enzyme assay system showed restoration of lost activity. Additive effect of raised serum tryptophan concentration and ultraviolet radiation in causing damage to the eye lens is suggested.

Dynamic Consequences of Mutation of Tryptophan 215 in Thrombin.

PubMed

Peacock, Riley B; Davis, Jessie R; Markwick, Phineus R L; Komives, Elizabeth A

2018-05-08

Thrombin normally cleaves fibrinogen to promote coagulation; however, binding of thrombomodulin to thrombin switches the specificity of thrombin toward protein C, triggering the anticoagulation pathway. The W215A thrombin mutant was reported to have decreased activity toward fibrinogen without significant loss of activity toward protein C. To understand how mutation of Trp215 may alter thrombin specificity, hydrogen-deuterium exchange experiments (HDXMS), accelerated molecular dynamics (AMD) simulations, and activity assays were carried out to compare the dynamics of Trp215 mutants with those of wild type (WT) thrombin. Variation in NaCl concentration had no detectable effect on the sodium-binding (220s CT ) loop, but appeared to affect other surface loops. Trp215 mutants showed significant increases in amide exchange in the 170s CT loop consistent with a loss of H-bonding in this loop identified by the AMD simulations. The W215A thrombin showed increased amide exchange in the 220s CT loop and in the N-terminus of the heavy chain. The AMD simulations showed that a transient conformation of the W215A thrombin has a distorted catalytic triad. HDXMS experiments revealed that mutation of Phe227, which engages in a π-stacking interaction with Trp215, also caused significantly increased amide exchange in the 170s CT loop. Activity assays showed that only the F227V mutant had wild type catalytic activity, whereas all other mutants showed markedly lower activity. Taken together, the results explain the reduced pro-coagulant activity of the W215A mutant and demonstrate the allosteric connection between Trp215, the sodium-binding loop, and the active site.

[Increase of physical activity by improvement of the nutritional status].

PubMed

Torún, B

1989-09-01

Physical activity is affected by nutritional modifications and, in turn, influences growth, cognition, social behavior, work performance and other functions. Studies in preschool children showed that: 1. A decrease in energy intake during four to seven days reduced the time allocated to energy-demanding activities and increased sedentary activities. 2. Children with mild weight deficit were more sedentary than well-nourished counterparts. 3. Children became more active when nutritional status improved. 4. A 10% reduction in energy intake reduced total energy expenditure by 15% without affecting weight gain nor basal metabolism. Studies of men working in non-mechanized agriculture showed that: 1. Dietary improvements led to faster salaried work, reduction of napping time and greater physical activity after work. 2. An increase in energy intake increased total daily energy expenditure, tending to maintain energy balance and relatively stable body weight within the cyclic variations of the agricultural year. 3. Food supplementation did not necessarily improve productivity. Other labor incentives without dietary improvements increased energy expenditure during working hours, which resulted in weight loss. In conclusion, good health and nutrition provide the biological basis for adequate physical activity that may improve cognitive development, social interactions, economic productivity and the quality of life of an individual or a population, but other incentives are required for the optimal expression of that biologic potential.

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

Tatsumi, Y.; Chachin, K.; Ogata, K.

The purpose of the experiment was to determine the changes of o- diphenol, ascorbic acid, and activities of polyphenol oxidase and peroxidase, accompanied with the browning by the low dose of gamma ray, in three parts of tuber tissue (cortex, vascular bundle, and pith), and to observe the relation between the browning and the changes of ihose compounds and enzyme activities. The odiphenol content increased in irradiated tabers and the increasing rate was greater in cortex and vascular bundle than in pith. The ascorbic acid content decreased with higher doses, and the decreasing rate was greater in cortex and vascularmore » bundle than in pith. The activities of polyphenol oxidase and peroxidase also increased in irradiated tubers. The activity of polyphenol oxidase increased more in cortex than in vascular bundle and pith and the activity of peroxidase increased more in vascular bundle than in cortex and pith. ln the potato tubers in which irradiation was conducted immediately after harvest, the browning was induced within several days after irradiation. However, in the potato tubers in which irradiation was conducted about 3 months, the browning did not occur after irradiation. The former showed the increase of o-diphenol content and the activities of these enzymes, and the decrease of ascorbic acid content, the latter did not show the changes of o-diphenol and ascorbic acid and activities of the enzymes. (auth)« less

An exploratory study of the effects of spatial working-memory load on prefrontal activation in low- and high-performing elderly.

PubMed

Vermeij, Anouk; van Beek, Arenda H E A; Reijs, Babette L R; Claassen, Jurgen A H R; Kessels, Roy P C

2014-01-01

Older adults show more bilateral prefrontal activation during cognitive performance than younger adults, who typically show unilateral activation. This over-recruitment has been interpreted as compensation for declining structure and function of the brain. Here we examined how the relationship between behavioral performance and prefrontal activation is modulated by different levels of working-memory load. Eighteen healthy older adults (70.8 ± 5.0 years; MMSE 29.3 ± 0.9) performed a spatial working-memory task (n-back). Oxygenated ([O2Hb]) and deoxygenated ([HHb]) hemoglobin concentration changes were registered by two functional Near-Infrared Spectroscopy (fNIRS) channels located over the left and right prefrontal cortex. Increased working-memory load resulted in worse performance compared to the control condition. [O2Hb] increased with rising working-memory load in both fNIRS channels. Based on the performance in the high working-memory load condition, the group was divided into low and high performers. A significant interaction effect of performance level and hemisphere on [O2Hb] increase was found, indicating that high performers were better able to keep the right prefrontal cortex engaged under high cognitive demand. Furthermore, in the low performers group, individuals with a larger decline in task performance from the control to the high working-memory load condition had a larger bilateral increase of [O2Hb]. The high performers did not show a correlation between performance decline and working-memory load related prefrontal activation changes. Thus, additional bilateral prefrontal activation in low performers did not necessarily result in better cognitive performance. Our study showed that bilateral prefrontal activation may not always be successfully compensatory. Individual behavioral performance should be taken into account to be able to distinguish successful and unsuccessful compensation or declined neural efficiency.

p75 Neurotrophin Receptor Signaling Activates Sterol Regulatory Element-binding Protein-2 in Hepatocyte Cells via p38 Mitogen-activated Protein Kinase and Caspase-3.

PubMed

Pham, Dan Duc; Do, Hai Thi; Bruelle, Céline; Kukkonen, Jyrki P; Eriksson, Ove; Mogollón, Isabel; Korhonen, Laura T; Arumäe, Urmas; Lindholm, Dan

2016-05-13

Nerve growth factor (NGF) influences the survival and differentiation of a specific population of neurons during development, but its role in non-neuronal cells has been less studied. We observed here that NGF and its pro-form, pro-NGF, are elevated in fatty livers from leptin-deficient mice compared with controls, concomitant with an increase in low density lipoprotein receptors (LDLRs). Stimulation of mouse primary hepatocytes with NGF or pro-NGF increased LDLR expression through the p75 neurotrophin receptor (p75NTR). Studies using Huh7 human hepatocyte cells showed that the neurotrophins activate the sterol regulatory element-binding protein-2 (SREBP2) that regulates genes involved in lipid metabolism. The mechanisms for this were related to stimulation of p38 mitogen-activated protein kinase (p38 MAPK) and activation of caspase-3 and SREBP2 cleavage following NGF and pro-NGF stimulations. Cell fractionation experiments showed that caspase-3 activity was increased particularly in the membrane fraction that harbors SREBP2 and caspase-2. Experiments showed further that caspase-2 interacts with pro-caspase-3 and that p38 MAPK reduced this interaction and caused caspase-3 activation. Because of the increased caspase-3 activity, the cells did not undergo cell death following p75NTR stimulation, possibly due to concomitant activation of nuclear factor-κB (NF-κB) pathway by the neurotrophins. These results identify a novel signaling pathway triggered by ligand-activated p75NTR that via p38 MAPK and caspase-3 mediate the activation of SREBP2. This pathway may regulate LDLRs and lipid uptake particularly after injury or during tissue inflammation accompanied by an increased production of growth factors, including NGF and pro-NGF. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The brain of opera singers: experience-dependent changes in functional activation.

PubMed

Kleber, B; Veit, R; Birbaumer, N; Gruzelier, J; Lotze, M

2010-05-01

Several studies have shown that motor-skill training over extended time periods results in reorganization of neural networks and changes in brain morphology. Yet, little is known about training-induced adaptive changes in the vocal system, which is largely subserved by intrinsic reflex mechanisms. We investigated highly accomplished opera singers, conservatory level vocal students, and laymen during overt singing of an Italian aria in a neuroimaging experiment. We provide the first evidence that the training of vocal skills is accompanied by increased functional activation of bilateral primary somatosensory cortex representing articulators and larynx. Opera singers showed additional activation in right primary sensorimotor cortex. Further training-related activation comprised the inferior parietal lobe and bilateral dorsolateral prefrontal cortex. At the subcortical level, expert singers showed increased activation in the basal ganglia, the thalamus, and the cerebellum. A regression analysis of functional activation with accumulated singing practice confirmed that vocal skills training correlates with increased activity of a cortical network for enhanced kinesthetic motor control and sensorimotor guidance together with increased involvement of implicit motor memory areas at the subcortical and cerebellar level. Our findings may have ramifications for both voice rehabilitation and deliberate practice of other implicit motor skills that require interoception.

[Response of soil hydrolase and oxidoreductase activities to free-air carbon dioxide enrichment (FACE) under rice-wheat rotation].

PubMed

Zhang, Yulan; Zhang, Lili; Chen, Lijun; Wu, Zhijie

2004-06-01

This paper studied the response of soil urease, phosphatase, arylsulphatase and dehydrogenase to 200 micromol x mol(-1) CO2 elevation under rice-wheat rotation. The results showed that under CO2 elevation, the urease activity in 0-10 cm soil layer was decreased at the early growth stages of wheat but increased at its booting stage; the activity increased at the early growth stages of rice but decreased at its ripening stage. Phosphatase activity was increased during the whole growth period of wheat; the activity increased at the tillering stage of rice but decreased at its later growth stages. Arylsulphatase activity was decreased at the over-wintering and booting stages of wheat but increased at its tillering and ripening stages. Dehydrogenase activity was decreased at the early growth stages of wheat and rice, but increased at their late growth stages.

dSir2 mediates the increased spontaneous physical activity in flies on calorie restriction.

PubMed

Parashar, Vijay; Rogina, Blanka

2009-06-22

Calorie restriction (CR) is the most effective way to increase life span and delay the onset of age-related symptoms in animals. We have previously reported that CR affects a variety of physiological phenotypes in flies and results in dramatic behavioral, physical and demographic changes. Here we show effects of low and high calorie levels on the spontaneous physical activity of flies. Wild type flies maintained on a low calorie diet exhibit higher spontaneous activity compared to flies on higher calorie diets. This increase is dependent on the presence of Sir2 since a low calorie diet does not increase the activity of dSir2 null flies. Similarly, increasing dSir2 activity by feeding flies resveratrol, a CR mimetic, increases spontaneous physical activity of flies on high caloric food. In Drosophila, spontaneous physical activity therefore closely mimics life span in its dependence on Sir2.

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

Do Inactive Older Adults who Increase Physical Activity Experience Less Disability: Evidence from the Osteoarthritis Initiative

PubMed Central

Song, Jing; Gilbert, Abigail L.; Chang, Rowland W.; Pellegrini, Christine A.; Ehrlich-Jones, Linda S.; Lee, Jungwha; Pinto, Daniel; Semanik, Pamela A.; Sharma, Leena; Kwoh, C. Kent; Jackson, Rebecca D.; Dunlop, Dorothy D.

2016-01-01

Background Physical inactivity is a leading risk factor for developing disability. Although randomized clinical trials have demonstrated improving physical activity can reduce this risk in older adults with arthritis, these studies did not specifically evaluate inactive adults. Objectives To evaluate the relationship of changes in physical activity with disability changes among initially inactive adults with or at high risk of knee OA from Osteoarthritis Initiative. Methods Inactive persons were identified at baseline based on the U.S. Department of Health and Human Services classification (no [zero] 10-minute session of moderate-to-vigorous activity over one week) from objective accelerometer monitoring. Two years later physical activity change status was classified as: (1) met Federal physical activity guidelines (≥150 moderate-to-vigorous minutes/week acquired in bouts ≥10 minutes), (2) insufficiently increased activity (some but <150 moderate-to-vigorous bout minutes/week) or (3) remained inactive. Disability at baseline and two years was assessed by Late Life Disability Instrument (LLDI) limitation and frequency scores. Multiple regression evaluated the relationship of physical activity change status with baseline-to-2 year changes in disability scores adjusting for socioeconomics, health factors, and baseline disability score. Results Increased physical activity showed a graded relationship with improved disability scores in LLDI limitation (P<0.001) and frequency scores (P=0.027). While increasing moderate-to-vigorous activity to guideline levels showed the greatest reduction, even insufficiently increased physical activity was related to reduced disability. Conclusions Findings support advice to increase moderate-to-vigorous physical activity to reduce disability among inactive adults with or at high risk for knee osteoarthritis, even when guidelines are not met. PMID:28002153

Increased active von Willebrand factor during disease development in the aging diabetic patient population.

PubMed

Chen, Shuang Feng; Xia, Zuo Li; Han, Ji Ju; Wang, Yi Ting; Wang, Ji Yue; Pan, Shao Dong; Wu, Ya Ping; Zhang, Bin; Li, Guang Yao; Du, Jing Wei; Gao, Hen Qiang; de Groot, Philip G; de Laat, Bas; Hollestelle, Martine J

2013-02-01

Type 2 diabetes is known to cause endothelial activation resulting in the secretion of von Willebrand factor (VWF). We have shown that levels of VWF in a glycoprotein Ib-binding conformation are increased in specific clinical settings. The aim of the current study is to investigate whether active VWF levels increase during aging and the development of diabetes within the population of patients suffering from type 2 diabetes. Patients and controls were divided into two groups based on age: older and younger than 60 years of age. VWF antigen, VWF propeptide, VWF activation factor and total active VWF were measured. Patients older than 60 years of age had increased levels of total active VWF, VWF activation factor and VWF propeptide compared to younger patients and controls. All measured VWF parameters were associated with age in diabetic patients. Total active VWF and VWF propeptide correlated with the period of being diagnosed with diabetes. Regression analyses showed that especially the VWF activation factor was strongly associated with diabetes in patients older than 60 years of age. In conclusion, we found that the conformation of VWF could be involved in the disease process of diabetes and that the VWF in a glycoprotein Ib-binding conformation could play a role as risk marker during the development of diabetes in combination with an increase in age. Our study shows that the active quality of VWF was more important than the quantity.

[The effect of UV-irradiation on telomerase activity and other stress-related proteins in human lens epithelial cells].

PubMed

Wu, Zhi-hong; Zhang, Jin-song

2005-05-01

To investigate the changes and the role of telomerase activity and other stress-related proteins in the process of UV-induced DNA damage and repair in human lens epithelial cells. Human lens epithelial cells were irradiated at UV-doses 0.0 (control group) and 0.5, 1.5, 2.5, 3.5, 5.0, 7.5, 10.0 mJ/cm(2) (treated 1-7 group). Telomerase activity was determined by Telomerase Repeat Amplification Protocol-Enzyme Linked Immunosorbent Assay (TRAP-ELISA), p53, growth arrest and DNA damage inducible (GADD45), proliferating cell nuclear antigen (PCNA) and p16 protein levels were analyzed by Western blotting. Telomerase activity in control group and treated 1-7 group showed increased tendency, the differences of telomerase activity in 8 groups were significantly (P < 0.01). The expression of p53, GADD45, PCNA, p16 proteins showed increased tendency in experimental group, comparing with the control group, there were significant difference (P < 0.01). During UV-induced DNA damage and repair in human lens epithelial cells, telomerase activity was upregulated and the expression of stress-related proteins levels was increased. Upregulated telomerase activity may play both a protective and a proliferative role in human lens epithelial cells. Increased stress-related proteins level is critic in UV-induced DNA damage and repair in human lens epithelial. Increased telomerase activity is associated with increased levels of the stress-related proteins.

τ kinases in the rat heat shock model: Possible implications for Alzheimer disease

PubMed Central

Shanavas, Alikunju; Papasozomenos, Sozos Ch.

2000-01-01

We have previously shown, by using the phosphate-dependent anti-τ antibodies Tau-1 and PHF-1, that heat shock induces rapid dephosphorylation of τ followed by hyperphosphorylation in female rats. In this study, we analyzed in forebrain homogenates from female Sprague–Dawley rats the activities of extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK), glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (Cdk5), cAMP-dependent protein kinase A (PKA), and Ca2+/calmodulin-dependent protein kinase II (CaMKII) at 0 (n = 5), 3 (n = 4), 6 (n = 5), and 12 (n = 5) h after heat shock and in non-heat-shocked controls (n = 5). Immunoprecipitation kinase assays at 0 h showed suppression of the activities of all kinases except of GSK-3β, which showed increased activity. At 3–6 h, the activities of ERK1/2, JNK, Cdk5, and GSK-3β toward selective substrates were increased; however, only JNK, Cdk5, and GSK-3β but not ERK1/2 were overactivated toward purified bovine τ. At 3–6 h, kinase assays specific for PKA and CaMKII showed no increased activity toward either τ or selective substrates. All of eight anti-τ antibodies tested showed dephosphorylation at 0 h and hyperphosphorylation at 3–6 h, except for 12E8, which showed hyperphosphorylation also at 0 h. Immunoblot analysis using activity-dependent antibodies against ERK1/2, JNK, and GSK-3β confirmed the above data. Increased activation and inhibition of kinases after heat shock were statistically significant in comparison with controls. Because τ is hyperphosphorylated in Alzheimer disease these findings suggest that JNK, GSK-3β, and Cdk5 may play a role in its pathogenesis. PMID:11121021

Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele.

PubMed

Anders, Silke; Sack, Benjamin; Pohl, Anna; Münte, Thomas; Pramstaller, Peter; Klein, Christine; Binkofski, Ferdinand

2012-04-01

Patients with Parkinson's disease suffer from significant motor impairments and accompanying cognitive and affective dysfunction due to progressive disturbances of basal ganglia-cortical gating loops. Parkinson's disease has a long presymptomatic stage, which indicates a substantial capacity of the human brain to compensate for dopaminergic nerve degeneration before clinical manifestation of the disease. Neuroimaging studies provide evidence that increased motor-related cortical activity can compensate for progressive dopaminergic nerve degeneration in carriers of a single mutant Parkin or PINK1 gene, who show a mild but significant reduction of dopamine metabolism in the basal ganglia in the complete absence of clinical motor signs. However, it is currently unknown whether similar compensatory mechanisms are effective in non-motor basal ganglia-cortical gating loops. Here, we ask whether asymptomatic Parkin mutation carriers show altered patterns of brain activity during processing of facial gestures, and whether this might compensate for latent facial emotion recognition deficits. Current theories in social neuroscience assume that execution and perception of facial gestures are linked by a special class of visuomotor neurons ('mirror neurons') in the ventrolateral premotor cortex/pars opercularis of the inferior frontal gyrus (Brodmann area 44/6). We hypothesized that asymptomatic Parkin mutation carriers would show increased activity in this area during processing of affective facial gestures, replicating the compensatory motor effects that have previously been observed in these individuals. Additionally, Parkin mutation carriers might show altered activity in other basal ganglia-cortical gating loops. Eight asymptomatic heterozygous Parkin mutation carriers and eight matched controls underwent functional magnetic resonance imaging and a subsequent facial emotion recognition task. As predicted, Parkin mutation carriers showed significantly stronger activity in the right ventrolateral premotor cortex during execution and perception of affective facial gestures than healthy controls. Furthermore, Parkin mutation carriers showed a slightly reduced ability to recognize facial emotions that was least severe in individuals who showed the strongest increase of ventrolateral premotor activity. In addition, Parkin mutation carriers showed a significantly weaker than normal increase of activity in the left lateral orbitofrontal cortex (inferior frontal gyrus pars orbitalis, Brodmann area 47), which was unrelated to facial emotion recognition ability. These findings are consistent with the hypothesis that compensatory activity in the ventrolateral premotor cortex during processing of affective facial gestures can reduce impairments in facial emotion recognition in subclinical Parkin mutation carriers. A breakdown of this compensatory mechanism might lead to the impairment of facial expressivity and facial emotion recognition observed in manifest Parkinson's disease.

Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele

PubMed Central

Sack, Benjamin; Pohl, Anna; Münte, Thomas; Pramstaller, Peter; Klein, Christine; Binkofski, Ferdinand

2012-01-01

Patients with Parkinson's disease suffer from significant motor impairments and accompanying cognitive and affective dysfunction due to progressive disturbances of basal ganglia–cortical gating loops. Parkinson's disease has a long presymptomatic stage, which indicates a substantial capacity of the human brain to compensate for dopaminergic nerve degeneration before clinical manifestation of the disease. Neuroimaging studies provide evidence that increased motor-related cortical activity can compensate for progressive dopaminergic nerve degeneration in carriers of a single mutant Parkin or PINK1 gene, who show a mild but significant reduction of dopamine metabolism in the basal ganglia in the complete absence of clinical motor signs. However, it is currently unknown whether similar compensatory mechanisms are effective in non-motor basal ganglia–cortical gating loops. Here, we ask whether asymptomatic Parkin mutation carriers show altered patterns of brain activity during processing of facial gestures, and whether this might compensate for latent facial emotion recognition deficits. Current theories in social neuroscience assume that execution and perception of facial gestures are linked by a special class of visuomotor neurons (‘mirror neurons’) in the ventrolateral premotor cortex/pars opercularis of the inferior frontal gyrus (Brodmann area 44/6). We hypothesized that asymptomatic Parkin mutation carriers would show increased activity in this area during processing of affective facial gestures, replicating the compensatory motor effects that have previously been observed in these individuals. Additionally, Parkin mutation carriers might show altered activity in other basal ganglia–cortical gating loops. Eight asymptomatic heterozygous Parkin mutation carriers and eight matched controls underwent functional magnetic resonance imaging and a subsequent facial emotion recognition task. As predicted, Parkin mutation carriers showed significantly stronger activity in the right ventrolateral premotor cortex during execution and perception of affective facial gestures than healthy controls. Furthermore, Parkin mutation carriers showed a slightly reduced ability to recognize facial emotions that was least severe in individuals who showed the strongest increase of ventrolateral premotor activity. In addition, Parkin mutation carriers showed a significantly weaker than normal increase of activity in the left lateral orbitofrontal cortex (inferior frontal gyrus pars orbitalis, Brodmann area 47), which was unrelated to facial emotion recognition ability. These findings are consistent with the hypothesis that compensatory activity in the ventrolateral premotor cortex during processing of affective facial gestures can reduce impairments in facial emotion recognition in subclinical Parkin mutation carriers. A breakdown of this compensatory mechanism might lead to the impairment of facial expressivity and facial emotion recognition observed in manifest Parkinson's disease. PMID:22434215

Temperature and population density effects on locomotor activity of Musca domestica (Diptera: Muscidae).

PubMed

Schou, T M; Faurby, S; Kjærsgaard, A; Pertoldi, C; Loeschcke, V; Hald, B; Bahrndorff, S

2013-12-01

The behavior of ectotherm organisms is affected by both abiotic and biotic factors. However, a limited number of studies have investigated the synergistic effects on behavioral traits. This study examined the effect of temperature and density on locomotor activity of Musca domestica (L.). Locomotor activity was measured for both sexes and at four densities (with mixed sexes) during a full light and dark (L:D) cycle at temperatures ranging from 10 to 40°C. Locomotor activity during daytime increased with temperature at all densities until reaching 30°C and then decreased. High-density treatments significantly reduced the locomotor activity per fly, except at 15°C. For both sexes, daytime activity also increased with temperature until reaching 30 and 35°C for males and females, respectively, and thereafter decreased. Furthermore, males showed a significantly higher and more predictable locomotor activity than females. During nighttime, locomotor activity was considerably lower for all treatments. Altogether the results of the current study show that there is a significant interaction of temperature and density on daytime locomotor activity of M. domestica and that houseflies are likely to show significant changes in locomotor activity with change in temperature.

Surface properties and graphitization of polyacrylonitrile based fiber electrodes affecting the negative half-cell reaction in vanadium redox flow batteries

NASA Astrophysics Data System (ADS)

Langner, J.; Bruns, M.; Dixon, D.; Nefedov, A.; Wöll, Ch.; Scheiba, F.; Ehrenberg, H.; Roth, C.; Melke, J.

2016-07-01

Carbon felt electrodes for vanadium redox flow batteries are obtained by the graphitization of polyacrylonitrile based felts at different temperatures. Subsequently, the surface of the felts is modified via thermal oxidation at various temperatures. A single-cell experiment shows that the voltage efficiency is increased by this treatment. Electrode potentials measured with reference electrode setup show that this voltage efficiency increase is caused mainly by a reduction of the overpotential of the negative half-cell reaction. Consequently, this reaction is investigated further by cyclic voltammetry and the electrode activity is correlated with structural and surface chemical properties of the carbon fibers. By Raman, X-ray photoelectron and near edge X-ray absorption fine structure spectroscopy the role of edge sites and oxygen containing functional groups (OCFs) for the electrochemical activity are elucidated. A significant activity increase is observed in correlation with these two characteristics. The amount of OCFs is correlated with structural defects (e.g. edge sites) of the carbon fibers and therefore decreases with an increasing graphitization degree. Thus, for the same thermal oxidation temperature carbon fibers graphitized at a lower temperature show higher activities than those graphitized at a higher temperature.

Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth

PubMed Central

Vornhagen, Jay; Quach, Phoenicia; Boldenow, Erica; Merillat, Sean; Whidbey, Christopher; Ngo, Lisa Y.; Adams Waldorf, K. M.

2016-01-01

ABSTRACT Preterm birth increases the risk of adverse birth outcomes and is the leading cause of neonatal mortality. A significant cause of preterm birth is in utero infection with vaginal microorganisms. These vaginal microorganisms are often recovered from the amniotic fluid of preterm birth cases. A vaginal microorganism frequently associated with preterm birth is group B streptococcus (GBS), or Streptococcus agalactiae. However, the molecular mechanisms underlying GBS ascension are poorly understood. Here, we describe the role of the GBS hyaluronidase in ascending infection and preterm birth. We show that clinical GBS strains associated with preterm labor or neonatal infections have increased hyaluronidase activity compared to commensal strains obtained from rectovaginal swabs of healthy women. Using a murine model of ascending infection, we show that hyaluronidase activity was associated with increased ascending GBS infection, preterm birth, and fetal demise. Interestingly, hyaluronidase activity reduced uterine inflammation but did not impact placental or fetal inflammation. Our study shows that hyaluronidase activity enables GBS to subvert uterine immune responses, leading to increased rates of ascending infection and preterm birth. These findings have important implications for the development of therapies to prevent in utero infection and preterm birth. PMID:27353757

AM fungal exudates activate MAP kinases in plant cells in dependence from cytosolic Ca(2+) increase.

PubMed

Francia, Doriana; Chiltz, Annick; Lo Schiavo, Fiorella; Pugin, Alain; Bonfante, Paola; Cardinale, Francesca

2011-09-01

The molecular dialogue occurring prior to direct contact between the fungal and plant partners of arbuscular-mycorrhizal (AM) symbioses begins with the release of fungal elicitors, so far only partially identified chemically, which can activate specific signaling pathways in the host plant. We show here that the activation of MAPK is also induced by exudates of germinating spores of Gigaspora margarita in cultured cells of the non-leguminous species tobacco (Nicotiana tabacum), as well as in those of the model legume Lotus japonicus. MAPK activity peaked about 15 min after the exposure of the host cells to the fungal exudates (FE). FE were also responsible for a rapid and transient increase in free cytosolic Ca(2+) in Nicotiana plumbaginifolia and tobacco cells, and pre-treatment with a Ca(2+)-channel blocker (La(3+)) showed that in these cells, MAPK activation was dependent on the cytosolic Ca(2+) increase. A partial dependence of MAPK activity on the common Sym pathway could be demonstrated for a cell line of L. japonicus defective for LjSym4 and hence unable to establish an AM symbiosis. Our results show that MAPK activation is triggered by an FE-induced cytosolic Ca(2+) transient, and that a Sym genetic determinant acts to modulate the intensity and duration of this activity. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

The Chromatin Assembly Factor Complex 1 (CAF1) and 5-Azacytidine (5-AzaC) Affect Cell Motility in Src-transformed Human Epithelial Cells.

PubMed

Endo, Akinori; Ly, Tony; Pippa, Raffaella; Bensaddek, Dalila; Nicolas, Armel; Lamond, Angus I

2017-01-06

Tumor invasion into surrounding stromal tissue is a hallmark of high grade, metastatic cancers. Oncogenic transformation of human epithelial cells in culture can be triggered by activation of v-Src kinase, resulting in increased cell motility, invasiveness, and tumorigenicity and provides a valuable model for studying how changes in gene expression cause cancer phenotypes. Here, we show that epithelial cells transformed by activated Src show increased levels of DNA methylation and that the methylation inhibitor 5-azacytidine (5-AzaC) potently blocks the increased cell motility and invasiveness induced by Src activation. A proteomic screen for chromatin regulators acting downstream of activated Src identified the replication-dependent histone chaperone CAF1 as an important factor for Src-mediated increased cell motility and invasion. We show that Src causes a 5-AzaC-sensitive decrease in both mRNA and protein levels of the p150 (CHAF1A) and p60 (CHAF1B), subunits of CAF1. Depletion of CAF1 in untransformed epithelial cells using siRNA was sufficient to recapitulate the increased motility and invasive phenotypes characteristic of transformed cells without activation of Src. Maintaining high levels of CAF1 by exogenous expression suppressed the increased cell motility and invasiveness phenotypes when Src was activated. These data identify a critical role of CAF1 in the dysregulation of cell invasion and motility phenotypes seen in transformed cells and also highlight an important role for epigenetic remodeling through DNA methylation for Src-mediated induction of cancer phenotypes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Higher Language Ability is Related to Angular Gyrus Activation Increase During Semantic Processing, Independent of Sentence Incongruency.

PubMed

Van Ettinger-Veenstra, Helene; McAllister, Anita; Lundberg, Peter; Karlsson, Thomas; Engström, Maria

2016-01-01

This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task-which tapped language comprehension and inference, and modulated sentence congruency-employing functional magnetic resonance imaging (fMRI). We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, there was a significant increase of activation in the inferior frontal gyrus (IFG) bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing, is opposed to what the neural efficiency hypothesis would predict. We can conclude that no evidence is found for an interaction between semantic congruency related brain activation and high-level language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation.

Higher Language Ability is Related to Angular Gyrus Activation Increase During Semantic Processing, Independent of Sentence Incongruency

PubMed Central

Van Ettinger-Veenstra, Helene; McAllister, Anita; Lundberg, Peter; Karlsson, Thomas; Engström, Maria

2016-01-01

This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task—which tapped language comprehension and inference, and modulated sentence congruency—employing functional magnetic resonance imaging (fMRI). We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, there was a significant increase of activation in the inferior frontal gyrus (IFG) bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing, is opposed to what the neural efficiency hypothesis would predict. We can conclude that no evidence is found for an interaction between semantic congruency related brain activation and high-level language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation. PMID:27014040

Recall versus familiarity when recall fails for words and scenes: the differential roles of the hippocampus, perirhinal cortex, and category-specific cortical regions.

PubMed

Ryals, Anthony J; Cleary, Anne M; Seger, Carol A

2013-01-25

This fMRI study examined recall and familiarity for words and scenes using the novel recognition without cued recall (RWCR) paradigm. Subjects performed a cued recall task in which half of the test cues resembled studied items (and thus were familiar) and half did not. Subjects also judged the familiarity of the cue itself. RWCR is the finding that, among cues for which recall fails, subjects generally rate cues that resemble studied items as more familiar than cues that do not. For words, left and right hippocampal activity increased when recall succeeded relative to when it failed. When recall failed, right hippocampal activity was decreased for familiar relative to unfamiliar cues. In contrast, right Prc activity increased for familiar cues for which recall failed relative to both familiar cues for which recall succeeded and to unfamiliar cues. For scenes, left hippocampal activity increased when recall succeeded relative to when it failed but did not differentiate familiar from unfamiliar cues when recall failed. In contrast, right Prc activity increased for familiar relative to unfamiliar cues when recall failed. Category-specific cortical regions showed effects unique to their respective stimulus types: The visual word form area (VWFA) showed effects for recall vs. familiarity specific to words, and the parahippocampal place area (PPA) showed effects for recall vs. familiarity specific to scenes. In both cases, these effects were such that there was increased activity occurring during recall relative to when recall failed, and decreased activity occurring for familiar relative to unfamiliar cues when recall failed. Copyright © 2012 Elsevier B.V. All rights reserved.

Activated protein C plays no major roles in the inhibition of coagulation or increased fibrinolysis in acute coagulopathy of trauma-shock: a systematic review.

PubMed

Gando, Satoshi; Mayumi, Toshihiko; Ukai, Tomohiko

2018-01-01

The pathophysiological mechanisms of acute coagulopathy of trauma-shock (ACOTS) are reported to include activated protein C-mediated suppression of thrombin generation via the proteolytic inactivation of activated Factor V (FVa) and FVIIIa; an increased fibrinolysis via neutralization of plasminogen activator inhibitor-1 (PAI-1) by activated protein C. The aims of this study are to review the evidences for the role of activated protein C in thrombin generation and fibrinolysis and to validate the diagnosis of ACOTS based on the activated protein C dynamics. We conducted systematic literature search (2007-2017) using PubMed, the Cochrane Database of Systematic Reviews (CDSR), and the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical studies on trauma that measured activated protein C or the circulating levels of activated protein C-related coagulation and fibrinolysis markers were included in our study. Out of 7613 studies, 17 clinical studies met the inclusion criteria. The levels of activated protein C in ACOTS were inconsistently decreased, showed no change, or were increased in comparison to the control groups. Irrespective of the activated protein C levels, thrombin generation was always preserved or highly elevated. There was no report on the activated protein C-mediated neutralization of PAI-1 with increased fibrinolysis. No included studies used unified diagnostic criteria to diagnose ACOTS and those studies also used different terms to refer to the condition known as ACOTS. None of the studies showed direct cause and effect relationships between activated protein C and the suppression of coagulation and increased fibrinolysis. No definitive diagnostic criteria or unified terminology have been established for ACOTS based on the activated protein C dynamics.

The changing face of emotion: age-related patterns of amygdala activation to salient faces.

PubMed

Todd, Rebecca M; Evans, Jennifer W; Morris, Drew; Lewis, Marc D; Taylor, Margot J

2011-01-01

The present study investigated age-related differences in the amygdala and other nodes of face-processing networks in response to facial expression and familiarity. fMRI data were analyzed from 31 children (3.5-8.5 years) and 14 young adults (18-33 years) who viewed pictures of familiar (mothers) and unfamiliar emotional faces. Results showed that amygdala activation for faces over a scrambled image baseline increased with age. Children, but not adults, showed greater amygdala activation to happy than angry faces; in addition, amygdala activation for angry faces increased with age. In keeping with growing evidence of a positivity bias in young children, our data suggest that children find happy faces to be more salient or meaningful than angry faces. Both children and adults showed preferential activation to mothers' over strangers' faces in a region of rostral anterior cingulate cortex associated with self-evaluation, suggesting that some nodes in frontal evaluative networks are active early in development. This study presents novel data on neural correlates of face processing in childhood and indicates that preferential amygdala activation for emotional expressions changes with age.

Polyamines and plant stress - Activation of putrescine biosynthesis by osmotic shock

NASA Technical Reports Server (NTRS)

Flores, H. E.; Galston, A. W.

1982-01-01

The putrescine content of oat leaf cells and protoplasts increases up to 60-fold within 6 hours of exposure to osmotic stress (0.4 to 0.6 molar sorbitol). Barley, corn, wheat, and wild oat leaves show a similar response. Increased arginine decarboxylase activity parallels the rise in putrescine, whereas ornithine decarboxylase remains unchanged. DL-alpha-Difluoromethylarginine, a specific irreversible inhibitor of arginine decarboxylase, prevents the stress-induced rise in increase in arginine decarboxylase activity and putrescine synthesis, indicating the preferential activation of this pathway.

The effects of DAT1 genotype on fMRI activation in an emotional go/no-go task.

PubMed

Brown, Brenna K; Murrell, Jill; Karne, Harish; Anand, Amit

2017-02-01

Dopaminergic brain circuits participate in emotional processing and impulsivity. The dopamine transporter (DAT) modulates dopamine reuptake. A variable number tandem repeat (VNTR) in the dopamine transporter gene (DAT1) affects DAT expression. The influence of DAT1 genotype on neural activation during emotional processing and impulse inhibition has not been examined. Forty-two healthy subjects were classified as 9DAT (n = 17) or 10DAT (n = 25) based on DAT1 genotype (9DAT = 9R/9R and 9R/10R; 10DAT = 10R/10R). Subjects underwent fMRI during non-emotional and emotional go/no-go tasks. Subjects were instructed to inhibit responses to letters, happy faces, or sad faces in separate blocks. Accuracy and reaction time did not differ between groups. Within group results showed activation in regions previously implicated in emotional processing and response inhibition. Between groups results showed increased activation in 9DAT individuals during inhibition. During letter inhibition, 9DAT individuals exhibited greater activation in right inferior parietal regions. During sad inhibition, 9DAT Individuals exhibited greater activation in frontal, posterior cingulate, precuneus, right cerebellar, left paracentral, and right occipital brain regions. The interaction between DAT genotype and response type in sad versus letter stimuli showed increased activation in 9DAT individuals during sad no-go responses in the anterior cingulate cortex, extending into frontal-orbital regions. 9DAT individuals have greater activation than 10DAT individuals during neutral and sad inhibition, showing that genotypic variation influencing basal dopamine levels can alter the neural basis of emotional processing and response inhibition. This may indicate that 9R carriers exert more effort to overcome increased basal dopamine activation when inhibiting responses in emotional contexts.

Altered olfactory processing and increased insula activity in patients with obsessive-compulsive disorder: an fMRI study

PubMed Central

Berlin, Heather A.; Stern, Emily R.; Ng, Johnny; Zhang, Sam; Rosenthal, David; Turetzky, Rachel; Tang, Cheuk; Goodman, Wayne

2017-01-01

Obsessive-compulsive disorder (OCD) patients show increased insula activation to disgust-inducing images compared to healthy controls (HC). We explored whether this disgust reactivity was also present in the olfactory domain by conducting the first fMRI study of olfaction in OCD. Neural activation in response to pleasant and unpleasant odors (vs. unscented air) was investigated in 15 OCD and 15 HC participants using fMRI. OCD participants (vs. HC) had increased left anterior insula activation to unpleasant odors (vs. unscented air), which positively correlated with their disgust sensitivity and ratings of the unpleasantness and intensity of those odors. OCD participants (vs. HC) showed increased activation of caudate nucleus and left anterior and posterior insula to pleasant odors (vs. unscented air), which positively correlated with their OCD symptom severity, trait anxiety, frequency of feeling disgust, and odor intensity ratings. OCD participants had increased anterior insula activation to both pleasant and unpleasant odors, which correlated with their OCD symptoms, anxiety, disgust sensitivity, and frequency of feeling disgust. OCD patients might have a negative cognitive bias and experience all stimuli, regardless of valence, as being more unpleasant than healthy people. These findings further elucidate the neural underpinnings of OCD and may contribute to more effective treatments. PMID:28208068

Protein kinase A is activated by the n–3 polyunsaturated fatty acid eicosapentaenoic acid in rat ventricular muscle

PubMed Central

Szentandrássy, Norbert; Pérez-Bido, M R; Alonzo, E; Negretti, N; O'Neill, Stephen C

2007-01-01

During cardiac ischaemia antiarrhythmic n–3 polyunsaturated fatty acids (PUFAs) are released following activation of phospholipase A2, if they are in the diet prior to ischaemia. Here we show a positive lusitropic effect of one such PUFA, eicosapentaenoic acid (EPA) in the antiarrhythmic concentration range in Langendorff hearts and isolated rat ventricular myocytes due to activation of protein kinase A (PKA). Several different approaches indicated activation of PKA by EPA (5–10 μmol l−1): the time constant of decay of the systolic Ca2+ transient decreased to 65.3 ± 5.0% of control, Western blot analysis showed a fourfold increase in phospholamban phosphorylation, and PKA activity increased by 21.0 ± 7.3%. In addition myofilament Ca2+ sensitivity was reduced in EPA; this too may have resulted from PKA activation. We also found that EPA inhibited L-type Ca2+ current by 38.7 ± 3.9% but this increased to 63.3 ± 3.4% in 10 μmol l−1 H89 (to inhibit PKA), providing further evidence of activation of PKA by EPA. PKA inhibition also prevented the lusitropic effect of EPA on the systolic Ca2+ transient and contraction. Our measurements show, however, PKA activation in EPA cannot be explained by increased cAMP levels and alternative mechanisms for PKA activation are discussed. The combined lusitropic effect and inhibition of contraction by EPA may, respectively, combat diastolic dysfunction in ischaemic cardiac muscle and promote cell survival by preserving ATP. This is a further level of protection for the heart in addition to the well-documented antiarrhythmic qualities of these fatty acids. PMID:17510185

Supporting Patient Behavior Change: Approaches Used by Primary Care Clinicians Whose Patients Have an Increase in Activation Levels.

PubMed

Greene, Jessica; Hibbard, Judith H; Alvarez, Carmen; Overton, Valerie

2016-03-01

We aimed to identify the strategies used to support patient behavior change by clinicians whose patients had an increase in patient activation. This mixed methods study was conducted in collaboration with Fairview Health Services, a Pioneer Accountable Care Organization. We aggregated data on the change in patient activation measure (PAM) score for 7,144 patients to the primary care clinician level. We conducted in-depth interviews with 10 clinicians whose patients' score increases were among the highest and 10 whose patients' score changes were among the lowest. Transcripts of the interviews were analyzed to identify key strategies that differentiated the clinicians whose patients had top PAM change scores. Clinicians whose patients had relatively large activation increases reported using 5 key strategies to support patient behavior change (mean = 3.9 strategies): emphasizing patient ownership; partnering with patients; identifying small steps; scheduling frequent follow-up visits to cheer successes, problem solve, or both; and showing caring and concern for patients. Clinicians whose patients had lesser change in activation were far less likely to describe using these approaches (mean = 1.3 strategies). Most clinicians, regardless of group, reported developing their own approach to support patient behavior change. Those whose patients showed high activation change reported spending more time with patients on counseling and education than did those whose patients showed less improvement in activation. Clinicians vary in the strategies they use to promote behavior change and in the time spent with patients on such activities. The 5 key strategies used by clinicians with high patient activation change are promising approaches to supporting patient behavior change that should be tested in a larger sample of clinicians to validate their effectiveness. © 2016 Annals of Family Medicine, Inc.

Normal vision can compensate for the loss of the circadian clock

PubMed Central

Schlichting, Matthias; Menegazzi, Pamela; Helfrich-Förster, Charlotte

2015-01-01

Circadian clocks are thought to be essential for timing the daily activity of animals, and consequently increase fitness. This view was recently challenged for clock-less fruit flies and mice that exhibited astonishingly normal activity rhythms under outdoor conditions. Compensatory mechanisms appear to enable even clock mutants to live a normal life in nature. Here, we show that gradual daily increases/decreases of light in the laboratory suffice to provoke normally timed sharp morning (M) and evening (E) activity peaks in clock-less flies. We also show that the compound eyes, but not Cryptochrome (CRY), mediate the precise timing of M and E peaks under natural-like conditions, as CRY-less flies do and eyeless flies do not show these sharp peaks independently of a functional clock. Nevertheless, the circadian clock appears critical for anticipating dusk, as well as for inhibiting sharp activity peaks during midnight. Clock-less flies only increase E activity after dusk and not before the beginning of dusk, and respond strongly to twilight exposure in the middle of the night. Furthermore, the circadian clock responds to natural-like light cycles, by slightly broadening Timeless (TIM) abundance in the clock neurons, and this effect is mediated by CRY. PMID:26378222

The Over-expression of the Plastidial Transglutaminase from Maize in Arabidopsis Increases the Activation Threshold of Photoprotection

PubMed Central

Ioannidis, Nikolaos E.; Malliarakis, Dimitris; Torné, Josep M.; Santos, Mireya; Kotzabasis, Kiriakos

2016-01-01

Plastidial transglutaminase is one of the most promising enzymes in chloroplast bioenergetics due to its link with polyamine pathways and the cross talk with signals such as Ca2+ and GTP. Here, we show the effect of the increase of transglutaminase activity in Arabidopsis by using genetic transformation techniques. These lines fulfill their biological cycle normally (normal growth in soil, production of viable seeds) and show a relatively mild increase in transglutaminase activity (127%). These overexpressors of transglutaminase (OE TGase) have an extended stroma thylakoid network (71% higher number of PSIIβ centers), similar chlorophyll content (-4%), higher linear electron flow (+13%), and higher threshold of photoprotection activation (∼100%). On the other hand OE TGase showed a reduced maximum photochemistry of PSII (-6.5%), a smaller antenna per photosystem II (-25%), a lower photoprotective “energization” quenching or qE (-77% at 490 μmol photons m-2 s-1) due to a higher threshold of qE activation and slightly lower light induced proton motive force (-17%). The role of the polyamines and of the transglutaminase in the regulation of chemiosmosis and photoprotection in chloroplasts is discussed. PMID:27242838

pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added phenolic antioxidants.

PubMed

Altunkaya, Arzu; Gökmen, Vural; Skibsted, Leif H

2016-01-01

Influence of pH on the antioxidant activities of combinations of lettuce extract (LE) with quercetin (QC), green tea extract (GTE) or grape seed extract (GSE) was investigated for both reduction of Fremy's salt in aqueous solution using direct electron spin resonance (ESR) spectroscopy and in L-α-phosphatidylcholine liposome peroxidation assay measured following formation of conjugated dienes. All examined phenolic antioxidants showed increasing radical scavenging effect with increasing pH values by using both methods. QC, GTE and GSE acted synergistically in combination with LE against oxidation of peroxidating liposomes and with QC showing the largest effect. The pH dependent increase of the antioxidant activity of the phenols is due to an increase of their electron-donating ability upon deprotonation and to their stabilization in alkaline solutions leading to polymerization reaction. Such polymerization reactions of polyphenolic antioxidants can form new oxidizable -OH moieties in their polymeric products resulting in a higher radical scavenging activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synaptic activity-related classical protein kinase C isoform localization in the adult rat neuromuscular synapse.

PubMed

Besalduch, Núria; Tomàs, Marta; Santafé, Manel M; Garcia, Neus; Tomàs, Josep; Lanuza, Maria Angel

2010-01-10

Protein kinase C (PKC) is essential for signal transduction in a variety of cells, including neurons and myocytes, and is involved in both acetylcholine release and muscle fiber contraction. Here, we demonstrate that the increases in synaptic activity by nerve stimulation couple PKC to transmitter release in the rat neuromuscular junction and increase the level of alpha, betaI, and betaII isoforms in the membrane when muscle contraction follows the stimulation. The phosphorylation activity of these classical PKCs also increases. It seems that the muscle has to contract in order to maintain or increase classical PKCs in the membrane. We use immunohistochemistry to show that PKCalpha and PKCbetaI were located in the nerve terminals, whereas PKCalpha and PKCbetaII were located in the postsynaptic and the Schwann cells. Stimulation and contraction do not change these cellular distributions, but our results show that the localization of classical PKC isoforms in the membrane is affected by synaptic activity.

Respiration in vitro: I. Spontaneous activity.

PubMed

Hamada, O; Garcia-Rill, E; Skinner, R D

1992-01-01

The present report describes respiratory-like activity recorded from intercostal muscles in the neonatal rat in vitro brain stem-spinal cord, rib-attached preparation. In this preparation from 1- to 4-day-old rats, spontaneous rhythmic and synchronized upward movements of the rib cage coincided with the recorded muscle activity. Spontaneous respiratory-like activity showed a frequency in the range of 0.05-0.2 Hz, with single-, double-, and mixed-burst patterns. Spontaneous activity declined over time, but increased in frequency as temperature increased. Multilevel recordings showed a cephalocaudal order of bursting of intercostal muscles. Brain stem transections at the prepontine level did not affect spontaneous frequency, whereas premedullary transections resulted in an increase in spontaneous respiratory frequency. High spinal transections eliminated spontaneous respiratory-like activity. These results suggest that there is a well-organized pontomedullary pattern generator for respiratory-like activity in this preparation, which can be modulated by temperature. The characteristics of these electromyographic (EMG) recordings allow comparison with previous in vitro studies of respiratory-like activity using nerve activity and in vivo studies using EMG activity. These results provide basic information on the spontaneous activity of this preparation as a prelude to the study of the effects of electrical stimulation of the spinal cord to induce respiratory-like activity, as described in the companion article.

Sports participation increased in Spain: a population-based time trend study of 21 381 adults in the years 2000, 2005 and 2010.

PubMed

Palacios-Ceña, Domingo; Fernandez-de-Las-Peñas, Cesar; Hernández-Barrera, Valentín; Jiménez-Garcia, Rodrigo; Alonso-Blanco, Cristina; Carrasco-Garrido, Pilar

2012-12-01

To assess the trend in prevalence of Spanish adults who engaged in sports activities from 2000 to 2010. Retrospective analysis of three population-based cross-sectional surveys conducted on a representative sample of Spanish adults: 2000 (N=5160), 2005 (N=8170) and 2010 (N=8925). The overall prevalence of sport-active men increased from 45.8% to 52.12% between 2000 and 2010. Among women the prevalence also increased from 27.26% to 33.27% (adjusted OR 1.03 95% CI 1.02 to 1.04). A significant decrease in the prevalence of sport-active subjects was found as the age increases. Adjusted time trends analysis showed that the prevalence of sport-active women and men increased over time in all age groups, with exception of women aged 15-25 years (adjusted OR 0.99, 0.97 to 1.01). Higher educational level was associated with more sport activity. The first reason for not practising sport was 'I have no time due to working or studying'. Less than 10% of women and men reported health problems as the reason for not practising any sport. Sports participation in Spain has increased between 2000 and 2010 among young-aged and middle-aged adults and decreased among older people. Women showed lower prevalence of sport activity as compared to men.

Phishing for suitable targets in the Netherlands: routine activity theory and phishing victimization.

PubMed

Leukfeldt, E Rutger

2014-08-01

This article investigates phishing victims, especially the increased or decreased risk of victimization, using data from a cybercrime victim survey in the Netherlands (n=10,316). Routine activity theory provides the theoretical perspective. According to routine activity theory, several factors influence the risk of victimization. A multivariate analysis was conducted to assess which factors actually lead to increased risk of victimization. The model included background and financial data of victims, their Internet activities, and the degree to which they were "digitally accessible" to an offender. The analysis showed that personal background and financial characteristics play no role in phishing victimization. Among eight Internet activities, only "targeted browsing" led to increased risk. As for accessibility, using popular operating systems and web browsers does not lead to greater risk, while having up-to-date antivirus software as a technically capable guardian has no effect. The analysis showed no one, clearly defined group has an increased chance of becoming a victim. Target hardening may help, but opportunities for prevention campaigns aimed at a specific target group or dangerous online activities are limited. Therefore, situational crime prevention will have to come from a different angle. Banks could play the role of capable guardian.

The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity

PubMed Central

Mhaske, Pallavi V.; Levit, Noah A.; Li, Leping; Wang, Hong-Zhan; Lee, Jack R.; Shuja, Zunaira; Brink, Peter R.

2013-01-01

Mutations in the human gene encoding connexin 26 (Cx26 or GJB2) cause either nonsyndromic deafness or syndromic deafness associated with skin diseases. That distinct clinical disorders can be caused by different mutations within the same gene suggests that different channel activities influence the ear and skin. Here we use three different expression systems to examine the functional characteristics of two Cx26 mutations causing either mild (Cx26-D50A) or lethal (Cx26-A88V) keratitis-ichthyosis-deafness (KID) syndrome. In either cRNA-injected Xenopus oocytes, transfected HeLa cells, or transfected primary human keratinocytes, we show that both Cx26-D50A and Cx26-A88V form active hemichannels that significantly increase membrane current flow compared with wild-type Cx26. This increased membrane current accelerated cell death in low extracellular calcium solutions and was not due to increased mutant protein expression. Elevated mutant hemichannel currents could be blocked by increased extracellular calcium concentration. These results show that these two mutations exhibit a shared gain of functional activity and support the hypothesis that increased hemichannel activity is a common feature of human Cx26 mutations responsible for KID syndrome. PMID:23447037

Antioxidant activity of fermented broccoli and spinach by Kombucha culture

NASA Astrophysics Data System (ADS)

Artanti, Nina; Susilowati, Agustine; Aspiyanto, Lotulung, Puspa Dewi Narrij; Maryati, Yati

2017-11-01

Broccoli (Brassica oleracea L.) and spinach (Amaranthus spp.) are vegetables that known to have many benefit for health. Previous studies on the fermentation of those vegetables using kombucha cultured showed increase in bioactive components such as total polyphenol content. The current studies was performed to evaluate the antioxidant activity of fermented spinach and broccoli before (feed) and after treatment with filtration (retentate and permeate). Filtration was conducted using Stirred Ultrafiltration Cell (SUFC) with UF membrane 100,000 MWCO mode at fixed condition (stirred rotation 300 rpm, room temperature, pressure 40 psia). Antioxidant evaluation was conducted using 2,2-diphenyl-1-picril hydrazyl (DPPH) free radical scavenging activity assay. The results showed that all samples from fermented broccoli showed antioxidant activity (feed 15.82% inhibition and retentate 15.29% inhibition), with the best antioxidant activity was obtained from permeate (75.98% inhibition). Whereas from fermented spinach only permeate showed antioxidant activity (21.84% inhibition) and it significantly lower than broccoli permeate. The mass spectrum of LCMS analysis on broccoli samples showed the present of several mass spectrum with (M+H) range from 148.1 to 442.5 in feed, retentate and permeate. In those samples (M+H) 360.4 always has the highest relative intensity. These results suggest that fermented broccoli has potential for development as functional drink for the source of antioxidant and the permeate obtained from filtration treatment significantly increased the antioxidant activity.

When transparency is opaque: Effects of diacritic marks and vowel letters on dyslexic Hebrew readers.

PubMed

Weiss, Yael; Katzir, Tami; Bitan, Tali

2016-10-01

The current study examined the effects of orthographic transparency and familiarity on brain mechanisms involved in word recognition in adult dyslexic Hebrew readers. We compared functional Magnetic Resonance Imaging (fMRI) brain activation in 21 dyslexic readers and 22 typical readers, and examined the effects of diacritic marks that provide transparent but less familiar information and vowel letters that increase orthographic transparency without compromising familiarity. Dyslexic readers demonstrated reduced activation in left supramarginal gyrus (SMG) as compared to typical readers, as well as different patterns of activation within the left inferior frontal gyrus (IFG). Furthermore, in contrast to typical readers, dyslexic readers did not show increased activation for diacritics in left temporo-parietal junction regions, associated with mapping orthography to phonology. Nevertheless, both groups showed the facilitation effect of vowel letters on regions associated with lexical-semantic access. Altogether the results suggest that while typical readers can compensate for the reduced familiarity of pointed words with increased reliance on decoding of smaller units, dyslexic readers do not, and therefore they show a higher cost. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation, characterization, nanostructures and bio functional analysis of sonicated protein co-precipitates from brewers' spent grain and soybean flour.

PubMed

Alu'datt, Muhammad H; Gammoh, Sana; Rababah, Taha; Almomani, Mohammed; Alhamad, Mohammad N; Ereifej, Khalil; Almajwal, Ali; Tahat, Asma; Hussein, Neveen M; Nasser, Sura Abou

2018-02-01

This investigation was performed to assess the effects of sonication on the structure of protein, extractability of phenolics, and biological properties of isolated proteins and protein co-precipitates prepared from brewers' spent grain and soybean flour. Scanning electron micrographs revealed that the sonicated protein isolates and co-precipitates had different microstructures with fewer aggregates and smaller particles down to the nanometer scale compared to non-sonicated samples. However, the levels of free and bound phenolics extracted from non-sonicated protein isolates and protein co-precipitates increased compared to sonicated samples. The bound phenolics extracted after acid hydrolysis of sonicated protein co-precipitates showed improved ACE inhibitory activity and diminished antioxidant potency compared to non-sonicated samples. However, the free phenolics extracted from sonicated protein co-precipitates showed decreased ACE inhibitory activity and increased antioxidant activities compared to non-sonicated samples. The free and bound phenolics extracted from sonicated protein co-precipitates showed increased alpha-amylase inhibitory activity compared to non-sonicated samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antihyperglycemic effect of syringaldehyde in streptozotocin-induced diabetic rats.

PubMed

Huang, Chia-Hsin; Chen, Mei-Fen; Chung, Hsien-Hui; Cheng, Juei-Tang

2012-08-24

The antihyperglycemic effect of syringaldehyde (1), purified from the stems of Hibiscus taiwanensis, was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats) showing type-1 like diabetes mellitus. Bolus intravenous injection of 1 showed antihyperglycemic activity in a dose-dependent manner in STZ-diabetic rats. An effective dose of 7.2 mg/kg of 1 attenuated significantly the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. A glucose uptake test showed that 1 exhibits an increase of glucose uptake activity in a concentration-related manner. Moreover, an effect by 1 was shown for insulin sensitivity in STZ-diabetic rats. The compound was found to increase insulin sensitivity in STZ-diabetic rats. These results suggest that syringaldehyde (1) can increase glucose utilization and insulin sensitivity to lower plasma glucose in diabetic rats.

Neutrophil activation during acetaminophen hepatotoxicity and repair in mice and humans

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

Williams, C. David; Bajt, Mary Lynn; Sharpe, Matthew R.

2014-03-01

Following acetaminophen (APAP) overdose there is an inflammatory response triggered by the release of cellular contents from necrotic hepatocytes into the systemic circulation which initiates the recruitment of neutrophils into the liver. It has been demonstrated that neutrophils do not contribute to APAP-induced liver injury, but their role and the role of NADPH oxidase in injury resolution are controversial. C57BL/6 mice were subjected to APAP overdose and neutrophil activation status was determined during liver injury and liver regeneration. Additionally, human APAP overdose patients (ALT: > 800 U/L) had serial blood draws during the injury and recovery phases for the determinationmore » of neutrophil activation. Neutrophils in the peripheral blood of mice showed an increasing activation status (CD11b expression and ROS priming) during and after the peak of injury but returned to baseline levels prior to complete injury resolution. Hepatic sequestered neutrophils showed an increased and sustained CD11b expression, but no ROS priming was observed. Confirming that NADPH oxidase is not critical to injury resolution, gp91{sup phox}−/− mice following APAP overdose displayed no alteration in injury resolution. Peripheral blood from APAP overdose patients also showed increased neutrophil activation status after the peak of liver injury and remained elevated until discharge from the hospital. In mice and humans, markers of activation, like ROS priming, were increased and sustained well after active liver injury had subsided. The similar findings between surviving patients and mice indicate that neutrophil activation may be a critical event for host defense or injury resolution following APAP overdose, but not a contributing factor to APAP-induced injury. - Highlights: • Neutrophil (PMN) function increases during liver repair after acetaminophen overdose. • Liver repair after acetaminophen (APAP)-overdose is not dependent on NADPH oxidase. • Human PMNs do not appear to contribute to acetaminophen (APAP)-induced injury. • Human PMNs have enhanced activation during the resolution of liver injury after APAP.« less

Solution Behavior and Activity of a Halophilic Esterase under High Salt Concentration

PubMed Central

Rao, Lang; Zhao, Xiubo; Pan, Fang; Li, Yin; Xue, Yanfen; Ma, Yanhe; Lu, Jian R.

2009-01-01

Background Halophiles are extremophiles that thrive in environments with very high concentrations of salt. Although the salt reliance and physiology of these extremophiles have been widely investigated, the molecular working mechanisms of their enzymes under salty conditions have been little explored. Methodology/Principal Findings A halophilic esterolytic enzyme LipC derived from archeaon Haloarcula marismortui was overexpressed from Escherichia coli BL21. The purified enzyme showed a range of hydrolytic activity towards the substrates of p-nitrophenyl esters with different alkyl chains (n = 2−16), with the highest activity being observed for p-nitrophenyl acetate, consistent with the basic character of an esterase. The optimal esterase activities were found to be at pH 9.5 and [NaCl] = 3.4 M or [KCl] = 3.0 M and at around 45°C. Interestingly, the hydrolysis activity showed a clear reversibility against changes in salt concentration. At the ambient temperature of 22°C, enzyme systems working under the optimal salt concentrations were very stable against time. Increase in temperature increased the activity but reduced its stability. Circular dichroism (CD), dynamic light scattering (DLS) and small angle neutron scattering (SANS) were deployed to determine the physical states of LipC in solution. As the salt concentration increased, DLS revealed substantial increase in aggregate sizes, but CD measurements revealed the maximal retention of the α-helical structure at the salt concentration matching the optimal activity. These observations were supported by SANS analysis that revealed the highest proportion of unimers and dimers around the optimal salt concentration, although the coexistent larger aggregates showed a trend of increasing size with salt concentration, consistent with the DLS data. Conclusions/Significance The solution α-helical structure and activity relation also matched the highest proportion of enzyme unimers and dimers. Given that all the solutions studied were structurally inhomogeneous, it is important for future work to understand how the LipC's solution aggregation affected its activity. PMID:19759821

Selenium/Tellurium-Containing Hyperbranched Polymers: Effect of Molecular Weight and Degree of Branching on Glutathione Peroxidase-Like Activity.

PubMed

Thomas, Joice; Dong, Zeyuan; Dehaen, Wim; Smet, Mario

2012-12-21

A series of novel hyperbranched polyselenides and polytellurides with multiple catalytic sites at the branching units has been synthesized via the polycondensation of A2 + B3 monomers. The GPx-like activities of these polymer mimics were assessed and it was found that the polytellurides showed higher GPx-like activities than the corresponding polyselenides. Interestingly, the polymers with higher molecular weights and degree of branching (DB) showed higher GPx-like activities than the analogous lower molecular weight polymer. The enhancement in the catalytical activity of the hyperbranched polymers with increasing molecular weight affirmed the importance of the incorporation of multiple catalytic groups in the macromolecule which increases the local concentration of catalytic sites. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Investigations on the effect of flavonoids from banana, Musa paradisiaca L. on lipid metabolism in rats.

PubMed

Vijayakumar, S; Presannakumar, G; Vijayalakshmi, N R

2009-01-01

Oral administration of flavonoids extracted from unripe fruits of Musa paradisiaca showed significant hypolipidemic activities in male rats (Sprague Dawley strain) at a dose of 1 mg/100 g body weight (BW)/day. Concentrations of cholesterol, phospholipids, free fatty acids, and triglycerides showed significant decrease in the serum, liver, kidney, and brain of experimental animals. HMG CoA reductase activity was found to be enhanced, while activities of glucose-6-phosphate dehydrogenase and malate dehydrogenase were significantly reduced. Activities of lipoprotein lipase and plasma LCAT showed significant enhancement. A significant increase in the concentrations of hepatic and fecal bile acids and fecal neutral sterols was also observed indicating a higher rate of degradation of cholesterol. The present study indicates that although there is an increase in the rate of synthesis of cholesterol in the liver, the process of degradation exceeds the rate of synthesis.

A Review of Psycho-Physiological Responses to Parabolic Flight

NASA Astrophysics Data System (ADS)

Brummer, Vera; Schneider, Stefan; Guardiera, Simon; Struder, Heiko K.

2008-06-01

This review combines and correlates data of several studies conducted in the recent years where we were able to show an increase in stress hormone concentrations, EEG activity and a decrease in mood during parabolic flights. The aim of these studies was to consider whether previous results showing a decrease in mental and perceptual motor performance during weightlessness were solely due to the changes in gravity itself or were also, at least partly, explainable by an increase of stress and/or arousal during parabolic flights. A correlation between stress hormones and mood but not between EEG activity and mood nor between stress hormones and EEG activity could be found. We propose two different stressors: First an activation of the adrenomedullary system, secondly a general increase of cortical arousal. Whereas the first one is perceived by subjects, this is not the case for the second one.

Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth.

PubMed

Vornhagen, Jay; Quach, Phoenicia; Boldenow, Erica; Merillat, Sean; Whidbey, Christopher; Ngo, Lisa Y; Adams Waldorf, K M; Rajagopal, Lakshmi

2016-06-28

Preterm birth increases the risk of adverse birth outcomes and is the leading cause of neonatal mortality. A significant cause of preterm birth is in utero infection with vaginal microorganisms. These vaginal microorganisms are often recovered from the amniotic fluid of preterm birth cases. A vaginal microorganism frequently associated with preterm birth is group B streptococcus (GBS), or Streptococcus agalactiae However, the molecular mechanisms underlying GBS ascension are poorly understood. Here, we describe the role of the GBS hyaluronidase in ascending infection and preterm birth. We show that clinical GBS strains associated with preterm labor or neonatal infections have increased hyaluronidase activity compared to commensal strains obtained from rectovaginal swabs of healthy women. Using a murine model of ascending infection, we show that hyaluronidase activity was associated with increased ascending GBS infection, preterm birth, and fetal demise. Interestingly, hyaluronidase activity reduced uterine inflammation but did not impact placental or fetal inflammation. Our study shows that hyaluronidase activity enables GBS to subvert uterine immune responses, leading to increased rates of ascending infection and preterm birth. These findings have important implications for the development of therapies to prevent in utero infection and preterm birth. GBS are a family of bacteria that frequently colonize the vagina of pregnant women. In some cases, GBS ascend from the vagina into the uterine space, leading to fetal injury and preterm birth. Unfortunately, little is known about the mechanisms underlying ascending GBS infection. In this study, we show that a GBS virulence factor, HylB, shows higher activity in strains isolated from cases of preterm birth than those isolates from rectovaginal swabs of healthy women. We discovered that GBS rely on HylB to avoid immune detection in uterine tissue, but not placental tissue, which leads to increased rates of fetal injury and preterm birth. These studies provide novel insight into the underlying mechanisms of ascending infection. Copyright © 2016 Vornhagen et al.

Evaluation of acetylcholinesterase in an animal model of maple syrup urine disease.

PubMed

Scaini, Giselli; de Rochi, Natália; Jeremias, Isabela C; Deroza, Pedro F; Zugno, Alexandra I; Pereira, Talita C B; Oliveira, Giovanna M T; Kist, Luiza W; Bogo, Maurício R; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

2012-04-01

Maple syrup urine disease is an inherited metabolic disease predominantly characterized by neurological dysfunction. However, the mechanisms underlying the neuropathology of this disease are still not defined. Therefore, the aim of this study was to investigate the effect of acute and chronic administration of a branched-chain amino acids (BCAA) pool (leucine, isoleucine, and valine) on acetylcholinesterase (AChE) activity and gene expression in the brain and serum of rats and to assess if antioxidant treatment prevented the alterations induced by BCAA administration. Our results show that the acute administration of a BCAA pool in 10- and 30-day-old rats increases AChE activity in the cerebral cortex, striatum, hippocampus, and serum. Moreover, chronic administration of the BCAA pool also increases AChE activity in the structures studied, and antioxidant treatment prevents this increase. In addition, we show a significant decrease in the mRNA expression of AChE in the hippocampus following acute administration in 10- and 30-day-old rats. On the other hand, AChE expression increased significantly after chronic administration of the BCAA pool. Interestingly, the antioxidant treatment was able to prevent the increased AChE activity without altering AChE expression. In conclusion, the results from the present study demonstrate a marked increase in AChE activity in all brain structures following the administration of a BCAA pool. Moreover, the increased AChE activity is prevented by the coadministration of N-acetylcysteine and deferoxamine as antioxidants.

Rapid activation of gill Na+,K+-ATPase in the euryhaline teleost Fundulus heteroclitus

USGS Publications Warehouse

Mancera, J.M.; McCormick, S.D.

2000-01-01

The rapid activation of gill Na+,K+-ATPase was analyzed in the mummichog (Fundulus heteroclitus) and Atlantic salmon (Salmo salar) transferred from low salinity (0.1 ppt) to high salinity (25-35 ppt). In parr and presmolt, Salmo salar gill Na+,K+-ATPase activity started to increase 3 days after transfer. Exposure of Fundulus heteroclitus to 35 ppt seawater (SW) induced a rise in gill Na+,K+-ATPase activity 3 hr after transfer. After 12 hr, the values dropped to initial levels but showed a second significant increase 3 days after transfer. The absence of detergent in the enzyme assay resulted in lower values of gill Na+,K+-ATPase, and the rapid increase after transfer to SW was not observed. Na+,K+-ATPase activity of gill filaments in vitro for 3 hr increased proportionally to the osmolality of the culture medium (600 mosm/kg > 500 mosm/kg > 300 mosm/kg). Osmolality of 800 mosm/kg resulted in lower gill Na+,K+-ATPase activity relative to 600 mosm/kg. Increasing medium osmolality to 600 mosm/kg with mannitol also increased gill Na+,K+-ATPase. Cycloheximide inhibited the increase in gill Na+,K+-ATPase activity observed in hyperosmotic medium in a dose-dependent manner (10-4 M > 10-5 M > 10-6 M). Actinomycin D or bumetanide in the culture (doses of 10-4 M, 10-5 M, and 10-6 M) did not affect gill Na+,K+-ATPase. Injection of fish with actinomycin D prior to gill organ culture, however, prevented the increase in gill Na+,K+-ATPase activity in hyperosmotic media. The results show a very rapid and transitory increase in gill Na+,K+-ATPase activity in the first hours after the transfer of Fundulus heteroclitus to SW that is dependent on translational and transcriptional processes. (C) 2000 Wiley-Liss, Inc.

ß-Lactoglobulin-chlorogenic acid conjugate-based nanoparticle for delivery of (-)-epigallocatechin-3-gallate

USDA-ARS?s Scientific Manuscript database

ß-Lactoglobulin (BLG)-chlorogenic acid (CA) conjugates were generated with a free radical induced grafting method. BLG-CA conjugates showed better antioxidant activities than that of BLG. The antioxidant activity increased with the increase of CA substitution. The particle sizes of (-)-epigallocatec...

Molecular Mechanisms of Prostate Cancer Progression

DTIC Science & Technology

2005-01-01

Beijersbergen RL, Knoll JH, Meyerson M, Weinberg RA (1999) Inhibition of telomerase limits the growth of human cancer cells. Nat Med 5:1164-70. Hayflick ...nontumorigenic cells and show an increase in p23 without a concomitant increase in telomerase activity, suggesting that p23 is not limiting in these cells...without an increase in assembly as chaperones are limiting . Interestingly, we observe a significant increase in activity after hTERT expression (see

Age-related increase in brain activity during task-related and -negative networks and numerical inductive reasoning

PubMed Central

Sun, Li; Liang, Peipeng; Jia, Xiuqin; Qi, Zhigang; Li, Kuncheng

2014-01-01

Objective: Recent neuroimaging studies have shown that elderly adults exhibit increased and decreased activation on various cognitive tasks, yet little is known about age-related changes in inductive reasoning. Methods: To investigate the neural basis for the aging effect on inductive reasoning, 15 young and 15 elderly subjects performed numerical inductive reasoning while in a magnetic resonance (MR) scanner. Results: Functional magnetic resonance imaging (fMRI) analysis revealed that numerical inductive reasoning, relative to rest, yielded multiple frontal, temporal, parietal, and some subcortical area activations for both age groups. In addition, the younger participants showed significant regions of task-induced deactivation, while no deactivation occurred in the elderly adults. Direct group comparisons showed that elderly adults exhibited greater activity in regions of task-related activation and areas showing task-induced deactivation (TID) in the younger group. Conclusions: Our findings suggest an age-related deficiency in neural function and resource allocation during inductive reasoning. PMID:25337240

Effect of uric acid on mitochondrial function and oxidative stress in hepatocytes.

PubMed

Yang, Y; Zhou, Y; Cheng, S; Sun, J L; Yao, H; Ma, L

2016-06-24

Here, we investigated the effect of uric acid (UA) on hepatocyte mitochondria. Hepatocytes cultured in vitro were treated with varying concentrations of UA. The change in apoptotic activity was detected by flow cytometry. The DNA damage index 8-hydroxy-deoxy-guanosine (8-OHdG) and mitochondrial function indices succinate dehydrogenase (SDH), cytochrome C oxidase (CCO), and adenosine triphosphate (ATP) were detected by enzyme assays. Reactive oxygen species (ROS) accumulation was confirmed by a dichloro-dihydro-fluorescein diacetate assay. We observed an increase in apoptotic activity, ROS accumulation, and 8-OHdG activity in hepatocytes treated with UA for extended periods, indicating DNA damage; specifically, we observed a significant increase in these activities 48, 72, and 96 h after UA addition, compared to those observed at 24 h (P < 0.05). Cells treated with 30 mg/dL UA for 96 h showed a peak in apoptotic activity. We also observed a significant decrease in ATP, SDH, and CCO activities with the increase in uric acid concentration over time. Cells treated with 30 mg/dL UA for 96 h showed the highest ATP levels, while SDH and CCO activities at 48, 72, and 96 h post-UA treatment were significantly lower than those at 24 h (P < 0.01). Moreover, cells treated with 30 mg/dL UA showed a 0.02 ± 0.02 and 0.15 ± 0.01 mmol/ mg/min decrease in SDH and CCO levels after 72 h. Therefore, we concluded that high concentrations of UA may induce oxidative stress in hepatocyte mitochondria, increasing ROS production and ultimately resulting in mitochondrial damage.

Promotion of beta-glucan synthase activity in corn microsomal membranes by calcium and protein phosphorylation

NASA Technical Reports Server (NTRS)

Paliyath, G.; Poovaiah, B. W.

1988-01-01

Regulation of the activity of beta-glucan synthase was studied using microsomal preparations from corn coleoptiles. The specific activity as measured by the incorporation of glucose from uridine diphospho-D-[U-14C]glucose varied between 5 to 15 pmol (mg protein)-1 min-1. Calcium promoted beta-glucan synthase activity and the promotion was observed at free calcium concentrations as low as 1 micromole. Kinetic analysis of substrate-velocity curve showed an apparent Km of 1.92 x 10(-4) M for UDPG. Calcium increased the Vmax from 5.88 x 10(-7) mol liter-1 min-1 in the absence of calcium to 9.52 x 10(-7) mol liter-1 min-1 and 1.66 x 10(-6) mol liter-1 min-1 in the presence of 0.5 mM and 1 mM calcium, respectively. The Km values remained the same under these conditions. Addition of ATP further increased the activity above the calcium-promoted level. Sodium fluoride, a phosphoprotein phosphatase inhibitor, promoted glucan synthase activity indicating that phosphorylation and dephosphorylation are involved in the regulation of the enzyme activity. Increasing the concentration of sodium fluoride from 0.25 mM to 10 mM increased glucan synthase activity five-fold over the + calcium + ATP control. Phosphorylation of membrane proteins also showed a similar increase under these conditions. Calmodulin, in the presence of calcium and ATP stimulated glucan synthase activity substantially, indicating that calmodulin could be involved in the calcium-dependent phosphorylation and promotion of beta-glucan synthase activity. The role of calcium in mediating auxin action is discussed.

A thermostable variant of fructose bisphosphate aldolase constructed by directed evolution also shows increased stability in organic solvents.

PubMed

Hao, Jijun; Berry, Alan

2004-09-01

Thermostable variants of the Class II fructose bisphosphate aldolase have been isolated following four rounds of directed evolution using DNA shuffling of the fda genes from Escherichia coli and Edwardsiella ictaluri. Variants from all four generations of evolution have been purified and characterized. The variants show increased thermostability with no loss of catalytic function at room temperature. The temperature at which 50% of the initial enzyme activity is lost after incubation for 10 min (T50) of the most stable variant, 4-43D6, is increased by 11-12 degrees C over the wild-type enzymes and the half-life of activity at 53 degrees C is increased approximately 190-fold. In addition, variant 4-43D6 shows increased stability to treatment with organic solvents. DNA sequencing of the evolved variants has identified the mutations which have been introduced and which lead to increased thermostability, and the role of the mutations introduced is discussed.

Nonlinear response of the anterior cingulate and prefrontal cortex in schizophrenia as a function of variable attentional control.

PubMed

Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Caforio, Grazia; Romano, Raffaella; Lobianco, Luciana; Fazio, Leonardo; Di Giorgio, Annabella; Latorre, Valeria; Sambataro, Fabio; Popolizio, Teresa; Nardini, Marcello; Mattay, Venkata S; Weinberger, Daniel R; Bertolino, Alessandro

2010-04-01

Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level-dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity.

Collective ratchet effects and reversals for active matter particles on quasi-one-dimensional asymmetric substrates.

PubMed

McDermott, Danielle; Olson Reichhardt, Cynthia J; Reichhardt, Charles

2016-10-19

Using computer simulations, we study a two-dimensional system of sterically interacting self-mobile run-and-tumble disk-shaped particles with an underlying periodic quasi-one-dimensional asymmetric substrate, and show that a rich variety of collective active ratchet behaviors arise as a function of particle density, activity, substrate period, and the maximum force exerted by the substrate. The net dc drift, or ratchet transport flux, is nonmonotonic since it increases with increased activity but is diminished by the onset of self-clustering of the active particles. Increasing the particle density decreases the ratchet transport flux for shallow substrates but increases the ratchet transport flux for deep substrates due to collective hopping events. At the highest particle densities, the ratchet motion is destroyed by a self-jamming effect. We show that it is possible to realize reversals of the direction of the net dc drift in the deep substrate limit when multiple rows of active particles can be confined in each substrate minimum, permitting emergent particle-like excitations to appear that experience an inverted effective substrate potential. We map out a phase diagram of the forward and reverse ratchet effects as a function of the particle density, activity, and substrate properties.

Sleep patterns during rearing under different environmental conditions in juvenile rats.

PubMed

Mirmiran, M; van den Dungen, H; Uylings, H B

1982-02-11

Male Wistar rats were chronically implanted at weaning with electrodes for recording EEG amd EMG. From one month of age, they were randomly assigned to either 24 h or 2 h daily 'enriched' (EC), 'standard' (SC) or 'isolated' (IC) rearing conditions. The 24 h-EC group showed the following changes with respect to both the SC and the IC groups: (a) more quiet sleep time; (b) more active sleep time, and (c) shorter active sleep latency. These differences were evident by the third week of environmental conditioning, became statistically significant by 4 weeks, and continued to increase throughout the rest of the enrichment period. None of the sleep parameters showed any significant differences between the SC and the IC groups. The 2 h-EC rats showed an increase in both quiet sleep and active sleep time during the experimental period, whereas the controls showed the expected decline. Morphological investigations at 3 months of age revealed a significant weight increase in the cerebral cortex, and even more so in the hypothalamus as compared with the control group in the 2 h-EC rats.

The postmitotic Saccharomyces cerevisiae after spaceflight showed higher viability

NASA Astrophysics Data System (ADS)

Yi, Zong-Chun; Li, Xiao-Fei; Wang, Yan; Wang, Jie; Sun, Yan; Zhuang, Feng-Yuan

2011-06-01

The budding yeast Saccharomyces cerevisiae has been proposed as an ideal model organism for clarifying the biological effects caused by spaceflight conditions. The postmitotic S. cerevisiae cells onboard Practice eight recoverable satellite were subjected to spaceflight for 15 days. After recovery, the viability, the glycogen content, the activities of carbohydrate metabolism enzymes, the DNA content and the lipid peroxidation level in yeast cells were analyzed. The viability of the postmitotic yeast cells after spaceflight showed a three-fold increase as compared with that of the ground control cells. Compared to the ground control cells, the lipid peroxidation level in the spaceflight yeast cells markedly decreased. The spaceflight yeast cells also showed an increase in G2/M cell population and a decrease in Sub-G1 cell population. The glycogen content and the activities of hexokinase and succinate dehydrogenase significantly decreased in the yeast cells after spaceflight. In contrast, the activity of malate dehydrogenase showed an obvious increase after spaceflight. These results suggested that microgravity or spaceflight could promote the survival of postmitotic S. cerevisiae cells through regulating carbohydrate metabolism, ROS level and cell cycle progression.

Characterization of resting state activity in MCI individuals

PubMed Central

Cieri, Filippo; Cera, Nicoletta

2013-01-01

Objectives. Aging is the major risk factor for Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). The aim of this study was to identify novel modifications of brain functional connectivity in MCI patients. MCI individuals were compared to healthy elderly subjects. Methods. We enrolled 37 subjects (age range 60–80 y.o.). Of these, 13 subjects were affected by MCI and 24 were age-matched healthy elderly control (HC). Subjects were evaluated with Mini Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and prose memory (Babcock story) tests. In addition, with functional Magnetic Resonance Imaging (fMRI), we investigated resting state network (RSN) activities. Resting state (Rs) fMRI data were analyzed by means of Independent Component Analysis (ICA). Subjects were followed-up with neuropsychological evaluations for three years. Results. Rs-fMRI of MCI subjects showed increased intrinsic connectivity in the Default Mode Network (DMN) and in the Somatomotor Network (SMN). Analysis of the DMN showed statistically significant increased activation in the posterior cingulate cortex (PCC) and left inferior parietal lobule (lIPL). During the three years follow-up, 4 MCI subjects converted to AD. The subset of MCI AD-converted patients showed increased connectivity in the right Inferior Parietal Lobule (rIPL). As for SMN activity, MCI and MCI-AD converted groups showed increased level of connectivity in correspondence of the right Supramarginal Gyrus (rSG). Conclusions. Our findings indicate alterations of DMN and SMN activity in MCI subjects, thereby providing potential imaging-based markers that can be helpful for the early diagnosis and monitoring of these patients. PMID:24010015

Sex differences in brain cholinergic activity in MSG-obese rats submitted to exercise.

PubMed

Sagae, Sara Cristina; Grassiolli, Sabrina; Raineki, Charlis; Balbo, Sandra Lucinei; Marques da Silva, Ana Carla

2011-11-01

Obesity is an epidemic disease most commonly caused by a combination of increased energy intake and lack of physical activity. The cholinergic system has been shown to be involved in the regulation of food intake and energy expenditure. Moreover, physical exercise promotes a reduction of fat pads and body mass by increasing energy expenditure, but also influences the cholinergic system. The aim of this study is to evaluate the interaction between physical exercise (swimming) and central cholinergic activity in rats treated with monosodium glutamate (MSG, a model for obesity) during infancy. Our results show that MSG treatment is able to induce obesity in male and female rats. Specifically, MSG-treated rats presented a reduced body mass and nasoanal length, and increased perigonadal and retroperitoneal fat pads in relation to the body mass. Physical exercise was able to reduce body mass in both male and female rats, but did not change the fat pads in MSG-treated rats. Increased food intake was only seen in MSG-treated females submitted to exercise. Cholinergic activity was increased in the cortex of MSG-treated females and physical exercise was able to reduce this activity. Thalamic cholinergic activity was higher in sedentary MSG-treated females and exercised MSG-treated males. Hypothalamic cholinergic activity was higher in male and female MSG-treated rats, and was not reduced by exercise in the 2 sexes. Taken together, these results show that MSG treatment and physical exercise have different effects in the cholinergic activity of males and females.

Altered olfactory processing of stress-related body odors and artificial odors in patients with panic disorder.

PubMed

Wintermann, Gloria-Beatrice; Donix, Markus; Joraschky, Peter; Gerber, Johannes; Petrowski, Katja

2013-01-01

Patients with Panic Disorder (PD) direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD. A sample of 13 patients with PD with/ without agoraphobia and 13 age- and gender-matched healthy controls underwent an fMRI investigation during olfactory stimulation with their stress-related sweat odors (TSST, ergometry) as well as artificial odors (peach, artificial sweat) as non-fearful non-body odors. The two groups did not differ with respect to their olfactory identification ability. Independent of the kind of odor, the patients with PD showed activations in fronto-cortical areas in contrast to the healthy controls who showed activations in olfaction-related areas such as the amygdalae and the hippocampus. For artificial odors, the patients with PD showed a decreased neuronal activation of the thalamus, the posterior cingulate cortex and the anterior cingulate cortex. Under the presentation of sweat odor caused by ergometric exercise, the patients with PD showed an increased activation in the superior temporal gyrus, the supramarginal gyrus, and the cingulate cortex which was positively correlated with the severity of the psychopathology. For the sweat odor from the anxiety condition, the patients with PD showed an increased activation in the gyrus frontalis inferior, which was positively correlated with the severity of the psychopathology. The results suggest altered neuronal processing of olfactory stimuli in PD. Both artificial odors and stress-related body odors activate specific parts of a fear-network which is associated with an increased severity of the psychopathology.

Capacitance enhancement of polyaniline coated curved-graphene supercapacitors in a redox-active electrolyte

NASA Astrophysics Data System (ADS)

Chen, Wei; Rakhi, R. B.; Alshareef, H. N.

2013-05-01

We show, for the first time, a redox-active electrolyte in combination with a polyaniline-coated curved graphene active material to achieve significant enhancement in the capacitance (36-92% increase) compared to supercapacitors that lack the redox-active contribution from the electrolyte. The supercapacitors based on the redox-active electrolyte also exhibit excellent rate capability and very long cycling performance (>50 000 cycles).We show, for the first time, a redox-active electrolyte in combination with a polyaniline-coated curved graphene active material to achieve significant enhancement in the capacitance (36-92% increase) compared to supercapacitors that lack the redox-active contribution from the electrolyte. The supercapacitors based on the redox-active electrolyte also exhibit excellent rate capability and very long cycling performance (>50 000 cycles). Electronic supplementary information (ESI) available: Experimental section, supporting figures including SEM, TEM, XPS, BET, CV and CD curves and a summary table of capacitance. See DOI: 10.1039/c3nr00773a

Always on guard: emotion regulation in women with borderline personality disorder compared to nonpatient controls and patients with cluster-C personality disorder

PubMed Central

van Zutphen, Linda; Siep, Nicolette; Jacob, Gitta A.; Domes, Gregor; Sprenger, Andreas; Willenborg, Bastian; Goebel, Rainer; Arntz, Arnoud

2018-01-01

Background Borderline personality disorder (BPD) is characterized by emotion dysregulation; however, it is unclear whether this is restricted to negative emotional stimuli or to what degree this is specific to BPD. We investigated neural correlates of hypothesized increased emotional sensitivity and impaired emotion regulation in patients with BPD. Methods During functional MRI (fMRI) scanning, patients with BPD, non-patient controls and patients with cluster-C personality disorder completed an emotion regulation task, including negative, positive and erotic social pictures. Results We included 55 patients with BPD, 42 nonpatient controls and 24 patients with cluster-C personality disorder in our analyses. Passive viewing of negative stimuli resulted in greater activity in the anterior insula, temporoparietal junction and dorsolateral prefrontal cortex in patients with BPD than in nonpatient controls. The increased activity in the anterior insula and temporoparietal junction was also present when patients with BPD viewed positive stimuli. During regulation of negative stimuli compared with passive viewing, nonpatient controls showed greater activity in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, middle temporal gyrus and bilateral inferior parietal lobule. Patients with BPD did not show this increase in activity. Limitations Findings cannot be generalized to men, and patients represented a heterogeneous group regarding comorbid diagnoses and medication. Conclusion When looking at emotional stimuli, patients with BPD showed a unique pattern of activity, suggesting an increase in brain activity involved in emotion generation. In the case of negative stimuli this is accompanied by increased activity in regulation areas. In contrast, increase of regulation processes seems absent when patients with BPD are explicitly instructed to regulate. Results of diagnosis specificity support a dimensional rather than a dichotomous differentiation between BPD and cluster-C personality disorder regarding emotional sensitivity and emotional regulation of social stimuli. PMID:29252164

High Glucose Forces a Positive Feedback Loop Connecting Akt Kinase and FoxO1 Transcription Factor to Activate mTORC1 Kinase for Mesangial Cell Hypertrophy and Matrix Protein Expression*

PubMed Central

Das, Falguni; Ghosh-Choudhury, Nandini; Dey, Nirmalya; Bera, Amit; Mariappan, Meenalakshmi M.; Kasinath, Balakuntalam S.; Ghosh Choudhury, Goutam

2014-01-01

High glucose-induced Akt acts as a signaling hub for mesangial cell hypertrophy and matrix expansion, which are recognized as cardinal signatures for the development of diabetic nephropathy. How mesangial cells sustain the activated state of Akt is not clearly understood. Here we show Akt-dependent phosphorylation of the transcription factor FoxO1 by high glucose. Phosphorylation-deficient, constitutively active FoxO1 inhibited the high glucose-induced phosphorylation of Akt to suppress the phosphorylation/inactivation of PRAS40 and mTORC1 activity. In contrast, dominant negative FoxO1 increased the phosphorylation of Akt, resulting in increased mTORC1 activity similar to high glucose treatment. Notably, FoxO1 regulates high glucose-induced protein synthesis, hypertrophy, and expression of fibronectin and PAI-1. High glucose paves the way for complications of diabetic nephropathy through the production of reactive oxygen species (ROS). We considered whether the FoxO1 target antioxidant enzyme catalase contributes to sustained activation of Akt. High glucose-inactivated FoxO1 decreases the expression of catalase to increase the production of ROS. Moreover, we show that catalase blocks high glucose-stimulated Akt phosphorylation to attenuate the inactivation of FoxO1 and PRAS40, resulting in the inhibition of mTORC1 and mesangial cell hypertrophy and fibronectin and PAI-1 expression. Finally, using kidney cortices from type 1 diabetic OVE26 mice, we show that increased FoxO1 phosphorylation is associated with decreased catalase expression and increased fibronectin and PAI-1 expression. Together, our results provide the first evidence for the presence of a positive feedback loop for the sustained activation of Akt involving inactivated FoxO1 and a decrease in catalase expression, leading to increased ROS and mesangial cell hypertrophy and matrix protein expression. PMID:25288788

Primary alcohols activate human TRPA1 channel in a carbon chain length-dependent manner.

PubMed

Komatsu, Tomoko; Uchida, Kunitoshi; Fujita, Fumitaka; Zhou, Yiming; Tominaga, Makoto

2012-04-01

Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel that is mainly expressed in primary nociceptive neurons. TRPA1 is activated by a variety of noxious stimuli, including cold temperatures, pungent compounds such as mustard oil and cinnamaldehyde, and intracellular alkalization. Here, we show that primary alcohols, which have been reported to cause skin, eye or nasal irritation, activate human TRPA1 (hTRPA1). We measured intracellular Ca(2+) changes in HEK293 cells expressing hTRPA1 induced by 1 mM primary alcohols. Higher alcohols (1-butanol to 1-octanol) showed Ca(2+) increases proportional to the carbon chain length. In whole-cell patch-clamp recordings, higher alcohols (1-hexanol to 1-octanol) activated hTRPA1 and the potency increased with the carbon chain length. Higher alcohols evoked single-channel opening of hTRPA1 in an inside-out configuration. In addition, cysteine at 665 in the N terminus and histidine at 983 in the C terminus were important for hTRPA1 activation by primary alcohols. Furthermore, straight-chain secondary alcohols increased intracellular Ca(2+) concentrations in HEK293 cells expressing hTRPA1, and both primary and secondary alcohols showed hTRPA1 activation activities that correlated highly with their octanol/water partition coefficients. On the other hand, mouse TRPA1 did not show a strong response to 1-hexanol or 1-octanol, nor did these alcohols evoke significant pain in mice. We conclude that primary and secondary alcohols activate hTRPA1 in a carbon chain length-dependent manner. TRPA1 could be a sensor of alcohols inducing skin, eye and nasal irritation in human.

Cadmium induction of lipid peroxidation and effects on root tip cells and antioxidant enzyme activities in Vicia faba L.

PubMed

Zhang, Shanshan; Zhang, Huimin; Qin, Rong; Jiang, Wusheng; Liu, Donghua

2009-10-01

The effects of different concentrations (1-50 microM) of Cd on root growth, cell division and nucleoli in root tip cells, protective enzyme activities and lipid peroxidation in Vicia faba were investigated in order to better understand the processes of Cd-induced senescence. The results indicated that lower concentration of Cd (1 microM) had no obviously influence on the root growth during 24-48 h treatment, but higher concentrations (5-50 microM) inhibited significantly after 48 and 72 h. The mitotic index decreased with increasing of Cd concentration and duration of treatment except for the group exposed to 1 microM Cd. Cd induced c-mitosis, chromosome bridges, chromosome stickiness and lagging chromosomes. The rate of aberrant dividing cells increased with prolonging duration of treatment and increasing of Cd concentration. On nucleolus, some particulates containing the argyrophilic proteins were extruded from the nucleus into the cytoplasm in the cells stressed by Cd and some were scattered in the nucleus. After the treatment with Cd (10 microM Cd, 48 h), the nucleolus did not disaggregate normally and still remain its characteristic structure during metaphase and the particles of similar silver-stained materials were localized on chromosomes. In leaves, Catalase (CAT) activity declined but Peroxidase (POD) activity increased with increasing of the duration of treatment. In roots, CAT activity increased with increasing of the duration of treatment, POD activity increased during early days and then declined. Superoxide dismutase (SOD) activity showed an upward trend with increasing of the duration of treatment after 3 and 6 days, then declined both in leaves and roots (9 days). SOD and POD had highest activities at 50 microM Cd in leaves. CAT activity was lowest at 50 microM Cd. Malondialdehyde (MDA) content increased with the increasing of Cd concentrations and duration of treatment in leaves. In roots, MDA content showed an upward trend with increasing of the duration of treatment at early time and then declined.

Intermittent hypoxia activates peptidylglycine α-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing

PubMed Central

Sharma, Suresh D.; Raghuraman, Gayatri; Lee, Myeong-Seon; Prabhakar, Nanduri R.; Kumar, Ganesh K.

2009-01-01

Intermittent hypoxia (IH) associated with sleep apneas leads to cardiorespiratory abnormalities that may involve altered neuropeptide signaling. The effects of IH on neuropeptide synthesis have not been investigated. Peptidylglycine α-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the α-amidation of neuropeptides, which confers biological activity to a large number of neuropeptides. PAM consists of O2-sensitive peptidylglycine α-hydroxylating monooxygenase (PHM) and peptidyl-α-hydroxyglycine α-amidating lyase (PAL) activities. Here, we examined whether IH alters neuropeptide synthesis by affecting PAM activity and, if so, by what mechanisms. Experiments were performed on the brain stem of adult male rats exposed to IH (5% O2 for 15 s followed by 21% O2 for 5 min; 8 h/day for up to 10 days) or continuous hypoxia (0.4 atm for 10 days). Analysis of brain stem extracts showed that IH, but not continuous hypoxia, increased PHM, but not PAL, activity of PAM and that the increase of PHM activity was associated with a concomitant elevation in the levels of α-amidated forms of substance P and neuropeptide Y. IH increased the relative abundance of 42- and 35-kDa forms of PHM (∼1.6- and 2.7-fold, respectively), suggesting enhanced proteolytic processing of PHM, which appears to be mediated by an IH-induced increase of endoprotease activity. Kinetic analysis showed that IH increases Vmax but has no effect on Km. IH increased generation of reactive oxygen species in the brain stem, and systemic administration of antioxidant prevented IH-evoked increases of PHM activity, proteolytic processing of PHM, endoprotease activity, and elevations in substance P and neuropeptide Y amide levels. Taken together, these results demonstrate that IH activates PHM in rat brain stem via reactive oxygen species-dependent posttranslational proteolytic processing and further suggest that PAM activation may contribute to IH-mediated peptidergic neurotransmission in rat brain stem. PMID:18818385

Intermittent hypoxia activates peptidylglycine alpha-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing.

PubMed

Sharma, Suresh D; Raghuraman, Gayatri; Lee, Myeong-Seon; Prabhakar, Nanduri R; Kumar, Ganesh K

2009-01-01

Intermittent hypoxia (IH) associated with sleep apneas leads to cardiorespiratory abnormalities that may involve altered neuropeptide signaling. The effects of IH on neuropeptide synthesis have not been investigated. Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the alpha-amidation of neuropeptides, which confers biological activity to a large number of neuropeptides. PAM consists of O(2)-sensitive peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) activities. Here, we examined whether IH alters neuropeptide synthesis by affecting PAM activity and, if so, by what mechanisms. Experiments were performed on the brain stem of adult male rats exposed to IH (5% O(2) for 15 s followed by 21% O(2) for 5 min; 8 h/day for up to 10 days) or continuous hypoxia (0.4 atm for 10 days). Analysis of brain stem extracts showed that IH, but not continuous hypoxia, increased PHM, but not PAL, activity of PAM and that the increase of PHM activity was associated with a concomitant elevation in the levels of alpha-amidated forms of substance P and neuropeptide Y. IH increased the relative abundance of 42- and 35-kDa forms of PHM ( approximately 1.6- and 2.7-fold, respectively), suggesting enhanced proteolytic processing of PHM, which appears to be mediated by an IH-induced increase of endoprotease activity. Kinetic analysis showed that IH increases V(max) but has no effect on K(m). IH increased generation of reactive oxygen species in the brain stem, and systemic administration of antioxidant prevented IH-evoked increases of PHM activity, proteolytic processing of PHM, endoprotease activity, and elevations in substance P and neuropeptide Y amide levels. Taken together, these results demonstrate that IH activates PHM in rat brain stem via reactive oxygen species-dependent posttranslational proteolytic processing and further suggest that PAM activation may contribute to IH-mediated peptidergic neurotransmission in rat brain stem.

Refolding of β-Stranded Class I Chitinases of Hippophae rhamnoides Enhances the Antifreeze Activity during Cold Acclimation

PubMed Central

Gupta, Ravi; Deswal, Renu

2014-01-01

Class I chitinases hydrolyse the β-1,4-linkage of chitin and also acquire antifreeze activity in some of the overwintering plants during cold stress. Two chitinases, HrCHT1a of 31 kDa and HrCHT1b of 34 kDa, were purified from cold acclimated and non-acclimated seabuckthorn seedlings using chitin affinity chromatography. 2-D gels of HrCHT1a and HrCHT1b showed single spots with pIs 7.0 and 4.6 respectively. N-terminal sequence of HrCHT1b matched with the class I chitinase of rice and antifreeze proteins while HrCHT1a could not be sequenced as it was N-terminally blocked. Unlike previous reports, where antifreeze activity of chitinase was cold inducible, our results showed that antifreeze activity is constitutive property of class I chitinase as both HrCHT1a and HrCHT1b isolated even from non-acclimated seedlings, exhibited antifreeze activity. Interestingly, HrCHT1a and HrCHT1b purified from cold acclimated seedlings, exhibited 4 and 2 times higher antifreeze activities than those purified from non-acclimated seedlings, suggesting that antifreeze activity increased during cold acclimation. HrCHT1b exhibited 23–33% higher hydrolytic activity and 2–4 times lower antifreeze activity than HrCHT1a did. HrCHT1b was found to be a glycoprotein; however, its antifreeze activity was independent of glycosylation as even deglycosylated HrCHT1b exhibited antifreeze activity. Circular dichroism (CD) analysis showed that both these chitinases were rich in unusual β-stranded conformation (36–43%) and the content of β-strand increased (∼11%) during cold acclimation. Surprisingly, calcium decreased both the activities of HrCHT1b while in case of HrCHT1a, a decrease in the hydrolytic activity and enhancement in its antifreeze activity was observed. CD results showed that addition of calcium also increased the β-stranded conformation of HrCHT1a and HrCHT1b. This is the first report, which shows that antifreeze activity is constitutive property of class I chitinase and cold acclimation and calcium regulate these activities of chitinases by changing the secondary structure. PMID:24626216

Refolding of β-stranded class I chitinases of Hippophae rhamnoides enhances the antifreeze activity during cold acclimation.

PubMed

Gupta, Ravi; Deswal, Renu

2014-01-01

Class I chitinases hydrolyse the β-1,4-linkage of chitin and also acquire antifreeze activity in some of the overwintering plants during cold stress. Two chitinases, HrCHT1a of 31 kDa and HrCHT1b of 34 kDa, were purified from cold acclimated and non-acclimated seabuckthorn seedlings using chitin affinity chromatography. 2-D gels of HrCHT1a and HrCHT1b showed single spots with pIs 7.0 and 4.6 respectively. N-terminal sequence of HrCHT1b matched with the class I chitinase of rice and antifreeze proteins while HrCHT1a could not be sequenced as it was N-terminally blocked. Unlike previous reports, where antifreeze activity of chitinase was cold inducible, our results showed that antifreeze activity is constitutive property of class I chitinase as both HrCHT1a and HrCHT1b isolated even from non-acclimated seedlings, exhibited antifreeze activity. Interestingly, HrCHT1a and HrCHT1b purified from cold acclimated seedlings, exhibited 4 and 2 times higher antifreeze activities than those purified from non-acclimated seedlings, suggesting that antifreeze activity increased during cold acclimation. HrCHT1b exhibited 23-33% higher hydrolytic activity and 2-4 times lower antifreeze activity than HrCHT1a did. HrCHT1b was found to be a glycoprotein; however, its antifreeze activity was independent of glycosylation as even deglycosylated HrCHT1b exhibited antifreeze activity. Circular dichroism (CD) analysis showed that both these chitinases were rich in unusual β-stranded conformation (36-43%) and the content of β-strand increased (∼11%) during cold acclimation. Surprisingly, calcium decreased both the activities of HrCHT1b while in case of HrCHT1a, a decrease in the hydrolytic activity and enhancement in its antifreeze activity was observed. CD results showed that addition of calcium also increased the β-stranded conformation of HrCHT1a and HrCHT1b. This is the first report, which shows that antifreeze activity is constitutive property of class I chitinase and cold acclimation and calcium regulate these activities of chitinases by changing the secondary structure.

The role of nitric oxide synthase in reduced vasocontractile responsiveness induced by prolonged α1-adrenergic receptor stimulation in rat thoracic aorta

PubMed Central

Gürdal, Hakan; Can, Alp; Uğur, Mehmet

2005-01-01

Prolonged exposure (6–12 h) of rat aorta to alpha1-adrenergic receptor (α1AR) agonist phenylephrine (Phe) leads to a decrease in α1AR-mediated vasoconstriction. This reduced responsiveness to α1AR stimulation was strongly dependent on the intactness of the endothelium. We examined the effect of Phe on nitric oxide synthase (NOS) activity by measuring the conversion of [3H]L-arginine to [3H]L-citrulline in rat aorta or in endothelial cells isolated from rat aorta. Phe stimulation increased NOS activity in control aortas. This response was antagonized by prazosin. However, Phe increased neither the activity of NOS nor intracellular Ca2+ in the isolated endothelial cells from the control aortas, whereas acetylcholine (Ach) was able to stimulate both responses in these cells. This result suggests that Phe stimulates α1AR on vascular smooth muscle cells and has an indirect influence on endothelial cells to increase NOS activity. In Phe-exposed aortic rings, basal NOS activity was found to have increased compared to vehicle-exposed control rings. Stimulation with Phe or Ach caused a small increase over basal NOS activity in these preparations. Prolonged exposure to Phe also caused an enhancement of Ach-mediated vasorelaxation in rat aorta. Immunoblot and reverse transcription–polymerase chain reaction experiments showed that prolonged exposure of rat aorta to Phe resulted in an increased expression of eNOS, but not iNOS. This increase was antagonized by nonselective antagonist prazosin. Immunohistochemical staining experiments also showed that expression of eNOS increased in endothelial cells after Phe exposure of the aortas. These results, all together, showed that prolonged exposure of rat aorta to α1AR agonist Phe enhanced the expression of eNOS and basal NOS activity, which probably causes a decreased vasocontractile response to Phe or to other agonists such as 5HT (5-hydroxytryptamine) in rat aorta. This phenomenon can be considered more as a functional antagonism of vasocontractile response to agonists mediated by endothelium than a specific desensitization of α1AR-mediated signalling in vascular smooth muscle cells. PMID:15753950

Neural processing of intentional biological motion in unaffected siblings of children with autism spectrum disorder: an fMRI study.

PubMed

Ahmed, Alex A; Vander Wyk, Brent C

2013-12-01

Despite often showing behaviorally typical levels of social cognitive ability, unaffected siblings of children with autism spectrum disorder have been found to show similar functional and morphological deficits within brain regions associated with social processing. They have also been reported to show increased activation to biological motion in these same regions, such as the posterior superior temporal sulcus (pSTS), relative to both children with autism and control children. It has been suggested that this increased activation may represent a compensatory reorganization of these regions as a result of the highly heritable genetic influence of autism. However, the response patterns of unaffected siblings in the domain of action perception are unstudied, and the phenomenon of compensatory activation has not yet been replicated. The present study used functional magnetic resonance imaging to determine the neural responses to intentional biological actions in 22 siblings of children with autism and 22 matched controls. The presented actions were either congruent or incongruent with the actor's emotional cue. Prior studies reported that typically developing children and adults, but not children with autism, show increased activation to incongruent actions (relative to congruent), within the pSTS and dorsolateral prefrontal cortex. We report that unaffected siblings did not show a compensatory response, or a preference for incongruent over congruent trials, in any brain region. Moreover, interaction analyses revealed a sub-region of the pSTS in which control children showed an incongruency preference to a significantly greater degree than siblings, which suggests a localized deficit in siblings. A sample of children with autism also did not show differential activation in the pSTS, providing further evidence that it is an area of selective disruption in children with autism and siblings. While reduced activation to both conditions was unique to the autism sample, lack of differentiation to incongruent and congruent intentional actions was common to both children with ASD and unaffected siblings. Copyright © 2013 Elsevier Inc. All rights reserved.

Six Classroom Exercises to Teach Natural Selection to Undergraduate Biology Students

PubMed Central

Kalinowski, Steven T.; Leonard, Mary J.; Andrews, Tessa M.; Litt, Andrea R.

2013-01-01

Students in introductory biology courses frequently have misconceptions regarding natural selection. In this paper, we describe six activities that biology instructors can use to teach undergraduate students in introductory biology courses how natural selection causes evolution. These activities begin with a lesson introducing students to natural selection and also include discussions on sexual selection, molecular evolution, evolution of complex traits, and the evolution of behavior. The set of six topics gives students the opportunity to see how natural selection operates in a variety of contexts. Pre- and postinstruction testing showed students’ understanding of natural selection increased substantially after completing this series of learning activities. Testing throughout this unit showed steadily increasing student understanding, and surveys indicated students enjoyed the activities. PMID:24006396

Surfaces of Fluorinated Pyridinium Block Copolymers with Enhanced Antibacterial Activity

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

Krishnan,S.; Ward, R.; Hexemer, A.

2006-01-01

Polystyrene-b-poly(4-vinylpyridine) copolymers were quaternized with 1-bromohexane and 6-perfluorooctyl-1-bromohexane. Surfaces prepared from these polymers were characterized by contact angle measurements, near-edge X-ray absorption fine structure spectroscopy and X-ray photoelectron spectroscopy. The fluorinated pyridinium surfaces showed enhanced antibacterial activity compared to their nonfluorinated counterparts. Even a polymer with a relatively low molecular weight pyridinium block showed high antimicrobial activity. The bactericidal effect was found to be related to the molecular composition and organization in the top 2-3 nm of the surface and increased with increasing hydrophilicity and pyridinium concentration of the surface.

Transitions to Synchrony in Coupled Bursting Neurons

NASA Astrophysics Data System (ADS)

Dhamala, Mukeshwar; Jirsa, Viktor K.; Ding, Mingzhou

2004-01-01

Certain cells in the brain, for example, thalamic neurons during sleep, show spike-burst activity. We study such spike-burst neural activity and the transitions to a synchronized state using a model of coupled bursting neurons. In an electrically coupled network, we show that the increase of coupling strength increases incoherence first and then induces two different transitions to synchronized states, one associated with bursts and the other with spikes. These sequential transitions to synchronized states are determined by the zero crossings of the maximum transverse Lyapunov exponents. These results suggest that synchronization of spike-burst activity is a multi-time-scale phenomenon and burst synchrony is a precursor to spike synchrony.

Activation of inflammatory signaling by lipopolysaccharide produces a prolonged increase of voluntary alcohol intake in mice

PubMed Central

Blednov, Y.A.; Benavidez, J.M.; Geil, C.; Perra, S.; Morikawa, H.; Harris, R.A.

2011-01-01

Previous studies showed that mice with genetic predisposition for high alcohol consumption as well as human alcoholics show changes in brain expression of genes related to immune signaling. In addition, mutant mice lacking genes related to immune function show decreased alcohol consumption (Blednov et al., in press), suggesting that immune signaling promotes alcohol consumption. To test the possibility that activation of immune signaling will increase alcohol consumption, we treated mice with lipopolysaccaride (LPS; 1 mg/kg, i.p.) and tested alcohol consumption in the continuous two-bottle choice test. To take advantage of the long-lasting activation of brain immune signaling by LPS, we measured drinking beginning one week or one month after LPS treatment and continued the studies for several months. LPS produced persistent increases in alcohol consumption in C57/Bl6 J (B6) inbred mice, FVBxB6F1 and B6xNZBF1 hybrid mice, but not in FVB inbred mice. To determine if this effect of LPS is mediated through binding to TLR4, we tested mice lacking CD14, a key component of TLR4 signaling. These null mutants showed no increase of alcohol intake after treatment with LPS. LPS treatment decreased ethanol-conditioned taste aversion but did not alter ethanol-conditioned place preference (B6xNZBF1 mice). Electro-physiological studies of dopamine neurons in the ventral tegmental area showed that pretreatment of mice with LPS decreased the neuronal firing rate. These results suggest that activation of immune signaling promotes alcohol consumption and alters certain aspects of alcohol reward/aversion. PMID:21266194

Adrenal gland involvement in the regulation of renal 11beta-hydroxysteroid dehydrogenase 2.

PubMed

Zallocchi, Marisa Laura; Matkovic, Laura; Calvo, Juan Carlos; Damasco, María Cristina

2004-06-01

Renal 11beta-hydroxysteroid dehydrogenase 2 (HSD2) catalyzes the conversion of active glucocorticoids to inert 11beta-keto compounds, thereby preventing the illicit binding of these hormones to mineralocorticoid receptors (MRs) and, thus, conferring aldosterone specificity. Absence or inhibition of HSD2 activity, originates a hypertensive syndrome with sodium retention and increased potassium elimination. Recent studies from our laboratory reported an increment of HSD2 activity in intact-stressed rats. To evaluate the adrenal involvement in this increase, we analyzed HSD2 activity and protein abundance in Intact, Sham-operated, and adrenalectomized rats under stress situations (gavage with an overload of 200 mM HCl (10 ml) and simulated gavage) or with corticosterone replacement. HSD2 activity was assessed in renal microsomal preparations obtained from different groups of animals. HSD2 protein abundance was measured by Western-blot. Circulating corticosterone was determined by radioimmunoassay. Sham-operated animals showed an increase in HSD2 activity and abundance compared to Intact and adrenalectomized rats suggesting the involvement of stress-related adrenal factors in HSD2 regulation. In the case of acidotic adrenalectomized animals, there was an increase in renal HSD2 activity when, along with the HCl overload, the rats were injected with corticosterone. This increment occurred without an increase in enzyme abundance. These results suggest the importance of circulating levels of glucocorticoids to respond to a metabolic acidosis, through regulation of HSD2 stimulation. The group subjected to a simulated gavage showed an increase in enzyme activity and protein abundance, thus demonstrating the need for both adrenal and extra-factors in the modulation of renal HSD2. The adrenalectomized animals injected with different doses of corticosterone, produced a progressive increase in enzyme activity and abundance, being significant for the dose of 68 microg corticosterone/100 g body weight. The highest dose (308 microg/100 g body weight) did not show any variation in activity and abundance compared to the control group. This biphasic effect of glucocorticoids could be explained taking into account their permissive and suppressive actions, depending on their blood levels. Knowing that stress induces multifactorial responses, it should not be surprising to observe a differential regulation in renal HSD2, confirming that different stressors act through different factors of both, adrenal and extra-adrenal origin. Copyright 2004 Wiley-Liss, Inc.

Combined effects Na and SO2 in flue gas on Mn-Ce/TiO2 catalyst for low temperature selective catalytic reduction of NO by NH3 simulated by Na2SO4 doping

NASA Astrophysics Data System (ADS)

Zhou, Aiyi; Yu, Danqing; Yang, Liu; Sheng, Zhongyi

2016-08-01

A series of Mn-Ce/TiO2 catalysts were synthesized through an impregnation method and used for low temperature selective catalytic reduction (SCR) of NOx with ammonia (NH3). Na2SO4 was added into the catalyst to simulate the combined effects of alkali metal and SO2 in the flue gas. Experimental results showed that Na2SO4 had strong and fluctuant influence on the activity of Mn-Ce/TiO2, because the effect of Na2SO4 included pore occlusion and sulfation effect simultaneously. When Na2SO4 loading content increased from 0 to 1 wt.%, the SCR activities of Na2SO4-doped catalysts decreased greatly. With further increasing amount of Na2SO4, however, the catalytic activity increased gradually. XRD results showed that Na2SO4 doping could induce the crystallization of MnOx phases, which were also confirmed by TEM and SEM results. BET results showed that the surface areas decreased and a new bimodal mesoporous structure formed gradually with the increasing amount of Na2SO4. XPS results indicated that part of Ce4+ and Mn3+ were transferred to Ce3+ and Mn4+ due to the sulfation after Na2SO4 deposition on the surface of the catalysts. When the doped amounts of Na2SO4 increased, NH3-TPD results showed that the Lewis acid sites decreased and the Brønsted acid sites of Mn-Ce/TiO2 increased quickly, which could be considered as another reason for the observed changes in the catalytic activity. The decreased Mn and Ce atomic concentration, the changes of their oxidative states, and the variation in acidic properties on the surface of Na2SO4-doped catalysts could be the reasons for the fluctuant changes of the catalytic activity.

Effects of water-soluble natural antioxidants on photosensitized oxidation of conjugated linoleic acid in an oil-in-water emulsion system.

PubMed

Liu, T-T; Yang, T-S

2008-05-01

The effect of photosensitized oxidation of conjugated linoleic acid in an oil-in-water (o/w) emulsion system was studied. Water-soluble natural antioxidants, including apple polyphenols from apple extract, green tea extract, 4-hydroxy-2(or 5)-ethyl-5(or2)-methyl-3(2H)-furanone(HEMF), 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF), and ascorbic acid, were tested for antioxidant activity in this system. The green tea extract showed the highest antioxidant activity followed by ascorbic acid. Apple polyphenols did not give significant antioxidant activity. HEMF and HDMF exhibited a prooxidant effect. The antioxidant activity of tea catechins was also investigated. Of them, EGCG and ECG exhibited antioxidant activity at 50 ppm, but the antioxidant activity between them was not significantly different (P < 0.05). Comparatively, EC, EGC, and GCG showed no significant antioxidative effect at 50 ppm. When the concentration increased to 100 ppm, the antioxidant activity of ECG and EGCG significantly increased compared with that at 50 ppm, and EGCG had higher antioxidant activity than ECG. GCG also showed significant antioxidant activity at 100 ppm. EGCG exhibited the highest antioxidant activity among the tea catechins in the emulsion system at 100 ppm.

Aβ mediates Sigma receptor degradation via CaN/NFAT pathway

PubMed Central

Fang, Min; Zhang, Pei; Zhao, Yanxin; Jin, Aiping; Liu, Xueyuan

2016-01-01

Sigma receptor is an endoplasmic reticulum protein and belongs to non-opioid receptor. Increasing evidence shows that Sigma receptor activation can significantly attenuate AD induced neurological dysfunction and the functional deficiency of Sigma receptor plays an important role in the Aβ induced neuronal loss. This study aimed to investigate the influence of extracellular accumulation of Aβ on the Sigma receptor expression. Our results showed the increase in extracellular Aβ had little influence on the mRNA expression of Sigma receptor, but gradually reduced its protein expression. Co-immunoprecipitation was employed to evaluate the interaction of Sigma receptor with other proteins. Results showed BIP could bind to Sigma receptor to affect the ubiquitination of Sigma receptor. Further investigation showed there was a NFAT binding site at the promoter of BIP. Then, Western blot assay was performed to detect NFAT expression. Results showed extracellular Aβ affected the nuclear translocation of NFAT and the CaN activity of NFAT also increased with the accumulation of extracellular Aβ. In this study, NFAT-BIP luciferase reporter gene system was constructed. Results showed NFAT was able to regulate the transcription of BIP. Thus, we speculate that extracellular Aβ accumulation may activate CaN/NFAT signaling pathway to induce chaperone BIP expression, which results in Sigma receptor ubiquitination and its degradation. PMID:27648137

Increased fMRI signal with age in familial Alzheimer’s disease mutation carriers

PubMed Central

Braskie, Meredith N.; Medina, Luis D.; Rodriguez-Agudelo, Yaneth; Geschwind, Daniel H.; Macias-Islas, Miguel Angel; Cummings, Jeffrey L.; Bookheimer, Susan Y.; Ringman, John M.

2010-01-01

Although many Alzheimer’s disease (AD) patients have a family history of the disease, it is rarely inherited in a predictable way. Functional magnetic resonance imaging (fMRI) studies of non-demented adults carrying familial AD mutations provide an opportunity to prospectively identify brain differences associated with early AD-related changes. We compared fMRI activity of 18 non-demented autosomal dominant AD mutation carriers with fMRI activity in 8 of their non-carrier relatives as they performed a novelty encoding task in which they viewed novel and repeated images. Because age of disease onset is relatively consistent within families, we also correlated fMRI activity with subjects’ distance from the median age of diagnosis for their family. Mutation carriers did not show significantly different voxelwise fMRI activity from non-carriers as a group. However, as they approached their family age of disease diagnosis, only mutation carriers showed increased fMRI activity in the fusiform and middle temporal gyri. This suggests that during novelty encoding, increased fMRI activity in the temporal lobe may relate to incipient AD processes. PMID:21129823

High glucose condition increases NADPH oxidase activity in endothelial microparticles that promote vascular inflammation.

PubMed

Jansen, Felix; Yang, Xiaoyan; Franklin, Bernardo S; Hoelscher, Marion; Schmitz, Theresa; Bedorf, Jörg; Nickenig, Georg; Werner, Nikos

2013-04-01

Diabetes is a major risk factor for cardiovascular diseases. Circulating endothelial microparticles (EMP) are increased in diabetic patients, but their potential contribution in atherogenesis is unclear. We sought to determine the role of EMP derived under high glucose conditions in the development of atherosclerosis. EMP were generated from human coronary endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions. These EMP were defined as 'injured' EMP (iEMP) and their effects were compared with EMP generated from 'healthy' untreated HCAEC. iEMP injection significantly impaired endothelial function in ApoE(-/-) mice compared with EMP and vehicle treatment. Immunofluorescent experiments showed increased macrophage infiltration and adhesion protein expression in atherosclerotic lesions of iEMP-treated ApoE(-/-) mice compared with controls. To further investigate the underlying mechanism of iEMP-induced vascular inflammation, additional in vitro experiments were performed. iEMP, but not EMP, induced activation of HCAEC in a time- and dose-dependent manner and increased monocyte adhesion. Further experiments demonstrated that iEMP induced activation of HCAEC by phosphorylation of p38 into its biologically active form phospho-p38. Inhibition of p38 activation abrogated iEMP-dependent induction of adhesion proteins and monocyte adhesion on HCAEC. Moreover, we could demonstrate that iEMP show increased NADPH oxidase activity and contain significantly higher level of reactive oxygen species (ROS) than EMP. iEMP triggered ROS production in HCAEC and thereby activate p38 in an ROS-dependent manner. High glucose condition increases NADPH oxidase activity in endothelial microparticles that amplify endothelial inflammation and impair endothelial function by promoting activation of the endothelium. These findings provide new insights into the pathogenesis of diabetes-associated atherosclerosis.

Treatment with endotracheal therapeutics after sarin microinstillation inhalation exposure increases blood cholinesterase levels in guinea pigs.

PubMed

Che, Magnus M; Song, Jian; Oguntayo, Samuel; Doctor, Bhupendra P; Rezk, Peter; Perkins, Michael W; Sciuto, Alfred M; Nambiar, Madhusoodana P

2012-05-01

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were measured in the blood and tissues of animals that are treated with a number of endotracheally aerosolized therapeutics for protection against inhalation toxicity to sarin. Therapeutics included, aerosolized atropine methyl bromide (AMB), scopolamine or combination of AMB with salbutamol, sphingosine 1-phosphate, keratinocyte growth factor, adenosine A1 receptor antisense oligonucleotide (EPI2010), 2,3-diacetyloxybenzoic acid (2,3 DABA), oxycyte, and survanta. Guinea pigs exposed to 677.4 mg/m(3) or 846.5 mg/m(3) (1.2 LCt(50)) sarin for 4 min using a microinstillation inhalation exposure technique and treated 1 min later with the aerosolized therapeutics. Treatment with all therapeutics significantly increased the survival rate with no convulsions throughout the 24 h study period. Blood AChE activity determined using acetylthiocholine as substrate showed 20% activity remaining in sarin-exposed animals compare to controls. In aerosolized AMB and scopolamine-treated animals the remaining AChE activity was significantly higher (45-60%) compared to sarin-exposed animals (p < 0.05). Similarly, treatment with all the combination therapeutics resulted in significant increase in blood AChE activity in comparison to sarin-exposed animals although the increases varied between treatments (p < 0.05). BChE activity was increased after treatment with aerosolized therapeutics but was lesser in magnitude compared to AChE activity changes. Various tissues showed elevated AChE activity after therapeutic treatment of sarin-exposed animals. Increased AChE and BChE activities in animals treated with nasal therapeutics suggest that enhanced breathing and reduced respiratory toxicity/lung injury possibly contribute to rapid normalization of chemical warfare nerve agent inhibited cholinesterases.

Activity Induces Fmr1-Sensitive Synaptic Capture of Anterograde Circulating Neuropeptide Vesicles

PubMed Central

Cavolo, Samantha L.; Bulgari, Dinara; Deitcher, David L.

2016-01-01

Synaptic neuropeptide and neurotrophin stores are maintained by constitutive bidirectional capture of dense-core vesicles (DCVs) as they circulate in and out of the nerve terminal. Activity increases DCV capture to rapidly replenish synaptic neuropeptide stores following release. However, it is not known whether this is due to enhanced bidirectional capture. Here experiments at the Drosophila neuromuscular junction, where DCVs contain neuropeptides and a bone morphogenic protein, show that activity-dependent replenishment of synaptic neuropeptides following release is evident after inhibiting the retrograde transport with the dynactin disruptor mycalolide B or photobleaching DCVs entering a synaptic bouton by retrograde transport. In contrast, photobleaching anterograde transport vesicles entering a bouton inhibits neuropeptide replenishment after activity. Furthermore, tracking of individual DCVs moving through boutons shows that activity selectively increases capture of DCVs undergoing anterograde transport. Finally, upregulating fragile X mental retardation 1 protein (Fmr1, also called FMRP) acts independently of futsch/MAP-1B to abolish activity-dependent, but not constitutive, capture. Fmr1 also reduces presynaptic neuropeptide stores without affecting activity-independent delivery and evoked release. Therefore, presynaptic motoneuron neuropeptide storage is increased by a vesicle capture mechanism that is distinguished from constitutive bidirectional capture by activity dependence, anterograde selectivity, and Fmr1 sensitivity. These results show that activity recruits a separate mechanism than used at rest to stimulate additional synaptic capture of DCVs for future release of neuropeptides and neurotrophins. SIGNIFICANCE STATEMENT Synaptic release of neuropeptides and neurotrophins depends on presynaptic accumulation of dense-core vesicles (DCVs). At rest, DCVs are captured bidirectionally as they circulate through Drosophila motoneuron terminals by anterograde and retrograde transport. Here we show that activity stimulates further synaptic capture that is distinguished from basal capture by its selectivity for anterograde DCVs and its inhibition by overexpression of the fragile X retardation protein Fmr1. Fmr1 dramatically lowers DCV numbers in synaptic boutons. Therefore, activity-dependent anterograde capture is a major determinant of presynaptic peptide stores. PMID:27852784

An HRE-Binding Py-Im Polyamide Impairs Hypoxic Signaling in Tumors.

PubMed

Szablowski, Jerzy O; Raskatov, Jevgenij A; Dervan, Peter B

2016-04-01

Hypoxic gene expression contributes to the pathogenesis of many diseases, including organ fibrosis, age-related macular degeneration, and cancer. Hypoxia-inducible factor-1 (HIF1), a transcription factor central to the hypoxic gene expression, mediates multiple processes including neovascularization, cancer metastasis, and cell survival. Pyrrole-imidazole polyamide 1: has been shown to inhibit HIF1-mediated gene expression in cell culture but its activity in vivo was unknown. This study reports activity of polyamide 1: in subcutaneous tumors capable of mounting a hypoxic response and showing neovascularization. We show that 1: distributes into subcutaneous tumor xenografts and normal tissues, reduces the expression of proangiogenic and prometastatic factors, inhibits the formation of new tumor blood vessels, and suppresses tumor growth. Tumors treated with 1: show no increase in HIF1α and have reduced ability to adapt to the hypoxic conditions, as evidenced by increased apoptosis in HIF1α-positive regions and the increased proximity of necrotic regions to vasculature. Overall, these results show that a molecule designed to block the transcriptional activity of HIF1 has potent antitumor activity in vivo, consistent with partial inhibition of the tumor hypoxic response. Mol Cancer Ther; 15(4); 608-17. ©2015 AACR. ©2015 American Association for Cancer Research.

Moderate physical activity of music aerobic exercise increases lymphocyte counts, specific subsets, and differentiation.

PubMed

Yeh, Shu-Hui; Lai, Hsiu-Ling; Hsiao, Chiu-Yueh; Lin, Li-Wei; Chuang, Yu-Kuan; Yang, Yu-Yeng; Yang, Kuender D

2014-09-01

Moderate physical activity has been shown to promote immunity. Different moderate physical activities may have different effects on immunity. This study investigated the impacts of a 12-week regular music aerobic exercise (MAE) program on leukocyte distribution, lymphocyte subsets, and lymphocyte polarization. The study used a case-control design with pretest and posttest. Forty-seven middle-age women were recruited for this study. Three participants dropped out, 22 completed the 12-week MAE program, and the other 22 participants who had heat-intolerance or limited schedule eligibility were enrolled as the control group without the MAE exercise. Results showed that the MAE exercise for 12 weeks didn't change red blood cells or total leukocytes but increased lymphocyte counts. The women in MAE group revealed significant increases (P ≤ 0.01) of CD3CD4, CD3CD8, and CD4CD25 cells, associated with Treg polarization showing enhanced FoxP3 but not T-bet, Gata-3, or RORγT expression (P < .01). The control group without exercise revealed insignificant change of lymphocyte subsets or lymphocyte polarization. This study shows that MAE increases specific lymphocyte subsets and enhances Treg cell differentiation. It is suggested to encourage moderate physical activity of music aerobic exercise to enhance lymphocyte function of middle-aged women.

Antioxidant Properties of Crude Extract, Partition Extract, and Fermented Medium of Dendrobium sabin Flower

PubMed Central

Abu, Farahziela; Mohd Akhir, Sobri

2017-01-01

Antioxidant properties of crude extract, partition extract, and fermented medium from Dendrobium sabin (DS) flower were investigated. The oven-dried DS flower was extracted using 100% methanol (w/v), 100% ethanol (w/v), and 100% water (w/v). The 100% methanolic crude extract showed the highest total phenolic content (40.33 ± mg GAE/g extract) and the best antioxidant properties as shown by DPPH, ABTS, and FRAP assays. A correlation relationship between antioxidant activity and total phenolic content showed that phenolic compounds were the dominant antioxidant components in this flower extract. The microbial fermentation on DS flower medium showed a potential in increasing the phenolic content and DPPH scavenging activity. The TPC of final fermented medium showed approximately 18% increment, while the DPPH of fermented medium increased significantly to approximately 80% at the end of the fermentation. Dendrobium sabin (DS) flower showed very good potential properties of antioxidant in crude extract and partition extract as well as better antioxidant activity in the flower fermented medium. PMID:28761496

Novel protective mechanism of reducing renal cell damage in diabetes: Activation AMPK by AICAR increased NRF2/OGG1 proteins and reduced oxidative DNA damage

PubMed Central

Habib, Samy L.; Yadav, Anamika; Kidane, Dawit; Weiss, Robert H.; Liang, Sitai

2016-01-01

ABSTRACT Exposure of renal cells to high glucose (HG) during diabetes has been recently proposed to be involved in renal injury. In the present study, we investigated a potential mechanism by which AICAR treatment regulates the DNA repair enzyme, 8-oxoG-DNA glycosylase (OGG1) in renal proximal tubular mouse cells exposed to HG and in kidney of db/db mice. Cells treated with HG for 2 days show inhibition in OGG1 promoter activity as well as OGG1 and Nrf2 protein expression. In addition, activation of AMPK by AICAR resulted in an increase raptor phosphorylation at Ser792 and leads to increase the promoter activity of OGG1 through upregulation of Nrf2. Downregulation of AMPK by DN-AMPK and raptor and Nrf2 by siRNA resulted in significant decease in promoter activity and protein expression of OGG1. On the other hand, downregulation of Akt by DN-Akt and rictor by siRNA resulted in significant increase in promoter activity and protein expression of Nrf2 and OGG1. Moreover, gel shift analysis shows reduction of Nrf2 binding to OGG1 promoter in cells treated with HG while cells treated with AICAR reversed the effect of HG. Furthermore, db/db mice treated with AICAR show significant increased in AMPK and raptor phosphroylation as well as OGG1 and Nrf2 protein expression that associated with significant decrease in oxidative DNA damage (8-oxodG) compared to non-treated mice. In summary, our data provide a novel protective mechanism by which AICAR prevents renal cell damage in diabetes and the consequence complications of hyperglycemia with a specific focus on nephropathy. PMID:27611085

Matrix metalloproteinase-14 triggers an anti-inflammatory proteolytic cascade in endotoxemia.

PubMed

Aguirre, Alina; Blázquez-Prieto, Jorge; Amado-Rodriguez, Laura; López-Alonso, Inés; Batalla-Solís, Estefanía; González-López, Adrián; Sánchez-Pérez, Moisés; Mayoral-Garcia, Carlos; Gutiérrez-Fernández, Ana; Albaiceta, Guillermo M

2017-05-01

ᅟ: Matrix metalloproteinases can modulate the inflammatory response through processing of cyto- and chemokines. Among them, MMP-14 is a non-dispensable collagenase responsible for the activation of other enzymes, triggering a proteolytic cascade. To identify the role of MMP-14 during the pro-inflammatory response, wildtype and Mmp14 -/- mice were challenged with lipopolysaccharide. MMP-14 levels decreased after endotoxemia. Mutant animals showed 100% mortality, compared to 50% in wildtype mice. The increased mortality was related to a more severe lung injury, an impaired lung MMP-2 activation, and increased levels of the alarmin S100A9. There were no differences in the expression of other mediators including Il6, Cxcl2, Tgfb, Il10, or S100a8. A similar result was observed in lung explants of both genotypes cultured in presence of lipopolysaccharide. In this ex vivo model, exogenous activated MMP-2 ameliorated the observed increase in alarmins. Samples from septic patients showed a decrease in serum MMP-14 and activated MMP-2 compared to non-septic critically ill patients. These results demonstrate that the MMP-14-MMP-2 axis is downregulated during sepsis, leading to a proinflammatory response involving S100A9 and a more severe lung injury. This anti-inflammatory role of MMP-14 could have a therapeutic value in sepsis. • MMP-14 levels decrease in lungs from endotoxemic mice and serum from septic patients. • Mmp14 -/- mice show increased lung injury and mortality following endotoxemia. • Absence of Mmp14 decreases activated MMP-2 and increases S100A9 levels in lung tissue. • MMP-14 ameliorates inflammation by promoting S100A9 cleavage by activated MMP-2.

Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons

PubMed Central

Yao, Pamela J.; Manor, Uri; Petralia, Ronald S.; Brose, Rebecca D.; Wu, Ryan T. Y.; Ott, Carolyn; Wang, Ya-Xian; Charnoff, Ari; Lippincott-Schwartz, Jennifer; Mattson, Mark P.

2017-01-01

Mitochondria are essential organelles whose biogenesis, structure, and function are regulated by many signaling pathways. We present evidence that, in hippocampal neurons, activation of the Sonic hedgehog (Shh) signaling pathway affects multiple aspects of mitochondria. Mitochondrial mass was increased significantly in neurons treated with Shh. Using biochemical and fluorescence imaging analyses, we show that Shh signaling activity reduces mitochondrial fission and promotes mitochondrial elongation, at least in part, via suppression of the mitochondrial fission protein dynamin-like GTPase Drp1. Mitochondria from Shh-treated neurons were more electron-dense, as revealed by electron microscopy, and had higher membrane potential and respiratory activity. We further show that Shh protects neurons against a variety of stresses, including the mitochondrial poison rotenone, amyloid β-peptide, hydrogen peroxide, and high levels of glutamate. Collectively our data suggest a link between Shh pathway activity and the physiological properties of mitochondria in hippocampal neurons. PMID:27932496

Prefrontal Cortex Activation and Young Driver Behaviour: A fNIRS Study

PubMed Central

Foy, Hannah J.; Runham, Patrick; Chapman, Peter

2016-01-01

Road traffic accidents consistently show a significant over-representation for young, novice and particularly male drivers. This research examines the prefrontal cortex activation of young drivers and the changes in activation associated with manipulations of mental workload and inhibitory control. It also considers the explanation that a lack of prefrontal cortex maturation is a contributing factor to the higher accident risk in this young driver population. The prefrontal cortex is associated with a number of factors including mental workload and inhibitory control, both of which are also related to road traffic accidents. This experiment used functional near infrared spectroscopy to measure prefrontal cortex activity during five simulated driving tasks: one following task and four overtaking tasks at varying traffic densities which aimed to dissociate workload and inhibitory control. Age, experience and gender were controlled for throughout the experiment. The results showed that younger drivers had reduced prefrontal cortex activity compared to older drivers. When both mental workload and inhibitory control increased prefrontal cortex activity also increased, however when inhibitory control alone increased there were no changes in activity. Along with an increase in activity during overtaking manoeuvres, these results suggest that prefrontal cortex activation is more indicative of workload in the current task. There were no differences in the number of overtakes completed by younger and older drivers but males overtook significantly more than females. We conclude that prefrontal cortex activity is associated with the mental workload required for overtaking. We additionally suggest that the reduced activation in younger drivers may be related to a lack of prefrontal maturation which could contribute to the increased crash risk seen in this population. PMID:27227990

Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice123

PubMed Central

Storey, Granville P.; Heimbigner, Lauren; Walwyn, Wendy M.; Bamford, Nigel S.

2016-01-01

Abstract Corticostriatal signaling participates in sensitized responses to drugs of abuse, where short-term increases in dopamine availability provoke persistent, yet reversible, changes in glutamate release. Prior studies in mice show that amphetamine withdrawal promotes a chronic presynaptic depression in glutamate release, whereas an amphetamine challenge reverses this depression by potentiating corticostriatal activity in direct pathway medium spiny neurons. This synaptic plasticity promotes corticostriatal activity and locomotor sensitization through upstream changes in the activity of tonically active cholinergic interneurons (ChIs). We used a model of operant drug-taking behaviors, in which mice self-administered amphetamine through an in-dwelling catheter. Mice acquired amphetamine self-administration under fixed and increasing schedules of reinforcement. Following a period of abstinence, we determined whether nicotinic acetylcholine receptors modified drug-seeking behavior and associated alterations in ChI firing and corticostriatal activity. Mice responding to conditioned reinforcement showed reduced ChI and corticostriatal activity ex vivo, which paradoxically increased following an amphetamine challenge. Nicotine, in a concentration that increases Ca2+ influx and desensitizes α4β2*-type nicotinic receptors, reduced amphetamine-seeking behaviors following abstinence and amphetamine-induced locomotor sensitization. Nicotine blocked the depression of ChI firing and corticostriatal activity and the potentiating response to an amphetamine challenge. Together, these results demonstrate that nicotine reduces reward-associated behaviors following repeated amphetamine and modifies the changes in ChIs firing and corticostriatal activity. By returning glutamatergic activity in amphetamine self-administering mice to a more stable and normalized state, nicotine limits the depression of striatal activity in withdrawal and the increase in activity following abstinence and a subsequent drug challenge. PMID:26866057

Motion sickness severity and physiological correlates during repeated exposures to a rotating optokinetic drum

NASA Technical Reports Server (NTRS)

Hu, Senqi; Grant, Wanda F.; Stern, Robert M.; Koch, Kenneth L.

1991-01-01

Fifty-two subjects were exposed to a rotating optokinetic drum. Ten of these subjects who became motion sick during the first session completed two additional sessions. Subjects' symptoms of motion sickness, perception of self-motion, electrogastrograms (EGGs), heart rate, mean successive differences of R-R intervals (RRI), and skin conductance were recorded for each session. The results from the first session indicated that the development of motion sickness was accompanied by increased EGG 4-9 cpm activity (gastric tachyarrhythmia), decreased mean succesive differences of RRI, increased skin conductance levels, and increased self-motion perception. The results from the subjects who had three repeated sessions showed that 4-9 cpm EGG activity, skin conductance levels, perception of self-motion, and symptoms of motion sickness all increased significantly during the drum rotation period of the first session, but increased significantly less during the following sessions. Mean successive differences of RRI decreased significantly during the drum rotation period for the first session, but decreased significantly less during the following sessions. Results show that the development of motion sickness is accompanied by an increase in gastric tachyarrhythmia, and an increase in sympathetic activity and a decrease in parasympathetic activity, and that adaptation to motion sickness is accompanied by the recovery of autonomic nervous system balance.

An fMRI study of sex differences in regional activation to a verbal and a spatial task.

PubMed

Gur, R C; Alsop, D; Glahn, D; Petty, R; Swanson, C L; Maldjian, J A; Turetsky, B I; Detre, J A; Gee, J; Gur, R E

2000-09-01

Sex differences in cognitive performance have been documented, women performing better on some phonological tasks and men on spatial tasks. An earlier fMRI study suggested sex differences in distributed brain activation during phonological processing, with bilateral activation seen in women while men showed primarily left-lateralized activation. This blood oxygen level-dependent fMRI study examined sex differences (14 men, 13 women) in activation for a spatial task (judgment of line orientation) compared to a verbal-reasoning task (analogies) that does not typically show sex differences. Task difficulty was manipulated. Hypothesized ROI-based analysis documented the expected left-lateralized changes for the verbal task in the inferior parietal and planum temporal regions in both men and women, but only men showed right-lateralized increase for the spatial task in these regions. Image-based analysis revealed a distributed network of cortical regions activated by the tasks, which consisted of the lateral frontal, medial frontal, mid-temporal, occipitoparietal, and occipital regions. The activation was more left lateralized for the verbal and more right for the spatial tasks, but men also showed some left activation for the spatial task, which was not seen in women. Increased task difficulty produced more distributed activation for the verbal and more circumscribed activation for the spatial task. The results suggest that failure to activate the appropriate hemisphere in regions directly involved in task performance may explain certain sex differences in performance. They also extend, for a spatial task, the principle that bilateral activation in a distributed cognitive system underlies sex differences in performance. Copyright 2000 Academic Press.

Association of Oxytocin and Parental Prefrontal Activation during Reunion with Infant: A Functional Near-Infrared Spectroscopy Study.

PubMed

Ito, Jun; Fujiwara, Takeo; Monden, Yukifumi; Yamagata, Takanori; Ohira, Hideki

2017-01-01

Although previous studies have revealed the role of oxytocin (OT) in parental behavior, the role of OT has not been investigated through the direct assessment of prefrontal brain activation during parenting. By using functional near-infrared spectroscopy, we aimed to show the relationship between parental [maternal ( N  = 15) and paternal ( N  = 21)] OT levels and the activation of the prefrontal cortex (PFC), while holding their infants after separation. Baseline OT levels were measured in the subjects' saliva samples before the experiment. Prefrontal brain activation was assessed in participants sitting alone on a chair (i.e., separation from their infant for 120 s) and during the target period (i.e., holding their infant for 45 s), which was done in triplicate. The oxygen hemoglobin (oxy-Hb) dissociation curve significantly increased in 9 out of 22 channels on the PFC when maternal and paternal samples were combined. However, only the fathers showed a correlation between salivary OT and oxy-Hb signal. Furthermore, while holding their infants, high-OT fathers showed left hemispheric dominance compared to low-OT fathers, while high-OT mothers showed right hemispheric dominance compared to low-OT mothers. This study showed that fathers with high-OT levels showed neural activation with left hemispheric dominance, while holding their infants, suggesting that increase of OT level might activate paternal PFC related to parenting behavior, although the same is not true for mothers.

Dextran: Influence of Molecular Weight in Antioxidant Properties and Immunomodulatory Potential.

PubMed

Soeiro, Vinicius C; Melo, Karoline R T; Alves, Monique G C F; Medeiros, Mayara J C; Grilo, Maria L P M; Almeida-Lima, Jailma; Pontes, Daniel L; Costa, Leandro S; Rocha, Hugo A O

2016-08-19

Dextrans (α-d-glucans) extracted from Leuconostoc mesenteroides, with molecular weights (MW) of 10 (D10), 40 (D40) and 147 (D147) kDa, were evaluated as antioxidant, anticoagulant and immunomodulatory drugs for the first time. None presented anticoagulant activity. As for the antioxidant and immunomodulatory tests, a specific test showed an increase in the dextran activity that was proportional to the increase in molecular weight. In a different assay, however, activity decreased or showed no correlation to the MW. As an example, the reducing power assay showed that D147 was twice as potent as other dextrans. On the other hand, all three samples showed similar activity (50%) when it came to scavenging the OH radical, whereas only the D10 sample showed sharp activity (50%) when it came to scavenging the superoxide ion. D40 was the single dextran that presented with immunomodulatory features since it stimulated the proliferation (~50%) of murine macrophages (RAW 264.7) and decreased the release of nitric oxide (~40%) by the cells, both in the absence and presence of lipopolysaccharides (LPS). In addition, D40 showed a greater scavenging activity (50%) for the hydrogen peroxide, which caused it to also be the more potent dextran when it came to inhibiting lipid peroxidation (70%). These points toward dextrans with a 40 kDa weight as being ideal for antioxidant and immunomodulatory use. However, future studies with the D40 and other similarly 40 kDa dextrans are underway to confirm this hypothesis.

Dextran: Influence of Molecular Weight in Antioxidant Properties and Immunomodulatory Potential

PubMed Central

Soeiro, Vinicius C.; Melo, Karoline R. T.; Alves, Monique G. C. F.; Medeiros, Mayara J. C.; Grilo, Maria L. P. M.; Almeida-Lima, Jailma; Pontes, Daniel L.; Costa, Leandro S.; Rocha, Hugo A. O.

2016-01-01

Dextrans (α-d-glucans) extracted from Leuconostoc mesenteroides, with molecular weights (MW) of 10 (D10), 40 (D40) and 147 (D147) kDa, were evaluated as antioxidant, anticoagulant and immunomodulatory drugs for the first time. None presented anticoagulant activity. As for the antioxidant and immunomodulatory tests, a specific test showed an increase in the dextran activity that was proportional to the increase in molecular weight. In a different assay, however, activity decreased or showed no correlation to the MW. As an example, the reducing power assay showed that D147 was twice as potent as other dextrans. On the other hand, all three samples showed similar activity (50%) when it came to scavenging the OH radical, whereas only the D10 sample showed sharp activity (50%) when it came to scavenging the superoxide ion. D40 was the single dextran that presented with immunomodulatory features since it stimulated the proliferation (~50%) of murine macrophages (RAW 264.7) and decreased the release of nitric oxide (~40%) by the cells, both in the absence and presence of lipopolysaccharides (LPS). In addition, D40 showed a greater scavenging activity (50%) for the hydrogen peroxide, which caused it to also be the more potent dextran when it came to inhibiting lipid peroxidation (70%). These points toward dextrans with a 40 kDa weight as being ideal for antioxidant and immunomodulatory use. However, future studies with the D40 and other similarly 40 kDa dextrans are underway to confirm this hypothesis. PMID:27548151

Surface topography, nano-mechanics and secondary structure of wheat gluten pretreated by alternate dual-frequency ultrasound and the correlation to enzymolysis.

PubMed

Zhang, Yanyan; Wang, Bei; Zhou, Cunshan; Atungulu, Griffiths G; Xu, Kangkang; Ma, Haile; Ye, Xiaofei; Abdualrahman, Mohammed A Y

2016-07-01

The effects of alternate dual-frequency ultrasound (ADFU) pretreatment on the degree of hydrolysis (DH) of wheat gluten (WG) and angiotensin I-converting enzyme (ACE) inhibitory activity were investigated in this research. The surface topography, nano-mechanics and secondary structure of WG were also determined using atomic force microscope (AFM) and circular dichroism (CD). The correlations of ACE inhibitory activity and DH with surface topography, nano-mechanics and secondary structure of WG were determined using Pearson's correlation analysis. The results showed that with an increase in either pretreatment duration or power, the ACE inhibitory activity of the hydrolysate also increases, reaching maximum at 10 min and 150 W/L, respectively, and then decreases thereafter. Similarly, AFM analysis showed that as the pretreatment duration or power increases, the surface roughness also increase and again a decrease occurs thereafter. As the pretreatment duration or power increased, the Young's modulus and adhesion of WG also increased and then declined. Young's modulus and adhesions average values were compared with ACE inhibitory activity reversely. The result of the CD spectra analysis exhibited losses in the relative percentage of α-helix of WG. Pearson's correlation analysis showed that the average values of Young's modulus and the relative percentage of α-helix correlated with ACE inhibitory activity of the hydrolysates linearly and significantly (P<0.05); the relative percentage of β-sheet correlated linearly with DH of WG significantly (P<0.05). In conclusion, ADFU pretreatment is an efficient method in proteolysis due to its physical and chemical effect on the Young's modulus, α-helix and β-sheet of WG. Copyright © 2015 Elsevier B.V. All rights reserved.

Variation of ecosystem services and human activities: A case study in the Yanhe Watershed of China

NASA Astrophysics Data System (ADS)

Su, Chang-hong; Fu, Bo-Jie; He, Chan-Sheng; Lü, Yi-He

2012-10-01

The concept of 'ecosystem service' provides cohesive views on mechanisms by which nature contributes to human well-being. Fast social and economic development calls for research on interactions between human and natural systems. We took the Yanhe Watershed as our study area, and valued the variation of ecosystem services and human activities of 2000 and 2008. Five ecosystem services were selected i.e. net primary production (NPP), carbon sequestration and oxygen production (CSOP), water conservation, soil conservation, and grain production. Human activity was represented by a composite human activity index (HAI) that integrates human population density, farmland ratio, influence of residential sites and road network. Analysis results of the five ecosystem services and human activity (HAI) are as follows: (i) NPP, CSOP, water conservation, and soil conservation increased from 2000 to 2008, while grain production declined. HAI decreased from 2000 to 2008. Spatially, NPP, CSOP, and water conservation in 2000 and 2008 roughly demonstrated a pattern of decline from south to north, while grain production shows an endocentric increasing spatial pattern. Soil conservation showed a spatial pattern of high in the south and low in the north in 2000 and a different pattern of high in the west and low in the east in 2008 respectively. HAI is proportional to the administrative level and economic development. Variation of NPP/CSOP between 2000 and 2008 show an increasing spatial pattern from northwest to southeast. In contrast, the variation of soil conservation shows an increasing pattern from southeast to northwest. Variation of water conservation shows a fanning out decreasing pattern. Variation of grain production doesn't show conspicuous spatial pattern. (ii) Variation of water conservation and of soil conservation is significantly positively correlated at 0.01 level. Both variations of water conservation and soil conservation are negatively correlated with variation of HAI at 0.01 level. Variations of NPP/CSOP are negatively correlated with variations of soil conservation and grain production at 0.05 level. (iii) Strong tradeoffs exist between regulation services and provision service, while synergies exist within regulation services. Driving effect of human activities on ecosystem services and tradeoffs and synergies among ecosystem service are also discussed.

Effect of citrate on Aspergillus niger phytase adsorption and catalytic activity in soil

NASA Astrophysics Data System (ADS)

Mezeli, Malika; Menezes-Blackburn, Daniel; Zhang, Hao; Giles, Courtney; George, Timothy; Shand, Charlie; Lumsdon, David; Cooper, Patricia; Wendler, Renate; Brown, Lawrie; Stutter, Marc; Blackwell, Martin; Darch, Tegan; Wearing, Catherine; Haygarth, Philip

2015-04-01

Current developments in cropping systems that promote mobilisation of phytate in agricultural soils, by exploiting plant-root exudation of phytase and organic acids, offer potential for developments in sustainable phosphorus use. However, phytase adsorption to soil particles and phytate complexion has been shown to inhibit phytate dephosphorylation, thereby inhibiting plant P uptake, increasing the risk of this pool contributing to diffuse pollution and reducing the potential benefits of biotechnologies and management strategies aimed to utilise this abundant reserve of 'legacy' phosphorus. Citrate has been seen to increase phytase catalytic efficiency towards complexed forms of phytate, but the mechanisms by which citrate promotes phytase remains poorly understood. In this study, we evaluated phytase (from Aspergillus niger) inactivation, and change in catalytic properties upon addition to soil and the effect citrate had on adsorption of phytase and hydrolysis towards free, precipitated and adsorbed phytate. A Langmuir model was fitted to phytase adsorption isotherms showing a maximum adsorption of 0.23 nKat g-1 (19 mg protein g-1) and affinity constant of 435 nKat gˉ1 (8.5 mg protein g-1 ), demonstrating that phytase from A.niger showed a relatively low affinity for our test soil (Tayport). Phytases were partially inhibited upon adsorption and the specific activity was of 40.44 nKat mgˉ1 protein for the free enzyme and 25.35 nKat mgˉ1 protein when immobilised. The kinetics of adsorption detailed that most of the adsorption occurred within the first 20 min upon addition to soil. Citrate had no effect on the rate or total amount of phytase adsorption or loss of activity, within the studied citrate concentrations (0-4mM). Free phytases in soil solution and phytase immobilised on soil particles showed optimum activity (>80%) at pH 4.5-5.5. Immobilised phytase showed greater loss of activity at pH levels over 5.5 and lower activities at the secondary peak at pH 2.5 when compared to the free enzymes or in soil solution. The effect of ionic strength on enzyme activity was studied by increasing NaCl concentration on the activity buffer. A significant loss of activity was seen at ionic strengths over 0.6 M but enzymes in soil solution showed increased loss of activity on initial increase in ionic strength. No significant effect of citrate on phytase catalytic efficiency was observed towards free, adsorbed and precipitated (Al, Fe, Ca) phytate, except for the free phytase towards adsorbed phytase which showed a ~160% increase in P release with the addition of citric acid. This data suggest that citrate addition has no impact on the adsorption or catalytic activity of phytase in soil solution or that immobilised on soil particles, suggesting that its impact is associated with the availability of the substrate rather than effects on the enzyme per se. The ionic strength of soil solution does, however, have an impact on phytase activity suggesting that both wetting/drying cycles and fertilisation will have discrete impacts on the activity of phytases once released to soil and thus their ability to make organic P available for uptake by plants and microbes.

Non-Ideal Detonation Properties of Ammonium Nitrate and Activated Carbon Mixtures

NASA Astrophysics Data System (ADS)

Miyake, Atsumi; Echigoya, Hiroshi; Kobayashi, Hidefumi; Ogawa, Terushige; Katoh, Katsumi; Kubota, Shiro; Wada, Yuji; Ogata, Yuji

To obtain a better understanding of detonation properties of ammonium nitrate (AN) and activated carbon (AC) mixtures, steel tube tests with several diameters were carried out for various compositions of powdered AN and AC mixtures and the influence of the charge diameter on the detonation velocity was investigated. The results showed that the detonation velocity increased with the increase of the charge diameter. The experimentally observed values were far below the theoretically predicted values made by the thermodynamic CHEETAH code and they showed so-called non-ideal detonation. The extrapolated detonation velocity of stoichiometric composition to the infinite diameter showed a good agreement with the theoretical value.

Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes

PubMed Central

Koh, Ho-Jin; Hirshman, Michael F.; He, Huamei; Li, Yangfeng; Manabe, Yasuko; Balschi, James A.; Goodyear, Laurie J.

2007-01-01

Exercise increases AMPK (AMP-activated protein kinase) activity in human and rat adipocytes, but the underlying molecular mechanisms and functional consequences of this activation are not known. Since adrenaline (epinephrine) concentrations increase with exercise, in the present study we hypothesized that adrenaline activates AMPK in adipocytes. We show that a single bout of exercise increases AMPKα1 and α2 activities and ACC (acetyl-CoA carboxylase) Ser79 phosphorylation in rat adipocytes. Similarly to exercise, adrenaline treatment in vivo increased AMPK activities and ACC phosphorylation. Pre-treatment of rats with the β-blocker propranolol fully blocked exercise-induced AMPK activation. Increased AMPK activity with exercise and adrenaline treatment in vivo was accompanied by an increased AMP/ATP ratio. Adrenaline incubation of isolated adipocytes also increased the AMP/ATP ratio and AMPK activities, an effect blocked by propranolol. Adrenaline incubation increased lipolysis in isolated adipocytes, and Compound C, an AMPK inhibitor, attenuated this effect. Finally, a potential role for AMPK in the decreased adiposity associated with chronic exercise was suggested by marked increases in AMPKα1 and α2 activities in adipocytes from rats trained for 6 weeks. In conclusion, both acute and chronic exercise are significant regulators of AMPK activity in rat adipocytes. Our findings suggest that adrenaline plays a critical role in exercise-stimulated AMPKα1 and α2 activities in adipocytes, and that AMPK can function in the regulation of lipolysis. PMID:17253964

Changes in behaviour and faecal glucocorticoid levels in response to increased human activities during weekends in the pin-tailed sandgrouse

NASA Astrophysics Data System (ADS)

Casas, Fabián; Benítez-López, Ana; Tarjuelo, Rocío; Barja, Isabel; Viñuela, Javier; García, Jesús T.; Morales, Manuel B.; Mougeot, Francois

2016-12-01

Human recreational activities are becoming increasingly widespread and frequent, a fact that may potentially exacerbate their effects on wildlife. These human-related disturbances on animals may induce behavioural and physiological changes that can ultimately affect their fitness, showing a similar anti-predator response that against natural predator or other threats. Here, we combine the use of behavioural and physiological approaches to assess the potential effect of winter human activities on a threatened farmland bird in Europe, the pin-tailed sandgrouse ( Pterocles alchata). We compared before, during and after weekend variations in human activity rates, pin-tailed sandgrouse behaviour (flocking and flying behaviour, interspecific association in mixed flocks and habitat use) and faecal glucocorticoid metabolite concentrations. Human disturbances, in particular those associated with hunting activities, peaked during weekends. Sandgrouse showed significant behavioural changes (increased sandgrouse-only flock sizes, increased proportion of birds flying and changes in habitat use) during weekends and higher faecal glucocorticoid metabolite concentrations after the weekends compared with during or before weekends. Therefore, physiological stress levels could be modulated by behavioural adjustments such as increased flock sizes and changes in habitat use that may allow sandgrouse to cope with increased human disturbance rates during weekends. Nevertheless, temporal and spatial organization of hunting days among groups of estates might be good strategies to buffer these potential adverse effects on wintering pin-tailed sandgrouse and other steppe species of conservation concern, while preserving a socio-economically important activity such as hunting.

Changes in behaviour and faecal glucocorticoid levels in response to increased human activities during weekends in the pin-tailed sandgrouse.

PubMed

Casas, Fabián; Benítez-López, Ana; Tarjuelo, Rocío; Barja, Isabel; Viñuela, Javier; García, Jesús T; Morales, Manuel B; Mougeot, Francois

2016-12-01

Human recreational activities are becoming increasingly widespread and frequent, a fact that may potentially exacerbate their effects on wildlife. These human-related disturbances on animals may induce behavioural and physiological changes that can ultimately affect their fitness, showing a similar anti-predator response that against natural predator or other threats. Here, we combine the use of behavioural and physiological approaches to assess the potential effect of winter human activities on a threatened farmland bird in Europe, the pin-tailed sandgrouse (Pterocles alchata). We compared before, during and after weekend variations in human activity rates, pin-tailed sandgrouse behaviour (flocking and flying behaviour, interspecific association in mixed flocks and habitat use) and faecal glucocorticoid metabolite concentrations. Human disturbances, in particular those associated with hunting activities, peaked during weekends. Sandgrouse showed significant behavioural changes (increased sandgrouse-only flock sizes, increased proportion of birds flying and changes in habitat use) during weekends and higher faecal glucocorticoid metabolite concentrations after the weekends compared with during or before weekends. Therefore, physiological stress levels could be modulated by behavioural adjustments such as increased flock sizes and changes in habitat use that may allow sandgrouse to cope with increased human disturbance rates during weekends. Nevertheless, temporal and spatial organization of hunting days among groups of estates might be good strategies to buffer these potential adverse effects on wintering pin-tailed sandgrouse and other steppe species of conservation concern, while preserving a socio-economically important activity such as hunting.

Quantification of the impacts of climate change and human agricultural activities on oasis water requirements in an arid region: a case study of the Heihe River basin, China

NASA Astrophysics Data System (ADS)

Liu, Xingran; Shen, Yanjun

2018-03-01

Ecological deterioration in arid regions caused by agricultural development has become a global issue. Understanding water requirements of the oasis ecosystems and the influences of human agricultural activities and climate change is important for the sustainable development of oasis ecosystems and water resource management in arid regions. In this study, water requirements of the main oasis in Heihe River basin during 1986-2013 were analyzed and the amount showed a sharp increase from 10.8 × 108 m3 in 1986 to 19.0 × 108 m3 in 2013. Both human agricultural activities and climate change could lead to the increase in water requirement. To quantify the contributions of agricultural activities and climate change to the increase in water requirements, partial derivative and slope method were used. Results showed that climate change and human agricultural activities, such as oasis expansion and changes in land cropping structure, has contributed to the increase in water requirement at rates of 6.9, 58.1, and 25.3 %, respectively. Overall, human agricultural activities were the dominant forces driving the increase in water requirement. In addition, the contribution of oasis expanding to the increased water requirement was significantly greater than that of other concerned variables. This reveals that controlling the oasis scale is extremely important and effective for balancing water for agriculture and ecosystems and to achieving a sustainable oasis development in arid regions.

Toxic reactivity of wheat (Triticum aestivum) plants to herbicide isoproturon.

PubMed

Yin, Xiao Le; Jiang, Lei; Song, Ning Hui; Yang, Hong

2008-06-25

The herbicide isoproturon is widely used for controlling weed/grass in agricultural practice. However, the side effect of isoproturon as contaminants on crops is unknown. In this study, we investigated isoproturon-induced oxidative stress in wheat ( Triticum aestivum). The plants were grown in soils with isoproturon at 0-20 mg/kg and showed negative biological responses. The growth of wheat seedlings with isoproturon was inhibited. Chlorophyll content significantly decreased at the low concentration of isoproturon (2 mg/kg), suggesting that chlorophyll was rather sensitive to isoproturon exposure. The level of thiobarbituric acid reactive substances (TBARS), an indicator of cellular peroxidation, showed an increase, indicating oxidative damage to plants. The isoproturon-induced oxidative stress resulted in a substantial change in activities of the majority of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX). Activities of the antioxidant enzymes showed a general increase at low isoproturon concentrations and a decrease at high isoproturon concentrations. Activities of CAT in leaves showed progressive suppression under the isoproturon exposure. Analysis of nondenaturing polyacrylamide gel electrophoresis (PAGE) confirmed these results. We also tested the activity of glutathione S-transferase (GST) and observed the activity stimulated by isoproturon at 2-10 mg/kg.

Role of Fas and Treg Cells in Fracture Healing as Characterized in the Fas-Deficient (lpr) Mouse Model of Lupus†

PubMed Central

Al-Sebaei, Maisa O; Daukss, Dana M; Belkina, Anna C; Kakar, Sanjeev; Wigner, Nathan A; Cusher, Daniel; Graves, Dana; Einhorn, Thomas; Morgan, Elise; Gerstenfeld, Louis C

2014-01-01

Previous studies showed that loss of tumor necrosis factor α (TNFα) signaling delayed fracture healing by delaying chondrocyte apoptosis and cartilage resorption. Mechanistic studies showed that TNFα induced Fas expression within chondrocytes; however, the degree to which chondrocyte apoptosis is mediated by TNFα alone or dependent on the induction of Fas is unclear. This question was addressed by assessing fracture healing in Fas-deficient B6.MRL/Faslpr/J mice. Loss of Fas delayed cartilage resorption but also lowered bone fraction in the calluses. The reduced bone fraction was related to elevated rates of coupled bone turnover in the B6.MRL/Faslpr/J calluses, as evidenced by higher osteoclast numbers and increased osteogenesis. Analysis of the apoptotic marker caspase 3 showed fewer positive chondrocytes and osteoclasts in calluses of B6.MRL/Faslpr/J mice. To determine if an active autoimmune state contributed to increased bone turnover, the levels of activated T cells and Treg cells were assessed. B6.MRL/Faslpr/J mice had elevated Treg cells in both spleens and bones of B6.MRL/Faslpr/J but decreased percentage of activated T cells in bone tissues. Fracture led to ∼30% to 60% systemic increase in Treg cells in both wild-type and B6.MRL/Faslpr/J bone tissues during the period of cartilage formation and resorption but either decreased (wild type) or left unchanged (B6.MRL/Faslpr/J) the numbers of activated T cells in bone. These results show that an active autoimmune state is inhibited during the period of cartilage resorption and suggest that iTreg cells play a functional role in this process. These data show that loss of Fas activity specifically in chondrocytes prolonged the life span of chondrocytes and that Fas synergized with TNFα signaling to mediate chondrocyte apoptosis. Conversely, loss of Fas systemically led to increased osteoclast numbers during later periods of fracture healing and increased osteogenesis. These findings suggest that retention of viable chondrocytes locally inhibits osteoclast activity or matrix proteolysis during cartilage resorption. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. PMID:24677136

Promoting physical activity using a wearable activity tracker in college students: A cluster randomized controlled trial.

PubMed

Kim, Youngdeok; Lumpkin, Angela; Lochbaum, Marc; Stegemeier, Steven; Kitten, Karla

2018-08-01

This study examined the effects of utilizing a wearable activity tracker in a credit-based physical activity instructional program (PAIP) for promoting physical activity (PA) in college students. Fourteen PAIP courses in a large public university were randomly assigned into intervention (k = 7; n = 101) and control (k = 7; n = 86) groups. All courses focused on a core curriculum that covers basic exercise and behavioral science contents through lectures and activity sessions. A Misfit Flash activity tracker was provided to students in the intervention group. Objective PA assessments occurred at baseline, mid-, and end-of-semester during a 15-week academic semester. The control group showed a significant reduction in moderate- and vigorous-intensity PA (MVPA) minutes from baseline to the end-of-semester (P <.05), whereas the intervention group showed no changes in MVPA minutes over time. However, the intervention group also showed increased sedentary time and decreased time spent in light-intensity PA during the intervention period. Taken together, the present study found null effects of utilizing the wearable activity tracker in promoting PA in college students suggesting that intervention of primary using the wearable activity tracker as a behavior change strategy may not be effective to increase in PA in this setting.

Dose-response effects of a Web-based physical activity program on body composition and metabolic health in inactive older adults: additional analyses of a randomized controlled trial.

PubMed

Vroege, David P; Wijsman, Carolien A; Broekhuizen, Karen; de Craen, Anton J M; van Heemst, Diana; van der Ouderaa, Frans J G; van Mechelen, Willem; Slagboom, P Eline; Catt, Michael; Westendorp, Rudi G J; Verhagen, Evert A L M; Mooijaart, Simon P

2014-12-04

Low physical activity is a major risk factor for several age-related diseases. Recently, we showed in a randomized controlled trial that a 12-week Web-based intervention (Philips DirectLife) to increase physical activity was effective in increasing physical activity levels and metabolic health in an inactive population aged 60-70 years. The goal of this paper was to assess how many participants successfully reached the physical activity level as targeted by the intervention and what the effects of the intervention on body composition and metabolic health in these successful individuals were to provide insight in the maximum attainable effect of the intervention. Among the 235 participants in a randomized controlled trial of the Actief en Gezond Oud (AGO) study, we assessed the effects of the intervention on metabolic parameters in those who had successfully reached their personalized physical activity target compared with the entire intervention group. Furthermore, we studied the dose-response effect of increase in physical activity on metabolic outcome within the intervention group. Of the intervention group, 50 of 119 (42.0%) participants successfully reached the physical activity target (corresponding to a 10% increased daily physical activity on average). This group showed markedly higher effects of the intervention compared to the entire intervention group, with greater decreases in body weight (2.74 vs 1.49 kg), waist circumference (3.74 vs 2.33 cm), insulin resistance (HOMA index: 0.23 vs 0.20), and in cholesterol/HDL ratio (0.39 vs 0.20) and Framingham risk score (0.90% vs 0.54%). We found that men compared to women were more likely to be successful. The dose-response analysis showed that there was a significant association between increase in minutes spent in moderate-to-vigorous activity and body weight loss, BMI reduction, waist circumference reduction, HDL cholesterol increasing, and cholesterol/HDL ratio lowering. Of the intervention group, 42.0% (50/119) reached their daily physical activity end goal, which was associated with a markedly better effect on body composition and metabolic health compared to the effect in the entire intervention group. In this population, men are more likely to be successful in increasing physical activity. Findings demonstrate that improving the effect of such physical activity interventions requires finding new ways to increase the proportion of the population reaching the targeted goal. Dutch Trial Registry: NTR 3045; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3045 (Archived by WebCite at http://www.webcitation.org/6KPw52dCc).

The changing face of emotion: age-related patterns of amygdala activation to salient faces

PubMed Central

Evans, Jennifer W.; Morris, Drew; Lewis, Marc D.; Taylor, Margot J.

2011-01-01

The present study investigated age-related differences in the amygdala and other nodes of face-processing networks in response to facial expression and familiarity. fMRI data were analyzed from 31 children (3.5–8.5 years) and 14 young adults (18–33 years) who viewed pictures of familiar (mothers) and unfamiliar emotional faces. Results showed that amygdala activation for faces over a scrambled image baseline increased with age. Children, but not adults, showed greater amygdala activation to happy than angry faces; in addition, amygdala activation for angry faces increased with age. In keeping with growing evidence of a positivity bias in young children, our data suggest that children find happy faces to be more salient or meaningful than angry faces. Both children and adults showed preferential activation to mothers’ over strangers’ faces in a region of rostral anterior cingulate cortex associated with self-evaluation, suggesting that some nodes in frontal evaluative networks are active early in development. This study presents novel data on neural correlates of face processing in childhood and indicates that preferential amygdala activation for emotional expressions changes with age. PMID:20194512

Selective Estrogen Receptor Modulation Increases Hippocampal Activity during Probabilistic Association Learning in Schizophrenia

PubMed Central

Kindler, Jochen; Weickert, Cynthia Shannon; Skilleter, Ashley J; Catts, Stanley V; Lenroot, Rhoshel; Weickert, Thomas W

2015-01-01

People with schizophrenia show probabilistic association learning impairment in conjunction with abnormal neural activity. The selective estrogen receptor modulator (SERM) raloxifene preserves neural activity during memory in healthy older men and improves memory in schizophrenia. Here, we tested the extent to which raloxifene modifies neural activity during learning in schizophrenia. Nineteen people with schizophrenia participated in a twelve-week randomized, double-blind, placebo-controlled, cross-over adjunctive treatment trial of the SERM raloxifene administered orally at 120 mg daily to assess brain activity during probabilistic association learning using functional magnetic resonance imaging (fMRI). Raloxifene improved probabilistic association learning and significantly increased fMRI BOLD activity in the hippocampus and parahippocampal gyrus relative to placebo. A separate region of interest confirmatory analysis in 21 patients vs 36 healthy controls showed a positive association between parahippocampal neural activity and learning in patients, but no such relationship in the parahippocampal gyrus of healthy controls. Thus, selective estrogen receptor modulation by raloxifene concurrently increases activity in the parahippocampal gyrus and improves probabilistic association learning in schizophrenia. These results support a role for estrogen receptor modulation of mesial temporal lobe neural activity in the remediation of learning disabilities in both men and women with schizophrenia. PMID:25829142

Effect of salinity on nitrogenase activity and composition of the active diazotrophic community in intertidal microbial mats.

PubMed

Severin, Ina; Confurius-Guns, Veronique; Stal, Lucas J

2012-06-01

Microbial mats are often found in intertidal areas experiencing a large range of salinities. This study investigated the effect of changing salinities on nitrogenase activity and on the composition of the active diazotrophic community (nifH transcript libraries) of three types of microbial mats situated along a littoral gradient. All three mat types exhibited highest nitrogenase activity at salinities close to ambient seawater or lower. The response to lower or higher salinity was strongest in mats higher up in the littoral zone. Changes in nitrogenase activity as the result of exposure to different salinities were accompanied by changes in the active diazotrophic community. The two stations higher up in the littoral zone showed nifH expression by Cyanobacteria (Oscillatoriales and Chroococcales) and Proteobacteria (Gammaproteobacteria and Deltaproteobacteria). At these stations, a decrease in the relative contribution of Cyanobacteria to the nifH transcript libraries was observed at increasing salinity coinciding with a decrease in nitrogenase activity. The station at the low water mark showed low cyanobacterial contribution to nifH transcript libraries at all salinities but an increase in deltaproteobacterial nifH transcripts under hypersaline conditions. In conclusion, increased salinities caused decreased nitrogenase activity and were accompanied by a lower proportion of cyanobacterial nifH transcripts.

Trapezius muscle activity increases during near work activity regardless of accommodation/vergence demand level.

PubMed

Richter, H O; Zetterberg, C; Forsman, M

2015-07-01

To investigate if trapezius muscle activity increases over time during visually demanding near work. The vision task consisted of sustained focusing on a contrast-varying black and white Gabor grating. Sixty-six participants with a median age of 38 (range 19-47) fixated the grating from a distance of 65 cm (1.5 D) during four counterbalanced 7-min periods: binocularly through -3.5 D lenses, and monocularly through -3.5 D, 0 D and +3.5 D. Accommodation, heart rate variability and trapezius muscle activity were recorded in parallel. General estimating equation analyses showed that trapezius muscle activity increased significantly over time in all four lens conditions. A concurrent effect of accommodation response on trapezius muscle activity was observed with the minus lenses irrespective of whether incongruence between accommodation and convergence was present or not. Trapezius muscle activity increased significantly over time during the near work task. The increase in muscle activity over time may be caused by an increased need of mental effort and visual attention to maintain performance during the visual tasks to counteract mental fatigue.

Clustering and heterogeneous dynamics in a kinetic Monte Carlo model of self-propelled hard disks

NASA Astrophysics Data System (ADS)

Levis, Demian; Berthier, Ludovic

2014-06-01

We introduce a kinetic Monte Carlo model for self-propelled hard disks to capture with minimal ingredients the interplay between thermal fluctuations, excluded volume, and self-propulsion in large assemblies of active particles. We analyze in detail the resulting (density, self-propulsion) nonequilibrium phase diagram over a broad range of parameters. We find that purely repulsive hard disks spontaneously aggregate into fractal clusters as self-propulsion is increased and rationalize the evolution of the average cluster size by developing a kinetic model of reversible aggregation. As density is increased, the nonequilibrium clusters percolate to form a ramified structure reminiscent of a physical gel. We show that the addition of a finite amount of noise is needed to trigger a nonequilibrium phase separation, showing that demixing in active Brownian particles results from a delicate balance between noise, interparticle interactions, and self-propulsion. We show that self-propulsion has a profound influence on the dynamics of the active fluid. We find that the diffusion constant has a nonmonotonic behavior as self-propulsion is increased at finite density and that activity produces strong deviations from Fickian diffusion that persist over large time scales and length scales, suggesting that systems of active particles generically behave as dynamically heterogeneous systems.

Effect of oxygen plasma treatment on the electrochemical performance of the rayon and polyacrylonitrile based carbon felt for the vanadium redox flow battery application

NASA Astrophysics Data System (ADS)

Dixon, D.; Babu, D. J.; Langner, J.; Bruns, M.; Pfaffmann, L.; Bhaskar, A.; Schneider, J. J.; Scheiba, F.; Ehrenberg, H.

2016-11-01

Oxygen plasma treatment was applied on commercially available graphite felt electrodes based on rayon (GFA) and polyacrylonitrile (GFD). The formation of functional groups on the surface of the felt was confirmed by X-ray photoelectron spectroscopy measurements. The BET studies of the plasma treated electrodes showed no significant increase in surface area for both the rayon as well as the PAN based felts. Both plasma treated electrodes showed significantly enhanced V3+/V2+ redox activity compared to the pristine electrodes. Since an increase of the surface area has been ruled out for plasma treated electrode the enhanced activity could be attributed to surface functional groups. Interestingly, plasma treated GFD felts showed less electrochemical activity towards V5+/V4+ compared to the pristine electrode. Nevertheless, an overall increase of the single cell performance was still observed as the negative electrode is known to be the performance limiting electrode. Thus, to a great extent the present work helps to preferentially understand the importance of functional groups on the electrochemical activity of negative and positive redox reaction. The study emphasizes the need of highly active electrodes especially at the negative electrode side as inactive electrodes can still facilitate hydrogen evolution and degrade the electrolyte in VRFBs.

Synthesis of lipophilic tyrosyl esters derivatives and assessment of their antimicrobial and antileishmania activities

PubMed Central

2012-01-01

Background Preparation of tyrosyl lipophilic derivatives was carried out as a response to the food, cosmetic and pharmaceutical industries' increasing demand for new lipophilic antioxidants. Results A large series of tyrosyl esters (TyC2 to TyC18:1) with increasing lipophilicity was synthesized in a good yield using lipase from Candida antarctica (Novozyme 435). Spectroscopic analyses of purified esters showed that the tyrosol was esterified on the primary hydroxyl group. Synthetized compounds were evaluated for either their antimicrobial activity, by both diffusion well and minimal inhibition concentration (MIC) methods, or their antileishmanial activity against Leishmania major and Leishmania infantum parasite species. Among all the tested compounds, our results showed that only TyC8, TyC10 and TyC12 exhibited antibacterial and antileishmanial activities. When MIC and IC50 values were plotted against the acyl chain length of each tyrosyl derivative, TyC10 showed a parabolic shape with a minimum value. This nonlinear dependency with the increase of the chain length indicates that biological activities are probably associated to the surfactant effectiveness of lipophilic derivatives. Conclusion These results open up potential applications to use medium tyrosyl derivatives surfactants, antioxidants, antimicrobial and antileishmanial compounds in cosmetic, food and pharmaceutical industries. PMID:22264330

Characterization of functional brain activity and connectivity using EEG and fMRI in patients with sickle cell disease.

PubMed

Case, Michelle; Zhang, Huishi; Mundahl, John; Datta, Yvonne; Nelson, Stephen; Gupta, Kalpna; He, Bin

2017-01-01

Sickle cell disease (SCD) is a red blood cell disorder that causes many complications including life-long pain. Treatment of pain remains challenging due to a poor understanding of the mechanisms and limitations to characterize and quantify pain. In the present study, we examined simultaneously recording functional MRI (fMRI) and electroencephalogram (EEG) to better understand neural connectivity as a consequence of chronic pain in SCD patients. We performed independent component analysis and seed-based connectivity on fMRI data. Spontaneous power and microstate analysis was performed on EEG-fMRI data. ICA analysis showed that patients lacked activity in the default mode network (DMN) and executive control network compared to controls. EEG-fMRI data revealed that the insula cortex's role in salience increases with age in patients. EEG microstate analysis showed patients had increased activity in pain processing regions. The cerebellum in patients showed a stronger connection to the periaqueductal gray matter (involved in pain inhibition), and negative connections to pain processing areas. These results suggest that patients have reduced activity of DMN and increased activity in pain processing regions during rest. The present findings suggest resting state connectivity differences between patients and controls can be used as novel biomarkers of SCD pain.

Effect of one step KOH activation and CaO modified carbon in transesterification reaction

NASA Astrophysics Data System (ADS)

Yacob, Abd Rahim; Zaki, Muhammad Azam Muhammad

2017-11-01

In this work, one step activation was introduced using potassium hydroxide (KOH) and calcium oxide (CaO) modified palm kernel shells. Various concentration of calcium oxide was used as catalyst while maintaining the same concentration of potassium hydroxide to activate and impregnate the palm kernel shell before calcined at 500°C for 5 hours. All the prepared samples were characterized using Fourier Transform Infrared (FTIR) and Field Emission Scanning Electron Microscope (FESEM). FTIR analysis of raw palm kernel shell showed the presence of various functional groups. However, after activation, most of the functional groups were eliminated. The basic strength of the prepared samples were determined using back titration method. The samples were then used as base heterogeneous catalyst for the transesterification reaction of rice bran oil with methanol. Analysis of the products were performed using Gas Chromatography Flame Ionization Detector (GC-FID) to calculate the percentage conversion of the biodiesel products. This study shows, as the percentage of one step activation potassium and calcium oxide doped carbon increases thus, the basic strength also increases followed by the increase in biodiesel production. Optimization study shows that the optimum biodiesel production was at 8 wt% catalyst loading, 9:1 methanol: oil molar ratio at 65°C and 6 hours which gives a conversion up to 95%.

Functional magnetic resonance imaging of working memory and response inhibition in children with mild traumatic brain injury.

PubMed

Krivitzky, Lauren S; Roebuck-Spencer, Tresa M; Roth, Robert M; Blackstone, Kaitlin; Johnson, Chad P; Gioia, Gerard

2011-11-01

The current pilot study examined functional magnetic resonance imaging (fMRI) activation in children with mild traumatic brain injury (mTBI) during tasks of working memory and inhibitory control, both of which are vulnerable to impairment following mTBI. Thirteen children with symptomatic mTBI and a group of controls completed a version of the Tasks of Executive Control (TEC) during fMRI scanning. Both groups showed greater prefrontal activation in response to increased working memory load. Activation patterns did not differ between groups on the working memory aspects of the task, but children with mTBI showed greater activation in the posterior cerebellum with the addition of a demand for inhibitory control. Children with mTBI showed greater impairment on symptom report and "real world" measures of executive functioning, but not on traditional "paper and pencil" tasks. Likewise, cognitive testing did not correlate significantly with imaging results, whereas increased report of post-concussive symptoms were correlated with increased cerebellar activation. Overall, results provide some evidence for the utility of symptom report as an indicator of recovery and the hypothesis that children with mTBI may experience disrupted neural circuitry during recovery. Limitations of the study included a small sample size, wide age range, and lack of in-scanner accuracy data.

Changes of phenolic profiles and antioxidant activity in canaryseed (Phalaris canariensis L.) during germination.

PubMed

Chen, Zhijie; Yu, Lilei; Wang, Xinkun; Gu, Zhenxin; Beta, Trust

2016-03-01

Canaryseed is an important cereal crop in western Canada. The changes of the total phenolic content (TPC), antioxidant activities, phenolic acid profiles (free and bound) of canaryseed during germination were investigated in the present study. The growth properties also were investigated. Fresh weight, shoot length and root length increased, whereas dry mass of canaryseed decreased during germination. A 22.3% loss of dry matter was observed at 120h of germination. The total phenolic content and antioxidant activities of free and bound extracts showed a general trend of germinated seeds>raw seeds>soaked seeds. Free, bound and total phenolic content significantly increased 1042%, 120% and 741% at the end of germination as compared to raw seeds (p<0.05). DPPH, ABTS and ORAC assays were employed to evaluate the antioxidant activity of canaryseed. There were high correlations between total phenolic content and antioxidant activities. TPC and ORAC values showed the highest correlation (r=0.9984). Six phenolic acids in free phenolic extracts and seven phenolic acids in bound phenolic extracts were detected, respectively. Bound ferulic acid, the dominant phenolic acid in canaryseed, significantly increased during germination (p<0.05). Study showed that germination provided a new approach to further develop canaryseed as a functional food for human consumption. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pilot randomized trial of a volitional help sheet-based tool to increase leisure time physical activity in breast cancer survivors.

PubMed

Chapman, Janine; Fletcher, Chloe; Flight, Ingrid; Wilson, Carlene

2018-05-16

To develop and test a volitional help sheet-based tool to improve physical activity in breast cancer survivors compared to a standard self-generated implementation intention intervention. Pilot randomized trial conducted online over 3 months. Participants were randomized to an online volitional help sheet (n = 50) or implementation intention (n = 51) intervention. Measures were taken at baseline, 1 and 3 months. The main outcome measure was moderate-strenuous leisure time physical activity. Secondary outcomes were health-related quality of life and mood. Participants exposed to the volitional help sheet and implementation intention interventions showed similar effects after 1 month, with both groups reporting a significant increase in moderate-strenuous physical activity. After 3 months, the initial increase in physical activity was maintained by the volitional help sheet group, but not the implementation intention group. Improvements were also found for negative affect and emotional quality of life. While both interventions show promise in promoting physical activity in breast cancer survivors, the volitional help sheet may be more effective for facilitating lasting change and emotional well-being. Findings suggest that the volitional help sheet may have potential to offer a cost-effective contribution to consumer-led tertiary preventive health. Future research should test these initial findings in a definitive trial. Statement of contribution What is already known on this subject? Physical activity is important for optimizing health in breast cancer survivors. Despite this, physical activity in this cohort remains low. Theory-based strategies are needed to help breast cancer survivors independently manage and maintain regular physical activity over the long term. What does this study add? Online planning interventions can improve physical activity in breast cancer survivors. Volitional help sheets, but not implementation intentions, show sustained effects for 3 months. The intervention shows promise as a potential low-cost addition to long-term survivorship care plans. © 2018 The British Psychological Society.

Hyperthyroidism results in increased glycolytic capacity in the rat heart. A 31P-NMR study.

PubMed

Seymour, A M; Eldar, H; Radda, G K

1990-11-12

We have investigated the metabolic adaptations that occur in the thyroxine-treated rat heart. Rats were made hyperthyroid by daily intra-peritoneal injections of thyroxine (35 micrograms/100 g body weight) over seven days. 31P-NMR investigations of isolated glucose-perfused isometric hearts showed that thyroxine treatment caused an increase in Pi (from 4.9 mumols.(g dry wt.)-1 in control hearts to 11.7 mumols.(g dry wt.)-1 in hyperthyroid hearts), a decrease in phosphocreatine (from 36.5 mumols.(g dry wt.)-1 to 21.8 mumols.(g dry wt.)-1) with no change in ATP or ADP concentrations under the same conditions of cardiac work. The unidirectional exchange flux Pi----ATP was measured by saturation transfer NMR in hyperthyroid rat hearts. This exchange (which has been shown to contain a significant glycolytic component) increased by 2.2-fold in thyroxine-treated hearts in comparison to control hearts (to 3.6 mumols.(g dry wt.)-1.s-1, from 1.6 mumols.(g dry wt.)-1.s-1). In parallel experiments, NMR analysis of extracts from hyperthyroid rat hearts showed significantly elevated levels of glucose 6-phosphate, and fructose 6-phosphate. Measurements of enzyme activities isolated from hyperthyroid and control tissue showed a 40% increase in phosphofructokinase activity. These data together with the increased concentration of Pi show that both glycolytic and glycogenolytic fluxes are increased in the hyperthyroid rat heart. This metabolic adaptation may be necessary to cope with the increased number and activity of Na+/K(+)-ATPase pumps that occur in response to thyroxine treatment.

Oligo-carrageenan kappa-induced reducing redox status and activation of TRR/TRX system increase the level of indole-3-acetic acid, gibberellin A3 and trans-zeatin in Eucalyptus globulus trees.

PubMed

González, Alberto; Contreras, Rodrigo A; Zúiga, Gustavo; Moenne, Alejandra

2014-08-20

Eucalyptus globulus trees treated with oligo-carrageenan (OC) kappa showed an increase in NADPH, ascorbate and glutathione levels and activation of the thioredoxin reductase (TRR)/thioredoxin (TRX) system which enhance photosynthesis, basal metabolism and growth. In order to analyze whether the reducing redox status and the activation of thioredoxin reductase (TRR)/thioredoxin (TRX) increased the level of growth-promoting hormones, trees were treated with water (control), with OC kappa, or with inhibitors of ascorbate synthesis, lycorine, glutathione synthesis, buthionine sulfoximine (BSO), NADPH synthesis, CHS-828, and thioredoxin reductase activity, auranofine, and with OC kappa, and cultivated for four additional months. Eucalyptus trees treated with OC kappa showed an increase in the levels of the auxin indole 3-acetic acid (IAA), gibberellin A3 (GA3) and the cytokinin trans-zeatin (t-Z) as well as a decrease in the level of the brassinosteroid epi-brassinolide (EB). In addition, treatment with lycorine, BSO, CHS-828 and auranofine inhibited the increase in IAA, GA3 and t-Z as well as the decrease in EB levels. Thus, the reducing redox status and the activation of TRR/TRX system induced by OC kappa increased the levels of IAA, GA3 and t-Z levels determining, at least in part, the stimulation of growth in Eucalyptus trees.

Effect of seasonality and Cr(VI) on starch-sucrose partitioning and related enzymes in floating leaves of Salvinia minima.

PubMed

Rosa, Mariana; Prado, Carolina; Chocobar-Ponce, Silvana; Pagano, Eduardo; Prado, Fernando

2017-09-01

Effects of seasonality and increasing Cr(VI) concentrations on leaf starch-sucrose partitioning, sucrose- and starch-related enzyme activities, and carbon allocation toward leaf development were analyzed in fronds (floating leaves) of the floating fern Salvinia minima. Carbohydrates and enzyme activities of Cr-exposed fronds showed different patterns in winter and summer. Total soluble sugars, starch, glucose and fructose increased in winter fronds, while sucrose was higher in summer ones. Starch and soluble carbohydrates, except glucose, increased under increasing Cr(VI) concentrations in winter fronds, while in summer ones only sucrose increased under Cr(VI) treatment. In summer fronds starch, total soluble sugars, fructose and glucose practically stayed without changes in all assayed Cr(VI) concentrations. Enzyme activities related to starch and sucrose metabolisms (e.g. ADPGase, SPS, SS and AI) were higher in winter fronds than in summer ones. Total amylase and cFBPase activities were higher in summer fronds. Cr(VI) treatment increased enzyme activities, except ADPGase, in both winter and summer fronds but no clear pattern changes were observed. Data of this study show clearly that carbohydrate metabolism is differently perturbed by both seasonality and Cr(VI) treatment in summer and winter fronds, which affects leaf starch-sucrose partitioning and specific leaf area (SLA) in terms of carbon investment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cortical Integration of Audio-Visual Information

PubMed Central

Vander Wyk, Brent C.; Ramsay, Gordon J.; Hudac, Caitlin M.; Jones, Warren; Lin, David; Klin, Ami; Lee, Su Mei; Pelphrey, Kevin A.

2013-01-01

We investigated the neural basis of audio-visual processing in speech and non-speech stimuli. Physically identical auditory stimuli (speech and sinusoidal tones) and visual stimuli (animated circles and ellipses) were used in this fMRI experiment. Relative to unimodal stimuli, each of the multimodal conjunctions showed increased activation in largely non-overlapping areas. The conjunction of Ellipse and Speech, which most resembles naturalistic audiovisual speech, showed higher activation in the right inferior frontal gyrus, fusiform gyri, left posterior superior temporal sulcus, and lateral occipital cortex. The conjunction of Circle and Tone, an arbitrary audio-visual pairing with no speech association, activated middle temporal gyri and lateral occipital cortex. The conjunction of Circle and Speech showed activation in lateral occipital cortex, and the conjunction of Ellipse and Tone did not show increased activation relative to unimodal stimuli. Further analysis revealed that middle temporal regions, although identified as multimodal only in the Circle-Tone condition, were more strongly active to Ellipse-Speech or Circle-Speech, but regions that were identified as multimodal for Ellipse-Speech were always strongest for Ellipse-Speech. Our results suggest that combinations of auditory and visual stimuli may together be processed by different cortical networks, depending on the extent to which speech or non-speech percepts are evoked. PMID:20709442

Investigation of repressive and enhancive effects of fruit extracts on the activity of glucose-6-phophatase.

PubMed

Zahoor, Muhammad; Jan, Muhammad Rasul; Naz, Sumaira

2016-11-01

Glucose-6-phosphatase is a key enzyme of glucose metabolic pathways. Deficiency of this enzyme leads to glycogen storage disease. This enzyme also plays a negative role in diabetes mellitus disorder in which the catalytic activity of this enzyme increases. Thus there is need for activators to enhance the activity of glucose-6-phosphatase in glycogen storage disease of type 1b while in diabetes mellitus repressors are needed to reduce its activity. Crude extracts of apricot, fig, mulberry and apple fruits were investigated for their repressive/enhancive effects on glucose-6-phosphatase in vivo. Albino mice were used as experimental animal. All the selected extracts showed depressive effects on glucose-6-phosphatase, which shows that all these extracts can be used as antidiabetic supplement of food. The inhibitory pattern was competitive one, which was evident from the effect of increasing dose from 1g/Kg body weight to 3g/Kg body weight for all the selected fruit extracts. However fig and apple fruit extracts showed high repressive effects for high doses as compared to apricot and mulberry fruit extracts. None of these selected fruit extracts showed enhancive effect on glucose-6-phosphatase activity. All these fruits or their extracts can be used as antidiabetic dietary supplement for diabetes mellitus.

Uterine activty and plasma progesterone levels in pregnant goats.

PubMed

Jones, D E; Kinfton, A

1977-01-01

Uterine activity was recorded during the last few weeks of pregnacy in goats, and related to changes in plasma progesterone concentration. In six of the 14 pregnancies, there was little activity until immediately pre-partum, but the remainder showed a progressive increase in uterine motility, particularly during the last seven days of pregnancy. There was a significant correlation between increased uterine activity and decline of peripheral plasma progesterone levels.

Differences in Brain Function and Changes with Intervention in Children with Poor Spelling and Reading Abilities

PubMed Central

Gebauer, Daniela; Fink, Andreas; Kargl, Reinhard; Reishofer, Gernot; Koschutnig, Karl; Purgstaller, Christian; Fazekas, Franz; Enzinger, Christian

2012-01-01

Previous fMRI studies in English-speaking samples suggested that specific interventions may alter brain function in language-relevant networks in children with reading and spelling difficulties, but this research strongly focused on reading impaired individuals. Only few studies so far investigated characteristics of brain activation associated with poor spelling ability and whether a specific spelling intervention may also be associated with distinct changes in brain activity patterns. We here investigated such effects of a morpheme-based spelling intervention on brain function in 20 children with comparatively poor spelling and reading abilities using repeated fMRI. Relative to 10 matched controls, children with comparatively poor spelling and reading abilities showed increased activation in frontal medial and right hemispheric regions and decreased activation in left occipito-temporal regions prior to the intervention, during processing of a lexical decision task. After five weeks of intervention, spelling and reading comprehension significantly improved in the training group, along with increased activation in the left temporal, parahippocampal and hippocampal regions. Conversely, the waiting group showed increases in right posterior regions. Our findings could indicate an increased left temporal activation associated with the recollection of the new learnt morpheme-based strategy related to successful training. PMID:22693600

Effects of processing steps on the phenolic content and antioxidant activity of beer.

PubMed

Leitao, Céline; Marchioni, Eric; Bergaentzlé, Martine; Zhao, Minjie; Didierjean, Luc; Taidi, Behnam; Ennahar, Saïd

2011-02-23

A new analytical method (liquid chromatography-antioxidant, LC-AOx) was used that is intended to separate beer polyphenols and to determine the potential antioxidant activity of these constituents after they were allowed to react online with a buffered solution of the radical cation 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(•+)). Using the LC-AOx method, it was possible to demonstrate that the extent of the antioxidant activity was very much dependent on the phenolic compound considered. The method was also applied to the analysis of beer extracts and allowed the evaluation of their antioxidant activity at different steps of beer processing: brewing, boiling, and fermentation. This study showed that the total antioxidant activity remained unchanged throughout beer processing, as opposed to the polyphenolic content, which showed a 3-fold increase. Hopping and fermentation steps were the main causes of this increase. However, the increase measured after fermentation was attributed to a better extraction of polyphenols due to the presence of ethanol, rather than to a real increase in their content. Moreover, this method allowed the detection of three unknown antioxidant compounds, which accounted for 64 ± 4% of the total antioxidant activity of beer and were individually more efficient than caffeic acid and epicatechin.

Influence of pressure changes on recruitment pattern and neck muscle activities during Cranio-Cervical Flexion Tests (CCFTs).

PubMed

Park, Junhyung; Hur, Jingang; Ko, Taesung

2015-01-01

The muscle activity of the deep cervical flexors is emphasized more than that of the superficial cervical flexors, and it has been reported that functional disorders of the longuscolli are found in patients who experience neck pain. The objective of this study was to analyze the recruitment patterns and muscle activities of the cervical flexors during Cranio-Cervical Flexion Tests (CCFTs) through real-time ultrasonography and surface electromyography with a view to presenting appropriate pressure levels for deep cervical flexor exercise protocols based on the results of the analysis. The twenty subjects without neck pain were trained until they became accustomed to CCFTs, and the pressure level was increased gradually from 20 mmHg to 40 mmHg by increasing the pressure level 5 mmHg at a time. Real-time ultrasonography images of the longuscolli and the sternocleidomastoid were taken to measure the amounts of changes in the thicknesses of these muscles, and surface electromyography was implemented to observe the muscle activity of the sternocleidomastoid. The measured value is RMS. According to the results of the ultrasonography, the muscle thicknesses of both the longuscolli and the sternocleidomastoid showed significant increases, as the pressure increased up to 40 mmHg (p< 0.05). The differences in the muscle thicknesses at all individual pressure levels showed significant increases (p< 0.05). According to the results of the electromyography, the muscle activity of the sternocleidomastoid gradually increased as the pressure increased up to 40 mmHg, the increases were significant between 20 mmHg and 25 mmHg, between 30 mmHg and 35 mmHg (p< 0.05). The pressure levels of exercise methods at which the muscle activity of the deep cervical flexors is maximally increased and the muscle activity of the superficial cervical flexors is minimally increased are 25 mmHg-30 mmHg.

Airport Performance and Construction Enlargement Activities

NASA Astrophysics Data System (ADS)

Hanun, Y.; Setiawan, M. I.; Kurniasih, N.; Hasyim, C.; Ahmar, A. S.

2018-01-01

The evaluation of transportation infrastructure project should consider the contribution towards infrastructure growth. This research aims to analyze the effect of Construction enlargement activities towards airport performance. This research is correlation study. The population includes 148 airports in Indonesia. By using total sampling, there were 148 sample airports. The result shows that the construction enlargement activities variable has relatively strong relationship to Airport Performance variable, while the adjusted R Square score shows the increasing construction enlargement activities that affected by the other factors aside from airport performance.

Anti-MRSA activity of isoplagiochin-type macrocyclic bis(bibenzyl)s is mediated through cell membrane damage.

PubMed

Onoda, Kenji; Sawada, Hiromi; Morita, Daichi; Fujii, Kana; Tokiwa, Hiroaki; Kuroda, Teruo; Miyachi, Hiroyuki

2015-07-01

We synthesized three geometrical isomers of a macrocyclic bis(bibenzyl) based on isoplagiochin, a natural product isolated from bryophytes, and evaluated their antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). The isomer containing a 1,4-linked ring (5) showed only weak activity, whereas the isomers containing a 1,3-linked (6) or 1,2-linked (7) C ring showed potent anti-MRSA activity. Molecular dynamics calculations indicated that these differences are probably due to differences in the conformational flexibility of the macrocyclic ring; the active compounds 6 and 7 were more rigid than 5. In order to understand the action mechanism of anti-MRSA activity, we investigated the cellular flux of a fluorescent DNA-binder, ethidium bromide (EtBr), in the presence and absence of these macrocycles. The active compound 6 increased the levels of EtBr inflow and outflow in S. aureus cells, as did our potent anti-MRSA riccardin derivative (4), indicating that these compounds increased the permeability of the cytoplasmic membrane. Inactive 5 had no effect on EtBr inflow or outflow. Furthermore, compound 6 abrogated the normal intracellular concentration gradients of Na(+) and K(+) in S. aureus cells, increasing the intracellular Na(+) concentration and decreasing the K(+) concentration, while 5 had no such effect. These results indicate that anti-MRSA-active macrocyclic bis(bibenzyl) derivatives directly damage the gram-positive bacterial membrane, resulting in increased permeability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Deletion of Wiskott–Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells

PubMed Central

Baptista, Marisa A. P.; Keszei, Marton; Oliveira, Mariana; Sunahara, Karen K. S.; Andersson, John; Dahlberg, Carin I. M.; Worth, Austen J.; Liedén, Agne; Kuo, I-Chun; Wallin, Robert P. A.; Snapper, Scott B.; Eidsmo, Liv; Scheynius, Annika; Karlsson, Mikael C. I.; Bouma, Gerben; Burns, Siobhan O.; Forsell, Mattias N. E.; Thrasher, Adrian J.; Nylén, Susanne; Westerberg, Lisa S.

2016-01-01

Wiskott–Aldrich syndrome (WAS) is caused by loss-of-function mutations in the WASp gene. Decreased cellular responses in WASp-deficient cells have been interpreted to mean that WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an exception to this concept and show that WASp-deficient dendritic cells have increased activation of Rac2 that support cross-presentation to CD8+ T cells. Using two different skin pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin and increased expansion of IFNγ-producing CD8+ T cells in the draining lymph node and spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8+ T cells at the expense of CD4+ T cells. WASp-deficient dendritic cells induce increased cross-presentation to CD8+ T cells by activating Rac2 that maintains a near neutral pH of phagosomes. Our data reveals an intricate balance between activation of WASp and Rac2 signalling pathways in dendritic cells. PMID:27425374

Increased Amino Acid Uptake Supports Autophagy-Deficient Cell Survival upon Glutamine Deprivation.

PubMed

Zhang, Nan; Yang, Xin; Yuan, Fengjie; Zhang, Luyao; Wang, Yanan; Wang, Lina; Mao, Zebin; Luo, Jianyuan; Zhang, Hongquan; Zhu, Wei-Guo; Zhao, Ying

2018-06-05

Autophagy is a protein degradation process by which intracellular materials are recycled for energy homeostasis. However, the metabolic status and energy source of autophagy-defective tumor cells are poorly understood. Here, our data show that amino acid uptake from the extracellular environment is increased in autophagy-deficient cells upon glutamine deprivation. This elevated amino acid uptake results from activating transcription factor 4 (ATF4)-dependent upregulation of AAT (amino acid transporter) gene expression. Furthermore, we identify SIRT6, a NAD + -dependent histone deacetylase, as a corepressor of ATF4 transcriptional activity. In autophagy-deficient cells, activated NRF2 enhances ATF4 transcriptional activity by disrupting the interaction between SIRT6 and ATF4. In this way, autophagy-deficient cells exhibit increased AAT expression and show increased amino acid uptake. Notably, inhibition of amino acid uptake reduces the viability of glutamine-deprived autophagy-deficient cells, but not significantly in wild-type cells, suggesting reliance of autophagy-deficient tumor cells on extracellular amino acid uptake. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Increased Staphylococcus-killing activity of an antimicrobial peptide, lactoferricin B, with minocycline and monoacylglycerol.

PubMed

Wakabayashi, Hiroyuki; Teraguchi, Susumu; Tamura, Yoshitaka

2002-10-01

This study aimed to find antibiotics or other compounds that could increase the antimicrobial activity of an antimicrobial peptide, lactoferricin B (LFcin B), against Staphylococcus aureus, including antibiotic-resistant strains. Among conventional antibiotics, minocycline increased the bactericidal activity of LFcin B against S. aureus, but methicillin, ceftizoxime, and sulfamethoxazole-trimethoprim did not have such an effect. The combination of minocycline and LFcin B had synergistic effects against three antibiotic-resistant strains of S. aureus, according to result of checkerboard analysis. Screening of 33 compounds, including acids and salts, alcohols, amino acids, proteins and peptides, sugar, and lipids, showed that medium-chain monoacylglycerols increased the bactericidal activity of LFcin B against three S. aureus strains. The short-term killing test in water and the killing curve test in growing cultures showed that a combination of LFcin B and monolaurin (a monoacylglycerol with a 12-carbon acyl chain) killed S. aureus more rapidly than either agent alone. These findings may be helpful in the application of antimicrobial peptides in medical or other situations.

The effects of rod and cone loss on the photic regulation of locomotor activity and heart rate.

PubMed

Thompson, Stewart; Lupi, Daniela; Hankins, Mark W; Peirson, Stuart N; Foster, Russell G

2008-08-01

Behavioral responses to light indirectly affect cardiovascular output, but in anesthetized rodents a direct effect of light on heart rate has also been described. Both the basis for this response and the contribution of rods, cones and melanopsin-based photosensitive retinal ganglion cells (pRGCs) remains unknown. To understand how light acutely regulates heart rate we studied responses to light in mice lacking all rod and cone photoreceptors (rd/rd cl ) along with wild-type controls. Our initial experiments delivered light to anesthetized mice at Zeitgeber time (ZT)16 (4 h after lights off, mid-activity phase) and produced an increase in heart rate in wild-type mice, but not in rd/rd cl animals. By contrast, parallel experiments in freely-moving mice demonstrated that light exposure at this time suppressed heart rate and activity in both genotypes. Because of the effects of anesthesia, all subsequent studies were conducted in freely-moving animals. The effects of light were also assessed at ZT6 (mid-rest phase). At this timepoint, wild-type mice showed an irradiance-dependent increase in heart rate and activity. By contrast, rd/rd cl mice failed to show any modulation of heart rate or activity, even at very high irradiances. Increases in heart rate preceded increases in locomotor activity and remained elevated when locomotor activity ceased, suggesting that these two responses are at least partially uncoupled. Collectively, our results show an acute and phase-dependent effect of light on cardiovascular output in mice. Surprisingly, this irradiance detection response is dependent upon rod and cone photoreceptors, with no apparent contribution from melanopsin pRGCs.

Ankle Ranges of Motion During Extended Activity Periods While Taped and Braced

PubMed Central

Paris, David L.; Kokkaliaris, Jimmy; Vardaxis, Vassilios

1995-01-01

Tape has traditionally been used to support the ankle during activity. More recently, commercial ankle braces have been worn as an alternative. The cumulative information on the effects of taped versus braced ankle support or interbrace comparisons is inconclusive. With few exceptions, ankle brace studies have collected data soon after support conditions were administered. Plantar-dorsiflexion and inversion-eversion ranges of motion (ROM) of 30 subjects were compared under conditions of unsupported, nonelastic adhesivetaped, and Swede-O and Sub Talar Support-braced ankles. We recorded measurements before activity and after periods of 15, 30, 45, and 60 minutes of selected activity on a motorized treadmill. All support conditions significantly reduced preactivity ROM in all directions compared to unsupported ankles. Results showed that the ankle significantly increased in plantarflexion ROM 15 minutes after the initiation of activity with tape or the SubTalar Support-brace, and after 30 minutes with the Swede-O brace. Tape showed further significant increases in plantarflexion ROM after 15-minute intervals of 30, 45, and 60 minutes of activity. All three support conditions had increased significantly in inversion ROM by 15 minutes of activity. The SubTalar Support brace showed a further significant inversion ROM increase between 15 and 30 minutes postactivity. We conclude that the Swede-O and SubTalar Support braces and tape offer significant preactivity ankle support in all four directions of movement. We also conclude that both braces offer longer postactivity support than tape. In inversion ROM and plantarflexion ROM, actions prevalent in ankle sprains, the Swede-O brace retained support longer than the SubTalar Support brace. ImagesFig 1.Fig 2.Fig 3. PMID:16558340

Differential loss of biological activity of the enkephalins induced by current.

PubMed

Kitchen, I; Hart, S L

1981-01-29

Passage of current across solutions of enkephalins caused loss of biological activity of the peptides, this loss increasing as current strength was increased. The presence of a vas deferens tissue prevented the current-induced loss of activity of Leu-enkephalin but had no effect on the loss of activity of Met-enkephalin. These results provide a possible explanation for the differential potency of the enkephalins on the vas and provide a reason for the inability of several laboratories to show electrically induced enkephalin release.

Engineering α-amylase levels in wheat grain suggests a highly sophisticated level of carbohydrate regulation during development

PubMed Central

Whan, Alex; Dielen, Anne-Sophie; Mieog, Jos; Bowerman, Andrew F.; Robinson, Hannah M.; Byrne, Keren; Colgrave, Michelle; Larkin, Philip J.; Howitt, Crispin A.; Morell, Matthew K.; Ral, Jean-Philippe

2014-01-01

Wheat starch degradation requires the synergistic action of different amylolytic enzymes. Our spatio-temporal study of wheat α-amylases throughout grain development shows that AMY3 is the most abundant isoform compared with the other known α-amylases. Endosperm-specific over-expression of AMY3 resulted in an increase of total α-amylase activity in harvested grains. Unexpectedly, increased activity did not have a significant impact on starch content or composition but led to an increase of soluble carbohydrate (mainly sucrose) in dry grain. In AMY3 overexpression lines (A3OE), germination was slightly delayed and triacylglycerol (TAG) content was increased in the endosperm of mature grain. Despite increased AMY3 transcript and protein content throughout grain development, alterations of α-amylase activity and starch granule degradation were not detected until grain maturation, suggesting a post-translational inhibition of α-amylase activity in the endosperm during the starch filling period. These findings show unexpected effects of a high level of α-amylase on grain development and composition, notably in carbon partitioning and TAG accumulation, and suggest the presence of a hitherto unknown regulatory pathway during grain filling. PMID:25053646

Nitric oxide and hypoxia stimulate erythropoietin receptor via MAPK kinase in endothelial cells

PubMed Central

Cokic, Bojana B Beleslin; Cokic, Vladan P; Suresh, Sukanya; Wirt, Stacey; Noguchi, Constance Tom

2014-01-01

Erythropoietin receptor (EPOR) expression level determines the extent of erythropoietin (EPO) response. Previously we showed that EPOR expression in endothelial cells is increased at low oxygen tension and that EPO stimulation of endothelial cells during hypoxia can increase endothelial nitric oxide (NO) synthase (eNOS) expression and activation as well as NO production. We now observe that while EPO can stimulate NO production, NO in turn can regulate EPOR expression. Human umbilical vein endothelial cells (HUVEC) treated with 10–50 μM of NO donor diethylenetriamine NONOate (DETANO) for 24 hours showed significant induction of EPOR gene expression at 5% and 2% of oxygen. Also human bone marrow microvascular endothelial cell line (TrHBMEC) cultured at 21 and 2% oxygen with 50 μM DETANO demonstrated a time and oxygen dependent induction of EPOR mRNA expression after 24 and 48 hours, particularly at low oxygen tension. EPOR protein was also induced by DETANO at 2% oxygen in TrHBMEC and HUVEC. The activation of signaling pathways by NO donor stimulation appeared to be distinct from EPO stimulation. In reporter gene assays, DETANO treatment of HeLa cells at 2% oxygen increased EPOR promoter activity indicated by a 48% increase in luciferase activity with a 2 kb EPOR promoter fragment and a 71% increase in activity with a minimal EPOR promoter fragment containing 0.2Kb 5′. We found that DETANO activated MAPK kinase in TrHBMEC both in normoxia and hypoxia, while MAPK kinase inhibition showed significant reduction of EPOR mRNA gene expression at low oxygen tension, suggesting MAPK involvement in NO mediated induction of EPOR. Furthermore, DETANO stimulated Akt anti-apoptotic activity after 30 minutes in normoxia, whereas it inhibited Akt phosphorylation in hypoxia. In contrast, EPO did not significantly increase MAPK activity while EPO stimulated Akt phosphorylation in TrHBMEC in normoxia and hypoxia. These observations provide a new effect of NO on EPOR expression to enhance EPO response in endothelial cells, particularly at low oxygen tensions. PMID:24518819

Nitric oxide and hypoxia stimulate erythropoietin receptor via MAPK kinase in endothelial cells.

PubMed

Cokic, Bojana B Beleslin; Cokic, Vladan P; Suresh, Sukanya; Wirt, Stacey; Noguchi, Constance Tom

2014-03-01

Erythropoietin receptor (EPOR) expression level determines the extent of erythropoietin (EPO) response. Previously we showed that EPOR expression in endothelial cells is increased at low oxygen tension and that EPO stimulation of endothelial cells during hypoxia can increase endothelial nitric oxide (NO) synthase (eNOS) expression and activation as well as NO production. We now observe that while EPO can stimulate NO production, NO in turn can regulate EPOR expression. Human umbilical vein endothelial cells (HUVEC) treated with 10-50 μM of NO donor diethylenetriamine NONOate (DETANO) for 24h showed significant induction of EPOR gene expression at 5% and 2% of oxygen. Also human bone marrow microvascular endothelial cell line (TrHBMEC) cultured at 21 and 2% oxygen with 50 μM DETANO demonstrated a time and oxygen dependent induction of EPOR mRNA expression after 24 and 48 h, particularly at low oxygen tension. EPOR protein was also induced by DETANO at 2% oxygen in TrHBMEC and HUVEC. The activation of signaling pathways by NO donor stimulation appeared to be distinct from EPO stimulation. In reporter gene assays, DETANO treatment of HeLa cells at 2% oxygen increased EPOR promoter activity indicated by a 48% increase in luciferase activity with a 2 kb EPOR promoter fragment and a 71% increase in activity with a minimal EPOR promoter fragment containing 0.2 kb 5'. We found that DETANO activated MAPK kinase in TrHBMEC both in normoxia and hypoxia, while MAPK kinase inhibition showed significant reduction of EPOR mRNA gene expression at low oxygen tension, suggesting MAPK involvement in NO mediated induction of EPOR. Furthermore, DETANO stimulated Akt anti-apoptotic activity after 30 min in normoxia, whereas it inhibited Akt phosphorylation in hypoxia. In contrast, EPO did not significantly increase MAPK activity while EPO stimulated Akt phosphorylation in TrHBMEC in normoxia and hypoxia. These observations provide a new effect of NO on EPOR expression to enhance EPO response in endothelial cells, particularly at low oxygen tensions. Copyright © 2014 Elsevier Inc. All rights reserved.

Fgf signaling controls pharyngeal taste bud formation through miR-200 and Delta-Notch activity.

PubMed

Kapsimali, Marika; Kaushik, Anna-Lila; Gibon, Guillaume; Dirian, Lara; Ernest, Sylvain; Rosa, Frederic M

2011-08-01

Taste buds, the taste sensory organs, are conserved in vertebrates and composed of distinct cell types, including taste receptor, basal/presynaptic and support cells. Here, we characterize zebrafish taste bud development and show that compromised Fgf signaling in the larva results in taste bud reduction and disorganization. We determine that Fgf activity is required within pharyngeal endoderm for formation of Calb2b(+) cells and reveal miR-200 and Delta-Notch signaling as key factors in this process. miR-200 knock down shows that miR-200 activity is required for taste bud formation and in particular for Calb2b(+) cell formation. Compromised delta activity in mib(-/-) dramatically reduces the number of Calb2b(+) cells and increases the number of 5HT(+) cells. Conversely, larvae with increased Notch activity and ascl1a(-/-) mutants are devoid of 5HT(+) cells, but have maintained and increased Calb2b(+) cells, respectively. These results show that Delta-Notch signaling is required for intact taste bud organ formation. Consistent with this, Notch activity restores Calb2b(+) cell formation in pharyngeal endoderm with compromised Fgf signaling, but fails to restore the formation of these cells after miR-200 knock down. Altogether, this study provides genetic evidence that supports a novel model where Fgf regulates Delta-Notch signaling, and subsequently miR-200 activity, in order to promote taste bud cell type differentiation.

Brain Activation for Language Dual-Tasking: Listening to Two People Speak at the Same Time and a Change in Network Timing

PubMed Central

Buchweitz, Augusto; Keller, Timothy A.; Meyler, Ann; Just, Marcel Adam

2011-01-01

The study used fMRI to investigate brain activation in participants who were able to listen to and successfully comprehend two people speaking at the same time (dual-tasking). The study identified brain mechanisms associated with high-level, concurrent dual-tasking, as compared to comprehending a single message. Results showed an increase in the functional connectivity among areas of the language network in the dual task. The increase in synchronization of brain activation for dual-tasking was brought about primarily by a change in the timing of left inferior frontal gyrus (LIFG) activation relative to posterior temporal activation, bringing the LIFG activation into closer correspondence with temporal activation. The results show that the change in LIFG timing was greater in participants with lower working memory capacity, and that recruitment of additional activation in the dual-task occurred only in the areas adjacent to the language network that was activated in the single task. The shift in LIFG activation may be a brain marker of how the brain adapts to high-level dual-tasking. PMID:21618666

Assessment of Maillard reaction evolution, prebiotic carbohydrates, antioxidant activity and α-amylase inhibition in pulse flours.

PubMed

Moussou, Nadia; Corzo-Martínez, Marta; Sanz, María Luz; Zaidi, Farid; Montilla, Antonia; Villamiel, Mar

2017-03-01

In this paper, the quality of bean, chickpea, fava beans, lentil and pea flours from Algeria has been evaluated. Maillard reaction (MR) indicators, modifications in the carbohydrate and protein fractions, antioxidant activity and α-amylase inhibitor of raw, toasted and stored samples were evaluated. Fava beans, beans and peas showed higher content of raffinose family oligosaccharides while chickpeas and lentils showed higher polyol content. Toasting and storage caused slightly change in pulse quality; MR showed slight losses of lysine but increased antioxidant activity. Moreover, inhibition of α-amylase was slightly augmented during processing; this could increase the undigested carbohydrates that reach the colon, modulating the glycemic response. These results point out the suitability of these flours for preparing high-quality foodstuffs intended for a wide spectrum of the population, including hyperglycemic and gluten intolerant individuals.

Testicular glucose and its transporter GLUT 8 as a marker of age-dependent variation and its role in steroidogenesis in mice.

PubMed

Banerjee, Arnab; Anuradha; Mukherjee, Kaustab; Krishna, Amitabh

2014-11-01

The present study evaluates the hypothesis, that glucose is essential for steroidogenesis and inadequate supply of glucose to the testis may be responsible for decline in steroidogenesis in mice during aging. Mice of different age groups (birth, weaning, puberty, reproductively active, and senescence) were utilized for this study. The changes in glucose, glucose transporter (GLUT), and insulin receptor (IR) level in the testis were evaluated and compared with the testicular steroidogenic parameters such as steroidogenic acute regulatory protein (StAR), 3β-hydroxy steroid dehydrogenase (3β-HSD) and circulating testosterone levels. The result showed significant correlation between changes in GLUT 8 and glucose levels with changes in StAR level in the testis and circulating testosterone level in the mice from birth to senescence. Immunohistochemical analysis showed intense immunostaining of GLUT 8 and IR in the interstitial cells, most likely Leydig cells, in testis of pubertal and reproductively active mice suggesting their relevance in steroidogenesis. The in vitro study showed a significant positive correlation between luteinizing hormone (LH)-induced increase in GLUT 8 and StAR (r = 0.82; P < 0.05) proteins level in the testes with increase in testosterone (r = 0.97; P < 0.05) synthesis of reproductively active mice. This study also showed increased release of lactate with increased uptake of glucose by the testis. Further, intra-testicular treatment of 2-deoxy glucose, to reproductively active mice caused a significant decrease in 3β-HSD enzyme activity in the testis. Based on these findings, it may be concluded that the changes in glucose level either directly or indirectly lead to changes in testicular steroidogenesis during aging. © 2014 Wiley Periodicals, Inc.

Study of ionospheric irregularities from Kolhapur (16.4°N, 74.2°E)

NASA Astrophysics Data System (ADS)

Sharma, A. K.; Chavan, G. A.; Gaikwad, H. P.; Gurav, O. B.; Nade, D. P.; Nikte, S. S.; Ghodpage, R. N.; Patil, P. T.

2018-04-01

The paper reports night time observations of ionospheric irregularities made through amplitude scintillation of 251 MHz signal at Kolhapur (16.4°N, 74.2°E), an equatorial Appleton anomaly region using spaced antenna system. Monthly and night time percentage of occurrence of scintillations, during increasing solar cycle from January 2011 to August 2015, is discussed. The parameters such as-maximum cross-correlation function (CI), Fade Rate are also studied. The percentage occurrence is observed to be higher in post sunset period and during equinoctial months than in winter and summer months. Scintillation occurrence is observed to be suppressed during increasing solar activity. CI shows seasonal changes. Percentage of occurrence of CI ≥ 0.5 decreases with increase in solar activity and fade rate also shows solar activity dependence.

Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway.

PubMed

Troutwine, B R; Ghezzi, A; Pietrzykowski, A Z; Atkinson, N S

2016-04-01

A growing body of evidence has shown that alcohol alters the activity of the innate immune system and that changes in innate immune system activity can influence alcohol-related behaviors. Here, we show that the Toll innate immune signaling pathway modulates the level of alcohol resistance in Drosophila. In humans, a low level of response to alcohol is correlated with increased risk of developing an alcohol use disorder. The Toll signaling pathway was originally discovered in, and has been extensively studied in Drosophila. The Toll pathway is a major regulator of innate immunity in Drosophila, and mammalian Toll-like receptor signaling has been implicated in alcohol responses. Here, we use Drosophila-specific genetic tools to test eight genes in the Toll signaling pathway for effects on the level of response to ethanol. We show that increasing the activity of the pathway increases ethanol resistance whereas decreasing the pathway activity reduces ethanol resistance. Furthermore, we show that gene products known to be outputs of innate immune signaling are rapidly induced following ethanol exposure. The interaction between the Toll signaling pathway and ethanol is rooted in the natural history of Drosophila melanogaster. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

ASTROCULTURE (TM) root metabolism and cytochemical analysis

NASA Technical Reports Server (NTRS)

Porterfield, D. M.; Barta, D. J.; Ming, D. W.; Morrow, R. C.; Musgrave, M. E.

2000-01-01

Physiology of the root system is dependent upon oxygen availability and tissue respiration. During hypoxia nutrient and water acquisition may be inhibited, thus affecting the overall biochemical and physiological status of the plant. For the Astroculture (TM) plant growth hardware, the availability of oxygen in the root zone was measured by examining the changes in alcohol dehydrogenase (ADH) activity within the root tissue. ADH activity is a sensitive biochemical indicator of hypoxic conditions in plants and was measured in both spaceflight and control roots. In addition to the biochemical enzyme assays, localization of ADH in the root tissue was examined cytochemically. The results of these analyses showed that ADH activity increased significantly as a result of spaceflight exposure. Enzyme activity increased 248% to 304% in dwarf wheat when compared with the ground controls and Brassica showed increases between 334% and 579% when compared with day zero controls. Cytochemical staining revealed no differences in ADH tissue localization in any of the dwarf wheat treatments. These results show the importance of considering root system oxygenation in designing and building nutrient delivery hardware for spaceflight plant cultivation and confirm previous reports of an ADH response associated with spaceflight exposure.

Effectiveness of "Step into Health" program in Qatar: a pedometer-based longitudinal study.

PubMed

Al-Kuwari, Mohamed G; Al-Mohannadi, Abdulla S; Sayegh, Suzan

2017-11-01

This study examines the impact of a one-year pedometer-based intervention on increasing the physical activity level among adult population in Qatar. This longitudinal study was conducted over a one-year period and included a total of 268 adults aged between 18-64 years old. Data were extracted and used from the "Step into Health" (SIH) program, a community-based program launched in 2012, as an approach to improve physical activity in Qatar. Walking intervention encouraged members of SIH to accumulate 10,000 steps or more per day and monitor their progress through a pedometer supported by a self-monitoring online account and a reinforcement system. This study shows a significant increase in average daily steps from 3933±3240 steps/day at baseline into 7507±5416 steps/week at the 12th month (P<0.001). It was found that 18.6% of participants met the daily target of 10,000 steps or more; however, there was a considerable increase of 39.2% by the 12th month. Females showed an increase in their physical activity; still, they remain less active than males. It was found that non-Arabs subgroup were more active than Arabs. Interestingly, older members (≥50 years old) were more active throughout the study period. Pedometer program was found to be effective in increasing the level of physical activity among participants. A decline in physical activity has been observed during hot weather, while re-enforcement campaign had a positive impact on the number of steps/day.

Antiaging Effects of an Intensive Mind and Body Therapeutic Program through Enhancement of Telomerase Activity and Adult Stem Cell Counts.

PubMed

Rao, Krishna S; Chakraharti, Swarup K; Dongare, Vaishali S; Chetana, K; Ramirez, Christina M; Koka, Prasad S; Deb, Kaushik D

2015-01-01

Key modalities of integrative medicine known to rejuvenate the mind and body are meditation, yoga, and controlled diet. It has been shown previously that intensive or prolonged mind and body therapies (MBT) may have beneficial effects on the well-being of healthy people and in patients. Telomerase activity and levels of peripheral blood adult pluripotent stem cells (PB-APSC) are reliable markers of long-term well-being that are known to decrease with age. The objective of this study is to understand the effect of our MBT program on telomerase activity and stem cells in blood collected from the participants. Here, we have investigated the effects of an intensive three weeks MBT retreat on telomerase activity and the peripheral blood stem cells in participants before and after the MBT. A total of 108 people were enrolled in the study; 38 men and 70 women (aged 18-90) randomly assigned for the study. Telomerase activity was greater in retreat participants at the end of the MBT retreat. About 45% of people showed more than one-fold increase of telomerase activity after our MBT program. Furthermore, about 27% of people showed more pronounced fold increase (2-fold) in telomerase activity after the MBT. In addition, a substantial percentage of people (about 90%) exhibited increased stem cell counts after the MBT. The data suggest increased telomerase activity and stem cells count in peripheral blood from MBT retreat participants that may lead to increased longevity and better quality of life at latter age.

Heterogeneity of cellular proliferation within transitional cell carcinoma: correlation of protein kinase C alpha/betaI expression and activity.

PubMed

Aaltonen, Vesa; Koivunen, Jussi; Laato, Matti; Peltonen, Juha

2006-07-01

A total of 18 histological samples containing both transitional cell carcinoma (TCC) and normal urothelial epithelium were analyzed for protein kinase C (PKC)-alpha and -betaI expression, and for their phosphorylated substrates. The results showed an increased expression of PKC-alpha in 13 out of 18 samples and -betaI in 11 out of 18 TCC samples when compared with normal urothelium. In addition, 11 out of 18 of the TCC tumors displayed heterogeneous expression of the PKC isoenzymes, with different levels of immunosignal in different areas of the tumor. Within the same sample, areas of highest PKC isoenzyme expression also showed highest classical PKC activity, as estimated by immunodetection of phosphorylated forms of PKC substrates. The areas of highest expression of PKC-alpha and/or -betaI isoenzymes showed also the highest number of cells positive for Ki67, an indicator of proliferation. Immunofluorescence and Western blotting demonstrated that in cultured TCC cells, PKC-alpha was located in the cytoplasm, whereas PKC-betaI was located primarily in the nucleus as a 65-kDa fragment and in the cytoplasm as a full-size 79-kDa protein. Our results indicate that increased expression of PKC-alpha and -betaI leads to increased total classical PKC kinase activity and suggest that increased activity of the isoenzymes plays a role in accelerated growth of TCC. Furthermore, these results suggest that even in carcinoma tissue, PKC expression and activity are under strict control.

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

Woloshuk, C.P.; Kolattukudy, P.E.

Spores of the phytopathogenic fungus Fusarium solani f. sp. pisi were shown to produce the extracellular enzyme, cutinase, only when cutin or cutin hydrolysate was added to the spore suspension. Dihydroxy-C/sub 16/ acid and trihydroxy-C/sub 18/ acid, which are unique cutin monomers, showed the greatest cutinase-inducing activity. Experiments with several compounds structurally related to these fatty acids suggested that both a omega-hydroxyl and a midchain hydroxyl are required for cutinase-inducing activity. Cutinase appeared in the medium 30-45 min after the addition of the inducers to the spore suspension, and the activity level increased for 6 hr. Addition of cycloheximide (5more » ..mu..g/ml) completely inhibited cutinase production, suggesting that protein synthesis was involved in the increase of cutinase activity. Immunoblot analysis with rabbit antibodies prepared against cutinase showed that cutinase protein increased in parallel with the increase in enzyme activity. Measurement of cutinase-specific RNA levels by dot-blot hybridization with /sup 32/P-labeled cutinase cDNA showed that the cutinase gene transcripts could be detected within 15 min after addition of the inducers. Addition of exogenous cutinase greatly enhanced the level of cutinase gene transcripts induced by cutin. These results strongly suggest that the fungal spore senses that it is in contact with the plant by the production of small amounts of cutin monomers catalyzed by the low level of cutinase carried by the spore and that these monomers induce the synthesis of cutinase needed for penetration of the fungus into the plant.« less

Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice.

PubMed

Akundi, Ravi S; Huang, Zhenyu; Eason, Joshua; Pandya, Jignesh D; Zhi, Lianteng; Cass, Wayne A; Sullivan, Patrick G; Büeler, Hansruedi

2011-01-13

PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice. Purified brain mitochondria of Pink1⁻/⁻ mice showed impaired Ca²+ storage capacity, resulting in increased Ca²+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1⁻/⁻ mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1⁻/⁻ mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1⁻/⁻ mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1⁻/⁻ embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1⁻/⁻ mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. Increased mitochondrial Ca²+ sensitivity and JNK activity are early defects in Pink1⁻/⁻ mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1⁻/⁻ mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1⁻/⁻ mice to inflammation and injury-induced cell death.

Quantitative Mapping of Cocaine-Induced ΔFosB Expression in the Striatum of Male and Female Rats

PubMed Central

Sato, Satoru M.; Wissman, Anne Marie; McCollum, Andrew F.; Woolley, Catherine S.

2011-01-01

ΔFosB plays a critical role in drug-induced long-term changes in the brain. In the current study, we evaluated locomotor activity in male and female rats treated with saline or cocaine for 2 weeks and quantitatively mapped ΔFosB expression in the dorsal striatum and nucleus accumbens of each animal by using an anti-FosB antibody that recognizes ΔFosB isoforms preferentially. Behavioral analysis showed that while there was little difference between males and females that sensitized to cocaine, nonsensitizing rats showed a large sex difference. Nonsensitizing males showed low behavioral activation in response to cocaine on the first day of treatment, and their activity remained low. In contrast, nonsensitizing females showed high activation on the first day of treatment and their activity remained high. Western blot and immunohistochemical analyses indicated that basal levels of ΔFosB were higher in the nucleus accumbens than the dorsal striatum, but that the effect of cocaine on ΔFosB was greater in the dorsal striatum. Immunostaining showed that the effect of cocaine in both the dorsal striatum and nucleus accumbens was primarily to increase the intensity of ΔFosB immunoreactivity in individual neurons, rather than to increase the number of cells that express ΔFosB. Detailed mapping of ΔFosB-labeled nuclei showed that basal ΔFosB levels were highest in the medial portion of the dorsal striatum and dorsomedial accumbens, particularly adjacent to the lateral ventricle, whereas the cocaine-induced increase in ΔFosB was most pronounced in the lateral dorsal striatum, where basal ΔFosB expression was lowest. Sex differences in ΔFosB expression were small and independent of cocaine treatment. We discuss implications of the sex difference in locomotor activation and regionally-specific ΔFosB induction by cocaine. PMID:21747956

Linoleic Acid Permeabilizes Gastric Epithelial Cells by Increasing Connexin43 Levels in the Cell Membrane Via a GPR40- and Akt-Dependent Mechanism

PubMed Central

Puebla, Carlos; Cisterna, Bruno A.; Salas, Daniela P.; Delgado-López, Fernando; Lampe, Paul D.; Sáez, Juan C.

2016-01-01

Linoleic acid (LA) is known to activate G-protein coupled receptors and connexin hemichannels (Cx HCs) but possible interlinks between these two responses remain unexplored. Here, we evaluated the mechanism of action of LA on the membrane permeability mediated by Cx HCs in MKN28 cells. These cells were found to express connexins, GPR40, GPR120, and CD36 receptors. The Cx HC activity of these cells increased after 5 min of treatment with LA or GW9508, an agonist of GPR40/GPR120; or exposure to extracellular divalent cation-free solution (DCFS), known to increase the open probability of Cx HCs, yields an immediate increase in Cx HC of similar intensity and additive with LA-induced change. Treatment with a CD36 blocker or transfection with siRNA-GPR120 maintain the LA-induced Cx HC activity. However, cells transfected with siRNA-GPR40 did not show LA-induced Cx HC activity but activity was increased upon exposure to DCFS, confirming the presence of activatable Cx HCs in the cell membrane. Treatment with AKTi (Akt inhibitor) abrogated the LA-induced Cx HC activity. In HeLa cells transfected with Cx43 (HeLa-Cx43), LA induced phosphorylation of surface Cx43 at serine 373 (S373), site for Akt phosphorylation. HeLa-Cx43 but not HeLa-Cx43 cells with a S373A mutation showed a LA-induced Cx HC activity directly related to an increase in cell surface Cx43 levels. Thus, the increase in membrane permeability induced by LA is mediated by an intracellular signaling pathway activated by GPR40 that leads to an increase in membrane levels of Cx43 phosphorylated at serine 373 via Akt. PMID:26869446

Heat Shock Protein-90 Inhibitors Enhance Antigen Expression on Melanomas and Increase T Cell Recognition of Tumor Cells

PubMed Central

Haggerty, Timothy J.; Dunn, Ian S.; Rose, Lenora B.; Newton, Estelle E.; Pandolfi, Franco; Kurnick, James T.

2014-01-01

In an effort to enhance antigen-specific T cell recognition of cancer cells, we have examined numerous modulators of antigen-expression. In this report we demonstrate that twelve different Hsp90 inhibitors (iHsp90) share the ability to increase the expression of differentiation antigens and MHC Class I antigens. These iHsp90 are active in several molecular and cellular assays on a series of tumor cell lines, including eleven human melanomas, a murine B16 melanoma, and two human glioma-derived cell lines. Intra-cytoplasmic antibody staining showed that all of the tested iHsp90 increased expression of the melanocyte differentiation antigens Melan-A/MART-1, gp100, and TRP-2, as well as MHC Class I. The gliomas showed enhanced gp100 and MHC staining. Quantitative analysis of mRNA levels showed a parallel increase in message transcription, and a reporter assay shows induction of promoter activity for Melan-A/MART-1 gene. In addition, iHsp90 increased recognition of tumor cells by T cells specific for Melan-A/MART-1. In contrast to direct Hsp90 client proteins, the increased levels of full-length differentiation antigens that result from iHsp90 treatment are most likely the result of transcriptional activation of their encoding genes. In combination, these results suggest that iHsp90 improve recognition of tumor cells by T cells specific for a melanoma-associated antigen as a result of increasing the expressed intracellular antigen pool available for processing and presentation by MHC Class I, along with increased levels of MHC Class I itself. As these Hsp90 inhibitors do not interfere with T cell function, they could have potential for use in immunotherapy of cancer. PMID:25503774

Soy isoflavone supplementation elevates erythrocyte superoxide dismutase, but not plasma ceruloplasmin in postmenopausal breast cancer survivors.

PubMed

DiSilvestro, Robert A; Goodman, Jaime; Dy, Emily; Lavalle, Gregory

2005-02-01

Soy isoflavone antioxidant effects may help prevent breast cancer re-occurrence, but isoflavone estrogen-like actions may increase breast cancer risk. These isoflavone actions can be reflected by effects on two copper enzymes activities, superoxide dismutase 1 (SOD 1), which has antioxidant function relevant to breast cancer prevention, and ceruloplasmin, which has its synthesis up-regulated by estrogen, and for which high values are associated with high breast cancer risk. A soy isoflavone-rich concentrate supplement was examined for effects on these two copper enzyme activities in post-menopausal breast cancer survivors (n = 7) in a crossover design with a placebo (24 days on supplement or placebo; 14 day wash out). The soy concentrate, but not the placebo, increased erythrocyte SOD 1 activities, but not ceruloplasmin activities or protein. The effect on superoxide dismutase activities was not likely due to increased copper intake since analysis of the soy extract showed little copper. The effect on superoxide dismutase was not accompanied by a change in urinary contents of 8-deoxyhydroxyguanosine, a DNA oxidant product, though perhaps this would change with a longer intervention. In summary, in regard to two copper enzyme activities, an isoflavone-rich soy concentrate showed an antioxidant effect considered relevant to breast cancer, but not an effect associated with estrogenic activity and increased breast cancer risk.

Treatment-Induced Autophagy Associated with Tumor Dormancy and Relapse

DTIC Science & Technology

2017-07-01

disease function by Ingenuity Pathway Analysis (IPA). The 239 genes involved in dormancy showed a z-score increase in disease states related to acute ...genes shared by both week 6 groups, one relapsing and the other dormant, showed predicted activation of both chronic and acute disease states. In...genes among 239 shared probe sets involved in maintenance of dormancy shows predicted activation of disease states related to acute inflammation, 682

Antimicrobial and antifungal activities of Cordia dichotoma (Forster F.) bark extracts

PubMed Central

Nariya, Pankaj B.; Bhalodia, Nayan R.; Shukla, V. J.; Acharya, R. N.

2011-01-01

Cordia dichotoma Forst.f. bark, identified as botanical source of Shlesmataka in Ayurvedic pharmacopoeias. Present study was carried out with an objective to investigate the antibacterial and antifungal potentials of Cordia dichotoma bark. Antibacterial activity of methanol and butanol extracts of the bark was carried out against two gram negative bacteria (Escherichia coli, and Pseudomonas aeruginosa) and two Gram positive bacteria (St. pyogenes and Staphylococcus aureus). The antifungal activity of the extracts was carried out against three common pathogenic fungi (Aspergillus niger, A.clavatus, and Candida albicans). Zone of inhibition of extracts was compared with that of different standards like Amplicilline, Ciprofloxacin, Norfloxacin and Chloramphenicol for antibacterial activity and Nystain and Greseofulvin for antifungal activity. The extracts showed remarkable inhibition of zone of bacterial growth and fungal growth and the results obtained were comparable with that of standards drugs against the organisms tested. The activity of extracts increased linearly with increase in concentration of extract (mg/ml). The results showed the antibacterial and antifungal activity against the organisms tested. PMID:22661859

Antimicrobial and antifungal activities of Cordia dichotoma (Forster F.) bark extracts.

PubMed

Nariya, Pankaj B; Bhalodia, Nayan R; Shukla, V J; Acharya, R N

2011-10-01

Cordia dichotoma Forst.f. bark, identified as botanical source of Shlesmataka in Ayurvedic pharmacopoeias. Present study was carried out with an objective to investigate the antibacterial and antifungal potentials of Cordia dichotoma bark. Antibacterial activity of methanol and butanol extracts of the bark was carried out against two gram negative bacteria (Escherichia coli, and Pseudomonas aeruginosa) and two Gram positive bacteria (St. pyogenes and Staphylococcus aureus). The antifungal activity of the extracts was carried out against three common pathogenic fungi (Aspergillus niger, A.clavatus, and Candida albicans). Zone of inhibition of extracts was compared with that of different standards like Amplicilline, Ciprofloxacin, Norfloxacin and Chloramphenicol for antibacterial activity and Nystain and Greseofulvin for antifungal activity. The extracts showed remarkable inhibition of zone of bacterial growth and fungal growth and the results obtained were comparable with that of standards drugs against the organisms tested. The activity of extracts increased linearly with increase in concentration of extract (mg/ml). The results showed the antibacterial and antifungal activity against the organisms tested.

Nanotechnology Enabled Enhancement of Enzyme Activity and Thermostability: Study on Impaired Pectate Lyase from Attenuated Macrophomina phaseolina in Presence of Hydroxyapatite Nanoparticle

PubMed Central

Dutta, Nalok; Mukhopadhyay, Arka; Dasgupta, Anjan Kr.; Chakrabarti, Krishanu

2013-01-01

In this paper we show that hydroxyapatite nanoparticles (NP) can not only act as a chaperon (by imparting thermostability) but can serve as a synthetic enhancer of activity of an isolated extracellular pectate lyase (APL) with low native state activity. The purified enzyme (an attenuated strain of Macrophomina phaseolina) showed feeble activity at 50°C and pH 5.6. However, on addition of 10.5 µg/ml of hydroxyapatite nanoparticles (NP), APL activity increased 27.7 fold with a 51 fold increase in half-life at a temperature of 90°C as compared to untreated APL. The chaperon like activity of NP was evident from entropy–enthalpy compensation profile of APL. The upper critical temperature for such compensation was elevated from 50°C to 90°C in presence of NP. This dual role of NP in enhancing activity and conferring thermostability to a functionally impaired enzyme is reported for the first time. PMID:23691068

Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency

NASA Technical Reports Server (NTRS)

Mukhopadhyay, C. K.; Mazumder, B.; Fox, P. L.

2000-01-01

A role of the copper protein ceruloplasmin (Cp) in iron metabolism is suggested by its ferroxidase activity and by the tissue iron overload in hereditary Cp deficiency patients. In addition, plasma Cp increases markedly in several conditions of anemia, e.g. iron deficiency, hemorrhage, renal failure, sickle cell disease, pregnancy, and inflammation. However, little is known about the cellular and molecular mechanism(s) involved. We have reported that iron chelators increase Cp mRNA expression and protein synthesis in human hepatocarcinoma HepG2 cells. Furthermore, we have shown that the increase in Cp mRNA is due to increased rate of transcription. We here report the results of new studies designed to elucidate the molecular mechanism underlying transcriptional activation of Cp by iron deficiency. The 5'-flanking region of the Cp gene was cloned from a human genomic library. A 4774-base pair segment of the Cp promoter/enhancer driving a luciferase reporter was transfected into HepG2 or Hep3B cells. Iron deficiency or hypoxia increased luciferase activity by 5-10-fold compared with untreated cells. Examination of the sequence showed three pairs of consensus hypoxia-responsive elements (HREs). Deletion and mutation analysis showed that a single HRE was necessary and sufficient for gene activation. The involvement of hypoxia-inducible factor-1 (HIF-1) was shown by gel-shift and supershift experiments that showed HIF-1alpha and HIF-1beta binding to a radiolabeled oligonucleotide containing the Cp promoter HRE. Furthermore, iron deficiency (and hypoxia) did not activate Cp gene expression in Hepa c4 hepatoma cells deficient in HIF-1beta, as shown functionally by the inactivity of a transfected Cp promoter-luciferase construct and by the failure of HIF-1 to bind the Cp HRE in nuclear extracts from these cells. These results are consistent with in vivo findings that iron deficiency increases plasma Cp and provides a molecular mechanism that may help to understand these observations.

Phosphorylation of deoxycytidine kinase on Ser-74: impact on kinetic properties and nucleoside analog activation in cancer cells.

PubMed

Amsailale, Rachid; Van Den Neste, Eric; Arts, Angélique; Starczewska, Eliza; Bontemps, Françoise; Smal, Caroline

2012-07-01

Deoxycytidine kinase (dCK) (EC 2.7.1.74) is a key enzyme in the activation of several therapeutic nucleoside analogs (NA). Its activity can be increased in vivo by Ser-74 phosphorylation, a property that could be used for enhancing NA activation and clinical efficacy. In line with this, studies with recombinant dCK showed that mimicking Ser-74 phosphorylation by a S74E mutation increases its activity toward pyrimidine analogs. However, purine analogs had not been investigated. Here, we show that the S74E mutation increased the k(cat) for cladribine (CdA) by 8- or 3-fold, depending on whether the phosphoryl donor was ATP or UTP, for clofarabine (CAFdA) by about 2-fold with both ATP and UTP, and for fludarabine (F-Ara-A) by 2-fold, but only with UTP. However, the catalytic efficiencies (k(cat)/Km) were not, or slightly, increased. The S74E mutation also sensitized dCK to feed-back inhibition by dCTP, regardless of the phosphoryl donor. Importantly, we did not observe an increase of endogenous dCK activity toward purine analogs after in vivo-induced increase of Ser-74 phosphorylation. Accordingly, treatment of CLL cells with aphidicolin, which enhances dCK activity through Ser-74 phosphorylation, did not modify the conversion of CdA or F-Ara-A into their active triphosphate form. Nevertheless, the same treatment enhanced activation of gemcitabine (dFdC) into dFdCTP in CLL as well as in HCT-116 cells and produced synergistic cytotoxicity. We conclude that increasing phosphorylation of dCK on Ser-74 might constitute a valuable strategy to enhance the clinical efficacy of some NA, like dFdC, but not of CdA or F-Ara-A. Copyright © 2012 Elsevier Inc. All rights reserved.

MEK1 inhibits cardiac PPARα activity by direct interaction and prevents its nuclear localization.

PubMed

el Azzouzi, Hamid; Leptidis, Stefanos; Bourajjaj, Meriem; van Bilsen, Marc; da Costa Martins, Paula A; De Windt, Leon J

2012-01-01

The response of the postnatal heart to growth and stress stimuli includes activation of a network of signal transduction cascades, including the stress activated protein kinases such as p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK) and the extracellular signal-regulated kinase (ERK1/2) pathways. In response to increased workload, the mitogen-activated protein kinase kinase (MAPKK) MEK1 has been shown to be active. Studies embarking on mitogen-activated protein kinase (MAPK) signaling cascades in the heart have indicated peroxisome-proliferators activated-receptors (PPARs) as downstream effectors that can be regulated by this signaling cascade. Despite the importance of PPARα in controlling cardiac metabolism, little is known about the relationship between MAPK signaling and cardiac PPARα signaling. Using co-immunoprecipitation and immunofluorescence approaches we show a complex formation of PPARα with MEK1 and not with ERK1/2. Binding of PPARα to MEK1 is mediated via a LXXLL motif and results in translocation from the nucleus towards the cytoplasm, hereby disabling the transcriptional activity of PPARα. Mice subjected to voluntary running-wheel exercise showed increased cardiac MEK1 activation and complex formation with PPARα, subsequently resulting in reduced PPARα activity. Inhibition of MEK1, using U0126, blunted this effect. Here we show that activation of the MEK1-ERK1/2 pathway leads to specific inhibition of PPARα transcriptional activity. Furthermore we show that this inhibitory effect is mediated by MEK1, and not by its downstream effector kinase ERK1/2, through a mechanism involving direct binding to PPARα and subsequent stimulation of PPARα export from the nucleus.

Multiple autophosphorylations significantly enhance the endoribonuclease activity of human inositol requiring enzyme 1α

PubMed Central

2014-01-01

Background Endoplasmic reticulum stress, caused by the presence of misfolded proteins, activates the stress sensor inositol-requiring enzyme 1α (IRE1α). The resulting increase in IRE1α RNase activity causes sequence-specific cleavage of X-box binding protein 1 (XBP1) mRNA, resulting in upregulation of the unfolded protein response and cellular adaptation to stress. The precise mechanism of human IRE1α activation is currently unclear. The role of IRE1α kinase activity is disputed, as results from the generation of various kinase-inactivating mutations in either yeast or human cells are discordant. Kinase activity can also be made redundant by small molecules which bind the ATP binding site. We set out to uncover a role for IRE1α kinase activity using wild-type cytosolic protein constructs. Results We show that concentration-dependent oligomerisation is sufficient to cause IRE1α cytosolic domain RNase activity in vitro. We demonstrate a role for the kinase activity by showing that autophosphorylation enhances RNase activity. Inclusion of the IRE1α linker domain in protein constructs allows hyperphosphorylation and further enhancement of RNase activity, highlighting the importance of kinase activity. We show that IRE1α phosphorylation status correlates with an increased propensity to form oligomeric complexes and that forced dimerisation causes great enhancement in RNase activity. In addition we demonstrate that even when IRE1α is forced to dimerise, by a GST-tag, phospho-enhancement of activity is still observed. Conclusions Taken together these experiments support the hypothesis that phosphorylation is important in modulating IRE1α RNase activity which is achieved by increasing the propensity of IRE1α to dimerise. This work supports the development of IRE1α kinase inhibitors for use in the treatment of secretory cancers. PMID:24524643

Studies to reveal the nature of interactions between catalase and curcumin using computational methods and optical techniques.

PubMed

Mofidi Najjar, Fayezeh; Ghadari, Rahim; Yousefi, Reza; Safari, Naser; Sheikhhasani, Vahid; Sheibani, Nader; Moosavi-Movahedi, Ali Akbar

2017-02-01

Curcumin is an important antioxidant compound, and is widely reported as an effective component for reducing complications of many diseases. However, the detailed mechanisms of its activity remain poorly understood. We found that curcumin can significantly increase catalase activity of BLC (bovine liver catalase). The mechanism of curcumin action was investigated using a computational method. We suggested that curcumin may activate BLC by modifying the bottleneck of its narrow channel. The molecular dynamic simulation data showed that placing curcumin on the structure of enzyme can increase the size of the bottleneck in the narrow channel of BLC, and readily allow the access of substrate to the active site. Because of the increase of the distance between amino acids of the bottleneck in the presence of curcumin, the entrance space of substrate increased from 250Å 3 to 440Å 3 . In addition, the increase in emission of intrinsic fluorescence of BLC in presence of curcumin demonstrated changes in tertiary structure of catalase, and possibility of less quenching. We also used circular dichroism (CD) spectropolarimetry to determine how curcumin may alter the enzyme secondary structure. Catalase spectra in the presence of various concentrations of curcumin showed an increase in the amount of α-helix content. Copyright © 2016 Elsevier B.V. All rights reserved.

The antibacterial activity and toxicity of enrofloxacin are decreased by nanocellulose conjugated with aminobenzyl purin.

PubMed

Yasini, Seyed Ali; Zadeh, Mohammad Hossein Balal; Shahdadi, Hossein

2015-11-01

The first aim of this study was to synthesize nanocellulose conjugated with aminobenzyl purin (NCABP), and the second aim was to evaluate the effect of NCABP on both toxicity and antibacterial activity of enrofloxacin. Here, the adsorption of enrofloxacin by NCABP was first modeled by molecular dynamic (MD) simulation. In the next step, NCABP was synthesized, and was exposed to enrofloxacin, 1000 μg mL(-1), at various conditions. Then, the quantity of adsorption and release was separately measured. Furthermore, both toxicity and antibacterial activity of NCABP, enrofloxacin, and (NCABP+enrofloxacin) were separately evaluated. In this study, MD simulation clearly showed the adsorption after 50 picoseconds. The adsorption tests revealed that the increase of incubation time and NCABP concentration, at range of 50-200 μg mL(-1), led to increase of adsorption. Moreover, the decrease of pH led to increase of adsorption. Interestingly, NCABP could adsorb enrofloxacin, up to 1000 μg mL(-1), in different types of meat. Moreover, the increase of incubation time and temperature did not release enrofloxacin, but the increase of pH increased release. This study showed that both toxicity and antibacterial activity of enrofloxacin were decreased when exposed together with NCABP. Copyright © 2015 Elsevier B.V. All rights reserved.

Antimicrobial activity of tiger's betel (Piper porphyrophyllum N.E. Br., Piperaceae).

PubMed

Wiart, C; Hannah, N A; Yassim, M; Hamimah, H; Sulaiman, M

2004-09-01

The ethanol extract of leaves of Piper porphyrophyllum N.E. Br. showed a broad spectrum of antibacterial activity. The activity was increased on fractionation (hexane, dichloromethane and aqueous), particularly in the aqueous fraction. No activity was shown against tested Candida albicans. Copyright (c) 2004 John Wiley & Sons, Ltd.

Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

USDA-ARS?s Scientific Manuscript database

Several benzoic acid analogs showed antifungal activity against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis. Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids increased by addition of a methyl, methoxyl...

Differential Expression of Adhesion-Related Proteins and MAPK Pathways Lead to Suitable Osteoblast Differentiation of Human Mesenchymal Stem Cells Subpopulations.

PubMed

Leyva-Leyva, Margarita; López-Díaz, Annia; Barrera, Lourdes; Camacho-Morales, Alberto; Hernandez-Aguilar, Felipe; Carrillo-Casas, Erika M; Arriaga-Pizano, Lourdes; Calderón-Pérez, Jaime; García-Álvarez, Jorge; Orozco-Hoyuela, Gabriel; Piña-Barba, Cristina; Rojas-Martínez, Augusto; Romero-Díaz, Víktor; Lara-Arias, Jorge; Rivera-Bolaños, Nancy; López-Camarillo, César; Moncada-Saucedo, Nidia; Galván-De los Santos, Alejandra; Meza-Urzúa, Fátima; Villarreal-Gómez, Luis; Fuentes-Mera, Lizeth

2015-11-01

Cellular adhesion enables communication between cells and their environment. Adhesion can be achieved throughout focal adhesions and its components influence osteoblast differentiation of human mesenchymal stem cells (hMSCs). Because cell adhesion and osteoblast differentiation are closely related, this article aimed to analyze the expression profiles of adhesion-related proteins during osteoblastic differentiation of two hMSCs subpopulations (CD105(+) and CD105(-)) and propose a strategy for assembling bone grafts based on its adhesion ability. In vitro experiments of osteogenic differentiation in CD105(-) cells showed superior adhesion efficiency and 2-fold increase of α-actinin expression compared with CD105(+) cells at the maturation stage. Interestingly, levels of activated β1-integrin increased in CD105(-) cells during the process. Additionally, the CD105(-) subpopulation showed 3-fold increase of phosphorylated FAK(Y397) compared to CD105(+) cells. Results also indicate that ERK1/2 was activated during CD105(-) bone differentiation and participation of mitogen-activated protein kinase (MAPK)-p38 in CD105(+) differentiation through a focal adhesion kinase (FAK)-independent pathway. In vivo trial demonstrated that grafts containing CD105(-) showed osteocytes embedded in a mineralized matrix, promoted adequate graft integration, increased host vascular infiltration, and efficient intramembranous repairing. In contrast, grafts containing CD105(+) showed deficient endochondral ossification and fibrocartilaginous tissue. Based on the expression of α-actinin, FAKy,(397) and ERK1/2 activation, we define maturation stage as critical for bone graft assembling. By in vitro assays, CD105(-) subpopulation showed superior adhesion efficiency compared to CD105(+) cells. Considering in vitro and in vivo assays, this study suggests that integration of a scaffold with CD105(-) subpopulation at the maturation stage represents an attractive strategy for clinical use in orthopedic bioengineering.

Cysteine Cathepsins in Human Carious Dentin

PubMed Central

Nascimento, F.D.; Minciotti, C.L.; Geraldeli, S.; Carrilho, M.R.; Pashley, D.H.; Tay, F.R.; Nader, H.B.; Salo, T.; Tjäderhane, L.; Tersariol, I.L.S.

2011-01-01

Matrix metalloproteinases (MMPs) are important in dentinal caries, and analysis of recent data demonstrates the presence of other collagen-degrading enzymes, cysteine cathepsins, in human dentin. This study aimed to examine the presence, source, and activity of cysteine cathepsins in human caries. Cathepsin B was detected with immunostaining. Saliva and dentin cysteine cathepsin and MMP activities on caries lesions were analyzed spectrofluorometrically. Immunostaining demonstrated stronger cathepsins B in carious than in healthy dentin. In carious dentin, cysteine cathepsin activity increased with increasing depth and age in chronic lesions, but decreased with age in active lesions. MMP activity decreased with age in both active and chronic lesions. Salivary MMP activities were higher in patients with active than chronic lesions and with increasing lesion depth, while cysteine cathepsin activities showed no differences. The results indicate that, along with MMPs, cysteine cathepsins are important, especially in active and deep caries. PMID:21248362

Online Actions with Offline Impact: How Online Social Networks Influence Online and Offline User Behavior.

PubMed

Althoff, Tim; Jindal, Pranav; Leskovec, Jure

2017-02-01

Many of today's most widely used computing applications utilize social networking features and allow users to connect, follow each other, share content, and comment on others' posts. However, despite the widespread adoption of these features, there is little understanding of the consequences that social networking has on user retention, engagement, and online as well as offline behavior. Here, we study how social networks influence user behavior in a physical activity tracking application. We analyze 791 million online and offline actions of 6 million users over the course of 5 years, and show that social networking leads to a significant increase in users' online as well as offline activities. Specifically, we establish a causal effect of how social networks influence user behavior. We show that the creation of new social connections increases user online in-application activity by 30%, user retention by 17%, and user offline real-world physical activity by 7% (about 400 steps per day). By exploiting a natural experiment we distinguish the effect of social influence of new social connections from the simultaneous increase in user's motivation to use the app and take more steps. We show that social influence accounts for 55% of the observed changes in user behavior, while the remaining 45% can be explained by the user's increased motivation to use the app. Further, we show that subsequent, individual edge formations in the social network lead to significant increases in daily steps. These effects diminish with each additional edge and vary based on edge attributes and user demographics. Finally, we utilize these insights to develop a model that accurately predicts which users will be most influenced by the creation of new social network connections.

Online Actions with Offline Impact: How Online Social Networks Influence Online and Offline User Behavior

PubMed Central

Althoff, Tim; Jindal, Pranav; Leskovec, Jure

2017-01-01

Many of today’s most widely used computing applications utilize social networking features and allow users to connect, follow each other, share content, and comment on others’ posts. However, despite the widespread adoption of these features, there is little understanding of the consequences that social networking has on user retention, engagement, and online as well as offline behavior. Here, we study how social networks influence user behavior in a physical activity tracking application. We analyze 791 million online and offline actions of 6 million users over the course of 5 years, and show that social networking leads to a significant increase in users’ online as well as offline activities. Specifically, we establish a causal effect of how social networks influence user behavior. We show that the creation of new social connections increases user online in-application activity by 30%, user retention by 17%, and user offline real-world physical activity by 7% (about 400 steps per day). By exploiting a natural experiment we distinguish the effect of social influence of new social connections from the simultaneous increase in user’s motivation to use the app and take more steps. We show that social influence accounts for 55% of the observed changes in user behavior, while the remaining 45% can be explained by the user’s increased motivation to use the app. Further, we show that subsequent, individual edge formations in the social network lead to significant increases in daily steps. These effects diminish with each additional edge and vary based on edge attributes and user demographics. Finally, we utilize these insights to develop a model that accurately predicts which users will be most influenced by the creation of new social network connections. PMID:28345078

Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study.

PubMed

Simonyan, Kristina; Ludlow, Christy L

2010-11-01

Spasmodic dysphonia (SD) is a task-specific focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speaking. Our aim was to identify symptom-specific functional brain activation abnormalities in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD). Both SD groups showed increased activation extent in the primary sensorimotor cortex, insula, and superior temporal gyrus during symptomatic and asymptomatic tasks and decreased activation extent in the basal ganglia, thalamus, and cerebellum during asymptomatic tasks. Increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production, which showed a tendency for correlation with ADSD symptoms. Both SD groups had lower correlation of activation intensities between the primary motor and sensory cortices and additional correlations between the basal ganglia, thalamus, and cerebellum during symptomatic and asymptomatic tasks. Compared with ADSD patients, ABSD patients had larger activation extent in the primary sensorimotor cortex and ventral thalamus during symptomatic task and in the inferior temporal cortex and cerebellum during symptomatic and asymptomatic voice production. The primary somatosensory cortex shows consistent abnormalities in activation extent, intensity, correlation with other brain regions, and symptom severity in SD patients and, therefore, may be involved in the pathophysiology of SD.

Abnormal Activation of the Primary Somatosensory Cortex in Spasmodic Dysphonia: An fMRI Study

PubMed Central

Ludlow, Christy L.

2010-01-01

Spasmodic dysphonia (SD) is a task-specific focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speaking. Our aim was to identify symptom-specific functional brain activation abnormalities in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD). Both SD groups showed increased activation extent in the primary sensorimotor cortex, insula, and superior temporal gyrus during symptomatic and asymptomatic tasks and decreased activation extent in the basal ganglia, thalamus, and cerebellum during asymptomatic tasks. Increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production, which showed a tendency for correlation with ADSD symptoms. Both SD groups had lower correlation of activation intensities between the primary motor and sensory cortices and additional correlations between the basal ganglia, thalamus, and cerebellum during symptomatic and asymptomatic tasks. Compared with ADSD patients, ABSD patients had larger activation extent in the primary sensorimotor cortex and ventral thalamus during symptomatic task and in the inferior temporal cortex and cerebellum during symptomatic and asymptomatic voice production. The primary somatosensory cortex shows consistent abnormalities in activation extent, intensity, correlation with other brain regions, and symptom severity in SD patients and, therefore, may be involved in the pathophysiology of SD. PMID:20194686

Secretory leukocyte protease inhibitor gene deletion alters bleomycin-induced lung injury, but not development of pulmonary fibrosis.

PubMed

Habgood, Anthony N; Tatler, Amanda L; Porte, Joanne; Wahl, Sharon M; Laurent, Geoffrey J; John, Alison E; Johnson, Simon R; Jenkins, Gisli

2016-06-01

Idiopathic pulmonary fibrosis is a progressive, fatal disease with limited treatment options. Protease-mediated transforming growth factor-β (TGF-β) activation has been proposed as a pathogenic mechanism of lung fibrosis. Protease activity in the lung is tightly regulated by protease inhibitors, particularly secretory leukocyte protease inhibitor (SLPI). The bleomycin model of lung fibrosis was used to determine the effect of increased protease activity in the lungs of Slpi(-/-) mice following injury. Slpi(-/-), and wild-type, mice received oropharyngeal administration of bleomycin (30 IU) and the development of pulmonary fibrosis was assessed. Pro and active forms of matrix metalloproteinase (MMP)-2 and MMP-9 were measured. Lung fibrosis was determined by collagen subtype-specific gene expression, hydroxyproline concentration, and histological assessment. Alveolar TGF-β activation was measured using bronchoalveolar lavage cell pSmad2 levels and global TGF-β activity was assessed by pSmad2 immunohistochemistry. The active-MMP-9 to pro-MMP-9 ratio was significantly increased in Slpi(-/-) animals compared with wild-type animals, demonstrating enhanced metalloproteinase activity. Wild-type animals showed an increase in TGF-β activation following bleomycin, with a progressive and sustained increase in collagen type I, alpha 1 (Col1α1), III, alpha 1(Col3α1), IV, alpha 1(Col4α1) mRNA expression, and a significant increase in total lung collagen 28 days post bleomycin. In contrast Slpi(-/-) mice showed no significant increase of alveolar TGF-β activity following bleomycin, above their already elevated levels, although global TGF-β activity did increase. Slpi(-/-) mice had impaired collagen gene expression but animals demonstrated minimal reduction in lung fibrosis compared with wild-type animals. These data suggest that enhanced proteolysis does not further enhance TGF-β activation, and inhibits sustained Col1α1, Col3α1, and Col4α1 gene expression following lung injury. However, these changes do not prevent the development of lung fibrosis. Overall, these data suggest that the absence of Slpi does not markedly modify the development of lung fibrosis following bleomycin-induced lung injury.

Successive and discrete spaced conditioning in active avoidance learning in young and aged zebrafish.

PubMed

Yang, Peng; Kajiwara, Riki; Tonoki, Ayako; Itoh, Motoyuki

2018-05-01

We designed an automated device to study active avoidance learning abilities of zebrafish. Open source tools were used for the device control, statistical computing, and graphic outputs of data. Using the system, we developed active avoidance tests to examine the effects of trial spacing and aging on learning. Seven-month-old fish showed stronger avoidance behavior as measured by color preference index with discrete spaced training as compared to successive spaced training. Fifteen-month-old fish showed a similar trend, but with reduced cognitive abilities compared with 7-month-old fish. Further, in 7-month-old fish, an increase in learning ability during trials was observed with discrete, but not successive, spaced training. In contrast, 15-month-old fish did not show increase in learning ability during trials. Therefore, these data suggest that discrete spacing is more effective for learning than successive spacing, with the zebrafish active avoidance paradigm, and that the time course analysis of active avoidance using discrete spaced training is useful to detect age-related learning impairment. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Antitumor activity of biflorin, an o-naphthoquinone isolated from Capraria biflora.

PubMed

Vasconcellos, Marne Carvalho de; Bezerra, Daniel Pereira; Fonseca, Aluísio Marques; Pereira, Márcio Roberto Pinho; Lemos, Telma Leda Gomes; Pessoa, Otília Deusdênia Loiola; Pessoa, Cláudia; Moraes, Manoel Odorico de; Alves, Ana Paula Negreiros Nunes; Costa-Lotufo, Letícia Veras

2007-08-01

Pharmacological studies with an aqueous extract obtained from leaves of Capraria biflora showed potent cytotoxic, analgesic, antimicrobial and anti-inflammatory activities. It has been demonstrated that biflorin possesses an in vitro cytotoxic activity against tumor cells. The in vivo antitumor activity of biflorin was evaluated on two mouse models, sarcoma 180 and Ehrlich carcinoma. Biflorin was active against both tumors with a very similar profile. In addition, biflorin was also able to increase the response elicited by 5-FU in mice inoculated with both tumors. The results showed a decrease in Ki67 staining in tumor cells from treated-animals when compared with non-treated groups, which suggests an inhibition of tumor proliferation rate. Histopathological analysis from kidneys and liver showed that biflorin possessed weak and reversible toxic effects. It was also demonstrated that biflorin acts as an immunoadjuvant agent, rising the production of ovalbumin-specific antibodies and inducing a discreet increase of the white pulp and nest of megakaryocytic in spleen of treated mice, which can be related to its antitumor properties.

Motivational activities based on previous knowledge of students

NASA Astrophysics Data System (ADS)

García, J. A.; Gómez-Robledo, L.; Huertas, R.; Perales, F. J.

2014-07-01

Academic results depend strongly on the individual circumstances of students: background, motivation and aptitude. We think that academic activities conducted to increase motivation must be tuned to the special situation of the students. Main goal of this work is analyze the students in the first year of the Degree in Optics and Optometry in the University of Granada and the suitability of an activity designed for those students. Initial data were obtained from a survey inquiring about the reasons to choose this degree, their knowledge of it, and previous academic backgrounds. Results show that: 1) the group is quite heterogeneous, since students have very different background. 2) Reasons to choose the Degree in Optics and Optometry are also very different, and in many cases were selected as a second option. 3) Knowledge and motivations about the Degree are in general quite low. Trying to increase the motivation of the students we designed an academic activity in which we show different topics studied in the Degree. Results show that students that have been involved in this activity are the most motivated and most satisfied with their election of the degree.

Removal of bromide and iodide anions from drinking water by silver-activated carbon aerogels.

PubMed

Sánchez-Polo, M; Rivera-Utrilla, J; Salhi, E; von Gunten, U

2006-08-01

The aim of this study is to analyze the use of Ag-doped activated carbon aerogels for bromide and iodide removal from drinking water and to study how the activation of Ag-doped aerogels affects their behavior. It has been observed that the carbonization treatment and activation process of Ag-doped aerogels increased the surface area value ( [Formula: see text] ), whereas the volume of meso-(V(2)) and macropores (V(3)) decreased slightly. Chemical characterization of the materials revealed that carbonization and especially activation process considerably increased the surface basicity of the sample. Original sample (A) presented acidic surface properties (pH(PZC)=4.5) with 21% surface oxygen, whereas the sample that underwent activation showed mainly basic surface chemical properties (pH(PZC)=9.5) with only 6% of surface oxygen. Carbonization and especially, activation process considerable increased the adsorption capacity of bromide and iodide ions. This would mainly be produced by (i) an increase in the microporosity of the sample, which increases Ag-adsorption sites available to halide anions, and (ii) a rise of the basicity of the sample, which produces an increase in attractive electrostatic interactions between the aerogel surface, positively charged at the working pH (pH(solution)

The neural basis of the bystander effect--the influence of group size on neural activity when witnessing an emergency.

PubMed

Hortensius, Ruud; de Gelder, Beatrice

2014-06-01

Naturalistic observation and experimental studies in humans and other primates show that observing an individual in need automatically triggers helping behavior. The aim of the present study is to clarify the neurofunctional basis of social influences on individual helping behavior. We investigate whether when participants witness an emergency, while performing an unrelated color-naming task in an fMRI scanner, the number of bystanders present at the emergency influences neural activity in regions related to action preparation. The results show a decrease in activity with the increase in group size in the left pre- and postcentral gyri and left medial frontal gyrus. In contrast, regions related to visual perception and attention show an increase in activity. These results demonstrate the neural mechanisms of social influence on automatic action preparation that is at the core of helping behavior when witnessing an emergency. Copyright © 2014 Elsevier Inc. All rights reserved.

Relevance of substrates and products on the desorption of lipases physically adsorbed on hydrophobic supports.

PubMed

Virgen-Ortíz, Jose J; Tacias-Pascacio, Veymar G; Hirata, Daniela B; Torrestiana-Sanchez, Beatriz; Rosales-Quintero, Arnulfo; Fernandez-Lafuente, Roberto

2017-01-01

Lipase B from Candida antarctica (CALB) has been physically immobilized on octyl-agarose via interfacial activation. The incubation of the enzyme in 80% ethanol at pH 5 and 25°C has not significant effect on enzyme activity. Moreover, the hydrolysis of 100mM tributyrin catalyzed by this biocatalyst exhibited a quite linear reaction course. However, a new cycle of tributyrin hydrolysis showed a drastic drop in the activity. SDS-PAGE gels of the supernatant and the biocatalyst showed a significant enzyme desorption after the reaction. Similar results could be appreciated using triacetin or sunflower oil, while using 300mM methyl phenyl acetate, butyl butyrate or ethyl butyrate most enzyme molecules remained immobilized. The results show that the detergent properties of some reaction products increase the enzyme release from the hydrophobic support, and this problem increased if the concentration of the reactants increased. Using 500mM tributyrin, even in fully aqueous medium, some enzyme desorption from the support may be observed. Thus, the results show a limitation of this kind of biocatalysts that should be considered in the selection of an industrial lipase biocatalyst. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhancing anaerobic digestion of waste activated sludge by pretreatment: effect of volatile to total solids.

PubMed

Wang, Xiao; Duan, Xu; Chen, Jianguang; Fang, Kuo; Feng, Leiyu; Yan, Yuanyuan; Zhou, Qi

2016-01-01

In this study the effect of volatile to total solids (VS/TS) on anaerobic digestion of waste activated sludge (WAS) pretreated by alkaline, thermal and thermal-alkaline strategies was studied. Experimental results showed that the production of methane from sludge was increased with VS/TS. When anaerobic digesters were fed with sludge pretreated by the thermal-alkaline method, the average methane yield was improved from 2.8 L/d at VS/TS 0.35 to 4.7 L/d at VS/TS 0.56. Also, the efficiency of VS reduction during sludge anaerobic digestion varied between 18.9% and 45.6%, and increased gradually with VS/TS. Mechanism investigation of VS/TS on WAS anaerobic digestion suggested that the general activities of anaerobic microorganisms, activities of key enzymes related to sludge hydrolysis, acidification and methanogenesis, and the ratio of Archaea to Bacteria were all increased with VS/TS, showing good agreement with methane production.

Catalytic Effect of Activated Carbon and Activated Carbon Fiber in Non-Equilibrium Plasma-Based Water Treatment

NASA Astrophysics Data System (ADS)

Zhang, Yanzong; Zheng, Jingtang; Qu, Xianfeng; Yu, Weizhao; Chen, Honggang

2008-06-01

Catalysis and regeneration efficiency of granular activated carbon (GAC) and activated carbon fiber (ACF) were investigated in a non-equilibrium plasma water treatment reactor with a combination of pulsed streamer discharge and GAC or ACF. The experimental results show that the degradation efficiency of methyl orange (MO) by the combined treatment can increase 22% (for GAC) and 24% (for ACF) respectively compared to pulsed discharge treatment alone, indicating that the combined treatment has a synergetic effect. The MO degradation efficiency by the combined treatment with pulsed discharge and saturated GAC or ACF can increase 12% and 17% respectively compared to pulsed discharge treatment alone. Both GAC and ACF show catalysis and the catalysis of ACF is prominent. Meanwhile, the regeneration of GAC and ACF are realized in this process. When H2O2 is introduced into the system, the utilization efficiency of ozone and ultraviolet light is improved and the regeneration efficiency of GAC and ACF is also increased.

The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ

PubMed Central

Appelberg, Rui; Moreira, Diana; Barreira-Silva, Palmira; Borges, Margarida; Silva, Letícia; Dinis-Oliveira, Ricardo Jorge; Resende, Mariana; Correia-Neves, Margarida; Jordan, Michael B; Ferreira, Nuno C; Abrunhosa, Antero J; Silvestre, Ricardo

2015-01-01

Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-γ (IFN-γ). Mycobacterium avium-infected mice lacking IFN-γ signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-γ signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-γ reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-γ displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-γ is responsible for the Warburg effect observed in organs infected with M. avium. PMID:25807843

P53 Suppression of Homologous Recombination and Tumorigenesis

DTIC Science & Technology

2012-01-01

mutation acted on both rad51 dependent gene conversion events and deletion events (6). Willers et al. also showed an increase in recombination...suffer from sarcomas. MEFs from these mice show aneuploidy, allelic loss and gene amplification. Most of these germline mutations are missense...the absence of tumor suppressor gene activity, such as p53, results in increased genomic instability and increased cancer predisposition

Stay tuned: active amplification tunes tree cricket ears to track temperature-dependent song frequency.

PubMed

Mhatre, Natasha; Pollack, Gerald; Mason, Andrew

2016-04-01

Tree cricket males produce tonal songs, used for mate attraction and male-male interactions. Active mechanics tunes hearing to conspecific song frequency. However, tree cricket song frequency increases with temperature, presenting a problem for tuned listeners. We show that the actively amplified frequency increases with temperature, thus shifting mechanical and neuronal auditory tuning to maintain a match with conspecific song frequency. Active auditory processes are known from several taxa, but their adaptive function has rarely been demonstrated. We show that tree crickets harness active processes to ensure that auditory tuning remains matched to conspecific song frequency, despite changing environmental conditions and signal characteristics. Adaptive tuning allows tree crickets to selectively detect potential mates or rivals over large distances and is likely to bestow a strong selective advantage by reducing mate-finding effort and facilitating intermale interactions. © 2016 The Author(s).

Resveratrol Reactivates Latent HIV through Increasing Histone Acetylation and Activating Heat Shock Factor 1.

PubMed

Zeng, Xiaoyun; Pan, Xiaoyan; Xu, Xinfeng; Lin, Jian; Que, Fuchang; Tian, Yuanxin; Li, Lin; Liu, Shuwen

2017-06-07

The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression, although its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Mode of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homologue 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC). However, latent HIV was reactivated by resveratrol mediated through increasing histone acetylation and activation of heat shock factor 1 (HSF1). Additionally, synergistic activation of the latent HIV reservoirs was observed under cotreatment with resveratrol and conventional LRAs. Collectively, this research reveals that resveratrol is a natural LRA and shows promise for HIV therapy.

Effects of aripiprazole versus risperidone on brain activation during planning and social-emotional evaluation in schizophrenia: A single-blind randomized exploratory study.

PubMed

Liemburg, Edith J; van Es, Frank; Knegtering, Henderikus; Aleman, André

2017-10-03

Impaired function of prefrontal brain networks may be the source of both negative symptoms and neurocognitive problems in psychotic disorders. Whereas most antipsychotics may decrease prefrontal activation, the partial dopamine D2-receptor agonist aripiprazole is hypothesized to improve prefrontal function. This study investigated whether patients with a psychotic disorder would show stronger activation of prefrontal areas and associated regions after treatment with aripiprazole compared to risperidone treatment. In this exploratory pharmacological neuroimaging study, 24 patients were randomly assigned to either aripiprazole or risperidone. At baseline and after nine weeks treatment they underwent an interview and MRI session. Here we report on brain activation (measured with arterial spin labeling) during performance of two tasks, the Tower of London and the Wall of Faces. Aripiprazole treatment decreased activation of the middle frontal, superior frontal and occipital gyrus (ToL) and medial temporal and inferior frontal gyrus, putamen and cuneus (WoF), while activation increased after risperidone. Activation increased in the ventral anterior cingulate and posterior insula (ToL), and superior frontal, superior temporal and precentral gyrus (WoF) after aripiprazole treatment and decreased after risperidone. Both treatment groups had increased ventral insula activation (ToL) and middle temporal gyrus (WoF), and decreased occipital cortex, precuneus and caudate head activation (ToL) activation. In conclusion, patients treated with aripiprazole may need less frontal resources for planning performance and may show increased frontotemporal and frontostriatal reactivity to emotional stimuli. More research is needed to corroborate and extend these preliminary findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Ionospheric acoustic and gravity wave activity above low-latitude thunderstorms

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

Lay, Erin Hoffmann

In this report, we study the correlation between thunderstorm activity and ionospheric gravity and acoustic waves in the low-latitude ionosphere. We use ionospheric total electron content (TEC) measurements from the Low Latitude Ionospheric Sensor Network (LISN) and lightning measurements from the World- Wide Lightning Location Network (WWLLN). We find that ionospheric acoustic waves show a strong diurnal pattern in summer, peaking in the pre-midnight time period. However, the peak magnitude does not correspond to thunderstorm area, and the peak time is significantly after the peak in thunderstorm activity. Wintertime acoustic wave activity has no discernable pattern in these data. Themore » coverage area of ionospheric gravity waves in the summer was found to increase with increasing thunderstorm activity. Wintertime gravity wave activity has an observable diurnal pattern unrelated to thunderstorm activity. These findings show that while thunderstorms are not the only, or dominant source of ionospheric perturbations at low-latitudes, they do have an observable effect on gravity wave activity and could be influential in acoustic wave activity.« less

Zinc triggers microglial activation.

PubMed

Kauppinen, Tiina M; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A

2008-05-28

Microglia are resident immune cells of the CNS. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, "ameboid" morphology and release matrix metalloproteinases, reactive oxygen species, and other proinflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here, we show that zinc directly triggers microglial activation. Microglia transfected with a nuclear factor-kappaB (NF-kappaB) reporter gene showed a severalfold increase in NF-kappaB activity in response to 30 microm zinc. Cultured mouse microglia exposed to 15-30 microm zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-kappaB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-kappaB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders.

Blockade of hyperpolarization-activated channels modifies the effect of beta-adrenoceptor stimulation.

PubMed

Zefirov, T L; Ziyatdinova, N I; Gainullin, A A; Zefirov, A L

2002-05-01

Experiments on rats showed that blockade of hyperpolarization-activated currents moderates tachycardia induced by beta-adrenoceptor agonist isoproterenol and potentiates the increase in stroke volume produced by this agonist. Electrical stimulation of the vagus nerve against the background of isoproterenol treatment augmented bradycardia and increased stroke volume. Blockade of hyperpolarization-activated currents followed by application of isoproterenol moderated vagus-induced bradycardia and had no effect on the dynamics of stroke volume.

Asset Inequality and Economic Activity in Artificial Societies

NASA Astrophysics Data System (ADS)

Kikuchi, Toshiko

In this paper, using multi-agent simulations, the effect asset inequality has on an artificial society is analyzed. It is shown that it is possible for a sustainable society to decrease in asset inequality and at the same time increase economic activity. In sustainable societies, the asset inequality increases as the consumption tax rate is raised, and in artificial societies where the tax rate is the same, inequality increases in the society in which agents with even small a surplus undertake unselfish actions. In sustainable societies which employ both income and consumption tax, an increase in asset inequalities leads to an increase economic activity. But, in sustainable societies which levy only the income tax, this result does not necessarily hold. These results show that if economic activity is increased in sustainable societies where the consumption tax rate is raised for the fiscal stability, an inequality expansion is an acceptable consequence. However, the sustainable society with the highest economic activity is realized when only the income tax is levied. In sustainable societies which levy only the income tax, it is possible to decrease inequality while simultaneously increasing economic activity.

Long-term effects of nickel oxide nanoparticles on performance, microbial enzymatic activity, and microbial community of a sequencing batch reactor.

PubMed

Wang, Sen; Li, Zhiwei; Gao, Mengchun; She, Zonglian; Guo, Liang; Zheng, Dong; Zhao, Yangguo; Ma, Bingrui; Gao, Feng; Wang, Xuejiao

2017-02-01

The nitrogen and phosphorus removal, microbial enzymatic activity, and microbial community of a sequencing batch reactor (SBR) were evaluated under long-term exposure to nickel oxide nanoparticles (NiO NPs). High NiO NP concentration (over 5 mg L -1 ) affected the removal of chemical oxygen demand, nitrogen, and phosphorus. The presence of NiO NP inhibited the microbial enzymatic activities and reduced the nitrogen and phosphorus removal rates of activated sludge. The microbial enzymatic activities of the activated sludge showed a similar variation trend to the nitrogen and phosphorus removal rates with the increase in NiO NP concentration from 0 to 60 mg L -1 . The Ni content in the effluent and activated sludge showed an increasing trend with the increase in NiO NP concentration. Some NiO NPs were absorbed on the sludge surface or penetrate the cell membrane into the interior of microbial cells in the activated sludge. NiO NP facilitated the increase in reactive oxygen species by disturbing the balance between the oxidation and anti-oxidation processes, and the variation in lactate dehydrogenase demonstrated that NiO NP could destroy the cytomembrane and cause variations in the microbial morphology and physiological function. High-throughput sequencing demonstrated that the microbial community of SBR had some obvious changes at 0-60 mg L -1 NiO NPs at the phyla, class and genus levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Publication activity at Aalborg Hospital].

PubMed

Andersen, Jens Peter; Skrubbeltrang, Conni; Gregersen, Hans

2010-04-26

In 2003 Aalborg Hospital became part of Aarhus University Hospital and in that context focus on research activities was increased. This article investigates whether the increased focus has led to changes in the quantity and/or quality of research publications in the following period. All scientific articles published by Aalborg Hospital in the period 2002-2008, as well as information about author affiliations comprise the data material for the analysis. Different levels of journal groups are created based on Journal Performance Indicators combined with peer-reviewing as a measure of publication quality, awarding publications in highly esteemed journals a higher score than those published in less recognized journals. Together with the number of publications, a measure of research quality and quantity is thereby achieved. This method is compared to the more traditional journal impact factor method. Data show an increase in total publications per year while the mean number of points per publication decreases during the period. Results also show a relation between the score level of publications and the number of collaborations for the publication, i.e. large collaborations are more frequently published in top journals. The study shows that the increased focus on research has led to increased publication activity without loss of quality, as the decrease in points per publication is associated with the increased mean number of collaborators. The results indicate that the method would benefit from a revision to facilitate clearer conclusions.

Effect of Chronic Athletic Activity on Brown Fat in Young Women.

PubMed

Singhal, Vibha; Maffazioli, Giovana D; Ackerman, Kate E; Lee, Hang; Elia, Elisa F; Woolley, Ryan; Kolodny, Gerald; Cypess, Aaron M; Misra, Madhusmita

2016-01-01

The effect of chronic exercise activity on brown adipose tissue (BAT) is not clear, with some studies showing positive and others showing negative associations. Chronic exercise is associated with increased resting energy expenditure (REE) secondary to increased lean mass and a probable increase in BAT. Many athletes are in a state of relative energy deficit suggested by lower fat mass and hypothalamic amenorrhea. States of severe energy deficit such as anorexia nervosa are associated with reduced BAT. There are no data regarding the impact of chronic exercise activity on BAT volume or activity in young women and it is unclear whether relative energy deficiency modifies the effects of exercise on BAT. We assessed cold induced BAT volume and activity in young female athletes compared with non-athletes, and further evaluated associations of BAT with measures of REE, body composition and menstrual status. The protocol was approved by our Institutional Review Board. Written informed consent was obtained from all participants prior to study initiation. This was a cross-sectional study of 24 women (16 athletes and8 non-athletes) between 18-25 years of age. Athletes were either oligo-amenorrheic (n = 8) or eumenorrheic (n = 8).We used PET/CT scans to determine cold induced BAT activity, VMAX Encore 29 metabolic cart to obtain measures of REE, and DXA for body composition. Athletes and non-athletes did not differ for age or BMI. Compared with non-athletes, athletes had lower percent body fat (p = 0.002), higher percent lean mass (p = 0.01) and trended higher in REE (p = 0.09). BAT volume and activity in athletes trended lower than in non-athletes (p = 0.06; p = 0.07, respectively). We found negative associations of BAT activity with duration of amenorrhea (r = -0.46, p = 0.02).BAT volume correlated inversely with lean mass (r = -0.46, p = 0.02), and positively with percent body fat, irisin and thyroid hormones. Our study shows a trend for lower BAT in young female athletes compared with non-athletes, and shows associations of brown fat with menstrual status and body composition. Brown fat may undergo adaptive reductions with increasing energy deficit.

Limbic and prefrontal responses to facial emotion expressions in depersonalization.

PubMed

Lemche, Erwin; Surguladze, Simon A; Giampietro, Vincent P; Anilkumar, Ananthapadmanabha; Brammer, Michael J; Sierra, Mauricio; Chitnis, Xavier; Williams, Steven C R; Gasston, David; Joraschky, Peter; David, Anthony S; Phillips, Mary L

2007-03-26

Depersonalization disorder, characterized by emotional detachment, has been associated with increased prefrontal cortical and decreased autonomic activity to emotional stimuli. Event-related fMRI with simultaneous measurements of skin conductance levels occurred in nine depersonalization disorder patients and 12 normal controls to neutral, mild and intense happy and sad facial expressions. Patients, but not controls, showed decreases in subcortical limbic activity to increasingly intense happy and sad facial expressions, respectively. For both happy and sad expressions, negative correlations between skin conductance measures in bilateral dorsal prefrontal cortices occurred only in depersonalization disorder patients. Abnormal decreases in limbic activity to increasingly intense emotional expressions, and increases in dorsal prefrontal cortical activity to emotionally arousing stimuli may underlie the emotional detachment of depersonalization disorder.

Mangiferin inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 expression and cellular invasion by suppressing nuclear factor-κB activity

PubMed Central

Dilshara, Matharage Gayani; Kang, Chang-Hee; Choi, Yung Hyun; Kim, Gi-Young

2015-01-01

We investigated the effects of mangiferin on the expression and activity of metalloproteinase (MMP)-9 and the invasion of tumor necrosis factor (TNF)-α-stimulated human LNCaP prostate carcinoma cells. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that mangiferin significantly reversed TNF-α-induced mRNA and protein expression of MMP-9 expression. Zymography data confirmed that stimulation of cells with TNF-α significantly increased MMP-9 activity. However, mangiferin substantially reduced the TNF-α-induced activity of MMP-9. Additionally, a matrigel invasion assay showed that mangiferin significantly reduced TNF-α-induced invasion of LNCaP cells. Compared to untreated controls, TNF-α-stimulated LNCaP cells showed a significant increase in nuclear factor-κB (NF-κB) luciferase activity. However, mangiferin treatment markedly decreased TNF-α-induced NF-κB luciferase activity. Furthermore, mangiferin suppressed nuclear translocation of the NF-κB subunits p65 and p50. Collectively, our results indicate that mangiferin is a potential anti-invasive agent that acts by suppressing NF-κB-mediated MMP-9 expression. [BMB Reports 2015; 48(10): 559-564] PMID:25739392

Mangiferin inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 expression and cellular invasion by suppressing nuclear factor-κB activity.

PubMed

Dilshara, Matharage Gayani; Kang, Chang-Hee; Choi, Yung Hyun; Kim, Gi-Young

2015-10-01

We investigated the effects of mangiferin on the expression and activity of metalloproteinase (MMP)-9 and the invasion of tumor necrosis factor (TNF)-α-stimulated human LNCaP prostate carcinoma cells. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that mangiferin significantly reversed TNF-α-induced mRNA and protein expression of MMP-9 expression. Zymography data confirmed that stimulation of cells with TNF-α significantly increased MMP-9 activity. However, mangiferin substantially reduced the TNF-α-induced activity of MMP-9. Additionally, a matrigel invasion assay showed that mangiferin significantly reduced TNF-α-induced invasion of LNCaP cells. Compared to untreated controls, TNF-α-stimulated LNCaP cells showed a significant increase in nuclear factor-κB (NF-κB) luciferase activity. However, mangiferin treatment markedly decreased TNF-α-induced NF-κB luciferase activity. Furthermore, mangiferin suppressed nuclear translocation of the NF-κB subunits p65 and p50. Collectively, our results indicate that mangiferin is a potential anti-invasive agent that acts by suppressing NF-κB-mediated MMP-9 expression.

Inhibition of the NorA efflux pump of Staphylococcus aureus by synthetic riparins.

PubMed

Costa, L M; de Macedo, E V; Oliveira, F A A; Ferreira, J H L; Gutierrez, S J C; Peláez, W J; Lima, F C A; de Siqueira Júnior, J P; Coutinho, H D M; Kaatz, G W; de Freitas, R M; Barreto, H M

2016-11-01

The goal of this study was to increase knowledge about the antimicrobial activity of some synthetic Riparin-derived compounds, alone or in combination with fluoroquinolone antibiotics, against a strain of Staphylococcus aureus resistant to fluoroquinolone by way of overexpression of the NorA efflux pump. Microdilution tests showed that Riparins A and B did not show any significant antibacterial activity against Staph. aureus strains. On the other hand, the intrinsic antibacterial activity increased with increasing lipophilicity of the compounds, in the following order: Riparin-D (MIC 256 μg ml -1 ; Log P 2·95) < Riparin-C (MIC 102 μg ml -1 ; Log P 3·22) < Riparin-E (MIC 16 μg ml -1 ; Log P 3·57). The addition of all riparins to growth media at subinhibitory concentrations caused an increase in the antibacterial activity of antibiotics against the NorA-overexpressing test strain. Riparin-B, which has two methoxyl groups at the phenethyl moiety, showed the best modulatory effect. Riparin-E is a good anti-staphylococci agent, while Riparin-B functions as a NorA efflux pump inhibitor. Our data suggest the possibility of using Riparin-B in combination with norfloxacin or ciprofloxacin for therapy of infections caused by multi-drug resistant Staph. aureus. © 2016 The Society for Applied Microbiology.

Prenatal Exposure to the Environmental Obesogen Tributyltin Predisposes Multipotent Stem Cells to Become Adipocytes

PubMed Central

Kirchner, Séverine; Kieu, Tiffany; Chow, Connie; Casey, Stephanie; Blumberg, Bruce

2010-01-01

The environmental obesogen hypothesis proposes that pre- and postnatal exposure to environmental chemicals contributes to adipogenesis and the development of obesity. Tributyltin (TBT) is an agonist of both retinoid X receptor (RXR) and peroxisome proliferator-activated receptor γ (PPARγ). Activation of these receptors can elevate adipose mass in adult mice exposed to the chemical in utero. Here we show that TBT sensitizes human and mouse multipotent stromal stem cells derived from white adipose tissue [adipose-derived stromal stem cells (ADSCs)] to undergo adipogenesis. In vitro exposure to TBT, or the PPARγ activator rosiglitazone increases adipogenesis, cellular lipid content, and expression of adipogenic genes. The adipogenic effects of TBT and rosiglitazone were blocked by the addition of PPARγ antagonists, suggesting that activation of PPARγ mediates the effect of both compounds on adipogenesis. ADSCs from mice exposed to TBT in utero showed increased adipogenic capacity and reduced osteogenic capacity with enhanced lipid accumulation in response to adipogenic induction. ADSCs retrieved from animals exposed to TBT in utero showed increased expression of PPARγ target genes such as the early adipogenic differentiation gene marker fatty acid-binding protein 4 and hypomethylation of the promoter/enhancer region of the fatty acid-binding protein 4 locus. Hence, TBT alters the stem cell compartment by sensitizing multipotent stromal stem cells to differentiate into adipocytes, an effect that could likely increase adipose mass over time. PMID:20160124

Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes.

PubMed

Kirchner, Séverine; Kieu, Tiffany; Chow, Connie; Casey, Stephanie; Blumberg, Bruce

2010-03-01

The environmental obesogen hypothesis proposes that pre- and postnatal exposure to environmental chemicals contributes to adipogenesis and the development of obesity. Tributyltin (TBT) is an agonist of both retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARgamma). Activation of these receptors can elevate adipose mass in adult mice exposed to the chemical in utero. Here we show that TBT sensitizes human and mouse multipotent stromal stem cells derived from white adipose tissue [adipose-derived stromal stem cells (ADSCs)] to undergo adipogenesis. In vitro exposure to TBT, or the PPARgamma activator rosiglitazone increases adipogenesis, cellular lipid content, and expression of adipogenic genes. The adipogenic effects of TBT and rosiglitazone were blocked by the addition of PPARgamma antagonists, suggesting that activation of PPARgamma mediates the effect of both compounds on adipogenesis. ADSCs from mice exposed to TBT in utero showed increased adipogenic capacity and reduced osteogenic capacity with enhanced lipid accumulation in response to adipogenic induction. ADSCs retrieved from animals exposed to TBT in utero showed increased expression of PPARgamma target genes such as the early adipogenic differentiation gene marker fatty acid-binding protein 4 and hypomethylation of the promoter/enhancer region of the fatty acid-binding protein 4 locus. Hence, TBT alters the stem cell compartment by sensitizing multipotent stromal stem cells to differentiate into adipocytes, an effect that could likely increase adipose mass over time.

Gamma delta T cell responses associated with the development of tuberculosis in health care workers.

PubMed

Ordway, Diane J; Pinto, Luisa; Costa, Leonor; Martins, Marta; Leandro, Clara; Viveiros, Miguel; Amaral, Leonard; Arroz, Maria J; Ventura, Fernando A; Dockrell, Hazel M

2005-03-01

This study evaluated T cell immune responses to purified protein derivative (PPD) and Mycobacterium tuberculosis (Mtb) in health care workers who remained free of active tuberculosis (HCWs w/o TB), health care workers who went on to develop active TB (HCWs w/TB), non-health care workers who were TB free (Non-HCWs) and tuberculosis patients presenting with minimal (Min TB) or advanced (Adv TB) disease. Peripheral blood mononuclear cells (PBMC) were stimulated with Mtb and PPD and the expression of T cell activation markers CD25+ and HLA-DR+, intracellular IL-4 and IFN-gamma production and cytotoxic responses were evaluated. PBMC from HCWs who developed TB showed decreased percentages of cells expressing CD8+CD25+ in comparison to HCWs who remained healthy. HCWs who developed TB showed increased gammadelta TCR+ cell cytotoxicity and decreased CD3+gammadelta TCR- cell cytotoxicity in comparison to HCWs who remained healthy. PBMC from TB patients with advanced disease showed decreased percentages of CD25+CD4+ and CD25+CD8+ T cells that were associated with increased IL-4 production in CD8+ and gammadelta TCR+ phenotypes, in comparison with TB patients presenting minimal disease. TB patients with advanced disease showed increased gammadelta TCR+ cytotoxicity and reduced CD3+gammadelta TCR- cell cytotoxicity. Our results suggest that HCWs who developed TB show an early compensatory mechanism involving an increase in lytic responses of gammadelta TCR+ cells which did not prevent TB.

Further studies on the structural requirements for mast cell degranulating (MCD) peptide-mediated histamine release.

PubMed

Buku, A; Price, J A

2001-12-01

Mast cell degranulating (MCD) peptide was modified in its two disulfide bridges and in the two arginine residues in order to measure the ability of these analogs to induce histamine release from mast cells in vitro. Analogs prepared were [Ala(3,15)]MCD, [Ala(5,19)]MCD, [Orn(16)]MCD, and [Orn(7,16)]MCD. Their histamine-releasing activity was determined spectrofluorometrically with peritoneal mast cells. The monocyclic analogs in which the cysteine residues were replaced pairwise with alanine residues showed three-to ten-fold diminished histamine-releasing activity respectively, compared with the parent MCD peptide. Substantial increases in activity were observed where arginine residues were replaced by ornithines. The ornithine-mono substituted analog showed an almost six-fold increase and the ornithine-doubly substituted analog three-fold increase in histamine-releasing activity compared with the parent MCD peptide. The structural changes associated with these activities were followed by circular dichroism (CD) spectroscopy. Changes in the shape and ellipticity of the CD spectra reflected a role for the disulfide bonds and the two arginine residues in the overall conformation and biological activity of the molecule.

Phosphatase activity and its relationship with physical and chemical parameters during vermicomposting of filter cake and cattle manure.

PubMed

Busato, Jader Galba; Papa, Gabriella; Canellas, Luciano Pasqualoto; Adani, Fabrizio; de Oliveira, Aline Lima; Leão, Tairone Paiva

2016-03-15

Recycling of phosphorus (P) from organic residues (ORs) is important to develop environmentally friendly agriculture. The use of this P source depends on phosphatase enzymes, which can be affected by a chain of parameters during maturation of ORs. In this study the phosphatase activity levels throughout vermicomposting of filter cake (FC) and cattle manure (CM) were correlated with different physical and chemical parameters in an effort to increase the knowledge about recycling of P from ORs. FC presented higher total nitrogen content (TNC), total organic carbon (TOC), humic acid (HA) content, water-soluble P (WSP), phosphatase activities and nanopore volume than CM during vermicomposting. Decreases in TOC of CM resulted from carbohydrate mineralization, which was not observed for FC. CM showed increased hydrophobic index during vermicomposting while FC showed a slight decrease. Phosphatase activities correlated positively with TOC, pH and WSP and negatively with HA content for both vermicomposts. Nanopore volume was negatively correlated with phosphatase activities for FC but not for CM. No correlations between hydrophobicity and phosphatase activities were found for FC. Increased hydrophobicity throughout vermicomposting of CM could be partially associated with decreases in phosphatase levels. © 2015 Society of Chemical Industry.

A pulse of blue light induces a transient increase in activity of apoplastic K+ in laminar pulvinus of Phaseolus vulgaris L.

PubMed

Okazaki, Y; Azuma, K; Nishizaki, Y

2000-02-01

A pulse of blue light induced both a transient increase in activity of apoplastic K+ and membrane depolarization in laminar pulvinus of Phaseolus vulgaris L. This shows that blue-light-induced net efflux of K+ from motor cells is closely related to membrane depolarization.

Transformation of Lettuce with rol ABC Genes: Extracts Show Enhanced Antioxidant, Analgesic, Anti-Inflammatory, Antidepressant, and Anticoagulant Activities in Rats.

PubMed

Ismail, Hammad; Dilshad, Erum; Waheed, Mohammad Tahir; Mirza, Bushra

2017-03-01

Lettuce is an edible crop that is well known for dietary and antioxidant benefits. The present study was conducted to investigate the effects of rol ABC genes on antioxidant and medicinal potential of lettuce by Agrobacterium-mediated transformation. Transgene integration and expression was confirmed through PCR and real-time RT-PCR, respectively. The transformed plants showed 91-102 % increase in total phenolic contents and 53-65 % increase in total flavonoid contents compared to untransformed plants. Total antioxidant capacity and total reducing power increased up to 112 and 133 % in transformed plants, respectively. Results of DPPH assay showed maximum 51 % increase, and lipid peroxidation assay exhibited 20 % increase in antioxidant activity of transformed plants compared to controls. Different in vivo assays were carried out in rats. The transgenic plants showed up to 80 % inhibition in both hot plate analgesic assay and carrageenan-induced hind paw edema test, while untransformed plants showed only 45 % inhibition. Antidepressant and anticoagulant potential of transformed plants was also significantly enhanced compared to untransformed plants. Taken together, the present work highlights the use of rol genes to enhance the secondary metabolite production in lettuce and improve its analgesic, anti-inflammatory, antidepressant, and anticoagulatory properties.

Alpha-tocopherol-dependent salt tolerance is more related with auxin synthesis rather than enhancement antioxidant defense in soybean roots.

PubMed

Sereflioglu, Seda; Dinler, Burcu Seckin; Tasci, Eda

2017-03-01

In this paper, we describe the alleviated effects of alpha-tocopherol (α-T) on oxidative damage and its possible role as a signal transmitter in plants during salt stress. The results show that exogenously applied α-T under salt stress increased root length and weight, but reduced hydrogen peroxide (H 2 O 2 ), superoxide anion radical (O 2 . -) and malondialdehyde (MDA) content in soybean roots. The proline content was reduced by α-T treatment. Interestingly, endogenous auxin (IAA) level was significantly increased after α-T application as compared to salt stress alone. Moreover, α-T reduced significantly superoxide dismutase (SOD) enzyme and isoenzyme activity but upregulated peroxidase (POX) 2, 3 and glutathione-s-transferase (GST) 1, 3 isoenzyme expression. However, ascorbate peroxidase (APX) enzyme activity was not affected at all. Consequently, the results show that α-T serves as a signal molecule under salinity from leaves to roots by increasing remarkably endogenous IAA levels and increasing partially antioxidant activity in roots.

Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans

PubMed Central

Hwang, Ara B.; Ryu, Eun-A; Artan, Murat; Chang, Hsin-Wen; Kabir, Mohammad Humayun; Nam, Hyun-Jun; Lee, Dongyeop; Yang, Jae-Seong; Kim, Sanguk; Mair, William B.; Lee, Cheolju; Lee, Siu Sylvia; Lee, Seung-Jae

2014-01-01

Mild inhibition of mitochondrial respiration extends the lifespan of many species. In Caenorhabditis elegans, reactive oxygen species (ROS) promote longevity by activating hypoxia-inducible factor 1 (HIF-1) in response to reduced mitochondrial respiration. However, the physiological role and mechanism of ROS-induced longevity are poorly understood. Here, we show that a modest increase in ROS increases the immunity and lifespan of C. elegans through feedback regulation by HIF-1 and AMP-activated protein kinase (AMPK). We found that activation of AMPK as well as HIF-1 mediates the longevity response to ROS. We further showed that AMPK reduces internal levels of ROS, whereas HIF-1 amplifies the levels of internal ROS under conditions that increase ROS. Moreover, mitochondrial ROS increase resistance to various pathogenic bacteria, suggesting a possible association between immunity and long lifespan. Thus, AMPK and HIF-1 may control immunity and longevity tightly by acting as feedback regulators of ROS. PMID:25288734

MYC-induced reprogramming of glutamine catabolism supports optimal virus replication

PubMed Central

Thai, Minh; Thaker, Shivani K.; Feng, Jun; Du, Yushen; Hu, Hailiang; Ting Wu, Ting; Graeber, Thomas G.; Braas, Daniel; Christofk, Heather R.

2015-01-01

Viruses rewire host cell glucose and glutamine metabolism to meet the bioenergetic and biosynthetic demands of viral propagation. However, the mechanism by which viruses reprogram glutamine metabolism and the metabolic fate of glutamine during adenovirus infection have remained elusive. Here, we show MYC activation is necessary for adenovirus-induced upregulation of host cell glutamine utilization and increased expression of glutamine transporters and glutamine catabolism enzymes. Adenovirus-induced MYC activation promotes increased glutamine uptake, increased use of glutamine in reductive carboxylation and increased use of glutamine in generating hexosamine pathway intermediates and specific amino acids. We identify glutaminase (GLS) as a critical enzyme for optimal adenovirus replication and demonstrate that GLS inhibition decreases replication of adenovirus, herpes simplex virus 1 and influenza A in cultured primary cells. Our findings show that adenovirus-induced reprogramming of glutamine metabolism through MYC activation promotes optimal progeny virion generation, and suggest that GLS inhibitors may be useful therapeutically to reduce replication of diverse viruses. PMID:26561297

Cooperative binding mitigates the high-dose hook effect.

PubMed

Roy, Ranjita Dutta; Rosenmund, Christian; Stefan, Melanie I

2017-08-14

The high-dose hook effect (also called prozone effect) refers to the observation that if a multivalent protein acts as a linker between two parts of a protein complex, then increasing the amount of linker protein in the mixture does not always increase the amount of fully formed complex. On the contrary, at a high enough concentration range the amount of fully formed complex actually decreases. It has been observed that allosterically regulated proteins seem less susceptible to this effect. The aim of this study was two-fold: First, to investigate the mathematical basis of how allostery mitigates the prozone effect. And second, to explore the consequences of allostery and the high-dose hook effect using the example of calmodulin, a calcium-sensing protein that regulates the switch between long-term potentiation and long-term depression in neurons. We use a combinatorial model of a "perfect linker protein" (with infinite binding affinity) to mathematically describe the hook effect and its behaviour under allosteric conditions. We show that allosteric regulation does indeed mitigate the high-dose hook effect. We then turn to calmodulin as a real-life example of an allosteric protein. Using kinetic simulations, we show that calmodulin is indeed subject to a hook effect. We also show that this effect is stronger in the presence of the allosteric activator Ca 2+ /calmodulin-dependent kinase II (CaMKII), because it reduces the overall cooperativity of the calcium-calmodulin system. It follows that, surprisingly, there are conditions where increased amounts of allosteric activator actually decrease the activity of a protein. We show that cooperative binding can indeed act as a protective mechanism against the hook effect. This will have implications in vivo where the extent of cooperativity of a protein can be modulated, for instance, by allosteric activators or inhibitors. This can result in counterintuitive effects of decreased activity with increased concentrations of both the allosteric protein itself and its allosteric activators.

Enhancing the biological degradability of sulfamethoxazole by ionizing radiation treatment in aqueous solution

NASA Astrophysics Data System (ADS)

Sági, Gyuri; Kovács, Krisztina; Bezsenyi, Anikó; Csay, Tamás; Takács, Erzsébet; Wojnárovits, László

2016-07-01

Changes of biodegradability and toxicity were followed up on aqueous solutions of sulfamethoxazole (SMX), during ionizing radiation treatment. The biodegradability of SMX (0.1 mmol dm-3) was specified by five-day biological oxygen demand (BOD5), using municipal activated sludge, and the results showed an improvement with applying only 0.4 kGy dose. BOD5 further increased with prolonged irradiation, indicating a conversion of SMX, a non-biodegradable compound, to biologically treatable substances. At 2.5 kGy dose, the BOD5/COD ratio increased from 0 to 0.16. The total organic carbon (TOC) content showed a decrease of only 15% at this point, thus high degree of mineralization is not necessary to make SMX digestible for the low concentrations of microorganisms used during BOD5 measurements. Increment in respiration inhibition of municipal activated sludge was observed with increasing the dose. The EC50 values showed a decrease of one order of magnitude when changing the dose from 0.4 kGy to 2.5 kGy. The increase of inhibition and formation of H2O2 showed a strong correlation.

Bioaccumulation and biodegradation of sulfamethazine in Chlorella pyrenoidosa

NASA Astrophysics Data System (ADS)

Sun, Ming; Lin, Hong; Guo, Wen; Zhao, Fazhen; Li, Jian

2017-12-01

Intensive use of sulfamethazine (SM2) in aquaculture has resulted in some detrimental effects to non-targeted organisms. In order to assess its potential ecological risk, it is crucial to have a good understanding on the bioaccumulation and biodegradation of SM2 in Chlorella pyrenoidosa. The microalgae were treated with 2, 4, and 8 mg L-1 of sulfamethazine for 13 days, respectively, showing that the inhibition effects of sulfamethazine on the growth of Chlorella pyrenoidosa increased progressively as the concentrations of sulfamethazine increasing from 2 to 8 mg L-1. The peak concentrations of sulfamethazine accumulated in C. pyrenoidosa were 0.225, 0.325, and 0.596 ng per mg FW on day 13 for three treatment groups, respectively, showing a great ability to deplete sulfamethazine from the culture media. On day 13, the percentages of biotic degradation were 48.45%, 60.21% and 69.93%, respectively. The EC50 of 10.05 mg L-1 was derived which showed no significant risk for C. pyrenoidosa with a calculated risk quotient < 1. The activities of superoxide dismutase and catalase increased progressively in response to sulfamethazine and showed a positive correlation to the treatment concentrations. The highest superoxide dismutase activity was achieved at the concentration of 8 mg L-1 after 2 d of exposure, which was 1.89 folds higher than that of the control. The activity of catalase has a similar pattern to that of superoxide dismutase with the maximum activity achieved at day 2, which was 3.11 folds higher compared to that of the control. In contrast to superoxide dismutase and catalase, the maximum glutathione S-transferase activity was observed at day 6, showing 2.2 folds higher than that of the control.

Increased alpha 2-macroglobulin in diabetes: a hyperglycemia related phenomenon associated with reduced antithrombin III activity.

PubMed

Ceriello, A; Giugliano, D; Quatraro, A; Stante, A; Dello Russo, P; Torella, R

1989-01-01

Increased alpha 2-macroglobulin (alpha 2M) activity and concentration, and decreased antithrombin III (ATIII) plasma concentration are reported in diabetic subjects. In diabetes an inverse correlation between ATIII activity and blood glucose, HbA1, alpha 2M activity and alpha 2M concentration, and a direct correlation between both alpha 2M activity and alpha 2M concentration with blood glucose and HbA1 are found. Moreover, a direct correlation between alpha 2M activity and alpha 2M concentration fails. In both diabetic and normal subjects induced hyperglycemia increases alpha 2M activity and alpha 2M concentration reduces ATIII activity, while ATIII concentration is not affected. These data which show that hyperglycemia may increase alpha 2M molecule levels while altering only the biological function of ATIII, provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may condition the levels of some risk factors for the development of diabetic complications such as alpha 2M.

Developmental changes in brain regions involved in phonological and orthographic processing during spoken language processing

PubMed Central

Cone, Nadia E.; Burman, Douglas D.; Bitan, Tali; Bolger, Donald J.; Booth, James R.

2008-01-01

Developmental differences in brain activation of 9- to 15-year-old children were examined during an auditory rhyme decision task to spoken words using functional magnetic resonance imaging (fMRI). As a group, children showed activation in left superior/middle temporal gyri (BA 22, 21), right middle temporal gyrus (BA 21), dorsal (BA 45, pars opercularis) and ventral (BA 46, pars triangularis) aspects of left inferior frontal gyrus, and left fusiform gyrus (BA 37). There was a developmental increase in activation in left middle temporal gyrus (BA 22) across all lexical conditions, suggesting that automatic semantic processing increases with age regardless of task demands. Activation in left dorsal inferior frontal gyrus also showed developmental increases for the conflicting (e.g. PINT-MINT) compared to the non-conflicting (e.g. PRESS-LIST) non-rhyming conditions, indicating that this area becomes increasingly involved in strategic phonological processing in the face of conflicting orthographic and phonological representations. Left inferior temporal/fusiform gyrus (BA 37) activation was also greater for the conflicting (e.g. PINT-MINT) condition, and a developmental increase was found in the positive relationship between individuals' reaction time and activation in left lingual/fusiform gyrus (BA 18) in this condition, indicating an age-related increase in the association between longer reaction times and greater visual-orthographic processing in this conflicting condition. These results suggest that orthographic processing is automatically engaged by children in a task that does not require access to orthographic information for correct performance, especially when orthographic and phonological representations conflict, and especially for longer response latencies in older children. PMID:18413290

Activation of lysosomal cathepsins in pregnant bovine leukocytes.

PubMed

Talukder, Md Abdus Shabur; Balboula, Ahmed Zaky; Shirozu, Takahiro; Kim, Sung Woo; Kunii, Hiroki; Suzuki, Toshiyuki; Ito, Tsukino; Kimura, Koji; Takahashi, Masashi

2018-06-01

In ruminants, interferon-tau (IFNT) - mediated expression of interferon-stimulated genes in peripheral blood leukocytes (PBLs) can indicate pregnancy. Recently, type 1 IFN-mediated activation of lysosomes and lysosomal cathepsins (CTSs) was observed in immune cells. This study investigated the status of lysosomal CTSs and lysosomes in PBLs collected from pregnant (P) and non-pregnant (NP) dairy cows, and conducted in vitro IFNT stimulation of NP blood leukocytes. Blood samples were collected 0, 7, 14 and 18 days post-artificial insemination, and the peripheral blood mononuclear cells (PBMCs) and polymorphonuclear granulocytes (PMNs) separated. The fluorescent activity of CTSB and CTSK in PMNs significantly increased with the progress of pregnancy, especially on day 18. In vitro supplementation of IFNT significantly increased the activities of CTSB and CTSK in NP PBMCs and PMNs. CTSB expression was significantly higher in PBMCs and PMNs collected from P day-18 cows than from NP cows, whereas there was no difference in CTSK expression. IFNT increased CTSB expression but did not affect CTSK expression. Immunodetection showed an increase of CTSB in P day-18 PBMCs and PMNs. In vitro stimulation of IFNT increased CTSB in NP PBMCs and PMNs. Lysosomal acidification showed a significant increase in P day-18 PBMCs and PMNs. IFNT also stimulated lysosomal acidification. Expressions of lysosome-associated membrane protein (LAMP) 1 and LAMP2 were significantly higher in P day-18 PBMCs and PMNs. The results suggest that pregnancy-specific activation of lysosomal functions by CTS activation in blood leukocytes is highly associated with IFNT during maternal and fetal recognition of pregnancy. © 2018 Society for Reproduction and Fertility.

Rapamycin treatment augments both protein ubiquitination and Akt activation in pressure-overloaded rat myocardium

PubMed Central

Harston, Rebecca K.; McKillop, John C.; Moschella, Phillip C.; Van Laer, An; Quinones, Lakeya S.; Baicu, Catalin F.; Balasubramanian, Sundaravadivel; Zile, Michael R.

2011-01-01

Ubiquitin-mediated protein degradation is necessary for both increased ventricular mass and survival signaling for compensated hypertrophy in pressure-overloaded (PO) myocardium. Another molecular keystone involved in the hypertrophic growth process is the mammalian target of rapamycin (mTOR), which forms two distinct functional complexes: mTORC1 that activates p70S6 kinase-1 to enhance protein synthesis and mTORC2 that activates Akt to promote cell survival. Independent studies in animal models show that rapamycin treatment that alters mTOR complexes also reduces hypertrophic growth and increases lifespan by an unknown mechanism. We tested whether the ubiquitin-mediated regulation of growth and survival in hypertrophic myocardium is linked to the mTOR pathway. For in vivo studies, right ventricle PO in rats was conducted by pulmonary artery banding; the normally loaded left ventricle served as an internal control. Rapamycin (0.75 mg/kg per day) or vehicle alone was administered intraperitoneally for 3 days or 2 wk. Immunoblot and immunofluorescence imaging showed that the level of ubiquitylated proteins in cardiomyocytes that increased following 48 h of PO was enhanced by rapamycin. Rapamycin pretreatment also significantly increased PO-induced Akt phosphorylation at S473, a finding confirmed in cardiomyocytes in vitro to be downstream of mTORC2. Analysis of prosurvival signaling in vivo showed that rapamycin increased PO-induced degradation of phosphorylated inhibitor of κB, enhanced expression of cellular inhibitor of apoptosis protein 1, and decreased active caspase-3. Long-term rapamycin treatment in 2-wk PO myocardium blunted hypertrophy, improved contractile function, and reduced caspase-3 and calpain activation. These data indicate potential cardioprotective benefits of rapamycin in PO hypertrophy. PMID:21357504

Protective Effect of Aerobic Physical Activity on Sleep Behavior in Breast Cancer Survivors.

PubMed

Roveda, Eliana; Vitale, Jacopo A; Bruno, Eleonora; Montaruli, Angela; Pasanisi, Patrizia; Villarini, Anna; Gargano, Giuliana; Galasso, Letizia; Berrino, Franco; Caumo, Andrea; Carandente, Franca

2017-03-01

Sleep disorders are associated with an increased risk of cancer, including breast cancer (BC). Physical activity (PA) can produce beneficial effects on sleep. We designed a randomized controlled trial to test the effect of 3 months of physical activity on sleep and circadian rhythm activity level evaluated by actigraphy. 40 BC women, aged 35-70 years, were randomized into an intervention (IG) and a control group (CG). IG performed a 3 month of aerobic exercise. At baseline and after 3 months, the following parameters were evaluated both for IG and CG: anthropometric and body composition measurements, energy expenditure and motion level; sleep parameters (Actual Sleep Time-AST, Actual Wake Time-AWT, Sleep Efficiency-SE, Sleep Latency-SL, Mean Activity Score-MAS, Movement and Fragmentation Index-MFI and Immobility Time-IT) and activity level circadian rhythm using the Actigraph Actiwatch. The CG showed a deterioration of sleep, whereas the IG showed a stable pattern. In the CG the SE, AST and IT decreased and the AWT, SL, MAS and MFI increased. In the IG, the SE, IT, AWT, SL, and MAS showed no changes and AST and MFI showed a less pronounced change in the IG than in the CG. The rhythmometric analysis revealed a significant circadian rhythm in two groups. After 3 months of PA, IG showed reduced fat mass %, while CG had improved weight and BMI. Physical activity may be beneficial against sleep disruption. Indeed, PA prevented sleep worsening in IG. PA can represent an integrative intervention therapy able to modify sleep behaviour.

Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in murine epidermis. Modulation of enzyme content and activation state by barrier requirements.

PubMed Central

Proksch, E; Elias, P M; Feingold, K R

1990-01-01

Epidermal cholesterol biosynthesis is regulated by barrier function. We quantitated the amount and activation state (phosphorylation-dephosphorylation) of the rate-limiting enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, in epidermis before and after barrier disruption. In murine epidermis we found high enzyme activity (1.75 +/- 0.02 nmol/min per mg protein). After acute barrier disruption, enzyme activity began to increase after 1.5 h, reaching a maximum increase by 2.5 h, and returned to normal by 15 h. Chronic barrier disruption increased total enzyme activity by 83%. In normal epidermis, measurement of HMG CoA reductase activity in microsomes isolated in NaF- vs. NaCl-containing buffers demonstrated that 46 +/- 2% of the enzyme was in the active form. After acute or chronic barrier disruption, a marked increase in the percentage of HMG CoA reductase in the active form was observed. Acute disruption increased enzyme activation state as early as 15 min, reaching a maximum after 2.5 h, with an increase still present at 15 h, indicating that changes in activation state had a close temporal relationship with barrier function. Increases in total HMG CoA reductase activity occurred only after profound barrier disruption, whereas changes in activation state occur with lesser degrees of barrier disruption. Artificial correction of barrier function prevented the increase in total HMG CoA reductase activity, and partially prevented the increase in enzyme activation. These results show that barrier requirements regulate epidermal cholesterol synthesis by modulating both the HMG CoA reductase amount and activation state. Images PMID:2312730

High altitude simulation, substance P and airway rapidly adapting receptor activity in rabbits.

PubMed

Bhagat, R; Yasir, A; Vashisht, A; Kulshreshtha, R; Singh, S B; Ravi, K

2011-09-15

To investigate whether there is a change in airway rapidly adapting receptor (RAR) activity during high altitude exposure, rabbits were placed in a high altitude simulation chamber (barometric pressure, 429 mm Hg). With 12 h exposure, when there was pulmonary congestion, an increase in basal RAR activity was observed. With 36 h exposure, when there was alveolar edema, there was a further increase in basal RAR activity. In these backgrounds, there was an increase in the sensitivity of the RARs to substance P (SP). To assess whether there was an increase in lung SP level, neutral endopeptidase activity was determined which showed a decrease in low barometric pressure exposed groups. It is concluded that along with the SP released, pulmonary congestion and edema produced, respectively by different durations of low barometric pressure exposure cause a progressive increase in RAR activity which may account for the respiratory symptoms reported in climbers who are unacclimatized. Copyright © 2011 Elsevier B.V. All rights reserved.

The subthalamic nucleus during decision-making with multiple alternatives.

PubMed

Keuken, Max C; Van Maanen, Leendert; Bogacz, Rafal; Schäfer, Andreas; Neumann, Jane; Turner, Robert; Forstmann, Birte U

2015-10-01

Several prominent neurocomputational models predict that an increase of choice alternatives is modulated by increased activity in the subthalamic nucleus (STN). In turn, increased STN activity allows prolonged accumulation of information. At the same time, areas in the medial frontal cortex such as the anterior cingulate cortex (ACC) and the pre-SMA are hypothesized to influence the information processing in the STN. This study set out to test concrete predictions of STN activity in multiple-alternative decision-making using a multimodal combination of 7 Tesla structural and functional Magnetic Resonance Imaging, and ancestral graph (AG) modeling. The results are in line with the predictions in that increased STN activity was found with an increasing amount of choice alternatives. In addition, our study shows that activity in the ACC is correlated with activity in the STN without directly modulating it. This result sheds new light on the information processing streams between medial frontal cortex and the basal ganglia. © 2015 Wiley Periodicals, Inc.

Activation of human naïve Th cells increases surface expression of GD3 and induces neoexpression of GD2 that colocalize with TCR clusters.

PubMed

Villanueva-Cabello, Tania M; Mollicone, Rosella; Cruz-Muñoz, Mario E; López-Guerrero, Delia V; Martínez-Duncker, Iván

2015-12-01

CD4+ T helper lymphocytes (Th) orchestrate the immune response after their activation by antigen-presenting cells. Activation of naïve Th cells is reported to generate the reduction in surface epitopes of sialic acid (Sia) in α2,3 and α2,6 linkages. In this work, we report that in spite of this glycophenotype, anti-CD3/anti-CD28-activated purified human naïve Th cells show a significant increase in surface Sia, as assessed by metabolic labeling, compared with resting naïve Th cells, suggesting an increased flux of Sia toward Siaα2,8 glycoconjugates. To understand this increase as a result of ganglioside up-regulation, we observed that very early after activation, human naïve Th cells show an increased expression in surface GD3 and neoexpression of surface GD2 gangliosides, the latter clustering with the T cell receptor (TCR). Also, we report that in contrast to GM2/GD2 synthase null mice, lentiviral vector-mediated silencing of the GM2/GD2 synthase in activated human naïve Th cells reduced efficient TCR clustering and downstream signaling, as assessed by proliferation assays and IL-2 and IL-2R expression, pointing to an important role of this enzyme in activation of human naive Th cells. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Environmental Estrogen, Nonylphenol, Activates the Constitutive Androstane Receptor

PubMed Central

Hernandez, Juan P.; Huang, Wendong; Chapman, Laura M.; Chua, Steven; Moore, David D.; Baldwin, William S.

2007-01-01

Nonylphenol (NP) and its parent compounds, the nonylphenol ethoxylates are some of the most prevalent chemicals found in U.S. waterways. NP is also resistant to biodegradation and is a known environmental estrogen, which makes NP a chemical of concern. Our data show that NP also activates the constitutive androstane receptor (CAR), an orphan nuclear receptor important in the induction of detoxification enzymes, including the P450s. Transactivation assays demonstrate that NP increases murine CAR (mCAR) transcriptional activity, and NP treatment can overcome the inhibitory effects of the inverse agonist, androstanol, on mCAR activation. Treatment of wild-type (CAR +/+) mice with NP at 50 or 75 mg/kg/day increases Cyp2b protein expression in a dose-dependent manner as demonstrated by Western blotting, and was confirmed by quantitative reverse transcription–PCR of Cyp2b10 transcript levels. CAR-null (CAR −/−) mice show no increased expression of Cyp2b following NP treatment, indicating that CAR is required for NP-mediated Cyp2b induction. In addition, NP increases the translocation of CAR into the nucleus, which is the key step in the commencement of CAR's transcriptional activity. NP also induced CYP2B6 in primary human hepatocytes, and increased Cyp2b10 messenger RNA and protein expression in humanized CAR mice, indicating that NP is an activator of human CAR as well. In conclusion, NP is a CAR activator, and this was demonstrated in vitro with transactivation assays and in vivo with transgenic CAR mouse models. PMID:17483497

Tolerance to hypometabolism and arousal induced by hibernation in the apple snail Pomacea canaliculata (Caenogastropoda, Ampullariidae).

PubMed

Giraud-Billoud, Maximiliano; Castro-Vazquez, Alfredo; Campoy-Diaz, Alejandra D; Giuffrida, Pablo M; Vega, Israel A

2017-12-19

Pomacea canaliculata may serve as a model organism for comparative studies of oxidative damage and antioxidant defenses in active, hibernating and arousing snails. Oxidative damage (as TBARS), free radical scavenging capacity (as ABTS + oxidation), uric acid (UA) and glutathione (GSH) concentrations, activities of superoxide dismutase (SOD) and catalase (CAT), and the protein expression levels of heat shock proteins (Hsp70, Hsc70, Hsp90) were studied in digestive gland, kidney and foot. Tissue TBARS of hibernating snails (45days) was higher than active snails. Hibernation produced an increase of ABTS + in digestive gland, probably because of the sustained antioxidant defenses (UA and/or GSH and SOD levels). Kidney protection during the activity-hibernation cycle seemed provided by increased UA concentrations. TBARS in the foot remained high 30min after arousal with no changes in ABTS + , but this tissue increased ABTS + oxidation at 24h to expenses increased UA and decreased GSH levels, and with no changes in SOD and CAT activities. The level of Hsp70 in kidney showed no changes throughout the activity-hibernation cycle but it increased in the foot after hibernation. The tissue levels of Hsp90 in snails hibernating were higher than active snails and returned to baseline 24h after arousal. Results showed that chronic cooling produces a significant oxidative damage in three studied tissues and that these tissue damages are overcome quickly (between 30min to 24h) with fluctuations in different antioxidant defenses (UA, GSH, CAT) and heat shock proteins (Hsp70 and Hsp90). Copyright © 2017 Elsevier Inc. All rights reserved.

Integration of actomyosin contractility with cell-cell adhesion during dorsal closure.

PubMed

Duque, Julia; Gorfinkiel, Nicole

2016-12-15

In this work, we combine genetic perturbation, time-lapse imaging and quantitative image analysis to investigate how pulsatile actomyosin contractility drives cell oscillations, apical cell contraction and tissue closure during morphogenesis of the amnioserosa, the main force-generating tissue during the dorsal closure in Drosophila We show that Myosin activity determines the oscillatory and contractile behaviour of amnioserosa cells. Reducing Myosin activity prevents cell shape oscillations and reduces cell contractility. By contrast, increasing Myosin activity increases the amplitude of cell shape oscillations and the time cells spend in the contracted phase relative to the expanded phase during an oscillatory cycle, promoting cell contractility and tissue closure. Furthermore, we show that in AS cells, Rok controls Myosin foci formation and Mbs regulates not only Myosin phosphorylation but also adhesion dynamics through control of Moesin phosphorylation, showing that Mbs coordinates actomyosin contractility with cell-cell adhesion during amnioserosa morphogenesis. © 2016. Published by The Company of Biologists Ltd.

Influence of alkyl sulfates on waste activated sludge fermentation at ambient temperature.

PubMed

Jiang, Su; Chen, Yinguang; Zhou, Qi

2007-09-05

Alkyl sulfates (AS), such as sodium dodecyl sulfate (SDS), are widely used in household and industrial products, and can be found in some wastewater and waste activated sludge (WAS). The effect of SDS on the fermentation of WAS at ambient temperature was investigated in this paper. Experimental results showed that the concentrations of protein and carbohydrate in aqueous phase increased with the amount of SDS. The concentrations of both NH(4)(+)-N and PO(4)(3-)-P in fermentation liquor also increased in the presence of SDS. In addition, it was observed that the fermentative short-chain fatty acids (SCFAs) concentration was affected by SDS. With the increase of SDS dosage, the maximum SCFAs concentration increased, and the fermentation time before reaching the maximum SCFAs concentration also increased. Further investigation showed that the produced SCFAs consisted of acetic, propionic, n-butyric, iso-butyric, n-valeric and iso-valeric acids, and acetic, iso-valeric and propionic acids were the three main products. The influence of SDS on methanogenesis was also investigated, and the inhibitory effect of SDS on methanogens activity was observed.

MKK6 controls T3-mediated browning of white adipose tissue.

PubMed

Matesanz, Nuria; Bernardo, Edgar; Acín-Pérez, Rebeca; Manieri, Elisa; Pérez-Sieira, Sonia; Hernández-Cosido, Lourdes; Montalvo-Romeral, Valle; Mora, Alfonso; Rodríguez, Elena; Leiva-Vega, Luis; Lechuga-Vieco, Ana Victoria; Ruiz-Cabello, Jesús; Torres, Jorge L; Crespo-Ruiz, Maria; Centeno, Francisco; Álvarez, Clara V; Marcos, Miguel; Enríquez, Jose Antonio; Nogueiras, Ruben; Sabio, Guadalupe

2017-10-11

Increasing the thermogenic capacity of adipose tissue to enhance organismal energy expenditure is considered a promising therapeutic strategy to combat obesity. Here, we report that expression of the p38 MAPK activator MKK6 is elevated in white adipose tissue of obese individuals. Using knockout animals and shRNA, we show that Mkk6 deletion increases energy expenditure and thermogenic capacity of white adipose tissue, protecting mice against diet-induced obesity and the development of diabetes. Deletion of Mkk6 increases T3-stimulated UCP1 expression in adipocytes, thereby increasing their thermogenic capacity. Mechanistically, we demonstrate that, in white adipose tissue, p38 is activated by an alternative pathway involving AMPK, TAK, and TAB. Our results identify MKK6 in adipocytes as a potential therapeutic target to reduce obesity.Brown and beige adipose tissues dissipate heat via uncoupling protein 1 (UCP1). Here the authors show that the stress activated kinase MKK6 acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure.

Distinct subcellular patterns of neprilysin protein and activity in the brains of Alzheimer’s disease patients, transgenic mice and cultured human neuronal cells

PubMed Central

Zhou, Li; Wei, Chunsheng; Huang, Wei; Bennett, David A; Dickson, Dennis W; Wang, Rui; Wang, Dengshun

2013-01-01

We investigated the subcellular distribution of NEP protein and activity in brains of human individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI) and AD dementia, as well as double transgenic mice and human neuronal cell line treated with Aβ and 4-hydroxy-2-nonenal (HNE). Total cortical neuronal-related NEP was significantly increased in MCI compared to NCI brains. NeuN was decreased in both MCI and AD, consistent with neuronal loss occurring in MCI and AD. Negative relationship between NEP protein and NeuN in MCI brains, and positive correlation between NEP and pan-cadherin in NCI and MCI brains, suggesting the increased NEP expression in NCI and MCI might be due to membrane associated NEP in non-neuronal cells. In subcellular extracts, NEP protein decreased in cytoplasmic fractions in MCI and AD, but increased in membrane fractions, with a significant increase in the membrane/cytoplasmic ratio of NEP protein in AD brains. By contrast, NEP activity was decreased in AD. Similar results were observed in AD-mimic transgenic mice. Studies of SH-SY5Y neuroblastoma showed an up-regulation of NEP protein in the cytoplasmic compartment induced by HNE and Aβ; however, NEP activity decreased in cytoplasmic fractions. Activity of NEP in membrane fractions increased at 48 hours and then significantly decreased after treatment with HNE and Aβ. The cytoplasmic/membrane ratio of NEP protein increased at 24 hours and then decreased in both HNE and Aβ treated cells. Both HNE and Aβ up-regulate NEP expression, but NEP enzyme activity did not show the same increase, possibly indicating immature cytoplasmic NEP is less active than membrane associated NEP. These observations indicate that modulation of NEP protein levels and its subcellular location influence the net proteolytic activity and this complex association might participate in deficiency of Aβ degradation that is associated with amyloid deposition in AD. PMID:24093058

Metal (Fe, Co, Ni) supported on different aluminas as Fischer-Tropsch catalyst

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

Dahlan; Marsih, I. Nyoman, E-mail: nyoman@chem.itb.ac.id; Ismunandar

2015-09-30

This research aimed to compare the physico-chemical properties of the same metal M (M = iron, cobalt, nickel) supported on aluminas with different morphology and pore size as Fischer-Tropsch catalyst. The aluminas applied as support were alumina synthesized through hydrothermal process, alumina formed by pretreatment of catapal and commercial alumina which named as Ahy, Aca, and Aco respectively. Ahy has uniform morphology of nanotubes while Aca and Aco showed non-uniform morphology of particle lumps. The particle lumps of Aca were larger than those of Aco. Ahy, Aca, and Aco respectively has average pore diameter of 2.75, 2.86 and 2.9 nm. Metalsmore » were deposited on the supports by incipient-wetness impregnation method. The catalysts were characterized by XRD, H{sub 2}-TPR, and H{sub 2} chemisorption. Catalyst acitivity test for Fischer-Tropsch reaction was carried out in a micro reactor at 200 °C and 1 atm, and molar ratio of H{sub 2}/CO = 2:1. The metal oxide particle size increased in the order M/Aco < M/Aca < M/Ahy. The catalysts reducibility also increased according to the order M/Aco < M/Aca < M/Ahy suggesting that the larger metal oxide particles are more reducible. The number of active site was not proportional to the reducibility because during the reduction, larger metal oxide particles were converted into larger metal particles. On the other hand, the number of active sites was inversely proportional to the particle sizes. The number of active site increased in the order M/Ahy < M/Aco < M/Aca. The catalytic activity also increased in the following order M/Ahy < M/Aco < M/Aca. The activity per active site increased according to the order M/Aca < M/Aco < M/Ahy meaning that for M/Ahy, a little increase in active site will lead to a significance increase in catalytic activity. It showed that Ahy has potential for the better support.« less

Reactive oxygen species in the tumor niche triggers altered activation of macrophages and immunosuppression: Role of fluoxetine.

PubMed

Ghosh, Sayan; Mukherjee, Sudeshna; Choudhury, Sreetama; Gupta, Payal; Adhikary, Arghya; Baral, Rathindranath; Chattopadhyay, Sreya

2015-07-01

Macrophages are projected as one of the key players responsible for the progression of cancer. Classically activated (M1) macrophages are pro-inflammatory and have a central role in host defense, while alternatively activated (M2) macrophages are associated with immunosuppression. Macrophages residing at the site of neoplastic growth are alternately activated and are referred to as tumor-associated macrophages (TAMs). These "cooperate" with tumor tissue, promoting increased proliferation and immune escape. Selective serotonin reuptake inhibitors like fluoxetine have recently been reported to possess anti-inflammatory activity. We used fluoxetine to target tumor-associated inflammation and consequent alternate polarization of macrophages. We established that murine peritoneal macrophages progressed towards an altered activation state when exposed to cell-free tumor fluid, as evidenced by increased IL-6, IL-4 and IL-10 levels. These polarized macrophages showed significant pro-oxidant bias and increased p65 nuclear localization. It was further observed that these altered macrophages could induce oxidative insult and apoptosis in cultured mouse CD3(+) T cells. To validate these findings, we replicated key experiments in vivo, and observed that there was increased serum IL-6, IL-4 and IL-10 in tumor-bearing animals, with increased % CD206(+) cells within the tumor niche. TAMs showed increased nuclear localization of p65 with decreased Nrf2 expression in the nucleus. These results were associated with increase in apoptosis of CD3(+) T cells co-cultured with TAM-spent media. We could establish that fluoxetine treatment could specifically re-educate the macrophages both in vitro and in vivo by skewing their phenotype such that immune suppression mediated by tumor-dictated macrophages was successfully mitigated. Copyright © 2015 Elsevier Inc. All rights reserved.

Switching catalysis from hydrolysis to perhydrolysis in P. fluorescens esterase

PubMed Central

Yin, De Lu (Tyler); Bernhardt, Peter; Morley, Krista L.; Jiang, Yun; Cheeseman, Jeremy D.; Purpero, Vincent; Schrag, Joseph D.; Kazlauskas, Romas J.

2010-01-01

Many serine hydrolases catalyze perhydrolysis – the reversible formation of per-acids from carboxylic acids and hydrogen peroxide. Recently we showed that a single amino acid substitution in the alcohol binding pocket - L29P - in Pseudomonas fluorescens (SIK WI) aryl esterase (PFE) increased the specificity constant of PFE for peracetic acid formation >100-fold [Bernhardt et al. Angew. Chem. Intl. Ed. 2005, 44, 2742]. In this paper, we extend this work to address the three following questions. First, what is the molecular basis of the increase in perhydrolysis activity? We previously proposed that the L29P substitution creates a hydrogen bond between the enzyme and hydrogen peroxide in the transition state. Here we report two x-ray structures of L29P PFE that support this proposal. Both structures show a main chain carbonyl oxygen closer to the active-site serine as expected. One structure further shows acetate in the active site in an orientation consistent with reaction by an acyl-enzyme mechanism. We also detected an acyl-enzyme intermediate in the hydrolysis of ε-caprolactone by mass spectrometry. Second, can we further increase perhydrolysis activity? We discovered that the reverse reaction – hydrolysis of peracetic acid to acetic acid and hydrogen peroxide – occurs at nearly the diffusion limited rate. Since the reverse reaction cannot increase further, neither can the forward reaction. Consistent with this prediction, two variants with additional amino acid substitutions showed two fold higher kcat, but Km also increased so the specificity constant, kcat/Km, remained similar. Third, how does the L29P substitution change the esterase activity? Ester hydrolysis decreased for most esters (75-fold for ethyl acetate), but not for methyl esters. In contrast, L29P PFE catalyzed hydrolysis of ε-caprolactone five times more efficiently than wild-type PFE. Molecular modeling suggests that moving the carbonyl group closer to the active site blocks access for larger alcohol moieties, but binds ε-caprolactone more tightly. These results are consistent with the natural function of perhydrolases being either hydrolysis of peroxycarboxylic acids or hydrolysis of lactones. PMID:20112920

Mediation of Short and Longer Term Effects of an Intervention Program to Enhance Resilience in Immigrants from Mainland China to Hong Kong

PubMed Central

Yu, Nancy X.; Lam, T. H.; Liu, Iris K. F.; Stewart, Sunita M.

2015-01-01

Few clinical trials report on the active intervention components that result in outcome changes, although this is relevant to further improving efficacy and adapting effective programs to other populations. This paper presents follow-up analyses of a randomized controlled trial to enhance adaptation by increasing knowledge and personal resilience in two separate brief interventions with immigrants from Mainland China to Hong Kong (Yu et al., 2014b). The present paper extends our previous one by reporting on the longer term effect of the interventions on personal resilience, and examining whether the Resilience intervention worked as designed to enhance personal resilience. The four-session intervention targeted at self-efficacy, positive thinking, altruism, and goal setting. In this randomized controlled trial, 220 immigrants were randomly allocated to three arms: Resilience, Information (an active control arm), and Control arms. Participants completed measures of the four active components (self-efficacy, positive thinking, altruism, and goal setting) at baseline and immediately after the intervention. Personal resilience was assessed at baseline, post-intervention, and 3- and 6-month follow-ups. The results showed that the Resilience arm had greater increases in the four active components post-intervention. Changes in each of the four active components at the post-intervention assessment mediated enhanced personal resilience at the 3-month follow-up in the Resilience arm. Changes in self-efficacy and goal setting showed the largest effect size, and altruism showed the smallest. The arm effects of the Resilience intervention on enhanced personal resilience at the 6-month follow-up were mediated by increases of personal resilience post-intervention (Resilience vs. Control) and at the 3-month follow-up (Resilience vs. Information). These findings showed that these four active components were all mediators in this Resilience intervention. Our results of the effects of short term increases in personal resilience on longer term increase in personal resilience in some models suggest how changes in intervention outcomes might persist over time. PMID:26640446

Tuning the Brake While Raising the Stake: Network Dynamics during Sequential Decision-Making.

PubMed

Meder, David; Haagensen, Brian Numelin; Hulme, Oliver; Morville, Tobias; Gelskov, Sofie; Herz, Damian Marc; Diomsina, Beata; Christensen, Mark Schram; Madsen, Kristoffer Hougaard; Siebner, Hartwig Roman

2016-05-11

When gathering valued goods, risk and reward are often coupled and escalate over time, for instance, during foraging, trading, or gambling. This escalating frame requires agents to continuously balance expectations of reward against those of risk. To address how the human brain dynamically computes these tradeoffs, we performed whole-brain fMRI while healthy young individuals engaged in a sequential gambling task. Participants were repeatedly confronted with the option to continue with throwing a die to accumulate monetary reward under escalating risk, or the alternative option to stop to bank the current balance. Within each gambling round, the accumulation of gains gradually increased reaction times for "continue" choices, indicating growing uncertainty in the decision to continue. Neural activity evoked by "continue" choices was associated with growing activity and connectivity of a cortico-subcortical "braking" network that positively scaled with the accumulated gains, including pre-supplementary motor area (pre-SMA), inferior frontal gyrus, caudate, and subthalamic nucleus (STN). The influence of the STN on continue-evoked activity in the pre-SMA was predicted by interindividual differences in risk-aversion attitudes expressed during the gambling task. Furthermore, activity in dorsal anterior cingulate cortex (ACC) reflected individual choice tendencies by showing increased activation when subjects made nondefault "continue" choices despite an increasing tendency to stop, but ACC activity did not change in proportion with subjective choice uncertainty. Together, the results implicate a key role of dorsal ACC, pre-SMA, inferior frontal gyrus, and STN in computing the trade-off between escalating reward and risk in sequential decision-making. Using a paradigm where subjects experienced increasing potential rewards coupled with increasing risk, this study addressed two unresolved questions in the field of decision-making: First, we investigated an "inhibitory" network of regions that has so far been investigated with externally cued action inhibition. In this study, we show that the dynamics in this network under increasingly risky decisions are predictive of subjects' risk attitudes. Second, we contribute to a currently ongoing debate about the anterior cingulate cortex's role in sequential foraging decisions by showing that its activity is related to making nondefault choices rather than to choice uncertainty. Copyright © 2016 Meder, Haagensen, et al.

Stabilization of α-amylase by using anionic surfactant during the immobilization process

NASA Astrophysics Data System (ADS)

El-Batal, A. I.; Atia, K. S.; Eid, M.

2005-10-01

This work describes the entrapment of α-amylase into butylacrylate-acrylic acid copolymer (BuA/AAc) using γ irradiation. The effect of an anionic surfactant (AOT), the reuse efficiency, and kinetic behavior of immobilized α-amylase were studied. Covering of α-amylase with bis-(2-ethylhexyl)sulfosuccinate sodium salt (AOT) made the enzyme more stable than the uncovered form. The hydrolytic activity of the pre-coated immobilized α-amylase was increased below the critical micelle concentration (cmc) (10 mmol/L). The results showed an increase in the relative activity with increase in the degree of hydration. The pre-coated immobilized α-amylase showed a higher k/K and lower activation energy compared to the free and uncoated-immobilized preparation, respectively. The results suggest that the immobilization of α-amylase is a potentially useful approach for commercial starch hydrolysis in two-phase systems.

Increased resting-state brain entropy in Alzheimer's disease.

PubMed

Xue, Shao-Wei; Guo, Yonghu

2018-03-07

Entropy analysis of resting-state functional MRI (R-fMRI) is a novel approach to characterize brain temporal dynamics and facilitates the identification of abnormal brain activity caused by several disease conditions. However, Alzheimer's disease (AD)-related brain entropy mapping based on R-fMRI has not been assessed. Here, we measured the sample entropy and voxel-wise connectivity of the network degree centrality (DC) of the intrinsic brain activity acquired by R-fMRI in 26 patients with AD and 26 healthy controls. Compared with the controls, AD patients showed increased entropy in the middle temporal gyrus and the precentral gyrus and also showed decreased DC in the precuneus. Moreover, the magnitude of the negative correlation between local brain activity (entropy) and network connectivity (DC) was increased in AD patients in comparison with healthy controls. These findings provide new evidence on AD-related brain entropy alterations.

Animal-Assisted Intervention and Dementia: A Systematic Review.

PubMed

Yakimicki, Michelle L; Edwards, Nancy E; Richards, Elizabeth; Beck, Alan M

2018-02-01

This review discusses the relationship between animal-assisted interventions (AAI) and behavioral and psychological symptoms of dementia (BPSD). A systematic search was conducted within CINAHL, Web of Science CAB Abstracts, PubMed, Abstracts in Social Gerontology, Google Scholar, and PsycINFO for primary research articles. A total of 32 studies were included in the final review. Variation was noted in study designs and in study setting. Twenty-seven of 32 studies used dogs as the intervention. Agitation/aggression showed a significant decrease in nine of 15 studies. Eleven of 12 studies demonstrated increased social interaction with AAI. Mood had mixed results in nine studies. Quality of life was increased in three of four studies. Resident activity and nutritional intake were each increased in two studies. Animal assisted activities/interventions showed a strong positive effect on social behaviors, physical activity, and dietary intake in dementia patients and a positive effect on agitation/aggression and quality of life.

Influence of botulinum toxin on rabbit jaw muscle activity and anatomy.

PubMed

Korfage, J A M; Wang, Jeffrey; Lie, S H J T J; Langenbach, Geerling E J

2012-05-01

Muscles can adapt their fiber properties to accommodate to new conditions. We investigated the extent to which a decrease in muscle activation can cause an adaptation of fiber properties in synergistic and antagonistic jaw muscles. Three months after the injection of botulinum toxin type A in one masseter (anterior or posterior) muscle changes in fiber type composition and fiber cross-sectional areas in jaw muscles were studied at the microscopic level. The injected masseter showed a steep increase in myosin type IIX fibers, whereas fast fibers decreased by about 50% in size. Depending on the injection site, both synergistic and antagonistic muscles showed a significant increase in the size of their fast IIA fibers, sometimes combined with an increased number of IIX fibers. Silencing the activity in the masseter not only causes changes in the fibers of the injected muscle but also leads to changes in other jaw muscles. Copyright © 2012 Wiley Periodicals, Inc.

Kinetics of photo-activated charge carriers in Sn:CdS

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

Patidar, Manju Mishra, E-mail: manjumishra.iuc@gmail.com; Gorli, V. R.; Gangrade, Mohan

2016-05-23

Kinetics of the photo-activated charge carriers has been investigated in Tin substituted Cadmium Sulphide, Cd{sub 1-x}Sn{sub x}S (x=0, 0.05, 0.10 and 0.15), thin films prepared by spray pyrolysis. X-Ray Diffraction shows an increase in strain that resulted in the decreased crystallite size upon Sn substitution. At the first sight, the photo current characteristics show a quenching effect on Sn substitution. However, survival of persistent photocurrents is seen even up to 15% of Sn substitution. Transient photo current decay could be explained with a 2τ relaxation model. CdS normally has an n-type character and the Sn doping expected to inject holemore » carriers. The two fold increase in τ{sub 1}, increase in activation energy and the decrease in photocurrents upon Sn substitution point towards a band gap cleaning scenario that include compensation and associated carrier injection dynamics. In addition Atomic Force Microscopy shows a drastic change in microstructure that modulates the carrier dynamics as a whole.« less

Active transportation measurement and benchmarking development : New Orleans state of active transportation report 2010.

DOT National Transportation Integrated Search

2012-01-01

Over the last decade, there has been a surge in bicycle and pedestrian use in communities that have invested in active transportation infrastruc-ture and programming. While these increases show potentially promising trends, many of the cities that ha...

Noise-induced effects on multicellular biopacemaker spontaneous activity: Differences between weak and strong pacemaker cells

NASA Astrophysics Data System (ADS)

Aghighi, Alireza; Comtois, Philippe

2017-09-01

Self-organization of spontaneous activity of a network of active elements is important to the general theory of reaction-diffusion systems as well as for pacemaking activity to initiate beating of the heart. Monolayer cultures of neonatal rat ventricular myocytes, consisting of resting and pacemaker cells, exhibit spontaneous activation of their electrical activity. Similarly, one proposed approach to the development of biopacemakers as an alternative to electronic pacemakers for cardiac therapy is based on heterogeneous cardiac cells with resting and spontaneously beating phenotypes. However, the combined effect of pacemaker characteristics, density, and spatial distribution of the pacemaker cells on spontaneous activity is unknown. Using a simple stochastic pattern formation algorithm, we previously showed a clear nonlinear dependency of spontaneous activity (occurrence and amplitude of spontaneous period) on the spatial patterns of pacemaker cells. In this study, we show that this behavior is dependent on the pacemaker cell characteristics, with weaker pacemaker cells requiring higher density and larger clusters to sustain multicellular activity. These multicellular structures also demonstrated an increased sensitivity to voltage noise that favored spontaneous activity at lower density while increasing temporal variation in the period of activity. This information will help researchers overcome the current limitations of biopacemakers.

Gender and neural substrates subserving implicit processing of death-related linguistic cues.

PubMed

Qin, Jungang; Shi, Zhenhao; Ma, Yina; Han, Shihui

2018-02-01

Our recent functional magnetic resonance imaging study revealed decreased activities in the anterior cingulate cortex (ACC) and bilateral insula for women during the implicit processing of death-related linguistic cues. Current work tested whether aforementioned activities are common for women and men and explored potential gender differences. We scanned twenty males while they performed a color-naming task on death-related, negative-valence, and neutral-valence words. Whole-brain analysis showed increased left frontal activity and decreased activities in the ACC and bilateral insula to death-related versus negative-valence words for both men and women. However, relative to women, men showed greater increased activity in the left middle frontal cortex and decreased activity in the right cerebellum to death-related versus negative-valence words. The results suggest, while implicit processing of death-related words is characterized with weakened sense of oneself for both women and men, men may recruit stronger cognitive regulation of emotion than women.

Irradiation effects on hydrases for biomedical applications

NASA Astrophysics Data System (ADS)

Furuta, Masakazu; Ohashi, Isao; Oka, Masahito; Hayashi, Toshio

2000-03-01

To apply an irradiation technique to sterilize "Hybrid" biomedical materials including enzymes, we selected papain, a well-characterized plant endopeptidase as a model to examine durability of enzyme activity under the practical irradiation condition in which limited data were available for irradiation inactivation of enzymes. Dry powder and frozen aqueous solution of papain showed significant durability against 60Co-gamma irradiation suggesting that, the commercial irradiation sterilizing method is applicable without modification. Although irradiation of unfrozen aqueous papain solution showed an unusual change of the enzymatic activity with the increasing doses, and was totally inactivated at 15 kGy, we managed to keep the residual activity more than 50% of initial activity after 30-kGy irradiation, taking such optimum conditions as increasing enzyme concentration from 10 to 100 mg/ml and purging with N 2 gas to suppress the formation of free radicals.

Rodent model of activity-based anorexia.

PubMed

Carrera, Olaia; Fraga, Ángela; Pellón, Ricardo; Gutiérrez, Emilio

2014-04-10

Activity-based anorexia (ABA) consists of a procedure that involves the simultaneous exposure of animals to a restricted feeding schedule, while free access is allowed to an activity wheel. Under these conditions, animals show a progressive increase in wheel running, a reduced efficiency in food intake to compensate for their increased activity, and a severe progression of weight loss. Due to the parallelism with the clinical manifestations of anorexia nervosa including increased activity, reduced food intake and severe weight loss, the ABA procedure has been proposed as the best analog of human anorexia nervosa (AN). Thus, ABA research could both allow a better understanding of the mechanisms underlying AN and generate useful leads for treatment development in AN. Copyright © 2014 John Wiley & Sons, Inc.

Physical activity, social network type, and depressive symptoms in late life: an analysis of data from the National Social Life, Health and Aging Project.

PubMed

Litwin, Howard

2012-01-01

To clarify whether physical activity among older Americans is associated with depressive symptoms, beyond the effects of social network type, physical health, and sociodemographic characteristics. The analysis used data from a sub-sample, aged 65–85, from the National Social Life, Health and Aging Project (N=1349). Hierarchical regressions examined the respective effects of selected network types and extent of engagement in physical activity on depressive symptoms, controlling for physical health and sociodemographic background. The findings showed that physical activity was correlated inversely with late life depressive symptoms. However, when interaction terms for the selected social network types and the extent of physical activity were also considered, the main effect of social network on depressive symptoms increased, while that of physical activity was eliminated. The results show that older American adults embedded in family network types are at risk of limited physical activity. However, interventions aimed to increase their engagement in physical activity might help to reduce depressive symptoms within this group.

Chronic innate immune activation of TBK1 suppresses mTORC1 activity and dysregulates cellular metabolism.

PubMed

Hasan, Maroof; Gonugunta, Vijay K; Dobbs, Nicole; Ali, Aktar; Palchik, Guillermo; Calvaruso, Maria A; DeBerardinis, Ralph J; Yan, Nan

2017-01-24

Three-prime repair exonuclease 1 knockout (Trex1 -/- ) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1 -/- mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism. We also genetically separated the inflammatory and metabolic phenotypes by showing that Sting deficiency rescued both inflammatory and metabolic phenotypes, whereas Irf3 deficiency only rescued inflammation on the Trex1 -/- background, and many metabolic defects persist in Trex1 -/- Irf3 -/- cells and mice. We also showed that Leptin deficiency (ob/ob) increased lipogenesis and prolonged survival of Trex1 -/- mice without dampening inflammation. Mechanistically, we identified TBK1 as a key regulator of mTORC1 activity in Trex1 -/- cells. Together, our data demonstrate that chronic innate immune activation of TBK1 suppresses mTORC1 activity, leading to dysregulated cellular metabolism.

Antioxidant Activity of Royal Jelly Hydrolysates Obtained by Enzymatic Treatment.

PubMed

Gu, Hyejung; Song, In-Bong; Han, Hye-Ju; Lee, Na-Young; Cha, Ji-Yun; Son, Yeon-Kyong; Kwon, Jungkee

2018-02-01

Recently, research on the processing of raw functional materials with the aim of improving various physiological activities has been conducted. In this study, we investigated the antioxidant activity of royal jelly (RJ) hydrolysates obtained from three commercial proteases. Enzyme-treated royal jelly (ERJ), in which the RJ hydrolysates were converted into easy-to-absorb shorter chain monomers through the removal of two known allergen proteins, showed no difference in the content of ( E )-10-hydroxydec-2-enoicacid (10-HDA) or the freshness parameter and showed a significant increase in total free amino acid content. The antioxidant activity of ERJ was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and chemical assays. The ERJ showed about 80% DPPH-radical scavenging activity at same concentration of ascorbic acid. The antioxidant effect of ERJ was confirmed to be due to reduction of intracellular reactive oxidative species (ROS) and nitric oxide (NO) production in LPS-treated macrophages. Moreover, ERJ significantly increased the activity of the antioxidant enzyme superoxide dismutase (SOD) and the level of the antioxidant glutathione (GSH) in a dose-dependent manner. Interestingly, these antioxidant activities of ERJ were stronger than those of non-treated RJ. These findings indicate that ERJ has high potential as an antioxidant agent for use in human and animal diets.

Effects of cue focality on the neural mechanisms of prospective memory: A meta-analysis of neuroimaging studies.

PubMed

Cona, Giorgia; Bisiacchi, Patrizia Silvia; Sartori, Giuseppe; Scarpazza, Cristina

2016-05-17

Remembering to execute pre-defined intentions at the appropriate time in the future is typically referred to as Prospective Memory (PM). Studies of PM showed that distinct cognitive processes underlie the execution of delayed intentions depending on whether the cue associated with such intentions is focal to ongoing activity processing or not (i.e., cue focality). The present activation likelihood estimation (ALE) meta-analysis revealed several differences in brain activity as a function of focality of the PM cue. The retrieval of intention is supported mainly by left anterior prefrontal cortex (Brodmann Area, BA 10) in nonfocal tasks, and by cerebellum and ventral parietal regions in focal tasks. Furthermore, the precuneus showed increased activation during the maintenance phase of intentions compared to the retrieval phase in nonfocal tasks, whereas the inferior parietal lobule showed increased activation during the retrieval of intention compared to maintenance phase in the focal tasks. Finally, the retrieval of intention relies more on the activity in anterior cingulate cortex for nonfocal tasks, and on posterior cingulate cortex for focal tasks. Such focality-related pattern of activations suggests that prospective remembering is mediated mainly by top-down and stimulus-independent processes in nonfocal tasks, whereas by more automatic, bottom-up, processes in focal tasks.

Potent Antiproliferative Effect on Liver Cancer of Medicinal Plants Selected from the Thai/Lanna Medicinal Plant Recipe Database “MANOSROI III”

PubMed Central

Manosroi, Aranya; Akazawa, Hiroyuki; Kitdamrongtham, Worapong; Akihisa, Toshihiro; Manosroi, Worapaka; Manosroi, Jiradej

2015-01-01

Thai/Lanna medicinal plant recipes have been used for the treatment of several diseases including liver cancer. In this study, methanolic extracts (MEs) of 23 plants were tested for antiproliferative activity on human hepatoma cell line (Hep G2) by the sulforhodamine B (SRB) assay. Nine MEs with potent antiproliferative activity (IC50 < 100 µg/mL) were obtained and further semipurified by liquid/liquid partition extraction. The semipurified fractions were tested for the antiproliferative and antioxidative activities. ME of Stemona collinsae and the semipurified extract and methanol-water fraction (MF) of Gloriosa superba gave the highest antiproliferative activity on HepG2 which were 4.79- and 50.07-fold cisplatin, respectively. The semipurified fractions showed an increased antiproliferative activity. MF of Caesalpinia sappan and HF of Senna alata showed the highest free radical scavenging and metal chelating activities, respectively. The compound in n-hexane fraction (HF) of Ventilago denticulata which showed an increase in antiproliferative activity comparing to its ME was isolated and identified as emodin. This study has demonstrated the potential of the ME from S. collinsae, MF from G. superba, and emodin isolated from V. denticulata, for further development as an antiliver cancer agent. PMID:26136809

Effects of cue focality on the neural mechanisms of prospective memory: A meta-analysis of neuroimaging studies

PubMed Central

Cona, Giorgia; Bisiacchi, Patrizia Silvia; Sartori, Giuseppe; Scarpazza, Cristina

2016-01-01

Remembering to execute pre-defined intentions at the appropriate time in the future is typically referred to as Prospective Memory (PM). Studies of PM showed that distinct cognitive processes underlie the execution of delayed intentions depending on whether the cue associated with such intentions is focal to ongoing activity processing or not (i.e., cue focality). The present activation likelihood estimation (ALE) meta-analysis revealed several differences in brain activity as a function of focality of the PM cue. The retrieval of intention is supported mainly by left anterior prefrontal cortex (Brodmann Area, BA 10) in nonfocal tasks, and by cerebellum and ventral parietal regions in focal tasks. Furthermore, the precuneus showed increased activation during the maintenance phase of intentions compared to the retrieval phase in nonfocal tasks, whereas the inferior parietal lobule showed increased activation during the retrieval of intention compared to maintenance phase in the focal tasks. Finally, the retrieval of intention relies more on the activity in anterior cingulate cortex for nonfocal tasks, and on posterior cingulate cortex for focal tasks. Such focality-related pattern of activations suggests that prospective remembering is mediated mainly by top-down and stimulus-independent processes in nonfocal tasks, whereas by more automatic, bottom-up, processes in focal tasks. PMID:27185531

Partial alanine scan of mast cell degranulating peptide (MCD): importance of the histidine- and arginine residues.

PubMed

Buku, Angeliki; Mendlowitz, Milton; Condie, Barry A; Price, Joseph A

2004-06-01

The influence of the two histidine and two arginine residues of mast cell degranulating peptide (MCD) in activity and binding was studied by replacing these amino acids in the MCD sequence with L-alanine. Their histamine releasing activity was determined on rat peritoneal mast cells. Their binding affinity to the FcepsilonRIalpha binding subunit of the human mast cell receptor protein, was carried out using fluorescence polarization. The histamine assay showed that replacement of His13 by Ala o ccurred without loss of activity compared with the activity of MCD. Alanine substitutions for Arg7 and His8 resulted in an approximately 40 fold increase, and for Arg16 in a 14-fold increase in histamine-releasing activity of MCD. The binding affinities of the analogs were tested by competitive displacement of bound fluorescent MCD peptide from the FcepsilonRIalpha binding protein of the mast cell receptor by the Ala analogs using fluorescence polarization. The analogs Ala8 (for His) and Ala16 (for Arg) showed the same binding affinities as MCD, whereas analog Ala7 (for Arg) and analog Ala13 (for His) showed slightly better binding affinity than the parent compound. This study showed that the introduction of alanine residues in these positions resulted in MCD agonists of diverse potency. These findings will be useful in further MCD structure-activity studies.

Neural activity related to cognitive and emotional empathy in post-traumatic stress disorder.

PubMed

Mazza, Monica; Tempesta, Daniela; Pino, Maria Chiara; Nigri, Anna; Catalucci, Alessia; Guadagni, Veronica; Gallucci, Massimo; Iaria, Giuseppe; Ferrara, Michele

2015-04-01

The aim of this study is to evaluate the empathic ability and its functional brain correlates in post-traumatic stress disorder subjects (PTSD). Seven PTSD subjects and ten healthy controls, all present in the L'Aquila area during the earthquake of the April 2009, underwent fMRI during which they performed a modified version of the Multifaceted Empathy Test. PTSD patients showed impairments in implicit and explicit emotional empathy, but not in cognitive empathy. Brain responses during cognitive empathy showed an increased activation in patients compared to controls in the right medial frontal gyrus and the left inferior frontal gyrus. During implicit emotional empathy responses patients with PTSD, compared to controls, exhibited greater neural activity in the left pallidum and right insula; instead the control group showed an increased activation in right inferior frontal gyrus. Finally, in the explicit emotional empathy responses the PTSD group showed a reduced neural activity in the left insula and the left inferior frontal gyrus. The behavioral deficit limited to the emotional empathy dimension, accompanied by different patterns of activation in empathy related brain structures, represent a first piece of evidence of a dissociation between emotional and cognitive empathy in PTSD patients. The present findings support the idea that empathy is a multidimensional process, with different facets depending on distinct anatomical substrates. Copyright © 2014 Elsevier B.V. All rights reserved.

Morphology-controlled electrodeposition of Cu{sub 2}O microcrystalline particle films for application in photocatalysis under sunlight

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

Wu, Guodong; Zhai, Wei; Sun, Fengqiang, E-mail: fqsun@scnu.edu.cn

2012-12-15

Graphical abstract: Display Omitted Highlights: ► PEG was used to electro-deposit Cu{sub 2}O microcrystalline particle films. ► Morphologies of Cu{sub 2}O microcrystals could be controlled by the amount of PEG. ► The films showed regularly varied photocatalytic activities under sunlight. ► The films could be recycled and showed stable activities. -- Abstract: Morphology-controlled Cu{sub 2}O microcrystalline particle films had been successfully electrodeposited on tin-doped indium oxide glass substrates in CuSO{sub 4} solutions containing different amounts of polyethylene glycol (PEG) additives. With an increase of PEG, microcrystals gradually changed from irregular shapes to cubes, octahedrons, and spherical shapes. Sizes increasingly becamemore » smaller with an increase of PEG under the same deposition time. These films had been first used as recyclable photocatalysts and showed excellent and photocatalytic activities in photodegradation of methylene blue (MB) under sunlight. Activities were regularly varied relative to the morphologies of films controlled by the amount of PEG and could be further enhanced by adding a little amount of hydrogen peroxide in the MB solution. The method for controllable preparation of Cu{sub 2}O microcrystals with photocatalytic activities was simple and inexpensive. The as-prepared particle films could also be used in photodegradation of many other pollutants under sunlight.« less

NDVI-Based analysis on the influence of human activities on vegetation variation on Hainan Island

NASA Astrophysics Data System (ADS)

Luo, Hongxia; Dai, Shengpei; Xie, Zhenghui; Fang, Jihua

2018-02-01

Using the Moderate Resolution Imaging Spectroradiometer-normalized difference vegetation index (NDVI) dataset, we analyzed the predicted NDVI values variation and the influence of human activities on vegetation on Hainan Island during 2001-2015. We investigated the roles of human activities in vegetation variation, particularly from 2002 when implemented the Grain-for-Greenprogram on Hainan Island. The trend analysis, linear regression model and residual analysis were used to analyze the data. The results of the study showed that (1) The predicted vegetation on Hainan Island showed an general upward trend with a linear growth rate of 0.0025/10y (p<0.05) over the past 15 years. The areas where vegetation increasedaccounted for 52.28%, while the areas where vegetation decreased accounted for 47.72%. (2) The residual NDVI values across the region significantly increased, with a growth rate of 0.023/10y.The vegetation increased across 35.95% of Hainan Island, while it decreased in 20.2% of the area as a result of human activities. (3) In general, human activities had played a positive role in the vegetation increase on Hainan Island, and the residual NDVI trend of this region showed positive outcomes for vegetation variation after implementing ecological engineering projects. However, it indicated a growing risk of vegetation degradation in the coastal region of Hainan Island as a result of rapid urbanization, land reclamation.

Activity Induces Fmr1-Sensitive Synaptic Capture of Anterograde Circulating Neuropeptide Vesicles.

PubMed

Cavolo, Samantha L; Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

2016-11-16

Synaptic neuropeptide and neurotrophin stores are maintained by constitutive bidirectional capture of dense-core vesicles (DCVs) as they circulate in and out of the nerve terminal. Activity increases DCV capture to rapidly replenish synaptic neuropeptide stores following release. However, it is not known whether this is due to enhanced bidirectional capture. Here experiments at the Drosophila neuromuscular junction, where DCVs contain neuropeptides and a bone morphogenic protein, show that activity-dependent replenishment of synaptic neuropeptides following release is evident after inhibiting the retrograde transport with the dynactin disruptor mycalolide B or photobleaching DCVs entering a synaptic bouton by retrograde transport. In contrast, photobleaching anterograde transport vesicles entering a bouton inhibits neuropeptide replenishment after activity. Furthermore, tracking of individual DCVs moving through boutons shows that activity selectively increases capture of DCVs undergoing anterograde transport. Finally, upregulating fragile X mental retardation 1 protein (Fmr1, also called FMRP) acts independently of futsch/MAP-1B to abolish activity-dependent, but not constitutive, capture. Fmr1 also reduces presynaptic neuropeptide stores without affecting activity-independent delivery and evoked release. Therefore, presynaptic motoneuron neuropeptide storage is increased by a vesicle capture mechanism that is distinguished from constitutive bidirectional capture by activity dependence, anterograde selectivity, and Fmr1 sensitivity. These results show that activity recruits a separate mechanism than used at rest to stimulate additional synaptic capture of DCVs for future release of neuropeptides and neurotrophins. Synaptic release of neuropeptides and neurotrophins depends on presynaptic accumulation of dense-core vesicles (DCVs). At rest, DCVs are captured bidirectionally as they circulate through Drosophila motoneuron terminals by anterograde and retrograde transport. Here we show that activity stimulates further synaptic capture that is distinguished from basal capture by its selectivity for anterograde DCVs and its inhibition by overexpression of the fragile X retardation protein Fmr1. Fmr1 dramatically lowers DCV numbers in synaptic boutons. Therefore, activity-dependent anterograde capture is a major determinant of presynaptic peptide stores. Copyright © 2016 the authors 0270-6474/16/3611781-07$15.00/0.

Older adults show higher increases in lower-limb muscle activity during whole-body vibration exercise.

PubMed

Lienhard, Karin; Vienneau, Jordyn; Nigg, Sandro; Friesenbichler, Bernd; Nigg, Benno M

2017-02-08

The purpose of this study was to compare lower limb muscle activity during whole-body vibration (WBV) exercise between a young and an older study population. Thirty young (25.9±4.3yrs) and thirty older (64.2±5.3yrs) individuals stood on a side-alternating WBV platform while surface electromyography (sEMG) was measured for the tibialis anterior (TA), gastrocnemius medialis (GM), soleus (SOL), vastus lateralis (VL), vastus medialis (VM), and biceps femoris (BF). The WBV protocol included nine vibration settings consisting of three frequencies (6, 11, 16Hz) x three amplitudes (0.9, 2.5, 4.0mm), and three control trials without vibration (narrow, medium, wide stance). The vertical platform acceleration (peak values of maximal displacement from equilibrium) was quantified during each vibration exercise using an accelerometer. The outcomes of this study showed that WBV significantly increased muscle activity in both groups for most vibration conditions in the TA (averaged absolute increase: young: +3.9%, older: +18.4%), GM (young: +4.1%, older: +9.5%), VL (young: +6.3%, older: +12.6%) and VM (young: +5.4%, older: +8.0%), and for the high frequency-amplitude combinations in the SOL (young: +7.5%, older: +12.6%) and BF (young: +1.9%, older: +7.5%). The increases in sEMG activity were significantly higher in the older than the young adults for all muscles, i.e., TA (absolute difference: 13.8%, P<0.001), GM (4.6%, P=0.034), VL (7.6%, P=0.001), VM (6.7%, P=0.042), BF (6.4%, P<0.001), except for the SOL (0.3%, P=0.248). Finally, the vertical platform acceleration was a significant predictor of the averaged lower limb muscle activity in the young (r=0.917, P<0.001) and older adults (r=0.931, P<0.001). In conclusion, the older population showed greater increases in lower limb muscle activity during WBV exercise than their young counterparts, meaning that they might benefit more from WBV exercises. Additionally, training intensity can be increased by increasing the vertical acceleration load. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thin and flexible active electrodes with shield for capacitive electrocardiogram measurement.

PubMed

Lee, Seung Min; Sim, Kyo Sik; Kim, Ko Keun; Lim, Yong Gyu; Park, Kwang Suk

2010-05-01

Capacitive electrocardiogram (ECG) measurement over clothing requires large electrodes that can remain in contact with curved body surfaces to increase the signal-to-noise ratio (SNR). In this article, we propose a new, thin, and flexible active electrode for use as a capacitive ECG measurement electrode. This electrode contains a shielding plate over its surface and it is extremely thin and can bend freely to cover larger body surfaces of the curve-shaped human torso. We evaluated the characteristics of flexible active electrodes under conditions of varying cloth thickness, electrode size, and contacting pressure. Electrodes of two sizes (45 and 12 cm(2)) were attached to a chest belt to measure the ECG from the human torso, and the results obtained for both the sizes were compared. Cloth thickness and electrode size showed a dominant effect on the SNR, whereas contacting pressure had almost no effect. The flexible active electrodes attached to chest belts wrapped closely and uniformly over the curved surface of the torso and SNR was increased with an increase in electrode size. Although the ECG signal became more distorted as the cloth thickness increased, the larger-sized flexible active electrode (45 cm(2)) showed less distortion than the smaller-sized one (12 cm(2)).

Frontal theta and beta synchronizations for monetary reward increase visual working memory capacity

PubMed Central

Yamaguchi, Yoko

2013-01-01

Visual working memory (VWM) capacity is affected by motivational influences; however, little is known about how reward-related brain activities facilitate the VWM systems. To investigate the dynamic relationship between VWM- and reward-related brain activities, we conducted time–frequency analyses using electroencephalograph (EEG) data obtained during a monetary-incentive delayed-response task that required participants to memorize the position of colored disks. In case of a correct answer, participants received a monetary reward (0, 10 or 50 Japanese yen) announced at the beginning of each trial. Behavioral results showed that VWM capacity under high-reward condition significantly increased compared with that under low- or no-reward condition. EEG results showed that frontal theta (6 Hz) amplitudes enhanced during delay periods and positively correlated with VWM capacity, indicating involvement of theta local synchronizations in VWM. Moreover, frontal beta activities (24 Hz) were identified as reward-related activities, because delay-period amplitudes correlated with increases in VWM capacity between high-reward and no-reward conditions. Interestingly, cross-frequency couplings between frontal theta and beta phases were observed only under high-reward conditions. These findings suggest that the functional dynamic linking between VWM-related theta and reward-related beta activities on the frontal regions plays an integral role in facilitating increases in VWM capacity. PMID:22349800

Frontal theta and beta synchronizations for monetary reward increase visual working memory capacity.

PubMed

Kawasaki, Masahiro; Yamaguchi, Yoko

2013-06-01

Visual working memory (VWM) capacity is affected by motivational influences; however, little is known about how reward-related brain activities facilitate the VWM systems. To investigate the dynamic relationship between VWM- and reward-related brain activities, we conducted time-frequency analyses using electroencephalograph (EEG) data obtained during a monetary-incentive delayed-response task that required participants to memorize the position of colored disks. In case of a correct answer, participants received a monetary reward (0, 10 or 50 Japanese yen) announced at the beginning of each trial. Behavioral results showed that VWM capacity under high-reward condition significantly increased compared with that under low- or no-reward condition. EEG results showed that frontal theta (6 Hz) amplitudes enhanced during delay periods and positively correlated with VWM capacity, indicating involvement of theta local synchronizations in VWM. Moreover, frontal beta activities (24 Hz) were identified as reward-related activities, because delay-period amplitudes correlated with increases in VWM capacity between high-reward and no-reward conditions. Interestingly, cross-frequency couplings between frontal theta and beta phases were observed only under high-reward conditions. These findings suggest that the functional dynamic linking between VWM-related theta and reward-related beta activities on the frontal regions plays an integral role in facilitating increases in VWM capacity.

Utilization of biochar and activated carbon to reduce Cd, Pb and Zn phytoavailability and phytotoxicity for plants.

PubMed

Břendová, Kateřina; Zemanová, Veronika; Pavlíková, Daniela; Tlustoš, Pavel

2016-10-01

In the present study, the content of risk elements and content of free amino acids were studied in spinach (Spinacia oleracea L.) and mustard (Sinapis alba L.) subsequently grown on uncontaminated and contaminated soils (5 mg Cd/kg, 1000 mg Pb/kg and 400 mg Zn/kg) with the addition of activated carbon (from coconut shells) or biochar (derived from local wood residues planted for phytoextaction) in different seasons (spring, summer and autumn). The results showed that activated carbon and biochar increased biomass production on contaminated site. Application of amendments decreased Cd and Zn uptake by spinach plants. Mustard significantly increased Pb accumulation in the biomass as well in subsequently grown autumn spinach. Glutamic acid and glutamine were major free amino acids in leaves of all plants (15-34% and 3-45%) from total content. Application of activated carbon and biochar increased content of glutamic acid in all plants on uncontaminated and contaminated soils. Activated carbon and biochar treatments also induced an increase of aspartic acid in spinach plants. Biochar produced from biomass originated from phytoextraction technologies promoted higher spinach biomass yield comparing unamended control and showed a tendency to reduce accumulation of cadmium and zinc and thus it is promising soil amendment. Copyright © 2016. Published by Elsevier Ltd.

Aqueous extracts of Lentinula edodes and Pleurotus sajor-caju exhibit high antioxidant capability and promising in vitro antitumor activity.

PubMed

Finimundy, T C; Gambato, G; Fontana, R; Camassola, M; Salvador, M; Moura, S; Hess, J; Henriques, J A P; Dillon, A J P; Roesch-Ely, M

2013-01-01

Mushroom extracts are increasingly sold as dietary supplements because of several of their properties, including the enhancement of immune function and antitumor activity. We hypothesized that soluble polar substances present in mushroom extracts may show antioxidant and anticancer properties. This report shows that Brazilian aqueous extracts of Lentinula edodes and Pleurotus sajor-caju exert inhibitory activity against the proliferation of the human tumor cell lines laryngeal carcinoma (Hep-2) and cervical adenocarcinoma (HeLa). Cell viability was determined after using 3 different temperatures (4°C, 22°C, and 50°C) for mushroom extraction. Biochemical assays carried out in parallel indicated higher amounts of polyphenols in the L edodes extracts at all extraction temperatures investigated. The scavenging ability of the 2,2-diphenyl-1-picrylhydrazyl radical showed higher activity for L edodes extracts. Superoxide dismutase-like activity showed no statistically significant difference among the groups for the 2 tested extracts, and catalase-like activity was increased with the L edodes extracts at 4°C. The results for the cytotoxic activity from P sajor-caju extracts at 22°C revealed the half maximal inhibitory concentration values of 0.64% ± 0.02% for Hep-2 and 0.25% ± 0.02% for HeLa. A higher cytotoxic activity was found for the L edodes extract at 22°C, with half maximal inhibitory concentration values of 0.78% ± 0.02% for Hep-2 and 0.57% ± 0.01% for HeLa. Substantial morphological modifications in cells were confirmed by Giemsa staining after treatment with either extract, suggesting inhibition of proliferation and induction of apoptosis with increasing extract concentrations. These results indicate that the aqueous extracts of Brazilian L edodes and P sajor-caju mushrooms are potential sources of antioxidant and anticancer compounds. However, further investigations are needed to exploit their valuable therapeutic uses and to elucidate their modes of action. Copyright © 2013 Elsevier Inc. All rights reserved.

The effects of humoral agents on the myoelectrical activity of the terminal ileum

PubMed Central

Waterfall, W. E.; Brown, B. H.; Duthie, H. L.; Whittaker, G. E.

1972-01-01

Electrical and motor activities of the terminal ileum have been recorded in 25 patients with a permanent ileostomy. Records made within a week of formation of the ileostomy show an increased motor activity which is significantly reduced after four weeks. Intravenous infusion of gastrin, 1 μg/kg-hr, was accompanied by a significant increase in action potentials and in the percentage motility. Conversely, secretin 1 unit/kg-hr was associated with a decrease in action potentials and in percentage motor activity. ImagesFig. 2Fig. 3 PMID:5069728

Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model

DTIC Science & Technology

2014-06-01

astrocyte activation can be seen in the CA1 region of the hippocampus (Figure 4). Neither IBA1 nor GFAP showed obvious increases in any other brain...0 4 8 IL6 DFP CORT DFP * * * 14 Chronic CORT pretreatment exacerbated the DFP-induced increase in activation of astrocytes specific to the CA1...may have caused a mild activation of astrocytes (Figure 18), there was no quantitative change in GFAP protein concentration in the hippocampus (data

Patterns of brain and cardiovascular activation while solving rule-discovery and rule-application numeric tasks.

PubMed

Sosnowski, Tytus; Rynkiewicz, Andrzej; Wordecha, Małgorzata; Kępkowicz, Anna; Majewska, Adrianna; Pstrągowska, Aleksandra; Oleksy, Tomasz; Wypych, Marek; Marchewka, Artur

2017-07-01

It is known that solving mental tasks leads to tonic increase in cardiovascular activity. Our previous research showed that tasks involving rule application (RA) caused greater tonic increase in cardiovascular activity than tasks requiring rule discovery (RD). However, it is not clear what brain mechanisms are responsible for this difference. The aim of two experimental studies was to compare the patterns of brain and cardiovascular activity while both RD and the RA numeric tasks were being solved. The fMRI study revealed greater brain activation while solving RD tasks than while solving RA tasks. In particular, RD tasks evoked greater activation of the left inferior frontal gyrus and selected areas in the parietal, and temporal cortices, including the precuneus, supramarginal gyrus, angular gyrus, inferior parietal lobule, and the superior temporal gyrus, and the cingulate cortex. In addition, RA tasks caused larger increases in HR than RD tasks. The second study, carried out in a cardiovascular laboratory, showed greater increases in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) while solving RA tasks than while solving RD tasks. The results support the hypothesis that RD and RA tasks involve different modes of information processing, but the neuronal mechanism responsible for the observed greater cardiovascular response to RA tasks than to RD tasks is not completely clear. Copyright © 2017. Published by Elsevier B.V.

RNase L Suppresses Androgen Receptor Signaling, Cell Migration and Matrix Metalloproteinase Activity in Prostate Cancer Cells

PubMed Central

Dayal, Shubham; Zhou, Jun; Manivannan, Praveen; Siddiqui, Mohammad Adnan; Ahmad, Omaima Farid; Clark, Matthew; Awadia, Sahezeel; Garcia-Mata, Rafael; Shemshedini, Lirim; Malathi, Krishnamurthy

2017-01-01

The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning and linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with prostate cancer, suggesting that RNase L may play additional roles in tumor suppression. Here, we demonstrate a role of RNase L as a suppressor of androgen receptor (AR) signaling, cell migration and matrix metalloproteinase activity. Using RNase L mutants, we show that its nucleolytic activity is dispensable for both AR signaling and migration. The most prevalent HPC1-associated mutations in RNase L, R462Q and E265X, enhance AR signaling and cell migration. RNase L negatively regulates cell migration and attachment on various extracellular matrices. We demonstrate that RNase L knockdown cells promote increased cell surface expression of integrin β1 which activates Focal Adhesion Kinase-Sarcoma (FAK-Src) pathway and Ras-related C3 botulinum toxin substrate 1-guanosine triphosphatase (Rac1-GTPase) activity to increase cell migration. Activity of matrix metalloproteinase (MMP)-2 and -9 is significantly increased in cells where RNase L levels are ablated. We show that mutations in RNase L found in HPC patients may promote prostate cancer by increasing expression of AR-responsive genes and cell motility and identify novel roles of RNase L as a prostate cancer susceptibility gene. PMID:28257035

30 min of treadmill walking at self-selected speed does not increase gait variability in independent elderly.

PubMed

Da Rocha, Emmanuel S; Kunzler, Marcos R; Bobbert, Maarten F; Duysens, Jacques; Carpes, Felipe P

2018-06-01

Walking is one of the preferred exercises among elderly, but could a prolonged walking increase gait variability, a risk factor for a fall in the elderly? Here we determine whether 30 min of treadmill walking increases coefficient of variation of gait in elderly. Because gait responses to exercise depend on fitness level, we included 15 sedentary and 15 active elderly. Sedentary participants preferred a lower gait speed and made smaller steps than the actives. Step length coefficient of variation decreased ~16.9% by the end of the exercise in both the groups. Stride length coefficient of variation decreased ~9% after 10 minutes of walking, and sedentary elderly showed a slightly larger step width coefficient of variation (~2%) at 10 min than active elderly. Active elderly showed higher walk ratio (step length/cadence) than sedentary in all times of walking, but the times did not differ in both the groups. In conclusion, treadmill gait kinematics differ between sedentary and active elderly, but changes over time are similar in sedentary and active elderly. As a practical implication, 30 min of walking might be a good strategy of exercise for elderly, independently of the fitness level, because it did not increase variability in step and stride kinematics, which is considered a risk of fall in this population.

Boys vs. girls: Gender differences in the neural development of trust and reciprocity depend on social context.

PubMed

Lemmers-Jansen, Imke L J; Krabbendam, Lydia; Veltman, Dick J; Fett, Anne-Kathrin J

2017-06-01

Trust and cooperation increase from adolescence to adulthood, but studies on gender differences in this development are rare. We investigated gender and age-related differences in trust and reciprocity and associated neural mechanisms in 43 individuals (16-27 years, 22 male). Participants played two multi-round trust games with a cooperative and an unfair partner. Males showed more basic trust towards unknown others than females. Both genders increased trust during cooperative interactions, with no differences in average trust. Age was unrelated to trust during cooperation. During unfair interactions males decreased their trust more with age than females. ROI analysis showed age-related increases in activation in the temporo-parietal junction (TPJ) and dorsolateral prefrontal cortex (dlPFC) during cooperative investments, and increased age-related caudate activation during both cooperative and unfair repayments. Gender differences in brain activation were only observed during cooperative repayments, with males activating the TPJ more than females, and females activating the caudate more. The findings suggest relatively mature processes of trust and reciprocity in the investigated age range. Gender differences only occur in unfair contexts, becoming more pronounced with age. Largely similar neural activation in males and females and few age effects suggest that similar, mature cognitive strategies are employed. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Trends in physical activity and participation in sports clubs among Icelandic adolescents.

PubMed

Eithsdóttir, Sigríthur Th; Kristjánsson, Alfgeir L; Sigfúsdóttir, Inga D; Allegrante, John P

2008-06-01

Physical activity among adolescents and its implications for health status is of increasing concern. We examined trends in physical activity and participation in sports clubs among Icelandic adolescents. Cross-sectional survey data were used to determine levels of vigorous physical activity and participation in sports clubs (defined as engaging in moderately intensive activity four times or more a week) for cohorts of Icelandic adolescents in 1992, 1997, 2000 and 2006. There was a 6% increase in the rate of vigorous physical activity and a 15% increase in active sports club participation among 14- and 15-year old Icelandic adolescents from 1992 to 2006. The trends were consistent across genders; however, only 53% of boys actually achieved the recommended criterion for vigorous physical activity, with the percentage of girls averaging 16% lower than that for boys. Additionally, there was an overall increase in the proportion of inactive adolescents, with girls consistently reporting higher levels of inactivity than boys even though the net increase in inactivity was higher for boys. Although our results show an overall increase in vigorous physical activity and participation in sports clubs over the past decade among both genders, our data also indicate that over half of all Icelandic adolescents are not achieving the recommended level of participation in physical activity. Furthermore, less than one third of the population studied is achieving the recommended level of activity through organized clubs. Initiatives to increase physical activity among the least active of adolescents should receive high priority in public health.

Low-intensity laser irradiation at 660 nm stimulates cytochrome c oxidase in stressed fibroblast cells.

PubMed

Houreld, Nicolette N; Masha, Roland T; Abrahamse, Heidi

2012-07-01

Low-intensity laser irradiation (LILI) has been used to modulate a variety of biological processes, including diabetic wound healing. The mechanism of action is thought to exist primarily with the mitochondria. This study aimed to determine the effect of irradiation on normal, diabetic, and ischemic mitochondrial electron transport chain (ETC) complexes. Normal, diabetic and ischemic human skin fibroblast mitochondria were irradiated in vitro at a wavelength of 660 nm and a fluence of either 5 or 15 J/cm(2). Non-irradiated mitochondria served as controls. Enzyme activities of mitochondrial complexes I, II, III, and IV were determined immediately post-irradiation. Normal, diabetic, and ischemic cells were irradiated and adenosine triphosphate (ATP) and active mitochondria were determined by luminescence and fluorescent microscopy, respectively. Irradiated diabetic mitochondria at a fluence of 15 J/cm(2) showed a significant decrease in complex III activity (P < 0.05). Normal (P < 0.01) and diabetic (P < 0.05) mitochondria irradiated at either 5 or 15 J/cm(2) showed a significant increase in complex IV activity. ATP results showed a significant increase in irradiated normal cells (5 J/cm(2); P < 0.05) and diabetic cells (15 J/cm(2); P < 0.01). There was a higher accumulation of active mitochondria in irradiated cells than non-irradiated cells. Irradiation at 660 nm has the ability to influence mitochondrial enzyme activity, in particular cytochrome c oxidase. This leads to increased mitochondrial activity and ATP synthesis. Copyright © 2012 Wiley Periodicals, Inc.

Body energy metabolism and oxidative stress in mice supplemented with conjugated linoleic acid (CLA) associated to oleic acid.

PubMed

Baraldi, Flavia; Dalalio, Felipe; Teodoro, Bruno; Prado, Ieda; Curti, Carlos; Alberici, Luciane

2014-10-01

Some fatty acids may play an important role in regulating metabolism through PPARs activation. Conjugated linoleic acid (CLA) has been shown to reduce body fat accumulation and increase body metabolism; this effect has been associated with up-regulation of mitochondrial uncoupling proteins (UCPs) and PPARalfa activation. Oleic acid has shown beneficial effects on health, decreasing oxidative stress and improving clinical conditions related to obesity. Therefore, in this work, we addressed the effects of a oleic plus CLA-supplemented murine diet on body metabolism, mitochondrial energetics and oxidative stress in the liver, as well as on other associated morphological and functional parameters in C57BL/6 mice. The diet was supplemented with 2% CLA mixture (cis-9, trans-10 and trans-10, cis-12 isomers; 45% of each isomer) and/or 0.7% olive oil on alternating days (60 days) by gavage. The results showed that diet supplementation with CLA increases body metabolism and reduces lipid accumulation in adipose tissues. Groups that received oleic acid (oleic and CLA oleic) showed decreased levels of total cholesterol and cholesterol non-HDL, and increased levels of HDL-cholesterol. Livers of mice fed a diet supplemented with CLA showed high levels UCP2 mRNA, and the isolated hepatic mitochondria showed indications of UCP activity and increased ROS generation. Oleic acid partially reversed the lower lipid accumulation increasing PPARgamma content, reversed the higher ROS generation by liver mitochondria and improved liver oxidative status. These results indicate a beneficial and secure dose of CLA and oleic acid for diet supplementation in mice, which increases body metabolism inducing UCP2 overexpression/activity in liver while preserving the redox state of the liver. Therefore, diet supplementation with CLA associated to oleic acid may be regarded as a potential strategy for controlling obesity and oxidative stress. Supported by FAPESP. Copyright © 2014. Published by Elsevier Inc.

Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states

PubMed Central

Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki

2017-01-01

Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases. PMID:29267380

Jojoba seed meal proteins associated with proteolytic and protease inhibitory activities.

PubMed

Shrestha, Madan K; Peri, Irena; Smirnoff, Patricia; Birk, Yehudith; Golan-Goldhirsh, Avi

2002-09-25

The jojoba, Simmondsia chinensis, is a characteristic desert plant native to the Sonoran desert. The jojoba meal after oil extraction is rich in protein. The major jojoba proteins were albumins (79%) and globulins (21%), which have similar amino acid compositions and also showed a labile thrombin-inhibitory activity. SDS-PAGE showed two major proteins at 50 kDa and 25 kDa both in the albumins and in the globulins. The 25 kDa protein has trypsin- and chymotrypsin-inhibitory activities. In vitro digestibility of the globulins and albumins resembled that of casein and soybean protein concentrates and was increased after heat treatment. The increased digestibility achieved by boiling may be attributed to inactivation of the protease inhibitors and denaturation of proteins.

Nitrogen recycling from the xylem in rice leaves: dependence upon metabolism and associated changes in xylem hydraulics

PubMed Central

Bailey, Karen J.

2016-01-01

Measurements of amino acids in the guttation fluid and in the xylem exudates of cut leaves from intact plants provide evidence of the remarkable efficiency with which these nitrogenous compounds are reabsorbed from the xylem sap. This could be achieved by mechanisms involving intercellular transport and/or metabolism. Developmental changes in transcripts and protein showed that transcripts for phosphoenolpyruvate carboxykinase (PEPCK) increased from the base to the leaf tip, and were markedly increased by supplying asparagine. Supplying amino acids also increased the amounts of protein of PEPCK and, to a lesser extent, of pyruvate, Pi dikinase. PEPCK is present in the hydathodes, stomata and vascular parenchyma of rice leaves. Evidence for the role of PEPCK was obtained by using 3-mercaptopicolinic acid (MPA), a specific inhibitor of PEPCK, and by using an activation-tagged rice line that had an increase in PEPCK activity, to show that activation of PEPCK resulted in a decrease in N in the guttation fluid and that treatment by MPA resulted in an increase in amino acids in the guttation fluid and xylem sap towards the leaf tip. Furthermore, increasing PEPCK activity decreased the amount of guttation fluid, whereas decreasing PEPCK activity increased the amount of xylem sap or guttation fluid towards the leaf tip. The findings suggest the following hypotheses: (i) both metabolism and transport are involved in xylem recycling and (ii) excess N is the signal involved in modulating xylem hydraulics, perhaps via nutrient regulation of water-transporting aquaporins. Water relations and vascular metabolism and transport are thus intimately linked. PMID:27053722

Antioxidant and neuroprotector effect of Lepidium meyenii (maca) methanol leaf extract against 6-hydroxy dopamine (6-OHDA)-induced toxicity in PC12 cells.

PubMed

Rodríguez-Huamán, Ángel; Casimiro-Gonzales, Sandra; Chávez-Pérez, Jorge Antonio; Gonzales-Arimborgo, Carla; Cisneros-Fernández, Richard; Aguilar-Mendoza, Luis Ángel; Gonzales, Gustavo F

2017-05-01

Reactive oxygen species (ROS) are normally produced during cell metabolism, there is strong evidence to suggest that ROS produced in excess impair the cell and may be etiologically related to various neurodegenerative diseases. This study was undertaken to examine the effects of Lepidium meyenii (MACA) methanol leaf extract on neurotoxicity in PC12 cell exposed to 6-hydroxydopamine (6-OHDA). Fresh samples of "maca" leaves were processed in order to obtain foliar extracts and to evaluate the neurobiological activity on PC12 cells, subjected to the cytotoxic effect of 6-OHDA through the determination of the capacity antioxidant, cell viability and cytotoxicity assays on PC12 cells. The results of the tests of antioxidant activity, showed maximum values of 2262.37 and 1305.36 expressed in Trolox equivalents (TEAC), for the methanolic and aqueous fractions respectively. Cell viability assays at a dose of 10 μg extract showed an increase of 31% and 60% at 6 and 12 h of pretreatment, respectively. Cytotoxicity assays at the same dose and exposure time showed a 31.4% and 47.8% reduction in lactate dehydrogenase (LDH) activity and an increase in superoxide dismutase (SOD) activity. The results allow us to affirm that the methanolic foliar extract of "maca" presents in vitro neurobiological activity of antioxidant protection, increase in cell viability and reduction of cytotoxicity against oxidative stress generated by 6-OHDA. In conclusion, the present study shows a protective role for Lepidium meyenii leaf extract on 6-OHDA-induced toxicity by an antioxidant effect.

Diagnosis of occlusal dysesthesia utilizing prefrontal hemodynamic activity with slight occlusal interference.

PubMed

Ono, Yumie; Ishikawa, Yu; Munakata, Motohiro; Shibuya, Tomoaki; Shimada, Atsushi; Miyachi, Hideo; Wake, Hiroyuki; Tamaki, Katsushi

2016-11-01

Clinical diagnosis of occlusal dysesthesia (OD), also referred to as phantom bite syndrome, is currently based on the absence of objective occlusal discrepancy despite the persistent complaint of uncomfortable bite sensation. We previously demonstrated that the subjective feeling of occlusal discomfort generated by artificial occlusal interference can be objectively evaluated using prefrontal hemodynamic activity in young healthy individuals. The aim of this study was to investigate whether dental patients with and without OD show distinct prefrontal activity during grinding behavior with an occlusal interference. Six dental patients with OD (OD group) and eight patients without OD (control group) grinded piled occlusal strips placed between their first molars and reported their perception and discomfort thresholds during continuous monitoring of prefrontal hemodynamic activity with a portable functional near-infrared spectroscopy. Although patients without OD showed the typical hemodynamic pattern of increased oxyhemoglobin and reduced deoxyhemoglobin (HHb) concentration, those with OD showed persistent incremental increases of HHb concentration that began at the loading of occlusal strips on their molars before they executed grinding. The intensities of the task-related HHb activities showed statistically significant differences between OD and control groups, particularly at channel 3, arranged over the left frontal pole cortex. When the discrimination criterion was set using the intensity values of channel 3 from both groups, the overall accuracy of the OD discrimination was 92.9%. Although physiological interpretation has yet to be elucidated, the task-related response of an increase in HHb may be a useful neuronal signature to characterize dental patients with OD.

Diagnosis of occlusal dysesthesia utilizing prefrontal hemodynamic activity with slight occlusal interference

PubMed Central

Ishikawa, Yu; Munakata, Motohiro; Shibuya, Tomoaki; Shimada, Atsushi; Miyachi, Hideo; Wake, Hiroyuki; Tamaki, Katsushi

2016-01-01

Clinical diagnosis of occlusal dysesthesia (OD), also referred to as phantom bite syndrome, is currently based on the absence of objective occlusal discrepancy despite the persistent complaint of uncomfortable bite sensation. We previously demonstrated that the subjective feeling of occlusal discomfort generated by artificial occlusal interference can be objectively evaluated using prefrontal hemodynamic activity in young healthy individuals. The aim of this study was to investigate whether dental patients with and without OD show distinct prefrontal activity during grinding behavior with an occlusal interference. Six dental patients with OD (OD group) and eight patients without OD (control group) grinded piled occlusal strips placed between their first molars and reported their perception and discomfort thresholds during continuous monitoring of prefrontal hemodynamic activity with a portable functional near‐infrared spectroscopy. Although patients without OD showed the typical hemodynamic pattern of increased oxyhemoglobin and reduced deoxyhemoglobin (HHb) concentration, those with OD showed persistent incremental increases of HHb concentration that began at the loading of occlusal strips on their molars before they executed grinding. The intensities of the task‐related HHb activities showed statistically significant differences between OD and control groups, particularly at channel 3, arranged over the left frontal pole cortex. When the discrimination criterion was set using the intensity values of channel 3 from both groups, the overall accuracy of the OD discrimination was 92.9%. Although physiological interpretation has yet to be elucidated, the task‐related response of an increase in HHb may be a useful neuronal signature to characterize dental patients with OD. PMID:29744159

Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity.

PubMed

Lee, Jae-Geun; Kang, Dong Gu; Yu, Jung Re; Kim, Youngree; Kim, Jinsoek; Koh, Gwanpyo; Lee, Daeho

2011-04-01

Dipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated whether ADA activity is specifically affected by treatment with DPP-4 inhibitor (DPP4I) compared with other anti-diabetic agents. Fasting ADA activity, in addition to various metabolic and biochemical parameters, were measured in 262 type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and in 46 non-diabetic control subjects. ADA activity was increased in T2DM patients compared with that in non-diabetic control subjects (mean±standard error, 23.1±0.6 U/L vs. 18.6±0.8 U/L; P<0.05). ADA activity was correlated with fasting plasma glucose (r=0.258, P<0.05), HbA1c (r=0.208, P<0.05), aspartate aminotransferase (r=0.325, P<0.05), and alanine aminotransferase (r=0.248, P<0.05). Compared with the well-controlled T2DM patients (HbA1c<7%), the poorly controlled group (HbA1c>9%) showed significantly increased ADA activity (21.1±0.8 U/L vs. 25.4±1.6 U/L; P<0.05). The effect of DPP4I on ADA activity in T2DM patients did not differ from those of other oral anti-diabetic agents or insulin. T2DM patients on metformin monotherapy showed a lower ADA activity (20.9±1.0 U/L vs. 28.1±2.8 U/L; P<0.05) compared with that of those on sulfonylurea monotherapy. Our results show that ADA activity is increased in T2DM patients compared to that in non-diabetic patients, is positively correlated with blood glucose level, and that DPP4I has no additional specific effect on ADA activity, except for a glycemic control- or HbA1c-dependent effect.

Heme Oxygenase Inhibition Sensitizes Neuroblastoma Cells to Carfilzomib.

PubMed

Barbagallo, Ignazio; Giallongo, Cesarina; Volti, Giovanni Li; Distefano, Alfio; Camiolo, Giuseppina; Raffaele, Marco; Salerno, Loredana; Pittalà, Valeria; Sorrenti, Valeria; Avola, Roberto; Di Rosa, Michelino; Vanella, Luca; Di Raimondo, Francesco; Tibullo, Daniele

2018-06-10

Neuroblastoma (NB) is an embryonic malignancy affecting the physiological development of adrenal medulla and paravertebral sympathetic ganglia in early infancy. Proteasome inhibitors (PIs) (i.e., carfilzomib (CFZ)) may represent a possible pharmacological treatment for solid tumors including NB. In the present study, we tested the effect of a novel non-competitive inhibitor of heme oxygenase-1 (HO-1), LS1/71, as a possible adjuvant therapy for the efficacy of CFZ in neuroblastoma cells. Our results showed that CFZ increased both HO-1 gene expression (about 18-fold) and HO activity (about 8-fold), following activation of the ER stress pathway. The involvement of HO-1 in CFZ-mediated cytotoxicity was further confirmed by the protective effect of pharmacological induction of HO-1, significantly attenuating cytotoxicity. In addition, HO-1 selective inhibition by a specific siRNA increased the cytotoxic effect following CFZ treatment in NB whereas SnMP, a competitive pharmacological inhibitor of HO, showed no changes in cytotoxicity. Our data suggest that treatment with CFZ produces ER stress in NB without activation of CHOP-mediated apoptosis, whereas co-treatment with CFZ and LS1/71 led to apoptosis activation and CHOP expression induction. In conclusion, our study showed that treatment with the non-competitive inhibitor of HO-1, LS1 / 71, increased cytotoxicity mediated by CFZ, triggering apoptosis following ER stress activation. These results suggest that PIs may represent a possible pharmacological treatment for solid tumors and that HO-1 inhibition may represent a possible strategy to overcome chemoresistance and increase the efficacy of chemotherapic regimens.

Increased working memory-related brain activity in middle-aged women with cognitive complaints.

PubMed

Dumas, Julie A; Kutz, Amanda M; McDonald, Brenna C; Naylor, Magdalena R; Pfaff, Ashley C; Saykin, Andrew J; Newhouse, Paul A

2013-04-01

Individuals who report subjective cognitive complaints but perform normally on neuropsychological tests might be at increased risk for pathological cognitive aging. The current study examined the effects of the presence of subjective cognitive complaints on functional brain activity during a working memory task in a sample of middle-aged postmenopausal women. Twenty-three postmenopausal women aged 50-60 completed a cognitive complaint battery of questionnaires. Using 20% of items endorsed as the threshold, 12 women were categorized as cognitive complainers (CC) and 11 were noncomplainers (NC). All subjects then took part in a functional magnetic resonance imaging scanning session during which they completed a visual-verbal N-back test of working memory. Results showed no difference in working memory performance between CC and NC groups. However, the CC group showed greater activation relative to the NC group in a broad network involved in working memory including the middle frontal gyrus (Brodmann area [BA] 9 and 10), the precuneus (BA 7), and the cingulate gyrus (BA 24 and 32). The CC group recruited additional regions of the working memory network compared with the NC group as the working memory load and difficulty of the task increased. This study showed brain activation differences during working memory performance in a middle-aged group of postmenopausal women with subjective cognitive complaints but without objective cognitive deficit. These findings suggest that subjective cognitive complaints in postmenopausal women might be associated with increased cortical activity during effort-demanding cognitive tasks. Copyright © 2013 Elsevier Inc. All rights reserved.

Melatonin and circadian rhythms in autism: Case report.

PubMed

Zuculo, Gabriela Melloni; Gonçalves, Bruno S B; Brittes, Clay; Menna-Barreto, Luiz; Pinato, Luciana

2017-01-01

Among the most co-occurring conditions in autism spectrum disorders (ASD), there are sleep disorders which may exacerbate associated behavioral disorders and lead to intensification of existing autistic symptoms. Several studies investigating the use of melatonin in the treatment of sleep disorders in ASD have shown comparative efficiency in sleep with little or no side effects. Here we report a case of ASD with non-24-hour rhythm and the effect of melatonin in circadian parameters by actigraphy. Visual analysis of the first 10 days recorded and the periodogram suggest that this patient showed a non-24-hour rhythm. This ASD subject showed before melatonin administration an activity/rest rhythm lower than 24 hours. The results show that melatonin increased approximately 4.7 times the regularity of circadian activity rhythm and resting staying on average between 00:00 and 06:00 and showed positive effects in improving the quality of sleep and behavior. So, the actigraphy showed an ASD subject with a non-24-hour activity/rest rhythm which changed this rhythm to a 24-hour rhythm after melatonin administration. This result reinforces the prospect of therapy with melatonin for synchronization (increased regularity) of endogenous rhythms and improve sleep quality and hence behavior and indicates the actigraphy as a choice tool to characterize several parameters of the activity/rest rhythm of ASD individuals.

Red Brain, Blue Brain: Evaluative Processes Differ in Democrats and Republicans

PubMed Central

Schreiber, Darren; Fonzo, Greg; Simmons, Alan N.; Dawes, Christopher T.; Flagan, Taru; Fowler, James H.; Paulus, Martin P.

2013-01-01

Liberals and conservatives exhibit different cognitive styles and converging lines of evidence suggest that biology influences differences in their political attitudes and beliefs. In particular, a recent study of young adults suggests that liberals and conservatives have significantly different brain structure, with liberals showing increased gray matter volume in the anterior cingulate cortex, and conservatives showing increased gray matter volume in the in the amygdala. Here, we explore differences in brain function in liberals and conservatives by matching publicly-available voter records to 82 subjects who performed a risk-taking task during functional imaging. Although the risk-taking behavior of Democrats (liberals) and Republicans (conservatives) did not differ, their brain activity did. Democrats showed significantly greater activity in the left insula, while Republicans showed significantly greater activity in the right amygdala. In fact, a two parameter model of partisanship based on amygdala and insula activations yields a better fitting model of partisanship than a well-established model based on parental socialization of party identification long thought to be one of the core findings of political science. These results suggest that liberals and conservatives engage different cognitive processes when they think about risk, and they support recent evidence that conservatives show greater sensitivity to threatening stimuli. PMID:23418419

Characterization of the Regulation and Function of Zinc-Dependent Histone Deacetylases During Mouse Liver Regeneration

PubMed Central

Huang, Jiansheng; Barr, Emily; Rudnick, David A.

2013-01-01

The studies reported here were undertaken to define the regulation and functional importance of zinc-dependent histone deacetylase (Zn-HDAC) activity during liver regeneration using the mouse partial hepatectomy (PH) model. The results showed that hepatic HDAC activity was significantly increased in nuclear and cytoplasmic fractions following PH. Further analyses showed isoform-specific effects of PH on HDAC mRNA and protein expression, with increased expression of the class I HDACs, 1 and 8, and class II HDAC4 in regenerating liver. Hepatic expression of (class II) HDAC5 was unchanged after PH; however HDAC5 exhibited transient nuclear accumulation in regenerating liver. These changes in hepatic HDAC expression, subcellular localization, and activity coincided with diminished histone acetylation in regenerating liver. The significance of these events was investigated by determining the effects of suberoylanilide hydroxyamic acid (SAHA, a specific inhibitor of Zn-HDAC activity) on hepatic regeneration. The results showed that SAHA-treatment suppressed the effects of PH on histone deacetylation and hepatocellular BrdU incorporation. Further examination showed that SAHA blunted hepatic expression and activation of cell cycle signals downstream of induction of cyclin D1 expression in mice subjected to PH. Conclusion The data reported here demonstrate isoform-specific regulation of Zn-HDAC expression, subcellular localization, and activity in regenerating liver. These studies also indicate that HDAC activity promotes liver regeneration by regulating hepatocellular cell cycle progression at a step downstream of cyclin D1 induction. PMID:23258575

(abstract) A Geomagnetic Contribution to Climate Change in this Century

NASA Technical Reports Server (NTRS)

Feynman, J.; Ruzmaikin, A.; Lawrence, J.

1996-01-01

There is a myth that all solar effects can be parameterized by the sun spot number. This is not true. For example, the level of geomagnetic activity during this century was not proportional to the sunspot number. Instead there is a large systematic increase in geomagnetic activity, not reflected in the sunspot number. This increase occurred gradually over at least 60 years. The 11 year solar cycle variation was superimposed on this systematic increase. Here we show that this systematic increase in activity is well correlated to the simultaneous increase in terrestrial temperature that occurred during the first half of this century. We discuss these findings in terms of mechanisms by which geomagnetics can be coupled to climate. These mechanisms include possible changes in weather patterns and cloud cover due to increased cosmic ray fluxes, or to increased fluxes of high energy electrons. We suggest that this systematic increase in geomagnetic activity contributed (along with anthropogenic effects and possible changes in solar irradiance) to the changes in climate recorded during this period.

Visual short-term memory load suppresses temporo-parietal junction activity and induces inattentional blindness.

PubMed

Todd, J Jay; Fougnie, Daryl; Marois, René

2005-12-01

The right temporo-parietal junction (TPJ) is critical for stimulus-driven attention and visual awareness. Here we show that as the visual short-term memory (VSTM) load of a task increases, activity in this region is increasingly suppressed. Correspondingly, increasing VSTM load impairs the ability of subjects to consciously detect the presence of a novel, unexpected object in the visual field. These results not only demonstrate that VSTM load suppresses TPJ activity and induces inattentional blindness, but also offer a plausible neural mechanism for this perceptual deficit: suppression of the stimulus-driven attentional network.

Physiochemical Studies of Sodium Chloride on Mungbean (Vigna radiata L. Wilczek) and Its Possible Recovery with Spermine and Gibberellic Acid

PubMed Central

Mitra, Sanglap; Paul, Atreyee

2015-01-01

The physiological and biochemical responses to increasing NaCl concentrations, along with low concentrations of gibberellic acid or spermine, either alone or in their combination, were studied in mungbean seedlings. In the test seedlings, the root-shoot elongation, biomass production, and the chlorophyll content were significantly decreased with increasing NaCl concentrations. Salt toxicity severely affected activities of different antioxidant enzymes and oxidative stress markers. Activities of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT) increased significantly over water control. Similarly, oxidative stress markers such as proline, malondialdehyde (MDA), and hydrogen peroxide (H2O2) contents also increased as a result of progressive increase in salt stress. Combined application of NaCl along with low concentrations of either gibberellic acid (5 µM) or spermine (50 µM) in the test seedlings showed significant alterations, that is, drastic increase in seedling elongation, increased biomass production, increased chlorophyll content, and significant lowering in all the antioxidant enzyme activities as well as oxidative stress marker contents in comparison to salt treated test seedlings, leading to better growth and metabolism. Our study shows that low concentrations of either gibberellic acid or spermine will be able to overcome the toxic effects of NaCl stress in mungbean seedlings. PMID:25734186

Load matters: neural correlates of verbal working memory in children with autism spectrum disorder.

PubMed

Vogan, Vanessa M; Francis, Kaitlyn E; Morgan, Benjamin R; Smith, Mary Lou; Taylor, Margot J

2018-06-01

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterised by diminished social reciprocity and communication skills and the presence of stereotyped and restricted behaviours. Executive functioning deficits, such as working memory, are associated with core ASD symptoms. Working memory allows for temporary storage and manipulation of information and relies heavily on frontal-parietal networks of the brain. There are few reports on the neural correlates of working memory in youth with ASD. The current study identified the neural systems underlying verbal working memory capacity in youth with and without ASD using functional magnetic resonance imaging (fMRI). Fifty-seven youth, 27 with ASD and 30 sex- and age-matched typically developing (TD) controls (9-16 years), completed a one-back letter matching task (LMT) with four levels of difficulty (i.e. cognitive load) while fMRI data were recorded. Linear trend analyses were conducted to examine brain regions that were recruited as a function of increasing cognitive load. We found similar behavioural performance on the LMT in terms of reaction times, but in the two higher load conditions, the ASD youth had lower accuracy than the TD group. Neural patterns of activations differed significantly between TD and ASD groups. In TD youth, areas classically used for working memory, including the lateral and medial frontal, as well as superior parietal brain regions, increased in activation with increasing task difficulty, while areas related to the default mode network (DMN) showed decreasing activation (i.e., deactivation). The youth with ASD did not appear to use this opposing cognitive processing system; they showed little recruitment of frontal and parietal regions across the load but did show similar modulation of the DMN. In a working memory task, where the load was manipulated without changing executive demands, TD youth showed increasing recruitment with increasing load of the classic fronto-parietal brain areas and decreasing involvement in default mode regions. In contrast, although they modulated the default mode network, youth with ASD did not show the modulation of increasing brain activation with increasing load, suggesting that they may be unable to manage increasing verbal information. Impaired verbal working memory in ASD would interfere with the youths' success academically and socially. Thus, determining the nature of atypical neural processing could help establish or monitor working memory interventions for ASD.

The suppression of ghrelin signaling mitigates age-associated thermogenic impairment

PubMed Central

Bongmba, Odelia Y. N.; Ma, Xiaojun; Zhu, Xiongwei; Sheikh-Hamad, David; Sun, Yuxiang

2014-01-01

Aging is associated with severe thermogenic impairment, which contributes to obesity and diabetes in aging. We previously reported that ablation of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), attenuates age-associated obesity and insulin resistance. Ghrelin and obestatin are derived from the same preproghrelin gene. Here we showed that in brown adipocytes, ghrelin decreases the expression of thermogenic regulator but obestatin increases it, thus showing the opposite effects. We also found that during aging, plasma ghrelin and GHS-R expression in brown adipose tissue (BAT) are increased, but plasma obestatin is unchanged. Increased plasma ghrelin and unchanged obestatin during aging may lead to an imbalance of thermogenic regulation, which may in turn exacerbate thermogenic impairment in aging. Moreover, we found that GHS-R ablation activates thermogenic signaling, enhances insulin activation, increases mitochondrial biogenesis, and improves mitochondrial dynamics of BAT. In addition, we detected increased norepinephrine in the circulation, and observed that GHS-R knockdown in brown adipocytes directly stimulates thermogenic activity, suggesting that GHS-R regulates thermogenesis via both central and peripheral mechanisms. Collectively, our studies demonstrate that ghrelin signaling is an important thermogenic regulator in aging. Antagonists of GHS-R may serve as unique anti-obesity agents, combating obesity by activating thermogenesis. PMID:25543537

Engineering α-amylase levels in wheat grain suggests a highly sophisticated level of carbohydrate regulation during development.

PubMed

Whan, Alex; Dielen, Anne-Sophie; Mieog, Jos; Bowerman, Andrew F; Robinson, Hannah M; Byrne, Keren; Colgrave, Michelle; Larkin, Philip J; Howitt, Crispin A; Morell, Matthew K; Ral, Jean-Philippe

2014-10-01

Wheat starch degradation requires the synergistic action of different amylolytic enzymes. Our spatio-temporal study of wheat α-amylases throughout grain development shows that AMY3 is the most abundant isoform compared with the other known α-amylases. Endosperm-specific over-expression of AMY3 resulted in an increase of total α-amylase activity in harvested grains. Unexpectedly, increased activity did not have a significant impact on starch content or composition but led to an increase of soluble carbohydrate (mainly sucrose) in dry grain. In AMY3 overexpression lines (A3OE), germination was slightly delayed and triacylglycerol (TAG) content was increased in the endosperm of mature grain. Despite increased AMY3 transcript and protein content throughout grain development, alterations of α-amylase activity and starch granule degradation were not detected until grain maturation, suggesting a post-translational inhibition of α-amylase activity in the endosperm during the starch filling period. These findings show unexpected effects of a high level of α-amylase on grain development and composition, notably in carbon partitioning and TAG accumulation, and suggest the presence of a hitherto unknown regulatory pathway during grain filling. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Ferroxidase activity of apoferritin is increased in the presence of platinum nanoparticles.

PubMed

Sennuga, Afolake; van Marwijk, Jacqueline; Whiteley, Chris G

2012-01-27

The ferroxidase activity of horse spleen apoferritin (HSAF) is increased by nine-fold in the presence of platinum nanoparticles. HSAF was mixed with varying concentrations of K2PtCl4 followed by a 20-fold concentration of sodium borohydride to afford Pt:HSAF nanoparticle complexes in a ratio of between 1:250 and 1:4000. Typical colour changes, from colourless or pale yellow to brown, occurred that were dependent on the amount of platinum present. These complexes were characterized by UV/vis, inductively coupled plasma optical emission spectroscopy, Fourier transform infrared, transmission electron microscopy and energy dispersive x-ray spectroscopy. Transmission electron microscopy analysis revealed that the size of nanoparticles increased as the molar ratio of platinum to HSAF increased with an average size diameter of 2-6 nm generated with HSAF:platinum molar ratios of 1:250-1:4000. Fourier transform infrared spectroscopy (FTIR) spectra showed no distinct changes in the structure of HSAF but confirmed that the nanoparticles were attached to the protein. The effect of platinum nanoparticles on the ferroxidase activity of HSAF showed a specific activity of 360 ρmol min(-1) mg(-1), (nine-fold increase over the control) at the molar ratio of HSAF:platinum nanoparticles of 1:1000.

Influence of local vibration on plasma creatine phosphokinase (CPK) activity.

PubMed Central

Okada, A; Okuda, H; Inaba, R; Ariizumi, M

1985-01-01

This study was designed to obtain basic information about the mechanism of the occurrence of muscular disorders after exposure to vibration. The hind legs of rats were exposed to acute and chronic local vibration at frequencies of 30, 60, 120, 240, 480, and 960 Hz with a constant acceleration of 50 m/sec2. The exposure time was four hours for acute, and four hours a day for two weeks continuously for chronic exposure. Blood was collected after exposure to measure plasma creatine phosphokinase (CPK) activity. In both exposure groups the activity of plasma CPK was significantly higher at 30, 60, 120, 240, and 480 Hz compared with the control group and was especially high at 30 Hz; there was no significant change at 960 Hz. As a result of an analysis of the CPK isoenzymes, the increase in plasma CPK activity was shown to be due to the activity of the plasma CPK-MM fraction, originating in the skeletal muscle. Plasma CPK activity showed a tendency to decrease gradually with the increase in vibration frequency during acute exposure but showed no such tendency during chronic exposure. There was no remarkable pathohistological change in muscle preparations from the hind legs, hence it was presumed that the increase in plasma CPK activity was caused not by the morphological changes of muscle but by other mechanisms, such as an increase in the permeability of the cell membrane. Images PMID:4041385

Neoadjuvant chemotherapy modifies serum angiotensinase activities in women with breast cancer.

PubMed

Ramírez-Expósito, María Jesús; Carrera-González, María del Pilar; Mayas, María Dolores; Dueñas, Basilio; Martínez-Ferrol, Julia; Martínez-Martos, José Manuel

2012-05-01

The aim of this study was to investigate the putative changes in serum angiotensinase activities (aminopeptidase N, APN; aminopeptidase B, APB; aminopeptidase A, APA; aspartyl aminopeptidase, ASAP) involved in the renin-angiotensin system (RAS) in women with breast cancer treated or not with a neoadjuvant therapy of paclitaxel and anthracycline and in healthy women volunteers. We fluorometrically analysed serum APN, APB, APA and ASAP activities using their corresponding aminoacyl-β-naphthylamides as substrates in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline. When compared with healthy controls, women with breast cancer not treated with neoadjuvant chemotherapy, showed a decrease in angiotensinase activity, which support the putative increase of angiotensin II (Ang II) levels, indicating that the tumour process would favour the development of the disease. Also, an increase in APN and APB activities was observed, which support a role for angiotensin IV (Ang IV). In women treated with a neoadjuvant therapy, we described an increase in ASAP and APA activities, supporting the idea that this treatment increases Ang II catabolism. The resulting decrease in Ang II level could lead to an inhibition of the tumour growth. Present results show changes in serum angiotensinase activities in women with breast cancer and in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline. Therefore, considerable attention should be focused on the development of RAS blockade therapy as a new strategy for breast cancer treatment. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Anxiolytic-like effect of 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol is mediated through the benzodiazepine and nicotinic pathways.

PubMed

Brito, Adriane F; Fajemiroye, James O; Neri, Hiasmin F S; Silva, Dayane M; Silva, Daiany P B; Sanz, Germán; Vaz, Boniek G; de Carvalho, Flávio S; Ghedini, Paulo C; Lião, Luciano M; Menegatti, Ricardo; Costa, Elson A

2017-09-01

In this study, we proposed the design, synthesis of a new compound 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol (LQFM032), and pharmacological evaluation of its anxiolytic-like effect. This new compound was subjected to pharmacological screening referred to as Irwin test, prior to sodium pentobarbital-induced sleep, open-field and wire tests. The anxiolytic-like effect of this compound was evaluated using elevated plus maze and light-dark box tests. In addition, the mnemonic activity was evaluated through step-down test. In sodium pentobarbital-induced sleep test, LQFM032 decreased latency and increased duration of sleep. In the open-field test, LQFM032 altered behavioral parameter, that suggested anxiolytic-like activity, as increased in crossings and time spent at the center of open field. In the plus maze test and light-dark box test, the LQFM032 showed anxiolytic-like activity, increased entries and time spent on open arms, and increased in number of transitions and time spent on light area, respectively. Those effects was antagonized by flumazenil but not with 1-(2-Methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN-190). The LQFM032 did not alter mnemonic activity. Moreover, the anxiolytic-like activity of LQFM032 was antagonized by mecamylamine. In summary, LQFM032 showed benzodiazepine and nicotinic pathways mediated anxiolytic-like activity without altering the mnemonic activity. © 2017 John Wiley & Sons A/S.

Texting to Increase Physical Activity Among Teenagers (TXT Me!): Rationale, Design, and Methods Proposal

PubMed Central

Cantu, Dora; Bhatt, Riddhi; Baranowski, Tom; Rodgers, Wendy; Jago, Russell; Anderson, Barbara; Liu, Yan; Mendoza, Jason A; Tapia, Ramsey; Buday, Richard

2014-01-01

Background Physical activity decreases from childhood through adulthood. Among youth, teenagers (teens) achieve the lowest levels of physical activity, and high school age youth are particularly at risk of inactivity. Effective methods are needed to increase youth physical activity in a way that can be maintained through adulthood. Because teens text a great deal, text messages promoting walking, a low cost physical activity, may be an effective method for promoting sustainable physical activity. Objective The objective of our study was to determine the effect of pedometers, self selected step goals, and texts grounded in the self-determination theory (SDT) on physical activity among the teens. Methods “TXT Me!” was a 12 week intervention that texted 14-17 year olds to increase their daily physical activity by increasing the number of steps they take each day. The intervention was grounded in the SDT. Formative research with the teens helped construct the intervention and develop the texts. A total of 84 texts were developed (12 to set a step goal, and 72 promoting autonomy, competence, and relatedness). The pilot evaluation used a four group, randomized design (n=160). After baseline data collection, the participants were randomized to one of four conditions (no treatment control, pedometer only, pedometer + weekly prompts, pedometer + weekly prompts + SDT grounded texts). Data were collected at baseline and immediately upon completion of the study. The primary outcome was physical activity, measured by 7 days of accelerometry. Basic psychological needs, physical activity motivation, process evaluation, and program satisfaction data were also collected. Results To our knowledge, this is one of the first studies to explore the use of stand alone, SDT grounded texts, supported by pedometers and prompts to set a self selected step goal, as a method for increasing physical activity among teens. Conclusions This pilot study will contribute valuable information regarding whether theoretically grounded text messages show promise as an effective method to increase physical activity among teens. Trial Registration Clinicaltrials.gov NCT01482234; http://clinicaltrials.gov/ct2/show/NCT01482234 (Archived by WebCite at http://www.webcitation.org/6NYvRMOoq). PMID:24622344

Foaming and emulsifying properties of pectin isolated from different plant materials

NASA Astrophysics Data System (ADS)

Yancheva, Nikoleta; Markova, Daniela; Murdzheva, Dilyana; Vasileva, Ivelina; Slavov, Anton

2016-03-01

The foaming and emulsifying properties of pectins obtained from waste rose petals, citrus pressings, grapefruit peels and celery were studied. It was found that the highest foaming capacity showed pectin derived from celery. The effect of pectin concentration on the foaming capacity of pectin solutions was investigated. For all the investigated pectins increasing the concentration led to increase of the foaming capacity. Emulsifying activity and emulsion stability of model emulsion systems (50 % oil phase) with 0.6 % pectic solutions were determined. The highest emulsifying activity and stability showed pectin isolated by dilute acid extraction from waste rose petals.

Fast Back-Propagation Learning Using Steep Activation Functions and Automatic Weight

Treesearch

Tai-Hoon Cho; Richard W. Conners; Philip A. Araman

1992-01-01

In this paper, several back-propagation (BP) learning speed-up algorithms that employ the ãgainä parameter, i.e., steepness of the activation function, are examined. Simulations will show that increasing the gain seemingly increases the speed of convergence and that these algorithms can converge faster than the standard BP learning algorithm on some problems. However,...

Marketing Feud: An Active Learning Game of (Mis)Perception

ERIC Educational Resources Information Center

Schee, Brian A. Vander

2011-01-01

This paper presents the results of implementing an active learning activity in the principles of marketing course adapted from the television show "Family Feud". The objectives of the Marketing Feud game include increasing awareness of marketing misperceptions, clarifying marketing misunderstandings, encouraging class participation, and building…

Brain activation for language dual-tasking: listening to two people speak at the same time and a change in network timing.

PubMed

Buchweitz, Augusto; Keller, Timothy A; Meyler, Ann; Just, Marcel Adam

2012-08-01

The study used fMRI to investigate brain activation in participants who were able to listen to and successfully comprehend two people speaking at the same time (dual-tasking). The study identified brain mechanisms associated with high-level, concurrent dual-tasking, as compared with comprehending a single message. Results showed an increase in the functional connectivity among areas of the language network in the dual task. The increase in synchronization of brain activation for dual-tasking was brought about primarily by a change in the timing of left inferior frontal gyrus (LIFG) activation relative to posterior temporal activation, bringing the LIFG activation into closer correspondence with temporal activation. The results show that the change in LIFG timing was greater in participants with lower working memory capacity, and that recruitment of additional activation in the dual-task occurred only in the areas adjacent to the language network that was activated in the single task. The shift in LIFG activation may be a brain marker of how the brain adapts to high-level dual-tasking. Copyright © 2011 Wiley Periodicals, Inc.

Reappraising the voices of wrath

PubMed Central

Frühholz, Sascha; Grandjean, Didier

2015-01-01

Cognitive reappraisal recruits prefrontal and parietal cortical areas. Because of the near exclusive usage in past research of visual stimuli to elicit emotions, it is unknown whether the same neural substrates underlie the reappraisal of emotions induced through other sensory modalities. Here, participants reappraised their emotions in order to increase or decrease their emotional response to angry prosody, or maintained their attention to it in a control condition. Neural activity was monitored with fMRI, and connectivity was investigated by using psychophysiological interaction analyses. A right-sided network encompassing the superior temporal gyrus, the superior temporal sulcus and the inferior frontal gyrus was found to underlie the processing of angry prosody. During reappraisal to increase emotional response, the left superior frontal gyrus showed increased activity and became functionally coupled to right auditory cortices. During reappraisal to decrease emotional response, a network that included the medial frontal gyrus and posterior parietal areas showed increased activation and greater functional connectivity with bilateral auditory regions. Activations pertaining to this network were more extended on the right side of the brain. Although directionality cannot be inferred from PPI analyses, the findings suggest a similar frontoparietal network for the reappraisal of visually and auditorily induced negative emotions. PMID:25964502

Suspected side effects of doxycycline use in dogs - a retrospective study of 386 cases.

PubMed

Schulz, B S; Hupfauer, S; Ammer, H; Sauter-Louis, C; Hartmann, K

2011-08-27

This study investigated doxycycline-related side effects in a large population of dogs. Data from 386 dogs that had received doxycycline for the treatment of various infectious diseases were analysed retrospectively. Potential side effects that developed during treatment were documented, and correlations with signalment, dose, duration of treatment, frequency of application, doxycycline preparation and use of additional drugs were investigated. Vomiting was reported in 18.3 per cent of dogs, 7.0 per cent developed diarrhoea and 2.5 per cent developed anorexia. While being treated with doxycycline, 39.4 per cent of dogs showed an increase in alanine aminotransferase (ALT) activity and 36.4 per cent showed an increase in alkaline phosphatase (ALP) activity. There was a dose-related risk of an increase in ALP activity (P=0.011, odds ratio [OR]=1.27, 95 per cent confidence interval [CI] 1.06 to 1.53), and older dogs treated with doxycycline were more likely to develop an increase in ALT activity (P=0.038, OR=1.23, 95 per cent CI 1.01 to 1.50) and vomiting (P=0.017, OR=1.11, 95 per cent CI 1.02 to 1.21).

Dendrimer-Linked Antifreeze Proteins Have Superior Activity and Thermal Recovery.

PubMed

Stevens, Corey A; Drori, Ran; Zalis, Shiran; Braslavsky, Ido; Davies, Peter L

2015-09-16

By binding to ice, antifreeze proteins (AFPs) depress the freezing point of a solution and inhibit ice recrystallization if freezing does occur. Previous work showed that the activity of an AFP was incrementally increased by fusing it to another protein. Even larger increases in activity were achieved by doubling the number of ice-binding sites by dimerization. Here, we have combined the two strategies by linking multiple outward-facing AFPs to a dendrimer to significantly increase both the size of the molecule and the number of ice-binding sites. Using a heterobifunctional cross-linker, we attached between 6 and 11 type III AFPs to a second-generation polyamidoamine (G2-PAMAM) dendrimer with 16 reactive termini. This heterogeneous sample of dendrimer-linked type III constructs showed a greater than 4-fold increase in freezing point depression over that of monomeric type III AFP. This multimerized AFP was particularly effective at ice recrystallization inhibition activity, likely because it can simultaneously bind multiple ice surfaces. Additionally, attachment to the dendrimer has afforded the AFP superior recovery from heat denaturation. Linking AFPs together via polymers can generate novel reagents for controlling ice growth and recrystallization.

Deficiency in Serine Protease Inhibitor Neuroserpin Exacerbates Ischemic Brain Injury by Increased Postischemic Inflammation

PubMed Central

Ludewig, Peter; Bernreuther, Christian; Krasemann, Susanne; Arunachalam, Priyadharshini; Gerloff, Christian; Glatzel, Markus; Magnus, Tim

2013-01-01

The only approved pharmacological treatment for ischemic stroke is intravenous administration of plasminogen activator (tPA) to re-canalize the occluded cerebral vessel. Not only reperfusion but also tPA itself can induce an inflammatory response. Microglia are the innate immune cells of the central nervous system and the first immune cells to become activated in stroke. Neuroserpin, an endogenous inhibitor of tPA, is up-regulated following cerebral ischemia. To examine neuroserpin-dependent mechanisms of neuroprotection in stroke, we studied neuroserpin deficient (Ns−/−) mice in an animal model of temporal focal ischemic stroke. Infarct size and neurological outcome were worse in neuroserpin deficient mice even though the fibrinolytic activity in the ischemic brain was increased. The increased infarct size was paralleled by a selective increase in proinflammatory microglia activation in Ns−/− mice. Our results show excessive microglial activation in Ns−/− mice mediated by an increased activity of tPA. This activation results in a worse outcome further underscoring the potential detrimental proinflammatory effects of tPA. PMID:23658802

Evaluation of the potential of Pistia stratiotes L. (water lettuce) for bioindication and phytoremediation of aquatic environments contaminated with arsenic.

PubMed

Farnese, F S; Oliveira, J A; Lima, F S; Leão, G A; Gusman, G S; Silva, L C

2014-08-01

Specimens of Pistia stratiotes were subjected to five concentrations of arsenic (As) for seven days. Growth, As absorption, malondialdehyde (MDA) content, photosynthetic pigments, enzymatic activities, amino acids content and anatomical changes were assessed. Plant arsenic accumulation increased with increasing metalloid in the solution, while growth rate and photosynthetic pigment content decreased. The MDA content increased, indicating oxidative stress. Enzymatic activity and amino acids content increased at the lower doses of As, subsequently declining in the higher concentrations. Chlorosis and necrosis were observed in the leaves. Leaves showed starch accumulation and increased thickness of the mesophyll. In the root system, there was a loss and darkening of roots. Cell layers formed at the insertion points on the root stems may have been responsible for the loss of roots. These results indicate that water lettuce shows potential for bioindication and phytoremediation of As-contaminated aquatic environments.

PKC-dependent stimulation of the human MCT1 promoter involves transcription factor AP2.

PubMed

Saksena, Seema; Dwivedi, Alka; Gill, Ravinder K; Singla, Amika; Alrefai, Waddah A; Malakooti, Jaleh; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K

2009-02-01

Monocarboxylate transporter (MCT1) plays an important role in the absorption of short-chain fatty acids (SCFA) such as butyrate in the human colon. Previous studies from our laboratory have demonstrated that phorbol ester, PMA (1 microM, 24 h), upregulates butyrate transport and MCT1 protein expression in human intestinal Caco-2 cells. However, the molecular mechanisms involved in the transcriptional regulation of MCT1 gene expression by PMA in the intestine are not known. In the present study, we showed that PMA (0.1 microM, 24 h) increased the MCT1 promoter activity (-871/+91) by approximately fourfold. A corresponding increase in MCT1 mRNA abundance in response to PMA was also observed. PMA-induced stimulation of MCT1 promoter activity was observed as early as 1 h and persisted until 24 h, suggesting that the effects of PMA are attributable to initial PKC activation. Kinase inhibitor and phosphorylation studies indicated that these effects may be mediated through activation of the atypical PKC-zeta isoform. 5'-deletion studies demonstrated that the MCT1 core promoter region (-229/+91) is the PMA-responsive region. Site-directed mutagenesis studies showed the predominant involvement of potential activator protein 2 (AP2) binding site in the activation of MCT1 promoter activity by PMA. In addition, overexpression of AP2 in Caco-2 cells significantly increased MCT1 promoter activity in a dose-dependent manner. These findings showing the regulation of MCT1 promoter by PKC and AP2 are of significant importance for an understanding of the molecular regulation of SCFA absorption in the human intestine.

[Effect of NF-κB activation on the radiation response of esophageal cancer cells].

PubMed

Li, Baozhong; Chen, Zhaoli; Zhou, Fang; He, Jie

2014-07-01

To investigate the effect of NF-κB activation on radiation response of esophageal carcinoma. The expression of NF-κB was detected in pretreatment and posttreatment specimens of patients with ESCC by immunohistochemistry. Electrophoretic mobility shift assay (EMSA) and Western blot were used to detect the activation of NF-κB in esophageal cancer cell line KYSE150 cells. SN50, a specific NF-κB inhibitor, was applied to inhibit the activation of NF-κB. Clone formation test was used to detect the radiosensitivity of esophageal cancer cells. The median survival time of patients with activated and inactivated NF-κB in the pretreatment specimens were 16 and 19 months, respectively, with a non-significant difference between the two groups (P > 0.05). As to the patients with activated and inactivated NF-κB in posttreatment specimens, the median survival times were 13 and 35 months, respectively, with a significant difference (P < 0.01) between them. Western blot showed that the cytoplasmic expression of NF-κB was reduced with increasing radiation dose at 1.5 and 3 hours after radiation treatment. However, the expression of NF-κB in the cell nuclei was increased under the same condition, showing a trend of increased nucleus/cytoplasm ratio. The clone number in SN50 group was 96.66, 64.66, 76.66 and 10.00 under 0, 2, 4 and 12 Gy irradiation, which demonstrated a significant difference compared with the control groups (P < 0.001). Our results show that activation of NF-κB is induced by radiotherapy. Activation of NF-κB reduces the outcome of radiation treatment of esophageal cancer patients.

Capsinoids activate brown adipose tissue (BAT) with increased energy expenditure associated with subthreshold 18-fluorine fluorodeoxyglucose uptake in BAT-positive humans confirmed by positron emission tomography scan.

PubMed

Sun, Lijuan; Camps, Stefan G; Goh, Hui Jen; Govindharajulu, Priya; Schaefferkoetter, Joshua D; Townsend, David W; Verma, Sanjay K; Velan, S Sendhil; Sun, Lei; Sze, Siu Kwan; Lim, Su Chi; Boehm, Bernhard Otto; Henry, Christiani Jeyakumar; Leow, Melvin Khee-Shing

2018-01-01

Capsinoids are reported to increase energy expenditure (EE) via brown adipose tissue (BAT) stimulation. However, imaging of BAT activation by capsinoids remains limited. Because BAT activation is a potential therapeutic strategy for obesity and related metabolic disorders, we sought to prove that capsinoid-induced BAT activation can be visualized by 18-fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). We compared capsinoids and cold exposure on BAT activation and whole-body EE. Twenty healthy participants (8 men, 12 women) with a mean age of 26 y (range: 21-35 y) and a body mass index (kg/m2) of 21.7 (range: 18.5-26.0) underwent 18F-FDG PET and whole-body calorimetry after ingestion of 12 mg capsinoids or ≤2 h of cold exposure (∼14.5°C) in a crossover design. Mean standardized uptake values (SUVs) of the region of interest and BAT volumes were calculated. Blood metabolites were measured before and 2 h after each treatment. All of the participants showed negligible 18F-FDG uptake post-capsinoid ingestion. Upon cold exposure, 12 participants showed avid 18F-FDG uptake into supraclavicular and lateral neck adipose tissues (BAT-positive group), whereas the remaining 8 participants (BAT-negative group) showed undetectable uptake. Capsinoids and cold exposure increased EE, although cold induced a 2-fold increase in whole-body EE and higher fat oxidation, insulin sensitivity, and HDL cholesterol compared with capsinoids. Capsinoids only increased EE in BAT-positive participants, which suggests that BAT mediates EE evoked by capsinoids. This implies that capsinoids stimulate BAT to a lesser degree than cold exposure as evidenced by 18F-FDG uptake below the presently accepted SUV thresholds defining BAT activation. This trial was registered at www.clinicaltrials.gov as NCT02964442. © 2018 American Society for Nutrition. All rights reserved.

Self-regulation of the anterior insula: Reinforcement learning using real-time fMRI neurofeedback.

PubMed

Lawrence, Emma J; Su, Li; Barker, Gareth J; Medford, Nick; Dalton, Jeffrey; Williams, Steve C R; Birbaumer, Niels; Veit, Ralf; Ranganatha, Sitaram; Bodurka, Jerzy; Brammer, Michael; Giampietro, Vincent; David, Anthony S

2014-03-01

The anterior insula (AI) plays a key role in affective processing, and insular dysfunction has been noted in several clinical conditions. Real-time functional MRI neurofeedback (rtfMRI-NF) provides a means of helping people learn to self-regulate activation in this brain region. Using the Blood Oxygenated Level Dependant (BOLD) signal from the right AI (RAI) as neurofeedback, we trained participants to increase RAI activation. In contrast, another group of participants was shown 'control' feedback from another brain area. Pre- and post-training affective probes were shown, with subjective ratings and skin conductance response (SCR) measured. We also investigated a reward-related reinforcement learning model of rtfMRI-NF. In contrast to the controls, we hypothesised a positive linear increase in RAI activation in participants shown feedback from this region, alongside increases in valence ratings and SCR to affective probes. Hypothesis-driven analyses showed a significant interaction between the RAI/control neurofeedback groups and the effect of self-regulation. Whole-brain analyses revealed a significant linear increase in RAI activation across four training runs in the group who received feedback from RAI. Increased activation was also observed in the caudate body and thalamus, likely representing feedback-related learning. No positive linear trend was observed in the RAI in the group receiving control feedback, suggesting that these data are not a general effect of cognitive strategy or control feedback. The control group did, however, show diffuse activation across the putamen, caudate and posterior insula which may indicate the representation of false feedback. No significant training-related behavioural differences were observed for valence ratings, or SCR. In addition, correlational analyses based on a reinforcement learning model showed that the dorsal anterior cingulate cortex underpinned learning in both groups. In summary, these data demonstrate that it is possible to regulate the RAI using rtfMRI-NF within one scanning session, and that such reward-related learning is mediated by the dorsal anterior cingulate. Copyright © 2013 Elsevier Inc. All rights reserved.

Wheat-water chestnut flour blends: effect of baking on antioxidant properties of cookies.

PubMed

Shafi, Musarat; Baba, Waqas N; Masoodi, Farooq Ahmad; Bazaz, Rafiya

2016-12-01

Proximate composition, mineral content, functional, pasting and antioxidant properties of water chestnut flour (WCF) were compared with refined wheat flour. WCF showed higher phenolic (4.25 gGAE/1000 g), flavonoid (1.92 g QE/1000 g) and mineral content (K, Mg, Zn, Cu) than wheat flour. WCF showed greater retrogradation tendency but lower peak viscosity than wheat flour. Wheat flour - WCF blends and cookies were evaluated for water activity, physical & textural properties. Water activity of cookies decreased significantly (0.415-0.311) with increase in level of WCF in wheat flour. Total phenolic content, flavonoid content and antioxidant activity (DPPH• scavenging capacity, FRAP) of WCF - wheat flour blends as well as their cookies was also determined. Baking led to a greater increase in DPPH• scavenging capacity of WCF cookies (33.8%) than WF cookies (25%). Baking had a similar effect on FRAP value. Wheat flour cookies showed a decrease of 51%, and 62% while WCF cookies showed a decrease of 36%, and 34% in TPC and TFC values respectively. WCF cookies thus showed better retention of antioxidant activities suggesting greater stability of WC phenolics than wheat phenolics. Sensory analysis showed cookies made from water chestnut (100%) had fair acceptability due to their characteristic flavor. Thus, water chestnut flour serves both as a gluten free as well as antioxidant rich flour for production of cookies.

Intra-Amygdala Muscimol Injections Impair Freezing and Place Avoidance in Aversive Contextual Conditioning

ERIC Educational Resources Information Center

Holahan, Matthew R.; White, Norman M.

2004-01-01

Rats were trained by shocking them in a closed compartment. When subsequently tested in the same closed compartment with no shock, normal rats showed an increased tendency to freeze. They also showed an increased tendency to actively avoid the compartment when given access to an adjacent neutral compartment for the first time. Amygdala…

Trichoderma harzianum containing 1-aminocyclopropane-1-carboxylate deaminase and chitinase improved growth and diminished adverse effect caused by Fusarium oxysporum in soybean.

PubMed

Zhang, Fuli; Chen, Can; Zhang, Fan; Gao, Lidong; Liu, Jidong; Chen, Long; Fan, Xiaoning; Liu, Chang; Zhang, Ke; He, Yuting; Chen, Chen; Ji, Xiue

2017-03-01

An isolate, named Trichoderma harzianum T-soybean, showed growth-promoting for soybean seedlings and induced resistance to Fusarium oxysporum under greenhouse. Compared to control soybean seedlings, fresh weight, dry weight, lateral root number, chlorophyll content, root activity and soluble protein of plants pretreated with T-soybean increased, but initial pod height reduced. Furthermore, we found that T-soybean inhibited the growth of F. oxysporum by parasitic function. In addition, plate test results showed that culture filtrates of T-soybean also inhibited significantly F. oxysporum growth. Meanwhile, T-soybean treatment obviously reduced disease severity and induced quickly the H 2 O 2 and O 2 - burst as well as pathogenesis related protein gene (PR3) expression after F. oxysporum inoculation, and subsequently diminished the cell damage in soybean caused by the pathogen challenge. Reactive oxygen species (ROS) scavenging enzymes activity analysis showed that the activities of peroxidase (POD), polyphenol oxidase (PPO) and superoxide dismutase (SOD) increased significantly in T-soybean pretreated plants. These results suggested that T-soybean treatment induced resistance in soybean seedlings to F. oxysporum by companying the production of ROS and the increasing of ROS scavenging enzymes activity as well as PR3 expression. Copyright © 2016 Elsevier GmbH. All rights reserved.

Increased SBPase activity improves photosynthesis and grain yield in wheat grown in greenhouse conditions.

PubMed

Driever, Steven M; Simkin, Andrew J; Alotaibi, Saqer; Fisk, Stuart J; Madgwick, Pippa J; Sparks, Caroline A; Jones, Huw D; Lawson, Tracy; Parry, Martin A J; Raines, Christine A

2017-09-26

To meet the growing demand for food, substantial improvements in yields are needed. This is particularly the case for wheat, where global yield has stagnated in recent years. Increasing photosynthesis has been identified as a primary target to achieve yield improvements. To increase leaf photosynthesis in wheat, the level of the Calvin-Benson cycle enzyme sedoheptulose-1,7-biphosphatase (SBPase) has been increased through transformation and expression of a Brachypodium distachyon SBPase gene construct. Transgenic lines with increased SBPase protein levels and activity were grown under greenhouse conditions and showed enhanced leaf photosynthesis and increased total biomass and dry seed yield. This showed the potential of improving yield potential by increasing leaf photosynthesis in a crop species such as wheat. The results are discussed with regard to future strategies for further improvement of photosynthesis in wheat.This article is part of the themed issue 'Enhancing photosynthesis in crop plants: targets for improvement'. © 2017 The Authors.

A novel cold-adapted esterase from Enterobacter cloacae: Characterization and improvement of its activity and thermostability via the site of Tyr193Cys.

PubMed

Gao, Haofeng; Li, Chanjuan; Bandikari, Ramesh; Liu, Ziduo; Hu, Nan; Yong, Qiang

2018-03-19

In industries lipolytic reactions occur in insensitive conditions such as high temperature thus novel stout esterases with unique properties are attracts to the industrial application. Protein engineering is the tool to obtain desirable characters of enzymes. A novel esterase gene was isolated from South China Sea and subjected to a random mutagenesis and site directed mutagenesis for higher activity and thermo-stability compared to wild type. A novel esterase showed the highest hydrolytic activity against p-nitrophenyl acetate (pNPA, C2) and the optimal activity at 40 °C and pH 8.5. It was a cold-adapted enzyme and retained approximately 40% of its maximum activity at 0 °C. A mutant, with higher activity and thermo-stability was obtained by random mutagenesis. Kinetic analysis indicated that the mutant Val29Ala/Tyr193Cys shown 43.5% decrease in K m , 2.6-fold increase in K cat , and 4.7-fold increase in K cat /K m relative to the wild type. Single mutants V29A and Y193C were constructed and their kinetic parameters were measured. The results showed that the values of K m , K cat , and K cat /K m of V29A were similar to those of the wild type while Y193C showed 52.7% decrease in K m , 2.7-fold increase in K cat , and 5.6-fold increase in K cat /K m compared with the wild type. The 3-D structure and docking analysis revealed that the replacement of Tyr by Cys could enlarge the binding pocket. Moreover Y193C also showed a better thermo-stability for the reason its higher hydrophobicity and retained 67% relative activity after incubation for 3 h at 50 °C. The superior quality of modified esterase suggested it has great potential application in extreme conditions and the mutational work recommended that important information for the study of esterase structure and function.

Fluid shear stress enhances the cell volume decrease of osteoblast cells by increasing the expression of the ClC-3 chloride channel

PubMed Central

LIU, LI; CAI, SIYI; QIU, GUIXING; LIN, JIN

2016-01-01

ClC-3 is a volume-sensitive chloride channel that is responsible for cell volume adjustment and regulatory cell volume decrease (RVD). In order to evaluate the effects of fluid shear stress (FSS) stimulation on the osteoblast ClC-3 chloride channel, MC3T3-E1 cells were stimulated by FSS in the experimental group. Fluorescence quantitative polymerase chain reaction was used to detect changes in ClC-3 mRNA expression, the chloride ion fluorescent probe N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) was used to detect the chloride channel activity, and whole-cell patch clamping was used to monitor the changes in the volume-sensitive chloride current activated by a hypotonic environment following mechanical stimulation. The results show that the expression of the osteoblast chloride channel ClC-3 was significantly higher in the FSS group compared with the control group. MQAE fluorescence intensity was significantly reduced in the FSS group compared to the control group, suggesting that mechanical stimulation increased chloride channel activity and increased the efflux of intracellular chloride ions. Image analysis of osteoblast volume changes showed that osteoblast RVD was enhanced by mechanical stimulation. Whole-cell patch clamping showed that the osteoblast volume-sensitive chloride current was larger in the stimulated group compared to the control group, suggesting that elevated ClC-3 chloride channel expression results in an increased volume-sensitive chloride current. In conclusion, FSS stimulation enhances the RVD of osteoblast cell by increasing the expression of the ClC-3 and enhancing the chloride channel activity. PMID:27073622

Zinc triggers microglial activation

PubMed Central

Kauppinen, Tiina M.; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A.

2009-01-01

Microglia are resident immune cells of the central nervous system. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, “amoeboid” morphology and release matrix metalloproteinases, reactive oxygen species, and other pro-inflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here we show that zinc directly triggers microglial activation. Microglia transfected with an NF-kB reporter gene showed a several-fold increase in NF-kB activity in response to 30 μM zinc. Cultured mouse microglia exposed to 15 – 30 μM zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-κB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-κB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders. PMID:18509044

Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK.

PubMed

Park, Sung-Jun; Ahmad, Faiyaz; Um, Jee-Hyun; Brown, Alexandra L; Xu, Xihui; Kang, Hyeog; Ke, Hengming; Feng, Xuesong; Ryall, James; Philp, Andrew; Schenk, Simon; Kim, Myung K; Sartorelli, Vittorio; Chung, Jay H

2017-04-01

The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK), an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE) in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1. Published by Elsevier B.V.

The influence of primary health care professionals in encouraging exercise and physical activity uptake among White and South Asian older adults: experiences of young older adults.

PubMed

Horne, Maria; Skelton, Dawn; Speed, Shaun; Todd, Chris

2010-01-01

To explore the influence of primary health care professionals in increasing exercise and physical activity among 60-70-year-old White and South Asian community dwellers. Fifteen focus groups and 40 in-depth interviews with community dwelling White and South Asian 60-70-year olds. The sample was selected to include people with very different experiences of participation and non-participation in exercise and physical activity. Data were analysed using framework analysis. Primary health care professionals' advice and support was found to be a motivator to the initiation of exercise and physical activity. However, this was usually in relation to advice on weight reduction, cardiac conditions and mobility issues, but not generally to improve or increase activity levels. An underlying attitude of genuine interest and empathy was valued and shaped decisions about initiating and/or increasing activity levels. Primary health care professionals should be encouraged to show interest and empathy with older people about the positive benefits of exercise and physical activity to them individually. This advice needs to be tailored to the older adult's symptoms. Primary health care professionals need to be able to provide specific advice as to the quantity (frequency, duration, intensity and type) of exercise or physical activity to undertake. Practitioners need to listen to their patients' needs, show empathy and avoid ageism during consultations.

Antiatherogenic effect of quercetin is mediated by proteasome inhibition in the aorta and circulating leukocytes.

PubMed

Pashevin, Denis A; Tumanovska, Lesya V; Dosenko, Victor E; Nagibin, Vasyl S; Gurianova, Veronika L; Moibenko, Alexey A

2011-01-01

Quercetin, a plant-derived flavonoid, has attracted considerable attention as promising compound for heart disease prevention and therapy. It has been linked to decreased mortality from heart disease and decreased incidence of stroke. Here, we report new data showing the angioprotective properties of quercetin mediated by its effect on proteasomal proteolysis. This study was designed to investigate the ability of quercetin to modulate proteasomal activity in a rabbit model of cholesterol-induced atherosclerosis. First, we show proteasomal trypsin-like (TL) activity increased up to 2.4-fold, chymotrypsin-like (CTL) activity increased by up to 43% and peptidyl-glutamyl peptide-hydrolyzing (PGPH) activity increased by up to 10% after 8 weeks of a cholesterol-rich diet. A single intravenous injection of the water-soluble form of quercetin (Corvitin) significantly decreased proteasomal TL activity 1.85-fold in monocytes, and decreased the CTL and PGPH activities more than 2-fold in polymorphonuclear leukocytes (PMNL) after 2 h. Prolonged administration (1 month) of Corvitin to animals following a cholesterol-rich diet significantly decreased all types of proteolytic proteasome activities both in tissues and in circulating leukocytes and was associated with the reduction of atherosclerotic lesion areas in the aorta. Additionally, the pharmacological form of quercetin (Quertin) was shown to have an antiatherogenic effect and an ability to inhibit proteasome activities.

Transient and sustained neural responses to death-related linguistic cues

PubMed Central

Shi, Zhenhao

2013-01-01

Recent research showed that perception of death-related vs death-unrelated linguistic cues produced increased frontoparietal activity but decreased insular activity. This study investigated (i) whether the increased frontoparietal and decreased insular activities are, respectively, associated with transient trial-specific processes of death-related linguistic cues and sustained death-related thought during death-relevance judgments on linguistic cues and (ii) whether the neural activity underlying death-related thought can predict individuals’ dispositional death anxiety. Participants were presented with death-related/unrelated words, life-related/unrelated words, and negative-valence/neutral words in separate sessions. Participants were scanned using functional magnetic resonance imaging while performing death-relevance, life-relevance, and valence judgments on the words, respectively. The contrast of death-related vs death-unrelated words during death-relevance judgments revealed transient increased activity in the left inferior parietal lobule, the right frontal eye field, and the right superior parietal lobule. The contrast of death-relevance judgments vs life-relevance/valence judgments showed decreased activity in the bilateral insula. The sustained insular activity was correlated with dispositional death anxiety, but only in those with weak transient frontoparietal responses to death-related words. Our results dissociate the transient and sustained neural responses to death-related linguistic cues and suggest that the combination of the transient and sustained neural activities can predict dispositional death anxiety. PMID:22422804

Quality Characteristics and Antioxidant Activity of Yogurt Supplemented with Aronia (Aronia melanocarpa) Juice.

PubMed

Nguyen, Linh; Hwang, Eun-Sun

2016-12-01

We investigated the quality characteristics and antioxidant activities of yogurt supplemented with 1%, 2%, and 3% aronia juice and fermented for 24 h at 37°C. The total acidity increased with increasing levels of aronia juice and incubation time. Lightness and yellowness of the yogurt decreased, but redness increased, with increasing aronia juice content and incubation time. The number of lactic acid bacteria (LAB) increased with increased incubation time, and yogurt containing 2% and 3% aronia juice showed higher LAB counts than 1% aroinia juice-supplemented yogurt. The total polyphenol and flavonoid contents increased proportionally with increasing levels of aronia juice. Antioxidant activity of aronia-containing yogurt was significantly higher than that of the control and increased proportionally with aronia juice concentration. Yogurt with 2% aronia juice had the best taste ( P <0.05). Aronia juice may be a useful additive for improving the taste and antioxidant potential of yogurt.

Quality Characteristics and Antioxidant Activity of Yogurt Supplemented with Aronia (Aronia melanocarpa) Juice

PubMed Central

Nguyen, Linh; Hwang, Eun-Sun

2016-01-01

We investigated the quality characteristics and antioxidant activities of yogurt supplemented with 1%, 2%, and 3% aronia juice and fermented for 24 h at 37°C. The total acidity increased with increasing levels of aronia juice and incubation time. Lightness and yellowness of the yogurt decreased, but redness increased, with increasing aronia juice content and incubation time. The number of lactic acid bacteria (LAB) increased with increased incubation time, and yogurt containing 2% and 3% aronia juice showed higher LAB counts than 1% aroinia juice-supplemented yogurt. The total polyphenol and flavonoid contents increased proportionally with increasing levels of aronia juice. Antioxidant activity of aronia-containing yogurt was significantly higher than that of the control and increased proportionally with aronia juice concentration. Yogurt with 2% aronia juice had the best taste (P<0.05). Aronia juice may be a useful additive for improving the taste and antioxidant potential of yogurt. PMID:28078255

A case of red-cell adenosine deaminase overproduction associated with hereditary hemolytic anemia found in Japan.

PubMed

Miwa, S; Fujii, H; Matsumoto, N; Nakatsuji, T; Oda, S; Asano, H; Asano, S

1978-01-01

A case of red cell adenosine deaminase (ADA) overproduction associated with hereditary hemolytic anemia is reported here. This appears to be the second report. Proband is a 38-year-old Japanese male who had hemoglobin, 15.8 g/100 ml; reticulocyte count, 4.5%; serum indirect bilirubin, 4.9 mg/100 ml; 51Cr-labeled red cell half-life, 12 days; red cells showed moderate stomatocytosis. His red cell ADA activity showed 40-fold increase while that of the mother showed 4-fold increase. The mother was hematologically normal. The father had a normal enzyme activity. The proband and the mother showed slightly high serum uric acid levels. The proband's red cell showed: ATP, 628 nmoles/ml (normal, 1,010--1,550); adenine nucleotide pool, 46% of the normal mean; 2,3-diphosphoglycerate content, 3,782 nmoles/ml (normal 4,170--5,300); increased oxygen affinity of hemoglobin, P50 of intact erythrocytes being 21.8 mmHg (normal, 24.1--26.1). Red cell glycolytic intermediates in the proband were low in general, and the rate of lactate production was low. Kinetic studies using crude hemolysate revealed a normal Km for adenosine, normal electrophoretic mobility but slightly abnormal pH curve and slightly low utilization of 2-deoxyadenosine. The ADA activity of lymphocytes was nearly normal.

Phasin Proteins Activate Aeromonas caviae Polyhydroxyalkanoate (PHA) Synthase but Not Ralstonia eutropha PHA Synthase

PubMed Central

Ushimaru, Kazunori; Motoda, Yoko; Numata, Keiji

2014-01-01

In this study, we performed in vitro and in vivo activity assays of polyhydroxyalkanoate (PHA) synthases (PhaCs) in the presence of phasin proteins (PhaPs), which revealed that PhaPs are activators of PhaC derived from Aeromonas caviae (PhaCAc). In in vitro assays, among the three PhaCs tested, PhaCAc was significantly activated when PhaPs were added at the beginning of polymerization (prepolymerization PhaCAc), whereas the prepolymerization PhaCRe (derived from Ralstonia eutropha) and PhaCDa (Delftia acidovorans) showed reduced activity with PhaPs. The PhaP-activated PhaCAc showed a slight shift of substrate preference toward 3-hydroxyhexanoyl-CoA (C6). PhaPAc also activated PhaCAc when it was added during polymerization (polymer-elongating PhaCAc), while this effect was not observed for PhaCRe. In an in vivo assay using Escherichia coli TOP10 as the host strain, the effect of PhaPAc expression on PHA synthesis by PhaCAc or PhaCRe was examined. As PhaPAc expression increased, PHA production was increased by up to 2.3-fold in the PhaCAc-expressing strain, whereas it was slightly increased in the PhaCRe-expressing strain. Taken together, this study provides evidence that PhaPs function as activators for PhaCAc both in vitro and in vivo but do not activate PhaCRe. This activating effect may be attributed to the new role of PhaPs in the polymerization reaction by PhaCAc. PMID:24584238

Characteristics and in vitro Anti-diabetic Properties of the Korean Rice Wine, Makgeolli Fermented with Laminaria japonica.

PubMed

Choi, Jae-Suk; Seo, Hyo Ju; Lee, Yu-Ri; Kwon, Su-Jung; Moon, Sun Hwa; Park, Sun-Mee; Sohn, Jae Hak

2014-06-01

New in vitro anti-diabetes makgeolli was produced from rice by adding various quantities of Laminaria japonica, and the fermentation characteristics of the L. japonica makgeolli during the fermentation process were investigated. The contents of alcohol and reducing sugar, and viable count of yeast, of L. japonica makgeolli were not significantly changed when the proportion of L. japonica was increased. The total acid content decreased with an increase in L. japonica concentration; the pH and total bacterial cell count increased in proportion with the increase in L. japonica concentration. The L. japonica makgeolli contents of free sugars, such as fructose, glucose, and sucrose, and of organic acids, such as acetic acid, citric acid, succinic acid, and lactic acid, were altered during fermentation and showed various patterns. The effects of the quantity of L. japonica added on the acceptability and anti-diabetes activities of L. japonica makgeolli were also investigated. In a sensory evaluation, L. japonica makgeolli brewed by adding 2.5 or 5% L. japonica to the mash showed the best overall acceptability; the 12.5% L. japonica sample was least favored due to its seaweed flavor. L. japonica addition did not increase the peroxynitrite-scavenging activity of makgeolli. L. japonica makgeolli showed potent anti-diabetes activity, particularly that containing >7.5% L. japonica. Therefore, L. japonica makgeolli may represent a new functional makgeolli with anti-diabetes properties.

Dynamic neural activity during stress signals resilient coping

PubMed Central

Sinha, Rajita; Lacadie, Cheryl M.; Constable, R. Todd; Seo, Dongju

2016-01-01

Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping. PMID:27432990

Investigating the effect of gallium curcumin and gallium diacetylcurcumin complexes on the structure, function and oxidative stability of the peroxidase enzyme and their anticancer and antibacterial activities.

PubMed

Jahangoshaei, Parisa; Hassani, Leila; Mohammadi, Fakhrossadat; Hamidi, Akram; Mohammadi, Khosro

2015-10-01

Curcumin has a wide spectrum of biological and pharmacological activities including anti-inflammatory, antioxidant, antiproliferative, antimicrobial and anticancer activities. Complexation of curcumin with metals has gained attention in recent years for improvement of its stability. In this study, the effect of gallium curcumin and gallium diacetylcurcumin on the structure, function and oxidative stability of horseradish peroxidase (HRP) enzyme were evaluated by spectroscopic techniques. In addition to the enzymatic investigation, the cytotoxic effect of the complexes was assessed on bladder, MCF-7 breast cancer and LNCaP prostate carcinoma cell lines by MTT assay. Furthermore, antibacterial activity of the complexes against S. aureus and E. coli was explored by dilution test method. The results showed that the complexes improve activity of HRP and also increase its tolerance against the oxidative condition. After addition of the complexes, affinity of HRP for hydrogen peroxide substrate decreases, while the affinity increases for phenol substrate. Circular dichroism, intrinsic and synchronous fluorescence spectra showed that the enzyme structure around the catalytic heme group becomes less compact and also the distance between the heme group and tryptophan residues increases due to binding of the complexes to HRP. On the whole, it can be concluded that the change in the enzyme structure upon binding to the gallium curcumin and gallium diacetylcurcumin complexes results in an increase in the antioxidant efficiency and activity of the peroxidise enzyme. The result of anticancer and antibacterial activities suggested that the complexes exhibit the potential for cancer treatment, but they have no significant antibacterial activity.

Macropinocytosis of the PDGF β-receptor promotes fibroblast transformation by H-RasG12V

PubMed Central

Schmees, C.; Villaseñor, R.; Zheng, W.; Ma, H.; Zerial, M.; Heldin, C.-H.; Hellberg, C.

2012-01-01

Receptor tyrosine kinase (RTK) signaling is frequently increased in tumor cells, sometimes as a result of decreased receptor down-regulation. The extent to which the endocytic trafficking routes can contribute to such RTK hyperactivation is unclear. Here, we show for the first time that fibroblast transformation by H-RasG12V induces the internalization of platelet-derived growth factor β-receptor (PDGFRβ) by macropinocytosis, enhancing its signaling activity and increasing anchorage-independent proliferation. H-RasG12V transformation and PDGFRβ activation were synergistic in stimulating phosphatidylinositol (PI) 3-kinase activity, leading to receptor macropinocytosis. PDGFRβ macropinocytosis was both necessary and sufficient for enhanced receptor activation. Blocking macropinocytosis by inhibition of PI 3-kinase prevented the increase in receptor activity in transformed cells. Conversely, increasing macropinocytosis by Rabankyrin-5 overexpression was sufficient to enhance PDGFRβ activation in nontransformed cells. Simultaneous stimulation with PDGF-BB and epidermal growth factor promoted macropinocytosis of both receptors and increased their activation in nontransformed cells. We propose that H-Ras transformation promotes tumor progression by enhancing growth factor receptor signaling as a result of increased receptor macropinocytosis. PMID:22573884

Cytochrome P450 Bioconjugate as a Nanovehicle for Improved Chemotherapy Treatment.

PubMed

Quester, Katrin; Juarez-Moreno, Karla; Secundino, Isamel; Roseinstein, Yvonne; Alejo, Karla P; Huerta-Saquero, Alejandro; Vazquez-Duhalt, Rafael

2017-05-01

Cancer is still a growing public health problem, especially breast cancer that is one of the most important cancers in women. Chemotherapy, even though a successful treatment, is accompanied by severe side effects. Moreover, most of the drugs used for chemotherapy are administered as prodrugs and need to be transformed to the active form by cytochromes P450 (CYPs). In addition, increasing numbers of cancer tissues show lower CYP activity than the surrounding healthy tissues in which prodrugs are preferentially activated causing cytotoxicity. Here, the design of a functionalized cytochrome P450 bioconjugate is reported as nanovehicle for the enzyme direct delivery to the tumor tissue in order to improve the local drug activation. MCF-7 breast cancer cells are treated with CYP-polyethylene glycol bioconjugate functionalized folic acid, where it activates the prodrug tamoxifen and significantly reduces the dose of tamoxifen needed to kill the tumor cells. The CYP bioconjugate covered with polyethylene glycol shows no immunogenic activity. The advantages of increasing the site-specific CYP activity in tumor tissues are discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats.

PubMed

Luine, V N

1985-08-01

Administration of estradiol to gonadectomized female, but not male rats, is associated with increased activity of choline acetyltransferase in the medial aspect of the horizontal diagonal band nucleus, the frontal cortex, and CA1 of the dorsal hippocampus. Four other basal forebrain cholinergic nuclei did not show changes in choline acetyltransferase activity after estradiol. These data have implications for possible benefits of estradiol administration to patients with senile dementia of the Alzheimer's type.

Effect of various factors on the activity of trehalase from the larvae of Sesamia inferens Walker (Insect).

PubMed

Agarwal, A K

1976-12-15

Trehalase from the salivary glands and the midgut of Sesamia inferens showed optimum activity at pH 5.8, and at temperatures of 50 and 60 degrees C respectively. The increase in the incubation period, enzyme concentration, and substrate concentration respectively increased the end-product, the hydrolysis, and the rate of hydrolysis of the substrate. Dialysis did not affect, tryptophan accelerated, and other amino acids and end-product inhibited the enzyme activity.

Mechanism of the melanogenesis stimulation activity of (-)-cubebin in murine B16 melanoma cells.

PubMed

Hirata, Noriko; Naruto, Shunsuke; Ohguchi, Kenji; Akao, Yukihiro; Nozawa, Yoshinori; Iinuma, Munekazu; Matsuda, Hideaki

2007-07-15

(-)-Cubebin showed a melanogenesis stimulation activity in a concentration-dependent manner in murine B16 melanoma cells without any significant effects on cell proliferation. Tyrosinase activity was increased at 24-72 h after addition of cubebin to B16 cells, and then intracellular melanin amount was increased at 48-96 h after the treatment. The expression levels of tyrosinase were time-dependently enhanced after the treatment with cubebin. At the same time, the expression levels of tyrosinase mRNA were also increased after addition of cubebin. Furthermore Western blot analysis revealed that cubebin elevated the level of phosphorylation of p38 mitogen-activated protein kinase (MAPK). SB203580, a selective inhibitor of p38 MAPK, completely blocked cubebin-induced expression of tyrosinase mRNA in B16 cells. These results suggested that cubebin increased melanogenesis in B16 cells through the enhancement of tyrosinase expression mediated by activation of p38 MAPK.

A Conceptual Framework for Organizing Active Learning Experiences in Biology Instruction

ERIC Educational Resources Information Center

Gardner, Joel; Belland, Brian R.

2012-01-01

Introductory biology courses form a cornerstone of undergraduate instruction. However, the predominantly used lecture approach fails to produce higher-order biology learning. Research shows that active learning strategies can increase student learning, yet few biology instructors use all identified active learning strategies. In this paper, we…

Characterizing Interactive Engagement Activities in a Flipped Introductory Physics Class

ERIC Educational Resources Information Center

Wood, Anna K.; Galloway, Ross K.; Donnelly, Robyn; Hardy, Judy

2016-01-01

Interactive engagement activities are increasingly common in undergraduate physics teaching. As research efforts move beyond simply showing that interactive engagement pedagogies work towards developing an understanding of "how" they lead to improved learning outcomes, a detailed analysis of the way in which these activities are used in…

Design and introduction of a disulfide bridge in firefly luciferase: increase of thermostability and decrease of pH sensitivity.

PubMed

Imani, Mehdi; Hosseinkhani, Saman; Ahmadian, Shahin; Nazari, Mahboobeh

2010-08-01

The thermal sensitivity and pH-sensitive spectral properties of firefly luciferase have hampered its application in a variety of fields. It is proposed that the stability of a protein can be increased by introduction of disulfide bridge that decreases the configurational entropy of unfolding. A disulfide bridge is introduced into Photinus pyralis firefly luciferase to make two separate mutant enzymes with a single bridge. Even though the A103C/S121C mutant showed remarkable thermal stability, its specific activity decreased, whereas the A296C/A326C mutant showed tremendous thermal stability, relative pH insensitivity and 7.3-fold increase of specific activity. Moreover, the bioluminescence emission spectrum of A296C/A326C was resistant against higher temperatures (37 degrees C). Far-UV CD analysis showed slight secondary structure changes for both mutants. Thermal denaturation analysis showed that conformational stabilities of A103C/S121C and A296C/A326C are more than native firefly luciferase. It is proposed that since A296 and A326 are situated in the vicinity of the enzyme active site microenvironment in comparison with A103 and S121, the formation of a disulfide bridge in this region has more impact on enzyme kinetic characteristics.

Increased Sleep Promotes Survival during a Bacterial Infection in Drosophila

PubMed Central

Kuo, Tzu-Hsing; Williams, Julie A.

2014-01-01

Study Objectives: The relationship between sleep and immune function is not well understood at a functional or molecular level. We therefore used a genetic approach in Drosophila to manipulate sleep and evaluated effects on the ability of flies to fight bacterial infection. Setting: Laboratory. Participants: Drosophila melanogaster. Methods and Results: We used a genetic approach to transiently alter neuronal excitability in the mushroom body, a region in the central brain that is known to regulate sleep. Flies with increased sleep for up to two days prior to a bacterial infection showed increased resistance to the infection and improved survival. These flies also had increased expression levels of a subset of anti-microbial peptide mRNA prior to infection, as well as increased NFκB activity during infection as indicated by in vivo luciferase reporter activity. In contrast, flies that experienced reduced sleep for up to two days prior to infection had no effect on survival or on NFκB activity during infection. However, flies with reduced sleep showed an altered defense mechanism, such that resistance to infection was increased, but at the expense of reduced tolerance. This effect was dependent on environmental condition. Conclusions: Increasing sleep enhanced activity of an NFκB transcription factor, increased resistance to infection, and strongly promoted survival. Together, these findings support the hypothesis that sleep is beneficial to the host by maintaining a robust immune system. Citation: Kuo TH, Williams JA. Increased sleep promotes survival during a bacterial infection in Drosophila. SLEEP 2014;37(6):1077-1086. PMID:24882902

Negative differential mobility and trapping in active matter systems

NASA Astrophysics Data System (ADS)

Reichhardt, C.; Reichhardt, C. J. O.

2018-01-01

Using simulations, we examine the average velocity as a function of applied drift force for active matter particles moving through a random obstacle array. We find that for low drift force, there is an initial flow regime where the mobility increases linearly with drive, while for higher drift forces a regime of negative differential mobility appears in which the velocity decreases with increasing drive due to the trapping of active particles behind obstacles. A fully clogged regime exists at very high drift forces when all the particles are permanently trapped behind obstacles. We find for increasing activity that the overall mobility is nonmonotonic, with an enhancement of the mobility for small levels of activity and a decrease in mobility for large activity levels. We show how these effects evolve as a function of disk and obstacle density, active run length, drift force, and motor force.

H+ -pyrophosphatase IbVP1 promotes efficient iron use in sweet potato [Ipomoea batatas (L.) Lam.].

PubMed

Fan, Weijuan; Wang, Hongxia; Wu, Yinliang; Yang, Nan; Yang, Jun; Zhang, Peng

2017-06-01

Iron (Fe) deficiency is one of the most common micronutrient deficiencies limiting crop production globally, especially in arid regions because of decreased availability of iron in alkaline soils. Sweet potato [Ipomoea batatas (L.) Lam.] grows well in arid regions and is tolerant to Fe deficiency. Here, we report that the transcription of type I H + -pyrophosphatase (H + -PPase) gene IbVP1 in sweet potato plants was strongly induced by Fe deficiency and auxin in hydroponics, improving Fe acquisition via increased rhizosphere acidification and auxin regulation. When overexpressed, transgenic plants show higher pyrophosphate hydrolysis and plasma membrane H + -ATPase activity compared with the wild type, leading to increased rhizosphere acidification. The IbVP1-overexpressing plants showed better growth, including enlarged root systems, under Fe-sufficient or Fe-deficient conditions. Increased ferric precipitation and ferric chelate reductase activity in the roots of transgenic lines indicate improved iron uptake, which is also confirmed by increased Fe content and up-regulation of Fe uptake genes, e.g. FRO2, IRT1 and FIT. Carbohydrate metabolism is significantly affected in the transgenic lines, showing increased sugar and starch content associated with the increased expression of AGPase and SUT1 genes and the decrease in β-amylase gene expression. Improved antioxidant capacities were also detected in the transgenic plants, which showed reduced H 2 O 2 accumulation associated with up-regulated ROS-scavenging activity. Therefore, H + -PPase plays a key role in the response to Fe deficiency by sweet potato and effectively improves the Fe acquisition by overexpressing IbVP1 in crops cultivated in micronutrient-deficient soils. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Oxidative stress responses of juvenile tambaqui Colossoma macropomum after short-term anesthesia with benzocaine and MS-222.

PubMed

Stringhetta, Giovanna R; Barbas, Luis A L; Maltez, Lucas C; Sampaio, Luís A; Monserrat, José M; Garcia, Luciano O

2017-01-01

The present study aimed to evaluate the effects of benzocaine and tricaine methanesulfonate on oxidative stress parameters of juvenile tambaqui tissues. Fish (n=80) were anesthetized with benzocaine (100 mg L-1) or tricaine (240 mg L-1) and two control groups were used (non-anesthetized fish and fish exposed to ethanol-only). After anesthetic induction 10 fish/anesthetic were euthanized after 3, 12 and 24 hours post-anesthesia and tissue samplings (gills, liver and brain) were performed. Samples were submitted to analyses of enzyme activity glutathione-S-transferase (GST), cellular lipid peroxidation (TBARS) and total antioxidant capacity (ACAP). ACAP increased in gills of benzocaine treatment after 12 hours. The liver showed a reduction in ACAP of tricaine treatment after 12 hours. Both anesthetic treatments showed an increase of ACAP at 24 hours compared to control group. The activity of the GST enzyme increased in the gills for treatments benzocaine and tricaine after 3 and 12 hours. Liver showed increased GST activity (benzocaine after 24 hours and tricaine after 3 and 24 hours). Lipid damage decreased in gills (both anesthetics) and brain (tricaine) after 24 hours. The results demonstrate that benzocaine and tricaine did not cause oxidative damage in juvenile tambaqui under the experimental conditions herein established.

Extraction of nobiletin from Citrus Unshiu peels by supercritical fluid and its CRE-mediated transcriptional activity.

PubMed

Oba, Chisato; Ota, Masaki; Nomura, Koichiro; Fujiwara, Hironori; Takito, Jiro; Sato, Yoshiyuki; Ohizumi, Yasushi; Inomata, Hiroshi

2017-04-15

Polymethoxyflavone (PMF) is one of bioactive compounds in Citrus Unshiu and included mainly in the peels rather than the fruits, seeds and leaves. Supercritical CO 2 extraction is one candidate for selective extraction of polymethoxyflavone and in this study, supercritical CO 2 extraction with/without ethanol entrainer from Citrus Unshiu peels was examined at a temperature of 333K and a pressure of 30MPa. CRE (cyclic AMP response element)-mediated transcriptional assay was examined by using the extracts from supercritical fluid extraction. The results showed that extracts including nobiletin increased with increasing ethanol concentration in supercritical CO 2 and the elapsed extraction time. Extracts at ethanol concentration of 5 mol% showed high CRE-mediated transcription activity. This can be caused by activity of the extract including nobiletin in addition to the other methoxylated flavonoid species such as tangeretin. Extracts at ethanol concentration of 50% showed the highest CRE-mediated transcription activity, which can be attributed to flavonoid glycoside such as hesperidin. From our investigations, flavonoid glycoside can be one of promoters of CRE-mediated transcription activity. Copyright © 2017 Elsevier GmbH. All rights reserved.

Loss of calreticulin function decreases NFκB activity by stabilizing IκB protein.

PubMed

Massaeli, Hamid; Jalali, Shahrzad; Viswanathan, Divya; Mesaeli, Nasrin

2014-11-01

Transcription factor NFκB is activated by several processes including inflammation, endoplasmic-reticulum (ER) stress, increase in Akt signaling and enhanced proteasomal degradation. Calreticulin (CRT) is an ER Ca(2+)-binding chaperone that regulates many cellular processes. Gene-targeted deletion of CRT has been shown to induce ER stress that is accompanied with a significant increase in the proteasome activity. Loss of CRT function increases the resistance of CRT-deficient (crt-/-) cells to UV- and drug-induced apoptosis. Based on these reports we hypothesized that loss of CRT will activate NFκB signaling thus contributing to enhanced resistance to apoptosis. In contrast to our hypothesis, we observed a significant decrease in the basal transcriptional activity of NFκB in CRT-deficient cells. Treatment with lipopolysaccharide failed to increase the transcriptional activity of NFκB in the crt-/- cells to the same level as in the wt cells. Our data illustrate that the mechanism of decreased NFκB activity in CRT-deficient cells is mediated by a significant increase in IκB protein expression. Furthermore, we showed a significant increase in protein phosphatase 2A activity inhibition which resulted in decreased IκBα protein level in CRT-deficient cells. Based on our data we concluded that loss of CRT increases the stability of IκB protein thus reducing NFκB activity. Copyright © 2014 Elsevier B.V. All rights reserved.

In vivo study of transepithelial potential difference (TEPD) in proximal convoluted tubules of rat kidney by synchronization modulation electric field.

PubMed

Clausell, Mathis; Fang, Zhihui; Chen, Wei

2014-07-01

Synchronization modulation (SM) electric field has been shown to effectively activate function of Na(+)/K(+) pumps in various cells and tissues, including skeletal muscle cells, cardiomyocyte, monolayer of cultured cell line, and peripheral blood vessels. We are now reporting the in vivo studies in application of the SM electric field to kidney of living rats. The field-induced changes in the transepithelial potential difference (TEPD) or the lumen potential from the proximal convoluted tubules were monitored. The results showed that a short time (20 s) application of the SM electric field can significantly increase the magnitude of TEPD from 1-2 mV to about 20 mV. The TEPD is an active potential representing the transport current of the Na/K pumps in epithelial wall of renal tubules. This study showed that SM electric field can increase TEPD by activation of the pump molecules. Considering renal tubules, many active transporters are driven by the Na(+) concentration gradient built by the Na(+)/K(+) pumps, activation of the pump functions and increase in the magnitude of TEPD imply that the SM electric field may improve reabsorption functions of the renal tubules.

Active versus passive listening to auditory streaming stimuli: a near-infrared spectroscopy study

NASA Astrophysics Data System (ADS)

Remijn, Gerard B.; Kojima, Haruyuki

2010-05-01

We use near-infrared spectroscopy (NIRS) to assess listeners' cortical responses to a 10-s series of pure tones separated in frequency. Listeners are instructed to either judge the rhythm of these ``streaming'' stimuli (active-response listening) or to listen to the stimuli passively. Experiment 1 shows that active-response listening causes increases in oxygenated hemoglobin (oxy-Hb) in response to all stimuli, generally over the (pre)motor cortices. The oxy-Hb increases are significantly larger over the right hemisphere than over the left for the final 5 s of the stimulus. Hemodynamic levels do not vary with changes in the frequency separation between the tones and corresponding changes in perceived rhythm (``gallop,'' ``streaming,'' or ``ambiguous''). Experiment 2 shows that hemodynamic levels are strongly influenced by listening mode. For the majority of time windows, active-response listening causes significantly larger oxy-Hb increases than passive listening, significantly over the left hemisphere during the stimulus and over both hemispheres after the stimulus. This difference cannot be attributed to physical motor activity and preparation related to button pressing after stimulus end, because this is required in both listening modes.

Active versus passive listening to auditory streaming stimuli: a near-infrared spectroscopy study.

PubMed

Remijn, Gerard B; Kojima, Haruyuki

2010-01-01

We use near-infrared spectroscopy (NIRS) to assess listeners' cortical responses to a 10-s series of pure tones separated in frequency. Listeners are instructed to either judge the rhythm of these "streaming" stimuli (active-response listening) or to listen to the stimuli passively. Experiment 1 shows that active-response listening causes increases in oxygenated hemoglobin (oxy-Hb) in response to all stimuli, generally over the (pre)motor cortices. The oxy-Hb increases are significantly larger over the right hemisphere than over the left for the final 5 s of the stimulus. Hemodynamic levels do not vary with changes in the frequency separation between the tones and corresponding changes in perceived rhythm ("gallop," "streaming," or "ambiguous"). Experiment 2 shows that hemodynamic levels are strongly influenced by listening mode. For the majority of time windows, active-response listening causes significantly larger oxy-Hb increases than passive listening, significantly over the left hemisphere during the stimulus and over both hemispheres after the stimulus. This difference cannot be attributed to physical motor activity and preparation related to button pressing after stimulus end, because this is required in both listening modes.

Activation of T-cell Protein-tyrosine Phosphatase Suppresses Keratinocyte Survival and Proliferation following UVB Irradiation*

PubMed Central

Lee, Hyunseung; Morales, Liza D.; Slaga, Thomas J.; Kim, Dae Joon

2015-01-01

Chronic exposure to UV radiation can contribute to the development of skin cancer by promoting protein-tyrosine kinase (PTK) signaling. Studies show that exposure to UV radiation increases the ligand-independent activation of PTKs and induces protein-tyrosine phosphatase (PTP) inactivation. In the present work, we report that T-cell PTP (TC-PTP) activity is stimulated during the initial response to UVB irradiation, which leads to suppression of keratinocyte cell survival and proliferation via the down-regulation of STAT3 signaling. Our results show that TC-PTP-deficient keratinocyte cell lines expressed a significantly increased level of phosphorylated STAT3 after exposure to low dose UVB. This increase corresponded with increased cell proliferation in TC-PTP-deficient keratinocytes following UVB irradiation. Loss of TC-PTP also reduced UVB-induced apoptosis. Corroborating with these results, overexpression of TC-PTP in keratinocyte cell lines yielded a decrease in phosphorylated STAT3 levels, which corresponded with a significant decrease in cell proliferation in response to low dose UVB. We demonstrate that TC-PTP activity was increased upon UVB exposure, and overexpression of TC-PTP in keratinocyte cell lines further increased its activity in the presence of UVB. Treatment of TC-PTP-deficient keratinocytes with the STAT3 inhibitor STA21 significantly reduced cell viability following UVB exposure in comparison with untreated TC-PTP-deficient keratinocytes, confirming that the effect of TC-PTP on cell viability is mediated by STAT3 dephosphorylation. Combined, our results indicate that UVB-mediated activation of TC-PTP plays an important role in the STAT3-dependent regulation of keratinocyte cell proliferation and survival. Furthermore, these results suggest that TC-PTP may be a novel potential target for the prevention of UVB-induced skin cancer. PMID:25406309

Evaluation of micronuclei induction capacity and mutagenicity of organochlorine and organophosphate pesticides.

PubMed

Yaduvanshi, Santosh K; Srivastava, Nalini; Marotta, Francesco; Jain, Shalini; Yadav, Hariom

2012-09-01

The genotoxic and mutagenic effects of two commonly used organochlorine pesticides, lindane (LND) and endosulfan (ENS), and two commonly used organophosphate pesticides, chlorpyrifos (CPF) and monocrotophos (MCP) were assessed using in vivo mouse bone marrow micronucleus test and in vitro Ames Salmonella/ microsome mutagenicity test. The results showed that these pesticides alone or in combination, induced significantly high frequency of micronuclei (MN) formation that increased with concentration of pesticides. All these four pesticides produced significant increase in the frequencies of micronucleated-polychromatic erythrocytes (MN-PCE) and decrease infrequencies of PCE in dose-dependent manner. The results indicate the suppression of proliferative activity of the bone marrow and increase in the extent of cell death. ENS and MCP showed mutagenic potential in Salmonella/ microsome assay. ENS induced mutagenic and nontoxic response only in TA98 tester strain of S.typhimurium at the dose of 500 μg/plate and in the absence of metabolic activation. MCP showed weak mutagenic and nontoxic effect only in TA100 tester strain at the dose of 5000 μg/plate in both assays, with or without metabolic activation when compared with negative control. MCP was toxic in TA98 tester strain at the dose of 5000 μg/plate in absence of metabolic activation while reduction in toxicity was seen on addition of S9 mixture. The study clearly showed the genotoxic potential of all these four pesticides and mutagenic response of endosulfan and monocrotophos.

Protease-activated receptor 2, a receptor involved in melanosome transfer, is upregulated in human skin by ultraviolet irradiation.

PubMed

Scott, G; Deng, A; Rodriguez-Burford, C; Seiberg, M; Han, R; Babiarz, L; Grizzle, W; Bell, W; Pentland, A

2001-12-01

Previous studies have shown that the protease-activated receptor 2 is involved in skin pigmentation through increased phagocytosis of melanosomes by keratinocytes. Ultraviolet irradiation is a potent stimulus for melanosome transfer. We show that protease-activated receptor 2 expression in human skin is upregulated by ultraviolet irradiation. Subjects with skin type I, II, or III were exposed to two or three minimal erythema doses of irradiation from a solar simulator. Biopsies were taken from nonexposed and irradiated skin 24 and 96 h after irradiation and protease-activated receptor 2 expression was detected using immunohistochemical staining. In nonirradiated skin, protease-activated receptor 2 expression was confined to keratinocytes in the lower one-third of the epidermis. After ultraviolet irradiation protease-activated receptor 2 expression was observed in keratinocytes in the upper two-thirds of the epidermis or the entire epidermis at both time points studied. Subjects with skin type I showed delayed upregulation of protease-activated receptor 2 expression, however, compared with subjects with skin types II and III. Irradiated cultured human keratinocytes showed upregulation in protease-activated receptor 2 expression as determined by immunofluorescence microscopy and Western blotting. Cell culture supernatants from irradiated keratinocytes also exhibited a dose-dependent increase in protease-activated receptor-2 cleavage activity. These results suggest an important role for protease-activated receptor-2 in pigmentation in vivo. Differences in protease-activated receptor 2 regulation in type I skin compared with skin types II and III suggest a potential mechanism for differences in tanning in subjects with different skin types.

Efficiency of activated carbon to transform ozone into *OH radicals: influence of operational parameters.

PubMed

Sánchez-Polo, M; von Gunten, U; Rivera-Utrilla, J

2005-09-01

Based on previous findings (Jans, U., Hoigné, J., 1998. Ozone Sci. Eng. 20, 67-87), the activity of activated carbon for the transformation of ozone into *OH radicals including the influence of operational parameters (carbon dose, ozone dose, carbon-type and carbon treatment time) was quantified. The ozone decomposition constant (k(D)) was increased by the presence of activated carbon in the system and depending on the type of activated carbon added, the ratio of the concentrations of *OH radicals and ozone, the R(ct) value ([*OH]/[O3]), was increased by a factor 3-5. The results obtained show that the surface chemical and textural characteristics of the activated carbon determines its activity for the transformation of ozone into *OH radicals. The most efficient carbons in this process are those with high basicity and large surface area. The obtained results show that the interaction between ozone and pyrrol groups present on the surface of activated carbon increase the concentration of O2*- radicals in the system, enhancing ozone transformation into *OH radicals. The activity of activated carbon decreases for extended ozone exposures. This may indicate that activated carbon does not really act as a catalyst but rather as a conventional initiator or promoter for the ozone transformation into *OH radicals. Ozonation of Lake Zurich water ([O3] = 1 mg/L) in presence of activated carbon (0.5 g/L) lead to an increase in the k(D) and R(ct) value by a factor of 10 and 39, respectively, thereby favouring the removal of ozone-resistant contaminants. Moreover, the presence of activated carbon during ozonation of Lake Zurich water led to a 40% reduction in the content of dissolved organic carbon during the first 60 min of treatment. The adsorption of low concentrations of dissolved organic matter (DOM) on activated carbon surfaces did not modify its capacity to initiate/promote ozone transformation into *OH radicals.

Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity

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

Das, Suvarthi; Kumar, Ashutosh; Seth, Ratanesh Kumar

Today's developed world faces a major public health challenge in the rise in the obese population and the increased incidence in fatty liver disease. There is a strong association among diet induced obesity, fatty liver disease and development of nonalcoholic steatohepatitis but the environmental link to disease progression remains unclear. Here we demonstrate that in obesity, early steatohepatitic lesions induced by the water disinfection byproduct bromodichloromethane are mediated by increased oxidative stress and leptin which act in synchrony to potentiate disease progression. Low acute exposure to bromodichloromethane (BDCM), in diet-induced obesity produced oxidative stress as shown by increased lipid peroxidation,more » protein free radical and nitrotyrosine formation and elevated leptin levels. Exposed obese mice showed histopathological signs of early steatohepatitic injury and necrosis. Spontaneous knockout mice for leptin or systemic leptin receptor knockout mice had significantly decreased oxidative stress and TNF-α levels. Co-incubation of leptin and BDCM caused Kupffer cell activation as shown by increased MCP-1 release and NADPH oxidase membrane assembly, a phenomenon that was decreased in Kupffer cells isolated from leptin receptor knockout mice. In obese mice that were BDCM-exposed, livers showed a significant increase in Kupffer cell activation marker CD68 and, increased necrosis as assessed by levels of isocitrate dehydrogenase, events that were decreased in the absence of leptin or its receptor. In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver. - Highlights: ► BDCM acute exposure sensitizes liver to increased free radical stress in obesity. ► BDCM-induced higher leptin contributes to early steatohepatitic lesions. ► Increased leptin mediates protein radical and 3-nitrotyrosine formation. ► BDCM exposure in obesity activates Kupffer cells and NADPH oxidase. ► BDCM/leptin synergy promotes necrotic cell-death and augments steatohepatitis.« less

Sensibility of male rats fertility against olive oil, Nigella sativa oil and pomegranate extract.

PubMed

Mansour, Sherif W; Sangi, Sibghatullah; Harsha, Sree; Khaleel, Mueen A; Ibrahim, A R N

2013-07-01

To clarify the modulatory effects of daily consumption of pomegranate extract (PE), olive oil (OO) and Nagilla sativa oil (NSO) on antioxidant activity, sperm quality and pituitary-testicular axis of adult male wistar rats. Thirty-two adult male Wistar rats were divided into four equal groups, eight rats each. Using rat gastric tubes, 1.0 mL distilled water, 1.0 mL PE, 0.4 mL NSO and 0.4 mL OO were orally administered daily for 6 weeks in the first, second, third and fourth groups, respectively. Reproductive organs, body weight, sperm criteria, testosterone, FSH, LH, inhibin-B, lipid peroxidation, and antioxidant enzyme activities were investigated. At the end of the study protocol, analyses occurred at the same time. Data were analysed by ANOVA test and P<0.05 was considered to be a significant value. In all studied groups, malondialdehyde level was significantly decreased accompanied with an increases in glutathione peroxidase and glutathione. Rats treated with PE showed an increase in catalase activities accompanied with an increase in sperm concentration which was also observed in NSO group. In PE treated group, sperm motility was also increased accompanied with decreased abnormal sperm rate. NSO, OO and PE treated groups shows an insignificant effect on testosterone, inhibin-B, FSH and LH in comparison with control group. These results show that administration of PE, NSO and OO could modify sperm characteristics and antioxidant activity of adult male wistar rats.

Leucine deprivation stimulates fat loss via increasing CRH expression in the hypothalamus and activating the sympathetic nervous system.

PubMed

Cheng, Ying; Zhang, Qian; Meng, Qingshu; Xia, Tingting; Huang, Zhiying; Wang, Chunxia; Liu, Bin; Chen, Shanghai; Xiao, Fei; Du, Ying; Guo, Feifan

2011-09-01

We previously showed that leucine deprivation decreases abdominal fat mass largely by increasing energy expenditure, as demonstrated by increased lipolysis in white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT). The goal of the present study was to investigate the possible involvement of central nervous system (CNS) in this regulation and elucidate underlying molecular mechanisms. For this purpose, levels of genes and proteins related to lipolysis in WAT and UCP1 expression in BAT were analyzed in wild-type mice after intracerebroventricular administration of leucine or corticotrophin-releasing hormone antibodies, or in mice deleted for three β-adrenergic receptors, after being maintained on a leucine-deficient diet for 7 d. Here, we show that intracerebroventricular administration of leucine significantly attenuates abdominal fat loss and blocks activation of hormone sensitive lipase in WAT and induction of UCP1 in BAT in leucine-deprived mice. Furthermore, we provide evidence that leucine deprivation stimulates fat loss by increasing expression of corticotrophin-releasing hormone in the hypothalamus via activation of stimulatory G protein/cAMP/protein kinase A/cAMP response element-binding protein pathway. Finally, we show that the effect of leucine deprivation on fat loss is mediated by activation of the sympathetic nervous system. These results suggest that CNS plays an important role in regulating fat loss under leucine deprivation and thereby provide novel and important insights concerning the importance of CNS leucine in the regulation of energy homeostasis.

The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways.

PubMed

Lee, Hee Jeong; Im, A-Rang; Kim, Su-Man; Kang, Hyung-Sik; Lee, Jae Dong; Chae, Sungwook

2018-01-30

Hesperidin is a flavonoid with antioxidant, anti-inflammatory, and immune modulatory activities. Photoaging is a consequence of chronic exposure to the sun and ultraviolet (UV) radiation. This study was designed to evaluate the efficacy of hesperidin against photoaging of dorsal skin in hairless mice. Hairless male mice (6-week-old) were divided into three groups (n = 7): control, UVB-treated vehicle, and UVB-treated hesperidin groups. UVB-irradiated mice from hesperidin group were orally administered 0.1 mL of water containing 100 mg/kg body weight per day hesperidin. The mean length and depth of wrinkles in the UVB-treated hesperidin group significantly improved after the oral administration of hesperidin, which significantly inhibited the increase in epidermal thickness and epidermal hypertrophy (P < 0.05). UVB irradiation of mice induced epidermal barrier dysfunction including an increase in the transepidermal water loss (TEWL); however, hesperidin decreased the TEWL. UVB irradiation increased the expression of MMP-9 and pro-inflammatory cytokines whereas UVB-treated hesperidin group showed reduced expression. These results indicate that hesperidin showed anti-photoaging activity in the UVB-irradiated hairless mice. In conclusion, hesperidin inhibited the UVB-induced increase in skin thickness, wrinkle formation, and collagen fiber loss in male hairless mice. These results suggest that hesperidin shows potent anti-photoaging activity by regulating MMP-9 expression through the suppression of MAPK-dependent signaling pathways.

METHOD OF SUPPRESSING GASTROINTESTINAL UREASE ACTIVITY

DOEpatents

Visek, W.J.

1963-04-23

This patent shows a method of increasing the growth rate of chicks. Certain diacyl substituted ureas such as alloxan, murexide, and barbituric acid are added to their feed, thereby suppressing gastrointestinal urease activity and thus promoting growth. (AEC)

Inhibition of norsolorinic acid accumulation to Aspergillus parasiticus by marine actinomycetes

NASA Astrophysics Data System (ADS)

Yan, Peisheng; Shi, Cuijuan; Shen, Jihong; Wang, Kai; Gao, Xiujun; Li, Ping

2014-11-01

Thirty-six strains of marine actinomycetes were isolated from a sample of marine sediment collected from the Yellow Sea and evaluated in terms of their inhibitory activity on the growth of Aspergillus parasiticus and the production of norsolorinic acid using dual culture plate assay and agar diffusion methods. Among them, three strains showed strong antifungal activity and were subsequently identified as Streptomyces sp. by 16S rRNA gene sequencing analysis. The supernatant from the fermentation of the MA01 strain was extracted sequentially with chloroform and ethyl acetate, and the activities of the extracts were determined by tip culture assay. The assay results show that both extracts inhibited mycelium growth and toxin production, and the inhibitory activities of the extracts increased as their concentrations increased. The results of this study suggest that marine actinomycetes are biologically important for the control of mycotoxins, and that these bacteria could be used as novel biopesticides against mycotoxins.

A Preliminary Test of a Student-Centered Intervention on Increasing Physical Activity in Underserved Adolescents

PubMed Central

Wilson, Dawn K.; Evans, Alexandra E.; Williams, Joel; Mixon, Gary; Sirard, John R.; Pate, Russell

2008-01-01

Background Previous studies have shown that choice and self-initiated behavior change are important for increasing intrinsic motivation and physical activity (PA), however, little of this research has focused on underserved adolescents. Purpose This study examined the effects of a 4-week student-centered intervention on increasing PA in underserved adolescents. Methods Twenty-eight students in the intervention school were matched (on race, percentage on free or reduced-price lunch program, gender, and age) with 20 students from another school who served as the comparison group (30 girls, 18 boys; ages 10–12 years; 83% African American; 83% on free or reduced-price lunch). The student-centered intervention was consistent with self-determination (motivation) theory and social cognitive theory in that it emphasized increasing intrinsic motivation and behavioral skills for PA. Intervention adolescents took ownership in selecting a variety of PA activities in which to participate, and they generated coping strategies for making effective PA behavior changes. Results Intervention participants showed greater increases in accelerometer estimates of time spent in moderate PA, moderate-to-vigorous PA, and vigorous PA from baseline to Week 4 of the intervention than the comparison group. Intervention participants also showed greater increases in PA motivation and positive self-concept for PA than comparison adolescents. Conclusions This study provides preliminary evidence that increasing adolescent involvement and choice of activities may be important in developing future PA interventions for underserved adolescents. PMID:16173908

Increased Mitochondrial Calcium Sensitivity and Abnormal Expression of Innate Immunity Genes Precede Dopaminergic Defects in Pink1-Deficient Mice

PubMed Central

Akundi, Ravi S.; Huang, Zhenyu; Eason, Joshua; Pandya, Jignesh D.; Zhi, Lianteng; Cass, Wayne A.; Sullivan, Patrick G.; Büeler, Hansruedi

2011-01-01

Background PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca2+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1−/− mice. Methods and Findings Purified brain mitochondria of Pink1−/− mice showed impaired Ca2+ storage capacity, resulting in increased Ca2+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1−/− mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1−/− mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1−/− mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1−/− embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1−/− mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. Conclusions Increased mitochondrial Ca2+ sensitivity and JNK activity are early defects in Pink1−/− mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1−/− mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1−/− mice to inflammation and injury-induced cell death. PMID:21249202

Increased brain connectivity and activation after cognitive rehabilitation in Parkinson's disease: a randomized controlled trial.

PubMed

Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Lucas-Jiménez, Olaia; Gómez-Esteban, Juan Carlos; Gómez-Beldarrain, Maria Ángeles; Ibarretxe-Bilbao, Naroa

2017-12-01

Cognitive rehabilitation programs have demonstrated efficacy in improving cognitive functions in Parkinson's disease (PD), but little is known about cerebral changes associated with an integrative cognitive rehabilitation in PD. To assess structural and functional cerebral changes in PD patients, after attending a three-month integrative cognitive rehabilitation program (REHACOP). Forty-four PD patients were randomly divided into REHACOP group (cognitive rehabilitation) and a control group (occupational therapy). T1-weighted, diffusion weighted and functional magnetic resonance images (fMRI) during resting-state and during a memory paradigm (with learning and recognition tasks) were acquired at pre-treatment and post-treatment. Cerebral changes were assessed with repeated measures ANOVA 2 × 2 for group x time interaction. During resting-state fMRI, the REHACOP group showed significantly increased brain connectivity between the left inferior temporal lobe and the bilateral dorsolateral prefrontal cortex compared to the control group. Moreover, during the recognition fMRI task, the REHACOP group showed significantly increased brain activation in the left middle temporal area compared to the control group. During the learning fMRI task, the REHACOP group showed increased brain activation in the left inferior frontal lobe at post-treatment compared to pre-treatment. No significant structural changes were found between pre- and post-treatment. Finally, the REHACOP group showed significant and positive correlations between the brain connectivity and activation and the cognitive performance at post-treatment. This randomized controlled trial suggests that an integrative cognitive rehabilitation program can produce significant functional cerebral changes in PD patients and adds evidence to the efficacy of cognitive rehabilitation programs in the therapeutic approach for PD.

Effect of different ripening stages on walnut kernel quality: antioxidant activities, lipid characterization and antibacterial properties.

PubMed

Amin, Furheen; Masoodi, F A; Baba, Waqas N; Khan, Asma Ashraf; Ganie, Bashir Ahmad

2017-11-01

Packing tissue between and around the kernel halves just turning brown (PTB) is a phenological indicator of kernel ripening at harvest in walnuts. The effect of three ripening stages (Pre-PTB, PTB and Post-PTB) on kernel quality characteristics, mineral composition, lipid characterization, sensory analysis, antioxidant and antibacterial activity were investigated in fresh kernels of indigenous numbered walnut selection of Kashmir valley "SKAU-02". Proximate composition, physical properties and sensory analysis of walnut kernels showed better results for Pre-PTB and PTB while higher mineral content was seen for kernels at Post-PTB stage in comparison to other stages of ripening. Kernels showed significantly higher levels of Omega-3 PUFA (C18:3 n3 ) and low n6/n3 ratio when harvested at Pre-PTB and PTB stages. The highest phenolic content and antioxidant activity was observed at the first stage of ripening and a steady decrease was observed at later stages. TBARS values increased as ripening advanced but did not show any significant difference in malonaldehyde formation during early ripening stages whereas it showed marked increase in walnut kernels at post-PTB stage. Walnut extracts inhibited growth of Gram-positive bacteria ( B. cereus, B. subtilis, and S. aureus ) with respective MICs of 1, 1 and 5 mg/mL and gram negative bacteria ( E. coli, P. and K. pneumonia ) with MIC of 100 mg/mL. Zone of inhibition obtained against all the bacterial strains from walnut kernel extracts increased with increase in the stage of ripening. It is concluded that Pre-PTB harvest stage with higher antioxidant activities, better fatty acid profile and consumer acceptability could be preferred harvesting stage for obtaining functionally superior walnut kernels.

Inhibition of SIRT1 by a small molecule induces apoptosis in breast cancer cells

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

Kalle, Arunasree M., E-mail: arunasreemk@ilsresearch.org; Mallika, A.; Badiger, Jayasree

2010-10-08

Research highlights: {yields} Novel small molecule SIRT1 inhibitor better than sirtinol. {yields} IC{sub 50} 500 nM. {yields} Specific tumor cytotoxicity towards breast cancer cells. {yields} Restoration of H3K9 acetylation levels to baseline when co-treated with SIRT1 activator (Activator X) and inhibitor (ILS-JGB-1741). -- Abstract: Overexpression of SIRT1, a NAD{sup +}-dependent class III histone deacetylases (HDACs), is implicated in many cancers and therefore could become a promising antitumor target. Here we demonstrate a small molecule SIRT1 inhibitor, ILS-JGB-1741(JGB1741) with potent inhibitory effects on the proliferation of human metastatic breast cancer cells, MDA-MB 231. The molecule has been designed using medicinal chemistrymore » approach based on known SIRT1 inhibitor, sirtinol. The molecule showed a significant inhibition of SIRT1 activity compared to sirtinol. Studies on the antitumor effects of JGB on three different cancer cell lines, K562, HepG2 and MDA-MB 231 showed an IC{sub 50} of 1, 10 and 0.5 {mu}M, respectively. Further studies on MDA-MB 231 cells showed a dose-dependent increase in K9 and K382 acetylation of H3 and p53, respectively. Results also demonstrated that JGB1741-induced apoptosis is associated with increase in cytochrome c release, modulation in Bax/Bcl2 ratio and cleavage of PARP. Flowcytometric analysis showed increased percentage of apoptotic cells, decrease in mitochondrial membrane potential and increase in multicaspase activation. In conclusion, the present study indicates the potent apoptotic effects of JGB1741 in MDA-MB 231 cells.« less

Glioblastoma chemotherapy adjunct via potent serotonin receptor-7 inhibition using currently marketed high-affinity antipsychotic medicines

PubMed Central

Kast, RE

2010-01-01

Glioblastoma treatment as now constituted offers increased survival measured in months over untreated patients. Because glioblastomas are active in synthesizing a bewildering variety of growth factors, a systematic approach to inhibiting these is being undertaken as treatment adjunct. The serotonin 7 receptor is commonly overexpressed in glioblastoma. Research documentation showing agonists at serotonin receptor 7 cause increased extracellular regulated kinase 1/2 activation, increased interleukin-6 synthesis, increased signal transducer and activator of transcription-3 activation, increased resistance to apoptosis and other growth enhancing changes in glioblastoma is reviewed in this paper. Because three drugs in wide use to treat thought disorders – paliperidone, pimozide and risperidone – are also potent and well-tolerated inhibitors at serotonin receptor 7, these drugs should be studied for growth factor deprivation in an adjunctive role in glioblastoma treatment. PMID:20880389

Morinda citrifolia Linn. fruit (Noni) juice induces an increase in NO production and death of Leishmania amazonensis amastigotes in peritoneal macrophages from BALB/c.

PubMed

Almeida-Souza, Fernando; de Souza, Celeste da Silva Freitas; Taniwaki, Noemi Nosomi; Silva, João José Mendes; de Oliveira, Renata Mondêgo; Abreu-Silva, Ana Lúcia; Calabrese, Kátia da Silva

2016-08-31

Leishmaniasis is a complex disease that is considered a serious public health problem. Due to the absence of an effective vaccine and debilitating chemotherapy better therapies are urgently needed. This situation has stimulated the search for alternative treatments such as the use of herbal medicines. Several studies conducted with Morinda citrifolia Linn. have shown various biological activities such as antitumor, immunomodulation and antileishmanial activity, however its mechanisms of action are still unknown. This study aimed to analyze the activity of M. citrifolia fruit juice against Leishmania amazonensis and its action on peritoneal macrophages from BALB/c infected with L. amazonensis. Activity against the promastigote forms showed IC50 at 275.3 μg/mL. Transmission electron microscopy was used to evaluate the ultrastructural alterations in the promastigotes treated with the juice and the results showed cytoplasmic vacuolization, lipid inclusion and increased activity of exocytosis. The juice treatment presented an IC50 at 208.4 μg/mL against intracellular amastigotes and led to an increased nitrite production in infected and non-infected macrophages. When macrophages were pre-treated with iNOS inhibitors, aminoguanidine or 1400W, the intracellular amastigotes increased, demonstrating the important role of NO production in M. citrifolia fruit activity. In conclusion, our results reveal that treatment with M. citrifolia fruit juice can increase NO production in peritoneal macrophages and this ability has an important role in the killing of L. amazonensis intracellular amastigotes. Copyright © 2016 Elsevier Inc. All rights reserved.

Distant influences of amygdala lesion on visual cortical activation during emotional face processing.

PubMed

Vuilleumier, Patrik; Richardson, Mark P; Armony, Jorge L; Driver, Jon; Dolan, Raymond J

2004-11-01

Emotional visual stimuli evoke enhanced responses in the visual cortex. To test whether this reflects modulatory influences from the amygdala on sensory processing, we used event-related functional magnetic resonance imaging (fMRI) in human patients with medial temporal lobe sclerosis. Twenty-six patients with lesions in the amygdala, the hippocampus or both, plus 13 matched healthy controls, were shown pictures of fearful or neutral faces in task-releant or task-irrelevant positions on the display. All subjects showed increased fusiform cortex activation when the faces were in task-relevant positions. Both healthy individuals and those with hippocampal damage showed increased activation in the fusiform and occipital cortex when they were shown fearful faces, but this was not the case for individuals with damage to the amygdala, even though visual areas were structurally intact. The distant influence of the amygdala was also evidenced by the parametric relationship between amygdala damage and the level of emotional activation in the fusiform cortex. Our data show that combining the fMRI and lesion approaches can help reveal the source of functional modulatory influences between distant but interconnected brain regions.

Structural analysis, and antioxidant and antibacterial properties of chitosan-poly (vinyl alcohol) biodegradable films.

PubMed

Hajji, Sawssen; Chaker, Achraf; Jridi, Mourad; Maalej, Hana; Jellouli, Kemel; Boufi, Sami; Nasri, Moncef

2016-08-01

The development and characterization of biodegradable blend films based on chitosan and poly (vinyl alcohol) for possible use in a variety of biological activities are reported. Fourier transform infrared spectroscopy (FTIR) spectra of chitosan-poly (vinyl alcohol) (Ch/PVA) films showed characteristics peaks shifting to a lower frequency range due to hydrogen bonding between -OH of PVA and -NH2 of chitosan. The chitosan and PVA polymers presented good compatibility. The morphology study of chitosan and composite films showed a compact and homogenous structure. The tensile strength and elongation at break increased with PVA content. In fact, the highest tensile strength and elongation at break (53.58 MPa and 454 %) occurs with pure PVA film. The results showed that PVA incorporation in the blends contributes to increase the intermolecular interactions, thus improving the mechanical properties. In addition, the prepared films demonstrated high antioxidant activities monitored by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging, reducing power, and β-carotene bleaching activity. Nevertheless, PVA addition reduced antioxidant and antibacterial activities against Gram-positive and Gram-negative bacteria tested.

Influence of solar variability on the occurrence of central European weather types from 1763 to 2009

NASA Astrophysics Data System (ADS)

Schwander, Mikhaël; Rohrer, Marco; Brönnimann, Stefan; Malik, Abdul

2017-09-01

The impact of solar variability on weather and climate in central Europe is still not well understood. In this paper we use a new time series of daily weather types to analyse the influence of the 11-year solar cycle on the tropospheric weather of central Europe. We employ a novel, daily weather type classification over the period 1763-2009 and investigate the occurrence frequency of weather types under low, moderate, and high solar activity level. Results show a tendency towards fewer days with westerly and west-southwesterly flow over central Europe under low solar activity. In parallel, the occurrence of northerly and easterly types increases. For the 1958-2009 period, a more detailed view can be gained from reanalysis data. Mean sea level pressure composites under low solar activity also show a reduced zonal flow, with an increase of the mean blocking frequency between Iceland and Scandinavia. Weather types and reanalysis data show that the 11-year solar cycle influences the late winter atmospheric circulation over central Europe with colder (warmer) conditions under low (high) solar activity.

A measurement-based study of concurrency in a multiprocessor

NASA Technical Reports Server (NTRS)

Mcguire, Patrick John

1987-01-01

A systematic measurement-based methodology for characterizing the amount of concurrency present in a workload, and the effect of concurrency on system performance indices such as cache miss rate and bus activity are developed. Hardware and software instrumentation of an Alliant FX/8 was used to obtain data from a real workload environment. Results show that 35% of the workload is concurrent, with the concurrent periods typically using all available processors. Measurements of periods of change in concurrency show uneven usage of processors during these times. Other system measures, including cache miss rate and processor bus activity, are analyzed with respect to the concurrency measures. Probability of a cache miss is seen to increase with concurrency. The change in cache miss rate is much more sensitive to the fraction of concurrent code in the worklaod than the number of processors active during concurrency. Regression models are developed to quantify the relationships between cache miss rate, bus activity, and the concurrency measures. The model for cache miss rate predicts an increase in the median miss rate value as much as 300% for a 100% increase in concurrency in the workload.

Purification and identification of a polysaccharide from medicinal mushroom Amauroderma rude with immunomodulatory activity and inhibitory effect on tumor growth.

PubMed

Pan, Honghui; Han, Yuanyuan; Huang, Jiguo; Yu, Xiongtao; Jiao, Chunwei; Yang, Xiaobing; Dhaliwal, Preet; Xie, Yizhen; Yang, Burton B

2015-07-10

Medicinal mushrooms in recent years have been the subject of many experiments searching for anticancer properties. We previously screened thirteen mushrooms for their potential in inhibiting tumor growth, and found that the water extract of Amauroderma rude exerted the highest activity. Previous studies have shown that the polysaccharides contained in the water extract were responsible for the anticancer properties. This study was designed to explore the potential effects of the polysaccharides on immune regulation and tumor growth. Using the crude Amauroderma rude extract, in vitro experiments showed that the capacities of spleen lymphocytes, macrophages, and natural killer cells were all increased. In vivo experiments showed that the extract increased macrophage metabolism, lymphocyte proliferation, and antibody production. In addition, the partially purified product stimulated the secretion of cytokines in vitro, and in vivo. Overall, the extract decreased tumor growth rates. Lastly, the active compound was purified and identified as polysaccharide F212. Most importantly, the purified polysaccharide had the highest activity in increasing lymphocyte proliferation. In summary, this molecule may serve as a lead compound for drug development.

DRP1 Suppresses Leptin and Glucose Sensing of POMC Neurons.

PubMed

Santoro, Anna; Campolo, Michela; Liu, Chen; Sesaki, Hiromi; Meli, Rosaria; Liu, Zhong-Wu; Kim, Jung Dae; Diano, Sabrina

2017-03-07

Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy and glucose metabolism. Intracellular mechanisms that enable these neurons to respond to changes in metabolic environment are ill defined. Here we show reduced expression of activated dynamin-related protein (pDRP1), a mitochondrial fission regulator, in POMC neurons of fed mice. These POMC neurons displayed increased mitochondrial size and aspect ratio compared to POMC neurons of fasted animals. Inducible deletion of DRP1 of mature POMC neurons (Drp1 fl/fl -POMC-cre:ER T2 ) resulted in improved leptin sensitivity and glucose responsiveness. In Drp1 fl/fl -POMC-cre:ER T2 mice, POMC neurons showed increased mitochondrial size, ROS production, and neuronal activation with increased expression of Kcnj11 mRNA regulated by peroxisome proliferator-activated receptor (PPAR). Furthermore, deletion of DRP1 enhanced the glucoprivic stimulus in these neurons, causing their stronger inhibition and a greater activation of counter-regulatory responses to hypoglycemia that were PPAR dependent. Together, these data unmasked a role for mitochondrial fission in leptin sensitivity and glucose sensing of POMC neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

Fatigue-Induced Changes in Movement Pattern and Muscle Activity During Ballet Releve on Demi-Pointe.

PubMed

Lin, Cheng-Feng; Lee, Wan-Chin; Chen, Yi-An; Hsue, Bih-Jen

2016-08-01

Fatigue in ballet dancers may lead to injury, particularly in the lower extremities. However, few studies have investigated the effects of fatigue on ballet dancers' performance and movement patterns. Thus, the current study examines the effect of fatigue on the balance, movement pattern, and muscle activities of the lower extremities in ballet dancers. Twenty healthy, female ballet dancers performed releve on demi-pointe before and after fatigue. The trajectory of the whole body movement and the muscle activities of the major lower extremity muscles were recorded continuously during task performance. The results show that fatigue increases the medial-lateral center of mass (COM) displacement and hip and trunk motion, but decreases the COM velocity and ankle motion. Moreover, fatigue reduces the activities of the hamstrings and tibialis anterior, but increases that of the soleus. Finally, greater proximal hip and trunk motions are applied to compensate for the effects of fatigue, leading to a greater COM movement. Overall, the present findings show that fatigue results in impaired movement control and may therefore increase the risk of dance injury.

SOS System Induction Inhibits the Assembly of Chemoreceptor Signaling Clusters in Salmonella enterica

PubMed Central

Irazoki, Oihane; Mayola, Albert; Campoy, Susana; Barbé, Jordi

2016-01-01

Swarming, a flagellar-driven multicellular form of motility, is associated with bacterial virulence and increased antibiotic resistance. In this work we demonstrate that activation of the SOS response reversibly inhibits swarming motility by preventing the assembly of chemoreceptor-signaling polar arrays. We also show that an increase in the concentration of the RecA protein, generated by SOS system activation, rather than another function of this genetic network impairs chemoreceptor polar cluster formation. Our data provide evidence that the molecular balance between RecA and CheW proteins is crucial to allow polar cluster formation in Salmonella enterica cells. Thus, activation of the SOS response by the presence of a DNA-injuring compound increases the RecA concentration, thereby disturbing the equilibrium between RecA and CheW and resulting in the cessation of swarming. Nevertheless, when the DNA-damage decreases and the SOS response is no longer activated, basal RecA levels and thus polar cluster assembly are reestablished. These results clearly show that bacterial populations moving over surfaces make use of specific mechanisms to avoid contact with DNA-damaging compounds. PMID:26784887

SOS System Induction Inhibits the Assembly of Chemoreceptor Signaling Clusters in Salmonella enterica.

PubMed

Irazoki, Oihane; Mayola, Albert; Campoy, Susana; Barbé, Jordi

2016-01-01

Swarming, a flagellar-driven multicellular form of motility, is associated with bacterial virulence and increased antibiotic resistance. In this work we demonstrate that activation of the SOS response reversibly inhibits swarming motility by preventing the assembly of chemoreceptor-signaling polar arrays. We also show that an increase in the concentration of the RecA protein, generated by SOS system activation, rather than another function of this genetic network impairs chemoreceptor polar cluster formation. Our data provide evidence that the molecular balance between RecA and CheW proteins is crucial to allow polar cluster formation in Salmonella enterica cells. Thus, activation of the SOS response by the presence of a DNA-injuring compound increases the RecA concentration, thereby disturbing the equilibrium between RecA and CheW and resulting in the cessation of swarming. Nevertheless, when the DNA-damage decreases and the SOS response is no longer activated, basal RecA levels and thus polar cluster assembly are reestablished. These results clearly show that bacterial populations moving over surfaces make use of specific mechanisms to avoid contact with DNA-damaging compounds.

Active video games and health indicators in children and youth: a systematic review.

PubMed

LeBlanc, Allana G; Chaput, Jean-Philippe; McFarlane, Allison; Colley, Rachel C; Thivel, David; Biddle, Stuart J H; Maddison, Ralph; Leatherdale, Scott T; Tremblay, Mark S

2013-01-01

Active video games (AVGs) have gained interest as a way to increase physical activity in children and youth. The effect of AVGs on acute energy expenditure (EE) has previously been reported; however, the influence of AVGs on other health-related lifestyle indicators remains unclear. This systematic review aimed to explain the relationship between AVGs and nine health and behavioural indicators in the pediatric population (aged 0-17 years). Online databases (MEDLINE, EMBASE, psycINFO, SPORTDiscus and Cochrane Central Database) and personal libraries were searched and content experts were consulted for additional material. Included articles were required to have a measure of AVG and at least one relevant health or behaviour indicator: EE (both habitual and acute), adherence and appeal (i.e., participation and enjoyment), opportunity cost (both time and financial considerations, and adverse events), adiposity, cardiometabolic health, energy intake, adaptation (effects of continued play), learning and rehabilitation, and video game evolution (i.e., sustainability of AVG technology). 51 unique studies, represented in 52 articles were included in the review. Data were available from 1992 participants, aged 3-17 years, from 8 countries, and published from 2006-2012. Overall, AVGs are associated with acute increases in EE, but effects on habitual physical activity are not clear. Further, AVGs show promise when used for learning and rehabilitation within special populations. Evidence related to other indicators was limited and inconclusive. Controlled studies show that AVGs acutely increase light- to moderate-intensity physical activity; however, the findings about if or how AVG lead to increases in habitual physical activity or decreases in sedentary behaviour are less clear. Although AVGs may elicit some health benefits in special populations, there is not sufficient evidence to recommend AVGs as a means of increasing daily physical activity.

Effects of manufactured nano-copper on copper uptake, bioaccumulation and enzyme activities in cowpea grown on soil substrate.

PubMed

Ogunkunle, Clement O; Jimoh, Mahboob A; Asogwa, Nnaemeka T; Viswanathan, K; Vishwakarma, Vinita; Fatoba, Paul O

2018-07-15

Increased use of nanoparticles-based products in agriculture portends important implications for agriculture. Therefore, the impact of nano-copper particles (<25 nm and 60-80 nm) on Cu uptake, bioaccumulation (roots, leaves and seeds), activity of ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and lipid peroxidation in leaves and roots of Vigna unguiculata (cowpea) was studied. Plants were exposed to four levels (0, 125, 500 and 1000 mg/kg) of 25 nm or 60-80 nm nano-Cu for 65 days. Results indicated significant (P<.05) uptake of Cu at all nano-Cu levels compared to control, and bioaccumulation increased in seeds by at least 250%. Response of antioxidant enzymes to both nano-Cu types was concentration-dependent. Activity of APX and GR was enhanced in leaves and roots in response to both nano-Cu treatments in similar patterns compared to control. Both nano-Cu increased CAT activity in roots while SOD activity reduced in both leaves and roots. This shows that response of antioxidant enzymes to nano-Cu toxicity was organ-specific in cowpea. Malondialdehyde, a measure of lipid peroxidation, increased at 500 -1000 mg/kg of 25 nm nano-Cu in leaves by average of 8.4%, and 60-80 nm nano-Cu in root by 52.8%, showing particle-size and organ-dependent toxicity of nano-Cu. In conclusion, exposure of cowpea to nano-Cu treatments increased both the uptake and bioaccumulation of Cu, and also promoted the activity of APX and GR in root and leaf tissues of cowpea. Therefore, APX- and GR-activity level could be a useful predictive biomarker of nano-Cu toxicity in cowpea. Copyright © 2018 Elsevier Inc. All rights reserved.

Med1 subunit of the mediator complex in nuclear receptor-regulated energy metabolism, liver regeneration, and hepatocarcinogenesis.

PubMed

Jia, Yuzhi; Viswakarma, Navin; Reddy, Janardan K

2014-01-01

Several nuclear receptors regulate diverse metabolic functions that impact on critical biological processes, such as development, differentiation, cellular regeneration, and neoplastic conversion. In the liver, some members of the nuclear receptor family, such as peroxisome proliferator-activated receptors (PPARs), constitutive androstane receptor (CAR), farnesoid X receptor (FXR), liver X receptor (LXR), pregnane X receptor (PXR), glucocorticoid receptor (GR), and others, regulate energy homeostasis, the formation and excretion of bile acids, and detoxification of xenobiotics. Excess energy burning resulting from increases in fatty acid oxidation systems in liver generates reactive oxygen species, and the resulting oxidative damage influences liver regeneration and liver tumor development. These nuclear receptors are important sensors of exogenous activators as well as receptor-specific endogenous ligands. In this regard, gene knockout mouse models revealed that some lipid-metabolizing enzymes generate PPARα-activating ligands, while others such as ACOX1 (fatty acyl-CoA oxidase1) inactivate these endogenous PPARα activators. In the absence of ACOX1, the unmetabolized ACOX1 substrates cause sustained activation of PPARα, and the resulting increase in energy burning leads to hepatocarcinogenesis. Ligand-activated nuclear receptors recruit the multisubunit Mediator complex for RNA polymerase II-dependent gene transcription. Evidence indicates that the Med1 subunit of the Mediator is essential for PPARα, PPARγ, CAR, and GR signaling in liver. Med1 null hepatocytes fail to respond to PPARα activators in that these cells do not show induction of peroxisome proliferation and increases in fatty acid oxidation enzymes. Med1-deficient hepatocytes show no increase in cell proliferation and do not give rise to liver tumors. Identification of nuclear receptor-specific coactivators and Mediator subunits should further our understanding of the complexities of metabolic diseases associated with increased energy combustion in liver.

Oligo-carrageenan kappa increases NADPH, ascorbate and glutathione syntheses and TRR/TRX activities enhancing photosynthesis, basal metabolism, and growth in Eucalyptus trees.

PubMed

González, Alberto; Moenne, Fabiola; Gómez, Melissa; Sáez, Claudio A; Contreras, Rodrigo A; Moenne, Alejandra

2014-01-01

In order to analyze the effect of OC kappa in redox status, photosynthesis, basal metabolism and growth in Eucalyptus globulus, trees were treated with water (control), with OC kappa at 1 mg mL(-1), or treated with inhibitors of NAD(P)H, ascorbate (ASC), and glutathione (GSH) syntheses and thioredoxin reductase (TRR) activity, CHS-828, lycorine, buthionine sulfoximine (BSO), and auranofin, respectively, and with OC kappa, and cultivated for 4 months. Treatment with OC kappa induced an increase in NADPH, ASC, and GSH syntheses, TRR and thioredoxin (TRX) activities, photosynthesis, growth and activities of basal metabolism enzymes such as rubisco, glutamine synthetase (GlnS), adenosine 5'-phosphosulfate reductase (APR), involved in C, N, and S assimilation, respectively, Krebs cycle and purine/pyrimidine synthesis enzymes. Treatment with inhibitors and OC kappa showed that increases in ASC, GSH, and TRR/TRX enhanced NADPH synthesis, increases in NADPH and TRR/TRX enhanced ASC and GSH syntheses, and only the increase in NADPH enhanced TRR/TRX activities. In addition, the increase in NADPH, ASC, GSH, and TRR/TRX enhanced photosynthesis and growth. Moreover, the increase in NADPH, ASC and TRR/TRX enhanced activities of rubisco, Krebs cycle, and purine/pyrimidine synthesis enzymes, the increase in GSH, NADPH, and TRR/TRX enhanced APR activity, and the increase in NADPH and TRR/TRX enhanced GlnS activity. Thus, OC kappa increases NADPH, ASC, and GSH syntheses leading to a more reducing redox status, the increase in NADPH, ASC, GSH syntheses, and TRR/TRX activities are cross-talking events leading to activation of photosynthesis, basal metabolism, and growth in Eucalyptus trees.

Design and synthesis of thienopyrimidine urea derivatives with potential cytotoxic and pro-apoptotic activity against breast cancer cell line MCF-7.

PubMed

Abdelhaleem, Eman F; Abdelhameid, Mohammed K; Kassab, Asmaa E; Kandeel, Manal M

2018-01-01

A series of novel tetrahydrobenzothieno[2,3-d]pyrimidine urea derivatives was synthesized according to fragment-based design strategy. They were evaluated for their anticancer activity against MCF-7 cell line. Three compounds 9c, 9d and 11b showed 1.5-1.03 folds more potent anticancer activity than doxorubicin. In this study, a promising multi-sited enzyme small molecule inhibitor 9c, which showed the most potent anti-proliferative activity, was identified. The anti-proliferative activity of this compound appears to correlate well with its ability to inhibit topoisomerase II (IC 50  = 9.29 μM). Moreover, compound 9c showed excellent VEGFR-2 inhibitory activity, at the sub-micromolar level with IC 50 value 0.2 μM, which is 2.1 folds more potent than sorafenib. Moreover, activation of damage response pathway of the DNA leads to cell cycle arrest at G2/M phase, accumulation of cells in pre-G1 phase and annexin-V and propidium iodide staining, indicating that cell death proceeds through an apoptotic mechanism. Compound 9c showed potent pro-apoptotic effect through induction of the intrinsic mitochondrial pathway of apoptosis. This mechanistic pathway was confirmed by a significant increase in the expression of the tumor suppressor gene p53, elevation in Bax/BCL-2 ratio and a significant increase in the level of active caspase-3. Quantitative structure-activity relationship (QSAR) studies delivered equations of five 3D descriptors with R 2  = 0.814. This QSAR model provides an effective technique for understanding the observed antitumor properties and thus could be adopted for developing effective lead structures. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Moderate intensity physical activity prevents increased blood glucose concentrations, fat pad deposition and cardiac action potential prolongation following diet-induced obesity in a juvenile-adolescent rat model.

PubMed

van Waveren, Alannah; Duncan, Mitch J; Coulson, Fiona R; Fenning, Andrew

2014-01-01

Both obesity and a lack of physical activity have been associated with an elevated risk of cardiovascular disease (CVD). The incidence of obesity is increasing, especially in juvenile-adolescents. While there is limited research examining the chronic effects of obesity in adolescent humans and animal models of this condition, little is also known concerning how moderate physical activity might prevent or attenuate secondary cardiovascular complications induced by obesity during adolescence. We investigated the effects of diet-induced obesity (consisting of a high-fat, high-carbohydrate diet (HFHC)) on biometric indices, vascular and airway function, cardiovascular function, systemic oxidative stress and markers of inflammation in a juvenile-adolescent rodent model. Four groups were used: control (CON), physical activity (PA) treated, HFHC and HFHC + PA (n = 16 per group). HFHC feeding started at 4 weeks of age for a period of 12 weeks. Physical activity treatment was initiated (PA and HFHC + PA groups) when the animals were 8 weeks of age, for 8 weeks. Physical activity in juvenile-adolescent healthy rats showed no change in comparison to the CON group in all experimental parameters except for increases in lipid peroxidation, decreases in inflammatory cytokines, improvements in vascular reactivity and decreased atrial responses to positive chronotropic agents. The HFHC animals were mildly hyperglycemic, hypertensive, displayed renal hypertrophy and showed increased retroperitoneal fat pad deposition compared to the CON group. HFHC + PA rats were also hypertensive, however showed improvements in cardiac electrophysiology, body weight, fat pad deposition and inflammatory signaling, in comparison to the HFHC fed rats and CON animals. In conclusion, in a juvenile-adolescent animal model of diet-induced obesity engagement in physical activity is beneficial in reducing the inflammatory effects of obesity.

Loss of Gi G-Protein-Coupled Receptor Signaling in Osteoblasts Accelerates Bone Fracture Healing.

PubMed

Wang, Liping; Hsiao, Edward C; Lieu, Shirley; Scott, Mark; O'Carroll, Dylan; Urrutia, Ashley; Conklin, Bruce R; Colnot, Celine; Nissenson, Robert A

2015-10-01

G-protein-coupled receptors (GPCRs) are key regulators of skeletal homeostasis and are likely important in fracture healing. Because GPCRs can activate multiple signaling pathways simultaneously, we used targeted disruption of G(i) -GPCR or activation of G(s) -GPCR pathways to test how each pathway functions in the skeleton. We previously demonstrated that blockade of G(i) signaling by pertussis toxin (PTX) transgene expression in maturing osteoblastic cells enhanced cortical and trabecular bone formation and prevented age-related bone loss in female mice. In addition, activation of G(s) signaling by expressing the G(s) -coupled engineered receptor Rs1 in maturing osteoblastic cells induced massive trabecular bone formation but cortical bone loss. Here, we test our hypothesis that the G(i) and G(s) pathways also have distinct functions in fracture repair. We applied closed, nonstabilized tibial fractures to mice in which endogenous G(i) signaling was inhibited by PTX, or to mice with activated G(s) signaling mediated by Rs1. Blockade of endogenous G(i) resulted in a smaller callus but increased bone formation in both young and old mice. PTX treatment decreased expression of Dkk1 and increased Lef1 mRNAs during fracture healing, suggesting a role for endogenous G(i) signaling in maintaining Dkk1 expression and suppressing Wnt signaling. In contrast, adult mice with activated Gs signaling showed a slight increase in the initial callus size with increased callus bone formation. These results show that G(i) blockade and G(s) activation of the same osteoblastic lineage cell can induce different biological responses during fracture healing. Our findings also show that manipulating the GPCR/cAMP signaling pathway by selective timing of G(s) and G(i) -GPCR activation may be important for optimizing fracture repair. © 2015 American Society for Bone and Mineral Research.

Uncoupled iron homeostasis in type 2 diabetes mellitus.

PubMed

Altamura, Sandro; Kopf, Stefan; Schmidt, Julia; Müdder, Katja; da Silva, Ana Rita; Nawroth, Peter; Muckenthaler, Martina U

2017-12-01

Diabetes mellitus is frequently associated with iron overload conditions, such as primary and secondary hemochromatosis. Conversely, patients affected by type 2 diabetes mellitus (T2DM) show elevated ferritin levels, a biomarker for increased body iron stores. Despite these documented associations between dysregulated iron metabolism and T2DM, the underlying mechanisms are poorly understood. Here, we show that T2DM patients have reduced serum levels of hepcidin, the iron-regulated hormone that maintains systemic iron homeostasis. Consistent with this finding, we also observed an increase in circulating iron and ferritin levels. Our analysis of db/db mice demonstrates that this model recapitulates the systemic alterations observed in patients. Interestingly, db/db mice show an overall hepatic iron deficiency despite unaltered expression of ferritin and the iron importer TfR1. In addition, the liver correctly senses increased circulating iron levels by activating the BMP/SMAD signaling pathway even though hepcidin expression is decreased. We show that increased AKT phosphorylation may override active BMP/SMAD signaling and decrease hepcidin expression in 10-week old db/db mice. We conclude that the metabolic alterations occurring in T2DM impact on the regulation of iron homeostasis on multiple levels. As a result, metabolic perturbations induce an "iron resistance" phenotype, whereby signals that translate increased circulating iron levels into hepcidin production, are dysregulated. T2DM patients show increased circulating iron levels. T2DM is associated with inappropriately low hepcidin levels. Metabolic alterations in T2DM induce an "iron resistance" phenotype.

Just Be It! Healthy and Fit Increases Fifth Graders' Fruit and Vegetable Intake, Physical Activity, and Nutrition Knowledge

ERIC Educational Resources Information Center

DelCampo, Diana; Baca, Jacqueline S.; Jimenez, Desaree; Sanchez, Paula Roybal; DelCampo, Robert

2011-01-01

Just Be It! Healthy and Fit reduces the risk factors for childhood obesity for fifth graders using hands-on field trips, in-class lessons, and parent outreach efforts. Pre-test and post-test scores from the year-long classroom instruction showed a statistically significant increase in fruit and vegetable intake, physical activity, and nutrition…

Running on Empty: Leptin Signaling in VTA Regulates Reward from Physical Activity.

PubMed

Chen, Zuxin; Kenny, Paul J

2015-10-06

Hunger increases physical activity and stamina to support food-directed foraging behaviors, but underlying mechanisms are unclear. In this issue, Fernandes et al. (2015) show that disruption of leptin-regulated STAT3 signaling in midbrain dopamine neurons increases the rewarding effects of running in mice, which could explain the "high" experienced by endurance runners. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of gamma irradiation on the antimicrobial and free radical scavenging activities of Glycyrrhiza glabra root

NASA Astrophysics Data System (ADS)

Fatima Khattak, Khanzadi; James Simpson, Thomas

2010-04-01

The efficacy of gamma irradiation as a method of decontamination for food and herbal materials is well established. In the present study, Glycyrrhiza glabra roots were irradiated at doses 5, 10, 15, 20 and 25 kGy in a cobalt-60 irradiator. The irradiated and un-irradiated control samples were evaluated for phenolic contents, antimicrobial activities and DPPH scavenging properties. The result of the present study showed that radiation treatment up to 20 kGy does not affect the antifungal and antibacterial activity of the plant. While sample irradiated at 25 kGy does showed changes in the antibacterial activity against some selected pathogens. No significant differences in the phenolic contents were observed for control and samples irradiated at 5, 10 and 15 kGy radiation doses. However, phenolic contents increased in samples treated with 20 and 25 kGy doses. The DPPH scavenging activity significantly ( p<0.05) increased in all irradiated samples of the plant.

Synaptic Phospholipid Signaling Modulates Axon Outgrowth via Glutamate-dependent Ca2+-mediated Molecular Pathways.

PubMed

Vogt, Johannes; Kirischuk, Sergei; Unichenko, Petr; Schlüter, Leslie; Pelosi, Assunta; Endle, Heiko; Yang, Jenq-Wei; Schmarowski, Nikolai; Cheng, Jin; Thalman, Carine; Strauss, Ulf; Prokudin, Alexey; Bharati, B Suman; Aoki, Junken; Chun, Jerold; Lutz, Beat; Luhmann, Heiko J; Nitsch, Robert

2017-01-01

Altered synaptic bioactive lipid signaling has been recently shown to augment neuronal excitation in the hippocampus of adult animals by activation of presynaptic LPA2-receptors leading to increased presynaptic glutamate release. Here, we show that this results in higher postsynaptic Ca2+ levels and in premature onset of spontaneous neuronal activity in the developing entorhinal cortex. Interestingly, increased synchronized neuronal activity led to reduced axon growth velocity of entorhinal neurons which project via the perforant path to the hippocampus. This was due to Ca2+-dependent molecular signaling to the axon affecting stabilization of the actin cytoskeleton. The spontaneous activity affected the entire entorhinal cortical network and thus led to reduced overall axon fiber numbers in the mature perforant path that is known to be important for specific memory functions. Our data show that precise regulation of early cortical activity by bioactive lipids is of critical importance for proper circuit formation. © The Author 2016. Published by Oxford University Press.

Synthesis, characterization and antimicrobial activity of biodegradable conducting polypyrrole-graft-chitosan copolymer

NASA Astrophysics Data System (ADS)

Cabuk, Mehmet; Alan, Yusuf; Yavuz, Mustafa; Unal, Halil Ibrahim

2014-11-01

In this study, polypyrrole-graft-chitosan (PPy-g-CS) copolymer was chemically synthesized and its structural and morphological properties characterized by FTIR, UV-vis, SEM, XRD, TGA and zeta-potential techniques. The results revealed that there were strong interactions between PPy and CS chains. The electrical conductivity of CS increased to semiconducting range by grafting. The crystallinity and thermal stability of PPy-g-CS copolymer improved when compared to CS. The copolymer was tested against various bacterial and fungal strains at various concentrations and results obtained were compared with the reference antibiotics. The results indicated that the antibacterial activity of PPy-g-CS copolymer was stronger than CS and PPy alone. The antibacterial activity of the PPy-g-CS copolymer observed to increase with rising concentration, and showed stronger activity against bacteria than Penicillin (10 mg), Rifampicin (5 mg) and Trimethoprim (25 mg), whereas showed equipotent activity with Amikacin (30 mg) and Erythromycin (15 mg) antibiotics.

Trivalent chromium activates Rac-1 and Src and induces switch in the cell death mode in human dermal fibroblasts.

PubMed

Rudolf, Emil; Cervinka, Miroslav

2009-08-10

In this study we examined interactions between human dermal fibroblasts and chromium acetate hydroxide originating from environmental waste sediments. We show that initially exposure of fibroblasts to Cr (III) induced membrane-dependent signaling including activation of Rac1 GTPase, Src and apoptosis signal-regulating kinase 1 (ASK-1) kinases leading to increased activities of p38 and particularly Jun N-terminal kinase (JNK) and subsequent activation of caspase-3. At later treatment intervals (48-96 h), caspase-3 activity became suppressed and markedly increased lactate dehydrogenase (LDH) release was observed. Further experiments demonstrated that LDH release occurred in the presence of increased oxidative stress, extensive DNA damage, overactivation of poly(ADP-ribose)polymerase-1 (PARP-1) and depletion of ATP. Using specific inhibitors it was demonstrated that oxidative stress along with PARP-1 activity are responsible for cell death mode switch and upon their inhibition caspase-3 activity could be restored. In conclusion, Cr (III) seems to induce a biphasic response in dermal fibroblasts, with initial apoptosis switched to necrosis via increased DNA damage and resulting PARP-1 activity.

MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo.

PubMed

Saporito, Michael S; Ochman, Alexander R; Lipinski, Christopher A; Handler, Jeffrey A; Reaume, Andrew G

2012-07-01

2(1H)-pyrimidinone,5-(3-methylphenoxy) (MLR-1023) is a candidate for the treatment of type 2 diabetes. The current studies were aimed at determining the mechanism by which MLR-1023 mediates glycemic control. In these studies, we showed that MLR-1023 reduced blood glucose levels without increasing insulin secretion in vivo. We have further determined that MLR-1023 did not activate peroxisome proliferator-activated α, δ, and γ receptors or glucagon-like peptide-1 receptors or inhibit dipeptidyl peptidase-4 or α-glucosidase enzyme activity. However, in an in vitro broad kinase screen MLR-1023 activated the nonreceptor-linked Src-related tyrosine kinase Lyn. MLR-1023 increased the V(max) of Lyn with an EC(50) of 63 nM. This Lyn kinase activation was ATP binding site independent, indicating that MLR-1023 regulated the kinase through an allosteric mechanism. We have established a link between Lyn activation and blood glucose lowering with studies showing that the glucose-lowering effects of MLR-1023 were abolished in Lyn knockout mice, consistent with existing literature linking Lyn kinase and the insulin-signaling pathway. In summary, these studies describe MLR-1023 as a unique blood glucose-lowering agent and show that MLR-1023-mediated blood glucose lowering depends on Lyn kinase activity. These results, coupled with other results (J Pharmacol Exp Ther 342:23-32, 2012), suggest that MLR-1023 and Lyn kinase activation may be a new treatment modality for type 2 diabetes.

Adsorption and Pore of Physical-Chemical Activated Coconut Shell Charcoal Carbon

NASA Astrophysics Data System (ADS)

Budi, E.; Umiatin, U.; Nasbey, H.; Bintoro, R. A.; Wulandari, Fi; Erlina, E.

2018-04-01

The adsorption of activated carbon of coconut shell charcoal on heavy metals (Cu and Fe) of the wastewater and its relation with the carbon pore structure was investigated. The coconut shell was pyrolized in kiln at temperature about 75 - 150 °C for about 6 hours to produce charcoal and then shieved into milimeter sized granule particles. Chemical activation was done by immersing the charcoal into chemical solution of KOH, NaOH, HCl and H3PO4, with various concentration. The activation was followed by physical activation using horizontal furnace at 400°C for 1 hours in argon gas environment with flow rate of 200 kg/m3. The surface morphology of activated carbon were characterized by using Scanning Electron Microscopy (SEM). Wastewater was made by dissolving CuSO4.5H2O and FeSO4.7H2O into aquades. The metal adsorption was analized by using Atomic Absorption Spectroscopy (AAS). The result shows that in general, the increase of chemical concentration cause the increase of pore number of activated carbon due to an excessive chemical attack and lead the increase of adsorption. However it tend to decrease as further increasing in chemical activator concentration due to carbon collapsing. In general, the adsorption of Cu and Fe metal from wastewater by activated carbon increased as the activator concentration was increased.

Lobbying for international health: the link between good ideas and funded programs: Bread for the World and the Agency for International Development.

PubMed

Quinley, J C; Baker, T D

1986-07-01

Historically, the Agency for International Development (AIDS) health budget has been closely tied to overall development spending. A large increase in the international health appropriations in 1984 broke this pattern. Investigation shows that active grass roots organizing and congressional lobbying are the most likely responsible factors in the increase. Maintenance and expansion of this success will require increased recognition of and participation in these activities by individuals and organizations involved in international health.

A single administration of methamphetamine to mice early in the light period decreases running wheel activity observed during the dark period

PubMed Central

Kitanaka, Nobue; Kitanaka, Junichi; Hall, F. Scott; Uhl, George R.; Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi; Tatsuta, Tomohiro; Morita, Yoshio; Takemura, Motohiko

2014-01-01

Repeated intermittent administration of amphetamines acutely increases appetitive and consummatory aspects of motivated behaviors as well as general activity and exploratory behavior, including voluntary running wheel activity. Subsequently, if the drug is withdrawn, the frequency of these behaviors decrease, which is thought to be indicative of dysphoric symptoms associated with amphetamine withdrawal. Such decreases may be observed after chronic treatment or even after single drug administrations. In the present study, the effect of acute methamphetamine (METH) on running wheel activity, horizontal locomotion, appetitive behavior (food access), and consummatory behavior (food and water intake) was investigated in mice. A multi-configuration behavior apparatus designed to monitor the five behaviors was developed, where combined measures were recorded simultaneously. In the first experiment, naïve male ICR mice showed gradually increasing running wheel activity over three consecutive days after exposure to a running wheel, while mice without a running wheel showed gradually decreasing horizontal locomotion, consistent with running wheel activity being a positively motivated form of natural motor activity. In experiment 2, increased horizontal locomotion and food access, and decreased food intake, were observed for the initial 3 h after acute METH challenge. Subsequently, during the dark phase period decreased running wheel activity and horizontal locomotion were observed. The reductions in running wheel activity and horizontal locomotion may be indicative of reduced dopaminergic function, although it remains to be seen if these changes may be more pronounced after more prolonged METH treatments. PMID:22079320

Neural response patterns in spider, blood-injection-injury and social fearful individuals: new insights from a simultaneous EEG/ECG-fMRI study.

PubMed

Michałowski, Jarosław M; Matuszewski, Jacek; Droździel, Dawid; Koziejowski, Wojciech; Rynkiewicz, Andrzej; Jednoróg, Katarzyna; Marchewka, Artur

2017-06-01

In the present simultaneous EEG/ECG-fMRI study we compared the temporal and spatial characteristics of the brain responses and the cardiac activity during fear picture processing between spider, blood-injection-injury (BII) and social fearful as well as healthy (non-fearful) volunteers. All participants were presented with two neutral and six fear-related blocks of pictures: two social, two spider and two blood/injection fear blocks. In a social fear block neutral images were occasionally interspersed with photographs of angry faces and social exposure scenes. In spider and blood/injection fear blocks neutral pictures were interspersed with spider fear-relevant and blood/injection pictures, respectively. When compared to healthy controls the social fear group responded with increased activations in the anterior orbital, middle/anterior cingulate and middle/superior temporal areas for pictures depicting angry faces and with a few elevated superior frontal activations for social exposure scenes. In the blood/injection fear group, heart rate was decreased and the activity in the middle/inferior frontal and visual processing regions was increased for blood/injection pictures. The HR decrease for blood/injection pictures correlated with increased frontal responses. In the spider fear group, spider fear-relevant pictures triggered increased activations within a broad subcortical and cortical neural fear network. The HR response for spider fear-relevant stimuli was increased and correlated with an increased insula and hippocampus activity. When compared to healthy controls, all fear groups showed higher LPP amplitudes for their feared cues and an overall greater P1 hypervigilance effect. Contrasts against the fear control groups showed that the increased responses for fear-specific stimuli are mostly related to specific fears and not to general anxiety proneness. The results suggest different engagement of cognitive evaluation and down-regulation strategies and an overall increased sensitization of the fear system in the three fear groups.

SNARE-dependent upregulation of KCC2 activity following metabotropic zinc receptor (mZnR/GPR39) activation in rat cortical neurons in vitro

PubMed Central

Saadi, Robert A.; He, Kai; Hartnett, Karen A.; Kandler, Karl; Hershfinkel, Michal; Aizenman, Elias

2012-01-01

The major outward chloride transporter in neurons is the potassium chloride co-transporter 2 (KCC2), critical for maintaining an inhibitory reversal potential for GABAA receptor channels. In a recent study, we showed that Zn2+ regulates GABAA reversal potentials in the hippocampus by enhancing the activity of KCC2 via an increase in its surface expression. Zn2+ initiates this process by activating the Gq-coupled metabotropic Zn2+ receptor mZnR/GPR39. Here, we first demonstrated that mZnR/GPR39 is functional in cortical neurons in culture and then tested the hypothesis that the increase in KCC2 activity is mediated through a SNARE-dependent process. We established the presence of functional mZnR in rat cultured cortical neurons by loading cells with a Ca2+ indicator and exposing cells to Zn2+, which triggered consistent Ca2+ responses that were blocked by the Gq antagonist YM-254890, but not by the metabotropic glutamate receptor antagonist MCPG. Importantly, Zn2+ treatment under these conditions did not increase the intracellular concentrations of Zn2+ itself. We then measured KCC2 activity by monitoring both the rate and relative amount of furosemide-sensitive NH4+ influx via the co-transporter using an intracellular pH sensitive fluorescent indicator. We observed that Zn2+ pretreatment induced a Ca2+-dependent increase in KCC2 activity. The effects of Zn2+ on KCC2 activity were also observed in wild-type mouse cortical neurons in culture, but not in neurons obtained from mZnR/GPR39−/− mice, suggesting that Zn2+ acts via mZnR/GPR39 activation to upregulate KCC2 activity. We next transfected rat cortical neurons with a plasmid encoding botulinum toxin C1 (Botox C1), which cleaves the SNARE proteins syntaxin 1 and SNAP-25. Basal KCC2 activity was similar in both transfected and non-transfected neurons. Non-transfected cells, or cells transfected with marker vector alone, showed a Zn2+-dependent increase in KCC2 activity. In contrast, KCC2 activity in neurons expressing Botox C1 was unchanged by Zn2+. These results suggest that SNARE proteins are necessary for the increased activity of KCC2 following Zn2+ stimulation of mZnR/GPR39. PMID:22441041

Neutral endopeptidase inhibition in diabetic wound repair.

PubMed

Spenny, Michelle L; Muangman, Pornprom; Sullivan, Stephen R; Bunnett, Nigel W; Ansel, John C; Olerud, John E; Gibran, Nicole S

2002-01-01

In response to cutaneous injury, sensory nerves release substance P, a proinflammatory neuropeptide. Substance P stimulates mitogenesis and migration of keratinocytes, fibroblasts, and endothelial cells. Neutral endopeptidase (NEP), a cell surface metallopeptidase, degrades substance P. Chronic nonhealing wounds and skin from patients with diabetes mellitus show increased NEP localization and activity. We hypothesized that increased NEP may retard wound healing and that NEP inhibition would improve closure kinetics in an excisional murine wound model. NEP enzyme activity was measured in skin samples from mutant diabetic mice (db/db) and nondiabetic (db/-) littermates by degradation of glutaryl-ala-ala-phe-4-methoxy-2-naphthylamine. Full-thickness 6-mm dorsal excisional wounds treated with normal saline or the NEP inhibitor thiorphan (10 microM or 25 microM) for 7 days were followed until closure. Histological examination and NEP activity were evaluated in a subset of wounds. NEP activity in unwounded db/db skin (20.6 pmol MNA/hr/ microg) significantly exceeded activity in db/-skin (7.9 pmol MNA/hr/ microg; p = 0.02). In db/db mice, 25 microM thiorphan shortened time to closure (18.0 days; p < 0.05) compared to normal saline (23.5 days). NEP inhibition did not alter closure kinetics in db/-mice. While the inflammatory response appeared enhanced in early wounds treated with thiorphan, blinded histological scoring of healed wounds using a semiquantitative scale showed no difference in inflammation. Unwounded skin from diabetic mice shows increased NEP activity and NEP inhibition improved wound closure kinetics without affecting contraction, suggesting that its principal effect was to augment epithelialization.

PPARδ activation in human myotubes increases mitochondrial fatty acid oxidative capacity and reduces glucose utilization by a switch in substrate preference.

PubMed

Feng, Yuan Z; Nikolić, Nataša; Bakke, Siril S; Boekschoten, Mark V; Kersten, Sander; Kase, Eili T; Rustan, Arild C; Thoresen, G Hege

2014-02-01

The role of peroxisome proliferator-activated receptor δ (PPARδ) activation on global gene expression and mitochondrial fuel utilization were investigated in human myotubes. Only 21 genes were up-regulated and 3 genes were down-regulated after activation by the PPARδ agonist GW501516. Pathway analysis showed up-regulated mitochondrial fatty acid oxidation, TCA cycle and cholesterol biosynthesis. GW501516 increased oleic acid oxidation and mitochondrial oxidative capacity by 2-fold. Glucose uptake and oxidation were reduced, but total substrate oxidation was not affected, indicating a fuel switch from glucose to fatty acid. Cholesterol biosynthesis was increased, but lipid biosynthesis and mitochondrial content were not affected. This study confirmed that the principal effect of PPARδ activation was to increase mitochondrial fatty acid oxidative capacity. Our results further suggest that PPARδ activation reduced glucose utilization through a switch in mitochondrial substrate preference by up-regulating pyruvate dehydrogenase kinase isozyme 4 and genes involved in lipid metabolism and fatty acid oxidation.

Postexercise whole-body sweating increases during muscle metaboreceptor activation in young men.

PubMed

Friesen, Brian J; Poirier, Martin P; Lamarche, Dallon T; D'Souza, Andrew W; Kim, Jung-Hyun; Notley, Sean R; Kenny, Glen P

2018-04-01

We assessed the effect of metaboreceptor activation on whole-body evaporative heat loss (WB-EHL) in 12 men (aged 24 ± 4 years) in the early-to-late stages of a 60-min exercise recovery in the heat. Metaboreceptor activation induced by 1-min isometric-handgrip (IHG) exercise followed by 5-min forearm ischemia to trap metabolites increased WB-EHL by 25%-31% and 26%-34% during the ischemic period relative to IHG-only and control (natural recovery only), respectively, throughout recovery. We show that metaboreceptor activation enhances WB-EHL in recovery.

Reading Embossed Capital Letters: An fMRI Study in Blind and Sighted Individuals

PubMed Central

Burton, H.; McLaren, D.G.; Sinclair, R.J.

2013-01-01

Reading Braille activates visual cortex in blind people [Burton et al., J Neurophysiol 2002;87: 589-611; Sadato et al., Nature 1996;380:526-528; Sadato et al., Brain 1998;121:1213-1229]. Because learning Braille requires extensive training, we had sighted and blind people read raised block capital letters to determine whether all groups engage visual cortex similarly when reading by touch. Letters were passively rubbed across the right index finger at 30 mm/s using an MR-compatible drum stimulator. Age-matched sighted, early blind (lost sight 0–5 years), and late blind (lost sight >5.5 years) volunteers performed three tasks: stating an identified letter, stating a verb containing an identified letter, and feeling a moving smooth surface. Responses were voiced immediately after the drum stopped moving across the fingertip. All groups showed increased activity in visual areas V1 and V2 during both letter identification tasks. Blind compared to sighted participants showed greater activation increases predominantly in the parafoveal-peripheral portions of visuotopic areas and posterior parts of BA 20 and 37. Sighted participants showed suppressed activity in most of the same areas except for small positive responses bilaterally in V1, left V5/MT+, and bilaterally in BA 37/20. Blind individuals showed suppression of the language areas in the frontal cortex, while sighted individuals showed slight positive responses. Early blind showed a more extensive distribution of activity in superior temporal sulcal multisensory areas. These results show cross-modal reorganization of visual cortex and altered response dynamics in nonvisual areas that plausibly reflect mechanisms for adaptive plasticity in blindness. PMID:16142777

Transgenic Expression of Osteoactivin/gpnmb Enhances Bone Formation In Vivo and Osteoprogenitor Differentiation Ex Vivo.

PubMed

Frara, Nagat; Abdelmagid, Samir M; Sondag, Gregory R; Moussa, Fouad M; Yingling, Vanessa R; Owen, Thomas A; Popoff, Steven N; Barbe, Mary F; Safadi, Fayez F

2016-01-01

Initial identification of osteoactivin (OA)/glycoprotein non-melanoma clone B (gpnmb) was demonstrated in an osteopetrotic rat model, where OA expression was increased threefold in mutant bones, compared to normal. OA mRNA and protein expression increase during active bone regeneration post-fracture, and primary rat osteoblasts show increased OA expression during differentiation in vitro. To further examine OA/gpnmb as an osteoinductive agent, we characterized the skeletal phenotype of transgenic mouse overexpressing OA/gpnmb under the CMV-promoter (OA-Tg). Western blot analysis showed increased OA/gpnmb in OA-Tg osteoblasts, compared to wild-type (WT). In OA-Tg mouse femurs versus WT littermates, micro-CT analysis showed increased trabecular bone volume and thickness, and cortical bone thickness; histomorphometry showed increased osteoblast numbers, bone formation and mineral apposition rates in OA-Tg mice; and biomechanical testing showed higher peak moment and stiffness. Given that OA/gpnmb is also over-expressed in osteoclasts in OA-Tg mice, we evaluated bone resorption by ELISA and histomorphometry, and observed decreased serum CTX-1 and RANK-L, and decreased osteoclast numbers in OA-Tg, compared to WT mice, indicating decreased bone remodeling in OA-Tg mice. The proliferation rate of OA-Tg osteoblasts in vitro was higher, compared to WT, as was alkaline phosphatase staining and activity, the latter indicating enhanced differentiation of OA-Tg osteoprogenitors. Quantitative RT-PCR analysis showed increased TGF-β1 and TGF-β receptors I and II expression in OA-Tg osteoblasts, compared to WT. Together, these data suggest that OA overexpression has an osteoinductive effect on bone mass in vivo and stimulates osteoprogenitor differentiation ex vivo. © 2015 Wiley Periodicals, Inc.

Gelatin hydrolysates from farmed Giant catfish skin using alkaline proteases and its antioxidative function of simulated gastro-intestinal digestion.

PubMed

Ketnawa, Sunantha; Martínez-Alvarez, Oscar; Benjakul, Soottawat; Rawdkuen, Saroat

2016-02-01

This work aims to evaluate the ability of different alkaline proteases to prepare active gelatin hydrolysates. Fish skin gelatin was hydrolysed by visceral alkaline-proteases from Giant catfish, commercial trypsin, and Izyme AL®. All antioxidant activity indices of the hydrolysates increased with increasing degree of hydrolysis (P<0.05). The hydrolysates obtained with Izyme AL® and visceral alkaline-proteases showed the highest and lowest radical scavenging capacity, while prepared with commercial trypsin was the most effective in reducing ferric ions and showed the best metal chelating properties. The hydrolysate obtained with Izyme AL® showed the lowest iron reducing ability, but provided the highest average molecular weight (⩾ 7 kDa), followed by commercial trypsin (2.2 kDa) and visceral alkaline-proteases (1.75 kDa). After in vitro gastrointestinal digestion, the hydrolysates showed significant higher radical scavenging, reducing ferric ions and chelating activities. Gelatin hydrolysates, from fish skin, could serve as a potential source of functional food ingredients for health promotion. Copyright © 2015 Elsevier Ltd. All rights reserved.

NbActiv4 medium improvement to Neurobasal/B27 increases neuron synapse densities and network spike rates on multielectrode arrays.

PubMed

Brewer, Gregory J; Boehler, Michael D; Jones, Torrie T; Wheeler, Bruce C

2008-05-30

The most interesting property of neurons is their long-distance propagation of signals as spiking action potentials. Since 1993, Neurobasal/B27 has been used as a serum-free medium optimized for hippocampal neuron survival. Neurons on microelectrode arrays (MEA) were used as an assay system to increase spontaneous spike rates in media of different compositions. We find spike rates of 0.5 s(-1) (Hz) for rat embryonic hippocampal neurons cultured in Neurobasal/B27, lower than cultures in serum-based media and offering an opportunity for improvement. NbActiv4 was formulated by addition of creatine, cholesterol and estrogen to Neurobasal/B27 that synergistically produced an eightfold increase in spontaneous spike activity. The increased activity with NbActiv4 correlated with a twofold increase in immunoreactive synaptophysin bright puncta and GluR1 total puncta. Characteristic of synaptic scaling, immunoreactive GABAAbeta puncta also increased 1.5-fold and NMDA-R1 puncta increased 1.8-fold. Neuron survival in NbActiv4 equaled that in Neurobasal/B27, but with slightly higher astroglia. Resting respiratory demand was decreased and demand capacity was increased in NbActiv4, indicating less stress and higher efficiency. These results show that NbActiv4 is an improvement to Neurobasal/B27 for cultured networks with an increased density of synapses and transmitter receptors which produces higher spontaneous spike rates in neuron networks.

Homocysteine activates T cells by enhancing endoplasmic reticulum-mitochondria coupling and increasing mitochondrial respiration.

PubMed

Feng, Juan; Lü, Silin; Ding, Yanhong; Zheng, Ming; Wang, Xian

2016-06-01

Hyperhomocysteinemia (HHcy) accelerates atherosclerosis by increasing proliferation and stimulating cytokine secretion in T cells. However, whether homocysteine (Hcy)-mediated T cell activation is associated with metabolic reprogramming is unclear. Here, our in vivo and in vitro studies showed that Hcy-stimulated splenic T-cell activation in mice was accompanied by increased levels of mitochondrial reactive oxygen species (ROS) and calcium, mitochondrial mass and respiration. Inhibiting mitochondrial ROS production and calcium signals or blocking mitochondrial respiration largely blunted Hcy-induced T-cell interferon γ (IFN-γ) secretion and proliferation. Hcy also enhanced endoplasmic reticulum (ER) stress in T cells, and inhibition of ER stress with 4-phenylbutyric acid blocked Hcy-induced T-cell activation. Mechanistically, Hcy increased ER-mitochondria coupling, and uncoupling ER-mitochondria by the microtubule inhibitor nocodazole attenuated Hcy-stimulated mitochondrial reprogramming, IFN-γ secretion and proliferation in T cells, suggesting that juxtaposition of ER and mitochondria is required for Hcy-promoted mitochondrial function and T-cell activation. In conclusion, Hcy promotes T-cell activation by increasing ER-mitochondria coupling and regulating metabolic reprogramming.

Changes in cortical, cerebellar and basal ganglia representation after comprehensive long term unilateral hand motor training.

PubMed

Walz, A D; Doppl, K; Kaza, E; Roschka, S; Platz, T; Lotze, M

2015-02-01

We were interested in motor performance gain after unilateral hand motor training and associated changes of cerebral and cerebellar movement representation tested with functional magnetic resonance imaging (fMRI) before and after training. Therefore, we trained the left hand of strongly right-handed healthy participants with a comprehensive training (arm ability training, AAT) over two weeks. Motor performance was tested for the trained and non-trained hand before and after the training period. Functional imaging was performed for the trained and the non-trained hand separately and comprised force modulation with the fist, sequential finger movements and a fast writing task. After the training period the performance gain of tapping movements was comparable for both hand sides, whereas the motor performance for writing showed a higher training effect for the trained hand. fMRI showed a reduction of activation in supplementary motor, dorsolateral prefrontal cortex, parietal cortical areas and lateral cerebellar areas during sequential finger movements over time. During left hand writing lateral cerebellar hemisphere also showed reduced activation, while activation of the anterior cerebellar hemisphere was increased. An initially high anterior cerebellar activation magnitude was a predictive value for high training outcome of finger tapping and visual guided movements. During the force modulation task we found increased activation in the striate. Overall, a comprehensive long-term training of the less skillful hand in healthy participants resulted in relevant motor performance improvements, as well as an intermanual learning transfer differently pronounced for the type of movement tested. Whereas cortical motor area activation decreased over time, cerebellar anterior hemisphere and striatum activity seem to represent increasing resources after long-term motor training. Copyright © 2014 Elsevier B.V. All rights reserved.

Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

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

Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won

2012-04-01

Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.1 cells as well as in mouse peritoneal macrophages. Furthermore, this activity was found to be correlated with Western blot findings in J774A.1 cells, which showed that MMP-9 expression was concentration- and time-dependently increased by Hcy. Inhibition of the ERK and Akt pathways ledmore » to a significant decrease in Hcy-induced MMP-9 expression, and combined treatment with inhibitors of the ERK and Akt pathways showed an additive effects. Activity assays for ERK and Akt showed that Hcy increased the phosphorylation of both, but these phosphorylation were not affected by inhibitors of the Akt and ERK pathways. In line with these findings, the molecular inhibition of ERK and Akt using siRNA did not affect the Hcy-induced phosphorylation of Akt and ERK, respectively. Taken together, these findings suggest that Hcy enhances MMP-9 production in murine macrophages by separately activating the ERK and Akt signaling pathways. -- Highlights: ► Homocysteine (Hcy) induced MMP-9 production in murine macrophages. ► Hcy induced MMP-9 production through ERK and Akt signaling pathways. ► ERK and Akt signaling pathways were activated by Hcy in murine macrophages. ► ERK and Akt pathways were additively act on Hcy-induced MMP-9 production. ► Hcy enhances MMP-9 production in macrophages via activation of ERK and Akt signaling pathways in an independent manner.« less

Biochemical characterisation of the esterase activities of wine lactic acid bacteria.

PubMed

Matthews, Angela; Grbin, Paul R; Jiranek, Vladimir

2007-11-01

Esters are an important group of volatile compounds that can contribute to wine flavour. Wine lactic acid bacteria (LAB) have been shown to produce esterases capable of hydrolysing ester substrates. This study aims to characterise the esterase activities of nine LAB strains under important wine conditions, namely, acidic conditions, low temperature (to 10 degrees C) and in the presence of ethanol (2-18% v/v). Esterase substrate specificity was also examined using seven different ester substrates. The bacteria were generally found to have a broad pH activity range, with the majority of strains showing maximum activity close to pH 6.0. Exceptions included an Oenococcus oeni strain that retained most activity even down to a pH of 4.0. Most strains exhibited highest activity across the range 30-40 degrees C. Increasing ethanol concentration stimulated activity in some of the strains. In particular, O. oeni showed an increase in activity up to a maximum ethanol concentration of around 16%. Generally, strains were found to have greater activity towards short-chained esters (C2-C8) compared to long-chained esters (C10-C18). Even though the optimal physicochemical conditions for enzyme activity differed from those found in wine, these findings are of potential importance to oenology because significant activities remained under wine-like conditions.

Short-Term Responses of Soil Respiration and C-Cycle Enzyme Activities to Additions of Biochar and Urea in a Calcareous Soil

PubMed Central

Song, Dali; Xi, Xiangyin; Huang, Shaomin; Liang, Guoqing; Sun, Jingwen; Zhou, Wei; Wang, Xiubin

2016-01-01

Biochar (BC) addition to soil is a proposed strategy to enhance soil fertility and crop productivity. However, there is limited knowledge regarding responses of soil respiration and C-cycle enzyme activities to BC and nitrogen (N) additions in a calcareous soil. A 56-day incubation experiment was conducted to investigate the combined effects of BC addition rates (0, 0.5, 1.0, 2.5 and 5.0% by mass) and urea (U) application on soil nutrients, soil respiration and C-cycle enzyme activities in a calcareous soil in the North China Plain. Our results showed soil pH values in both U-only and U plus BC treatments significantly decreased within the first 14 days and then stabilized, and CO2emission rate in all U plus BC soils decreased exponentially, while there was no significant difference in the contents of soil total organic carbon (TOC), dissolved organic carbon (DOC), total nitrogen (TN), and C/N ratio in each treatment over time. At each incubation time, soil pH, electrical conductivity (EC), TOC, TN, C/N ratio, DOC and cumulative CO2 emission significantly increased with increasing BC addition rate, while soil potential activities of the four hydrolytic enzymes increased first and then decreased with increasing BC addition rate, with the largest values in the U + 1.0%BC treatment. However, phenol oxidase activity in all U plus BC soils showed a decreasing trend with the increase of BC addition rate. Our results suggest that U plus BC application at a rate of 1% promotes increases in hydrolytic enzymes, does not highly increase C/N and C mineralization, and can improve in soil fertility. PMID:27589265

Nitrogen recycling from the xylem in rice leaves: dependence upon metabolism and associated changes in xylem hydraulics.

PubMed

Bailey, Karen J; Leegood, Richard C

2016-04-01

Measurements of amino acids in the guttation fluid and in the xylem exudates of cut leaves from intact plants provide evidence of the remarkable efficiency with which these nitrogenous compounds are reabsorbed from the xylem sap. This could be achieved by mechanisms involving intercellular transport and/or metabolism. Developmental changes in transcripts and protein showed that transcripts for phosphoenolpyruvate carboxykinase (PEPCK) increased from the base to the leaf tip, and were markedly increased by supplying asparagine. Supplying amino acids also increased the amounts of protein of PEPCK and, to a lesser extent, of pyruvate, Pi dikinase. PEPCK is present in the hydathodes, stomata and vascular parenchyma of rice leaves. Evidence for the role of PEPCK was obtained by using 3-mercaptopicolinic acid (MPA), a specific inhibitor of PEPCK, and by using an activation-tagged rice line that had an increase in PEPCK activity, to show that activation of PEPCK resulted in a decrease in N in the guttation fluid and that treatment by MPA resulted in an increase in amino acids in the guttation fluid and xylem sap towards the leaf tip. Furthermore, increasing PEPCK activity decreased the amount of guttation fluid, whereas decreasing PEPCK activity increased the amount of xylem sap or guttation fluid towards the leaf tip. The findings suggest the following hypotheses: (i) both metabolism and transport are involved in xylem recycling and (ii) excess N is the signal involved in modulating xylem hydraulics, perhaps via nutrient regulation of water-transporting aquaporins. Water relations and vascular metabolism and transport are thus intimately linked. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Roles of the Adenosine Receptor and CD73 in the Regulatory Effect of γδ T Cells

PubMed Central

Liang, Dongchun; Zuo, Aijun; Shao, Hui; Chen, Mingjiazi; Kaplan, Henry J.; Sun, Deming

2014-01-01

The adenosine A2A receptor (A2AR), the main functional adenosine receptor on murine T cells, plays a unique role in the attenuation of inflammation and tissue damage in vivo. Here, we showed that, of the immune cell types tested, activated γδ T cells expressed the highest levels of A2AR mRNA and that A2AR ligation inhibited αβ T cell activation, but enhanced γδ T cell activation. We also showed that the inhibitory effect of an adenosine receptor agonist on autoreactive T cells was prevented by addition of a low percentage of activated γδ T cells. Furthermore, compared to resting cells, activated γδ T cells expressed significantly lower levels of CD73, an enzyme involved in the generation of extracellular adenosine. Exogenous AMP had a significant inhibitory effect on autoreactive T cell responses, but only in the presence of CD73+ γδ T cells, and this effect was abolished by a CD73 inhibitor. Our results show that expression of increased amounts of A2AR allows γδ T cells to bind adenosine and thereby attenuate its suppressive effect, while decreased expression of CD73 results in less generation of adenosine in the inflammatory site. Together, these events allow activated γδ T cells to acquire increased proinflammatory activity, leading to augmented autoimmune responses. PMID:25268760

Bringing MapReduce Closer To Data With Active Drives

NASA Astrophysics Data System (ADS)

Golpayegani, N.; Prathapan, S.; Warmka, R.; Wyatt, B.; Halem, M.; Trantham, J. D.; Markey, C. A.

2017-12-01

Moving computation closer to the data location has been a much theorized improvement to computation for decades. The increase in processor performance, the decrease in processor size and power requirement combined with the increase in data intensive computing has created a push to move computation as close to data as possible. We will show the next logical step in this evolution in computing: moving computation directly to storage. Hypothetical systems, known as Active Drives, have been proposed as early as 1998. These Active Drives would have a general-purpose CPU on each disk allowing for computations to be performed on them without the need to transfer the data to the computer over the system bus or via a network. We will utilize Seagate's Active Drives to perform general purpose parallel computing using the MapReduce programming model directly on each drive. We will detail how the MapReduce programming model can be adapted to the Active Drive compute model to perform general purpose computing with comparable results to traditional MapReduce computations performed via Hadoop. We will show how an Active Drive based approach significantly reduces the amount of data leaving the drive when performing several common algorithms: subsetting and gridding. We will show that an Active Drive based design significantly improves data transfer speeds into and out of drives compared to Hadoop's HDFS while at the same time keeping comparable compute speeds as Hadoop.

Rivastigmine is Associated with Restoration of Left Frontal Brain Activity in Parkinson’s Disease

PubMed Central

Possin, Katherine L.; Kang, Gail A.; Guo, Christine; Fine, Eric M.; Trujillo, Andrew J.; Racine, Caroline A.; Wilheim, Reva; Johnson, Erica T.; Witt, Jennifer L.; Seeley, William W.; Miller, Bruce L.; Kramer, Joel H.

2013-01-01

Objective To investigate how acetylcholinesterase inhibitor (ChEI) treatment impacts brain function in Parkinson’s disease (PD). Methods Twelve patients with PD and either dementia or mild cognitive impairment underwent task-free functional magnetic resonance imaging before and after three months of ChEI treatment and were compared to 15 age and sex matched neurologically healthy controls. Regional spontaneous brain activity was measured using the fractional amplitude of low frequency fluctuations. Results At baseline, patients showed reduced spontaneous brain activity in regions important for motor control (e.g., caudate, supplementary motor area, precentral gyrus, thalamus), attention and executive functions (e.g., lateral prefrontal cortex), and episodic memory (e.g., precuneus, angular gyrus, hippocampus). After treatment, the patients showed a similar but less extensive pattern of reduced spontaneous brain activity relative to controls. Spontaneous brain activity deficits in the left premotor cortex, inferior frontal gyrus, and supplementary motor area were restored such that the activity was increased post-treatment compared to baseline and was no longer different from controls. Treatment-related increases in left premotor and inferior frontal cortex spontaneous brain activity correlated with parallel reaction time improvement on a test of controlled attention. Conclusions PD patients with cognitive impairment show numerous regions of decreased spontaneous brain function compared to controls, and rivastigmine is associated with performance-related normalization in left frontal cortex function. PMID:23847120

Increased error-related thalamic activity during early compared to late cocaine abstinence.

PubMed

Li, Chiang-Shan R; Luo, Xi; Sinha, Rajita; Rounsaville, Bruce J; Carroll, Kathleen M; Malison, Robert T; Ding, Yu-Shin; Zhang, Sheng; Ide, Jaime S

2010-06-01

Altered cognitive control is implicated in the shaping of cocaine dependence. One of the key component processes of cognitive control is error monitoring. Our previous imaging work highlighted greater activity in distinct cortical and subcortical regions including the dorsal anterior cingulate cortex (dACC), thalamus and insula when participants committed an error during the stop signal task (Li et al., 2008b). Importantly, dACC, thalamic and insular activity has been associated with drug craving. One hypothesis is that the intense interoceptive activity during craving prevents these cerebral structures from adequately registering error and/or monitoring performance. Alternatively, the dACC, thalamus and insula show abnormally heightened responses to performance errors, suggesting that excessive responses to salient stimuli such as drug cues could precipitate craving. The two hypotheses would each predict decreased and increased activity during stop error (SE) as compared to stop success (SS) trials in the SST. Here we showed that cocaine dependent patients (PCD) experienced greater subjective feeling of loss of control and cocaine craving during early (average of day 6) compared to late (average of day 18) abstinence. Furthermore, compared to PCD during late abstinence, PCD scanned during early abstinence showed increased thalamic as well as insular but not dACC responses to errors (SE>SS). These findings support the hypothesis that heightened thalamic reactivity to salient stimuli co-occur with cocaine craving and loss of self control. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis

PubMed Central

Bridgewood, Charlie; Fearnley, Gareth W.; Berekmeri, Anna; Laws, Philip; Macleod, Tom; Ponnambalam, Sreenivasan; Stacey, Martin; Graham, Anne; Wittmann, Miriam

2018-01-01

The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks of which involve the activation of both resident and infiltrating inflammatory myeloid cells and aberrant angiogenesis. This research demonstrates a role for IL-36γ in both myeloid activation and angiogenesis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23 and TNFα) and that this response is enhanced in macrophages from psoriasis patients. This effect is specific for IL-36γ and could not be mimicked by other IL-1 family cytokines such as IL-1α. IL-36γ was also demonstrated to induce endothelial tube formation and branching, in a VEGF-A-dependent manner. Furthermore, IL-36γ-stimulated macrophages potently activated endothelial cells and led to increased adherence of monocytes, effects that were markedly more pronounced for psoriatic macrophages. Interestingly, regardless of stimulus, psoriasis monocytes showed increased adherence to both the stimulated and unstimulated endothelium when compared with monocytes from healthy individuals. Collectively, these findings show that IL-36γ has the potential to enhance endothelium directed leucocyte infiltration into the skin and strengthen the IL-23/IL-17 pathway adding to the growing evidence of pathogenetic roles for IL-36γ in psoriatic responses. Our findings also point to a cellular response, which could potentially explain cardiovascular comorbidities in psoriasis in the form of endothelial activation and increased monocyte adherence. PMID:29535706

Effect of LED photobiomodulation on fluorescent light induced changes in cellular ATPases and Cytochrome c oxidase activity in Wistar rat.

PubMed

A, Ahamed Basha; C, Mathangi D; R, Shyamala

2016-12-01

Fluorescent light exposure at night alters cellular enzyme activities resulting in health defects. Studies have demonstrated that light emitting diode photobiomodulation enhances cellular enzyme activities. The objectives of this study are to evaluate the effects of fluorescent light induced changes in cellular enzymes and to assess the protective role of pre exposure to 670 nm LED in rat model. Male Wistar albino rats were divided into 10 groups of 6 animals each based on duration of exposure (1, 15, and 30 days) and exposure regimen (cage control, exposure to fluorescent light [1800 lx], LED preexposure followed by fluorescent light exposure and only LED exposure). Na + -K + ATPase, Ca 2+ ATPase, and cytochrome c oxidase of the brain, heart, kidney, liver, and skeletal muscle were assayed. Animals of the fluorescent light exposure group showed a significant reduction in Na + -K + ATPase and Ca 2+ ATPase activities in 1 and 15 days and their increase in animals of 30-day group in most of the regions studied. Cytochrome c oxidase showed increase in their level at all the time points assessed in most of the tissues. LED light preexposure showed a significant enhancement in the degree of increase in the enzyme activities in almost all the tissues and at all the time points assessed. This study demonstrates the protective effect of 670 nm LED pre exposure on cellular enzymes against fluorescent light induced change.

The Alveolar Microenvironment of Patients Infected with Human Immunodeficiency Virus Does Not Modify Alveolar Macrophage Interactions with Streptococcus pneumoniae

PubMed Central

Jagoe, R. Thomas; Jarman, Elizabeth R.; North, James C.; Pridmore, Alison; Musaya, Janelisa; French, Neil; Zijlstra, Eduard E.; Molyneux, Malcolm E.; Read, Robert C.

2013-01-01

We tested the hypothesis that HIV infection results in activation of alveolar macrophages and that this might be associated with impaired defense against pneumococcus. We compared alveolar macrophages and lymphocytes in 131 bronchoalveolar lavage samples from HIV-infected and healthy controls using inflammatory gene microarrays, flow cytometry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA) to determine the pattern of macrophage activation associated with HIV infection and the effect of this activation on defense against pneumococcus. We used gamma interferon (IFN-γ) priming to mimic the cellular milieu in HIV-infected lungs. InnateDB and BioLayout 3D were used to analyze the interactions of the upregulated genes. Alveolar macrophages from HIV-infected adults showed increased gene expression and cytokine production in a classical pattern. Bronchoalveolar lavage from HIV-infected subjects showed excess CD8+ lymphocytes with activated phenotype. Toll-like receptor 4 (TLR4) expression was increased in macrophages from HIV-infected subjects, but function was similar between the groups; lung lavage fluid did not inhibit TLR function in transfected HeLa cells. Alveolar macrophages from HIV-infected subjects showed normal binding and internalization of opsonized pneumococci, with or without IFN-γ priming. Alveolar macrophages from HIV-infected subjects showed classical activation compared to that of healthy controls, but this does not alter macrophage interactions with pneumococci. PMID:23576675

I know I've seen you before: Distinguishing recent-single-exposure-based familiarity from pre-existing familiarity

PubMed Central

Gimbel, Sarah I.; Brewer, James B.; Maril, Anat

2018-01-01

This study examines how individuals differentiate recent-single-exposure-based familiarity from pre-existing familiarity. If these are two distinct cognitive processes, are they supported by the same neural bases? This study examines how recent-single-exposure-based familiarity and multiple-previous-exposure-based familiarity are supported and represented in the brain using functional MRI. In a novel approach, we first behaviorally show that subjects can divide retrieval of items in pre-existing memory into judgments of recollection and familiarity. Then, using functional magnetic resonance imaging, we examine the differences in blood oxygen level dependent activity and regional connectivity during judgments of recent-single-exposure-based and pre-existing familiarity. Judgments of these two types of familiarity showed distinct regions of activation in a whole-brain analysis, in medial temporal lobe (MTL) substructures, and in MTL substructure functional-correlations with other brain regions. Specifically, within the MTL, perirhinal cortex showed increased activation during recent-single-exposure-based familiarity while parahippocampal cortex showed increased activation during judgments of pre-existing familiarity. We find that recent-single-exposure-based and pre-existing familiarity are represented as distinct neural processes in the brain; this is supported by differing patterns of brain activation and regional correlations. This spatially distinct regional brain involvement suggests that the two separate experiences of familiarity, recent-exposure-based familiarity and pre-existing familiarity, may be cognitively distinct. PMID:28073651

QEEG characteristics and spectrum weighted frequency for children diagnosed as autistic spectrum disorder.

PubMed

Pop-Jordanova, Nada; Zorcec, Tatjana; Demerdzieva, Aneta; Gucev, Zoran

2010-09-30

Autistic spectrum disorders are a group of neurological and developmental disorders associated with social, communication, sensory, behavioral and cognitive impairments, as well as restricted, repetitive patterns of behavior, activities, or interests.The aim of this study was a) to analyze QEEG findings of autistic patients and to compare the results with data base; and b) to introduce the calculation of spectrum weighted frequency (brain rate) as an indicator of general mental arousal in these patients. Results for Q-EEG shows generally increased delta-theta activity in frontal region of the brain. Changes in QEEG pattern appeared to be in a non-linear correlation with maturational processes.Brain rate measured in CZ shows slow brain activity (5. 86) which is significantly lower than normal and corresponds to low general mental arousal.Recent research has shown that autistic disorders have as their basis disturbances of neural connectivity. Neurofeedback seems capable of remediating such disturbances when these data are considered as part of treatment planning. Prognosis of this pervasive disorder depends on the intellectual abilities: the better intellectual functioning, the possibilities for life adaptation are higherQEEG shows generally increased delta-theta activity in frontal region of the brain which is related to poor cognitive abilities.Brain rate measured in CZ shows slow brain activity related to under arousal.Pharmacotherapy combined with behavior therapy, social support and especially neurofeedback technique promise slight improvements.

Effect of Chronic Athletic Activity on Brown Fat in Young Women

PubMed Central

Singhal, Vibha; Maffazioli, Giovana D.; Ackerman, Kate E.; Lee, Hang; Elia, Elisa F.; Woolley, Ryan; Kolodny, Gerald; Cypess, Aaron M.; Misra, Madhusmita

2016-01-01

Background The effect of chronic exercise activity on brown adipose tissue (BAT) is not clear, with some studies showing positive and others showing negative associations. Chronic exercise is associated with increased resting energy expenditure (REE) secondary to increased lean mass and a probable increase in BAT. Many athletes are in a state of relative energy deficit suggested by lower fat mass and hypothalamic amenorrhea. States of severe energy deficit such as anorexia nervosa are associated with reduced BAT. There are no data regarding the impact of chronic exercise activity on BAT volume or activity in young women and it is unclear whether relative energy deficiency modifies the effects of exercise on BAT. Purpose We assessed cold induced BAT volume and activity in young female athletes compared with non-athletes, and further evaluated associations of BAT with measures of REE, body composition and menstrual status. Methods The protocol was approved by our Institutional Review Board. Written informed consent was obtained from all participants prior to study initiation. This was a cross-sectional study of 24 women (16 athletes and8 non-athletes) between 18–25 years of age. Athletes were either oligo-amenorrheic (n = 8) or eumenorrheic (n = 8).We used PET/CT scans to determine cold induced BAT activity, VMAX Encore 29 metabolic cart to obtain measures of REE, and DXA for body composition. Results Athletes and non-athletes did not differ for age or BMI. Compared with non-athletes, athletes had lower percent body fat (p = 0.002), higher percent lean mass (p = 0.01) and trended higher in REE (p = 0.09). BAT volume and activity in athletes trended lower than in non-athletes (p = 0.06; p = 0.07, respectively). We found negative associations of BAT activity with duration of amenorrhea (r = -0.46, p = 0.02).BAT volume correlated inversely with lean mass (r = -0.46, p = 0.02), and positively with percent body fat, irisin and thyroid hormones. Conclusions Our study shows a trend for lower BAT in young female athletes compared with non-athletes, and shows associations of brown fat with menstrual status and body composition. Brown fat may undergo adaptive reductions with increasing energy deficit. PMID:27243823

Shift from posttranscriptional to predominant transcriptional control of the expression of the GM-CSF gene during activation of human Jurkat cells.

PubMed

Razanajaona, D; Maroc, C; Lopez, M; Mannoni, P; Gabert, J

1992-05-01

The expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene is differentially regulated in various cell types. We investigated the mechanisms controlling its expression in 12-O-tetradecanoylphorbol-13-acetate plus phytohemagglutinin-stimulated Jurkat cells, a human T-cell line. In unstimulated cells, GM-CSF mRNA was undetectable by Northern blot. Upon activation, it was detected from 3 h onward, with a progressive increase in the levels of the transcript up to 24 h of stimulation. Whereas cycloheximide treatment at the time of stimulation blocked mRNA induction, its addition at later times resulted in a marked increase in transcript levels. Run-on analysis showed that transcription of the GM-CSF gene was low to undetectable in unstimulated cells; stimulation led to transcriptional activation, which was weak at 6 h but had increased 16-fold at 24 h. In addition, the mRNA half-life decreased during activation, from 2.5 h at 6 h down to 45 min at 24 h. Cycloheximide treatment increased GM-CSF mRNA half-life (3- and 4-fold, respectively). Our results show: (a) both transcriptional and posttranscriptional signals regulate GM-CSF mRNA levels in activated Jurkat cells, (b) de novo protein synthesis is required for mRNA induction, whereas destabilizing labile proteins control the transcript stability, and (c) a shift from a posttranscriptional to a predominant transcriptional control of GM-CSF gene expression occurs during activation.