10 CFR 960.4-2-2 - Geochemistry.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REPOSITORY Postclosure Guidelines § 960.4-2-2 Geochemistry. (a) Qualifying condition. The present and... future, not affect or would favorably affect the ability of the geologic repository to isolate the waste... subjected to expected repository conditions, would remain unaltered or would alter to mineral assemblages...

Moon Illusion: An Observation.

PubMed

Goldstein, G

1962-12-21

Size comparisons of the moon are made from different locations by direct viewing (as opposed to comparisons by instrumental techniques). Under the proper conditions, the illusion is seen while the moon's position remains essentially unaltered. By this means, evidence is adduced in favor of Ptolemy's apparent-distance hypothesis.

Physiochemical charge stabilization of silver nanoparticles and its antibacterial applications

NASA Astrophysics Data System (ADS)

Vanitha, G.; Rajavel, K.; Boopathy, G.; Veeravazhuthi, V.; Neelamegam, P.

2017-02-01

Environmental standardization and stabilization of surface charges of silver nanoparticles (AgNPs) is important in biological systems and interest in bio-interfacial interaction. Different synthesized AgNPs in chemical reduced (AgNO3 (0.01, 0.1 and 0.5 M); NaBH4 and Na3C6H5O7) garnered for analysis of physico-chemical charge stabilization by means of different pH (1-13) and ionic interferences (NaCl, Ca(NO3)2, Na2CO3 and NaNO3). The uniform sized (size: ∼22 nm) and highly charged (zeta potential: -37.9 mV) AgNPs with uniform dispersion remains unaltered in high ionic interferences. Highest antifungal activity of AgNPs against Candida albicans and moderate activity against Staphylococcus aureus are correlated.

p39, the Primary Activator for Cyclin-dependent Kinase 5 (Cdk5) in Oligodendroglia, Is Essential for Oligodendroglia Differentiation and Myelin Repair*

PubMed Central

Bankston, Andrew N.; Li, Wenqi; Zhang, Hui; Ku, Li; Liu, Guanglu; Papa, Filomena; Zhao, Lixia; Bibb, James A.; Cambi, Franca; Tiwari-Woodruff, Seema K.; Feng, Yue

2013-01-01

Cyclin-dependent kinase 5 (Cdk5) plays key roles in normal brain development and function. Dysregulation of Cdk5 may cause neurodegeneration and cognitive impairment. Besides the well demonstrated role of Cdk5 in neurons, emerging evidence suggests the functional requirement of Cdk5 in oligodendroglia (OL) and CNS myelin development. However, whether neurons and OLs employ similar or distinct mechanisms to regulate Cdk5 activity remains elusive. We report here that in contrast to neurons that harbor high levels of two Cdk5 activators, p35 and p39, OLs express abundant p39 but negligible p35. In addition, p39 is selectively up-regulated in OLs during differentiation along with elevated Cdk5 activity, whereas p35 expression remains unaltered. Specific knockdown of p39 by siRNA significantly attenuates Cdk5 activity and OL differentiation without affecting p35. Finally, expression of p39, but not p35, is increased during myelin repair, and remyelination is impaired in p39−/− mice. Together, these results reveal that neurons and OLs harbor distinct preference of Cdk5 activators and demonstrate important functions of p39-dependent Cdk5 activation in OL differentiation during de novo myelin development and myelin repair. PMID:23645679

Alterations in the Helicoverpa armigera Midgut Digestive Physiology after Ingestion of Pigeon Pea Inducible Leucine Aminopeptidase

PubMed Central

Lomate, Purushottam R.; Jadhav, Bhakti R.; Giri, Ashok P.; Hivrale, Vandana K.

2013-01-01

Jasmonate inducible plant leucine aminopeptidase (LAP) is proposed to serve as direct defense in the insect midgut. However, exact functions of inducible plant LAPs in the insect midgut remain to be estimated. In the present investigation, we report the direct defensive role of pigeon pea inducible LAP in the midgut of Helicoverpa armigera (Lepidoptera: Noctuidae) and responses of midgut soluble aminopeptidases and serine proteinases upon LAP ingestion. Larval growth and survival was significantly reduced on the diets supplemented with pigeon pea LAP. Aminopeptidase activities in larvae remain unaltered in presence or absence of inducible LAP in the diet. On the contrary, serine proteinase activities were significantly decreased in the larvae reared on pigeon pea LAP containing diet as compared to larvae fed on diet without LAP. Our data suggest that pigeon pea inducible LAP is responsible for the degradation of midgut serine proteinases upon ingestion. Reduction in the aminopeptidase activity with LpNA in the H. armigera larvae was compensated with an induction of aminopeptidase activity with ApNA. Our findings could be helpful to further dissect the roles of plant inducible LAPs in the direct plant defense against herbivory. PMID:24098675

Alterations in the Helicoverpa armigera midgut digestive physiology after ingestion of pigeon pea inducible leucine aminopeptidase.

PubMed

Lomate, Purushottam R; Jadhav, Bhakti R; Giri, Ashok P; Hivrale, Vandana K

2013-01-01

Jasmonate inducible plant leucine aminopeptidase (LAP) is proposed to serve as direct defense in the insect midgut. However, exact functions of inducible plant LAPs in the insect midgut remain to be estimated. In the present investigation, we report the direct defensive role of pigeon pea inducible LAP in the midgut of Helicoverpa armigera (Lepidoptera: Noctuidae) and responses of midgut soluble aminopeptidases and serine proteinases upon LAP ingestion. Larval growth and survival was significantly reduced on the diets supplemented with pigeon pea LAP. Aminopeptidase activities in larvae remain unaltered in presence or absence of inducible LAP in the diet. On the contrary, serine proteinase activities were significantly decreased in the larvae reared on pigeon pea LAP containing diet as compared to larvae fed on diet without LAP. Our data suggest that pigeon pea inducible LAP is responsible for the degradation of midgut serine proteinases upon ingestion. Reduction in the aminopeptidase activity with LpNA in the H. armigera larvae was compensated with an induction of aminopeptidase activity with ApNA. Our findings could be helpful to further dissect the roles of plant inducible LAPs in the direct plant defense against herbivory.

UBC-Nepal Expedition: acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea level and high altitude.

PubMed

Tymko, Michael M; Tremblay, Joshua C; Steinback, Craig D; Moore, Jonathan P; Hansen, Alex B; Patrician, Alexander; Howe, Connor A; Hoiland, Ryan L; Green, Daniel J; Ainslie, Philip N

2017-11-01

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g., shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that 1 ) at rest, SNA would be elevated and FMD would be reduced at HA compared with sea-level (SL); and 2 ) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344 m) and HA (5,050 m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants ( n = 5). Our findings were 1 ) at rest, SNA was elevated ( P < 0.01), and absolute FMD was reduced ( P = 0.024), but relative FMD remained unaltered ( P = 0.061), at HA compared with SL; and 2 ) despite significantly altering SNA with LBNP (+60.3 ± 25.5%) and LBPP (-37.2 ± 12.7%) ( P < 0.01), FMD was unaltered at SL ( P = 0.448) and HA ( P = 0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA. NEW & NOTEWORTHY The role of the sympathetic nervous system on endothelial function remains unclear. We used lower-body negative and positive pressure to manipulate sympathetic nervous activity at sea level and high altitude and measured brachial endothelial function via flow-mediated dilation. We found that acutely altering sympathetic nervous activity had no effect on endothelial function. Copyright © 2017 the American Physiological Society.

Recyclable Thermoresponsive Polymer-β-Glucosidase Conjugate with Intact Hydrolysis Activity.

PubMed

Mukherjee, Ishita; Sinha, Sushant K; Datta, Supratim; De, Priyadarsi

2018-06-11

β-Glucosidase (BG) catalyzes the hydrolysis of cellobiose to glucose and is a rate-limiting enzyme in the conversion of lignocellulosic biomass to sugars toward biofuels. Since the cost of enzyme is a major contributor to biofuel economics, we report the bioconjugation of a temperature-responsive polymer with the highly active thermophilic β-glucosidase (B8CYA8) from Halothermothrix orenii toward improving enzyme recyclability. The bioconjugate, with a lower critical solution temperature (LCST) of 33 °C withstands high temperatures up to 70 °C. Though the secondary structure of the enzyme in the conjugate is slightly distorted with a higher percentage of β-sheet like structure, the stability and specific activity of B8CYA8 in the conjugate remains unaltered up to 30 °C and retains more than 70% specific activity of the unmodified enzyme at 70 °C. The conjugate can be reused for β-glucosidic bond cleavage of cellobiose for at least four cycles without any significant loss in specific activity.

21 CFR 137.190 - Cracked wheat.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Cracked wheat. 137.190 Section 137.190 Food and... Related Products § 137.190 Cracked wheat. Cracked wheat is the food prepared by so cracking or cutting... such wheat, other than moisture, remain unaltered. Cracked wheat contains not more than 15 percent of...

Osborne. A Teacher's Handbook.

ERIC Educational Resources Information Center

Cooper, Rosemary; Fordham, Jennie

Osborne, located on the Isle of Wight, is almost entirely Victorian. It was designed, built, and furnished to the royal family's specifications (as a holiday home), and remains largely unaltered since Queen Victoria died in 1901. It offers unique resources for those studying not only the Victorian royal family but other aspects of 19th-century…

The Mississippi River: A place for fish

USGS Publications Warehouse

Schramm, Harold; Ickes, Brian; Chen, Yushun; Chapman, Duane C.; Jackson, John; Chen, Daqing; Li, Zhongjie; Kilgore, Jack; Phelps, Quinton E.; Eggleton, Michael

2016-01-01

The Mississippi River flows 3,734 km from its source at Lake Itasca, Minnesota to its outlet at the Gulf of Mexico. Along its course, it collects water from portions of two Canadian provinces and 41 % of the conterminous United States. Although greatly altered for navigation and flood control throughout much of its length, the Mississippi River remains an important fishery resource that provides habitat for 188 species of fishes and recreational and commercial fishing opportunities. The objectives of this chapter are to describe the contemporary fisheries habitat throughout the Mississippi River, identify how management to achieve human benefits influences the fishes and their habitats, and summarize efforts to conserve and enhance fish habitat. The 826-km headwater reach is entirely in Minnesota and remains largely unaltered. The reaches that extend 1,059 km from St. Anthony Falls, Minnesota to above the confluence with the Missouri River near St. Louis, Missouri have been altered by impoundment that has affected floodplain function, increased sedimentation of backwaters, and homogenized the formerly diverse aquatic habitats. After the confluence with the Missouri River, the Mississippi River flows freely for 1,849 km to the Gulf of Mexico. The alterations of the free-flowing reaches of greatest significance to the fisheries resource are reducing the duration and height of the flood pulse as a consequence of shortening the river channel, disconnection of the river from its historic and present floodplain, and loss of secondary channel-island complexes. Engineering features to improve commercial navigation have also added habitat and, when wisely manipulated, can be used to rehabilitate habitat. Some aspects of water quality have improved, but legacy chemicals and nutrient-laden inflows and sediments remain problems. Although true restoration in the sense of restoring all environmental conditions to an unaltered state is unlikely, the future value of the Mississippi River as a fisheries resource will depend on actively maintaining diverse and accessible aquatic habitats to support food webs and water quality suitable for fishes.

Nicorandil improves post-fatigue tension in slow skeletal muscle fibers by modulating glutathione redox state.

PubMed

Sánchez-Duarte, E; Trujillo, X; Cortés-Rojo, C; Saavedra-Molina, A; Camargo, G; Hernández, L; Huerta, M; Montoya-Pérez, R

2017-04-01

Fatigue is a phenomenon in which force reduction has been linked to impairment of several biochemical processes. In skeletal muscle, the ATP-sensitive potassium channels (K ATP ) are actively involved in myoprotection against metabolic stress. They are present in sarcolemma and mitochondria (mitoK ATP channels). K + channel openers like nicorandil has been recognized for their ability to protect skeletal muscle from ischemia-reperfusion injury, however, the effects of nicorandil on fatigue in slow skeletal muscle fibers has not been explored, being the aim of this study. Nicorandil (10 μM), improved the muscle function reversing fatigue as increased post-fatigue tension in the peak and total tension significantly with respect to the fatigued condition. However, this beneficial effect was prevented by the mitoK ATP channel blocker 5-hydroxydecanoate (5-HD, 500 μM) and by the free radical scavenger N-2-mercaptopropionyl glycine (MPG, 1 mM), but not by the nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μM). Nicorandil also decreased lipid peroxidation and maintained both reduced glutathione (GSH) levels and an elevated GSH/GSSG ratio, whereas total glutathione (TGSH) remained unaltered during post-fatigue tension. In addition, NO production, measured through nitrite concentrations was significantly increased with nicorandil during post-fatigue tension; this increase remained unaltered in the presence of nicorandil plus L-NAME, nonetheless, this effect was reversed with nicorandil plus MPG. Hence, these results suggest that nicorandil improves the muscle function reversing fatigue in slow skeletal muscle fibers of chicken through its effects not only as a mitoK ATP channel opener but also as NO donor and as an antioxidant.

Alkaloids in plants and root cultures of Atropa belladonna overexpressing putrescine N-methyltransferase.

PubMed

Rothe, Grit; Hachiya, Akira; Yamada, Yasuyuki; Hashimoto, Takashi; Dräger, Birgit

2003-09-01

Putrescine N-methyltransferase (PMT) is the first alkaloid-specific enzyme for nicotine and tropane alkaloid formation. The pmt gene from Nicotiana tabacum was fused to the CaMV 35S promoter and integrated into the Atropa belladonna genome. Transgenic plants and derived root cultures were analysed for gene expression and for levels of alkaloids and their precursors. Scopolamine, hyoscyamine, tropine, pseudotropine, tropinone, and calystegines were found unaltered or somewhat decreased in pmt-overexpressing lines compared to controls. When root cultures were treated with 5% sucrose, calystegine levels were elevated in control roots, but were not affected in pmt-overexpressing roots. 1 microM auxin reduced calystegine levels in control roots, while in pmt-overexpressing roots all alkaloids remained unaltered. Expression level of pmt alone is apparently not limiting for tropane alkaloid formation in A. belladonna.

Influence of reagents reacting with metal, thiol and amino sites of catalytic activity and l-phenylalanine inhibition of rat intestinal alkaline phosphatase

PubMed Central

Fishman, William H.; Ghosh, Nimai K.

1967-01-01

1. Studies on the inactivation of rat intestinal alkaline phosphatase by several metal-binding agents, namely EDTA, 8-hydroxyquinoline, pyridine-2,6-dicarboxylic acid, αα′-bipyridyl, o-phenanthroline and sodium cyanide, indicated the functional role of a metal, probably zinc, in the catalysis. The metal ligands lowered stereospecific uncompetitive inhibition of the enzyme by l-phenylalanine by an extent that paralleled the decline in enzyme activity. 2. The thiol reagents p-hydroxymercuribenzoate, iodoacetamide and iodine inactivated rat intestinal phosphatase. The enzyme could be protected from inactivation by either cysteine or substrate. The l-phenylalanine inhibition remained unchanged only in the presence of moderately inactivating concentrations of the thiol reagents. 3. Inactivation of the enzyme by the amino-group-blocking reagent, O-methylisourea, provided ample evidence for the participation in the catalysis of the ∈-amino group of lysine. At the same time, l-phenylalanine inhibition remained unaltered even when the enzyme was strongly inactivated. This ∈-amino-group-blocked enzyme exhibited no change in migration in starch gel, in contrast with enzyme treated with acetic anhydride, formaldehyde or succinic anhydride. The Michaelis constant of the enzyme was enhanced by such modifications, but the optimum pH remained the same. 4. d-Phenylalanine acted as a competitive or `co-operative' activator for intestinal alkaline phosphatase after it had been modified by acetylation. PMID:16742542

Theoretical analysis and modeling of a photonic integrated circuit for frequency 8-tupled and 24-tupled millimeter wave signal generation: erratum.

PubMed

Hasan, Mehedi; Guemri, Rabiaa; Maldonado-Basilio, Ramón; Lucarz, Frédéric; de Bougrenet de la Tocnaye, Jean-Louis; Hall, Trevor

2015-12-15

A novel photonic circuit design for implementing frequency 8-tupling and 24-tupling was presented [Opt. Lett.39, 6950 (2014)10.1364/OL.39.006950OPLEDP0146-9592], and although its key message remains unaltered, there were typographical errors in the equations that are corrected in this erratum.

Gender Significance of Dress in the Organizational Setting.

ERIC Educational Resources Information Center

Patton, Eleanor Nyquist; Patton, Bobby R.

Which, when, and how elements of a fashion are adopted by a particular person or group are indicators of how that person or group is viewed by others within their society. For men who have worked in business and commerce, the clothing has changed little since the rise of the commercial middle class. The business suit remains unaltered because its…

Stability of bioactive compounds in butiá (Butia odorata) fruit pulp and nectar.

PubMed

Hoffmann, Jessica Fernanda; Zandoná, Giovana Paula; Dos Santos, Priscila Silveira; Dallmann, Camila Müller; Madruga, Francine Bonemann; Rombaldi, Cesar Valmor; Chaves, Fábio Clasen

2017-12-15

Butia odorata is a palm tree native to southern Brazil whose fruit (known as butiá) and leaves are used to make many food products and crafts. Butiá contain several biologically active compounds with potential health benefits. However, processing conditions can alter quality attributes including bioactive compound content. This study evaluated the stability of bioactive compounds in butiá pulp upon pasteurization, during 12months of frozen storage, and in butiá nectar after a 3-month storage period. Pulp pasteurization resulted in a reduction in phenolic, flavonoid, carotenoid, and ascorbic acid contents. After a 12-month frozen storage period, flavonoid, phenolic, and ascorbic acid contents decreased while carotenoid content remained unaltered. Carotenoid, ascorbic acid, and phenolic contents were unaffected by the 3-month storage of butiá nectar; however, flavonoid content and antioxidant potential were reduced. Despite bioactive compound degradation upon heat treatment and storage, butiá nectar remained rich in phenolics, especially (-)-epicatechin, rutin, and (+)-catechin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Testicular cell population dynamics following palmitine hydroxide treatment in male dogs.

PubMed

Gupta, R S; Dixit, V P

1989-04-01

Palmitine hydroxide isolated from the roots of Berberis chitria administered orally to dogs 30 mg/kg per day for 60 days brings about a consistent impairment of primary and secondary spermatocytes and elongated spermatids (Stages IV-VIII). The primary and secondary spermatocytes were reduced by 60 and 68%, respectively, and the elongated spermatids were decreased by 58%. The number of spermatogonia and Sertoli cells remained unaltered. The production of immature and mature Leydig cells decreased by 66% and 27%, respectively. Protein, sialic acid and glycogen content and acid phosphatase activity of testes and epididymides were lowered to varying extents. Testicular cholesterol was elevated significantly. Weights of the testes and epididymides were significantly reduced. The antispermatogenic action of palmitine hydroxide may be mediated by disturbances in Leydig cell function.

Altered Plasticity of Glycogen Phosphorylase in Forebrain Gliosomes Obtained from Insulinoma Patients.

PubMed

Tao, Zhen; Cheng, Ming; Hu, Huaiqiang; Wang, Shucai; Su, Jing; Lv, Wei; Guo, Hongwei; Tang, Jigang; Cao, Bingzhen

2015-09-01

We investigated a control model of hypoglycemia-exposed brain tissues from a small series of patients with insulinoma, immediately dissect them, and perform a differential cold centrifugation to obtain gliosomes and examine alterations of glycogenolytic mechanisms. The BB as well as MM isoforms of glycogen phosphorylase enzymatic protein expression remained unaltered between insulinoma and control subjects within the gliosomes. However, the glycogen phosphorylase remained in a form that was potentially activated several folds on placing the gliosomes in a glucose-free medium. This was examined by its increased interaction with protein kinase A. Inhibitors of glycogen phosphorylase was used as controls. Furthermore, we demonstrated that glucose-depleted medium enhanced production of both ATP and lactate by the gliosomes. It is possible that a portion of glucose obtained from glycogen breakdown was circuited through glycolytic pathways to generate ATP. It has been reported earlier that ATP within gliosomes plays a major role in glutamate uptake, thus potentially preventing seizure during active bouts of hypoglycemia. Lactate shuttle from astrocytes is a potential mechanism to balance neuronal bioenergetics during events of hypoglycemia. Newer approaches to pharmacologically modulate glycogen phosphorylase may prove to be rational approach for neuroprotective therapy in this common clinical syndrome of hypoglycemia.

Gastric Electrical Stimulation Decreases Gastric Distension-Induced Central Nociception Response through Direct Action on Primary Afferents

PubMed Central

Ouelaa, Wassila; Ghouzali, Ibtissem; Langlois, Ludovic; Fetissov, Serguei; Déchelotte, Pierre; Ducrotté, Philippe; Leroi, Anne Marie; Gourcerol, Guillaume

2012-01-01

Background & Aims Gastric electrical stimulation (GES) is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. Methods Gastric pain was induced by performing gastric distension (GD) in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation), while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. Results GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9–T10), the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. Conclusions GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception. PMID:23284611

Elimination of GRK2 from cholinergic neurons reduces behavioral sensitivity to muscarinic receptor activation.

PubMed

Daigle, Tanya L; Caron, Marc G

2012-08-15

Although G-protein-coupled receptor kinase 2 (GRK2) is the most widely studied member of a family of kinases that has been shown to exert powerful influences on a variety of G-protein-coupled receptors, its role in the brain remains largely unknown. Here we report the localization of GRK2 in the mouse brain and generate novel conditional knock-out (KO) mice to assess the physiological importance of this kinase in cholinergic neurons. Mice with the selective deletion of GRK2 in this cell population (ChAT(IRES-cre)Grk2(f/f) KO mice) exhibit reduced behavioral responsiveness to challenge with oxotremorine-M (Oxo-M), a nonselective muscarinic acetylcholine receptor agonist. Specifically, Oxo-M-induced hypothermia, hypolocomotion, and salivation were markedly reduced in these animals, while analgesic responses were unaltered. In contrast, we found that GRK2 deficiency in cholinergic neurons does not alter cocaine-induced psychomotor activation, behavioral sensitization, or conditioned place preference. These results demonstrate that the elimination of GRK2 in cholinergic neurons reduces sensitivity to select muscarinic-mediated behaviors, while dopaminergic effects remain intact and further suggests that GRK2 may selectively impair muscarinic acetylcholine receptor-mediated function in vivo.

Evaluation of the use of scientific information in developing the 1997 Forest plan for the Tongass National Forest.

Treesearch

Fred H. Everest; Douglas N. Swanston; Charles G. Shaw; Winston P. Smith; Kent R. Julin; Stewart D. Allen

1997-01-01

The Tongass National Forest is the largest remaining relatively unaltered coastal temperate rain forest in the world. The Forest consists of 16.9 million acres of land distributed across more that 22,000 islands and a narrow strip of mainland in southeast Alaska. The Forest contains abundant timber, wildlife, fisheries, mineral, and scenic resources. The authors...

Pain sensitivity in patients with haemophilia following moderate aerobic exercise intervention.

PubMed

Krüger, S; Weitz, C; Runkel, B; Hilberg, T

2016-11-01

Physical activity is influenced by pain and vice versa. Although studies recommend exercise therapy for patients with haemophilia (PwH), the influence of physical activity on the pain condition in PwH has not been investigated so far. Aim of this study was to examine the effect of a treadmill intervention with self-chosen velocity on the acute pain sensitivity in PwH. Twenty PwH [aged 24-58 years, moderate (n = 3) to severe (n = 17) haemophilia A (n = 17) or B (n = 3)] and 20 control subjects (aged 26-61 years) were included in this study. Eighteen PwH and all controls completed a treadmill intervention for 30 min. Pressure pain thresholds (PPT) in Newton (N) were measured at both the knees, ankles and elbows, sternum and forehead before (pre) and immediately after walking (post). PwH and controls walked with comparable speed (mean speed in km h -1 ; PwH: 3.5, controls: 3.8), resulting in significantly different values of performance-related parameters such as heart rate (mean heart rate per minute; PwH: 102, controls: 86; P ≤ 0.01). Compared to baseline values, PPT remained unaltered at all landmarks in both groups after walking (e.g. pre/post in Newton; knee right: PwH: 63.1/63.0, controls: 93.8/93.8; left knee: PwH: 62.1/62.7, controls: 90.0/93.4), indicating a non-increasing pain condition. Findings of unaltered PPT following moderate aerobic exercise showed initial evidence that PwH are able to perform an endurance exercise with self-chosen velocity for 30 min as recommended, without increasing the acute pain condition. By doing so, PwH can benefit from the positive effects of endurance exercise. © 2016 John Wiley & Sons Ltd.

Application of sodium carbonate prevents sulphur poisoning of catalysts in automated total mercury analysis

NASA Astrophysics Data System (ADS)

McLagan, David S.; Huang, Haiyong; Lei, Ying D.; Wania, Frank; Mitchell, Carl P. J.

2017-07-01

Analysis of high sulphur-containing samples for total mercury content using automated thermal decomposition, amalgamation, and atomic absorption spectroscopy instruments (USEPA Method 7473) leads to rapid and costly SO2 poisoning of catalysts. In an effort to overcome this issue, we tested whether the addition of powdered sodium carbonate (Na2CO3) to the catalyst and/or directly on top of sample material increases throughput of sulphur-impregnated (8-15 wt%) activated carbon samples per catalyst tube. Adding 5 g of Na2CO3 to the catalyst alone only marginally increases the functional lifetime of the catalyst (31 ± 4 g of activated carbon analyzed per catalyst tube) in relation to unaltered catalyst of the AMA254 total mercury analyzer (17 ± 4 g of activated carbon). Adding ≈ 0.2 g of Na2CO3 to samples substantially increases (81 ± 17 g of activated carbon) catalyst life over the unaltered catalyst. The greatest improvement is achieved by adding Na2CO3 to both catalyst and samples (200 ± 70 g of activated carbon), which significantly increases catalyst performance over all other treatments and enables an order of magnitude greater sample throughput than the unaltered samples and catalyst. It is likely that Na2CO3 efficiently sequesters SO2, even at high furnace temperatures to produce Na2SO4 and CO2, largely negating the poisonous impact of SO2 on the catalyst material. Increased corrosion of nickel sampling boats resulting from this methodological variation is easily resolved by substituting quartz boats. Overall, this variation enables an efficient and significantly more affordable means of employing automated atomic absorption spectrometry instruments for total mercury analysis of high-sulphur matrices.

Mice Lacking the SLAM Family Member CD84 Display Unaltered Platelet Function in Hemostasis and Thrombosis

PubMed Central

Hofmann, Sebastian; Braun, Attila; Pozgaj, Rastislav; Morowski, Martina; Vögtle, Timo; Nieswandt, Bernhard

2014-01-01

Background Platelets are anuclear cell fragments derived from bone marrow megakaryocytes that safeguard vascular integrity by forming thrombi at sites of vascular injury. Although the early events of thrombus formation—platelet adhesion and aggregation—have been intensively studied, less is known about the mechanisms and receptors that stabilize platelet-platelet interactions once a thrombus has formed. One receptor that has been implicated in this process is the signaling lymphocyte activation molecule (SLAM) family member CD84, which can undergo homophilic interactions and becomes phosphorylated upon platelet aggregation. Objective The role of CD84 in platelet physiology and thrombus formation was investigated in CD84-deficient mice. Methods and Results We generated CD84-deficient mice and analyzed their platelets in vitro and in vivo. Cd84−/− platelets exhibited normal activation and aggregation responses to classical platelet agonists. Furthermore, CD84 deficiency did not affect integrin-mediated clot retraction and spreading of activated platelets on fibrinogen. Notably, also the formation of stable three-dimensional thrombi on collagen-coated surfaces under flow ex vivo was unaltered in the blood of Cd84−/− mice. In vivo, Cd84−/− mice exhibited unaltered hemostatic function and arterial thrombus formation. Conclusion These results show that CD84 is dispensable for thrombus formation and stabilization, indicating that its deficiency may be functionally compensated by other receptors or that it may be important for platelet functions different from platelet-platelet interactions. PMID:25551754

Using Silica Sol as a Nanoglue to Prepare Nanoscale Mesoporous Composite Gel and Aerogels

DTIC Science & Technology

2000-03-31

solution-phase reactants remain unaltered. Furthermore, the composite constitutes a rigid solid architecture, such that the silica aerogel structure...nm) was immobilized in a silica aerogel structure according to the method of the present invention. The optical properties of 9 these materials...Aerogel Preparation. Acid- and base-catalyzed silica aerogels were prepared by procedures similarto those previously published in Russo et al.J.Non

Mechanistic insight into ultrasound induced enhancement of simultaneous saccharification and fermentation of Parthenium hysterophorus for ethanol production.

PubMed

Singh, Shuchi; Agarwal, Mayank; Sarma, Shyamali; Goyal, Arun; Moholkar, Vijayanand S

2015-09-01

This paper presents investigations into mechanism of ultrasound assisted bioethanol synthesis using Parthenium hysterophorus biomass through simultaneous saccharification and fermentation (SSF) mode. Approach of coupling experimental results to mathematical model for SSF using Genetic Algorithm based optimization has been adopted. Comparison of model parameters for experiments with mechanical shaking and sonication (10% duty cycle) give an interesting mechanistic account of influence of ultrasound on SSF system. A 4-fold rise in ethanol and cell mass productivity is seen with ultrasound. The analysis reveals following facets of influence of ultrasound on SSF: increase in Monod constant for glucose for cell growth, maximal specific growth rate and inhibition constant of cell growth by glucose and reduction in specific cell death rate. Values of inhibition constant of cell growth by ethanol (K3E), and constants for growth associated (a) and non-growth associated (b) ethanol production remained unaltered with sonication. Beneficial effects of ultrasound are attributed to enhanced cellulose hydrolysis, enhanced trans-membrane transport of substrate and products as well as dilution of the toxic substances due to micro-convection induced by ultrasound. Intrinsic physiological functioning of cells remained unaffected by ultrasound as indicated by unaltered values of K3E, a and b. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of some essential oils for their toxicity against fungi causing deterioration of stored food commodities.

PubMed

Mishra, A K; Dubey, N K

1994-04-01

During screening of essential oils for their antifungal activities against Aspergillus flavus, the essential oil of Cymbopogon citratus was found to exhibit fungitoxicity. The MIC of the oil was found to be 1,000 ppm, at which it showed its fungistatic nature, wide fungitoxic spectrum, nonphytotoxic nature, and superiority over synthetic fungicides, i.e., Agrosan G. N., Thiride, Ceresan, Dithane M-45, Agrozim, Bavistin, Emison, Thiovit, wettable sulfur, and copper oxychloride. The fungitoxic potency of the oil remained unaltered for 7 months of storage and upon introduction of high doses of inoculum of the test fungus. It was thermostable in nature with treatment at 5 to 100 degrees C. These findings thus indicate the possibility of exploitation of the essential oil of C. citratus as an effective inhibitor of storage fungi.

Evaluation of some essential oils for their toxicity against fungi causing deterioration of stored food commodities.

PubMed Central

Mishra, A K; Dubey, N K

1994-01-01

During screening of essential oils for their antifungal activities against Aspergillus flavus, the essential oil of Cymbopogon citratus was found to exhibit fungitoxicity. The MIC of the oil was found to be 1,000 ppm, at which it showed its fungistatic nature, wide fungitoxic spectrum, nonphytotoxic nature, and superiority over synthetic fungicides, i.e., Agrosan G. N., Thiride, Ceresan, Dithane M-45, Agrozim, Bavistin, Emison, Thiovit, wettable sulfur, and copper oxychloride. The fungitoxic potency of the oil remained unaltered for 7 months of storage and upon introduction of high doses of inoculum of the test fungus. It was thermostable in nature with treatment at 5 to 100 degrees C. These findings thus indicate the possibility of exploitation of the essential oil of C. citratus as an effective inhibitor of storage fungi. PMID:8017906

Sharp wave ripples during learning stabilize hippocampal spatial map

PubMed Central

Roux, Lisa; Hu, Bo; Eichler, Ronny; Stark, Eran; Buzsáki, György

2017-01-01

Cognitive representation of the environment requires a stable hippocampal map but the mechanisms maintaining map representation are unknown. Because sharp wave-ripples (SPW-R) orchestrate both retrospective and prospective spatial information, we hypothesized that disrupting neuronal activity during SPW-Rs affects spatial representation. Mice learned daily a new set of three goal locations on a multi-well maze. We used closed-loop SPW-R detection at goal locations to trigger optogenetic silencing of a subset of CA1 pyramidal neurons. Control place cells (non-silenced or silenced outside SPW-Rs) largely maintained the location of their place fields after learning and showed increased spatial information content. In contrast, the place fields of SPW-R-silenced place cells remapped, and their spatial information remained unaltered. SPW-R silencing did not impact the firing rates or the proportions of place cells. These results suggest that interference with SPW-R-associated activity during learning prevents the stabilization and refinement of the hippocampal map. PMID:28394323

[Pattern of growth and metabolism of thermotolerant microorganisms on media containing carbohydrates and hydrocarbons].

PubMed

Kvasnikov, E I; Isakova, D M; Eliseeva, G S; Loiko, Z I

1977-01-01

Experiments were carried out to examine the growth and metabolism of thermotolerant yeast Candida tropicalis K-41 and bacteria Micrococcus freudenreichii that do not have a single temperature point but instead have an optimal temperature plateau at which the growth rate and biosynthetic activity remain unaltered or change insignificantly. Upon transition from the carbohydrate to the hydrocarbon pattern of nutrition these microorganisms show significant changes in metabolic processes: optimal concentration of biotin in the medium decreases significantly; the synthesis of riboflavin, nicotinic and pantothenic acids increases in yeast; the synthesis of nicotinic acid, biotin and vitamin B12 increases in bacteria. During microbial cultivation on hydrocarbons the content of cell lipids grows; yeast accumulate actively phospholipids and free fatty acids; bacteria build up intensively waxes and phospholipids. With the near-maximal growth rate the total synthesis of lipids decreases on carbohydrates and increases drastically on hydrocarbons, primarily at the expense of the above fractions.

Formation of ohmic contacts to MOCVD grown p-GaN by controlled activation of Mg

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

Kaminska, E.; Piotrowska, A.; Barcz, A.

2000-11-27

We report on the formation of low resistivity ohmic contacts to p-GaN, r{sub c} < 10{sup {minus}4}{Omega}cm{sup 2}, by increasing the concentration of the active Mg in the subcontact zone, via Zr-mediated release of hydrogen. We have investigated the process of evolution of hydrogen from MOCVD grown p-GaN via Zr-based metallization, and determined the optimum processing conditions (temperature and gas ambient) for fabrication of low resistance ohmic contacts. When the process is conducted in N{sub 2} flow, the metallization remains stable at temperatures required to achieve the ohmic behavior, and the morphology of the metal/semiconductor interface is unaltered by suchmore » a heat treatment. The processing in O{sub 2}, on the contrary, causes the interdiffusion of metallization constituents and the incorporation of oxygen into the semiconductor subcontact region, which could be responsible for increased resistivity of these contacts.« less

Thermal stability and haemolytic effects of depolymerized guar gum derivatives.

PubMed

Hussain, Majid; Zahoor, Tahir; Akhtar, Saeed; Ismail, Amir; Hameed, Aneela

2018-03-01

The purpose of current study was to purify and partially depolymerize guar gum by β-mannanase, HCl, Ba(OH) 2 actions and subjected to inspect compositional, thermogravimetric analysis (TGA) and haemolytic activity. Chemical composition revealed mannose and galactose ratio remained un-altered even after process of purification and hydrolysis. TGA thermograms affirmed initial and final decomposition temperature in various zones. Major decomposition stages apparently revealed partially hydrolyzed guar gum (PHGG) exhibited better heat stable properties having more zones of degradation than crude one. Furthermore, all guar fractions (2.5-250 mg/mL) were subjected to haemolysis to evaluate toxic effects during process of hydrolysis. The crude and hydrolyzed guar galactomannans exhibited minor haemolytic activity (1.9 ± 0.03-7.24 ± 0.02%) when compared to 0.1% Triton-X 100 (100% haemolysis) showing no toxic effects to human RBC's. Conclusively, hydrolyzed guar-galactomannans are safe and can be used in food products with improved heat stability.

Strong induction of iodothyronine deiodinases by chemotherapeutic selenocompounds.

PubMed

Stoedter, M; Renko, K; Ibáñez, E; Plano, D; Becker, N-P; Martitz, J; Palop, J A; Calvo, A; Sanmartín, C; Schomburg, L

2015-02-01

The biological activity of thyroid hormones (TH) is regulated by selenoenzymes of the iodothyronine deiodinase (DIO) family catalysing TH activating and inactivating reactions. Besides TH metabolism, several studies indicate an important role of DIO isoenzymes in tumorigenesis and cancer growth. It is therefore of therapeutic importance to identify modulators of DIO expression. We have synthesized and studied a series of selenocompounds containing a methyl- or benzyl-imidoselenocarbamate backbone. One of these novel compounds had chemotherapeutic activities in a murine xenograft tumour model by an unknown mechanism. Therefore, we tested their effects on DIO expression in vitro. In HepG2 hepatocarcinoma cells, DIO1 activity was strongly (up to 10-fold) increased by the methyl- but not by the corresponding benzyl-imidoselenocarbamates. Steady-state mRNA levels remained unaltered under these conditions indicating a post-transcriptional mode of action. The effects were further characterized in HEK293 cells stably expressing DIO1, DIO2 or DIO3. Even within the artificial genetic context of the expression vectors, all three DIO isoenzymes were up-regulated by the methyl- and to a lesser extent by the benzyl-imidoselenocarbamates. Consistent stimulating effects were observed with methyl-N,N'-di(quinolin-3-ylcarbonyl)-imidoselenocarbamate (EI201), a selenocompound known for its anti-tumour activity. DIO inducing effects were unrelated to the intracellular accumulation of selenium, yet the precise mode of action remains elusive. Collectively, our data highlight that these selenocompounds may constitute interesting pharmacological compounds for modifying DIO expression potentially affecting the balance between cell differentiation and proliferation.

Naproxen, a Nonsteroidal Anti-Inflammatory Drug, Can Affect Daily Hypobaric Hypoxia-Induced Alterations of Monoamine Levels in Different Areas of the Brain in Male Rats.

PubMed

Goswami, Ananda Raj; Dutta, Goutam; Ghosh, Tusharkanti

2016-06-01

Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH)-induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS.

Additive manufactured serialization

DOEpatents

Bobbitt, III, John T.

2017-04-18

Methods for forming an identifying mark in a structure are described. The method is used in conjunction with an additive manufacturing method and includes the alteration of a process parameter during the manufacturing process. The method can form in a unique identifying mark within or on the surface of a structure that is virtually impossible to be replicated. Methods can provide a high level of confidence that the identifying mark will remain unaltered on the formed structure.

Susceptibility Profiles of Amphotericin B and Posaconazole against Clinically Relevant Mucorales Species under Hypoxic Conditions

PubMed Central

Maurer, Elisabeth; Sparber, Manuela; Lackner, Michaela; Caramalho, Rita; Lass-Flörl, Cornelia

2014-01-01

The effect of hypoxic conditions on the in vitro efficacy of amphotericin B and posaconazole against Mucorales was evaluated by defining MICs with Etest and broth microdilution and identifying minimal fungicidal concentrations (MFCs). With Etest, oxygen-dependent changes were detected, while the MIC and the MFC determined with broth microdilution remained unaltered with reduced oxygen levels. The observed differences depended on the method used. PMID:25451049

Validation of an improved abnormality insertion method for medical image perception investigations

NASA Astrophysics Data System (ADS)

Madsen, Mark T.; Durst, Gregory R.; Caldwell, Robert T.; Schartz, Kevin M.; Thompson, Brad H.; Berbaum, Kevin S.

2009-02-01

The ability to insert abnormalities in clinical tomographic images makes image perception studies with medical images practical. We describe a new insertion technique and its experimental validation that uses complementary image masks to select an abnormality from a library and place it at a desired location. The method was validated using a 4-alternative forced-choice experiment. For each case, four quadrants were simultaneously displayed consisting of 5 consecutive frames of a chest CT with a pulmonary nodule. One quadrant was unaltered, while the other 3 had the nodule from the unaltered quadrant artificially inserted. 26 different sets were generated and repeated with order scrambling for a total of 52 cases. The cases were viewed by radiology staff and residents who ranked each quadrant by realistic appearance. On average, the observers were able to correctly identify the unaltered quadrant in 42% of cases, and identify the unaltered quadrant both times it appeared in 25% of cases. Consensus, defined by a majority of readers, correctly identified the unaltered quadrant in only 29% of 52 cases. For repeats, the consensus observer successfully identified the unaltered quadrant only once. We conclude that the insertion method can be used to reliably place abnormalities in perception experiments.

Biomarkers of oxidative stress and inflammation after wood smoke exposure in a reconstructed Viking Age house.

PubMed

Jensen, Annie; Karottki, Dorina Gabriela; Christensen, Jannie Marie; Bønløkke, Jakob Hjort; Sigsgaard, Torben; Glasius, Marianne; Loft, Steffen; Møller, Peter

2014-10-01

Exposure to particles from combustion of wood is associated with respiratory symptoms, whereas there is limited knowledge about systemic effects. We investigated effects on systemic inflammation, oxidative stress and DNA damage in humans who lived in a reconstructed Viking Age house, with indoor combustion of wood for heating and cooking. The subjects were exposed to high indoor concentrations of PM2.5 (700-3,600 µg/m(3)), CO (10.7-15.3 ppm) and NO2 (140-154 µg/m(3)) during a 1-week stay. Nevertheless, there were unaltered levels of genotoxicity, determined as DNA strand breaks and formamidopyrimidine DNA glycosylase and oxoguanine DNA glycosylase 1 sensitive sites in peripheral blood mononuclear cells. There were also unaltered expression levels of OGG1, HMOX1, CCL2, IL8, and TNF levels in leukocytes. In serum, there were unaltered levels of C-reactive protein, IL6, IL8, TNF, lactate dehydrogenase, cholesterol, triglycerides, and high-density lipoproteins. The wood smoke exposure was associated with decreased serum levels of sICAM-1, and a tendency to decreased sVCAM-1 levels. There was a minor increase in the levels of circulating monocytes expressing CD31, whereas there were unaltered expression levels of CD11b, CD49d, and CD62L on monocytes after the stay in the house. In conclusion, even a high inhalation exposure to wood smoke was associated with limited systemic effects on markers of oxidative stress, DNA damage, inflammation, and monocyte activation. © 2014 Wiley Periodicals, Inc.

Auto-inhibition and phosphorylation-induced activation of PLC-γ isozymes

PubMed Central

Hajicek, Nicole; Charpentier, Thomas H.; Rush, Jeremy R.; Harden, T. Kendall; Sondek, John

2013-01-01

Multiple extracellular stimuli, such as growth factors and antigens, initiate signaling cascades through tyrosine phosphorylation and activation of phospholipase C (PLC)-γ isozymes. Like most other PLCs, PLC-γ1 is basally auto-inhibited by its X-Y linker, which separates the X-and Y-boxes of the catalytic core. The C-terminal SH2 (cSH2) domain within the X-Y linker is the critical determinant for auto-inhibition of phospholipase activity. Release of auto-inhibition requires an intramolecular interaction between the cSH2 domain and a phosphorylated tyrosine, Tyr783, also located within the X-Y linker. The molecular mechanisms that mediate auto-inhibition and phosphorylation-induced activation have not been defined. Here, we describe structures of the cSH2 domain both alone and bound to a PLC-γ1 peptide encompassing phosphorylated Tyr783. The cSH2 domain remains largely unaltered by peptide engagement. Point mutations in the cSH2 domain located at the interface with the peptide were sufficient to constitutively activate PLC-γ1 suggesting that peptide engagement directly interferes with the capacity of the cSH2 domain to block the lipase active site. This idea is supported by mutations in a complimentary surface of the catalytic core that also enhanced phospholipase activity. PMID:23777354

Orbital elements of Charon from speckle interferometry

NASA Technical Reports Server (NTRS)

Beletic, J. W.; Goody, R. M.; Tholen, D. J.

1989-01-01

The semimajor axis and the inclination are the two most important quantities presently determined from 56 well-calibrated speckle-interferometric observations of the position of Charon, which are presented in conjunction with an orbit solution that incorporates them. Both values in the best solution obtained are noted to significantly differ from earlier determinations. The new value for the semimajor axis represents a 2.7 percent increase over the previously accepted value; the mean density of the system, however, remains unaltered.

Chromosomal context and replication properties of ARS plasmids in Schizosaccharomyces pombe.

PubMed

Pratihar, Aditya S; Tripathi, Vishnu P; Yadav, Mukesh P; Dubey, Dharani D

2015-12-01

Short, specific DNA sequences called as Autonomously Replicating Sequence (ARS) elements function as plasmid as well as chromosomal replication origins in yeasts. As compared to ARSs, different chromosomal origins vary greatly in their efficiency and timing of replication probably due to their wider chromosomal context. The two Schizosaccharomyces pombe ARS elements, ars727 and ars2004, represent two extremities in their chromosomal origin activity - ars727 is inactive and late replicating, while ars2004 is a highly active, early-firing origin. To determine the effect of chromosomal context on the activity of these ARS elements, we have cloned them with their extended chromosomal context as well as in the context of each other in both orientations and analysed their replication efficiency by ARS and plasmid stability assays. We found that these ARS elements retain their origin activity in their extended/altered context. However, deletion of a 133-bp region of the previously reported ars727- associated late replication enforcing element (LRE) caused advancement in replication timing of the resulting plasmid. These results confirm the role of LRE in directing plasmid replication timing and suggest that the plasmid origin efficiency of ars2004 or ars727 remains unaltered by the extended chromosomal context.

Antibiotic loading and release studies of LSMO nanoparticles embedded in an acrylic polymer

NASA Astrophysics Data System (ADS)

Biswas, Sonali; Keshri, Sunita; Goswami, Sudipta; Isaac, Jinu; Ganguly, Swastika; Perov, Nikolai

2016-12-01

In this paper, we present the drug loading and release works of ? (LSMO) manganite nanoparticles (NPs). The LSMO NPs, grown using the sol-gel method, were embedded in an acrylic interpenetrating polymer network to make the sample applicable for biomedical purposes. The results of scanning electron microscopy showed that these NPs were well dispersed in the polymer. The grain size of these NPs lies in the range of 25-45 nm, as confirmed by transmission electron microscopy. The measurements of DC magnetization and hysteresis loops reveal that the basic magnetic behaviour of the LSMO NPs remained almost unaltered even after embedding in polymer, but with lower saturation value of magnetization. The drug loading and release studies of the grown sample were carried out using an antibiotic, ciprofloxacin. The minimum inhibitory effect of the sample loaded with this drug has exhibited high activity against different strains of bacteria, comparable to the pure ciprofloxacin.

Effects of ionizing radiation on bio-active plant extracts useful for preventing oxidative damages.

PubMed

Mulinacci, Nadia; Valletta, Alessio; Pasqualetti, Valentina; Innocenti, Marzia; Giuliani, Camilla; Bellumori, Maria; De Angelis, Giulia; Carnevale, Alessia; Locato, Vittoria; Di Venanzio, Cristina; De Gara, Laura; Pasqua, Gabriella

2018-04-02

Humans are exposed to ionizing radiations in medical radiodiagnosis and radiotherapy that cause oxidative damages and degenerative diseases. Airplane pilots, and even more astronauts, are exposed to a variety of potentially harmful factors, including cosmic radiations. Among the phytochemicals, phenols are particularly efficient in countering the oxidative stress. In the present study, different extracts obtained from plant food, plant by-products and dietary supplements, have been compared for their antioxidant properties before and after irradiation of 140 cGy, a dose absorbed during a hypothetical stay of three years in the space. All the dry extracts, characterized in terms of vitamin C and phenolic content, remained chemically unaltered and maintained their antioxidant capability after irradiation. Our results suggest the potential use of these extracts as nutraceuticals to protect humans from oxidative damages, even when these extracts must be stored in an environment exposed to cosmic radiations as in a space station.

Glial activation and post-synaptic neurotoxicity: the key events in Streptozotocin (ICV) induced memory impairment in rats.

PubMed

Rai, Shivika; Kamat, Pradeep K; Nath, Chandishwar; Shukla, Rakesh

2014-02-01

In the present study the role of glial activation and post synaptic toxicity in ICV Streptozotocin (STZ) induced memory impaired rats was explored. In experiment set up 1: Memory deficit was found in Morris water maze test on 14-16 days after STZ (ICV; 3mg/Kg) administration. STZ causes increased expression of GFAP, CD11b and TNF-α indicating glial activation and neuroinflammation. STZ also significantly increased the level of ROS, nitrite, Ca(2+) and reduced the mitochondrial activity in synaptosomal preparation illustrating free radical generation and excitotoxicity. Increased expression and activity of Caspase-3 was also observed in STZ treated rat which specify apoptotic cell death in hippocampus and cortex. STZ treatment showed decrease expression of post synaptic markers CaMKIIα and PSD-95, while, expression of pre synaptic markers (synaptophysin and SNAP-25) remains unaltered indicating selective post synaptic neurotoxicity. Oral treatment with Memantine (10mg/kg) and Ibuprofen (50 mg/kg) daily for 13 days attenuated STZ induced glial activation, apoptotic cell death and post synaptic neurotoxicity in rat brain. Further, in experiment set up 2: where memory function was not affected i.e. 7-9 days after STZ treatment. The level of GFAP, CD11b, TNF-α, ROS and nitrite levels were increased. On the other hand, apoptotic marker, synaptic markers, mitochondrial activity and Ca(2+) levels remained unaffected. Collective data indicates that neuroinflammatory process and oxidative stress occurs earlier to apoptosis and does not affect memory function. Present study clearly suggests that glial activation and post synaptic neurotoxicity are the key factors in STZ induced memory impairment and neuronal cell death. Copyright © 2013 Elsevier Inc. All rights reserved.

Leaf litter decomposition and microbial activity in nutrient-enriched and unaltered reaches of a headwater stream

Treesearch

Vladislav Gulis; Keller Suberkropp

2003-01-01

1. Decomposition of red maple (Acer rubrum) and rhododendron (Rhododendron maximum) leaves and activity of associated microorganisms were compared in two reaches of a headwater stream in Coweeta Hydrologic Laboratory, NC, U.S.A. The downstream reach was enriched with ammonium, nitrate, and phosphate whereas the upstream reach was not altered.2. Decomposition...

Soil-plant-microbial relations in hydrothermally altered soils of Northern California

USDA-ARS?s Scientific Manuscript database

Soils developed on relict hydrothermally altered soils throughout the Western United States present unique opportunities to study the role of geology on above and belowground biotic activity and composition. Soil and vegetation samples were taken at three unaltered andesite and three hydrothermally ...

Susceptibility profiles of amphotericin B and posaconazole against clinically relevant mucorales species under hypoxic conditions.

PubMed

Maurer, Elisabeth; Binder, Ulrike; Sparber, Manuela; Lackner, Michaela; Caramalho, Rita; Lass-Flörl, Cornelia

2015-02-01

The effect of hypoxic conditions on the in vitro efficacy of amphotericin B and posaconazole against Mucorales was evaluated by defining MICs with Etest and broth microdilution and identifying minimal fungicidal concentrations (MFCs). With Etest, oxygen-dependent changes were detected, while the MIC and the MFC determined with broth microdilution remained unaltered with reduced oxygen levels. The observed differences depended on the method used. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Erratum: Evidence of b -jet quenching in PbPb collisions at s N N = 2.76 TeV [Phys. Rev. Lett. 113 , 132301 (2014)

DOE PAGES

Chatrchyan, S.

2015-07-10

In our Letter, there was a component of the statistical uncertainty from the simulated PbPb Monte Carlo samples. This uncertainty was not propagated to all of the results. Figures 3 and 4 have been updated to reflect this source of uncertainty. In this case, the statistical uncertainties remain smaller than the systematic uncertainties in all cases such that the conclusions of the Letter are unaltered.

Effects of season on boar semen parameters and antioxidant enzymes in the south subtropical region in Brazil.

PubMed

Argenti, L E; Parmeggiani, B S; Leipnitz, G; Weber, A; Pereira, G R; Bustamante-Filho, I C

2018-02-01

Although boar semen productivity is affected by seasonality, its effects are not equal among different regions which raise concerns regarding the profitability of boar stud farms. Therefore, the goals of this study were (i) to evaluate the seasonal effect on semen production in a commercial boar stud farm located in a subtropical climate region and (ii) to verify whether the activities of superoxide dismutase and glutathione peroxidase in spermatozoa and seminal plasma were associated with seminal traits of fresh and cooled semen. Nine boars were collected twice per season, and routine seminal parameter analyses were performed together with superoxide dismutase and glutathione peroxidase activities in seminal plasma and spermatozoa. Despite a reduction in sperm concentration in spring and summer, most seminal parameters were constant year-round. Temperature-humidity index was higher in the summer compared to spring, autumn and winter (p < .05). Superoxide dismutase activity in spermatozoa was increased in summer compared to autumn and winter (p < .05). The activities of both enzymes in seminal plasma and spermatozoa glutathione peroxidase remained unaltered throughout the seasons. In conclusion, seasonality showed little influence in overall boar seminal parameters despite microclimatic differences among seasons, and spermatozoa collected during summer increased superoxide dismutase activity. © 2018 Blackwell Verlag GmbH.

A reusable multipurpose magnetic nanobiocatalyst for industrial applications.

PubMed

Perwez, Mohammad; Ahmad, Razi; Sardar, Meryam

2017-10-01

A multipurpose magnetic nanobiocatalyst is developed by conjugating Pectinex 3XL (a commercial enzyme containing pectinase, xylanase and cellulase activities) on 3-aminopropyl triethoxysilane activated magnetic nanoparticles. The nanobiocatalyst retained 87% of pectinase, 69% of xylanase and 58% of cellulase activity after conjugation on modified nanoparticles as compared to their soluble counterparts. Thermal stability data at 70°C showed increase in enzyme stability after conjugation to nanoparticles and the kinetic parameters (K m and V max ) remain unaltered after immobilization. The immobilized enzyme system can be successfully used upto 5th cycle after that slight decrease in enzyme activities was observed. The nanobiocatalyst retained high pectinase activities in organic solvents and chemical reagents as compared to free enzymes. DLS data shows that the nanoparticles size increases from 63nm to 86nm after immobilization. Atomic Force Microscopy data confirms the deposition of enzymes on the nanoparticles. The nanobiocatalyst was used for the clarification of pine apple and orange juice and was also used for the production of bioethanol. Hydrolysis of pretreated wheat straw produced 1.39g/l and 1.59g/l after treatment with free Pectinex 3xL and nanobiocatalyst respectively. The concentration of bioethanol also increases by 1.4 fold as compared to the free enzyme. Copyright © 2017 Elsevier B.V. All rights reserved.

Antiproliferative effect on human prostate cancer cells by a stinging nettle root (Urtica dioica) extract.

PubMed

Konrad, L; Müller, H H; Lenz, C; Laubinger, H; Aumüller, G; Lichius, J J

2000-02-01

In the present study the activity of a 20% methanolic extract of stinging nettle roots (Urtica dioica L., Urticaceae) on the proliferative activity of human prostatic epithelial (LNCaP) and stromal (hPCPs) cells was evaluated using a colorimetric assay. A concentration-dependent and significant (p < 0.05) antiproliferative effect of the extract was observed only on LNCaP cells during 7 days, whereas stromal cell growth remained unaltered. The inhibition was time-dependent with the maximum of growth reduction (30%) at a concentration of 1.0E-6 mg/ml on day 5 compared to the untreated control. On day 4 and 6, the reduction in proliferation of LNCaP cells showed the minimal effective dose at 1.0E-9 mg/ml. No cytotoxic effect of ME-20 on cell proliferation was observed. The antiproliferative effect of ME-20 of stinging nettle roots observed both in an in vivo model and in an in vitro system clearly indicates a biologically relevant effect of compounds present in the extract.

Plasticity of Astrocytic Coverage and Glutamate Transporter Expression in Adult Mouse Cortex

PubMed Central

Steiner, Pascal; Hirling, Harald; Welker, Egbert; Knott, Graham W

2006-01-01

Astrocytes play a major role in the removal of glutamate from the extracellular compartment. This clearance limits the glutamate receptor activation and affects the synaptic response. This function of the astrocyte is dependent on its positioning around the synapse, as well as on the level of expression of its high-affinity glutamate transporters, GLT1 and GLAST. Using Western blot analysis and serial section electron microscopy, we studied how a change in sensory activity affected these parameters in the adult cortex. Using mice, we found that 24 h of whisker stimulation elicited a 2-fold increase in the expression of GLT1 and GLAST in the corresponding cortical column of the barrel cortex. This returns to basal levels 4 d after the stimulation was stopped, whereas the expression of the neuronal glutamate transporter EAAC1 remained unaltered throughout. Ultrastructural analysis from the same region showed that sensory stimulation also causes a significant increase in the astrocytic envelopment of excitatory synapses on dendritic spines. We conclude that a period of modified neuronal activity and synaptic release of glutamate leads to an increased astrocytic coverage of the bouton–spine interface and an increase in glutamate transporter expression in astrocytic processes. PMID:17048987

Astrocyte Sodium Signalling and Panglial Spread of Sodium Signals in Brain White Matter.

PubMed

Moshrefi-Ravasdjani, Behrouz; Hammel, Evelyn L; Kafitz, Karl W; Rose, Christine R

2017-09-01

In brain grey matter, excitatory synaptic transmission activates glutamate uptake into astrocytes, inducing sodium signals which propagate into neighboring astrocytes through gap junctions. These sodium signals have been suggested to serve an important role in neuro-metabolic coupling. So far, it is unknown if astrocytes in white matter-that is in brain regions devoid of synapses-are also able to undergo such intra- and intercellular sodium signalling. In the present study, we have addressed this question by performing quantitative sodium imaging in acute tissue slices of mouse corpus callosum. Focal application of glutamate induced sodium transients in SR101-positive astrocytes. These were largely unaltered in the presence of ionotropic glutamate receptors blockers, but strongly dampened upon pharmacological inhibition of glutamate uptake. Sodium signals induced in individual astrocytes readily spread into neighboring SR101-positive cells with peak amplitudes decaying monoexponentially with distance from the stimulated cell. In addition, spread of sodium was largely unaltered during pharmacological inhibition of purinergic and glutamate receptors, indicating gap junction-mediated, passive diffusion of sodium between astrocytes. Using cell-type-specific, transgenic reporter mice, we found that sodium signals also propagated, albeit less effectively, from astrocytes to neighboring oligodendrocytes and NG2 cells. Again, panglial spread was unaltered with purinergic and glutamate receptors blocked. Taken together, our results demonstrate that activation of sodium-dependent glutamate transporters induces sodium signals in white matter astrocytes, which spread within the astrocyte syncytium. In addition, we found a panglial passage of sodium signals from astrocytes to NG2 cells and oligodendrocytes, indicating functional coupling between these macroglial cells in white matter.

DNA strand breaks and TDP-43 mislocation are absent in the murine hSOD1G93A model of amyotrophic lateral sclerosis in vivo and in vitro

PubMed Central

Witte, Otto W.; Grosskreutz, Julian

2017-01-01

Mutations in the human Cu/Zn superoxide dismutase type-1 (hSOD1) gene are common in familial amyotrophic lateral sclerosis (fALS). The pathophysiology has been linked to, e.g., organelle dysfunction, RNA metabolism and oxidative DNA damage conferred by SOD1 malfunction. However, apart from metabolically evoked DNA oxidation, it is unclear whether severe genotoxicity including DNA single-strand breaks (SSBs) and double-strand breaks (DSBs), originates from loss of function of nuclear SOD1 enzyme. Factors that endogenously interfere with DNA integrity and repair complexes in hSOD1-mediated fALS remain similarly unexplored. In this regard, uncontrolled activation of transposable elements (TEs) might contribute to DNA disintegration and neurodegeneration. The aim of this study was to elucidate the role of the fALS-causing hSOD1G93A mutation in the generation of severe DNA damage beyond well-characterized DNA base oxidation. Therefore, DNA damage was assessed in spinal tissue of hSOD1G93A-overexpressing mice and in corresponding motor neuron-enriched cell cultures in vitro. Overexpression of the hSOD1G93A locus did not change the threshold for severe DNA damage per se. We found that levels of SSBs and DSBs were unaltered between hSOD1G93A and control conditions, as demonstrated in post-mitotic motor neurons and in astrocytes susceptible to replication-dependent DNA breakage. Analogously, parameters indicative of DNA damage response processes were not activated in vivo or in vitro. Evidence for a mutation-related elevation in TE activation was not detected, in accordance with the absence of TAR DNA binding protein 43 (TDP-43) proteinopathy in terms of cytoplasmic mislocation or nuclear loss, as nuclear TDP-43 is supposed to silence TEs physiologically. Conclusively, the superoxide dismutase function of SOD1 might not be required to preserve DNA integrity in motor neurons, at least when the function of TDP-43 is unaltered. Our data establish a foundation for further investigations addressing functional TDP-43 interaction with ALS-relevant genetic mutations. PMID:28832631

Assessment of skeletal changes after post-mortem exposure to fire as an indicator of decomposition stage.

PubMed

Keough, N; L'Abbé, E N; Steyn, M; Pretorius, S

2015-01-01

Forensic anthropologists are tasked with interpreting the sequence of events from death to the discovery of a body. Burned bone often evokes questions as to the timing of burning events. The purpose of this study was to assess the progression of thermal damage on bones with advancement in decomposition. Twenty-five pigs in various stages of decomposition (fresh, early, advanced, early and late skeletonisation) were exposed to fire for 30 min. The scored heat-related features on bone included colour change (unaltered, charred, calcined), brown and heat borders, heat lines, delineation, greasy bone, joint shielding, predictable and minimal cracking, delamination and heat-induced fractures. Colour changes were scored according to a ranked percentage scale (0-3) and the remaining traits as absent or present (0/1). Kappa statistics was used to evaluate intra- and inter-observer error. Transition analysis was used to formulate probability mass functions [P(X=j|i)] to predict decomposition stage from the scored features of thermal destruction. Nine traits displayed potential to predict decomposition stage from burned remains. An increase in calcined and charred bone occurred synchronously with advancement of decomposition with subsequent decrease in unaltered surfaces. Greasy bone appeared more often in the early/fresh stages (fleshed bone). Heat borders, heat lines, delineation, joint shielding, predictable and minimal cracking are associated with advanced decomposition, when bone remains wet but lacks extensive soft tissue protection. Brown burn/borders, delamination and other heat-induced fractures are associated with early and late skeletonisation, showing that organic composition of bone and percentage of flesh present affect the manner in which it burns. No statistically significant difference was noted among observers for the majority of the traits, indicating that they can be scored reliably. Based on the data analysis, the pattern of heat-induced changes may assist in estimating decomposition stage from unknown, burned remains. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Intrinsic attenuation of post-irradiation calcium and ER stress imparts significant radioprotection to lepidopteran insect cells.

PubMed

Guleria, Ayushi; Thukral, Neha; Chandna, Sudhir

2018-04-15

Sf9 lepidopteran insect cells are 100-200 times more radioresistant than mammalian cells. This distinctive feature thus makes them suitable for studies exploring radioprotective molecular mechanisms. It has been established from previous studies of our group that downstream mitochondrial apoptotic signaling pathways in Sf9 cells are quite similar to mammalian cells, implicating the upstream signaling pathways in their extensive radioresistance. In the present study, intracellular and mitochondrial calcium levels remained unaltered in Sf9 cells in response to radiation, in sharp contrast to human (HEK293T) cells. The isolated mitochondria from Sf9 cells exhibited nearly 1.5 times greater calcium retention capacity than mammalian cells, highlighting their inherent stress resilience. Importantly, UPR/ER stress marker proteins (p-eIF2α, GRP4 and SERCA) remained unaltered by radiation and suggested highly attenuated ER and calcium stress. Lack of SERCA induction further corroborates the lack of radiation-induced calcium mobilization in these cells. The expression of CaMKII, an important effector molecule of calcium signaling, did not alter in response to radiation. Inhibiting CaMKII by KN-93 or suppressing CaM by siRNA failed to alter Sf9 cells response to radiation and suggests CaM-CaMKII independent radiation signaling. Therefore, this study suggests that attenuated calcium signaling/ER stress is an important determinant of lepidopteran cell radioresistance. Copyright © 2018 Elsevier Inc. All rights reserved.

Human impacts quantification on the coastal landforms of Gran Canaria Island (Canary Islands)

NASA Astrophysics Data System (ADS)

Ferrer-Valero, Nicolás; Hernández-Calvento, Luis; Hernández-Cordero, Antonio I.

2017-06-01

The coastal areas of the Canary Islands are particularly sensitive to changes, both from a natural perspective and for their potential socio-economic implications. In this paper, the state of conservation of an insular coast is approached from a geomorphological point of view, considering recent changes induced by urban and tourism development. The analysis is applied to the coast of Gran Canaria, a small Atlantic island of volcanic origin, subject to a high degree of human pressure on its coastal areas, especially in recent decades. Currently, much of the economic activity of Gran Canaria is linked to mass tourism, associated with climatic and geomorphological features of the coast. This work is addressed through detailed mapping of coastal landforms across the island (256 km perimeter), corresponding to the period before the urban and tourism development (late 19th century for the island's capital, mid-20th century for the rest of the island) and today. The comparison between the coastal geomorphology before and after the urban and tourism development was established through four categories of human impacts, related to their conservation state: unaltered, altered, semi-destroyed and extinct. The results indicate that 43% of coastal landforms have been affected by human impacts, while 57% remain unaltered. The most affected are sedimentary landforms, namely coastal dunes, palaeo-dunes, beaches and wetlands. Geodiversity loss was also evaluated by applying two diversity indices. The coastal geodiversity loss by total or partial destruction of landforms is estimated at - 15.2%, according to Shannon index (H‧), while it increases to - 32.1% according to an index proposed in this paper. We conclude that the transformations of the coast of Gran Canaria induced by urban and tourism development have heavily affected the most singular coastal landforms (dunes, palaeo-dunes and wetlands), reducing significantly its geodiversity.

Impairment of the liver insulin receptor autoactivation cascade at full-term pregnancy in the rat.

PubMed

Martinez, C; Molero, J C; Ruiz, P; Del Arco, A; Andres, A; Carrascosa, J M

1995-10-15

Partially purified liver insulin receptors from full-term pregnant rats show decreased autophosphorylation rates if compared with receptors from virgins. We studied the molecular mechanism of this phenomenon, looking at possible structural and functional changes of several domains. The ATP-binding domain seems to be unaltered in receptors from pregnant rats since Km for ATP was similar to that observed in virgins. In contrast, the Vmax. is decreased some 45%, suggesting changes in the kinase domain. Truncation of a fragment of 10 kDa from the C-terminal tail does not normalize the kinase activity in receptors from pregnant rats, suggesting that this domain is not involved in the inhibitory regulation. Treatment with alkaline phosphatase increases the [32P]Pi incorporation into receptors from pregnant rats; however, the autophosphorylation remains lower than that observed in virgin rats. Tryptic phosphopeptide maps of phosphorylated receptors show that the same phosphopeptides are present in receptors from virgin and pregnant rats. However, the progression through the autoactivation cascade in the kinase domain is impaired in receptors from pregnant rats. Differences in the cleavage by trypsin at the two alternative sites in the kinase domain were observed, indicating possible structural changes in receptors from pregnant rats that could be related to the impairment of the autoactivation cascade. Integrity of the alpha- and beta-subunits, as well as differential expression of the two receptor isotypes, were shown to be unaltered. We conclude that (1) the decreased autophosphorylation rate of the liver insulin receptor from pregnant rats is associated with the impairment of its autoactivation cascade, probably as a consequence of the basal Ser/Thr phosphorylation; and (2) the inhibition of the autoactivation cascade does not account for the overall inhibition of autophosphorylation observed in receptors from pregnant rats.

Chemopreventive effects of Cuminum cyminum in chemically induced forestomach and uterine cervix tumors in murine model systems.

PubMed

Gagandeep; Dhanalakshmi, Sivanandhan; Méndiz, Ester; Rao, Agra Ramesha; Kale, Raosaheb Kathalupant

2003-01-01

Lately, a strong correlation has been established between diet and cancer. For ages, cumin has been a part of the diet. It is a popular spice regularly used as a flavoring agent in a number of ethnic cousins. In the present study, cancer chemopreventive potentials of different doses of a cumin seed-mixed diet were evaluated against benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis and 3-methylcholanthrene (MCA)-induced uterine cervix tumorigenesis. Results showed a significant inhibition of stomach tumor burden (tumors per mouse) by cumin. Tumor burden was 7.33 +/- 2.10 in the B(a)P-treated control group, whereas it reduced to 3.10 +/- 0.57 (P < 0.001) by a 2.5% dose and 3.11 +/- 0.60 (P <0.001) by a 5% dose of cumin seeds. Cervical carcinoma incidence, compared with the MCA-treated control group (66.67%), reduced to 27.27% (P < 0.05) by a diet of 5% cumin seeds and to 12.50% (P < 0.05) by a diet of 7.5% cumin seeds. The effect of 2.5 and 5% cumin seed-mixed diets was also examined on carcinogen/xenobiotic metabolizing phase I and phase II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase (LDH), and lipid peroxidation in the liver of Swiss albino mice. Levels of cytochrome P-450 (cyt P-450) and cytochrome b5 (cyt b(5)) were significantly augmented (P < 0.05) by the 2.5% dose of cumin seed diet. The levels of cyt P-450 reductase and cyt b(5) reductase were increased (significance level being from P < 0.05 to P < 0.01) by both doses of cumin. Among the phase II enzymes, glutathione S-transferase specific activity increased (P < 0.005) by the 5% dose, whereas that of DT-diaphorase increased significantly (P < 0.05) by both doses used (2.5 and 5%). In the antioxidant system, significant elevation of the specific activities of superoxide dismutase (P < 0.01) and catalase (P < 0.05) was observed with the 5% dose of cumin. The activities of glutathione peroxidase and glutathione reductase remained unaltered by both doses of cumin. The level of reduced glutathione measured as nonprotein sulfhydryl content was elevated (significance level being from P < 0.05 to P < 0.01) by both doses of cumin. Lipid peroxidation measured as formation of MDA production showed significant inhibition (P < 0.05 to P < 0.01) by both doses of cumin. LDH activity remained unaltered by both doses of cumin. The results strongly suggest the cancer chemopreventive potentials of cumin seed and could be attributed to its ability to modulate carcinogen metabolism.

Perinatal hypothyroidism modulates antioxidant defence status in the developing rat liver and heart.

PubMed

Zhang, Hongmei; Dong, Yan; Su, Qing

2017-02-01

In the present study, we investigated oxidative stress parameters and antioxidant defence status in perinatal hypothyroid rat liver and heart. We found that the proteincarbonyl content did not differ significantly between the three groups both in the pup liver and in the heart. The OH˙ level was significantly decreased in the hypothyroid heart but not in the liver compared with controls. A slight but not significant decrease in SOD activity was observed in both perinatal hypothyroid liver and heart. A significantly increased activity of CAT was observed in the liver but not in the heart of hypothyroid pups. The GPx activity was considerably increased compared with controls in the perinatal hypothyroid heart and was unaltered in the liver of hypothyroid pups. We also found that vitamin E levels in the liver decreased significantly in hypothyroidism and were unaltered in the heart of perinatal hypothyroid rats. The GSH content was elevated significantly in both hypothyroid liver and heart. The total antioxidant capacity was higher in the liver of the hypothyroid group but not in the hypothyroid heart. Thyroxine replacement could not repair the above changes to normal. In conclusion, perinatal hypothyroidism modulates the oxidative stress status of the perinatal liver and heart.

Biological Invasion Influences the Outcome of Plant-Soil Feedback in the Invasive Plant Species from the Brazilian Semi-arid.

PubMed

de Souza, Tancredo Augusto Feitosa; de Andrade, Leonaldo Alves; Freitas, Helena; da Silva Sandim, Aline

2017-05-30

Plant-soil feedback is recognized as the mutual interaction between plants and soil microorganisms, but its role on the biological invasion of the Brazilian tropical seasonal dry forest by invasive plants still remains unclear. Here, we analyzed and compared the arbuscular mycorrhizal fungi (AMF) communities and soil characteristics from the root zone of invasive and native plants, and tested how these AMF communities affect the development of four invasive plant species (Cryptostegia madagascariensis, Parkinsonia aculeata, Prosopis juliflora, and Sesbania virgata). Our field sampling revealed that AMF diversity and frequency of the Order Diversisporales were positively correlated with the root zone of the native plants, whereas AMF dominance and frequency of the Order Glomerales were positively correlated with the root zone of invasive plants. We grew the invasive plants in soil inoculated with AMF species from the root zone of invasive (I changed ) and native (I unaltered ) plant species. We also performed a third treatment with sterilized soil inoculum (control). We examined the effects of these three AMF inoculums on plant dry biomass, root colonization, plant phosphorous concentration, and plant responsiveness to mycorrhizas. We found that I unaltered and I changed promoted the growth of all invasive plants and led to a higher plant dry biomass, mycorrhizal colonization, and P uptake than control, but I changed showed better results on these variables than I unaltered . For plant responsiveness to mycorrhizas and fungal inoculum effect on plant P concentration, we found positive feedback between changed-AMF community (I changed ) and three of the studied invasive plants: C. madagascariensis, P. aculeata, and S. virgata.

Mitochondrial dysfunction is responsible for the intestinal calcium absorption inhibition induced by menadione.

PubMed

Marchionatti, Ana M; Perez, Adriana V; Diaz de Barboza, Gabriela E; Pereira, Beatriz M; Tolosa de Talamoni, Nori G

2008-02-01

Menadione (MEN) inhibits intestinal calcium absorption by a mechanism not completely understood. The aim of this work was to find out the role of mitochondria in this inhibitory mechanism. Hence, normal chicks treated with one i.p. dose of MEN were studied in comparison with controls. Intestinal calcium absorption was measured by the in situ ligated intestinal segment technique. GSH, oxidoreductase activities from the Krebs cycle and enzymes of the antioxidant system were measured in isolated mitochondria. Mitochondrial membrane potential was measured by a flow cytometer technique. DNA fragmentation and cytochrome c localization were determined by immunocytochemistry. Data indicate that in 30 min, MEN decreases intestinal Ca(2+) absorption, which returns to the control values after 10 h. GSH was only decreased for half an hour, while the activity of malate dehydrogenase and alpha-ketoglutarate dehydrogenase was diminished for 48 h. Mn(2+)-superoxide dismutase activity was increased in 30 min, whereas the activity of catalase and glutathione peroxidase remained unaltered. DNA fragmentation and cytochrome c release were maximal in 30 min, but were recovered after 15 h. In conclusion, MEN inhibits intestinal Ca(2+) absorption by mitochondrial dysfunction as revealed by GSH depletion and alteration of the permeability triggering the release of cytochrome c and DNA fragmentation.

Intestinal epithelial cell surface glycosylation in mice. I. Effect of high-protein diet.

PubMed

Gupta, R; Jaswal, V M; Meenu Mahmood, A

1992-01-01

The effects of variation in dietary protein content have been investigated on brush border glycosylation and enzyme activities in mice small intestine. The comparison of different parameters was made between the mice fed 30% (high protein, HP) and 18% protein (pair-fed, PF, and ad libitum-fed) for 21 days. The activities of brush border sucrase, lactase, p-nitrophenyl (PNP)-beta-D-glucosidase and PNP-beta-D-galactosidase were reduced in the HP diet-fed mice compared to PF and ad libitum-fed controls. Alkaline phosphatase and leucine amino-peptidase activities were significantly enhanced while gamma-glutamyl transpeptidase activity was unaltered under these conditions. Total hexoses and sialic acid content in the brush borders were reduced significantly in the test group compared to the controls while hexosamine and fucose contents remained essentially similar in different groups. The results on the binding of wheat germ agglutinin and Ulex europaeus agglutininI to microvillus membranes corroborated the chemical analysis data on sialic acid and fucose contents of the membranes. Peanut agglutinin binding was enhanced in mice from the HP group. Incorporation of (14C)-mannose into membranes was significantly less in HP diet-fed mice. These results indicate that the feeding of HP diet to mice brings about marked alterations in small intestinal epithelial cell surface glycosylation and enzyme functions.

Exploring the Metabolic Stability of Engineered Hairy Roots after 16 Years Maintenance.

PubMed

Häkkinen, Suvi T; Moyano, Elisabeth; Cusidó, Rosa M; Oksman-Caldentey, Kirsi-Marja

2016-01-01

Plants remain a major source of new drugs, leads and fine chemicals. Cell cultures deriving from plants offer a fascinating tool to study plant metabolic pathways and offer large scale production systems for valuable compounds - commercial examples include compounds such as paclitaxel. The major constraint with undifferentiated cell cultures is that they are generally considered to be genetically unstable and cultured cells tend to produce low yields of secondary metabolites especially over time. Hairy roots, a tumor tissue caused by infection of Agrobacterium rhizogenes is a relevant alternative for plant secondary metabolite production for being fast growing, able to grow without phytohormones, and displaying higher stability than undifferentiated cells. Although genetic and metabolic stability has often been connected to transgenic hairy roots, there are only few reports on how a very long-term subculturing effects on the production capacity of hairy roots. In this study, hairy roots producing high tropane alkaloid levels were subjected to 16-year follow-up in relation to genetic and metabolic stability. Cryopreservation method for hairy roots of Hyoscyamus muticus was developed to replace laborious subculturing, and although the post-thaw recovery rates remained low, the expression of transgene remained unaltered in cryopreserved roots. It was shown that although displaying some fluctuation in the metabolite yields, even an exceedingly long-term subculturing was successfully applied without significant loss of metabolic activity.

Regulation of PSMB5 Protein and β Subunits of Mammalian Proteasome by Constitutively Activated Signal Transducer and Activator of Transcription 3 (STAT3)

PubMed Central

Vangala, Janakiram Reddy; Dudem, Srikanth; Jain, Nishant; Kalivendi, Shasi V.

2014-01-01

The ubiquitin-proteasome system facilitates the degradation of ubiquitin-tagged proteins and performs a regulatory role in cells. Elevated proteasome activity and subunit expression are found in several cancers. However, the inherent molecular mechanisms responsible for increased proteasome function in cancers remain unclear despite the well investigated and defined role of the mammalian proteasome. This study was initiated to elucidate the mechanisms involved in the regulation of β subunits of the mammalian proteasome. Suppression of STAT3 tyrosine phosphorylation coordinately decreased the mRNA and protein levels of the β subunits of the 20 S core complex in DU145 cells. Notably, PSMB5, a molecular target of bortezomib, was shown to be a target of STAT3. Knockdown of STAT3 decreased PSMB5 protein. Inhibition of phospho-STAT3 substantially reduced PSMB5 protein levels in cells expressing constitutively active-STAT3. Accumulation of activated STAT3 resulted in the induction of PSMB5 promoter and protein levels. In addition, a direct correlation was observed between the endogenous levels of PSMB5 and constitutively active STAT3. PSMB5 and STAT3 protein levels remained unaltered following the inhibition of proteasome activity. The EGF-induced concerted increase of β subunits was blocked by inhibition of the EGF receptor or STAT3 but not by the PI3K/AKT or MEK/ERK pathways. Decreased proteasome activities were due to reduced protein levels of catalytic subunits of the proteasome in STAT3-inhibited cells. Combined treatments with bortezomib and inhibitor of STAT3 abrogated proteasome activity and enhanced cellular apoptosis. Overall, we demonstrate that aberrant activation of STAT3 regulates the expression of β subunits, in particular PSMB5, and the catalytic activity of the proteasome. PMID:24627483

Extended effective field theory of inflation

NASA Astrophysics Data System (ADS)

Ashoorioon, Amjad; Casadio, Roberto; Cicoli, Michele; Geshnizjani, Ghazal; Kim, Hyung J.

2018-02-01

We present a general framework where the effective field theory of single field inflation is extended by the inclusion of operators with mass dimension 3 and 4 in the unitary gauge. These higher dimensional operators introduce quartic and sextic corrections to the dispersion relation. We study the regime of validity of this extended effective field theory of inflation and the effect of these higher dimensional operators on CMB observables associated with scalar perturbations, such as the speed of sound, the amplitude of the power spectrum and the tensor-to-scalar ratio. Tensor perturbations remain instead, unaltered.

Two-phase flow in short horizontal rectangular microchannels with a height of 300 μm

NASA Astrophysics Data System (ADS)

Chinnov, E. A.; Ron'shin, F. V.; Kabov, O. A.

2015-09-01

The two-phase flow in a narrow short horizontal channel with a rectangular cross section is studied experimentally. The channel has a width of 10, 20, or 30 mm and a height of 300 μm. The specifics of formation of such two-phase flows are investigated. It is demonstrated that the regions of bubble and churn flow regimes grow and constrain the region of jet flow as the channel gets wider. The boundaries of the regions of annular and stratified flow regimes remain almost unaltered.

Remarkable preservation of terpenoids and record of volatile signalling in plant-animal interactions from Miocene amber.

PubMed

Dutta, Suryendu; Mehrotra, Rakesh C; Paul, Swagata; Tiwari, R P; Bhattacharya, Sharmila; Srivastava, Gaurav; Ralte, V Z; Zoramthara, C

2017-09-08

Plants produce and release a large array of volatile organic compounds that play many ecological functions. These volatile plant metabolites serve as pollinator attractants, herbivore and pathogen repellents and protect plants from abiotic stresses. To date, the geological evolution of these organic compounds remains unknown. The preservation potential of these metabolites in the fossil record is very poor due to their low boiling points. Here we report a series of volatile sesquiterpenoids, including δ-elemene, α-copaene, β-elemene, β-caryophyllene, α-humulene, germacrene D, δ-cadiene and spathunenol, from early Miocene (~17 million year) amber from eastern India. The survival of these unaltered bioterpenoids can be attributed to the existence of extraordinary taphonomic conditions conducive to the preservation of volatile biomolecules through deep time. Furthermore, the occurrence of these volatiles in the early Miocene amber suggests that the plants from this period had evolved metabolic pathways to synthesize these organic molecules to play an active role in forest ecology, especially in plant-animal interactions.

Amyloid-carbon hybrid membranes for universal water purification

NASA Astrophysics Data System (ADS)

Bolisetty, Sreenath; Mezzenga, Raffaele

2016-04-01

Industrial development, energy production and mining have led to dramatically increased levels of environmental pollutants such as heavy metal ions, metal cyanides and nuclear waste. Current technologies for purifying contaminated waters are typically expensive and ion specific, and there is therefore a significant need for new approaches. Here, we report inexpensive hybrid membranes made from protein amyloid fibrils and activated porous carbon that can be used to remove heavy metal ions and radioactive waste from water. During filtration, the concentration of heavy metal ions drops by three to five orders of magnitude per passage and the process can be repeated numerous times. Notably, their efficiency remains unaltered when filtering several ions simultaneously. The performance of the membrane is enabled by the ability of the amyloids to selectively absorb heavy metal pollutants from solutions. We also show that our membranes can be used to recycle valuable heavy metal contaminants by thermally reducing ions trapped in saturated membranes, leading to the creation of elemental metal nanoparticles and films.

Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment.

PubMed

Lin, Yin Chiu; Kuo, Yu-Min; Liao, Pao-Chi; Cherng, Chianfang G; Su, Su-Wen; Yu, Lung

2007-04-30

Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.

Biological activity of the azlactone derivative EPA-35 against Trypanosoma cruzi.

PubMed

de Azeredo, Camila Maria Oliveira; Ávila, Eloah Pereira; Pinheiro, Danielle Lobo Justo; Amarante, Giovanni Wilson; Soares, Maurilio José

2017-02-01

Chagas disease, caused by Trypanosoma cruzi, affects six to seven million people worldwide. Treatment is based on benznidazole, producing several side effects and debatable efficacy, highlighting the need for new alternative drugs. We investigated the activity of four C-4 functionalized azlactone derivatives (EPA-27, EPA-35, EPA-63 and EPA-91) as potential T. cruzi inhibitors. Screening with epimastigotes indicated EPA-35 as the best compound (IC50/24 h: 33 μM). This compound was 14.1 times more potent against intracellular amastigotes (IC50/24 h: 2.34 μM). Treatment of infected Vero cells for 72 h (up to 30 μM EPA-35) resulted in a dose-dependent decrease in number of trypomastigotes and amastigotes released in the supernatant, but the amastigote/trypomastigote ratio remained constant, indicating that amastigote growth was disturbed, but cell differentiation was unaffected. Analysis of treated epimastigotes by flow cytometry indicated that the plasma membrane remained intact, but there was a significant decrease in mitochondrial membrane potential. The pattern of cell distribution in the cell cycle stages (G1, G2, M) was unaltered in treated epimastigotes, indicating a trypanocidal rather than a trypanostatic activity. Scanning electron microscopy and flow cytometry showed epimastigotes with a round shape and decrease in cell size. Taken together, our data indicate that the EPA-35 is effective against T. cruzi. Synthetic transformation of EPA-35 into other derivatives may provide promising compounds for further evaluation against this parasite. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Carbohydrates and activity of natural and recombinant tissue factor.

PubMed

Krudysz-Amblo, Jolanta; Jennings, Mark E; Mann, Kenneth G; Butenas, Saulius

2010-01-29

The effect of glycosylation on tissue factor (TF) activity was evaluated, and site-specific glycosylation of full-length recombinant TF (rTF) and that of natural TF from human placenta (pTF) were studied by liquid chromatography-tandem mass spectrometry. The amidolytic activity of the TF.factor VIIa (FVIIa) complex toward a fluorogenic substrate showed that the catalytic efficiency (V(max)) of the complex increased in the order rTF(1-243) (Escherichia coli) < rTF(1-263) (Sf9 insect cells) < pTF for the glycosylated and deglycosylated forms. Substrate hydrolysis was unaltered by deglycosylation. In FXase, the K(m) of FX for rTF(1-263)-FVIIa remained unchanged after deglycosylation, whereas the k(cat) decreased slightly. A pronounced decrease, 4-fold, in k(cat) was observed for pTF.FVIIa upon deglycosylation, whereas the K(m) was minimally altered. The parameters of FX activation by both rTF(1-263D)-FVIIa and pTF(D)-FVIIa were identical and similar to those for rTF(1-243)-FVIIa. In conclusion, carbohydrates significantly influence the activity of TF proteins. Carbohydrate analysis revealed glycosylation on asparagines 11, 124, and 137 in both rTF(1-263) and pTF. The carbohydrates of rTF(1-263) contain high mannose, hybrid, and fucosylated glycans. Natural pTF contains no high mannose glycans but is modified with hybrid, highly fucosylated, and sialylated sugars.

From perceptual to lexico-semantic analysis--cortical plasticity enabling new levels of processing.

PubMed

Schlaffke, Lara; Rüther, Naima N; Heba, Stefanie; Haag, Lauren M; Schultz, Thomas; Rosengarth, Katharina; Tegenthoff, Martin; Bellebaum, Christian; Schmidt-Wilcke, Tobias

2015-11-01

Certain kinds of stimuli can be processed on multiple levels. While the neural correlates of different levels of processing (LOPs) have been investigated to some extent, most of the studies involve skills and/or knowledge already present when performing the task. In this study we specifically sought to identify neural correlates of an evolving skill that allows the transition from perceptual to a lexico-semantic stimulus analysis. Eighteen participants were trained to decode 12 letters of Morse code that were presented acoustically inside and outside of the scanner environment. Morse code was presented in trains of three letters while brain activity was assessed with fMRI. Participants either attended to the stimulus length (perceptual analysis), or evaluated its meaning distinguishing words from nonwords (lexico-semantic analysis). Perceptual and lexico-semantic analyses shared a mutual network comprising the left premotor cortex, the supplementary motor area (SMA) and the inferior parietal lobule (IPL). Perceptual analysis was associated with a strong brain activation in the SMA and the superior temporal gyrus bilaterally (STG), which remained unaltered from pre and post training. In the lexico-semantic analysis post learning, study participants showed additional activation in the left inferior frontal cortex (IFC) and in the left occipitotemporal cortex (OTC), regions known to be critically involved in lexical processing. Our data provide evidence for cortical plasticity evolving with a learning process enabling the transition from perceptual to lexico-semantic stimulus analysis. Importantly, the activation pattern remains task-related LOP and is thus the result of a decision process as to which LOP to engage in. © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

Mitogen-Activated Protein Kinase Phosphatase-2 Deletion Impairs Synaptic Plasticity and Hippocampal-Dependent Memory.

PubMed

Abdul Rahman, Nor Zaihana; Greenwood, Sam M; Brett, Ros R; Tossell, Kyoko; Ungless, Mark A; Plevin, Robin; Bushell, Trevor J

2016-02-24

Mitogen-activated protein kinases (MAPKs) regulate brain function and their dysfunction is implicated in a number of brain disorders, including Alzheimer's disease. Thus, there is great interest in understanding the signaling systems that control MAPK function. One family of proteins that contribute to this process, the mitogen-activated protein kinase phosphatases (MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have identified novel functions of MKPs in development, the immune system, and cancer. However, a significant gap in our knowledge remains in relation to their role in brain functioning. Here, using transgenic mice where the Dusp4 gene encoding MKP-2 has been knocked out (MKP-2(-/-) mice), we show that long-term potentiation is impaired in MKP-2(-/-) mice compared with MKP-2(+/+) controls whereas neuronal excitability, evoked synaptic transmission, and paired-pulse facilitation remain unaltered. Furthermore, spontaneous EPSC (sEPSC) frequency was increased in acute slices and primary hippocampal cultures prepared from MKP-2(-/-) mice with no effect on EPSC amplitude observed. An increase in synapse number was evident in primary hippocampal cultures, which may account for the increase in sEPSC frequency. In addition, no change in ERK activity was detected in both brain tissue and primary hippocampal cultures, suggesting that the effects of MKP-2 deletion were MAPK independent. Consistent with these alterations in hippocampal function, MKP-2(-/-) mice show deficits in spatial reference and working memory when investigated using the Morris water maze. These data show that MKP-2 plays a role in regulating hippocampal function and that this effect may be independent of MAPK signaling. Copyright © 2016 Abdul Rahman et al.

From perceptual to lexico‐semantic analysis—cortical plasticity enabling new levels of processing

PubMed Central

Schlaffke, Lara; Rüther, Naima N.; Heba, Stefanie; Haag, Lauren M.; Schultz, Thomas; Rosengarth, Katharina; Tegenthoff, Martin; Bellebaum, Christian

2015-01-01

Abstract Certain kinds of stimuli can be processed on multiple levels. While the neural correlates of different levels of processing (LOPs) have been investigated to some extent, most of the studies involve skills and/or knowledge already present when performing the task. In this study we specifically sought to identify neural correlates of an evolving skill that allows the transition from perceptual to a lexico‐semantic stimulus analysis. Eighteen participants were trained to decode 12 letters of Morse code that were presented acoustically inside and outside of the scanner environment. Morse code was presented in trains of three letters while brain activity was assessed with fMRI. Participants either attended to the stimulus length (perceptual analysis), or evaluated its meaning distinguishing words from nonwords (lexico‐semantic analysis). Perceptual and lexico‐semantic analyses shared a mutual network comprising the left premotor cortex, the supplementary motor area (SMA) and the inferior parietal lobule (IPL). Perceptual analysis was associated with a strong brain activation in the SMA and the superior temporal gyrus bilaterally (STG), which remained unaltered from pre and post training. In the lexico‐semantic analysis post learning, study participants showed additional activation in the left inferior frontal cortex (IFC) and in the left occipitotemporal cortex (OTC), regions known to be critically involved in lexical processing. Our data provide evidence for cortical plasticity evolving with a learning process enabling the transition from perceptual to lexico‐semantic stimulus analysis. Importantly, the activation pattern remains task‐related LOP and is thus the result of a decision process as to which LOP to engage in. Hum Brain Mapp 36:4512–4528, 2015. © 2015 The Authors. Human Brain Mapping Published byWiley Periodicals, Inc. PMID:26304153

Retigabine holds KV7 channels open and stabilizes the resting potential

PubMed Central

Corbin-Leftwich, Aaron; Mossadeq, Sayeed M.; Ha, Junghoon; Ruchala, Iwona; Le, Audrey Han Ngoc

2016-01-01

The anticonvulsant Retigabine is a KV7 channel agonist used to treat hyperexcitability disorders in humans. Retigabine shifts the voltage dependence for activation of the heteromeric KV7.2/KV7.3 channel to more negative potentials, thus facilitating activation. Although the molecular mechanism underlying Retigabine’s action remains unknown, previous studies have identified the pore region of KV7 channels as the drug’s target. This suggested that the Retigabine-induced shift in voltage dependence likely derives from the stabilization of the pore domain in an open (conducting) conformation. Testing this idea, we show that the heteromeric KV7.2/KV7.3 channel has at least two open states, which we named O1 and O2, with O2 being more stable. The O1 state was reached after short membrane depolarizations, whereas O2 was reached after prolonged depolarization or during steady state at the typical neuronal resting potentials. We also found that activation and deactivation seem to follow distinct pathways, suggesting that the KV7.2/KV7.3 channel activity displays hysteresis. As for the action of Retigabine, we discovered that this agonist discriminates between open states, preferentially acting on the O2 state and further stabilizing it. Based on these findings, we proposed a novel mechanism for the therapeutic effect of Retigabine whereby this drug reduces excitability by enhancing the resting potential open state stability of KV7.2/KV7.3 channels. To address this hypothesis, we used a model for action potential (AP) in Xenopus laevis oocytes and found that the resting membrane potential became more negative as a function of Retigabine concentration, whereas the threshold potential for AP firing remained unaltered. PMID:26880756

Retigabine holds KV7 channels open and stabilizes the resting potential.

PubMed

Corbin-Leftwich, Aaron; Mossadeq, Sayeed M; Ha, Junghoon; Ruchala, Iwona; Le, Audrey Han Ngoc; Villalba-Galea, Carlos A

2016-03-01

The anticonvulsant Retigabine is a KV7 channel agonist used to treat hyperexcitability disorders in humans. Retigabine shifts the voltage dependence for activation of the heteromeric KV7.2/KV7.3 channel to more negative potentials, thus facilitating activation. Although the molecular mechanism underlying Retigabine's action remains unknown, previous studies have identified the pore region of KV7 channels as the drug's target. This suggested that the Retigabine-induced shift in voltage dependence likely derives from the stabilization of the pore domain in an open (conducting) conformation. Testing this idea, we show that the heteromeric KV7.2/KV7.3 channel has at least two open states, which we named O1 and O2, with O2 being more stable. The O1 state was reached after short membrane depolarizations, whereas O2 was reached after prolonged depolarization or during steady state at the typical neuronal resting potentials. We also found that activation and deactivation seem to follow distinct pathways, suggesting that the KV7.2/KV7.3 channel activity displays hysteresis. As for the action of Retigabine, we discovered that this agonist discriminates between open states, preferentially acting on the O2 state and further stabilizing it. Based on these findings, we proposed a novel mechanism for the therapeutic effect of Retigabine whereby this drug reduces excitability by enhancing the resting potential open state stability of KV7.2/KV7.3 channels. To address this hypothesis, we used a model for action potential (AP) in Xenopus laevis oocytes and found that the resting membrane potential became more negative as a function of Retigabine concentration, whereas the threshold potential for AP firing remained unaltered. © 2016 Corbin-Leftwich et al.

Monitoring of Streambank Stabilization and River Restoration Structures on Ice-Affected Rivers in Northern Vermont

DTIC Science & Technology

2009-08-01

Site Characteristics River Site Drainage Area ( mi2 ) Valley Bottom Slope Bank- full Width (ft) Bank- full Depth (ft) Bankfull...relatively unaltered by human activities. Drainage areas range from 990 ERDC/CRREL TR-09-14 17 mi2 on the lower Winooski to 44 mi2 on the upper Trout

Hydrothermal alteration of a rhyolitic hyaloclastite from Ponza Island, Italy

NASA Astrophysics Data System (ADS)

Ylagan, Robert F.; Altaner, Stephen P.; Pozzuoli, Antonio

1996-12-01

A rhyolitic hyaloclastite from Ponza island, Italy, has been hydrothermally altered producing four distinct alteration zones based on XRD and field textures: (1) non-pervasive argillic zone; (2) propylitic zone; (3) silicic zone; and (4) sericitic zone. The unaltered hyaloclastite is a volcanic breccia with clasts of vesiculated obsidian in a matrix of predominantly pumice lapilli. Incomplete alteration of the hyaloclastite resulted in the non pervasive argillic zone, characterized by smectite and disordered opal-CT. Obsidian clasts, some pumice lapilli, and pyrogenic plagioclase and biotite are unaltered. Smectite has an irregular flakey morphology, although euhedral particles are occasionally observed. The propylitic zone is characterized by mixed-layer illite/smectite (I/S) with 10 to 85% illite (I), mordenite, opal-C and authigenic K-feldspar (akspar). The matrix of the hyaloclastite is completely altered and obsidian clasts are silicified; however, plagioclase and biotite phenocrysts remain unaltered. Flakey I/S replaces pumice, and mordenite, akspar and silica line and fill pores. I/S particles are composed predominantly of subequant plates and euhedral laths. The silicic zone is characterized by highly illitic I/S with ≥ 90% I, quartz, akspar and occasional albite. In this zone the matrix and clasts are completely altered, and pyrogenic plagioclase shows significant alteration. Illitic I/S has a euhedral lath-like morphology. In the sericitic zone the hyaloclastite altered primarily to illitic I/S with ≥ 66% I, quartz, and minor akspar and pyrite. Clay minerals completely replace pyrogenic feldspars and little evidence remains of the original hyaloclastite texture. Unlike other zones, illitic I/S is fibrous and pure illite samples are composed of euhedral laths and hexagonal plates. The temperatures of hydrothermal alteration likely ranged from 30 to 90 °C for the argillic zone, from 110 to 160 °C for the propylitic zone, from 160 to 270 °C for the silicic zone, and were possibly as high as 300 °C for the sericitic zone. The four zones occur as linear bands that increase in intensity north of the bentonite mine at Cala dell'Acqua. The alteration zones have two orientations and may be structurally controlled by E-W- and NE-SW-trending faulting which is consistent with the dominant structural trends of the Pontine archipelago. Finally, hydrothermal alteration most likely involved seawater based on the geologic evolution of Ponza.

Hsp90 and environmental stress transform the adaptive value of natural genetic variation.

PubMed

Jarosz, Daniel F; Lindquist, Susan

2010-12-24

How can species remain unaltered for long periods yet also undergo rapid diversification? By linking genetic variation to phenotypic variation via environmental stress, the Hsp90 protein-folding reservoir might promote both stasis and change. However, the nature and adaptive value of Hsp90-contingent traits remain uncertain. In ecologically and genetically diverse yeasts, we find such traits to be both common and frequently adaptive. Most are based on preexisting variation, with causative polymorphisms occurring in coding and regulatory sequences alike. A common temperature stress alters phenotypes similarly. Both selective inhibition of Hsp90 and temperature stress increase correlations between genotype and phenotype. This system broadly determines the adaptive value of standing genetic variation and, in so doing, has influenced the evolution of current genomes.

Increased GABA(A) inhibition of the RVLM after hindlimb unloading in rats

NASA Technical Reports Server (NTRS)

Moffitt, Julia A.; Heesch, Cheryl M.; Hasser, Eileen M.

2002-01-01

Attenuated baroreflex-mediated increases in renal sympathetic nerve activity (RSNA) in hindlimb unloaded (HU) rats apparently are due to changes within the central nervous system. We hypothesized that GABA(A) receptor-mediated inhibition of the rostral ventrolateral medulla (RVLM) is increased after hindlimb unloading. Responses to bilateral microinjection of the GABA(A) antagonist (-)-bicuculline methiodide (BIC) into the RVLM were examined before and during caudal ventrolateral medulla (CVLM) inhibition in Inactin-anesthetized control and HU rats. Increases in mean arterial pressure (MAP), heart rate (HR), and RSNA in response to BIC in the RVLM were significantly enhanced in HU rats. Responses to bilateral CVLM blockade were not different. When remaining GABA(A) inhibition in the RVLM was blocked by BIC during CVLM inhibition, the additional increases in MAP and RSNA were significantly greater in HU rats. These data indicate that GABA(A) receptor-mediated inhibition of RVLM neurons is augmented after hindlimb unloading. Effects of input from the CVLM were unaltered. Thus, after cardiovascular deconditioning in rodents, the attenuated increase in sympathetic nerve activity in response to hypotension is associated with greater GABA(A) receptor-mediated inhibition of RVLM neurons originating at least in part from sources other than the CVLM.

Effects of hydrothermal alteration on the magnetic mineralogy of mid-ocean ridge basalts, IODP Site 1301B, Juan de Fuca Ridge

NASA Astrophysics Data System (ADS)

Linville, L. M.; Housen, B.; Sager, W.

2005-12-01

Pairs of young (3.5 Ma) altered and unaltered MORB from the Juan de Fuca Ridge collected from IODP Expedition 301, Hole 1301B were studied to better understand how hydrothermal alteration affects the magnetization of oceanic crust. Thermomagnetic analysis (performed with both a VSM and Kappabridge) revealed characteristically different Curie temperatures and degree of non-reversibility between altered and unaltered samples. Magnetic contributions outlined by these methods, in addition to IRM and hysteresis parameters, indicate that samples are dominated by single domain titanomagnetite and titanomaghemite, with a titanium content of approximately TM45. Petrological analysis with a SEM confirmed the presence of abundant Fe-Ti oxides. Despite the preponderance of titanomagnetite in unaltered samples, shrinkage cracks, which offer direct evidence of maghemitization, were seen in both altered and unaltered samples, indicating (as do irreversible cooling curves for all samples) that even supposedly unaltered samples have undergone some degree of low temperature oxidation. Preliminary paleomagnetic data in related samples indicates normal polarity and inclinations that are approximately what is expected for this site. The samples also exhibit both streaked and well defined, non-streaked magnetizations. This study intends to utilize the information obtained by procedures described above to test for correlations between characteristic magnetization directions and degree of oxidation, in order to further our understanding of the effect maghemitization has on the paleomagnetism of oceanic rocks.

A uniform input data convention for the CALL 3-D crash victim simulation

NASA Astrophysics Data System (ADS)

Shaibani, S. J.

1982-07-01

Logical schemes for the labelling of planes (cards D) and functions (cards E) in the input decks used for the Calspan 3-D Crash Victim Simulation (CVS) program are proposed. One benefit of introducing such a standardized format for these inputs would be to facilitate greatly the interchange of data for different vehicles. A further advantage would be that the table of allowed contacts (cards F) could remain largely unaltered. It is hoped that the uniformity of the convention described by these schemes would help to promote the exchange of readily usable data between CVS users.

DIBALH mediated reduction of the acetal moiety on perhydrofuro[2,3-b]pyran derivatives.

PubMed

Marco-Contelles, J; Ruiz-Caro, J

2001-09-21

The reaction of DIBALH with bis(heteroannulated)-pyranosides containing the perhydrofuro[2,3-b]pyran moiety is described. The hydride attack at the anomeric carbon (C-9a) resulted in the exclusive tetrahydrofuran ring opening. The selectivity of this reaction has been evaluated as other benzylidene acetals built on these substrates remain practically or partially unaltered in these conditions depending on the steric volume of the O-protecting group located at C-4 (TBDMS vs. Me). This protocol can be considered as a new entry for the synthesis of chiral and highly functionalized cyclopentanes.

Liability and ophthalmic drug use.

PubMed

Classé, J G

1992-01-01

Ophthalmic drug use has been an aspect of optometry for more than two decades. Although utilization of these drugs has produced significant changes in the clinical and legal responsibilities of optometrists, the liability posture of the profession has remained unaltered. Studies of malpractice claims against optometrists and ophthalmologists have demonstrated that ophthalmologists are much more likely to be charged with negligence for adverse drug reactions and that drug-related malpractice claims are not a liability issue for optometrists. Based on the experiences of both professions, this paper describes the adverse effects of common ophthalmic drugs, with emphasis on those drug reactions that have resulted in litigation.

Dynamic Control of Aerodynamic Instabilities in Gas Turbine Engines

NASA Technical Reports Server (NTRS)

Greitzer, E. M.; Epstein, A. H.; Guenette, G. R.; Gysling, D. L.; Haynes, J.; Hendricks, G. J.; Paduano, J.; Simon, J. S.; Valavani, L.

1992-01-01

This lecture discusses the use of closed loop control at the component level to enhance the performance of gas turbine engines. The general theme is the suppression of flow instabilities (rotating stall and surge) through use of feedback, either actively or by means of the aeromechanical coupling provided by tailored structures. The basic concepts that underlie active control of turbomachinery instability, and their experimental demonstration, are first described for a centrifugal compressor. It is shown that the mechanism for stabilization is associated with damping of unsteady perturbations in the compression system, and the steady-state performance can thus remain virtually unaltered. Control of instability using a tailored structure is then discussed, along with experimental results illustrating the flow range extension achievable using this technique. A considerably more complex problem is presented by active control or rotating stall where the multi-dimensional features mean that distributed sensing and actuation are required. In addition, there are basic questions concerning unsteady fluid mechanics; these imply the need to resolve issues connected with identification of suitable signals as well as with definition of appropriate wave launchers for implementing the feedback. These issues are discussed and the results of initial successful demonstrations of active control of rotating stall in a single-stage and a three-stage axial compressor are presented. The lecture concludes with suggestions for future research on dynamic control of gas turbine engines.

Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees

PubMed Central

1994-01-01

The role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is controversial. To assess the part of IL-6 in inflammatory responses to endotoxin, we investigated eight chimpanzees after either a bolus intravenous injection of Escherichia coli endotoxin (n = 4; 4 ng/kg) or after the same dose of endotoxin with a simultaneous bolus intravenous injection of an anti-IL-6 mAb (30 mg; n = 4). Anti-IL-6 did not affect the induction of the cytokine network (tumor necrosis factor [TNF], soluble TNF receptors types I and II, and IL-8) by endotoxin, nor did it influence the occurrence of a neutrophilic leukocytosis and neutrophil degranulation, as monitored by the measurement of elastase- alpha 1-antitrypsin complexes. In contrast, anti-IL-6 markedly attenuated endotoxin-induced activation of coagulation, monitored with the plasma levels of the prothrombin fragment F1+2 and thrombin- antithrombin III complexes, whereas activation of fibrinolysis, determined with the plasma concentrations of plasmin-alpha 2- antiplasmin complexes, remained unaltered. We conclude that IL-6 does not have a feedback effect on the release of other cytokines after injection of endotoxin, and that it is not involved in endotoxin- induced neutrophilia or neutrophil degranulation. IL-6 is, however, an important intermediate factor in activation of coagulation in low grade endotoxemia in chimpanzees. PMID:8145042

40 CFR 436.32 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Construction Sand and Gravel Subcategory § 436.32 Effluent limitations guidelines representing the degree of... unaltered by man's activities, is or would be less than 6.0 and water quality criteria in water quality... adjusted downward to the pH water quality criterion for the receiving waters. In no case shall a pH...

Curcumin induces Apaf-1-dependent, p21-mediated caspase activation and apoptosis

PubMed Central

Zhang, Honghao; Jones, Anthony; Verone, Alissa; Pitarresi, Jason; Jandhyam, Sirisha; Prabhu, Varun; Black, Jennifer D

2011-01-01

Previous studies have demonstrated that curcumin induces mitochondria-mediated apoptosis. However, understanding of the molecular mechanisms underlying curcumin-induced cell death remains limited. In this study, we demonstrate that curcumin treatment of cancer cells caused dose- and time-dependent caspase 3 activation, which is required for apoptosis as confirmed using the pan-caspase inhibitor, z-VAD. Knockdown experiments and knockout cells excluded a role for caspase 8 in curcumin-induced caspase 3 activation. In contrast, Apaf-1 deficiency or silencing inhibited the activity of caspase 3, pointing to a requisite role of Apaf-1 in curcumin-induced apoptotic cell death. Curcumin treatment led to Apaf-1 upregulation, both at the protein and mRNA levels. Cytochrome c release from mitochondria to the cytosol in curcumin-treated cells was associated with upregulation of pro-apoptotic proteins, such as Bax, Bak, Bid and Bim. Cross-linking experiments demonstrated Bax oligomerization during curcumin-induced apoptosis, suggesting that induced expression of Bax, Bid and Bim causes Bax channel formation on the mitochondrial membrane. The release of cytochrome c was unaltered in p53-deficient cells, whereas absence of p21 blocked cytochrome c release, caspase activation and apoptosis. Importantly, p21 deficiency resulted in reduced expression of Apaf-1 during curcumin treatment, indicating a requirement for p21 in Apaf-1-dependent caspase activation and apoptosis. Together, our findings identify Apaf-1, Bax and p21 as novel potential targets for curcumin or curcumin-based anticancer agents. PMID:22101335

Charcoal as a capture material for silver nanoparticles in the aquatic environment

NASA Astrophysics Data System (ADS)

McGillicuddy, Eoin; Morrison, Liam; Cormican, Martin; Morris, Dearbháile

2017-04-01

Background: The reported antibacterial activity of silver nanoparticles (AgNPs) has led to their incorporation into numerous consumer products including; textiles, domestic appliances, food containers, cosmetics, paints, medical and medicinal products. The AgNPs incorporated into these products can be released into the environment and aquatic system during their production, use and end of life disposal. In the aquatic environment, uncertainties surround the concentration, fate and effects of AgNPs. The aim of this project is to examine charcoal as a potential material for capture of silver nanoparticles from the aquatic environment. Material/methods: Activated charcoal is a commonly used filter material and was selected for this project to determine its suitability as a capture material for AgNPs in water samples. Activated charcoal (Norit® CA1 (Sigma-Aldrich)) was exposed to 100 ppb, 25 nm PVP coated AgNPs (nanoComposix) prepared in Milli-Q water. These solutions were exposed to unaltered charcoal granules for 20 hours after which the decrease of silver in the solution was measured using ICP-MS. In order to improve the removal, the surface area of the charcoal was increased firstly by grinding with a pestle and mortar and secondly by milling the charcoal. The milled charcoal was prepared using an agate ball mill running at 500 rpm for 5 minutes. The activated charcoal was then exposed to samples containing 10 ppb AgNPs. Results: In the initial tests, approximately 10% of the silver was removed from the water samples using the unaltered activated charcoal granules. Further experiments were carried out to compare the unaltered granules with the ground and milled charcoal. These tests were carried out similarly to the previous test however lower concentration of 10 ppb was used. After 20 hours of exposure the granule samples, as previously, showed approximately a 10% reduction in silver content with the ground charcoal giving approximately 30% reduction in silver concentration and in the sample exposed to milled charcoal, approximately 60% reduction in silver concentration was observed. These tests found that increasing the surface area of the charcoal increased the silver reduction in the solution. Conclusions: Data suggest that charcoal may be a suitable material for use in the capture of AgNPs from water samples

Earth's early atmosphere as seen from carbon and nitrogen isotopic analysis of Archean sediments

NASA Technical Reports Server (NTRS)

Gibson, E. K., Jr.; Carr, L. P.; Gilmour, I.; Pillinger, C. T.

1986-01-01

The origin and evolution of the Earth's early atmosphere has long been a topic of great interest but determination of actual compositions over geologic time is a difficult problem. However, recent systematic studies of stromatolite deposits (Precambrian Paleobiology Research Group) has extended our knowledge of Archean ecosystems. It has been shown that many stromatolite deposits have undergone negligible alteration since their time of formation. The discovery of primary fluid inclusions within unaltered 3.5 b.y. old Archiean sediments and the observation that the 3.3 b.y. old Barberton cherts have remained closed to argon loss and have not been subjected to thermal metamorphism suggests that an opportunity exists for the direct measurement of the volatile constituents present at their time of formation. Of primary interest to this study was the possibility that the stromatolites and other Archean sediments might retain a vestige of the atmosphere and thus afford an indication of the variations in carbon dioxide and nitrogen isotopic compositions with time. A suite of essentially unaltered Archean stromatolites and the cherts of different ages and geologic sites have been analyzed for their trapped carbon dioxide and nitrogen compositions by the stepped combustion extraction tech nique utilizing static mass spectrometers for the isotope measurements.

Influence of inclination angles on intra- and inter-limb load-sharing during uphill walking.

PubMed

Hong, Shih-Wun; Leu, Tsai-Hsueh; Li, Jia-Da; Wang, Ting-Ming; Ho, Wei-Ping; Lu, Tung-Wu

2014-01-01

Uphill walking is an inevitable part of daily living, placing more challenges on the locomotor system with greater risk of falls than level walking does. The current study aimed to investigate the effects of inclination angles on the inter-joint and inter-limb load-sharing during uphill walking in terms of total support moment and contributions of individual joint moments to the total support moment. Fifteen young adults walked up walkways with 0°, 5°, 10° and 15° of slope while kinematic and kinetic data were collected and analyzed. With increasing inclination angles, the first peak of the total support moment was increased with unaltered individual joint contributions, suggesting an unaltered inter-joint control pattern in the leading limb to meet the increased demands. The second peak of the total support moment remained unchanged with increasing inclination angles primarily through a compensatory redistribution of the hip and knee moments. During DLS, the leading limb shared the majority of the whole body support moments. The current results reveal basic intra- and inter-limb load-sharing patterns of uphill walking, which will be helpful for a better understanding of the control strategies adopted and for subsequent clinical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

The influence of altered working-side occlusal guidance on masticatory muscles and related jaw movement.

PubMed

Belser, U C; Hannam, A G

1985-03-01

The effect of four different occlusal situations (group function, canine guidance, working side occlusal interference, and hyperbalancing occlusal interference) on EMG activity in jaw elevator muscles and related mandibular movement was investigated on 12 subjects. With a computer-based system, EMG and displacement signals were collected simultaneously during specific functional (unilateral chewing) and parafunctional tasks (mandibular gliding movements and various tooth clenching efforts) and analyzed quantitatively. When a naturally acquired group function was temporarily and artificially changed into a dominant canine guidance, a significant general reduction of elevator muscle activity was observed when subjects exerted full isometric tooth-clenching efforts in a lateral mandibular position. The original muscular coordination pattern (relative contraction from muscle to muscle) remained unaltered during this test. With respect to unilateral chewing, no significant alterations in the activity or coordination of the muscles occurred when an artificial canine guidance was introduced. Introduction of a hyperbalancing occlusal contact caused significant alterations in muscle activity and coordination during maximal tooth clenching in a lateral mandibular position. A marked shift of temporal muscle EMG activity toward the side of the interference and unchanged bilateral activity of the two masseter muscles were observed. The results suggest that canine-protected occlusions do not significantly alter muscle activity during mastication but significantly reduce muscle activity during parafunctional clenching. They also suggest that non-working side contacts dramatically alter the distribution of muscle activity during parafunctional clenching, and that this redistribution may affect the nature of reaction forces at the temporomandibular joints.

Moessbauer Mineralogy of Rock, Soil, and Dust at Gusev Crater, Mars: Spirit's Journey through Weakly Altered Olivine Basalt on the Plains and Pervasively Altered Basalt in the Columbia Hills

NASA Technical Reports Server (NTRS)

Morris, R. V.; Klingelhoefer, G.; Schroeder, C.; Rodionov, D. S.; Yen, A.; Ming, D. W.; deSouza, P. A., Jr.; Fleischer, I.; Wdowiak, T.; Gellert, R.;

Dissolution of biogenic ooze over basement edifices in the equatorial Pacific with implications for hydrothermal ventilation of the oceanic crust

USGS Publications Warehouse

Bekins, B.A.; Spivack, A.J.; Davis, E.E.; Mayer, L.A.

2007-01-01

Recent observations indicate that curious closed depressions in carbonate sediments overlying basement edifices are widespread in the equatorial Pacific. A possible mechanism for their creation is dissolution by fluids exiting basement vents from off-axis hydrothermal flow. Quantitative analysis based on the retrograde solubility of calcium carbonate and cooling of basement fluids during ascent provides an estimate for the dissolution capacity of the venting fluids. Comparison of the dissolution capacity and fluid flux with typical equatorial Pacific carbonate mass accumulation rates shows that this mechanism is feasible. By maintaining sediment-free basement outcrops, the process may promote widespread circulation of relatively unaltered seawater in the basement in an area where average sediment thicknesses are 300-500 m. The enhanced ventilation can explain several previously puzzling observations in this region, including anomalously low heat flux, relatively unaltered seawater in the basement, and aerobic and nitrate-reducing microbial activity at the base of the sediments. ?? 2007 The Geological Society of America.

Behavioural responses to novelty or to a predator stimulus are not altered in adult zebrafish by early embryonic alcohol exposure

PubMed Central

Seguin, Diane; Shams, Soaleha; Gerlai, Robert

2016-01-01

Background Fetal Alcohol Spectrum Disorders (FASD) may vary in symptoms and severity. In the milder and more prevalent forms of the disease, behavioural abnormalities may include impaired social behaviour, e.g. difficulty interpreting social cues. FASD patients remain often undiagnosed due to lack of biomarkers, and treatment is unavailable because the mechanisms of the disease are not yet understood. Animal models have been proposed to facilitate addressing these problems. More recently, short exposure of the zebrafish embryo to low concentrations of alcohol was shown to lead to significant and lasting impairment of behaviour in response to social stimuli. The impairment may be the result of abnormal social behaviour or altered fear/anxiety. The goal of the current study was to investigate the latter. Methods Here, we employed the alcohol exposure regimen used previously (exposure of 24th hour post-fertilization embryos to 0.00, 0.25, 0.50, 0.75 or 1.00 vol/vol % alcohol for 2 hours), allowed the fish to reach adulthood, and measured the behavioural responses of these adults to a novel tank (anxiety related behaviours) as well as to an animated image of a sympatric predator of zebrafish (fear related behaviours). Results We found behavioural responses of embryonic alcohol exposed adult fish to remain statistically indistinguishable from those of controls, suggesting unaltered anxiety and fear in the embryonic alcohol treated fish. Conclusions Given that motor and perceptual function was previously shown to be also unaltered in the adults after embryonic alcohol exposure, our current results suggest that the impaired response of these fish to social stimuli may be the result of abnormal social behaviour. PMID:27790739

The pool of fast releasing vesicles is augmented by myosin light chain kinase inhibition at the calyx of Held synapse.

PubMed

Srinivasan, Geetha; Kim, Jun Hee; von Gersdorff, Henrique

2008-04-01

Synaptic strength is determined by release probability and the size of the readily releasable pool of docked vesicles. Here we describe the effects of blocking myosin light chain kinase (MLCK), a cytoskeletal regulatory protein thought to be involved in myosin-mediated vesicle transport, on synaptic transmission at the mouse calyx of Held synapse. Application of three different MLCK inhibitors increased the amplitude of the early excitatory postsynaptic currents (EPSCs) in a stimulus train, without affecting the late steady-state EPSCs. A presynaptic locus of action for MLCK inhibitors was confirmed by an increase in the frequency of miniature EPSCs that left their average amplitude unchanged. MLCK inhibition did not affect presynaptic Ca(2+) currents or action potential waveform. Moreover, Ca(2+) imaging experiments showed that [Ca(2+)](i) transients elicited by 100-Hz stimulus trains were not altered by MLCK inhibition. Studies using high-frequency stimulus trains indicated that MLCK inhibitors increase vesicle pool size, but do not significantly alter release probability. Accordingly, when AMPA-receptor desensitization was minimized, EPSC paired-pulse ratios were unaltered by MLCK inhibition, suggesting that release probability remains unaltered. MLCK inhibition potentiated EPSCs even when presynaptic Ca(2+) buffering was greatly enhanced by treating slices with EGTA-AM. In addition, MLCK inhibition did not affect the rate of recovery from short-term depression. Finally, developmental studies revealed that EPSC potentiation by MLCK inhibition starts at postnatal day 5 (P5) and remains strong during synaptic maturation up to P18. Overall, our data suggest that MLCK plays a crucial role in determining the size of the pool of synaptic vesicles that undergo fast release at a CNS synapse.

The MAP kinase JNK2 mediates cigarette smoke-induced arterial thrombosis.

PubMed

Breitenstein, Alexander; Stämpfli, Simon F; Reiner, Martin F; Shi, Yi; Keller, Stephan; Akhmedov, Alexander; Schaub Clerigué, Ariane; Spescha, Remo D; Beer, Hans-Jürg; Lüscher, Thomas F; Tanner, Felix C; Camici, Giovanni G

2017-01-05

Despite public awareness of its deleterious effects, smoking remains a major cause of death. Indeed, it is a risk factor for atherothrombotic complications and in line with this, the introduction of smoking ban in public areas reduced smoking-associated cardiovascular complications. Nonetheless, smoking remains a major concern, and molecular mechanisms by which it causes cardiovascular disease are not known. Peripheral blood monocytes from healthy smokers displayed increased JNK2 and tissue factor (TF) gene expression compared to non-smokers (n=15, p<0.05). Similarly, human aortic endothelial cells exposed to cigarette smoke total particulate matter (CS-TPM) revealed increased TF expression mediated by JNK2 (n=4; p<0.05). Wild-type and JNK2 -/- mice were exposed to cigarette smoke for two weeks after which arterial thrombosis was investigated. Wild-type mice exposed to smoke displayed reduced time to thrombotic arterial occlusion (n=8; p<0.05) and increased tissue factor activity (n=7; p<0.05) as compared to wild-type controls (n=6), while JNK2 -/- mice exposed to smoke maintained an unaltered thrombotic potential (n=8; p=NS) and tissue factor activity (n=8) comparable to that of JNK2 -/- and wild-type controls (n=6; p=NS). Smoking caused an increased production of reactive oxygen species (ROS) in wild-type but not in JNK2 -/- mice (n=7; p<0.05 for wild-type mice and n=5-6; p=NS for JNK2 -/- mice). In conclusion, the MAP kinase JNK2 mediates cigarette smoke-induced TF activation, arterial thrombosis and ROS production. These results underscore a major role of JNK2 in smoke-mediated thrombus formation and may offer an attractive target to prevent smoke-related thrombosis in those subjects which do not manage quitting.

Molecular mechanism underlying muscle mass retention in hibernating bats: role of periodic arousal.

PubMed

Lee, Kisoo; So, Hyekyoung; Gwag, Taesik; Ju, Hyunwoo; Lee, Ju-Woon; Yamashita, Masamichi; Choi, Inho

2010-02-01

Hibernators like bats show only marginal muscle atrophy during prolonged hibernation. The current study was designed to test the hypothesis that hibernators use periodic arousal to increase protein anabolism that compensates for the continuous muscle proteolysis during disuse. To test this hypothesis, we investigated the effects of 3-month hibernation (HB) and 7-day post-arousal torpor (TP) followed by re-arousal (RA) on signaling activities in the pectoral muscles of summer-active (SA) and dormant Murina leucogaster bats. The bats did not lose muscle mass relative to body mass during the HB or TP-to-RA period. For the first 30-min following arousal, the peak amplitude and frequency of electromyographic spikes increased 3.1- and 1.4-fold, respectively, indicating massive myofiber recruitment and elevated motor signaling during shivering. Immunoblot analyses of whole-tissue lysates revealed several principal outcomes: (1) for the 3-month HB, the phosphorylation levels of Akt1 (p-Akt1) and p-mTOR decreased significantly compared to SA bats, but p-FoxO1 levels remained unaltered; (2) for the TP-to-RA period, p-Akt1 and p-FoxO1 varied little, while p-mTOR showed biphasic oscillation; (3) proteolytic signals (i.e., atrogin-1, MuRF1, Skp2 and calpain-1) remained constant during the HB and TP-to-RA period. These results suggest that the resistive properties of torpid bat muscle against atrophy might be attained primarily by relatively constant proteolysis in combination with oscillatory anabolic activity (e.g., p-mTOR) corresponding to the frequency of arousals occurring throughout hibernation. (c) 2009 Wiley-Liss, Inc.

Galectin-9 Produced by Intestinal Epithelial Cells Enhances Aldehyde Dehydrogenase Activity in Dendritic Cells in a PI3K- and p38-Dependent Manner.

PubMed

de Kivit, Sander; Kostadinova, Atanaska I; Kerperien, JoAnn; Ayechu Muruzabal, Veronica; Morgan, Mary E; Knippels, Leon M J; Kraneveld, Aletta D; Garssen, Johan; Willemsen, Linette E M

2017-01-01

Intestinal epithelial cells (IEC) drive regulatory T cell (Treg) responses by promoting the differentiation of aldehyde dehydrogenase (ALDH)-expressing CD103+ dendritic cells (DC). Apical stimulation of TLR9 by CpG DNA on IEC supports galectin-9 expression by IEC, which is promoted by short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (GF). While galectin-9 can induce the maturation of monocyte-derived DC (moDC), the contribution of galectin-9 on the induction of ALDH activity in DC is not known. To this end, DC were stimulated with galectin-9, and ALDH activity and the expression of CD103 were assessed. ALDH activity was increased by moDC exposed to galectin-9, while the expression of CD103 remained unaltered. Galectin-9 secreted by IEC apically exposed to CpG DNA and GF enhanced ALDH activity, but not CD103 expression by moDC, which was abrogated upon galectin-9 neutralization. Similar observations were found in murine GM-CSF-cultured bone marrow-derived DC (BMDC). Using Flt3L-cultured BMDC and ex vivo murine splenic DC, it was observed that galectin-9 only enhanced ALDH activity in the presence of GM-CSF in CD103- cells. The induction of ALDH activity in BMDC was dependent on p38 and PI3K signaling. These data indicate a novel role for galectin-9 in modulating innate immunity by inducing ALDH activity in DC. © 2017 S. Karger AG, Basel.

Gastroprotective effect of Piper betle Linn. leaves grown in Sri Lanka.

PubMed

Arawwawala, L D A M; Arambewela, L S R; Ratnasooriya, W D

2014-01-01

Piper betle Linn. (Piperaceae) is used as a remedy for gastric ulcers in traditional medicinal systems in Sri Lanka. However, the gastroprotective activity has never been proven scientifically using betel leaves grown in Sri Lanka. To evaluate the gastroprotective activity of hot aqueous extract (HAE) and cold ethanolic extract (CEE) of P. betle in rats as the experimental model. Three doses (200, 300, and 500 mg/kg/bw) of both extracts were evaluated for the gastroprotective activity against ethanol induced gastric ulcers in rats. The parameters evaluated were (a) effects of HAE on mucus content adhering to the wall of the gastric mucosa, (b) acidity (total and free), (c) volume and (d) pH of the gastric juice. ORAL ADMINISTRATION OF HAE AND CEE PROVIDED MARKED DOSE DEPENDENT (HAE: r (2) = 0.97; CEE: r (2) = 0.96) and significant (P ≤ 0.05) protection against gastric damage caused by absolute ethanol. The gastroprotective effect of CEE was comparable with that of HAE. Further, gastroprotective activity of the highest dose of both extracts were significantly greater (P ≤ 0.05) than that of misoprostol, the reference drug. The HAE significantly (P ≤ 0.05) increased the mucus content adhering to the wall of the gastric mucosa and inhibited the volume of gastric acid. However, acidity (total and free) and pH of the gastric juice remained unaltered. It is concluded that both HAE and CEE of P. betle leaves have a strong gastroprotective activity.

Human papillomavirus (HPV) oncoprotein E6 facilitates Calcineurin-Nuclear factor for activated T cells 2 (NFAT2) signaling to promote cellular proliferation in cervical cell carcinoma.

PubMed

Ram, Babul Moni; Dolpady, Jayashree; Kulkarni, Rakesh; Usha, R; Bhoria, Usha; Poli, Usha Rani; Islam, Mojahidul; Trehanpati, Nirupma; Ramakrishna, Gayatri

2018-01-01

The calcineurin-NFAT signaling pathway regulates cell proliferation, differentiation, and development in diverse cell types and organ systems. Deregulation of calcineurin-NFAT signaling has been reported in leukaemias and few solid tumors such as breast and colon. In the present study, we found elevated calcineurin protein levels and phosphatase activity in cervical cancer cell lines and depletion of the same attenuated cell proliferation. Additionally, nuclear levels of NFAT2, a downstream target of calcineurin, viz, was found elevated in human papillomavirus (HPV) infected cells, HeLa and SiHa, compared to the HPV negative cells, HaCaT and C33A, indicative of its higher DNA binding activity. The nuclear levels of both NFAT1 and NFAT3 remain unaltered implicating they have little role in cervical carcinogenesis. Similar to the in vitro studies, the HPV infected human squamous cell carcinoma specimens showed higher NFAT2 levels compared to the normal cervical epithelium. Depletion of NFAT2 by RNAi attenuated growth of SiHa cells. Overexpression of HPV16 oncoproteins viz, E6 and E7 increased NFAT2 expression levels and DNA binding activity, while knockdown of E6 by RNAi decreased the same. Briefly, we now report an activation of calcineurin-NFAT2 axis in cervical cancer and a novel role of HPV oncoprotein in facilitating NFAT2 dependent cell proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

Endothelial CaMKII as a regulator of eNOS activity and NO-mediated vasoreactivity

PubMed Central

Murthy, Shubha; Koval, Olha M.; Ramiro Diaz, Juan M.; Kumar, Santosh; Nuno, Daniel; Scott, Jason A.; Allamargot, Chantal; Zhu, Linda J.; Broadhurst, Kim; Santhana, Velarchana; Kutschke, William J.; Irani, Kaikobad; Lamping, Kathryn G.; Grumbach, Isabella M.

2017-01-01

The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase important in transducing intracellular Ca2+ signals. While in vitro data regarding the role of CaMKII in the regulation of endothelial nitric oxide synthase (eNOS) are contradictory, its role in endothelial function in vivo remains unknown. Using two novel transgenic models to express CaMKII inhibitor peptides selectively in endothelium, we examined the effect of CaMKII on eNOS activation, NO production, vasomotor tone and blood pressure. Under baseline conditions, CaMKII activation was low in the aortic wall. Consistently, systolic and diastolic blood pressure, heart rate and plasma NO levels were unaltered by endothelial CaMKII inhibition. Moreover, endothelial CaMKII inhibition had no significant effect on NO-dependent vasodilation. These results were confirmed in studies of aortic rings transduced with adenovirus expressing a CaMKII inhibitor peptide. In cultured endothelial cells, bradykinin treatment produced the anticipated rapid influx of Ca2+ and transient CaMKII and eNOS activation, whereas CaMKII inhibition blocked eNOS phosphorylation on Ser-1179 and dephosphorylation at Thr-497. Ca2+/CaM binding to eNOS and resultant NO production in vitro were decreased under CaMKII inhibition. Our results demonstrate that CaMKII plays an important role in transient bradykinin-driven eNOS activation in vitro, but does not regulate NO production, vasorelaxation or blood pressure in vivo under baseline conditions. PMID:29059213

Genetic Separation of Hypoxanthine and Guanine-Xanthine Phosphoribosyltransferase Activities by Deletion Mutations in Salmonella typhimurium

PubMed Central

Gots, Joseph S.; Benson, Charles E.; Shumas, Susan R.

1972-01-01

Certain proAB deletion mutants of Salmonella typhimurium were found to be simultaneously deleted in a gene required for the utilization of guanine and xanthine (designated gxu). These mutants were resistant to 8-azaguanine and when carrying an additional pur mutation were unable to use guanine or xanthine as a purine source. The defect was correlated with deficiencies in the uptake and phosphoribosyltransferase activities for guanine and xanthine. Hypoxanthine and adenine activities were unaltered. The deficiency was restored to normal by transduction to pro+ and in F′ merodiploids. PMID:4563984

Lipophilization of somatostatin analog RC-160 with long chain fatty acid improves its antiproliferative and antiangiogenic activity in vitro.

PubMed

Dasgupta, P; Mukherjee, R

2000-01-01

The therapeutic potential of the somatostatin analogue RC-160 having antiproliferative activity, is limited by its short serum half life. To overcome this limitation, fatty acids namely butanoic acid and myristic acid were conjugated to the N-terminal residue of RC-160. The lipophilized derivatives of RC-160 were synthesized, purified by reverse phase HPLC and characterized by ES-mass spectroscopy. The antiproliferative activity of lipophilized derivatives of RC-160 on the growth of MIA-PaCa2 (human pancreatic carcinoma), DU145 (human prostate carcinoma), ECV304 (human umbilical chord endothelioma), as well as their antiangiogenic activity was evaluated in vitro. The relative stability of myristoyl-RC-160 towards degradation by proteases and serum was also determined. Myristoyl-RC-160 exhibited significantly higher antiproliferative efficacy than RC-160, on the above cell lines (P<0.01). Receptor binding assays, demonstrated that the affinity of RC-160 towards somatostatin receptors remains unaltered by myristoylation. Unlike RC-160, the myristoylated derivative was found to have significantly greater resistance to protease and serum degradation (P<0.01). Myristoyl-RC-160 exhibited significantly greater antiproliferative activity on ECV304, than RC-160 (P<0.01). Myristoyl RC-160 could also inhibit capillary tube formation more efficiently than RC-160 in a dose dependent manner, suggesting that it possessed enhanced antiangiogenic activity in vitro (P<0.001). Lipophilization of RC-160 with long chain fatty acids like myristic acid endows it with improved antiproliferative and antiangiogenic activity, stability and therapeutic index. British Journal of Pharmacology (2000) 109, 101 - 109

Lipophilization of somatostatin analog RC-160 with long chain fatty acid improves its antiproliferative and antiangiogenic activity in vitro

PubMed Central

Dasgupta, P; Mukherjee, R

2000-01-01

The therapeutic potential of the somatostatin analogue RC-160 having antiproliferative activity, is limited by its short serum half life. To overcome this limitation, fatty acids namely butanoic acid and myristic acid were conjugated to the N-terminal residue of RC-160. The lipophilized derivatives of RC-160 were synthesized, purified by reverse phase HPLC and characterized by ES-mass spectroscopy. The antiproliferative activity of lipophilized derivatives of RC-160 on the growth of MIA-PaCa2 (human pancreatic carcinoma), DU145 (human prostate carcinoma), ECV304 (human umbilical chord endothelioma), as well as their antiangiogenic activity was evaluated in vitro. The relative stability of myristoyl-RC-160 towards degradation by proteases and serum was also determined. Myristoyl-RC-160 exhibited significantly higher antiproliferative efficacy than RC-160, on the above cell lines (P<0.01). Receptor binding assays, demonstrated that the affinity of RC-160 towards somatostatin receptors remains unaltered by myristoylation. Unlike RC-160, the myristoylated derivative was found to have significantly greater resistance to protease and serum degradation (P<0.01). Myristoyl-RC-160 exhibited significantly greater antiproliferative activity on ECV304, than RC-160 (P<0.01). Myristoyl RC-160 could also inhibit capillary tube formation more efficiently than RC-160 in a dose dependent manner, suggesting that it possessed enhanced antiangiogenic activity in vitro (P<0.001). Lipophilization of RC-160 with long chain fatty acids like myristic acid endows it with improved antiproliferative and antiangiogenic activity, stability and therapeutic index. PMID:10694208

On the temperature-programmed reduction of Pt-Ir/. gamma. -Al/sub 2/O/sub 3/ catalysts

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

Wagstaff, N.; Prins, R.

1979-10-15

Temperature-programed reduction of a catalyst containing 0.37% Pt and 0.37% Ir on chlorided alumina and treated as previously described for a Pt-Re bimetallic catalyst showed a single reduction peak at 105/sup 0/C, almost exactly at the midpoint between the reduction peaks of the pure platimun and pure iridium peaks treated identically. This peak remained unaltered after fairly severe oxidation treatment (350/sup 0/C). The results indicated that the catalyst formed bimetallic clusters in the reduced state which were more stable than the Pt-Re clusters and did not segregate on oxidation.

Unaltered ethical standards for individual physicians in the face of drastically reduced resources resulting from an improvised nuclear device event.

PubMed

Caro, J Jaime; Coleman, C Norman; Knebel, Ann; DeRenzo, Evan G

2011-01-01

When disaster disrupts healthcare and other systems, the ethical allocation of resources should follow principles of justice, defined as fairness, established for normal clinical practice. Standards of clinical practice may be altered during disaster, but ethical standards must remain centered on prioritizing the treatment of patients according to need and the effectiveness of treatment. Should resources become extremely limited, it is fair to restrict their use to patients who have the highest needs, provided that the intervention is effective. When resources become more available, patients with lower priority can be increasingly accommodated.

A two-dimensional kinematic dynamo model of the ionospheric magnetic field at Venus

NASA Technical Reports Server (NTRS)

Cravens, T. E.; Wu, D.; Shinagawa, H.

1990-01-01

The results of a high-resolution, two-dimensional, time dependent, kinematic dynamo model of the ionospheric magnetic field of Venus are presented. Various one-dimensional models are considered and the two-dimensional model is then detailed. In this model, the two-dimensional magnetic induction equation, the magnetic diffusion-convection equation, is numerically solved using specified plasma velocities. Origins of the vertical velocity profile and of the horizontal velocities are discussed. It is argued that the basic features of the vertical magnetic field profile remain unaltered by horizontal flow effects and also that horizontal plasma flow can strongly affect the magnetic field for altitudes above 300 km.

Purine-related metabolites and their converting enzymes are altered in frontal, parietal and temporal cortex at early stages of Alzheimer's disease pathology.

PubMed

Alonso-Andrés, Patricia; Albasanz, José Luis; Ferrer, Isidro; Martín, Mairena

2018-01-24

Adenosine, hypoxanthine, xanthine, guanosine and inosine levels were assessed by HPLC, and the activity of related enzymes 5'-nucleotidase (5'-NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) measured in frontal (FC), parietal (PC) and temporal (TC) cortices at different stages of disease progression in Alzheimer's disease (AD) and in age-matched controls. Significantly decreased levels of adenosine, guanosine, hypoxanthine and xanthine, and apparently less inosine, are found in FC from the early stages of AD; PC and TC show an opposing pattern, as adenosine, guanosine and inosine are significantly increased at least at determinate stages of AD whereas hypoxanthine and xanthine levels remain unaltered. 5'-NT is reduced in membranes and cytosol in FC mainly at early stages but not in PC, and only at advanced stages in cytosol in TC. ADA activity is decreased in AD when considered as a whole but increased at early stages in TC. Finally, PNP activity is increased only in TC at early stages. Purine metabolism alterations occur at early stages of AD independently of neurofibrillary tangles and β-amyloid plaques. Alterations are stage dependent and region dependent, the latter showing opposite patterns in FC compared with PC and TC. Adenosine is the most affected of the assessed purines. © 2018 International Society of Neuropathology.

Recovery of rat alveolar macrophages by bronchoalveolar lavage under normal and activated conditions.

PubMed Central

Rehn, B; Bruch, J; Zou, T; Hobusch, G

1992-01-01

When rat (female Wistar) lungs were lavaged (bronchoalveolar lavage, BAL) six times with physiological saline, approximately the same number of alveolar macrophages (AM) were found in the first and second BAL, whereas in the third fourth, fifth, and sixth BAL, the number of AM decreased exponentially. Morphometric counting of the number of AM in histological sections of lung tissue showed that only 14% of the AM population had been recovered by BAL. Although additives to the BAL fluid such as lidocaine and/or fetal calf serum increased the AM count in the first washing considerably, the total number of AM washed out remained unaltered. Addition of the phagocytosis stimulant zymosan increased the AM count in BAL by a factor of more than 2. On stimulation of the lungs with an inert dust (silicon carbide), the AM count in the BAL and the lung was only slightly increased 8 weeks after intratracheal instillation. In contrast, after exposure to fibrogenic and cytotoxic quartz, the AM count in BAL and lung was significantly increased, and the recovery of AM had also increased by a factor of approximately 2. The experiments show that it is the micromilieu of the alveoli and the condition of the AM (certain physiological activation states, such as phagocytic activity) that essentially determine the degree of recovery. PMID:1396444

Endoplasmic Reticulum Stress Sensor IRE1α Enhances IL-23 Expression by Human Dendritic Cells.

PubMed

Márquez, Saioa; Fernández, José Javier; Terán-Cabanillas, Eli; Herrero, Carmen; Alonso, Sara; Azogil, Alicia; Montero, Olimpio; Iwawaki, Takao; Cubillos-Ruiz, Juan R; Fernández, Nieves; Crespo, Mariano Sánchez

2017-01-01

Human monocyte-derived dendritic cells (DCs) exposed to pathogen-associated molecular patterns (PAMPs) undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexokinase inhibitor 2-deoxy-d-glucose (2-DG) modulated cytokine expression in stimulated DCs. Strikingly, IL23A was markedly induced upon 2-DG treatment, but not during glucose deprivation. Since 2-DG can also rapidly inhibit protein N-glycosylation, we postulated that this compound could induce IL-23 in DCs via activation of the endoplasmic reticulum (ER) stress response. Indeed, stimulation of DCs with PAMPs in the presence of 2-DG robustly activated inositol-requiring protein 1α (IRE1α) signaling and to a lesser extent the PERK arm of the unfolded protein response. Additional ER stressors such as tunicamycin and thapsigargin also promoted IL-23 expression by PAMP-stimulated DCs. Pharmacological, biochemical, and genetic analyses using conditional knockout mice revealed that IL-23 induction in ER stressed DCs stimulated with PAMPs was IRE1α/X-box binding protein 1-dependent upon zymosan stimulation. Interestingly, we further evidenced PERK-mediated and CAAT/enhancer-binding protein β-dependent trans -activation of IL23A upon lipopolysaccharide treatment. Our findings uncover that the ER stress response can potently modulate cytokine expression in PAMP-stimulated human DCs.

Endoplasmic Reticulum Stress Sensor IRE1α Enhances IL-23 Expression by Human Dendritic Cells

PubMed Central

Márquez, Saioa; Fernández, José Javier; Terán-Cabanillas, Eli; Herrero, Carmen; Alonso, Sara; Azogil, Alicia; Montero, Olimpio; Iwawaki, Takao; Cubillos-Ruiz, Juan R.; Fernández, Nieves; Crespo, Mariano Sánchez

2017-01-01

Human monocyte-derived dendritic cells (DCs) exposed to pathogen-associated molecular patterns (PAMPs) undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexokinase inhibitor 2-deoxy-d-glucose (2-DG) modulated cytokine expression in stimulated DCs. Strikingly, IL23A was markedly induced upon 2-DG treatment, but not during glucose deprivation. Since 2-DG can also rapidly inhibit protein N-glycosylation, we postulated that this compound could induce IL-23 in DCs via activation of the endoplasmic reticulum (ER) stress response. Indeed, stimulation of DCs with PAMPs in the presence of 2-DG robustly activated inositol-requiring protein 1α (IRE1α) signaling and to a lesser extent the PERK arm of the unfolded protein response. Additional ER stressors such as tunicamycin and thapsigargin also promoted IL-23 expression by PAMP-stimulated DCs. Pharmacological, biochemical, and genetic analyses using conditional knockout mice revealed that IL-23 induction in ER stressed DCs stimulated with PAMPs was IRE1α/X-box binding protein 1-dependent upon zymosan stimulation. Interestingly, we further evidenced PERK-mediated and CAAT/enhancer-binding protein β-dependent trans-activation of IL23A upon lipopolysaccharide treatment. Our findings uncover that the ER stress response can potently modulate cytokine expression in PAMP-stimulated human DCs. PMID:28674530

Effects of mild running on substantia nigra during early neurodegeneration.

PubMed

Almeida, Michael F; Silva, Carolliny M; Chaves, Rodrigo S; Lima, Nathan C R; Almeida, Renato S; Melo, Karla P; Demasi, Marilene; Fernandes, Tiago; Oliveira, Edilamar M; Netto, Luis E S; Cardoso, Sandra M; Ferrari, Merari F R

2018-06-01

Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8 weeks) and 6 weeks of moderate treadmill running, beginning 4 weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level. It was demonstrated that moderate treadmill running, practiced during early neurodegeneration, prevented the increase of alpha-synuclein and maintained the levels of TH unaltered in substantia nigra of aged rats. Physical exercise also stimulated autophagy and prevented impairment of mitophagy, but decreased proteasome activity in rotenone-exposed aged rats. Physical activity also prevented H 2 O 2 increase during early neurodegeneration, although the involved mechanism remains to be elucidated. TrkB levels and its anterograde trafficking seem not to be influenced by moderate treadmill running. In conclusion, moderate physical training could prevent early neurodegeneration in substantia nigra through the improvement of autophagy and mitophagy.

Modulation of oxidative responses by a virulent isolate of Colletotrichum fructicola in apple leaves.

PubMed

Velho, Aline Cristina; Rockenbach, Mathias F; Mondino, Pedro; Stadnik, Marciel J

2016-10-01

Apple bitter rot (ABR) and Glomerella leaf spot (GLS) can be caused by Colletotrichum fructicola. Although both diseases can occur simultaneously in orchards, some isolates show clear organ specialization. Thus, this work was aimed to compare microscopically the development of preinfective structures of ABR- and GLS isolates and their impact on the enzymatic oxidant defense system during the leaf infection process. On leaves, conidial germlings of GLS-isolate formed appressoria mostly sessile. In contrast, those of ABR-isolate were pedicellate and formed multiple melanized appressoria probably as a sign of unsuccessful infection attempts. Neither ABR- nor GLS isolate triggered hypersensitive response in apple leaves. In overall, the activity of scavenging enzymes was higher and long-lasting in leaves inoculated by GLS- than by ABR isolate and control. Guaiacol peroxidase, catalase, and glutathione reductase had activity peaks within 24 h after inoculation (HAI). Ascorbate peroxidase activity was higher only in GLS-infected leaves at 6 HAI, while superoxide dismutase remained unaltered. A lower level of hydrogen peroxide (H2O2) was determined in GLS-infected plants at 48 HAI, but the electrolyte leakage markedly increased. Disease symptoms in leaves were only caused by GLS-isolate. Results suggest that the virulent isolate coordinately downregulates the oxidative plant defense responses enabling its successful establishment in apple leaves. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Characterizing Sub-Daily Flow Regimes: Implications of Hydrologic Resolution on Ecohydrology Studies

DOE PAGES

Bevelhimer, Mark S.; McManamay, Ryan A.; O'Connor, B.

2014-05-26

Natural variability in flow is a primary factor controlling geomorphic and ecological processes in riverine ecosystems. Within the hydropower industry, there is growing pressure from environmental groups and natural resource managers to change reservoir releases from daily peaking to run-of-river operations on the basis of the assumption that downstream biological communities will improve under a more natural flow regime. In this paper, we discuss the importance of assessing sub-daily flows for understanding the physical and ecological dynamics within river systems. We present a variety of metrics for characterizing sub-daily flow variation and use these metrics to evaluate general trends amongmore » streams affected by peaking hydroelectric projects, run-of-river projects and streams that are largely unaffected by flow altering activities. Univariate and multivariate techniques were used to assess similarity among different stream types on the basis of these sub-daily metrics. For comparison, similar analyses were performed using analogous metrics calculated with mean daily flow values. Our results confirm that sub-daily flow metrics reveal variation among and within streams that are not captured by daily flow statistics. Using sub-daily flow statistics, we were able to quantify the degree of difference between unaltered and peaking streams and the amount of similarity between unaltered and run-of-river streams. The sub-daily statistics were largely uncorrelated with daily statistics of similar scope. Furthermore, on short temporal scales, sub-daily statistics reveal the relatively constant nature of unaltered streamreaches and the highly variable nature of hydropower-affected streams, whereas daily statistics show just the opposite over longer temporal scales.« less

Use for Teachers and Students | Galaxy of Images

Science.gov Websites

the website. Some Frequently Asked Questions by Students and Teachers May I put unaltered images, text Libraries (http://www.sil.si.edu). May I put unaltered images, text or content from this website on my should include a link back to Smithsonian Libraries (http://www.sil.si.edu). May I put images, text or

A First Look at Airborne Imaging Spectrometer (AIS) Data in an Area of Altered Volcanic Rocks and Carbonate Formations, Hot Creek Range, South Central Nevada

NASA Technical Reports Server (NTRS)

Feldman, S. C.; Taranik, J. V.; Mouat, D. A.

1985-01-01

Three flight lines of Airborne Imaging Spectrometer (AIS) data were collected in 128 bands between 1.2 and 2.4 microns in the Hot Creek Range, Nevada on July 25, 1984. The flight lines are underlain by hydrothermally altered and unaltered Paleozoic carbonates and Tertiary rhyolitic to latitic volcanics in the Tybo mining district. The original project objectives were to discriminate carbonate rocks from other rock types, to distinguish limestone from dolomite, and to discriminate carbonate units from each other using AIS imagery. Because of high cloud cover over the prime carbonate flight line and because of the acquisition of another flight line in altered and unaltered volcanics, the study has been extended to the discrimination of alteration products. In an area of altered and unaltered rhyolites and latites in Red Rock Canyon, altered and unaltered rock could be discriminated from each other using spectral features in the 1.16 to 2.34 micron range. The altered spectral signatures resembled montmorillonite and kaolinite. Field samples were gathered and the presence of montmorillonite was confirmed by X-ray analysis.

The effect of food on gastrointestinal (GI) transit of sustained-release ibuprofen tablets as evaluated by gamma scintigraphy

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

Borin, M.T.; Khare, S.; Beihn, R.M.

1990-03-01

The GI transit of radiolabeled sustained-release ibuprofen 800-mg tablets in eight healthy, fed volunteers was monitored using external gamma scintigraphy. Ibuprofen serum concentrations were determined from blood samples drawn over 36 hr following dosing. Sustained-release ibuprofen tablets containing 0.18% of 170Er2O3 (greater than 96% 170Er) in the bulk formulation were manufactured under pilot-scale conditions and were radiolabeled utilizing a neutron activation procedure which converted stable 170Er to radioactive 171Er (t1/2 = 7.5 hr). At the time of dosing, each tablet contained 50 mu Ci of 171Er. Dosage form position were reported at various time intervals. In five subjects the sustained-releasemore » tablet remained in the stomach and eroded slowly over 7-12 hr, resulting in gradual increases in small bowel radioactivity. In the remaining three subjects, the intact tablet was ejected from the stomach and a gastric residence time of approximately 4 hr was measured. This is in marked contrast to a previous study conducted in fasted volunteers in which gastric retention time ranged from 10 to 60 min. Differences in GI transit between fed and fasted volunteers had little effect on ibuprofen bioavailability. AUC and Tmax were unaltered and Cmax was increased by 24%, which is in agreement with results from a previous, crossover-design food effect study.« less

Restraint stress enhances arterial thrombosis in vivo--role of the sympathetic nervous system.

PubMed

Stämpfli, Simon F; Camici, Giovanni G; Keller, Stephan; Rozenberg, Izabela; Arras, Margarete; Schuler, Beat; Gassmann, Max; Garcia, Irene; Lüscher, Thomas F; Tanner, Felix C

2014-01-01

Stress is known to correlate with the incidence of acute myocardial infarction. However, the molecular mechanisms underlying this correlation are not known. This study was designed to assess the effect of experimental stress on arterial thrombus formation, the key event in acute myocardial infarction. Mice exposed to 20 h of restraint stress displayed an increased arterial prothrombotic potential as assessed by photochemical injury-induced time to thrombotic occlusion. This increase was prevented by chemical sympathectomy performed through 6-hydroxydopamine (6-OHDA). Blood-born tissue factor (TF) activity was enhanced by stress and this increase could be prevented by 6-OHDA treatment. Vessel wall TF, platelet count, platelet aggregation, coagulation times (PT, aPTT), fibrinolytic system (t-PA and PAI-1) and tail bleeding time remained unaltered. Telemetric analysis revealed only minor hemodynamic changes throughout the stress protocol. Plasma catecholamines remained unaffected after restraint stress. Tumor necrosis factor alpha (TNF-α) plasma levels were unchanged and inhibition of TNF-α had no effect on stress-enhanced thrombosis. These results indicate that restraint stress enhances arterial thrombosis via the sympathetic nervous system. Blood-borne TF contributes, at least in part, to the observed effect whereas vessel wall TF, platelets, circulating coagulation factors, fibrinolysis and inflammation do not appear to play a role. These findings shed new light on the understanding of stress-induced cardiovascular events.

Human immunodeficiency virus infection of helper T cell clones. Early proliferative defects despite intact antigen-specific recognition and interleukin 4 secretion.

PubMed Central

Laurence, J; Friedman, S M; Chartash, E K; Crow, M K; Posnett, D N

1989-01-01

HIV selectively inhibited the proliferative response of clonal CD4+ T lymphocytes to alloantigen while other alloantigen-dependent responses were unperturbed. Specifically, impaired blastogenesis could be dissociated from alloantigen-specific induction of the B cell activation molecule CD23, IL-4 release, and inositol lipid hydrolysis. In addition, membrane expression of pertinent T cell receptor molecules, including CD2, CD3, and T cell antigen receptor (Ti), remained intact. Using two MHC class II-specific human CD4+ helper T cell clones, the proliferative defect was shown to be an early consequence of HIV infection, occurring within 4 d of viral inoculation and preceding increases in mature virion production. It was generalizable to three distinct methods of T cell activation, all independent of antigen-presenting cells: anti-CD3 mediated cross-linking of the CD3/Ti complex; anti-CD2 and phorbol 12-myristic 13-acetate (PMA); and anti-CD28 plus PMA. These abnormalities were not mitigated by addition of exogenous IL-2, even though expression of the IL-2 receptor (CD25) was unaltered. These studies define a selective blockade in T cell function early after HIV exposure that could serve as a model for certain in vivo manifestations of AIDS. PMID:2470786

Unaltered repopulation properties of mouse hematopoietic stem cells transduced with lentiviral vectors

PubMed Central

Gonzalez-Murillo, Africa; Lozano, M. Luz; Montini, Eugenio; Bueren, Juan A.

2008-01-01

Recent studies of retroviral-mediated gene transfer have shown that retroviral integrations themselves may trigger nonmalignant clonal expansion of hematopoietic stem cells (HSCs) in transplant recipients. These observations suggested that previous conclusions of HSC dynamics based on gamma-retroviral gene marking should be confirmed with improved vectors having a more limited capacity to transactivate endogenous genes. Because of the low trans-activation activity of self-inactivating lentiviral vectors (LVs), we have investigated whether the LV marking of mouse HSCs induces a competitive repopulation advantage in recipients of serially transplants. As deduced from analyses conducted in primary and secondary recipients, we concluded that lentivirally transduced HSCs have no competitive repopulation advantages over untransduced HSCs. By linear amplification-mediated polymerase chain reaction (LAM-PCR) analysis, we characterized LV-targeted genes in HSC clones that engrafted up to quaternary recipients. Although 9 clones harbored integrations close to defined retroviral insertion sites, none was characterized as a common integration site, and none was present in HSC clones repopulating quaternary recipients. Taken together, our results show unaltered repopulation properties of HSCs transduced with LVs, and confirm early studies suggesting the natural capacity of a few HSC clones to generate a monoclonal or oligoclonal hematopoiesis in transplant recipients. PMID:18684860

Hot-spring sinter deposits in the Alvord-Pueblo Valley, Harney County, Oregon

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

Cummings, M.L.; St. John, A.M.

1993-04-01

Silica sinter deposits occur at Borax Lake, Alvord Hot Springs, and Mickey Springs in the Alvord-Pueblo Valley. Although the sinter deposits occur in areas of active hot springs, sinter is not being deposited. Hot springs are localized along faults that have been active since the Pleistocene. The sinter deposits formed after the drying of glacial Lake Alvord, but before and during extensive wind deflation of glacial-lacustrine sediments. At Mickey Springs, sinter rests directly on unaltered, unconsolidated lithic-rich sand. At Borax Lake, sinter overlies unaltered diatomite, but some armoring, presumably by silica, of the 30 m vent has developed. Field relationsmore » suggest rapid dumping of silica from solution without alteration of the country rock at the vent. Discharge of thermal fluids and cold groundwater along the same structure may have produced colloidal silica carried in a solution stripped of dissolved silica. Sinter is composed of opal-a, traces of detrital feldspar and quartz, and evaporation-related boracite. The concentration of Sb is similar among the three sinter deposits (20 to 70 ppm); however, As, Cs, and Br are highest at Borax Lake (5 to 560 ppm; 26 to 118 ppm; 5 to 1,040 ppm) while Hg is highest at Mickey Springs (1.0 to 5.2 ppm).« less

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

Allison, N.; Finch, A.A.; Tudhope, A.W.

The Sr/Ca of coral skeletons demonstrates potential as an indicator of sea surface temperatures (SSTs). However, the glacial-interglacial SST ranges predicted from Sr/Ca of fossil corals are usually higher than from other marine proxies. We observed infilling of secondary aragonite, characterized by high Sr/Ca ratios, along intraskeletal pores of a fossil coral from Papua New Guinea that grew during the penultimate deglaciation (130 {+-} 2 ka). Selective microanalysis of unaltered areas of the fossil coral indicates that SSTs at {approx}130 ka were {le} 1 C cooler than at present in contrast with bulk measurements (combining infilled and unaltered areas) whichmore » indicate a difference of 6-7 C. The analysis of unaltered areas of fossil skeletons by microprobe techniques may offer a route to more accurate reconstruction of past SSTs.« less

Clay facial masks: physicochemical stability at different storage temperatures.

PubMed

Zague, Vivian; de Almeida Silva, Diego; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles

2007-01-01

Clay facial masks--formulations that contain a high percentage of solids dispersed in a liquid vehicle--have become of special interest due to specific properties presented by clays, such as particle size, cooling index, high adsorption capacity, and plasticity. Although most of the physicochemical properties of clay dispersions have been studied, specific aspects concerning the physicochemical stability of clay mask products remain unclear. This work aimed at investigating the accelerated physicochemical stability of clay mask formulations stored at different temperatures. Formulations were subjected to centrifuge testing and to thermal treatment for 15 days, during which temperature was varied from -5.0 degrees to 45.0 degrees C. The apparent viscosity and visual aspect (homogeneity) of all formulations were affected by temperature variation, whereas color, odor, and pH value remained unaltered. These results, besides the estimation of physicochemical stability under aging, can be useful in determining the best storage conditions for clay-based formulations.

An Ecoregion-Based Approach to Protecting Half the Terrestrial Realm.

PubMed

Dinerstein, Eric; Olson, David; Joshi, Anup; Vynne, Carly; Burgess, Neil D; Wikramanayake, Eric; Hahn, Nathan; Palminteri, Suzanne; Hedao, Prashant; Noss, Reed; Hansen, Matt; Locke, Harvey; Ellis, Erle C; Jones, Benjamin; Barber, Charles Victor; Hayes, Randy; Kormos, Cyril; Martin, Vance; Crist, Eileen; Sechrest, Wes; Price, Lori; Baillie, Jonathan E M; Weeden, Don; Suckling, Kierán; Davis, Crystal; Sizer, Nigel; Moore, Rebecca; Thau, David; Birch, Tanya; Potapov, Peter; Turubanova, Svetlana; Tyukavina, Alexandra; de Souza, Nadia; Pintea, Lilian; Brito, José C; Llewellyn, Othman A; Miller, Anthony G; Patzelt, Annette; Ghazanfar, Shahina A; Timberlake, Jonathan; Klöser, Heinz; Shennan-Farpón, Yara; Kindt, Roeland; Lillesø, Jens-Peter Barnekow; van Breugel, Paulo; Graudal, Lars; Voge, Maianna; Al-Shammari, Khalaf F; Saleem, Muhammad

2017-06-01

We assess progress toward the protection of 50% of the terrestrial biosphere to address the species-extinction crisis and conserve a global ecological heritage for future generations. Using a map of Earth's 846 terrestrial ecoregions, we show that 98 ecoregions (12%) exceed Half Protected; 313 ecoregions (37%) fall short of Half Protected but have sufficient unaltered habitat remaining to reach the target; and 207 ecoregions (24%) are in peril, where an average of only 4% of natural habitat remains. We propose a Global Deal for Nature-a companion to the Paris Climate Deal-to promote increased habitat protection and restoration, national- and ecoregion-scale conservation strategies, and the empowerment of indigenous peoples to protect their sovereign lands. The goal of such an accord would be to protect half the terrestrial realm by 2050 to halt the extinction crisis while sustaining human livelihoods.

An Ecoregion-Based Approach to Protecting Half the Terrestrial Realm

PubMed Central

Olson, David; Joshi, Anup; Burgess, Neil D.; Wikramanayake, Eric; Hahn, Nathan; Palminteri, Suzanne; Hedao, Prashant; Noss, Reed; Hansen, Matt; Locke, Harvey; Ellis, Erle C; Jones, Benjamin; Barber, Charles Victor; Hayes, Randy; Kormos, Cyril; Martin, Vance; Crist, Eileen; Sechrest, Wes; Price, Lori; Baillie, Jonathan E. M.; Weeden, Don; Suckling, Kierán; Davis, Crystal; Sizer, Nigel; Moore, Rebecca; Thau, David; Birch, Tanya; Potapov, Peter; Turubanova, Svetlana; Tyukavina, Alexandra; de Souza, Nadia; Pintea, Lilian; Brito, José C.; Llewellyn, Othman A.; Miller, Anthony G.; Patzelt, Annette; Ghazanfar, Shahina A.; Timberlake, Jonathan; Klöser, Heinz; Shennan-Farpón, Yara; Kindt, Roeland; Lillesø, Jens-Peter Barnekow; van Breugel, Paulo; Graudal, Lars; Voge, Maianna; Al-Shammari, Khalaf F.; Saleem, Muhammad

2017-01-01

Abstract We assess progress toward the protection of 50% of the terrestrial biosphere to address the species-extinction crisis and conserve a global ecological heritage for future generations. Using a map of Earth's 846 terrestrial ecoregions, we show that 98 ecoregions (12%) exceed Half Protected; 313 ecoregions (37%) fall short of Half Protected but have sufficient unaltered habitat remaining to reach the target; and 207 ecoregions (24%) are in peril, where an average of only 4% of natural habitat remains. We propose a Global Deal for Nature—a companion to the Paris Climate Deal—to promote increased habitat protection and restoration, national- and ecoregion-scale conservation strategies, and the empowerment of indigenous peoples to protect their sovereign lands. The goal of such an accord would be to protect half the terrestrial realm by 2050 to halt the extinction crisis while sustaining human livelihoods. PMID:28608869

An exploratory study into the putative prebiotic activity of fructans isolated from Agave angustifolia and the associated anticancer activity.

PubMed

Allsopp, Philip; Possemiers, Sam; Campbell, David; Oyarzábal, Iván Saldaña; Gill, Chris; Rowland, Ian

2013-08-01

Linear inulin-type fructan (ITF) prebiotics have a putative role in the prevention of colorectal cancer, whereas relatively little is known about branched fructans. This study aims to investigate the fermentation properties and potential prebiotic activity of branched fructans derived from Agave angustifolia Haw, using the Simulator of Human Intestinal Microbial Ecosystem (SHIME) model. The proximal, transverse and distal vessels were used to investigate fructan fermentation throughout the colon and to assess the alterations of the microbial composition and fermentation metabolites (short chain fatty acids and ammonia). The influence on bioactivity of the fermentation supernatant was assessed by MTT, Comet and transepithelial electrical resistance (TER), respectively. Addition of Agave fructan to the SHIME model significantly increased (P < 0.05), bifidobacteria populations (proximal and transverse), SCFA concentrations (proximal, transverse and distal) and decreased ammonia concentrations in the distal vessel. Furthermore, the fermentation supernatant significantly (P < 0.05) increased the TER of a Caco-2 cell monolayer (%) and decreased fluorescein-based paracellular flux, suggesting enhanced barrier function and reduced epithelial barrier permeability (proximal and distal vessel). While cytotoxicity and genotoxicity remained unaltered in response to the presence of Agave fructans. To conclude, branched Agave fructans show indications of prebiotic activity, particularly in relation to colon health by exerting a positive influence on gut barrier function, an important aspect of colon carcinogenesis. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Pathological histone acetylation in Parkinson's disease: Neuroprotection and inhibition of microglial activation through SIRT 2 inhibition.

PubMed

Harrison, Ian F; Smith, Andrew D; Dexter, David T

2018-02-14

Parkinson's disease (PD) is associated with degeneration of nigrostriatal neurons due to intracytoplasmic inclusions composed predominantly of a synaptic protein called α-synuclein. Accumulations of α-synuclein are thought to 'mask' acetylation sites on histone proteins, inhibiting the action of histone acetyltransferase (HAT) enzymes in their equilibrium with histone deacetylases (HDACs), thus deregulating the dynamic control of gene transcription. It is therefore hypothesised that the misbalance in the actions of HATs/HDACs in neurodegeneration can be rectified with the use of HDAC inhibitors, limiting the deregulation of transcription and aiding neuronal homeostasis and neuroprotection in disorders such as PD. Here we quantify histone acetylation in the Substantia Nigra pars compacta (SNpc) in the brains of control, early and late stage PD cases to determine if histone acetylation is a function of disease progression. PD development is associated with Braak-dependent increases in histone acetylation. Concurrently, we show that as expected disease progression is associated with reduced markers of dopaminergic neurons and increased markers of activated microglia. We go on to demonstrate that in vitro, degenerating dopaminergic neurons exhibit histone hypoacetylation whereas activated microglia exhibit histone hyperacetylation. This suggests that the disease-dependent increase in histone acetylation observed in human PD cases is likely a combination of the contributions of both degenerating dopaminergic neurons and infiltrating activated microglia. The HDAC SIRT 2 has become increasingly implicated as a novel target for mediation of neuroprotection in PD: the neuronal and microglial specific effects of its inhibition however remain unclear. We demonstrate that SIRT 2 expression in the SNpc of PD brains remains relatively unchanged from controls and that SIRT 2 inhibition, via AGK2 treatment of neuronal and microglial cultures, results in neuroprotection of dopaminergic neurons and reduced activation of microglial cells. Taken together, here we demonstrate that histone acetylation is disease-dependently altered in PD, likely due the effects of dopaminergic neurodegeneration and microglial infiltration; yet SIRT 2 remains relatively unaltered with disease. Given the stable nature of SIRT 2 expression with disease and the effects of SIRT 2 inhibitor treatment on degenerating dopaminergic neurons and activated microglia detected in vitro, SIRT 2 inhibitors warrant further investigation as potential therapeutics for the treatment of the PD. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Discovery of gemfibrozil analogues that activate PPARα and enhance the expression of gene CPT1A involved in fatty acids catabolism.

PubMed

De Filippis, Barbara; Giancristofaro, Antonella; Ammazzalorso, Alessandra; D'Angelo, Alessandra; Fantacuzzi, Marialuigia; Giampietro, Letizia; Maccallini, Cristina; Petruzzelli, Michele; Amoroso, Rosa

2011-10-01

A new series of gemfibrozil analogues conjugated with α-asarone, trans-stilbene, chalcone, and their bioisosteric modifications were synthesized and evaluated to develop PPARα agonists. In this attempt, we have removed the methyls on the phenyl ring of gemfibrozil and introduced the above scaffolds in para position synthesizing two series of derivatives, keeping the dimethylpentanoic skeleton of gemfibrozil unaltered or demethylated. Four compounds exhibited good activation of the PPARα receptor and were also screened for their activity on PPARα-regulated gene CPT1A. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Continuous exposure to a novel stressor based on water aversion induces abnormal circadian locomotor rhythms and sleep-wake cycles in mice.

PubMed

Miyazaki, Koyomi; Itoh, Nanako; Ohyama, Sumika; Kadota, Koji; Oishi, Katsutaka

2013-01-01

Psychological stressors prominently affect diurnal rhythms, including locomotor activity, sleep, blood pressure, and body temperature, in humans. Here, we found that a novel continuous stress imposed by the perpetual avoidance of water on a wheel (PAWW) affected several physiological diurnal rhythms in mice. One week of PAWW stress decayed robust circadian locomotor rhythmicity, while locomotor activity was evident even during the light period when the mice are normally asleep. Daytime activity was significantly upregulated, whereas nighttime activity was downregulated, resulting in a low amplitude of activity. Total daily activity gradually decreased with increasing exposure to PAWW stress. The mice could be exposed to PAWW stress for over 3 weeks without adaptation. Furthermore, continuous PAWW stress enhanced food intake, but decreased body weight and plasma leptin levels, indicating that sleep loss and PAWW stress altered the energy balance in these mice. The diurnal rhythm of corticosterone levels was not severely affected. The body temperature rhythm was diurnal in the stressed mice, but significantly dysregulated during the dark period. Plasma catecholamines were elevated in the stressed mice. Continuous PAWW stress reduced the duration of daytime sleep, especially during the first half of the light period, and increased nighttime sleepiness. Continuous PAWW stress also simultaneously obscured sleep/wake and locomotor activity rhythms compared with control mice. These sleep architecture phenotypes under stress are similar to those of patients with insomnia. The stressed mice could be entrained to the light/dark cycle, and when they were transferred to constant darkness, they exhibited a free-running circadian rhythm with a timing of activity onset predicted by the phase of their entrained rhythms. Circadian gene expression in the liver and muscle was unaltered, indicating that the peripheral clocks in these tissues remained intact.

N-terminal acylation of somatostatin analog with long chain fatty acids enhances its stability and anti-proliferative activity in human breast adenocarcinoma cells.

PubMed

Dasgupta, Piyali; Singh, Anu; Mukherjee, Rama

2002-01-01

The anti-proliferative activity of the somatostatin analog RC-160 is limited by its short serum half life. To circumvent this limitation, fatty acids of chain lengths ranging from 4 to 18 were individually conjugated to the N-terminal residue of RC-160. The lipophilized derivatives of RC-160 were synthesized, purified and characterized. The anti-proliferative activity of lipophilized-RC-160 on the human breast carcinoma cell line MCF-7, was evaluated in vitro. The long chain lipopeptides like pamitoyl-RC-160 exhibited significantly higher anti-proliferative activity on MCF-7 cells (p<0.001), relative to RC-160. The affinity of RC-160 towards somatostatin receptors remained unaltered by pamitoylation. However, the observed increase in bioactivity was manifested within an optimum range of chain length of the lipoppetide. Increasing the peptide hydrophobicity beyond this range reduced the bioactivity of lipophilized-RC-160. Accordingly, stearoyl-RC-160, manifested lower anti-neoplastic activity and receptor affinity relative to pamitoyl-RC-160 and RC-160 itself. The signaling pathways underlying the antineoplastic activity of these lipopeptides were found to be similar to RC-160. Pamitoyl-RC-160 displayed enhanced inhibition of protein tyrosine kinase activity and intracellular cAMP levels in MCF-7 cells, relative to butanoyl-RC-160 or RC-160 itself. Pamitoyl-RC-160 also displayed greater resistance towards trypsin and serum degradation than RC-160. Lipophilization of RC-160 with long chain fatty acids like pamitic acid improves its stability and anti-proliferative activity, thereby improving the scope of enhancing its therapeutic index. However, the optimization of peptide hydrophobicity seems to be a crucial factor governing the efficacy of bioactive lipopeptides.

Compositional variation of glauconites in Upper Cretaceous-Paleogene sedimentary iron-ore deposits in South-eastern Western Siberia

NASA Astrophysics Data System (ADS)

Rudmin, Maxim; Banerjee, Santanu; Mazurov, Aleksey

2017-06-01

Glauconite occurs either as unaltered greenish or as altered brownish variety in Upper Cretaceous-Palaeocene sediments in the southeastern corner of Western Siberia. Studied section within the Bakchar iron-ore deposit includes Ipatovo, Slavgorod, Gan'kino and Lyulinvor formations, which are represented by sandstones, siltstones, claystones and oolitic ironstones of coastal-marine facies. The origin of unaltered glauconite is explained by the ;verdissement theory;. Transgressions during Lower Coniacian, Santonian and Campanian favored the formation of unaltered glauconites in dysoxic to anoxic conditions. Subaerial exposure of glauconite resulted in leaching of potassium, oxidation of iron and formation of iron hydroxides in Upper Coniacian, Maastrichtian and Palaeocene. Glauconite ultimately converts to leptochlorite and hydrogoethite by this alteration. Abundant microscopic gold inclusions, besides sulphides, sulphates, oxides and silicates characterize this glauconite. Mineral inclusions include precious, rare metals and non-ferrous metals. The concentration of gold in glauconite may be as high as 42.9 ppb. Abundant inclusions of various compositions in glauconites indicate enrichment of marine sediments in precious and non-precious metals. While major element composition of glauconites is affected by subaerial exposure, the broadly similar micro-inclusions in both altered and unaltered varieties are possibly related to the comparatively immobile nature of REE and trace elements.

Na intercalation in Fe-MIL-100 for aqueous Na-ion batteries

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

Chavez, James S.; Harrison, Katharine L.; Sava Gallis, Dorina F.

Here we report for the first time the feasibility of using metal–organic frameworks (MOFs) as electrodes for aqueous Na-ion batteries. We show that Fe-MIL-100, a known redox-active MOF, is electrochemically active in a Na aqueous electrolyte, under various compositions. Emphasis was placed on investigating the electrode–electrolyte interface, with a focus on identifying the relationship between additives in the composition of the working electrode, particle size and overall performance. We found that the energy storage capacity is primarily dependent on the binder additive in the composite; the best activity for this MOF is obtained with Nafion as a binder, owing tomore » its hydrophilic and ion conducting nature. Kynar-bound electrodes are clearly less effective, due to their hydrophobic character, which impedes wetting of the electrode. The binder-free systems show the poorest electrochemical activity. There is little difference in the overall performance as function of particle size (micro vs. nano), implying the storage capacities in this study are not limited by ionic and/or electronic conductivity. Excellent reversibility and high coulombic efficiency are achieved at higher potential ranges, observed after cycle 20. That is despite progressive capacity decay observed in the initial cycles. Importantly, structural analyses of cycled working electrodes confirm that the long range crystallinity remains mainly unaltered with cycling. These findings suggest that limited reversibility of the intercalated Na ions in the lower potential range, together with the gradual lack of available active sites in subsequent cycles is responsible for the rapid decay in capacity retention.« less

Na intercalation in Fe-MIL-100 for aqueous Na-ion batteries

DOE PAGES

Chavez, James S.; Harrison, Katharine L.; Sava Gallis, Dorina F.

2017-05-04

Here we report for the first time the feasibility of using metal–organic frameworks (MOFs) as electrodes for aqueous Na-ion batteries. We show that Fe-MIL-100, a known redox-active MOF, is electrochemically active in a Na aqueous electrolyte, under various compositions. Emphasis was placed on investigating the electrode–electrolyte interface, with a focus on identifying the relationship between additives in the composition of the working electrode, particle size and overall performance. We found that the energy storage capacity is primarily dependent on the binder additive in the composite; the best activity for this MOF is obtained with Nafion as a binder, owing tomore » its hydrophilic and ion conducting nature. Kynar-bound electrodes are clearly less effective, due to their hydrophobic character, which impedes wetting of the electrode. The binder-free systems show the poorest electrochemical activity. There is little difference in the overall performance as function of particle size (micro vs. nano), implying the storage capacities in this study are not limited by ionic and/or electronic conductivity. Excellent reversibility and high coulombic efficiency are achieved at higher potential ranges, observed after cycle 20. That is despite progressive capacity decay observed in the initial cycles. Importantly, structural analyses of cycled working electrodes confirm that the long range crystallinity remains mainly unaltered with cycling. These findings suggest that limited reversibility of the intercalated Na ions in the lower potential range, together with the gradual lack of available active sites in subsequent cycles is responsible for the rapid decay in capacity retention.« less

Gastroprotective effect of Piper betle Linn. leaves grown in Sri Lanka

PubMed Central

Arawwawala, L. D. A. M.; Arambewela, L. S. R.; Ratnasooriya, W. D.

2014-01-01

Background: Piper betle Linn. (Piperaceae) is used as a remedy for gastric ulcers in traditional medicinal systems in Sri Lanka. However, the gastroprotective activity has never been proven scientifically using betel leaves grown in Sri Lanka. Objective: To evaluate the gastroprotective activity of hot aqueous extract (HAE) and cold ethanolic extract (CEE) of P. betle in rats as the experimental model. Materials and Methods: Three doses (200, 300, and 500 mg/kg/bw) of both extracts were evaluated for the gastroprotective activity against ethanol induced gastric ulcers in rats. The parameters evaluated were (a) effects of HAE on mucus content adhering to the wall of the gastric mucosa, (b) acidity (total and free), (c) volume and (d) pH of the gastric juice. Results: Oral administration of HAE and CEE provided marked dose dependent (HAE: r2 = 0.97; CEE: r2 = 0.96) and significant (P ≤ 0.05) protection against gastric damage caused by absolute ethanol. The gastroprotective effect of CEE was comparable with that of HAE. Further, gastroprotective activity of the highest dose of both extracts were significantly greater (P ≤ 0.05) than that of misoprostol, the reference drug. The HAE significantly (P ≤ 0.05) increased the mucus content adhering to the wall of the gastric mucosa and inhibited the volume of gastric acid. However, acidity (total and free) and pH of the gastric juice remained unaltered. Conclusion: It is concluded that both HAE and CEE of P. betle leaves have a strong gastroprotective activity. PMID:24812474

Activation of Extracellular Signal-Regulated Kinases (ERK 1/2) in the Locus Coeruleus Contributes to Pain-Related Anxiety in Arthritic Male Rats

PubMed Central

Borges, Gisela; Miguelez, Cristina; Neto, Fani; Mico, Juan Antonio; Ugedo, Luisa

2017-01-01

Abstract Background: There is increasing evidence suggesting that the Locus Coeruleus plays a role in pain-related anxiety. Indeed, we previously found that prolonged arthritis produces anxiety-like behavior in rats, along with enhanced expression of phosphorylated extracellular signal-regulated kinase 1/2 (a marker of plasticity) in the Locus Coeruleus. However, it is unknown how this effect correlates with the electrophysiological activity of Locus Coeruleus neurons or pain-related anxiety. Methods: Using the complete Freund’s adjuvant model of monoarthritis in male Sprague-Dawley rats, we studied the behavioral attributes of pain and anxiety as well as Locus Coeruleus electrophysiology in vivo 1 (MA1W) and 4 weeks (MA4W) after disease induction. Results: The manifestation of anxiety in MA4W was accompanied by dampened tonic Locus Coeruleus activity, which was coupled to an exacerbated evoked Locus Coeruleus response to noxious stimulation of the inflamed and healthy paw. When a mitogen-activating extracellular kinase inhibitor was administered to the contralateral Locus Coeruleus of MA4W, the phosphorylated extracellular signal-regulated kinase 1/2 levels in the Locus Coeruleus were restored and the exaggerated evoked response was blocked, reversing the anxiogenic-like behavior while pain hypersensitivity remained unaltered. Conclusion: As phosphorylated extracellular signal-regulated kinase 1/2 blockade in the Locus Coeruleus relieved anxiety and counteracted altered LC function, we propose that phosphorylated extracellular signal-regulated kinase 1/2 activation in the Locus Coeruleus plays a crucial role in pain-related anxiety. PMID:28158734

Activation of Extracellular Signal-Regulated Kinases (ERK 1/2) in the Locus Coeruleus Contributes to Pain-Related Anxiety in Arthritic Male Rats.

PubMed

Borges, Gisela; Miguelez, Cristina; Neto, Fani; Mico, Juan Antonio; Ugedo, Luisa; Berrocoso, Esther

2017-06-01

There is increasing evidence suggesting that the Locus Coeruleus plays a role in pain-related anxiety. Indeed, we previously found that prolonged arthritis produces anxiety-like behavior in rats, along with enhanced expression of phosphorylated extracellular signal-regulated kinase 1/2 (a marker of plasticity) in the Locus Coeruleus. However, it is unknown how this effect correlates with the electrophysiological activity of Locus Coeruleus neurons or pain-related anxiety. Using the complete Freund's adjuvant model of monoarthritis in male Sprague-Dawley rats, we studied the behavioral attributes of pain and anxiety as well as Locus Coeruleus electrophysiology in vivo 1 (MA1W) and 4 weeks (MA4W) after disease induction. The manifestation of anxiety in MA4W was accompanied by dampened tonic Locus Coeruleus activity, which was coupled to an exacerbated evoked Locus Coeruleus response to noxious stimulation of the inflamed and healthy paw. When a mitogen-activating extracellular kinase inhibitor was administered to the contralateral Locus Coeruleus of MA4W, the phosphorylated extracellular signal-regulated kinase 1/2 levels in the Locus Coeruleus were restored and the exaggerated evoked response was blocked, reversing the anxiogenic-like behavior while pain hypersensitivity remained unaltered. As phosphorylated extracellular signal-regulated kinase 1/2 blockade in the Locus Coeruleus relieved anxiety and counteracted altered LC function, we propose that phosphorylated extracellular signal-regulated kinase 1/2 activation in the Locus Coeruleus plays a crucial role in pain-related anxiety. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Acute effect on ambulatory blood pressure from aerobic exercise: a randomised cross-over study among female cleaners.

PubMed

Lund Rasmussen, Charlotte; Nielsen, Line; Linander Henriksen, Marie; Søgaard, Karen; Krustrup, Peter; Holtermann, Andreas; Korshøj, Mette

2018-02-01

High occupational physical activity (OPA) is shown to increase the risk for elevated blood pressure, cardiovascular diseases and mortality. Conversely, aerobic exercise acutely lowers the blood pressure up to 25 h post exercise. However, it is unknown if this beneficial effect also apply for workers exposed to high levels of OPA. Cleaners constitute a relevant occupational group for this investigation because of a high prevalence of OPA and cardiovascular disease. Accordingly, the objective was to investigate the acute effects on ambulatory blood pressure from a single aerobic exercise session among female cleaners. Twenty-two female cleaners were randomised to a cross-over study with a reference and an aerobic exercise session. Differences in 24-h, work hours, leisure time, and sleep ambulatory blood pressure (ABP) were evaluated using repeated measure 2 × 2 mixed-models. After the aerobic exercise session, the 24-h systolic ambulatory blood pressure was significantly lowered by 2.4 mmHg (p < 0.01) compared to the reference session. The 24-h diastolic ABP was unaltered. During work hours, a lowered systolic ABP of 2.2 mmHg (p = 0.02) and a higher diastolic ABP of 1.5 mmHg (p = 0.03) were found after the aerobic exercise session. During leisure time, the systolic ABP was lowered by 1.7 mmHg (p = 0.04) and the diastolic ABP was unaltered. During sleep, the systolic and diastolic ABP was unaltered. A single aerobic exercise session lowered 24-h systolic ABP of 2.4 mmHg. Thus, an aerobic exercise session seems to be beneficial for lowering the risk of hypertension among cleaners.

Ring discharge on the backsurface of a composite skin with ohmic anisotropy in response to frontal high current injection

NASA Astrophysics Data System (ADS)

Lee, T. S.; Robb, J. D.

The ring discharge hazard to a carbon-reinforced-composites fuel tank skin under lightning strike conditions is investigated. A model of anisotropy in electric conductivity is adopted whereby longitudinal conductivity and transverse conductivity are considered separately. It is concluded that the current flow pattern contains a stagnation-dominated near-field region and a geometry-dominated far-field decaying region. While this pattern is unaltered by anisotropy in conductivity, the accompanying nonliner electrical field pattern is greatly distorted. It is noted that conclusions applicable to the ignition hazard which were derived from the model of a uniform scalar conductivity for the skin still remain intact.

Insulin-like growth factor-I stimulates H{sub 4}II rat hepatoma cell proliferation: Dominant role of PI-3'K/Akt signaling

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

Alexia, Catherine; Fourmatgeat, Pascal; Delautier, Daniele

2006-04-15

Although hepatocytes are the primary source of endocrine IGF-I and -II in mammals, their autocrine/paracrine role in the dysregulation of proliferation and apoptosis during hepatocarcinogenesis and in hepatocarcinomas (HCC) remains to be elucidated. Indeed, IGF-II and type-I IGF receptors are overexpressed in HCC cells, and IGF-I is synthesized in adjacent non-tumoral liver tissue. In the present study, we have investigated the effects of type-I IGF receptor signaling on H{sub 4}II rat hepatoma cell proliferation, as estimated by {sup 3}H-thymidine incorporation into DNA. IGF-I stimulated the rate of DNA synthesis of serum-deprived H{sub 4}II cells, stimulation being maximal 3 h aftermore » the onset of IGF-I treatment and remaining elevated until at least 6 h. The IGF-I-induced increase in DNA replication was abolished by LY294002 and only partially inhibited by PD98059, suggesting that phosphoinositol-3' kinase (PI-3'K) and to a lesser extent MEK/Erk signaling were involved. Furthermore, the 3- to 19-fold activation of the Erks in the presence of LY294002 suggested a down-regulation of the MEK/Erk cascade by PI-3'K signaling. Finally, the effect of IGF-I on DNA replication was almost completely abolished in clones of H{sub 4}II cells expressing a dominant-negative form of Akt but was unaltered by rapamycin treatment of wild-type H{sub 4}II cells. Altogether, these data support the notion that the stimulation of H{sub 4}II rat hepatoma cell proliferation by IGF-I is especially dependent on Akt activation but independent on the Akt/mTOR signal0009i.« less

Modulation of elevated plus maze behavior after chronic exposure to the anabolic steroid 17alpha-methyltestosterone in adult mice.

PubMed

Rojas-Ortiz, Yoel Antonio; Rundle-González, Valerie; Rivera-Ramos, Isamar; Jorge, Juan Carlos

2006-01-01

Exposure to supraphysiological doses of androgens may disrupt affective components of behavior. In this study, behavior of adult C57Bl/6 male mice was studied after exposure to the anabolic androgenic steroid (AAS) 17alpha-methyltestosterone (17alpha-meT; 7.5 mg/kg) via a subcutaneous osmotic pump for 17 days. Controls received vehicle implants (0.9% NaCl + 30% cyclodextrine). On day 15, experimental animals were challenged with an ethanol (EtOH) injection (i.p.; 1 g/kg) while controls received saline injections. Five minutes after the injection, animals were tested in an automated elevated plus maze (EPM) or in automated activity chambers. In addition, injection-free animals were tested for ethanol consumption on day 16 after an overnight water deprivation period. Whereas chronic exposure to 17alpha-meT did not modulate open arm behavior, EtOH-exposed animals made more entries into the open arms than controls (P < 0.05). A significant reduction of risk assessment behaviors (rearing, flat approach behavior, and stretch attended posture) over the EPM was noted for EtOH-exposed animals whereas a reduction in stretch attended postures was observed among 17alpha-meT-exposed animals. Locomotor activity, and light-dark transitions in activity chambers remained unaltered. Exposure to AAS did not modulate EtOH consumption. Our data suggest that exposure to a supraphysiological dose of 17alpha-meT has minimal effects on exploratory-based anxiety.

Dopamine, Noradrenaline and Serotonin Receptor Densities in the Striatum of Hemiparkinsonian Rats following Botulinum Neurotoxin-A Injection.

PubMed

Mann, T; Zilles, K; Dikow, H; Hellfritsch, A; Cremer, M; Piel, M; Rösch, F; Hawlitschka, A; Schmitt, O; Wree, A

2018-03-15

Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D 1 , D 2 /D 3 , α 1 , α 2 , and 5HT 2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autoradiography. We found a moderate increase in D 1 receptor density 3 weeks post lesion that decreased during longer survival times, a significant increase of D 2 /D 3 receptor density, and 50% reduction in 5HT 2A receptor density. α 1 receptor density remained unaltered in hemi-PD and α 2 receptors demonstrated a slight right-left difference increasing with post lesion survival. In a second step, the possible role of receptors on the known reduction of apomorphine-induced rotations in hemi-PD rats by intrastriatally injected Botulinum neurotoxin-A (BoNT-A) was analyzed by measuring the receptor densities after BoNT-A injection. The application of this neurotoxin reduced D 2 /D 3 receptor density, whereas the other receptors mainly remained unaltered. Our results provide novel data for an understanding of the postlesional plasticity of dopaminergic, noradrenergic and serotonergic receptors in the hemi-PD rat model. The results further suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing the interhemispheric imbalance in D 2 /D 3 receptor density. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Functional Accumulation of Antenna Proteins in Chlorophyll b-Less Mutants of Chlamydomonas reinhardtii.

PubMed

Bujaldon, Sandrine; Kodama, Natsumi; Rappaport, Fabrice; Subramanyam, Rajagopal; de Vitry, Catherine; Takahashi, Yuichiro; Wollman, Francis-André

2017-01-09

The green alga Chlamydomonas reinhardtii contains several light-harvesting chlorophyll a/b complexes (LHC): four major LHCIIs, two minor LHCIIs, and nine LHCIs. We characterized three chlorophyll b-less mutants to assess the effect of chlorophyll b deficiency on the function, assembly, and stability of these chlorophyll a/b binding proteins. We identified point mutations in two mutants that inactivate the CAO gene responsible for chlorophyll a to chlorophyll b conversion. All LHCIIs accumulated to wild-type levels in a CAO mutant but their light-harvesting function for photosystem II was impaired. In contrast, most LHCIs accumulated to wild-type levels in the mutant and their light-harvesting capability for photosystem I remained unaltered. Unexpectedly, LHCI accumulation and the photosystem I functional antenna size increased in the mutant compared with in the wild type when grown in dim light. When the CAO mutation was placed in a yellow-in-the-dark background (yid-BF3), in which chlorophyll a synthesis remains limited in dim light, accumulation of the major LHCIIs and of most LHCIs was markedly reduced, indicating that sustained synthesis of chlorophyll a is required to preserve the proteolytic resistance of antenna proteins. Indeed, after crossing yid-BF3 with a mutant defective for the thylakoid FtsH protease activity, yid-BF3-ftsh1 restored wild-type levels of LHCI, which defines LHCI as a new substrate for the FtsH protease. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Roles of sedentary aging and lifelong physical activity in exchange of glutathione across exercising human skeletal muscle.

PubMed

Nyberg, Michael; Mortensen, Stefan P; Cabo, Helena; Gomez-Cabrera, Mari-Carmen; Viña, Jose; Hellsten, Ylva

2014-08-01

Reactive oxygen species (ROS) are important signaling molecules with regulatory functions, and in young and adult organisms, the formation of ROS is increased during skeletal muscle contractions. However, ROS can be deleterious to cells when not sufficiently counterbalanced by the antioxidant system. Aging is associated with accumulation of oxidative damage to lipids, DNA, and proteins. Given the pro-oxidant effect of skeletal muscle contractions, this effect of age could be a result of excessive ROS formation. We evaluated the effect of acute exercise on changes in blood redox state across the leg of young (23 ± 1 years) and older (66 ± 2 years) sedentary humans by measuring the whole blood concentration of the reduced (GSH) and oxidized (GSSG) forms of the antioxidant glutathione. To assess the role of physical activity, lifelong physically active older subjects (62 ± 2 years) were included. Exercise increased the venous concentration of GSSG in an intensity-dependent manner in young sedentary subjects, suggesting an exercise-induced increase in ROS formation. In contrast, venous GSSG levels remained unaltered during exercise in the older sedentary and active groups despite a higher skeletal muscle expression of the superoxide-generating enzyme NADPH oxidase. Arterial concentration of GSH and expression of antioxidant enzymes in skeletal muscle of older active subjects were increased. The potential impairment in exercise-induced ROS formation may be an important mechanism underlying skeletal muscle and vascular dysfunction with sedentary aging. Lifelong physical activity upregulates antioxidant systems, which may be one of the mechanisms underlying the lack of exercise-induced increase in GSSG. Copyright © 2014 Elsevier Inc. All rights reserved.

Activity and protein expression of the Na+/H+ exchanger is reduced in syncytiotrophoblast microvillous plasma membranes isolated from preterm intrauterine growth restriction pregnancies.

PubMed

Johansson, M; Glazier, J D; Sibley, C P; Jansson, T; Powell, T L

2002-12-01

Regulation of syncytiotrophoblast intracellular pH is critical to optimum enzymatic and transport functions of the placenta. Previous studies of Na(+)/H(+) exchanger (NHE) activity in the placenta from pregnancies complicated by intrauterine growth restriction (IUGR) have produced conflicting results. The possible role of altered placental pH regulation in the development of acidosis in some fetuses subjected to IUGR remains to be fully established. We investigated the activity and protein expression of the NHE in syncytiotrophoblast microvillous (MVM) plasma membranes isolated from preterm and term placentas obtained from uncomplicated and IUGR pregnancies. Western blotting showed that the expression of NHE isoforms 1, 2, and 3 was approximately 10-fold greater in MVM than in basal plasma membrane (BM). Immunohistochemistry localized NHE-1 and NHE-2 to MVM and BM and NHE-3 to the MVM, BM, and cytoplasm of the syncytiotrophoblast. NHE-1 expression in MVM from preterm IUGR placentas was reduced by 55%, compared with gestational age-matched controls (P < 0.05, n = 6 and n = 16, respectively), whereas NHE-1 expression was unaltered in term IUGR placentas (n = 8). The activity (amiloride-sensitive Na(+) uptake) of NHE in MVM from IUGR preterm placentas was reduced by 48% (P < 0.05, n = 6). In contrast, MVM NHE activity was unchanged in term IUGR (n = 7). Using Northern blotting, no difference could be demonstrated in NHE-1 mRNA expression between IUGR and control groups. The reduced activity and expression of NHE in MVM of preterm IUGR placentas may compromise placental function and may contribute to the development of fetal acidosis in preterm IUGR fetuses.

Dynamics of post-translationally modified histones during barley pollen embryogenesis in the presence or absence of the epi-drug trichostatin A.

PubMed

Pandey, Pooja; Daghma, Diaa S; Houben, Andreas; Kumlehn, Jochen; Melzer, Michael; Rutten, Twan

2017-06-01

Improving pollen embryogenesis. Despite the agro-economic importance of pollen embryogenesis, the mechanisms underlying this process are still poorly understood. We describe the dynamics of chromatin modifications (histones H3K4me2, H3K9ac, H3K9me2, and H3K27me3) and chromatin marks (RNA polymerase II CDC phospho-Ser5, and CENH3) during barley pollen embryogenesis. Immunolabeling results show that, in reaction to stress, immature pollen rapidly starts reorganizing several important chromatin modifications indicative of a change in cell fate. This new chromatin modification pattern was accomplished within 24 h from whereon it remained unaltered during subsequent mitotic activity. This indicates that cell fate transition, the central element of pollen embryogenesis, is completed early on during the induction process. Application of the histone deacetylase inhibitor trichostatin A stimulated pollen embryogenesis when used on pollen with a gametophytic style chromatin pattern. However, when this drug was administered to embryogenic pollen, the chromatin markers reversed toward a gametophytic profile, embryogenesis was halted and all pollen invariably died.

A Robust Open Framework Formed by Decavanadate Clusters and Copper(II) Complexes of Macrocyclic Polyamines: Permanent Microporosity and Catalytic Oxidation of Cycloalkanes.

PubMed

Martín-Caballero, Jagoba; San José Wéry, Ana; Reinoso, Santiago; Artetxe, Beñat; San Felices, Leire; El Bakkali, Bouchra; Trautwein, Guido; Alcañiz-Monge, Juan; Vilas, José Luis; Gutiérrez-Zorrilla, Juan M

2016-05-16

The first decavanadate-based microporous hybrid, namely, [Cu(cyclam)][{Cu(cyclam)}2(V10O28)]·10H2O (1, cyclam = 1,4,8,11-tetraazacyclotetradecane) was prepared by reaction of (VO3)(-) anions and {Cu(cyclam)}(2+) complexes in NaCl (aq) at pH 4.6-4.7 and characterized by elemental analyses, thermogravimetry, and X-ray diffraction (powder, single-crystal) techniques. Compound 1 exhibits a POMOF-like supramolecular open-framework built of covalent decavanadate/metalorganic layers with square-like voids, the stacking of which is aided by interlamellar cementing complexes and generates water-filled channels with approximate cross sections of 10.4 × 8.8 Å(2). The framework is robust enough to remain virtually unaltered upon thermal evacuation of all water molecules of hydration, as demonstrated through single-crystal X-ray diffraction studies on the anhydrous phase 1a. This permanent microporosity renders interesting functionality to 1, such as selective adsorption of CO2 over N2 and remarkable activity as heterogeneous catalyst toward the H2O2-based oxidation of the highly-stable, tricyclic alkane adamantane.

Leishmania donovani Resistance to Miltefosine Involves a Defective Inward Translocation of the Drug

PubMed Central

Pérez-Victoria, F. Javier; Castanys, Santiago; Gamarro, Francisco

2003-01-01

Miltefosine (hexadecylphosphocholine [HePC]) is the first drug approved for the oral treatment of visceral leishmaniasis. As part of a study on the mechanisms of action of this drug and on the rates of resistance to this drug, we have been working in vitro with an Leishmania donovani line that was previously shown to be 15-fold more resistant to HePC. We have studied the accumulation of [14C]HePC by L. donovani promastigotes and have found a drastic reduction (>95%) in the ability of the resistant line to internalize the drug. Binding of HePC to the plasma membrane and drug efflux from preloaded cells were similar in both drug-sensitive and -resistant lines, and no [14C]HePC metabolism was evident in either line. Resistant parasites were also unable to take up other short-chain phospholipid analogs, independently of their polar head group, even though endocytosis remained unaltered. Finally, HePC uptake was temperature and energy dependent and sensitive to the thiol-reactive agent N-ethylmaleimide. We propose that inward translocation of a short-chain phospholipid across the plasma membrane may exist in Leishmania promastigotes and that such activity is defective in the resistant line. PMID:12878496

Stellate nonhereditary idiopathic foveomacular retinoschisis concomitant to exudative maculopathies

PubMed Central

Casalino, G; Upendran, M; Bandello, F; Chakravarthy, U

2016-01-01

Purpose To report the clinical course of patients presenting with stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) concomitant with exudative maculopathies. Methods Retrospective case series. Multimodal imaging findings, including spectral-domain optical coherence tomography (SD-OCT) were reviewed. Genetic testing for the RS1 gene was performed in one patient. Results We identified two female patients who fit the definition of SNIFR and presented with concomitant neovascular age-related macular degeneration (n-AMD). In both the patients, SD-OCT showed exudative macular features and splitting (bilateral in patient 1, unilateral in patient 2) of the outer plexiform layer (OPL) in the macula with no other evidence of hereditary or an acquired predisposing condition. Genetic testing excluded mutation of RS1 gene in patient 1. The fundi of both the patients showed characteristic signs of active choroidal neovascularization (CNV) and following anti-VEGF treatment, visual acuity improved and CNV-related exudative changes resolved. However, the split along the OPL remained unaltered. Conclusions SNIFR may be associated with n-AMD. It is important to recognise the presence of retinoschisis when there is other exudative pathology as the former may be misinterpreted as intraretinal fluid, prompting unnecessary treatment. PMID:26915743

Recent temporal trends in sleep duration, domain-specific sedentary behaviour and physical activity. A survey among 25-79-year-old Danish adults.

PubMed

Aadahl, Mette; Andreasen, Anne Helms; Hammer-Helmich, Lene; Buhelt, Lone; Jørgensen, Torben; Glümer, Charlotte

2013-11-01

Prevalence of sedentary behaviour is high in many countries, but little is known about temporal trends in sitting time. To examine temporal changes in sleep and domain-specific sedentary behaviour and moderate to vigorous leisure time physical activity (MVPA). Two cross-sectional population-based surveys of 25-79-year-old inhabitants were conducted in The Capital Region of Denmark in 2007 (N = 69.800, response rate 52.3%) and 2010 (N = 77.517, response rate 54.8%). Information on sedentary behaviour and physical activity was obtained from self-report questionnaire and sociodemographic information from central registers. Data were weighted for survey design and for non-response and were analysed by multiple regression analyses. In 2007, the entire survey population reported a mean daily sleeping duration of 7.4 hours, leisure time sitting of 3.4 hours per day, occupational sitting of 4.4 hours per day, MVPA of 0.87 hours per day and a total 24-hour energy expenditure of 40.12 METs per day. In 2010, duration of sleep was unaltered (p = 0.1), sedentary leisure time and sedentary work time had increased by 12.6 minutes (p < 0.0001) and 13.2 minutes (p < 0.0001) per day, respectively. Time spent on MVPA had increased by 2.9 minutes per day (p < 0.0001). The 24-hour energy expenditure had decreased by 0.41 METs (p < 0.0001). Adult Danish men and women spend an increased amount of time sitting down at work and during leisure time, but also on leisure time MVPA. As duration of sleep is unaltered findings suggest that low intensity physical activity may be displaced in everyday life.

Peripheral cannabinoid receptor, CB2, regulates bone mass

PubMed Central

Ofek, Orr; Karsak, Meliha; Leclerc, Nathalie; Fogel, Meirav; Frenkel, Baruch; Wright, Karen; Tam, Joseph; Attar-Namdar, Malka; Kram, Vardit; Shohami, Esther; Mechoulam, Raphael; Zimmer, Andreas; Bab, Itai

2006-01-01

The endogenous cannabinoids bind to and activate two G protein-coupled receptors, the predominantly central cannabinoid receptor type 1 (CB1) and peripheral cannabinoid receptor type 2 (CB2). Whereas CB1 mediates the cannabinoid psychotropic, analgesic, and orectic effects, CB2 has been implicated recently in the regulation of liver fibrosis and atherosclerosis. Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered. These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling. The CB2–/– phenotype is also characterized by increased activity of trabecular osteoblasts (bone-forming cells), increased osteoclast (the bone-resorbing cell) number, and a markedly decreased number of diaphyseal osteoblast precursors. CB2 is expressed in osteoblasts, osteocytes, and osteoclasts. A CB2-specific agonist that does not have any psychotropic effects enhances endocortical osteoblast number and activity and restrains trabecular osteoclastogenesis, apparently by inhibiting proliferation of osteoclast precursors and receptor activator of NF-κB ligand expression in bone marrow-derived osteoblasts/stromal cells. The same agonist attenuates ovariectomy-induced bone loss and markedly stimulates cortical thickness through the respective suppression of osteoclast number and stimulation of endocortical bone formation. These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries. PMID:16407142

Dependence on nuclear factor of activated T-cells (NFAT) levels discriminates conventional T cells from Foxp3+ regulatory T cells

PubMed Central

Vaeth, Martin; Schliesser, Ulrike; Müller, Gerd; Reissig, Sonja; Satoh, Kazuki; Tuettenberg, Andrea; Jonuleit, Helmut; Waisman, Ari; Müller, Martin R.; Serfling, Edgar; Sawitzki, Birgit S.; Berberich-Siebelt, Friederike

2012-01-01

Several lines of evidence suggest nuclear factor of activated T-cells (NFAT) to control regulatory T cells: thymus-derived naturally occurring regulatory T cells (nTreg) depend on calcium signals, the Foxp3 gene harbors several NFAT binding sites, and the Foxp3 (Fork head box P3) protein interacts with NFAT. Therefore, we investigated the impact of NFAT on Foxp3 expression. Indeed, the generation of peripherally induced Treg (iTreg) by TGF-β was highly dependent on NFAT expression because the ability of CD4+ T cells to differentiate into iTreg diminished markedly with the number of NFAT family members missing. It can be concluded that the expression of Foxp3 in TGF-β–induced iTreg depends on the threshold value of NFAT rather than on an individual member present. This is specific for iTreg development, because frequency of nTreg remained unaltered in mice lacking NFAT1, NFAT2, or NFAT4 alone or in combination. Different from expectation, however, the function of both nTreg and iTreg was independent on robust NFAT levels, reflected by less nuclear NFAT in nTreg and iTreg. Accordingly, absence of one or two NFAT members did not alter suppressor activity in vitro or during colitis and transplantation in vivo. This scenario emphasizes an inhibition of high NFAT activity as treatment for autoimmune diseases and in transplantation, selectively targeting the proinflammatory conventional T cells, while keeping Treg functional. PMID:22991461

DNA damage and transcriptional changes induced by tributyltin (TBT) after short in vivo exposures of Chironomus riparius (Diptera) larvae.

PubMed

Morales, Mónica; Martínez-Paz, Pedro; Ozáez, Irene; Martínez-Guitarte, José Luis; Morcillo, Gloria

2013-08-01

Tributyltin (TBT) is a widespread environmental contaminant in aquatic systems whose adverse effects in development and reproduction are related to its well-known endocrine-disrupting activity. In this work, the early molecular effects of TBT in Chironomus riparius (Diptera) were evaluated by analyzing its DNA damaging potential and the transcriptional response of different endocrine-related genes. Twenty-four-hour in vivo exposures of the aquatic larvae, at environmentally relevant doses of TBT, revealed genotoxic activity as shown by significant increases in DNA strand breaks quantified with the comet assay. TBT was also able to induce significant increases in transcripts from the ecdysone receptor gene (EcR), the ultraspiracle gene (usp) (insect ortholog of the retinoid X receptor), the estrogen-related receptor (ERR) gene and the E74 early ecdysone-inducible gene, as measured by real-time RT-PCR. In contrast, the expression of the vitellogenin (vg) gene remained unaltered, while the hsp70 gene appeared to be down-regulated. The ability of TBT to up-regulate hormonal target genes provides the first evidence, at genomic level, of its endocrine disruptive effects and also suggests a mechanism of action that mimics ecdysteroid hormones in insects. These data reveal for the first time the early genomic effects of TBT on an insect genome. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of (Pro)Renin Receptor in Albumin Overload-Induced Nephropathy in Rats.

PubMed

Fang, Hui; Deng, Mokan; Zhang, Linlin; Lu, Aihua; Su, Jiahui; Xu, Chuanming; Zhou, Li; Wang, Lei; Ou, Jing-Song; Wang, Weidong; Yang, Tianxin

2018-05-30

Proteinuria is not only a common feature of chronic kidney diseases (CKD) but also an independent risk factor promoting CKD progression to end-stage renal failure. However, the underlying molecular mechanisms for protein overload-induced renal injury remain elusive. The present study examined the role of (pro)renin receptor (PRR) in pathogenesis of albumin overload (AO)-induced nephropathy and activation of intrarenal renin-angiotensin system (RAS) in rats. Wistar rats underwent unilateral nephrectomy and were treated for 7 weeks with vehicle, bovine serum albumin (5 g/kg/d via a single i.p. injection) alone or in conjunction with a PRR decoy inhibitor PRO20 (500 μg/kg/d via 3 s.c. injections). The AO rat model exhibited severe proteinuria, tubular necrosis, and interstitial fibrosis, oxidative stress, inflammation, accompanied by elevated urinary N-acetyl-beta-D-glucosaminidase activity and urinary β2-microglobulin secretion, all of which were significantly attenuated by PRO20. Urinary and renal levels of renin, angiotensinogen (AGT), and Ang II were elevated by AO and suppressed by PRO20, contrasting to largely unaltered plasma levels of the RAS parameters. The AO model also showed increased renal expression of full-length PRR and soluble PRR (sPRR) and urinary excretion of sPRR. Taken together, we conclude that PRR antagonism with PRO20 alleviates AO-induced nephropathy via inhibition of intrarenal RAS.

Iron alters cell survival in a mitochondria-dependent pathway in ovarian cancer cells

PubMed Central

Bauckman, Kyle; Haller, Edward; Taran, Nicholas; Rockfield, Stephanie; Ruiz-Rivera, Abigail; Nanjundan, Meera

2015-01-01

The role of iron in the development of cancer remains unclear. We previously reported that iron reduces cell survival in a Ras/mitogen-activated protein kinase (MAPK)-dependent manner in ovarian cells; however, the underlying downstream pathway leading to reduced survival was unclear. Although levels of intracellular iron, ferritin/CD71 protein and reactive oxygen species did not correlate with iron-induced cell survival changes, we identified mitochondrial damage (via TEM) and reduced expression of outer mitochondrial membrane proteins (translocase of outer membrane: TOM20 and TOM70) in cell lines sensitive to iron. Interestingly, Ru360 (an inhibitor of the mitochondrial calcium uniporter) reversed mitochondrial changes and restored cell survival in HEY ovarian carcinoma cells treated with iron. Further, cells treated with Ru360 and iron also had reduced autophagic punctae with increased lysosomal numbers, implying cross-talk between these compartments. Mitochondrial changes were dependent on activation of the Ras/MAPK pathway since treatment with a MAPK inhibitor restored expression of TOM20/TOM70 proteins. Although glutathione antioxidant levels were reduced in HEY treated with iron, extracellular glutamate levels were unaltered. Strikingly, oxalomalate (inhibitor of aconitase, involved in glutamate production) reversed iron-induced responses in a similar manner to Ru360. Collectively, our results implicate iron in modulating cell survival in a mitochondria-dependent manner in ovarian cancer cells. PMID:25697096

Optimum Parameters for Freeze-Drying Decellularized Arterial Scaffolds

PubMed Central

Sheridan, William S.; Duffy, Garry P.

2013-01-01

Decellularized arterial scaffolds have achieved success in advancing toward clinical use as vascular grafts. However, concerns remain regarding long-term preservation and sterilization of these scaffolds. Freeze drying offers a means of overcoming these concerns. In this study, we investigated the effects of various freeze-drying protocols on decellularized porcine carotid arteries and consequently, determined the optimum parameters to fabricate a stable, preserved scaffold with unaltered mechanical properties. Freeze drying by constant slow cooling to two final temperatures ((Tf), −10°C and −40°C) versus instant freezing was investigated by histological examination and mechanical testing. Slow cooling to Tf= −10°C produced a stiffer and less distensible response than the non freeze-dried scaffolds and resulted in disruption to the collagen fibers. The mechanical response of Tf= −40°C scaffolds demonstrated disruption to the elastin network, which was confirmed with histology. Snap freezing scaffolds in liquid nitrogen and freeze drying to Tf= −40°C with a precooled shelf at −60°C produced scaffolds with unaltered mechanical properties and a histology resembling non-freeze-dried scaffolds. The results of this study demonstrate the importance of optimizing the nucleation and ice crystal growth/size to ensure homogenous drying, preventing extracellular matrix disruption and subsequent inferior mechanical properties. This new manufacturing protocol creates the means for the preservation and sterilization of decellularized arterial scaffolds while simultaneously maintaining the mechanical properties of the tissue. PMID:23614758

Preparation and characterization of protein-loaded poly(epsilon-caprolactone) microparticles for oral vaccine delivery.

PubMed

Benoit, M A; Baras, B; Gillard, J

1999-07-05

This paper describes the conditions of preparation of poly(epsilon-caprolactone) (PCL) microparticles with a mean size between 5 and 10 microm, obtained by a double emulsion-solvent evaporation technique, suitable for oral vaccine delivery. Bovine serum albumin (BSA) was used as water-soluble model antigen for encapsulation. Different parameters influencing the microparticle size, the BSA loading and entrapment efficiency were investigated. Spherical, smooth and homogeneously distributed microparticles were produced with a BSA loading and entrapment efficiency reaching, respectively, 5% (w/w) and 30%. Polyacrylamide gel electrophoresis (PAGE) and isoelectric focusing (IEF) analyses of BSA released from these particles confirmed that the entrapped protein seemed to remain unaltered by the protein encapsulation process. Copyright.

Immunomodulatory effect of albizzia lebbeck.

PubMed

Barua, C C; Gupta, P P; Patnaik, G K; Misra-Bhattacharya, S; Goel, R K; Kulshrestha, D K; Dubey, M P; Dhawan, B N

2000-01-01

The immunomodulatory effect of the bark of Albizzia lebbeck (Sirisha) was evaluated by studying humoral and cell mediated immune responses. The hot aqueous extract and its butanolic fraction were administered once daily for one week in mice, immunised previously with sheep red blood cells (SRBC). At the dose levels tested (6.25, 12.5 and 25 mg/kg, p.o.), A. lebbeck treated mice developed higher serum antibody titres compared to the vehicle treated group and the effect was comparable to the standard drug muramyl dipeptide (MDP). Delayed type hypersensitivity response was suppressed in SRBC immunised mice treated with A. lebbeck extract. The macrophage migration index remained unaltered in both mice and rats. These results are discussed in the light of possible immunopotentiating effects of A. lebbeck.

Photodynamic inactivation of antigenic determinants of single-stranded DNA bacteriophage phiX174

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

Khan, N.C.; Poddar, R.K.

1974-05-01

Bacteriophage phi X174 when photodynamically inactivated (i.e., when rendered unable to produce plaques as a result of exposure to visible light in air in the presence of proflavine) progressively lost their capacity to bind efficiently with homologous antiserum. Such loss of serum-blocking power was evident with heat-inactivated but not with uv-irradiated phage. The ability of the phages to adsorb to host cells, however, remained practically unaltered even after photodynamic inactivation. It thus appears that photodynamic damages in the so-called ''jacket'' component of the phi X174 coat proteins are partly responsible for the loss of plaque-forming ability, whereas the ''spikes'' aremore » either poor antigens or insensitive to photodynamic treatment. (auth)« less

["Entero-insular axis" and regulation of blood sugar and insulin levels following oral glucose loading].

PubMed

Kuznetsov, B G

1978-11-01

The mineral water Essentuki 17 administered per so with glucose exerted a modifying effect on the regulation of glycaemia and insulinaemia in intact rats. This effect undergoes a few phases of changing and disappears by the 30th day. Under conditions of this adaptation, the glycaemia regulation is somewhat worsening. After i.v. administration of glucose during this period the regulation of glycaemia and insulinaemia remains unaltered. This suggests that the mineral water exerts its biological effect, mainly, on the entero-insular axis system (Unger and Eisentraut, 1969) and that the modifying effect is due not to a concrete complex of the mineral water electrolytes but rather to the unspecific factor of "perturbation" in the enteral medium.

Coupling multiscale X-ray physics and micromechanics for bone tissue composition and elasticity determination from micro-CT data, by example of femora from OVX and sham rats

NASA Astrophysics Data System (ADS)

Hasslinger, Patricia; Vass, Viktoria; Dejaco, Alexander; Blanchard, Romane; Örlygsson, Gissur; Gargiulo, Paolo; Hellmich, Christian

2016-05-01

Due to its high resolution, micro-CT (Computed Tomograph) scanning is the key to assess bone quality of sham and OVX (ovariectomized) rats. Combination of basic X-ray physics, such as the energy- and chemistry-dependence of attenuation coefficients, with results from ashing tests on rat bones, delivers mineral, organic, and water volume fractions within the voxels. Additional use of a microelastic model for bone provides voxel-specific elastic properties. The new method delivers realistic bone mass densities, and reveals that OVX protocols may indeed induce some bone mass loss, while the average composition of the bone tissue remains largely unaltered.

Antisense Inhibition of the 2-Oxoglutarate Dehydrogenase Complex in Tomato Demonstrates Its Importance for Plant Respiration and during Leaf Senescence and Fruit Maturation[W][OA

PubMed Central

Araújo, Wagner L.; Tohge, Takayuki; Osorio, Sonia; Lohse, Marc; Balbo, Ilse; Krahnert, Ina; Sienkiewicz-Porzucek, Agata; Usadel, Björn; Nunes-Nesi, Adriano; Fernie, Alisdair R.

2012-01-01

Transgenic tomato (Solanum lycopersicum) plants expressing a fragment of the gene encoding the E1 subunit of the 2-oxoglutarate dehydrogenase complex in the antisense orientation and exhibiting substantial reductions in the activity of this enzyme exhibit a considerably reduced rate of respiration. They were, however, characterized by largely unaltered photosynthetic rates and fruit yields but restricted leaf, stem, and root growth. These lines displayed markedly altered metabolic profiles, including changes in tricarboxylic acid cycle intermediates and in the majority of the amino acids but unaltered pyridine nucleotide content both in leaves and during the progression of fruit ripening. Moreover, they displayed a generally accelerated development exhibiting early flowering, accelerated fruit ripening, and a markedly earlier onset of leaf senescence. In addition, transcript and selective hormone profiling of gibberellins and abscisic acid revealed changes only in the former coupled to changes in transcripts encoding enzymes of gibberellin biosynthesis. The data obtained are discussed in the context of the importance of this enzyme in both photosynthetic and respiratory metabolism as well as in programs of plant development connected to carbon–nitrogen interactions. PMID:22751214

Comparison of species composition and richness of fish assemblages in altered and unaltered littoral habitats

USGS Publications Warehouse

Poe, T.P.; Hatcher, C.O.; Brown, C.L.; Schloesser, D.W.

1986-01-01

Species composition and richness of fish assemblages in altered and unaltered littoral habitats in Lake St. Clair, Michigan, differed between areas. A percid-cyprinid-cyprinodontid assemblage dominated in the unaltered area, Muscamoot Bay, which has a natural shoreline (with almost no alteration due to dredging or bulkheading), high water quality, and high species richness of aquatic macrophytes. A centrarchid assemblage dominated in the altered area, Belvidere Bay, which has a bulkheaded shoreline, many dredged areas, reduced water quality due to inputs of nutrients from a nearby river, and relatively low species richness of aquatic macrophytes. Habitat factors, species richness and abundance of aquatic macrophytes, had the most influence on fish community structure in both areas. The percid-cyprinid-cyprinodontid assemblage was significantly correlated with six species of macrophytes whereas the centrarchid assemblage was significantly correlated with only four. These patterns suggest that preference for diverse habitats was higher, and tolerance to habitat alteration lower, in percid-cyprinid-cyprinodontid assemblages than in centrarchid assemblages.

S-adenosylmethionine regulates thiopurine methyltransferase activity and decreases 6-mercaptopurine cytotoxicity in MOLT lymphoblasts.

PubMed

Milek, Miha; Karas Kuzelicki, Natasa; Smid, Alenka; Mlinaric-Rascan, Irena

2009-06-15

Six-mercaptopurine (6-MP) is a pro-drug widely used in treatment of various diseases, including acute lymphoblastic leukaemia (ALL). Side-effects of thiopurine therapy have been correlated with thiopurine methyltransferase (TPMT) activity. We propose a novel TPMT-mediated mechanism of S-adenosylmethionine (SAM)-specific effects on 6-mercaptopurine (6-MP) induced cytotoxicity in a model cell line for acute lymphoblastic leukemia (MOLT). Our results show that exogenous SAM (10-50microM) rescues cells from the toxic effects of 6-MP (5microM) by delaying the onset of apoptosis. We prove that the extent of methylthioinosine monophosphate (MeTIMP) induced inhibition of de novo purine synthesis (DNPS) determines the concentrations of intracellular ATP, and consequently SAM, which acts as a positive modulator of TPMT activity. This leads to a greater conversion of 6-MP to inactive 6-methylmercaptopurine, and thus lower availability of thioinosine monophosphate for the biotransformation to cytotoxic thioguanine nucleotides (TGNs) and MeTIMP. We further show that the addition of exogenous SAM to 6-MP treated cells maintains intracellular SAM levels, TPMT activity and protein levels, all of which are diminished in cells incubated with 6-MP. Since TPMT mRNA levels remained unaltered, the effect of SAM appears to be restricted to protein stabilisation rather than an increase of TPMT expression. We thus propose that SAM reverses the extent of 6-MP cytotoxicity, by acting as a TPMT-stabilizing factor. This study provides new insights into the pharmacogenetics of thiopurine drugs. Identification of SAM as critical modulator of TPMT activity and consequently thiopurine toxicity may set novel grounds for the rationalization of thiopurine therapy.

Effect of high hydrostatic pressure on Aeromonas hydrophila AH 191 growth in milk.

PubMed

Durães-Carvalho, Ricardo; Souza, Ancelmo R; Martins, Luciano M; Sprogis, Adriane C S; Bispo, Jose A C; Bonafe, Carlos F S; Yano, Tomomasa

2012-08-01

Exposure to high pressure is an efficient method of bacterial inactivation that is particularly important for reducing the microbial load present in foods. In this study, we examined the high pressure inactivation of Aeromonas hydrophila AH 191, a virulent strain that produces aerolysin, a cytotoxic, enterotoxic, and hemolytic toxin. High pressure treatment (250 MPa for 30 min at 25 °C in 0.1 M PBS, pH 7.4) of A. hydrophila grown in milk reduced bacterial viability by at least 9 orders of magnitude. Under these conditions, the enterotoxic, hemolytic, and cytotoxic activities of A. hydrophila culture supernatants were unaltered. These results indicate the need for caution in the use of high pressure for food processing since although truly toxigenic bacteria may be inactivated, their toxins may not be, thus posing a risk to human health. At higher pressure (350 MPa) the inactivation of bacteria was much more effective. Scanning electron microscopy showed a significant decrease in the number of bacteria after higher pressurization (350 MPa for 1 h) and transmission electron microscopy showed irregular shaped bacteria, suggestive of important cell wall and membrane damage, and cytoplasm condensation. High pressure inactivates Aeromonas hydrophila efficiently but is enhanced when combined with moderate temperature (40 °C). The biological activities of toxins from this bacterium are unaltered under these conditions. Journal of Food Science © 2012 Institute of Food Technologists® No claim to original US government works.

Peptides of the Constant Region of Antibodies Display Fungicidal Activity

PubMed Central

Polonelli, Luciano; Ciociola, Tecla; Magliani, Walter; Zanello, Pier Paolo; D'Adda, Tiziana; Galati, Serena; De Bernardis, Flavia; Arancia, Silvia; Gabrielli, Elena; Pericolini, Eva; Vecchiarelli, Anna; Arruda, Denise C.; Pinto, Marcia R.; Travassos, Luiz R.; Pertinhez, Thelma A.; Spisni, Alberto; Conti, Stefania

2012-01-01

Synthetic peptides with sequences identical to fragments of the constant region of different classes (IgG, IgM, IgA) of antibodies (Fc-peptides) exerted a fungicidal activity in vitro against pathogenic yeasts, such as Candida albicans, Candida glabrata, Cryptococcus neoformans, and Malassezia furfur, including caspofungin and triazole resistant strains. Alanine-substituted derivatives of fungicidal Fc-peptides, tested to evaluate the critical role of each residue, displayed unaltered, increased or decreased candidacidal activity in vitro. An Fc-peptide, included in all human IgGs, displayed a therapeutic effect against experimental mucosal and systemic candidiasis in mouse models. It is intriguing to hypothesize that some Fc-peptides may influence the antifungal immune response and constitute the basis for devising new antifungal agents. PMID:22470523

Cascade Bioassay Evidence for the Existence of Urothelium-Derived Inhibitory Factor in Guinea Pig Urinary Bladder

PubMed Central

Guan, Na N.; Thor, Anna; Hallén, Katarina; Wiklund, N. Peter; Gustafsson, Lars E.

2014-01-01

Our aim was to investigate whether guinea pig urothelium-derived bioactivities compatible with the existence of urothelium-derived inhibitory factor could be demonstrated by in vitro serial bioassay and whether purinergic P1 receptor agonists, nitric oxide, nitrite or prostaglandins might explain observed activities. In a cascade superfusion system, urothelium-denuded guinea pig ureters were used as bioassay tissues, recording their spontaneous rhythmic contractions in presence of scopolamine. Urothelium-intact or -denuded guinea pig urinary bladders were used as donor tissues, stimulated by intermittent application of carbachol before or during the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the adenosine/P1 nucleoside receptor antagonist 8-(p-sulfophenyl)theophylline (8-PST) or the cyclo-oxygenase inhibitor diclofenac infused to bath donor and bioassay tissues. The spontaneous contractions of bioassay ureters were unaltered by application of carbachol 1–5 µM in the presence of scopolamine 5–30 µM. When carbachol was applied over the urothelium-denuded bladder, the assay ureter contraction rate was unaltered. Introducing carbachol over the everted urothelium-intact bladder significantly inhibited the contraction frequency of the assay ureter, suggesting the transfer of an inhibitory activity from the bladder to the assay ureter. The transmissible inhibitory activity was not markedly antagonized by L-NAME, 8-PST or diclofenac, while L-NAME nearly abolished nitrite release from the urothelium-intact bladder preparations. We suggest that urothelium-derived inhibitory factor is a transmissible entity over a significant distance as demonstrated in this novel cascade superfusion assay and seems less likely to be nitric oxide, nitrite, an adenosine receptor agonist or subject to inhibition by administration of a cyclo-oxygenase inhibitor. PMID:25084114

Cascade bioassay evidence for the existence of urothelium-derived inhibitory factor in Guinea pig urinary bladder.

PubMed

Guan, Na N; Thor, Anna; Hallén, Katarina; Wiklund, N Peter; Gustafsson, Lars E

2014-01-01

Our aim was to investigate whether guinea pig urothelium-derived bioactivities compatible with the existence of urothelium-derived inhibitory factor could be demonstrated by in vitro serial bioassay and whether purinergic P1 receptor agonists, nitric oxide, nitrite or prostaglandins might explain observed activities. In a cascade superfusion system, urothelium-denuded guinea pig ureters were used as bioassay tissues, recording their spontaneous rhythmic contractions in presence of scopolamine. Urothelium-intact or -denuded guinea pig urinary bladders were used as donor tissues, stimulated by intermittent application of carbachol before or during the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the adenosine/P1 nucleoside receptor antagonist 8-(p-sulfophenyl)theophylline (8-PST) or the cyclo-oxygenase inhibitor diclofenac infused to bath donor and bioassay tissues. The spontaneous contractions of bioassay ureters were unaltered by application of carbachol 1-5 µM in the presence of scopolamine 5-30 µM. When carbachol was applied over the urothelium-denuded bladder, the assay ureter contraction rate was unaltered. Introducing carbachol over the everted urothelium-intact bladder significantly inhibited the contraction frequency of the assay ureter, suggesting the transfer of an inhibitory activity from the bladder to the assay ureter. The transmissible inhibitory activity was not markedly antagonized by L-NAME, 8-PST or diclofenac, while L-NAME nearly abolished nitrite release from the urothelium-intact bladder preparations. We suggest that urothelium-derived inhibitory factor is a transmissible entity over a significant distance as demonstrated in this novel cascade superfusion assay and seems less likely to be nitric oxide, nitrite, an adenosine receptor agonist or subject to inhibition by administration of a cyclo-oxygenase inhibitor.

Revisiting the slow force response: the role of the PKG signaling pathway in the normal and the ischemic heart.

PubMed

Castro-Ferreira, Ricardo; Neves, João Sérgio; Ladeiras-Lopes, Ricardo; Leite-Moreira, André M; Neiva-Sousa, Manuel; Almeida-Coelho, João; Ferreira-Martins, João; F Leite-Moreira, Adelino

2014-09-01

The myocardial response to acute stretch consists of a two-phase increase in contractility: an acute increase by the Frank-Starling mechanism and a gradual and time-dependent increase in force generated known as the slow force response (SFR). The SFR is actively modulated by different signaling pathways, but the role of protein kinase G (PKG) signaling is unknown. In this study we aim to characterize the role of the PKG signaling pathway in the SFR under normal and ischemic conditions. Rabbit papillary muscles were stretched from 92 to 100% of maximum length (Lmax) under basal conditions, in the absence (1) or presence of: a PKG agonist (2) and a PKG inhibitor (3); under ischemic conditions in the absence (4) or presence of: a PKG agonist (5); a nitric oxide (NO) donor (6) and a phosphodiesterase 5 (PDE5) inhibitor (7). Under normoxia, the SFR was significantly attenuated by inhibition of PKG and remained unaltered with PKG activation. Ischemia induced a progressive decrease in myocardial contractility after stretch. Neither the PKG agonist nor the NO donor altered the myocardial response to stretch under ischemic conditions. However, the use of a PDE5 inhibitor in ischemia partially reversed the progressive deterioration in contractility. PKG activity is essential for the SFR. During ischemia, a progressive decline in the force is observed in response to acute myocardial stretch. This dysfunctional response can be partially reversed by the use of PDE5 inhibitors. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats.

PubMed

Fuentes, Silvia; Carrasco, Javier; Armario, Antonio; Nadal, Roser

2014-08-01

Exposure to stress during childhood and adolescence increases vulnerability to developing several psychopathologies in adulthood and alters the activity of the hypothalamic-pituitary-adrenal (HPA) axis, the prototypical stress system. Rodent models of juvenile stress appear to support this hypothesis because juvenile stress can result in reduced activity/exploration and enhanced anxiety, although results are not always consistent. Moreover, an in-depth characterization of changes in the HPA axis is lacking. In the present study, the long-lasting effects of juvenile stress on adult behavior and HPA function were evaluated in male rats. The juvenile stress consisted of a combination of stressors (cat odor, forced swim and footshock) during postnatal days 23-28. Juvenile stress reduced the maximum amplitude of the adrenocorticotropic hormone (ACTH) levels (reduced peak at lights off), without affecting the circadian corticosterone rhythm, but other aspects of the HPA function (negative glucocorticoid feedback, responsiveness to further stressors and brain gene expression of corticotrophin-releasing hormone and corticosteroid receptors) remained unaltered. The behavioral effects of juvenile stress itself at adulthood were modest (decreased activity in the circular corridor) with no evidence of enhanced anxiety. Imposition of an acute severe stressor (immobilization on boards, IMO) did not increase anxiety in control animals, as evaluated one week later in the elevated-plus maze (EPM), but it potentiated the acoustic startle response (ASR). However, acute IMO did enhance anxiety in the EPM, in juvenile stressed rats, thereby suggesting that juvenile stress sensitizes rats to the effects of additional stressors. Copyright © 2014 Elsevier Inc. All rights reserved.

Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice

PubMed Central

Dinger, Katharina; Kasper, Philipp; Hucklenbruch-Rother, Eva; Vohlen, Christina; Jobst, Eva; Janoschek, Ruth; Bae-Gartz, Inga; van Koningsbruggen-Rietschel, Silke; Plank, Christian; Dötsch, Jörg; Alejandre Alcázar, Miguel Angel

2016-01-01

Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma. PMID:27087690

Physiological assessment of deer populations by analysis of urine in snow

USGS Publications Warehouse

DelGiudice, G.D.; Mech, L.D.; Seal, U.S.

1989-01-01

We compared the nutritional status of free-ranging white-tailed deer (Odocoileus virginianus) in 3 natural yards and 1 yard where deer were supplementally fed from 1 January to 31 March 1985 in northeastern Minnesota. We monitored deer nutritonal status by sequential collection and chemical analysis of urine in snow (snow-urine) for urea nitrogen (U), sodium (Na), potassium (K), calcium (Ca), and phosphorus (P). Dilution of urine by snow was corrected by comparing these data as ratios to creatinine (C). All deer remained in an early phase of undernutrition; however, declining trends of U:C, Na:C, and K:C in 2 natural yards indicated increasingly inadequate nutrition as winter progressed. Unaltered values of these ratios and P.C in snow-urine collected from the third natural yard reflected stable levels of nutrient availability. Significant (P < 0.05) elevations of Na:C, K:C, and P:C in 2 natural yards with similar snow regimes suggested initiation of nutritional recovery in deer during late March. In contrast, deep snow in the third natural yard restricted feeding activity and was associated with ratios that remained diminished. Elevated U:C, Na:C, and K:C provided physiological evidence of the higher nutritional status of supplementally fed deer throughout winter and their ability to increase nutrient intake during late March despite prolonged deep snow cover. Frequent and quantitative assessments of the physiological status of deer by snow-urine analysis provided an improved understanding of the relationship between snow cover and the nutritional well-being of these deer.

Alteration of Daily and Circadian Rhythms following Dopamine Depletion in MPTP Treated Non-Human Primates

PubMed Central

Fifel, Karim; Vezoli, Julien; Dzahini, Kwamivi; Claustrat, Bruno; Leviel, Vincent; Kennedy, Henry; Procyk, Emmanuel; Dkhissi-Benyahya, Ouria; Gronfier, Claude; Cooper, Howard M.

2014-01-01

Disturbances of the daily sleep/wake cycle are common non-motor symptoms of Parkinson's disease (PD). However, the impact of dopamine (DA) depletion on circadian rhythms in PD patients or non-human primate (NHP) models of the disorder have not been investigated. We evaluated alterations of circadian rhythms in NHP following MPTP lesion of the dopaminergic nigro-striatal system. DA degeneration was assessed by in vivo PET ([11C]-PE2I) and post-mortem TH and DAT quantification. In a light∶dark cycle, control and MPTP-treated NHP both exhibit rest-wake locomotor rhythms, although DA-depleted NHP show reduced amplitude, decreased stability and increased fragmentation. In all animals, 6-sulphatoxymelatonin peaks at night and cortisol in early morning. When the circadian system is challenged by exposure to constant light, controls retain locomotor rest-wake and hormonal rhythms that free-run with stable phase relationships whereas in the DA-depleted NHP, locomotor rhythms are severely disturbed or completely abolished. The amplitude and phase relations of hormonal rhythms nevertheless remain unaltered. Use of a light-dark masking paradigm shows that expression of daily rest-wake activity in MPTP monkeys requires the stimulatory and inhibitory effects of light and darkness. These results suggest that following DA lesion, the central clock in the SCN remains intact but, in the absence of environmental timing cues, is unable to drive downstream rhythmic processes of striatal clock gene and dopaminergic functions that control locomotor output. These findings suggest that the circadian component of the sleep-wake disturbances in PD is more profoundly affected than previously assumed. PMID:24465981

Dysregulation of autophagy in rat liver with mitochondrial DNA depletion induced by the nucleoside analogue zidovudine.

PubMed

Santos-Llamas, Ana; Monte, Maria J; Marin, Jose J G; Perez, Maria J

2018-03-28

The nucleoside reverse transcriptase inhibitor zidovudine (AZT), used in HIV infection treatment, induces mitochondrial DNA (mtDNA) depletion. A cause-effect relationship between mtDNA status alterations and autophagy has been reported. Both events are common in several liver diseases, including hepatocellular carcinoma. Here, we have studied autophagy activation in rat liver with mtDNA depletion induced by AZT administration in drinking water for 35 days. AZT at a concentration of 1 mg/ml, but not 0.5 mg/ml in the drinking water, decreased mtDNA levels in rat liver and extrahepatic tissues. In liver, mtDNA-encoded cytochrome c oxidase 1 protein levels were decreased. Although serum biomarkers of liver and kidney toxicity remained unaltered, β-hydroxybutyrate levels were increased in liver of AZT-treated rats. Moreover, autophagy was dysregulated at two levels: (i) decreased induction signalling of this process as indicated by increases in autophagy inhibitors activity (AKT/mTOR), and absence of changes (Beclin-1, Atg5, Atg7) or decreases (AMPK/ULK1) in the expression/activity of pro-autophagy proteins; and (ii) reduced autophagosome degradation as indicated by decreases in the lysosome abundance (LAMP2 marker) and the transcription factor TFEB controlling lysosome biogenesis. This resulted in increased autophagosome abundance (LC3-II marker) and accumulation of the protein selectively degraded by autophagy p62, and the transcription factor Nrf2 in liver of AZT-treated rats. Nrf2 was activated as indicated by the up-regulation of antioxidant target genes Nqo1 and Hmox-1. In conclusion, rat liver with AZT-induced mtDNA depletion presented dysregulations in autophagosome formation and degradation balance, which results in accumulation of these structures in parenchymal liver cells, favouring hepatocarcinogenesis.

An In Vitro Model to Probe the Regulation of Adipocyte Differentiation under Hyperglycemia

PubMed Central

Shilpa, Kusampudi; Dinesh, Thangaraj

2013-01-01

Background The aim of this study was an in vitro investigation of the effect of high glucose concentration on adipogenesis, as prolonged hyperglycemia alters adipocyte differentiation. Methods 3T3-L1 preadipocytes differentiated in the presence of varying concentrations of glucose (25, 45, 65, 85, and 105 mM) were assessed for adipogenesis using AdipoRed (Lonza) assay. Cell viability and proliferation were measured using MTT reduction and [3H] thymidine incorporation assay. The extent of glucose uptake and glycogen synthesis were measured using radiolabelled 2-deoxy-D-[1-3H] glucose and [14C]-UDP-glucose. The gene level expression was evaluated using reverse transcription-polymerase chain reaction and protein expression was studied using Western blot analysis. Results Glucose at 105 mM concentration was observed to inhibit adipogenesis through inhibition of CCAAT-enhancer-binding proteins, sterol regulatory element-binding protein, peroxisome proliferator-activated receptor and adiponectin. High concentration of glucose induced stress by increasing levels of toll-like receptor 4, nuclear factor κB and tumor necrosis factor α thereby generating activated preadipocytes. These cells entered the state of hyperplasia through inhibition of p27 and proliferation was found to increase through activation of protein kinase B via phosphoinositide 3 kinase dependent pathway. This condition inhibited insulin signaling through decrease in insulin receptor β. Although the glucose transporter 4 (GLUT4) protein remained unaltered with the glycogen synthesis inhibited, the cells were found to exhibit an increase in glucose uptake via GLUT1. Conclusion Adipogenesis in the presence of 105 mM glucose leads to an uncontrolled proliferation of activated preadipocytes providing an insight towards understanding obesity. PMID:23807920

Application of the Copenhagen Soccer Test in high-level women players - locomotor activities, physiological response and sprint performance.

PubMed

Bendiksen, Mads; Pettersen, Svein Arne; Ingebrigtsen, Jørgen; Randers, Morten B; Brito, João; Mohr, Magni; Bangsbo, Jens; Krustrup, Peter

2013-12-01

We evaluated the physiological response, sprint performance and technical ability in various phases of the Copenhagen Soccer Test for Women (CSTw) and investigated whether the locomotor activities of the CSTw were comparable to competitive match-play (CM). Physiological measurements and physical/technical assessments were performed during CSTw for eleven Norwegian high-level women soccer players. The activity pattern during CSTw and CM was monitored using the ZXY tracking system. No differences were observed between CSTw and CM with regards to total distance covered (10093±94 and 9674±191m), high intensity running (1278±67 and 1193±115m) or sprinting (422±55 and 372±46m) (p>.05). During CSTw, average HR was 85±2%HRmax with 35±2% playing time >90%HRmax. Blood lactate increased (p<.05) from 1.4±0.3mM at rest to an average of 4.7±0.5mM during CSTw, with no changes during the test. Blood glucose was 5.4±0.3mM at rest and remained unaltered during CSTw. Sprint performance (2×20m) decreased (p<.05) by 3% during CSTw (8.19±0.06-8.47±0.10s). In conclusion, the locomotor activities during CSTw were comparable to that of high-level competitive match-play. The physiological demands of the CSTw were high, with no changes in heart rate, blood lactate or technical performance during the test, but a lowered sprint performance towards the end of the test. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of a 5-day treatment with the UV-filter octyl-methoxycinnamate (OMC) on the function of the hypothalamo-pituitary-thyroid function in rats.

PubMed

Klammer, Holger; Schlecht, Christiane; Wuttke, Wolfgang; Schmutzler, Cornelia; Gotthardt, Inka; Köhrle, Josef; Jarry, Hubertus

2007-09-05

Octyl-methoxycinnamate (OMC) is one of the most frequently used UV-filters in sunscreens to protect the skin against the noxious influence of UV radiation. Recently, OMC was suspected to act as an "endocrine active chemical" (EAC) with estrogenic actions. While EACs have been investigated thoroughly for interference with reproductive function in mammalians, surprisingly little efforts have been made to investigate an interference of EACs with the hypothalamo-pituitary-thyroid (HPT) axis despite the expression of estrogen receptors in all parts of this axis. Therefore, we conducted an in vivo study with ovariectomised rats treated for 5 days with different doses of OMC or 17beta-estradiol (E2) as a control. Determined parameters comprised serum levels of TSH, T4 and T3, hypothalamic TRH mRNA expression, protein-expression of the sodium-iodide-symporter (NIS) and the TSH receptor and the activities of thyroid peroxidase (TPO) in the thyroid and the T3-responsive hepatic type I 5'deiodinase (Dio1) in the liver. While E2 did not affect TSH-, T4- or T3-levels, OMC caused a dose-dependent decrease of serum concentrations of all of these hormones. TRH expression remained unaffected, while in the thyroid, expression of the TSH receptor but not of NIS was stimulated by OMC. TPO activity was unaltered but Dio1 activity was reduced by OMC. Thus, our results demonstrate a non-estrogenic interference of OMC within the rodent HPT axis with inadequate feedback response to impaired thyroid hormone status, indicated by decreased serum thyroid hormone and hepatic Dio1 levels.

BRCA1 haploinsufficiency cell-autonomously activates RANKL expression and generates denosumab-responsive breast cancer-initiating cells.

PubMed

Cuyàs, Elisabet; Corominas-Faja, Bruna; Martín, María Muñoz-San; Martin-Castillo, Begoña; Lupu, Ruth; Brunet, Joan; Bosch-Barrera, Joaquim; Menendez, Javier A

2017-05-23

Denosumab, a monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), might be a novel preventative therapy for BRCA1-mutation carriers at high risk of developing breast cancer. Beyond its well-recognized bone-targeted activity impeding osteoclastogenesis, denosumab has been proposed to interfere with the cross-talk between RANKL-producing sensor cells and cancer-initiating RANK+ responder cells that reside within premalignant tissues of BRCA1-mutation carriers. We herein tested the alternative but not mutually exclusive hypothesis that BRCA1 deficiency might cell-autonomously activate RANKL expression to generate cellular states with cancer stem cell (CSC)-like properties. Using isogenic pairs of normal-like human breast epithelial cells in which the inactivation of a single BRCA1 allele results in genomic instability, we assessed the impact of BRCA1 haploinsufficiency on the expression status of RANK and RANKL. RANK expression remained unaltered but RANKL was dramatically up-regulated in BRCA1mut/+ haploinsufficient cells relative to isogenic BRCA1+/+ parental cells. Neutralizing RANKL with denosumab significantly abrogated the ability of BRCA1 haploinsufficient cells to survive and proliferate as floating microtumors or "mammospheres" under non-adherent/non-differentiating conditions, an accepted surrogate of the relative proportion and survival of CSCs. Intriguingly, CSC-like states driven by epithelial-to-mesenchymal transition or HER2 overexpression traits responded to some extent to denosumab. We propose that breast epithelium-specific mono-allelic inactivation of BRCA1 might suffice to cell-autonomously generate RANKL-addicted, denosumab-responsive CSC-like states. The convergent addiction to a hyperactive RANKL/RANK axis of CSC-like states from genetically diverse breast cancer subtypes might inaugurate a new era of cancer prevention and treatment based on denosumab as a CSC-targeted agent.

Reduced cholesterol levels in renal membranes of undernourished rats may account for urinary Na⁺ loss.

PubMed

Oliveira, Fabiana S T; Vieira-Filho, Leucio D; Cabral, Edjair V; Sampaio, Luzia S; Silva, Paulo A; Carvalho, Vera C O; Vieyra, Adalberto; Einicker-Lamas, Marcelo; Lima, Vera L M; Paixão, Ana D O

2013-04-01

It has been demonstrated that reabsorption of Na⁺ in the thick ascending limb is reduced and the ability to concentrate urine can be compromised in undernourished individuals. Alterations in phospholipid and cholesterol content in renal membranes, leading to Na⁺ loss and the inability to concentrate urine, were investigated in undernourished rats. Sixty-day-old male Wistar rats were utilized to evaluate (1) phospholipid and cholesterol content in the membrane fraction of whole kidneys, (2) cholesterol content and the levels of active Na⁺ transporters, (Na⁺ + K⁺)ATPase and Na⁺-ATPase, in basolateral membranes of kidney proximal tubules, and (3) functional indicators of medullary urine concentration. Body weight in the undernourished group was 73 % lower than in control. Undernourishment did not affect the levels of cholesterol in serum or in renal homogenates. However, membranes of whole kidneys revealed 56 and 66 % reduction in the levels of total phospholipids and cholesterol, respectively. Furthermore, cholesterol and (Na⁺ + K⁺)ATPase activity in proximal tubule membranes were reduced by 55 and 68 %, respectively. Oxidative stress remained unaltered in the kidneys of undernourished rats. In contrast, Na⁺-ATPase activity, an enzyme with all regulatory components in membrane, was increased in the proximal tubules of undernourished rats. Free water clearance and fractional Na⁺ excretion were increased by 86 and 24 %, respectively, and urinary osmolal concentration was 21 % lower in undernourished rats than controls. Life-long undernutrition reduces the levels of total phospholipids and cholesterol in membranes of renal tubular cells. This alteration in membrane integrity could diminish (Na⁺ + K⁺)ATPase activity resulting in reduced Na⁺ reabsorption and urinary concentrating ability.

The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter

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

Miyata, Ryohei; Eeden, Stephan F. van, E-mail: Stephan.vanEeden@hli.ubc.ca

Emerging epidemiological evidence suggests that exposure to particulate matter (PM) air pollution increases the risk of cardiovascular events but the exact mechanism by which PM has adverse effects is still unclear. Alveolar macrophages (AM) play a major role in clearing and processing inhaled PM. This comprehensive review of research findings on immunological interactions between AM and PM provides potential pathophysiological pathways that interconnect PM exposure with adverse cardiovascular effects. Coarse particles (10 {mu}m or less, PM{sub 10}) induce innate immune responses via endotoxin-toll-like receptor (TLR) 4 pathway while fine (2.5 {mu}m or less, PM{sub 2.5}) and ultrafine particles (0.1 {mu}mmore » or less, UFP) induce via reactive oxygen species generation by transition metals and/or polyaromatic hydrocarbons. The innate immune responses are characterized by activation of transcription factors [nuclear factor (NF)-{kappa}B and activator protein-1] and the downstream proinflammatory cytokine [interleukin (IL)-1{beta}, IL-6, and tumor necrosis factor-{alpha}] production. In addition to the conventional opsonin-dependent phagocytosis by AM, PM can also be endocytosed by an opsonin-independent pathway via scavenger receptors. Activation of scavenger receptors negatively regulates the TLR4-NF-{kappa}B pathway. Internalized particles are subsequently subjected to adaptive immunity involving major histocompatibility complex class II (MHC II) expression, recruitment of costimulatory molecules, and the modulation of the T helper (Th) responses. AM show atypical antigen presenting cell maturation in which phagocytic activity decreases while both MHC II and costimulatory molecules remain unaltered. PM drives AM towards a Th1 profile but secondary responses in a Th1- or Th-2 up-regulated milieu drive the response in favor of a Th2 profile.« less

Mechanism of the stationary canalicular excretion of tributylmethyl ammonium in rats with a CCl4-induced acute hepatic injury.

PubMed

Choi, Min-Koo; Song, Im-Sook; Park, So-Ra; Hong, Soon-Sun; Kim, Dae-Duk; Chung, Suk-Jae; Shim, Chang-Koo

2005-02-01

The in vivo canalicular excretion clearance of tributylmethyl ammonium (TBuMA), a P-glycoprotein (P-gp) substrate, was previously reported to be unaffected by the induction of an experimental hepatic injury (EHI) by CCl(4) despite the increased expression of P-gp in the EHI liver. The objective of this study, therefore, was to elucidate the mechanism for the unchanged canalicular excretion clearance of TBuMA in EHI rats. TBuMA uptake was increased in cLPM vesicles from EHI rats compared with that from control rats. The total bile salt concentration in EHI liver was significantly reduced compared with that in a control liver. Because, in our previous studies, the uptake of TBuMA by cLPM vesicles was found to be significantly enhanced in the presence of bile salts, the reduction in bile salt levels in the EHI liver may be related to the unaltered TBuMA clearance. Despite the fact that the uptake of TBuMA by cLPM vesicles was increased by the addition of an EHI liver extract, the extent of the increase was comparatively less compared to the addition of a control liver extract. The in vivo excretion clearance of TBuMA was increased in a taurodeoxycholate dose-dependent manner in EHI rats. These observations suggest, therefore, that despite the induction of P-gp expression by the EHI, the in vivo canalicular excretion clearance of TBuMA remains unaltered as the result of an offset by reduced levels of bile salt(s). Copyright 2004 Wiley-Liss, Inc.

Photosynthesis, Dark Respiration, and Growth of Rumex patientia L. Exposed to Ultraviolet Irradiance (288 to 315 Nanometers) Simulating a Reduced Atmospheric Ozone Column 1

PubMed Central

Sisson, William B.; Caldwell, Martyn M.

1976-01-01

Net photosynthesis, dark respiration, and growth of Rumex patientia L. exposed to a ultraviolet irradiance (288-315 nanometers) simulating a 0.18 atm·cm stratospheric ozone column were determined. The ultraviolet irradiance corresponding to this 38% ozone decrease from normal was shown to be an effective inhibitor of photosynthesis and leaf growth. The repressive action on photosynthesis accumulated through time whereas leaf growth was retarded only during the initial few days of exposure. Small increases in dark respiration rates occurred but did not continue to increase with longer exposure periods. A reduction in total plant dry weight and leaf area of approximately 50% occurred after 22 days of treatment, whereas chlorophyll concentrations remained unaltered. PMID:16659718

Solar, planetary, and other inert gases in two sieve fractions of a disaggregated Allende sample - A study by stepwise heating extraction

NASA Technical Reports Server (NTRS)

Palma, R. L.; Heymann, D.

1988-01-01

Inert gases released by stepwise heating of unaltered, strongly magnetic, and weakly magnetic samples from the 0-64 micron and the 105-250 micron fractions of a disaggregated and sieved sample of the Allende meteorite reveal the occurrence of both solar and planetary neon. The origin of the solar neon is thought to be implantation of solar wind ions. The origin of the planetary neon remains unresolved. Heavy isotope enriched components of krypton and xenon have been detected and there are some indications that a light krypton component may also be present. Other than a larger concentration of Xe-129 in the weakly magnetic samples, the signatures of the magnetic separates are isotopically very similar.

Water chemistry at Snowshoe Mountain, Colorado: mixed processes in a common bedrock

USGS Publications Warehouse

Hoch, A.R.; Reddy, M.M.

2001-01-01

At Snowshoe Mountain the primary bedrock is quite homogeneous, but weathering processes vary as waters moves through the soils, vadose zone and phreatic zone of the subsurface. In the thin soil, physical degradation of tuff facilitates preferential dissolution of potassium ion from glass within the rock matrix, while other silicate minerals remain unaltered. In the vadose zone, in the upper few meters of fractured bedrock, dilute water infiltrates during spring snowmelt and summer storms, leading to preferential dissolution of augite exposed on fracture surfaces. Deeper yet, in the phreatic zone of the fractured bedrock, Pleistocene calcite fracture fillings dissolve, and dioctahedral and trioctahedral clays form as penetrative weathering alters feldspar and pyroxene. Alkalinity is generated and silica concentrations are buffered by mineral alteration reactions.

A Note on the Wave Action Density of a Viscous Instability Mode on a Laminar Free-shear Flow

NASA Technical Reports Server (NTRS)

Balsa, Thomas F.

1994-01-01

Using the assumptions of an incompressible and viscous flow at large Reynolds number, we derive the evolution equation for the wave action density of an instability wave traveling on top of a laminar free-shear flow. The instability is considered to be viscous; the purpose of the present work is to include the cumulative effect of the (locally) small viscous correction to the wave, over length and time scales on which the underlying base flow appears inhomogeneous owing to its viscous diffusion. As such, we generalize our previous work for inviscid waves. This generalization appears as an additional (but usually non-negligible) term in the equation for the wave action. The basic structure of the equation remains unaltered.

Functionalized Graphene Metal-Free Carbocatalysis of Persulfate and Emerging Contaminant Oxidative Degradation

NASA Astrophysics Data System (ADS)

Carroll, K. C.; Chen, H.

2016-12-01

We evaluated three types of functionalized, graphene-based materials for activating persulfate (PS) and removing (i.e., sorption and oxidation) sulfamethoxazole (SMX) as a model emerging contaminant. Although advanced oxidative water treatment requires PS activation, activation requires energy or chemical inputs, and toxic substances are contained in many catalysts. Graphene-based materials were examined herein as an alternative to metal-based catalysts. Results show that nitrogen-doped graphene (N-GP) and aminated graphene (NH2-GP) can effectively activate PS. Overall, PS activation by graphene oxide was not observed in this study. N-GP (50 mg L-1) can rapidly activate PS (1 mM) to remove >99.9% SMX within 3 hours, and NH2-GP (50 mg L-1) activated PS (1 mM) can also remove 50% SMX within 10 hours. SMX sorption and total removal was greater for N-GP, which suggests oxidation was enhanced by increasing proximity to PS activation sites. Increasing pH enhanced the N-GP catalytic ability, and >99.9% SMX removal time decreased from 3 hours to 1 hour when pH increased from 3 to 9. However, the PS catalytic ability was inhibited at pH 9 for NH2-GP. Increases in ionic strength (100 mM NaCl or Na2SO4) and addition of radical scavengers (500 mM ethanol) both had negligible impacts on SMX removal. With bicarbonate addition (100 mM), while the catalytic ability of N-GP remained unaltered, NH2-GP catalytic ability was inhibited completely. Humic acid (250 mg L-1) was partially effective in inhibiting SMX removal in both N-GP and NH2-GP systems. These results have implications for elucidating oxidant catalysis mechanisms, and they quantify the ability of functionalization of graphene with hetero-atom doping to effectively catalyze PS for water treatment of organic pollutants including emerging contaminants.

Use of imaging in the 0.46-2.36 [micrometers] spectral region for alteration mapping in the Cuprite mining district, Nevada

USGS Publications Warehouse

Abrams, Michael J.; Ashley, R.P.; Rowan, L.C.; Goetz, A.F.H.; Kahle, A.B.

1977-01-01

Color composites of Landsat MSS ratio images that display variations in the intensity of ferric-iron absorption bands are highly effective for mapping limonitic altered rocks, but ineffective for mapping nonlimonitic altered rocks. Analysis of 0.45-2.5 ?m field and laboratory spectra shows that iron-deficient opalites in the Cuprite mining district, Nevada, have an intense OH-absorption band near 2.2 ?m owing to their clay mineral and alunite contents and that this spectral feature is absent or weak in adjacent unaltered tuff and basalt. To evaluate the usefulness of this spectral feature for discriminating between altered and unaltered rocks, we generated color-ratio composite images from multispectral (0.46-2.36 ?m) aircraft data. The altered rocks in the district can be discriminated from unaltered rocks with few ambiguities; in addition, some effects of mineralogical zoning can be discriminated within the altered area. Only variations in amounts of limonite can be discerned in shorter wavelength aircraft data, Landsat MSS bands, and color aerial photographs.

Effect of bovine somatotropin (500 mg) administered at ten-day intervals on ovulatory responses, expression of estrus, and fertility in dairy cows.

PubMed

Rivera, F; Narciso, C; Oliveira, R; Cerri, R L A; Correa-Calderón, A; Chebel, R C; Santos, J E P

2010-04-01

The objectives of this study were to evaluate the effect of administering 500 mg of recombinant bovine somatotropin (bST) every 10 d on ovulatory responses, estrous behavior, and fertility of lactating Holstein cows. Lactating dairy cows were assigned to 1 of 2 treatments: a control with no administration of bST (73 primiparous and 120 multiparous cows) or 6 consecutive administrations of 500 mg of bST (83 primiparous and 123 multiparous cows) given subcutaneously at 10-d intervals starting 61+/-3 d postpartum (study d 0), concurrent with the initiation of the timed artificial insemination (AI). Blood samples were collected thrice weekly from 61+/-3 to 124+/-3 d in milk (DIM), and plasma samples were analyzed for concentrations of estradiol, glucose, insulin, insulin-like growth factor 1, and progesterone. The estrous cycle of cows was presynchronized with 2 injections of PGF(2alpha) at 37+/-3 and 51+/-3 DIM, and the Ovsynch timed AI protocol was initiated at 61+/-3 DIM. Ovaries were scanned to determine ovulatory responses during the Ovsynch protocol. Pregnancy was diagnosed at 33 and 66 d after AI. Body condition was scored on study d 0, 10, 42, and 76. Sixty-four cows were fitted with a pressure mounting sensor with radiotelemetric transmitters to monitor estrous behavior. Treatment of lactating dairy cows with 500 mg of bST at 10-d intervals increased yields of milk and milk components in the first 2 mo after treatment. Body condition of bST-treated cows remained unaltered, whereas control cows gained BCS. Treatment with bST increased concentrations of insulin-like growth factor 1 chronically, but concentrations of insulin and glucose increased only transiently in the first 7 d after the first injection of bST. Concentrations of progesterone during and after the Ovsynch protocol remained unaltered after treatment with bST; likewise, ovulatory responses during the Ovsynch protocol were mostly unaltered by treatment. Concentration of estradiol tended to be greater for bST cows than for control cows immediately before induction of ovulation in the Ovsynch protocol. Similarly, the mean and the peak concentrations of estradiol were greater for bST cows than for control cows when monitored during spontaneous estrus. Nevertheless, duration of estrus and the median number of standing events were less for bST cows than for control cows. Pregnancies per AI after the first and second postpartum inseminations were not affected by bST treatment. Treatment of lactating dairy cows with 500 mg of bST every 10 d improved lactation performance, but it did not affect pregnancies per AI and it reduced expression of estrus. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effect of Enterococcus faecium SF68 on serum cobalamin and folate concentrations in healthy dogs.

PubMed

Lucena, R; Olmedilla, A B; Blanco, B; Novales, M; Ginel, P J

2018-04-17

To study the effect of a 14-day administration of the probiotic Enterococcus faecium SF68 on serum concentrations of cobalamin and folate in healthy dogs. Thirty-six healthy dogs were randomly allocated between probiotic and control groups. Enterococcus faecium SF68 was administered to the probiotic group for 14 days whereas the control group did not receive any product. A blood sample was taken from all dogs when starting the administration (day 1), when the administration ended (day 14) and 14 days later (day 28). Serum cobalamin and folate concentrations and the canine inflammatory bowel disease activity index scores were determined at each time point. There was a progressive reduction of mean serum cobalamin in the probiotic group during the 28-day study, with significantly lower concentration at day 28 compared to baseline and day 14 concentrations. Moderate hypocobalaminaemia was observed in eight dogs at day 28. Probiotic administration was associated with a non-significant increase in mean serum folate concentration at day 14, and a significant decrease at day 28 compared with day 1. The canine inflammatory bowel disease activity index score remained unaltered during the study. Short-term Enterococcus faecium SF68 administration caused a significant reduction of mean cobalamin concentration and moderate hypocobolaminaemia in eight of 18 dogs. Monitoring serum folate appears unnecessary because the probiotic caused a non-significant increase that returned to baseline values after administration was discontinued. © 2018 British Small Animal Veterinary Association.

Intrinsic fluorescence biomarkers in cells treated with chemopreventive drugs

NASA Astrophysics Data System (ADS)

Kirkpatrick, Nathaniel D.; Brands, William R.; Zou, Changping; Brewer, Molly A.; Utzinger, Urs

2005-03-01

Non-invasive monitoring of cellular metabolism offers promising insights into areas ranging from biomarkers for drug activity to cancer diagnosis. Fluorescence spectroscopy can be utilized in order to exploit endogenous fluorophores, typically metabolic co-factors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), and estimate the redox status of the sample. Fluorescence spectroscopy was applied to follow metabolic changes in epithelial ovarian cells as well as bladder epithelial cancer cells during treatment with a chemopreventive drug that initiates cellular quiescence. Fluorescence signals consistent with NADH, FAD, and tryptophan were measured to monitor cellular activity, redox status, and protein content. Cells were treated with varying concentrations of N-4-(hydroxyphenyl) retinamide (4-HPR) and measured in a stable environment with a sensitive fluorescence spectrometer. A subset of measurements was completed on a low concentration of cells to demonstrate feasibility for medical application such as in bladder or ovary washes. Results suggest that all of the cells responded with similar dose dependence but started at different estimated redox ratio baseline levels correlating with cell cycle, growth inhibition, and apoptosis assays. NADH and tryptophan related fluorescence changed significantly while FAD related fluorescence remained unaltered. Fluorescence data collected from approximately 1000 - 2000 cells, comparable to a bladder or ovary wash, was measurable and useful for future experiments. This study suggests that future intrinsic biomarker measurements may need to be most sensitive to changes in NADH and tryptophan related fluorescence while using FAD related fluorescence to help estimate the baseline redox ratio and predict response to chemopreventive agents.

Immobilization of Bacillus sp. in mesoporous activated carbon for degradation of sulphonated phenolic compound in wastewater.

PubMed

Sekaran, G; Karthikeyan, S; Gupta, V K; Boopathy, R; Maharaja, P

2013-03-01

Xenobiotic compounds are used in considerable quantities in leather industries besides natural organic and inorganic compounds. These compounds resist biological degradation and thus they remain in the treated wastewater in the unaltered molecular configurations. Immobilization of organisms in carrier matrices protects them from shock load application and from the toxicity of chemicals in bulk liquid phase. Mesoporous activated carbon (MAC) has been considered in the present study as the carrier matrix for the immobilization of Bacillus sp. isolated from Effluent Treatment Plant (ETP) employed for the treatment of wastewater containing sulphonated phenolic (SP) compounds. Temperature, pH, concentration, particle size and mass of MAC were observed to influence the immobilization behavior of Bacillus sp. The percentage immobilization of Bacillus sp. was the maximum at pH 7.0, temperature 20 °C and at particle size 300 μm. Enthalpy, free energy and entropy of immobilization were -46.9 kJ mol(-1), -1.19 kJ mol(-1) and -161.36 JK(-1)mol(-1) respectively at pH 7.0, temperature 20 °C and particle size 300 μm. Higher values of ΔH(0) indicate the firm bonding of the Bacillus sp. in MAC. Degradation of aqueous sulphonated phenolic compound by Bacillus sp. immobilized in MAC followed pseudo first order rate kinetics with rate constant 1.12 × 10(-2) min(-1). Copyright © 2012 Elsevier B.V. All rights reserved.

Adaptations of motoneuron properties to chronic compensatory muscle overload

PubMed Central

Hałuszka, A.; Mrówczyński, W.; Gardiner, P. F.; Celichowski, J.

2015-01-01

The aim of the study was to determine whether chronic muscle overload has measurable effect on electrophysiological properties of motoneurons (MNs), and whether duration of this overload influences intensity of adaptations. The compensatory overload was induced in the rat medial gastrocnemius (MG) by bilateral tenotomy of its synergists (lateral gastrocnemius, soleus, and plantaris); as a result, only the MG was able to evoke the foot plantar flexion. To assure regular activation of the MG muscle, rats were placed in wheel-equipped cages and subjected to a low-level treadmill exercise. The intracellular recordings from MG motoneurons were made after 5 or 12 wk of the overload, and in a control group of intact rats. Some of the passive and threshold membrane properties as well as rhythmic firing properties were considerably modified in fast-type MNs, while remaining unaltered in slow-type MNs. The significant changes included a shortening of the spike duration and the spike rise time, an increase of the afterhyperpolarization amplitude, an increase of the input resistance, a decrease of the rheobase, and a decrease of the minimum current necessary to evoke steady-state firing. The data suggest higher excitability of fast-type MNs innervating the overloaded muscle, and a shift towards electrophysiological properties of slow-type MNs. All of the adaptations could be observed after 5 wk of the compensatory overload with no further changes occurring after 12 wk. This indicates that the response to an increased level of chronic activation of MNs is relatively quick and stable. PMID:25695651

Factors affecting the performance of a single-chamber microbial fuel cell-type biological oxygen demand sensor.

PubMed

Yang, Gai-Xiu; Sun, Yong-Ming; Kong, Xiao-Ying; Zhen, Feng; Li, Ying; Li, Lian-Hua; Lei, Ting-Zhou; Yuan, Zhen-Hong; Chen, Guan-Yi

2013-01-01

Microbial fuel cells (MFCs) are devices that exploit microorganisms as biocatalysts to degrade organic matter or sludge present in wastewater (WW), and thereby generate electricity. We developed a simple, low-cost single-chamber microbial fuel cell (SCMFC)-type biochemical oxygen demand (BOD) sensor using carbon felt (anode) and activated sludge, and demonstrated its feasibility in the construction of a real-time BOD measurement system. Further, the effects of anodic pH and organic concentration on SCMFC performance were examined, and the correlation between BOD concentration and its response time was analyzed. Our results demonstrated that the SCMFC exhibited a stable voltage after 132 min following the addition of synthetic WW (BOD concentration: 200 mg/L). Notably, the response signal increased with an increase in BOD concentration (range: 5-200 mg/L) and was found to be directly proportional to the substrate concentration. However, at higher BOD concentrations (>120 mg/L) the response signal remained unaltered. Furthermore, we optimized the SCMFC using synthetic WW, and tested it with real WW. Upon feeding real WW, the BOD values exhibited a standard deviation from 2.08 to 8.3% when compared to the standard BOD5 method, thus demonstrating the practical applicability of the developed system to real treatment effluents.

Ascorbate modulates antibacterial mechanisms in experimental pneumococcal pneumonia.

PubMed

Esposito, A L

1986-04-01

To evaluate the influence of vitamin C on pulmonary antibacterial mechanisms, normal CD-1 mice were administered sodium ascorbate (200 mg/kg/24 h) and challenged intratracheally with type 3 Streptococcus pneumoniae. Survival rates were similar in ascorbate-treated and control animals. When infected with a high inoculum (1 X 10(6) cfu), animals given vitamin C demonstrated a significant enhancement in their capacity to clear viable pneumococci from the lungs at 24 h after challenge; the augmented pulmonary clearance was associated with an increased influx of granulocytes at 6 and 24 h. After infection with a lower inoculum (1 X 10(5) cfu), animals treated with the vitamin exhibited a significant advantage in pulmonary clearance and granulocyte recruitment but at 6 h only. After a very low inoculum challenge (1 X 10(4) cfu), the clearance of viable pneumococci was retarded in ascorbate-treated mice. In vitro, the pneumococcidal capacity of resident alveolar macrophages from animals given vitamin C was significantly reduced, but the ability of these cells to generate leukocyte chemoattractant activity after stimulation with the calcium ionophore A23187 remained unaltered. We conclude that in the mouse, large doses of vitamin C alter pulmonary defense mechanisms against S. pneumoniae; however, these changes do not appear to convey a substantial advantage to the host.

Nonadiabatic small-polaron hopping conduction in Li-doped and undoped Bi4Sr3Ca3CuyOx (0<=y<=5)

NASA Astrophysics Data System (ADS)

Mollah, S.; Som, K. K.; Bose, K.; Chakravorty, A. K.; Chaudhuri, B. K.

1992-11-01

Detailed experimental results of temperature- and CuO-concentration-dependent dc conductivities of semiconducting Bi4Sr3Ca3CuyOx (y=0 to 5) and Li-doped Bi4Sr3Ca3-zLizCu4Ox (z=0.1, 0.5, and 1.0) glasses are reported. The variation of activation energy with glass compositions dominates the conductivity. Unlike many glasses with transition-metal ions, a strong preexponential factor containing the ``small-polaron'' tunneling term [exp(-2αR)] is observed. Nonadiabatic small-polaron hopping mechanism is found to be appropriate for explaining the conductivity data of both glass systems. Addition of alkali-metal ions decreases the conductivities and causes appreciable change of some model parameters obtained from least-squares fittings of the experimental data. The overall thermal behavior of the electrical conductivities of the glasses, however, remains unaltered. This indicates that small (less than 10 wt.%) amount of Li or other alkali-metal ions in these glasses acts as a flux to keep the oxygen content fixed in the corresponding glass-ceramic (superconducting) phases. This in turn helps increase the superconducting transition temperature of the glass ceramics and also lower the sintering and melting temperatures of the glasses.

Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep Brain Stimulation.

PubMed

Etiévant, A; Oosterhof, C; Bétry, C; Abrial, E; Novo-Perez, M; Rovera, R; Scarna, H; Devader, C; Mazella, J; Wegener, G; Sánchez, C; Dkhissi-Benyahya, O; Gronfier, C; Coizet, V; Beaulieu, J M; Blier, P; Lucas, G; Haddjeri, N

2015-08-01

Although deep brain stimulation (DBS) shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC) DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K(+) buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz) DBS. It is proposed that an unaltered neuronal-glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders.

Midgut microbiota and host immunocompetence underlie Bacillus thuringiensis killing mechanism

PubMed Central

Caccia, Silvia; Di Lelio, Ilaria; La Storia, Antonietta; Marinelli, Adriana; Varricchio, Paola; Franzetti, Eleonora; Banyuls, Núria; Tettamanti, Gianluca; Casartelli, Morena; Giordana, Barbara; Ferré, Juan; Gigliotti, Silvia; Pennacchio, Francesco

2016-01-01

Bacillus thuringiensis is a widely used bacterial entomopathogen producing insecticidal toxins, some of which are expressed in insect-resistant transgenic crops. Surprisingly, the killing mechanism of B. thuringiensis remains controversial. In particular, the importance of the septicemia induced by the host midgut microbiota is still debated as a result of the lack of experimental evidence obtained without drastic manipulation of the midgut and its content. Here this key issue is addressed by RNAi-mediated silencing of an immune gene in a lepidopteran host Spodoptera littoralis, leaving the midgut microbiota unaltered. The resulting cellular immunosuppression was characterized by a reduced nodulation response, which was associated with a significant enhancement of host larvae mortality triggered by B. thuringiensis and a Cry toxin. This was determined by an uncontrolled proliferation of midgut bacteria, after entering the body cavity through toxin-induced epithelial lesions. Consequently, the hemolymphatic microbiota dramatically changed upon treatment with Cry1Ca toxin, showing a remarkable predominance of Serratia and Clostridium species, which switched from asymptomatic gut symbionts to hemocoelic pathogens. These experimental results demonstrate the important contribution of host enteric flora in B. thuringiensis-killing activity and provide a sound foundation for developing new insect control strategies aimed at enhancing the impact of biocontrol agents by reducing the immunocompetence of the host. PMID:27506800

Regional-specific effect of fluoxetine on rapidly dividing progenitors along the dorsoventral axis of the hippocampus.

PubMed

Zhou, Qi-Gang; Lee, Daehoon; Ro, Eun Jeoung; Suh, Hoonkyo

2016-10-19

Hippocampus-dependent cognitive and emotional function appears to be regionally dissociated along the dorsoventral (DV) axis of the hippocampus. Recent observations that adult hippocampal neurogenesis plays a critical role in both cognition and emotion raised an interesting question whether adult neurogenesis within specific subregions of the hippocampus contributes to these distinct functions. We examined the regional-specific and cell type-specific effects of fluoxetine, which requires adult hippocampal neurogenesis to function as an antidepressant, on the proliferation of hippocampal neural stem cells (NSCs). Fluoxetine specifically increased proliferation of NSCs located in the ventral region of the hippocampus while the mitotic index of NSCs in the dorsal portion of the hippocampus remained unaltered. Moreover, within the ventral hippocampus, type II NSC and neuroblast populations specifically responded to fluoxetine, showing increased proliferation; however, proliferation of type I NSCs was unchanged in response to fluoxetine. Activation or inhibition of serotonin receptor 1A (5-HTR1A) recapitulated or abolished the effect of fluoxetine on proliferation of type II NSCs and neuroblast populations in the ventral hippocampus. Our study showed that the effect of fluoxetine on proliferation is dependent upon the type and the position of the NSCs along the DV axis of the hippocampus.

Lack of enzyme induction with oxcarbazepine (600 mg daily) in healthy subjects.

PubMed Central

Larkin, J G; McKee, P J; Forrest, G; Beastall, G H; Park, B K; Lowrie, J I; Lloyd, P; Brodie, M J

1991-01-01

1. Oxcarbazepine (OXC), the 10-keto analogue of carbamazepine (CBZ), has similar anticonvulsant efficacy and possibly improved patient tolerability. Unlike CBZ, it is metabolised by reduction and may not induce hepatic monooxygenase enzymes. 2. Serum concentrations of OXC and its active metabolite 10-OH-carbazepine (10-OH-CZ) were followed after a single 300 mg dose and during and after 300 mg OXC twice daily for 29 doses in eight healthy male volunteers. 3. Antipyrine metabolism, urinary 6-beta-hydroxycortisol excretion, sex hormone binding globulin (SHBG) levels and circulating androgens were measured as indices of hepatic enzyme induction before, during and after treatment with OXC. 4. Elimination half-lives (mean +/- s.e. mean) of 10-OH-CZ were unaltered by 2 weeks' therapy with OXC (before 11.3 +/- 1.1 h; after 13.9 +/- 3 h). Trough plasma concentrations of 10-OH-CZ at steady-state (31 +/- 2.2 mumol l-1) were higher than predicted (16.5 +/- 4 mumol l-1). 5. Antipyrine metabolism, urinary 6-beta-hydroxycortisol excretion, SHBG levels and circulating androgens were unaltered by treatment with OXC. 6. OXC (600 mg daily) does not induce hepatic monooxygenase enzymes and so is likely to have more predictable dose-concentration relationships and to produce fewer physiological and pharmacological interactions than CBZ. PMID:2015172

TCF7L2 mediates the cellular and behavioral response to chronic lithium treatment in animal models.

PubMed

Misztal, Katarzyna; Brozko, Nikola; Nagalski, Andrzej; Szewczyk, Lukasz M; Krolak, Marta; Brzozowska, Katarzyna; Kuznicki, Jacek; Wisniewska, Marta B

2017-02-01

The mechanism of lithium's therapeutic action remains obscure, hindering the discovery of safer treatments for bipolar disorder. Lithium can act as an inhibitor of the kinase GSK3α/β, which in turn negatively regulates β-catenin, a co-activator of LEF1/TCF transcription factors. However, unclear is whether therapeutic levels of lithium activate β-catenin in the brain, and whether this activation could have a therapeutic significance. To address this issue we chronically treated mice with lithium. Although the level of non-phospho-β-catenin increased in all of the brain areas examined, β-catenin translocated into cellular nuclei only in the thalamus. Similar results were obtained when thalamic and cortical neurons were treated with a therapeutically relevant concentration of lithium in vitro. We tested if TCF7L2, a member of LEF1/TCF family that is highly expressed in the thalamus, facilitated the activation of β-catenin. Silencing of Tcf7l2 in thalamic neurons prevented β-catenin from entering the nucleus, even when the cells were treated with lithium. Conversely, when Tcf7l2 was ectopically expressed in cortical neurons, β-catenin shifted to the nucleus, and lithium augmented this process. Lastly, we silenced tcf7l2 in zebrafish and exposed them to lithium for 3 days, to evaluate whether TCF7L2 is involved in the behavioral response. Lithium decreased the dark-induced activity of control zebrafish, whereas the activity of zebrafish with tcf7l2 knockdown was unaltered. We conclude that therapeutic levels of lithium activate β-catenin selectively in thalamic neurons. This effect is determined by the presence of TCF7L2, and potentially contributes to the therapeutic response. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Synaptic Activity and Muscle Contraction Increases PDK1 and PKCβI Phosphorylation in the Presynaptic Membrane of the Neuromuscular Junction.

PubMed

Hurtado, Erica; Cilleros, Víctor; Just, Laia; Simó, Anna; Nadal, Laura; Tomàs, Marta; Garcia, Neus; Lanuza, Maria A; Tomàs, Josep

2017-01-01

Conventional protein kinase C βI (cPKCβI) is a conventional protein kinase C (PKC) isoform directly involved in the regulation of neurotransmitter release in the neuromuscular junction (NMJ). It is located exclusively at the nerve terminal and both synaptic activity and muscle contraction modulate its protein levels and phosphorylation. cPKCβI molecular maturation includes a series of phosphorylation steps, the first of which is mediated by phosphoinositide-dependent kinase 1 (PDK1). Here, we sought to localize PDK1 in the NMJ and investigate the hypothesis that synaptic activity and muscle contraction regulate in parallel PDK1 and cPKCβI phosphorylation in the membrane fraction. To differentiate the presynaptic and postsynaptic activities, we abolished muscle contraction with μ-conotoxin GIIIB (μ-CgTx-GIIIB) in some experiments before stimulation of the phrenic nerve (1 Hz, 30 min). Then, we analyzed total and membrane/cytosol fractions of skeletal muscle by Western blotting. Results showed that PDK1 is located exclusively in the nerve terminal of the NMJ. After nerve stimulation with and without coincident muscle contraction, total PDK1 and phosphorylated PDK1 (pPDK1) protein levels remained unaltered. However, synaptic activity specifically enhanced phosphorylation of PDK1 in the membrane, an important subcellular location for PDK1 function. This increase in pPDK1 coincides with a significant increase in the phosphorylation of its substrate cPKCβI also in the membrane fraction. Moreover, muscle contraction maintains PDK1 and pPDK1 but increases cPKCβI protein levels and its phosphorylation. Thus, even though PDK1 activity is maintained, pcPKCβI levels increase in concordance with total cPKCβI. Together, these results indicate that neuromuscular activity could induce the membrane targeting of pPDK1 in the nerve terminal of the NMJ to promote the phosphorylation of the cPKCβI, which is involved in ACh release.

Synaptic Activity and Muscle Contraction Increases PDK1 and PKCβI Phosphorylation in the Presynaptic Membrane of the Neuromuscular Junction

PubMed Central

Hurtado, Erica; Cilleros, Víctor; Just, Laia; Simó, Anna; Nadal, Laura; Tomàs, Marta; Garcia, Neus; Lanuza, Maria A.; Tomàs, Josep

2017-01-01

Conventional protein kinase C βI (cPKCβI) is a conventional protein kinase C (PKC) isoform directly involved in the regulation of neurotransmitter release in the neuromuscular junction (NMJ). It is located exclusively at the nerve terminal and both synaptic activity and muscle contraction modulate its protein levels and phosphorylation. cPKCβI molecular maturation includes a series of phosphorylation steps, the first of which is mediated by phosphoinositide-dependent kinase 1 (PDK1). Here, we sought to localize PDK1 in the NMJ and investigate the hypothesis that synaptic activity and muscle contraction regulate in parallel PDK1 and cPKCβI phosphorylation in the membrane fraction. To differentiate the presynaptic and postsynaptic activities, we abolished muscle contraction with μ-conotoxin GIIIB (μ-CgTx-GIIIB) in some experiments before stimulation of the phrenic nerve (1 Hz, 30 min). Then, we analyzed total and membrane/cytosol fractions of skeletal muscle by Western blotting. Results showed that PDK1 is located exclusively in the nerve terminal of the NMJ. After nerve stimulation with and without coincident muscle contraction, total PDK1 and phosphorylated PDK1 (pPDK1) protein levels remained unaltered. However, synaptic activity specifically enhanced phosphorylation of PDK1 in the membrane, an important subcellular location for PDK1 function. This increase in pPDK1 coincides with a significant increase in the phosphorylation of its substrate cPKCβI also in the membrane fraction. Moreover, muscle contraction maintains PDK1 and pPDK1 but increases cPKCβI protein levels and its phosphorylation. Thus, even though PDK1 activity is maintained, pcPKCβI levels increase in concordance with total cPKCβI. Together, these results indicate that neuromuscular activity could induce the membrane targeting of pPDK1 in the nerve terminal of the NMJ to promote the phosphorylation of the cPKCβI, which is involved in ACh release. PMID:28890686

Living Without Creatine: Unchanged Exercise Capacity and Response to Chronic Myocardial Infarction in Creatine-Deficient Mice

PubMed Central

Lygate, Craig A.; Aksentijevic, Dunja; Dawson, Dana; Hove, Michiel ten; Phillips, Darci; de Bono, Joseph P.; Medway, Debra J.; Sebag-Montefiore, Liam; Hunyor, Imre; Channon, Keith M.; Clarke, Kieran; Zervou, Sevasti; Watkins, Hugh; Balaban, Robert S.; Neubauer, Stefan

2014-01-01

Rationale Creatine is thought to be involved in the spatial and temporal buffering of ATP in energetic organs such as heart and skeletal muscle. Creatine depletion affects force generation during maximal stimulation, while reduced levels of myocardial creatine are a hallmark of the failing heart, leading to the widely held view that creatine is important at high workloads and under conditions of pathological stress. Objective We therefore hypothesised that the consequences of creatine-deficiency in mice would be impaired running capacity, and exacerbation of heart failure following myocardial infarction. Methods and Results Surprisingly, mice with whole-body creatine deficiency due to knockout of the biosynthetic enzyme (guanidinoacetate N-methyltransferase – GAMT) voluntarily ran just as fast and as far as controls (>10km/night) and performed the same level of work when tested to exhaustion on a treadmill. Furthermore, survival following myocardial infarction was not altered, nor was subsequent LV remodelling and development of chronic heart failure exacerbated, as measured by 3D-echocardiography and invasive hemodynamics. These findings could not be accounted for by compensatory adaptations, with no differences detected between WT and GAMT−/− proteomes. Alternative phosphotransfer mechanisms were explored; adenylate kinase activity was unaltered, and although GAMT−/− hearts accumulated the creatine pre-cursor guanidinoacetate, this had negligible energy-transfer activity, while mitochondria retained near normal function. Conclusions Creatine-deficient mice show unaltered maximal exercise capacity and response to chronic myocardial infarction, and no obvious metabolic adaptations. Our results question the paradigm that creatine is essential for high workload and chronic stress responses in heart and skeletal muscle. PMID:23325497

Early-life inflammation with LPS delays fear extinction in adult rodents.

PubMed

Doenni, V M; Song, C M; Hill, M N; Pittman, Q J

2017-07-01

A large body of evidence has been brought forward connecting developmental immune activation to abnormal fear and anxiety levels. Anxiety disorders have extremely high lifetime prevalence, yet susceptibility factors that contribute to their emergence are poorly understood. In this research we investigated whether an inflammatory insult early in life can alter the response to fear conditioning in adulthood. Fear learning and extinction are important and adaptive behaviors, mediated largely by the amygdala and its interconnectivity with cortico-limbic circuits. Male and female rat pups were given LPS (100μg/kg i.p.) or saline at postnatal day 14; LPS activated cFos expression in the central amygdala 2.5h after exposure, but not the basal or lateral nuclei. When tested in adulthood, acquisition of an auditory cued or contextual learned fear memory was largely unaffected as was the extinction of fear to a conditioned context. However, we detected a deficit in auditory fear extinction in male and female rats that experienced early-life inflammation, such that there is a significant delay in fear extinction processes resulting in more sustained fear behaviors in response to a conditioned cue. This response was specific to extinction training and did not persist into extinction recall. The effect could not be explained by differences in pain threshold (unaltered) or in baseline anxiety, which was elevated in adolescent females only and unaltered in adolescent males and adult males and females. This research provides further evidence for the involvement of the immune system during development in the shaping of fear and anxiety related behaviors. Copyright © 2016 Elsevier Inc. All rights reserved.

Silver Nanoparticles Synthesized Using Mint Extract and their Application in Chitosan/Gelatin Composite Packaging Film

NASA Astrophysics Data System (ADS)

Bhoir, Shraddha A.; Chawla, S. P.

The present study reports synthesis of silver nanoparticles (AgNPs) using mint extract (ME) in the presence of polyvinyl alcohol (PVA) as capping material. PVA, ME and silver nitrate at concentration of 1%, 0.01% and 0.02%, respectively were found to be optimum for the synthesis of nanoparticles. The formation of AgNPs was confirmed by measuring surface plasmon resonance (SPR) peak. The intensity of SPR peak remained unaltered thus suggesting stability of colloid without aggregation during storage. The nanoparticles inhibited the growth of food borne bacteria namely Escherichia coli, Pseudomonas aeruginosa and Bacillus cereus. The incorporation of these nanoparticles in chitosan and gelatin blend resulted in homogenous films. Mechanical properties and water vapor transmission rate of chitosan-gelatin films improved due to addition of AgNPs, whereas optical (opacity and UV light transmittance) and oxygen permeability properties remained unchanged. These films had the ability to inhibit growth of 5 log CFU of the above test organisms. These findings suggest that the AgNPs obtained by reduction of silver by ME can be effectively utilized to prepare antibacterial eco-friendly food packaging material.

Could the Mantle Under Island Arcs Contribute to Long Wavelength Magnetic Anomalies?

NASA Astrophysics Data System (ADS)

Friedman, S. A.; Ferre, E. C.; Martin-Hernandez, F.; Feinberg, J. M.; Conder, J. A.

2016-12-01

Some island arcs show significant long-wavelength positive magnetic anomalies with potential sources in the mantle wedge while others do not. Here we compare the magnetic properties of mantle xenoliths form metasomatized mantle wedges with counterparts from pristine unaltered mantle and we discuss the role mantle processes may play in producing these anomalies. Samples for this study originate from four localities displaying different degrees of metasomatism, as evidenced by the presence of phlogophite, pargasite, and secondary minerals (olv, cpx, opx): a) Five samples from Ichinomegata crater, Megata volcano, in NE Japan are characteristically lherzolitic with metasomatic pargasite present; b) Six samples from Kurose, SW Japan are mainly harzburgites that contain rare, late stage metasomatic sulfides; c) Ten samples from the Iraya volcano, Batan Island, in the Philippines are lherzolites, harzburgites, and dunites that contain metasomatic olivine, orthopyroxene, clinopyroxene and pargasite; and d) Ten samples from Avacha and Shiveluch volcanoes in Kamchatka, consists of unaltered harzburgites supported by an LOI <1%. Sample localities come from subduction zones of the western Pacific Ocean, where the angle of subduction varies (from 10° in SW Japan to 55° in the Kamchatka and Taiwan-Luzon arcs). When present, ferromagnetic minerals include stoichiometric magnetite with occasional pyrrhotite only in metasomatized samples. Ultimately, metasomatized mantle material has a Koenigsberger ratio less than 1.0 indicating it would not primarily contribute to satellite-altitude magnetic anomalies. While unaltered mantle material may produce a Koenigsberger ratio greater than 1.0, and would thus, contribute to long wavelength magnetic anomalies. The presence of both metasomatized and unaltered mantle material beneath island arcs would be supportive of the positive magnetic anomaly found in some subduction zones.

Cross-modal enhancement of speech detection in young and older adults: does signal content matter?

PubMed

Tye-Murray, Nancy; Spehar, Brent; Myerson, Joel; Sommers, Mitchell S; Hale, Sandra

2011-01-01

The purpose of the present study was to examine the effects of age and visual content on cross-modal enhancement of auditory speech detection. Visual content consisted of three clearly distinct types of visual information: an unaltered video clip of a talker's face, a low-contrast version of the same clip, and a mouth-like Lissajous figure. It was hypothesized that both young and older adults would exhibit reduced enhancement as visual content diverged from the original clip of the talker's face, but that the decrease would be greater for older participants. Nineteen young adults and 19 older adults were asked to detect a single spoken syllable (/ba/) in speech-shaped noise, and the level of the signal was adaptively varied to establish the signal-to-noise ratio (SNR) at threshold. There was an auditory-only baseline condition and three audiovisual conditions in which the syllable was accompanied by one of the three visual signals (the unaltered clip of the talker's face, the low-contrast version of that clip, or the Lissajous figure). For each audiovisual condition, the SNR at threshold was compared with the SNR at threshold for the auditory-only condition to measure the amount of cross-modal enhancement. Young adults exhibited significant cross-modal enhancement with all three types of visual stimuli, with the greatest amount of enhancement observed for the unaltered clip of the talker's face. Older adults, in contrast, exhibited significant cross-modal enhancement only with the unaltered face. Results of this study suggest that visual signal content affects cross-modal enhancement of speech detection in both young and older adults. They also support a hypothesized age-related deficit in processing low-contrast visual speech stimuli, even in older adults with normal contrast sensitivity.

Interleukin (IL)-23 Stimulates IFN-γ Secretion by CD56bright Natural Killer Cells and Enhances IL-18-Driven Dendritic Cells Activation.

PubMed

Ziblat, Andrea; Nuñez, Sol Y; Raffo Iraolagoitia, Ximena Lucía; Spallanzani, Raúl German; Torres, Nicolás I; Sierra, Jessica M; Secchiari, Florencia; Domaica, Carolina I; Fuertes, Mercedes B; Zwirner, Norberto W

2017-01-01

Interleukin (IL)-23 is a member of the IL-12 family of cytokines that, as the other members of this family, is secreted by monocytes, macrophages, and dendritic cells (DC) upon recognition of bacterial, viral, and fungal components. IL-23 is critical during immunity against acute infections, and it is also involved in the development of autoimmune diseases. Although immunoregulatory effects of IL-23 on mouse natural killer (NK) cells have been described, the effect of IL-23 on human NK cells remains ill-defined. In this study, we observed that monocytes stimulated with LPS secreted IL-23 and that blockade of this cytokine during monocyte and NK cell coculture led to a diminished production of IFN-γ by NK cells. Accordingly, rIL-23-induced NK cell activation and stimulated IFN-γ production by CD56 bright NK cells. This effect involved MEK1/MEK2, JNK, PI3K, mammalian target of rapamycin, and NF-κB, but not STAT-1, STAT-3, nor p38 MAPK pathways. Moreover, while NK cell-mediated cytotoxicity remained unaltered, antibody-dependent cellular cytotoxicity (ADCC) was enhanced after IL-23 stimulation. In addition, IL-23 displayed a synergistic effect with IL-18 for IFN-γ production by both CD56 bright and CD56 dim NK cells, and this effect was due to a priming effect of IL-23 for IL-18 responsiveness. Furthermore, NK cells pre-stimulated with IL-18 promoted an increase in CD86 expression and IL-12 secretion by DC treated with LPS, and IL-23 potentiated these effects. Moreover, IL-23-driven enhancement of NK cell "helper" function was dependent on NK cell-derived IFN-γ. Therefore, our results suggest that IL-23 may trigger NK cell-mediated "helper" effects on adaptive immunity, shaping T cell responses during different pathological situations through the regulation of DC maturation.

Interleukin (IL)-23 Stimulates IFN-γ Secretion by CD56bright Natural Killer Cells and Enhances IL-18-Driven Dendritic Cells Activation

PubMed Central

Ziblat, Andrea; Nuñez, Sol Y.; Raffo Iraolagoitia, Ximena Lucía; Spallanzani, Raúl German; Torres, Nicolás I.; Sierra, Jessica M.; Secchiari, Florencia; Domaica, Carolina I.; Fuertes, Mercedes B.; Zwirner, Norberto W.

2018-01-01

Interleukin (IL)-23 is a member of the IL-12 family of cytokines that, as the other members of this family, is secreted by monocytes, macrophages, and dendritic cells (DC) upon recognition of bacterial, viral, and fungal components. IL-23 is critical during immunity against acute infections, and it is also involved in the development of autoimmune diseases. Although immunoregulatory effects of IL-23 on mouse natural killer (NK) cells have been described, the effect of IL-23 on human NK cells remains ill-defined. In this study, we observed that monocytes stimulated with LPS secreted IL-23 and that blockade of this cytokine during monocyte and NK cell coculture led to a diminished production of IFN-γ by NK cells. Accordingly, rIL-23-induced NK cell activation and stimulated IFN-γ production by CD56bright NK cells. This effect involved MEK1/MEK2, JNK, PI3K, mammalian target of rapamycin, and NF-κB, but not STAT-1, STAT-3, nor p38 MAPK pathways. Moreover, while NK cell-mediated cytotoxicity remained unaltered, antibody-dependent cellular cytotoxicity (ADCC) was enhanced after IL-23 stimulation. In addition, IL-23 displayed a synergistic effect with IL-18 for IFN-γ production by both CD56bright and CD56dim NK cells, and this effect was due to a priming effect of IL-23 for IL-18 responsiveness. Furthermore, NK cells pre-stimulated with IL-18 promoted an increase in CD86 expression and IL-12 secretion by DC treated with LPS, and IL-23 potentiated these effects. Moreover, IL-23-driven enhancement of NK cell “helper” function was dependent on NK cell-derived IFN-γ. Therefore, our results suggest that IL-23 may trigger NK cell-mediated “helper” effects on adaptive immunity, shaping T cell responses during different pathological situations through the regulation of DC maturation. PMID:29403472

Reduced task-induced variations in the distribution of activity across back muscle regions in individuals with low back pain.

PubMed

Falla, Deborah; Gizzi, Leonardo; Tschapek, Marika; Erlenwein, Joachim; Petzke, Frank

2014-05-01

This study investigated change in the distribution of lumbar erector spinae muscle activity and pressure pain sensitivity across the low back in individuals with low back pain (LBP) and healthy controls. Surface electromyographic (EMG) signals were recorded from multiple locations over the lumbar erector spinae muscle with a 13×5 grid of electrodes from 19 people with chronic nonspecific LBP and 17 control subjects as they performed a repetitive lifting task. The EMG root mean square (RMS) was computed for each location of the grid to form a map of the EMG amplitude distribution. Pressure pain thresholds (PPT) were recorded before and after the lifting task over a similar area of the back. For the control subjects, the EMG RMS progressively increased more in the caudal region of the lumbar erector spinae during the repetitive task, resulting in a shift in the distribution of muscle activity. In contrast, the distribution of muscle activity remained unaltered in the LBP group despite an overall increase in EMG amplitude. PPT was lower in the LBP group after completion of the repetitive task compared to baseline (average across all locations: pre: 268.0±165.9 kPa; post: 242.0±166.7 kPa), whereas no change in PPT over time was observed for the control group (320.1±162.1 kPa; post: 322.0±179.5 kPa). The results demonstrate that LBP alters the normal adaptation of lumbar erector spinae muscle activity to exercise, which occurs in the presence of exercise-induced hyperalgesia. Reduced variability of muscle activity may have important implications for the provocation and recurrence of LBP due to repetitive tasks. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Depressed Frank-Starling mechanism in the left ventricular muscle of the knock-in mouse model of dilated cardiomyopathy with troponin T deletion mutation ΔK210.

PubMed

Inoue, Takahiro; Kobirumaki-Shimozawa, Fuyu; Kagemoto, Tatsuya; Fujii, Teruyuki; Terui, Takako; Kusakari, Yoichiro; Hongo, Kenichi; Morimoto, Sachio; Ohtsuki, Iwao; Hashimoto, Kazuhiro; Fukuda, Norio

2013-10-01

It has been reported that the Frank-Starling mechanism is coordinately regulated in cardiac muscle via thin filament "on-off" equilibrium and titin-based lattice spacing changes. In the present study, we tested the hypothesis that the deletion mutation ΔK210 in the cardiac troponin T gene shifts the equilibrium toward the "off" state and accordingly attenuate the sarcomere length (SL) dependence of active force production, via reduced cross-bridge formation. Confocal imaging in isolated hearts revealed that the cardiomyocytes were enlarged, especially in the longitudinal direction, in ΔK210 hearts, with striation patterns similar to those in wild type (WT) hearts, suggesting that the number of sarcomeres is increased in cardiomyocytes but the sarcomere length remains unaltered. For analysis of the SL dependence of active force, skinned muscle preparations were obtained from the left ventricle of WT and knock-in (ΔK210) mice. An increase in SL from 1.90 to 2.20μm shifted the mid-point (pCa50) of the force-pCa curve leftward by ~0.21pCa units in WT preparations. In ΔK210 muscles, Ca(2+) sensitivity was lower by ~0.37pCa units, and the SL-dependent shift of pCa50, i.e., ΔpCa50, was less pronounced (~0.11pCa units), with and without protein kinase A treatment. The rate of active force redevelopment was lower in ΔK210 preparations than in WT preparations, showing blunted thin filament cooperative activation. An increase in thin filament cooperative activation upon an increase in the fraction of strongly bound cross-bridges by MgADP increased ΔpCa50 to ~0.21pCa units. The depressed Frank-Starling mechanism in ΔK210 hearts is the result of a reduction in thin filament cooperative activation. © 2013.

The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

PubMed

Glynn, Nigel; Kenny, Helena; Quisenberry, Leah; Halsall, David J; Cook, Paul; Kyaw Tun, Tommy; McDermott, John H; Smith, Diarmuid; Thompson, Christopher J; O'Gorman, Donal J; Boelen, Anita; Lado-Abeal, Joaquin; Agha, Amar

2017-05-01

Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. A prospective, observational study of patients receiving GH replacement as part of routine clinical care. Twenty adult hypopituitary men. Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle. © 2016 John Wiley & Sons Ltd.

Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum

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

Wu, Yang-Chang; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan; Sureshbabu, Munisamy

Fissistigma bracteolatum is widely used in traditional medicine to treat inflammatory diseases. However, its active components and mechanisms of action remain unclear. In this study, (3Z)-6,7-dihydroxy-4-methoxy-3-(phenylmethylidene)-5-(3-phenylpropanoyl) -1-benzofuran-2(3H) (bractelactone), a novel chalcone from F. bracteolatum, showed potent inhibitory effects against superoxide anion (O{sub 2}{sup ·−}) production, elastase release, and CD11b expression in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced human neutrophils. However, bractelactone showed only weak inhibition of phorbol myristate acetate-caused O{sub 2}{sup ·−} production. The peak cytosolic calcium concentration ([Ca{sup 2+}]{sub i}) was unaltered by bractelactone in FMLP-induced neutrophils, but the decay time of [Ca{sup 2+}]{sub i} was significantly shortened. In a calcium-free solution, changesmore » in [Ca{sup 2+}]{sub i} caused by the addition of extracellular Ca{sup 2+} were inhibited by bractelactone in FMLP-activated cells. In addition, bractelactone did not alter the phosphorylation of p38 MAPK, ERK, JNK, or AKT or the concentration of cAMP. These results suggest that bractelactone selectively inhibits store-operated calcium entry (SOCE). In agreement with this concept, bractelactone suppressed sustained [Ca{sup 2+}]{sub i} changes in thapsigargin-activated neutrophils. Furthermore, bractelactone did not alter FMLP-induced formation of inositol 1,4,5-triphosphate. Taken together, our results demonstrate that the anti-inflammatory effects of bractelactone, an active ingredient of F. bracteolatum, in human neutrophils are through the selective inhibition of SOCE. Highlights: ► Bractelactone isolated from Fissistigma bracteolatum. ► Bractelactone inhibited FMLP-induced human neutrophil activations. ► Bractelactone had no effect on IP3 formation. ► Bractelactone did not alter MAPKs, AKT, and cAMP pathways. ► Bractelactone inhibited store-operated calcium entry.« less

Transformation of Mouse Macrophages by Simian Virus 40

PubMed Central

Stone, Lawrence B.; Takemoto, Kenneth K.

1970-01-01

Studies were undertaken to prove that simian virus 40 (SV40) can transform the mouse macrophage, a cell type naturally restricted from deoxyribonucleic acid (DNA) replication. Balb/C macrophages infected with SV40 demonstrated T-antigen production and induced DNA synthesis simultaneously. In the absence of apparent division, these cells remained T antigen-positive for at least 45 days. SV40 could be rescued from nondividing, unaltered macrophages during the T antigen-producing period. Proliferating transformants appeared at an average of 66 days post-SV40 infection. Established cell lines were T antigen-positive and were negative for infectious virus, but yielded SV40 after fusion with African green monkey kidney cells. Their identity as transformed macrophages was substantiated by evaluation of cellular morphology, phagocytosis, acid phosphatase, β1c synthesis, and aminoacridine incorporation. Images PMID:4320698

Recycled-tire pyrolytic carbon made functional: A high-arsenite [As(III)] uptake material PyrC350®.

PubMed

Mouzourakis, E; Georgiou, Y; Louloudi, M; Konstantinou, I; Deligiannakis, Y

2017-03-15

A novel material, PyrC 350 ® , has been developed from pyrolytic-tire char (PyrC), as an efficient low-cost Arsenite [As(III)] adsorbent from water. PyrC 350 ® achieves 31mgg -1 As(III) uptake, that remains unaltered at pH=4-8.5. A theoretical Surface Complexation Model has been developed that explains the adsorption mechanism, showing that in situ formed Fe 3 C, ZnS particles act cooperatively with the carbon matrix for As(III) adsorption. Addressing the key-issue of cost-effectiveness, we provide a comparison of As(III)-uptake effectiveness in conjunction with a cost analysis, showing that PyrC 350 ® stands in the top of [effectiveness/cost] vs. existing carbon-based, low-cost materials. Copyright © 2016 Elsevier B.V. All rights reserved.

Pre-task music improves swimming performance.

PubMed

Smirmaul, B P; Dos Santos, R V; Da Silva Neto, L V

2015-12-01

The purpose of this study was to investigate the effects of pre-task music on swimming performance and other psychological variables. A randomized counterbalanced within-subjects (experimental and control condition) design was employed. Eighteen regional level male swimmers performed two 200-m freestyle swimming time trials. Participants were exposed to either 5 minutes of self-selected music (pre-task music condition) or 5 minutes of silence (control condition) and, after 1 minute, performed the swimming task. Swimming time was significantly shorter (-1.44%) in the pre-task music condition. Listening to pre-task music increased motivation to perform the swimming task, while arousal remained unchanged. While fatigue increased after the swimming task in both conditions, vigor, ratings of perceived exertion and affective valence were unaltered. It is concluded, for the first time, that pre-task music improves swimming performance.

Orthograde retreatment failure with extruded MTA apical plug in a large periradicular lesion followed by surgical intervention: case report.

PubMed

Brito-Junior, Manoel; Faria-e-Silva, Andre Luis; Quintino, Alex Carvalho; Moreira-Junior, Gil; Geber, Mauro; Camilo, Carla Cristina; Soares, Janir Alves

2012-01-01

Absence of periapical healing after orthograde retreatment using an apical plug with mineral trioxide aggregate (MTA) can require surgical intervention. A patient with a root-filled maxillary central incisor with chronic apical periodontitis and sinus tract was referred for endodontic retreatment. Excessive apical enlargement was verified, indicating an MTA apical plug placement; however, an unintentional extrusion of MTA occurred during this step. The root canal was filled with gutta-percha and sealer, and periodic recalls were scheduled. The sinus tract was observed after six months and the lesion remained unaltered, although the extruded MTA had resorbed; therefore, an apicoectomy and retrograde root-end filling with MTA were performed. Absence of sinus tract, normal clinical aspect, and complete repair of the lesion were observed at the two-year follow-up.

Magnetic property zonation in a thick lava flow

NASA Astrophysics Data System (ADS)

Audunsson, Haraldur; Levi, Shaul; Hodges, Floyd

1992-04-01

Intraflow structures and magmatic evolution in an extensive and thick (30-60 m) basaltic lava flow are examined on the basis of grain size and composition-dependent magnetic properties of titanomagnetite materials. Microprobe data indicate that the intraflow oxidation state Fe(3+)/Fe(2+) of the initially precipitated primary titanomagnetites increases with falling equilibrium temperature from the flow margins to a maximum near the center, the position of lowest equilibrium temperature. In contrast, Curie temperature measurements indicate that titanomagnetite oxidation increases with height in the flow. Modification of the initially symmetric equilibrium titanomagnetite compositions was caused by subsolidus high-temperature oxidation possibly due to hydrogen loss produced by dissociation of magmatic water, as well as unknown contributions of circulating air and percolating water from above. The titanomagnetites of the basal layer of the flow remain essentially unaltered.

Ischemic preconditioning increases GSK-3β/β-catenin levels and ameliorates liver ischemia/reperfusion injury in rats.

PubMed

Yan, Yichao; Li, Guangying; Tian, Xiaofeng; Ye, Yingjiang; Gao, Zhidong; Yao, Jihong; Zhang, Feng; Wang, Shan

2015-06-01

Ischemic preconditioning (IPC) ameliorates ischemia/reperfusion (I/R) injury in a number of organs, and the glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway regulates I/R-induced proliferation and apoptosis in the central nervous system and heart. However, the function of this signaling pathway in IPC during liver I/R remains unclear. Thus, in this study, we aimed to investigte the role of the GSK-3β/β-catenin pathway during I/R and following ischemic preconditioning. For this purpose, 30 Sprague-Dawley rats were randomly divided into the sham-operated, the I/R and the IPC groups (n=10). Following reperfusion, liver pathology, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), maleic dialdehyde (MDA) and superoxide dismutase (SOD) levels were assessed. Western blot analysis was performed to quantify the GSK-3β, Ser9-phospho-GSK-3β (p-GSK-3β), cytosolic and nuclear β-catenin, vascular endothelial growth factor (VEGF), Bcl-2 and survivin levels. In addition, the Bcl-2 and survivin mRNA levels were assessed by RT-qPCR. Compared with the sham-operated group, I/R increased serum ALT, AST and MDA activity and decreased SOD levels, while IPC significantly decreased serum ALT, AST and MDA activity and increased SOD levels, compared with the I/R group. Simultaneously, I/R increased p-GSK-3β protein expression, and decreased Bcl-2 and survivin protein and mRNA levels. IPC further increased the protein expression of p-GSK-3β, and also increased cytosolic and nuclear β-catenin and VEGF expression compared with the I/R group; the expression of Bcl-2 and survivin was also increased by IPC, both at the mRNA and protein level. The total GSK-3β expression remained unaltered in all the groups. In conclusion, our data demonstrate that IPC exerts protective effects against liver injury induced by I/R and activates the GSK-3β/β-catenin signaling pathway.

Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice.

PubMed

Hänninen, Arno; Toivonen, Raine; Pöysti, Sakari; Belzer, Clara; Plovier, Hubert; Ouwerkerk, Janneke P; Emani, Rohini; Cani, Patrice D; De Vos, Willem M

2017-12-21

Intestinal microbiota is implicated in the pathogenesis of autoimmune type 1 diabetes in humans and in non-obese diabetic (NOD) mice, but evidence on its causality and on the role of individual microbiota members is limited. We investigated if different diabetes incidence in two NOD colonies was due to microbiota differences and aimed to identify individual microbiota members with potential significance. We profiled intestinal microbiota between two NOD mouse colonies showing high or low diabetes incidence by 16S ribosomal RNA gene sequencing and colonised the high-incidence colony with the microbiota of the low-incidence colony. Based on unaltered incidence, we identified a few taxa which were not effectively transferred and thereafter, transferred experimentally one of these to test its potential significance. Although the high-incidence colony adopted most microbial taxa present in the low-incidence colony, diabetes incidence remained unaltered. Among the few taxa which were not transferred, Akkermansia muciniphila was identified. As A. muciniphila abundancy is inversely correlated to the risk of developing type 1 diabetes-related autoantibodies, we transferred A. muciniphila experimentally to the high-incidence colony. A. muciniphila transfer promoted mucus production and increased expression of antimicrobial peptide Reg3γ , outcompeted Ruminococcus torques from the microbiota, lowered serum endotoxin levels and islet toll-like receptor expression, promoted regulatory immunity and delayed diabetes development. Transfer of the whole microbiota may not reduce diabetes incidence despite a major change in gut microbiota, but single symbionts such as A. muciniphila with beneficial metabolic and immune signalling effects may reduce diabetes incidence when administered as a probiotic. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Determinism in fish assemblages of floodplain lakes of the vastly disturbed Mississippi Alluvial Valley

USGS Publications Warehouse

Miranda, L.E.; Lucas, G.M.

2004-01-01

The Mississippi Alluvial Valley between southern Illinois and southern Louisiana contains hundreds of floodplain lakes, most of which have been adversely affected by landscape modifications used to control flooding and support agriculture. We examined fish assemblages in lakes of this region to determine whether deterministic patterns developed in relation to prominent abiotic lake characteristics and to explore whether relevant abiotic factors could be linked to specific assemblage structuring mechanisms. The distributions of 14 taxa in 29 lakes were governed primarily by two gradients that contrasted assemblages in terms of lake area, lake elongation, and water clarity. The knowledge of whether a lake was clear or turbid, large or small, and long or short helped determine fish assemblage characteristics. Abiotic factors influenced fish assemblage structures, plausibly through limitations on foraging and physiological tolerances. Determinism in assemblage organization of floodplain lakes relative to recurrence in physicochemical features has been documented for unaltered rivers. Whereas the Mississippi Alluvial Valley has been subjected to vast anthropogenic disturbances and is not a fully functional floodplain river, fish assemblages in its floodplain lakes remain deterministic and organized by the underlying factors that also dictate assemblages in unaltered rivers. In advanced stages of lake aging, fish assemblages in these lakes are expected to largely include species that thrive in turbid, shallow systems with few predators and low oxygen concentrations. The observed patterns related to physical characteristics of these lakes suggest three general conservation foci, including (1) watershed management to control erosion, (2) removal of sediments or increases in water level to alleviate depth reductions and derived detriments to water physicochemistry, and (3) management of fish populations through stockings, removals, and harvest regulations.

Real-time differentiation of adenomatous and hyperplastic diminutive colorectal polyps during analysis of unaltered videos of standard colonoscopy using a deep learning model.

PubMed

Byrne, Michael F; Chapados, Nicolas; Soudan, Florian; Oertel, Clemens; Linares Pérez, Milagros; Kelly, Raymond; Iqbal, Nadeem; Chandelier, Florent; Rex, Douglas K

2017-10-24

In general, academic but not community endoscopists have demonstrated adequate endoscopic differentiation accuracy to make the 'resect and discard' paradigm for diminutive colorectal polyps workable. Computer analysis of video could potentially eliminate the obstacle of interobserver variability in endoscopic polyp interpretation and enable widespread acceptance of 'resect and discard'. We developed an artificial intelligence (AI) model for real-time assessment of endoscopic video images of colorectal polyps. A deep convolutional neural network model was used. Only narrow band imaging video frames were used, split equally between relevant multiclasses. Unaltered videos from routine exams not specifically designed or adapted for AI classification were used to train and validate the model. The model was tested on a separate series of 125 videos of consecutively encountered diminutive polyps that were proven to be adenomas or hyperplastic polyps. The AI model works with a confidence mechanism and did not generate sufficient confidence to predict the histology of 19 polyps in the test set, representing 15% of the polyps. For the remaining 106 diminutive polyps, the accuracy of the model was 94% (95% CI 86% to 97%), the sensitivity for identification of adenomas was 98% (95% CI 92% to 100%), specificity was 83% (95% CI 67% to 93%), negative predictive value 97% and positive predictive value 90%. An AI model trained on endoscopic video can differentiate diminutive adenomas from hyperplastic polyps with high accuracy. Additional study of this programme in a live patient clinical trial setting to address resect and discard is planned. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Nonmonotonic variation of seawater [sup 87]Sr/[sup 86]Sr across the Ivorian/Chadian boundary (Mississippian, Osagean): Evidence from marine cements within the Irish Waulsortian Limestone

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

Douthit, T.L.; Meyers, W.J.; Hanson, G.N.

1993-05-01

Detailed analysis of compositionally unaltered marine fibrous cements (MFC) from a single core through the Mississippian irish Waulsortian Limestone indicates that the variation of seawater [sup 87]Sr/[sup 86]Sr is nonmonotonic across the Ivorian-Chadian boundary. This nonmonotonic variation has not been recognized by previous studies. Furthermore, marine cement yielded [sup 87]Sr/[sup 86]Sr ratios lower than previously reported values for the Ivorian-Chadian (sagean). Marine fibrous cements are interpreted to be compositionally unaltered on the basis of nonluminescent character and stable isotope (C, O) composition comparable to previous estimates of Mississippian marine calcite. The isotope chemistry (C, O, Sr) and cathodoluminescent character ofmore » the marine fibrous cements therefore remained intact during their conversion from high-Mg calcite to low-Mg calcite + microdolomite, a conversion that probably took place in marine water during precipitation of Zone 1 calcite cement, the oldest non-MFC cement. High stratigraphic resolution was obtained by restricting the sample set to a single core, 429 m long, thereby eliminating chronostratigraphic correlation errors. The core is estimated to represent about 9.8 million years of Waulsortian Limestone deposition. The maximum rate of change in seawater [sup 87]Sr/[sup 86]Sr is [minus]0.00012/Ma, comparable in magnitude to Tertiary values. The authors data document the presence of fine-scale seawater [sup 87]Sr/[sup 86]Sr modulations for the Ivorian/Chadian, in contrast to the previously published monotonic seawater [sup 87]Sr/[sup 86]Sr curve for this interval, and emphasize the importance of well characterized intraformational isotopic baselines.« less

Intermediate-Depth Subduction Earthquakes Recorded by Pseudotachylyte in Dry Eclogite-Facies Oceanic Lithosphere from the Alps

NASA Astrophysics Data System (ADS)

Scambelluri, M.; Pennacchioni, G.; Gilio, M.; Bestmann, M.

2016-12-01

While geophysical studies and laboratory experiments provide much information on subduction earthquakes, field studies identifying the rock types for earthquake development and the deep seismogenic environments are still scarce. To date, fluid overpressure and volume decrease during hydrous mineral breakdown the widely favoured trigger of subduction earthquakes in serpentinized lithospheric mantle and hydrated low-velocity layers atop slabs. Here we document up to 40 cm-thick pseudotachylyte (PST) in Alpine oceanic gabbro and peridotite (2-2.5 GPa-550-620°C), the analogue of a modern cold subducting oceanic lithosphere. These rocks mostly remained unaltered dry systems; only very minor domains (<1%) record partial hydration and static eclogitic metamorphism. Meta-peridotite shows high-pressure olivine + antigorite (garnet + zoisite + chlorite after mantle plagioclase); meta-gabbro develops omphacite + zoisite + talc + chloritoid + garnet. Abundant syn-eclogitic pseudotachylyte cut the dry gabbro-peridotite and the eclogitized domains. In meta-peridotite, PST shows olivine, orthopyroxene, spinel microliths and clasts of high-pressure olivine + antigorite and garnet + zoisite + chlorite aggregates. In metagabbro, microfaults in damage zones near PST cut brecciated igneous pyroxene cemented by omphacite. In unaltered gabbro, glassy PST contains micron-scale garnet replacing plagioclase microliths during, or soon after, PST cooling. In the host rock, garnet coronas between igneous olivine and plagioclase only occur near PST and between closely spaced PST veins. Absence of garnet away from PST indicates that garnet growth was triggered by mineral seeds and by heat released by PST. The above evidence shows that pseudotachylyte formed at eclogite-facies conditions. In such setting, strong, dry, metastable gabbro-peridotite concentrate stress to generate large intermediate depth subduction earthquakes without much involvement of free fluid.

Decreased insulin secretion in pregnant rats fed a low protein diet.

PubMed

Gao, Haijun; Ho, Eric; Balakrishnan, Meena; Yechoor, Vijay; Yallampalli, Chandra

2017-10-01

Low protein (LP) diet during pregnancy leads to reduced plasma insulin levels in rodents, but the underlying mechanisms remain unclear. Glucose is the primary insulin secretagogue, and enhanced glucose-stimulated insulin secretion (GSIS) in beta cells contributes to compensation for insulin resistance and maintenance of glucose homeostasis during pregnancy. In this study, we hypothesized that plasma insulin levels in pregnant rats fed LP diet are reduced due to disrupted GSIS of pancreatic islets. We first confirmed reduced plasma insulin levels, then investigated in vivo insulin secretion by glucose tolerance test and ex vivo GSIS of pancreatic islets in the presence of glucose at different doses, and KCl, glibenclamide, and L-arginine. Main findings include (1) plasma insulin levels were unaltered on day 10, but significantly reduced on days 14-22 of pregnancy in rats fed LP diet compared to those of control (CT) rats; (2) insulin sensitivity was unchanged, but glucose intolerance was more severe in pregnant rats fed LP diet; (3) GSIS in pancreatic islets was lower in LP rats compared to CT rats in the presence of glucose, KCl, and glibenclamide, and the response to L-arginine was abolished in LP rats; and (4) the total insulin content in pancreatic islets and expression of Ins2 were reduced in LP rats, but expression of Gcg was unaltered. These studies demonstrate that decreased GSIS in beta cells of LP rats contributes to reduced plasma insulin levels, which may lead to placental and fetal growth restriction and programs hypertension and other metabolic diseases in offspring. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Brain region-selective cellular redistribution of mGlu5 but not GABA(B) receptors following methamphetamine-induced associative learning.

PubMed

Herrold, Amy A; Voigt, Robin M; Napier, T Celeste

2011-12-01

Alterations in receptor expression and distribution between cell surface and cytoplasm are means by which psychostimulants regulate neurotransmission. Metabotropic glutamate receptor group I, subtype 5 (mGluR5) and GABA(B) receptors (GABA(B) R) are critically involved in the development and expression of stimulant-induced behaviors, including conditioned place preference (CPP), an index of drug-seeking. However, it is not known if psychostimulant-induced CPP alters the trafficking of these receptors. To fill this gap, this study used methamphetamine (Meth)-induced CPP in rats to ascertain if receptor changes occur in limbic brain regions that regulate drug-seeking, the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and ventral pallidum (VP). To do so, ex vivo tissue was assessed for changes in expression and surface vs. intracellular distribution of mGluR5 and GABA(B) Rs. There was a decrease in the surface to intracellular ratio of mGluR5 in the mPFC in Meth-conditioned rats, commensurate with an increase in intracellular levels. mGluR5 levels in the NAc or the VP were unaltered. There were no changes for GABA(B) R in any brain region assayed. This ex vivo snapshot of metabotropic glutamate and GABA receptor cellular distribution following induction of Meth-induced CPP is the first report to determine if these receptors are differentially altered after Meth-induced CPP. The results suggest that this Meth treatment paradigm likely induced a compensatory change in mGluR5 surface to intracellular ratio such that the surface remains unaltered while an increase in intracellular protein occurred. Copyright © 2011 Wiley-Liss, Inc.

The Influence of Mineral Matrices on the Thermal Behavior of Glycine

NASA Astrophysics Data System (ADS)

Dalai, Punam; Pleyer, Hannes Lukas; Strasdeit, Henry; Fox, Stefan

2017-12-01

On the Hadean-Early Archean Earth, the first islands must have provided hot and dry environments for abiotically formed organic molecules. The heat sources, mainly volcanism and meteorite impacts, were also available on Mars during the Noachian period. In recent work simulating this scenario, we have shown that neat glycine forms a black, sparingly water-soluble polymer ("thermomelanoid") when dry-heated at 200 °C under pure nitrogen. The present study explores whether relevant minerals and mineral mixtures can change this thermal behavior. Most experiments were conducted at 200 or 250 °C for 2 or 7 days. The mineral matrices used were phyllosilicates (Ca-montmorillonites SAz-1 and STx-1, Na-montmorillonite SAz-1-Na, nontronite NAu-1, kaolinite KGa-1), salts (NaCl, NaCl-KCl, CaCl2, artificial sea salt, gypsum, magnesite), picritic basalt, and three Martian regolith simulants (P-MRS, S-MRS, JSC Mars-1A). The main analytical method employed was high-performance liquid chromatography (HPLC). Glycine intercalated in SAz-1 and SAz-1-Na was well protected against thermomelanoid formation and sublimation at 200 °C: after 2 days, 95 and 79 %, respectively, had either survived unaltered or been transformed into the cyclic dipeptide (DKP) and linear peptides up to Gly6. The glycine survival rate followed the order SAz-1 > SAz-1-Na > STx-1 ≈ NAu-1 > KGa-1. Very good protection was also provided by artificial sea salt (84 % unaltered glycine after 200 °C for 7 days). P-MRS promoted the condensation up to Gly6, consistent with its high phyllosilicate content. The remaining matrices were less effective in preserving glycine as such or as peptides.

Asymmetry and Electronegativity in the Electron Capture Activation of the Se-Se Bond: σ*(Se-Se) vs σ*(Se-X).

PubMed

Gámez, José A; Yáñez, Manuel

2010-10-12

The effects of electron capture on the structure of XSeSeX' diselenide derivatives in which the substituents attached to the selenium atoms have different electronegativities have been investigated at different levels of theory, namely, DFT, MP2, CCSD, G2, and CASSCF/CASPT2. An analysis of the bonding changes upon electron attachment shows that when the diselenides bear low-electronegativity substituents, the Se-Se bond becomes activated upon electron capture, as previous studies have shown. However, this is no longer the case for very electronegative substituents, where this bond remains practically unaltered and is the Se-X bond the one which becomes strongly activated through a preferential population of the σ*(Se-X) antibonding orbital rather than the σ*(Se-Se) one. When this is the case, several anionic species are also encountered, namely, stretched, bent, and book structures. The present findings are similar to those obtained for a series of analogous disulfide compounds, which points out that these results are not unique and could be extrapolated to a wider range of compounds than the ones covered here. The Se-Se (Se-X) linkage in CH3SeSeOH, CH3SeSeF, FSeSeOH, and FSeSeF bears some of the characteristics of the so-called charge-shift bonds, with a clear charge fluctuation between both selenium atoms. This is more evident in their anions where the bonding reflects the important contribution of the ionic resonant forms Se-Se(-) ↔ (-)Se-Se vs the covalent component Se∴Se. This resonance changes with the nature of the substituents but also depends on the asymmetry of the substitution.

N-terminal nesprin-2 variants regulate β-catenin signalling

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

Zhang, Qiuping; Minaisah, Rose-Marie; Ferraro, Elisa

2016-07-15

The spatial compartmentalisation of biochemical signalling pathways is essential for cell function. Nesprins are a multi-isomeric family of proteins that have emerged as signalling scaffolds, herein, we investigate the localisation and function of novel nesprin-2 N-terminal variants. We show that these nesprin-2 variants display cell specific distribution and reside in both the cytoplasm and nucleus. Immunofluorescence microscopy revealed that nesprin-2 N-terminal variants colocalised with β-catenin at cell-cell junctions in U2OS cells. Calcium switch assays demonstrated that nesprin-2 and β-catenin are lost from cell-cell junctions in low calcium conditions whereas emerin localisation at the NE remained unaltered, furthermore, an N-terminal fragmentmore » of nesprin-2 was sufficient for cell-cell junction localisation and interacted with β-catenin. Disruption of these N-terminal nesprin-2 variants, using siRNA depletion resulted in loss of β-catenin from cell-cell junctions, nuclear accumulation of active β-catenin and augmented β-catenin transcriptional activity. Importantly, we show that U2OS cells lack nesprin-2 giant, suggesting that the N-terminal nesprin-2 variants regulate β-catenin signalling independently of the NE. Together, these data identify N-terminal nesprin-2 variants as novel regulators of β-catenin signalling that tether β-catenin to cell-cell contacts to inhibit β-catenin transcriptional activity. - Highlights: • N-terminal nesprin-2 variants display cell specific expression patterns. • N-terminal spectrin repeats of nesprin-2 interact with β-catenin. • N-terminal nesprin-2 variants scaffold β-catenin at cell-cell junctions.. • Nesprin-2 variants play multiple roles in β-catenin signalling.« less

High-fat diet affects gut nutrients transporters in hypo and hyperthyroid mice by PPAR-a independent mechanism.

PubMed

Losacco, Mariana Cerqueira; de Almeida, Carolina Fernanda Theodora; Hijo, Andressa Harumi Torelli; Bargi-Souza, Paula; Gama, Patricia; Nunes, Maria Tereza; Goulart-Silva, Francemilson

2018-06-01

High fat diet consumes and thyroid hormones (THs) disorders may affect nutrients metabolism, but their impact on the absorptive epithelium, the first place of nutrients access, remains unknown. Our aim was to evaluate the intestinal morphology and nutrients transporters content in mice fed standard (LFD) or high fat (HFD) diets in hypo or hyperthyroidism-induced condition. C57BL/6 male mice fed LFD or HFD diets for 12 weeks, followed by saline, PTU (antithyroid drug) or T3 treatment up to 30 days. The mice were euthanized and proximal intestine was removed to study GLUT2, GLUT5, PEPT1, FAT-CD36, FATP4, NPC1L1 and NHE3 distribution by Western blotting. Since PPAR-a is activated by fatty acids, which is abundant in the HFD, we also evaluated whether PPAR-a affects nutrients transporters. Thus, mice were treated with fenofibrate, a PPAR-a agonist. HFD decreased GLUT2, PEPT1, FAT-CD6 and NPC1L1, but increased NHE3, while GLUT5 and FATP4 remained unaltered. THs did not alter distribution of nutrients transporters neither in LFD nor in HFD groups, but they increased villi length and depth crypt in LFD and HFD, respectively. Fenofibrate did not affect content of nutrients transporters, excluding PPAR-a involvement on the HFD-induced changes. We assume that chronic HFD consumption reduced most of the nutrients transporters content in the small intestine of mice, which might limit the entrance of nutrients and gain weight. Since NHE3 promotes sodium absorption, and it was increased in HFD group, this finding could contribute to explain the hypertension observed in obesity. Copyright © 2018 Elsevier Inc. All rights reserved.

Sodium lauryl sulphate alters the mRNA expression of lipid-metabolizing enzymes and PPAR signalling in normal human skin in vivo.

PubMed

Törmä, Hans; Berne, Berit

2009-12-01

Detergents irritate skin and affect skin barrier homeostasis. In this study, healthy skin was exposed to 1% sodium lauryl sulphate (SLS) in water for 24 h. Biopsies were taken 6 h to 8 days post exposure. Lipid patterns were stained in situ and real-time polymerase chain reaction (PCR) was used to examine mRNA expression of enzymes synthesizing barrier lipids, peroxisome proliferator-activated receptors (PPAR) and lipoxygenases. The lipid pattern was disorganized from 6 h to 3 days after SLS exposure. Concomitant changes in mRNA expression included: (i) reduction, followed by induction, of ceramide-generating beta-glucocerebrosidase, (ii) increase on day 1 of two other enzymes for ceramide biosynthesis and (iii) persistent reduction of acetyl-CoA carboxylase-B, a key enzyme in fatty acid synthesis. Surprisingly, the rate-limiting enzyme in cholesterol synthesis, HMG-CoA reductase, was unaltered. Among putative regulators of barrier lipids synthesis, PPARalpha and PPARgamma exhibited reduced mRNA expression, while PPARbeta/delta and LXRbeta were unaltered. Epidermal lipoxygenase-3, which may generate PPARalpha agonists, exhibited reduced expression. In conclusion, SLS induces reorganization of lipids in the stratum corneum, which play a role in detergents' destruction of the barrier. The changes in mRNA expression of enzymes involved in synthesizing barrier lipids are probably important for the restoration of the barrier.

Long-term alterations in neuroimmune responses after neonatal exposure to lipopolysaccharide.

PubMed

Boissé, Lysa; Mouihate, Abdeslam; Ellis, Shaun; Pittman, Quentin J

2004-05-26

Fever is an integral part of the host's defense to infection that is orchestrated by the brain. A reduced febrile response is associated with reduced survival. Consequently, we have asked if early life immune exposure will alter febrile and neurochemical responses to immune stress in adulthood. Fourteen-day-old neonatal male rats were given Escherichia coli lipopolysaccharide (LPS) that caused either fever or hypothermia depending on ambient temperature. Control rats were given pyrogen-free saline. Regardless of the presence of neonatal fever, adult animals that had been neonatally exposed to LPS displayed attenuated fevers in response to intraperitoneal LPS but unaltered responses to intraperitoneal interleukin 1beta or intracerebroventricular prostaglandin E(2). The characteristic reduction in activity that accompanies fever was unaltered, however, as a function of neonatal LPS exposure. Treatment of neonates with an antigenically dissimilar LPS (Salmonella enteritidis) was equally effective in reducing adult responses to E. coli LPS, indicating an alteration in the innate immune response. In adults treated as neonates with LPS, basal levels of hypothalamic cyclooxygenase 2 (COX-2), determined by semiquantitative Western blot analysis, were significantly elevated compared with controls. In addition, whereas adult controls responded to LPS with the expected induction of COX-2, adults pretreated neonatally with LPS responded to LPS with a reduction in COX-2. Thus, neonatal LPS can alter CNS-mediated inflammatory responses in adult rats.

Effects of igneous intrusion on microporosity and gas adsorption capacity of coals in the Haizi Mine, China.

PubMed

Jiang, Jingyu; Cheng, Yuanping

2014-01-01

This paper describes the effects of igneous intrusions on pore structure and adsorption capacity of the Permian coals in the Huaibei Coalfield, China. Twelve coal samples were obtained at different distances from a ~120 m extremely thick sill. Comparisons were made between unaltered and heat-affected coals using geochemical data, pore-fracture characteristics, and adsorption properties. Thermal alteration occurs down to ~1.3 × sill thickness. Approaching the sill, the vitrinite reflectance (R(o)) increased from 2.30% to 2.78%, forming devolatilization vacuoles and a fine mosaic texture. Volatile matter (VM) decreased from 17.6% to 10.0% and the moisture decreased from 3.0% to 1.6%. With decreasing distance to the sill, the micropore volumes initially increased from 0.0054 cm(3)/g to a maximum of 0.0146 cm(3)/g and then decreased to 0.0079 cm(3)/g. The results show that the thermal evolution of the sill obviously changed the coal geochemistry and increased the micropore volume and adsorption capacity of heat-affected coal (60-160 m from the sill) compared with the unaltered coals. The trap effect of the sill prevented the high-pressure gas from being released, forming gas pocket. Mining activities near the sill created a low pressure zone leading to the rapid accumulation of methane and gas outbursts in the Haizi Mine.

Heat-activated persulfate oxidation of PFOA, 6:2 fluorotelomer sulfonate, and PFOS under conditions suitable for in-situ groundwater remediation.

PubMed

Park, Saerom; Lee, Linda S; Medina, Victor F; Zull, Aaron; Waisner, Scott

2016-02-01

PFOA (perfluorooctanoic acid) oxidation (0.121-6.04 μM) by heat-activated persulfate was evaluated at 20-60 °C with 4.2-84 mM [Formula: see text] and in the presence of soluble fuel components to assess feasibility for in-situ remediation of groundwater. 6:2 fluorotelomer sulfonic acid/sulfonate (6:2 FTSA) and PFOS (perfluorooctanesulfonic acid) persulfate oxidation was also evaluated in a subset of conditions given their co-occurrence at many sites. High performance liquid chromatography electron spray tandem mass spectrometry was used for organic analysis and fluoride was measured using a fluoride-specific electrode. PFOA pseudo-1st order transformation rates (k1,PFOA) increased with increasing temperature (half-lives from 0.1 to 7 d for 60 to 30 °C) sequentially removing CF2 groups ('unzipping') to shorter chain perfluoroalkyl carboxylic acids (PFCAs) and F(-). At 50 °C, a 5-fold increase in [Formula: see text] led to a 5-fold increase in k1,PFOA after which self-scavenging by sulfate radicals decreased the relative rate of increase with more [Formula: see text] . Benzene, toluene, ethylbenzene and xylene did not affect k1,PFOA even at 40 times higher molar concentrations than PFOA. A modeling approach to explore pathways strongly supported that for 6:2 FTSA, both the ethyl linkage and CF2-CH2 bond of 6:2 FTSA oxidize simultaneously, resulting in a ratio of ∼25/75 PFHpA/PFHxA. The effectiveness of heat-activated [Formula: see text] on PFOA oxidation was reduced in a soil slurry; therefore, repeated persulfate injections are required to efficiently achieve complete oxidation in the field. However, PFOS remained unaltered even at higher activation temperatures, thus limiting the sole use of heat-activated persulfate for perfluoroalkyl substances removal in the field. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of physiotherapy in addition to testosterone replacement therapy on the efficiency of the motor system in men with hypogonadism.

PubMed

Bacevičienė, Rasa; Valonytė, Laura; Ceponis, Jonas

2013-01-01

The aim of this study was to analyze whether the addition of physiotherapy to testosterone replacement therapy provides added benefit in improving functional capacity of the motor system in men with hypogonadism. The study involved 3 groups of subjects: group 1, healthy men (n=20); group 2, men with hypogonadism who underwent testosterone replacement therapy with physiotherapy (TRT+PT) (n=8); and group 3, men with hypogonadism who underwent testosterone replacement therapy alone (TRT) (n=10). Physical activity (International Physical Activity Questionnaire [IPAQ]) and body composition (X-SCAN analysis) were analyzed; the vertical jump test (Leonardo Mechanography®) was applied. The application of testosterone replacement therapy together with physiotherapy for 6 months significantly increased the maximum and relative power of jump in the subjects in the TRT+PT group; however, in the TRT group, no statistically significant difference was observed. The maximum jump height for the subjects in the TRT+PT group significantly increased 6 months after the intervention; however, in the TRT group, this index remained unaltered. The lean body mass of the subjects in the TRT+PT group increased (P<0.05); however, in the TRT group, it did not change. The relative fat body mass in the TRT+PT group decreased significantly (P<0.05), but, in the TRT group, it had a tendency to increase, though insignificantly. Our results suggest that the application of testosterone replacement therapy together with physiotherapy (1 hour twice weekly) in men with hypogonadism may lead to earlier and better results in comparison with testosterone replacement therapy applied alone.

Impact of coupling techniques of an active middle ear device to the round window membrane for the backward stimulation of the cochlea.

PubMed

Gostian, Antoniu-Oreste; Pazen, David; Ortmann, Magdalene; Luers, Jan-Christoffer; Anagiotos, Andreas; Hüttenbrink, Karl-Bernd; Beutner, Dirk

2015-01-01

Interposed cartilage and the round window coupler (RWC) increase the efficiency of cochlea stimulation with the floating mass transducer (FMT) of a single active middle ear implant (AMEI) placed against the round window membrane. Treatment of mixed and conductive hearing loss with an AMEI attached to the round window is effective, yet the best placement technique of its FMT for the most efficient stimulation of the cochlea remains to be determined. Experimental study on human temporal bones with the FMT placed against firstly the unaltered round window niche and then subsequently against the fully exposed round window membrane with and without interposed cartilage and the RWC. Cochlea stimulation is measured by the volume velocities of the stapes footplate using LASER vibrometry. At the undrilled round window niche, placement of the FMT by itself and with the RWC resulted in similar volume velocities. The response was significantly raised by interposing cartilage into the undrilled round window niche. Complete exposure of the round window membrane allowed for significantly increased volume velocities. Among these, coupling of the FMT with interposed cartilage yielded responses of similar magnitude compared with the RWC but significantly higher compared with the FMT by itself. Good contact to the round window membrane is essential for efficient stimulation of the cochlea. Therefore, interposing cartilage into the undrilled round window niche is a viable option. At the drilled round window membrane, the FMT with interposed cartilage and attached to the RWC are similarly effective.

Differences in lead tolerance between Kandelia obovata and Acanthus ilicifolius seedlings under varying treatment times.

PubMed

Yan, Zhongzheng; Tam, Nora Fung Yee

2013-01-15

The effects of short-term (1 day) and long-term (49 days) of lead (Pb) stress on growth and physiological responses in the leaves and roots of two mangrove plants, Kandelia obovata and Acanthus ilicifolius, were compared. The growth of both species was affected by Pb at Day 49, whereas the root to shoot ratio of K. obovata remained unchanged. Compared with A. ilicifolius, less Pb accumulated in leaves of K. obovata, which indicates that this species is a typical Pb-excluder. Significant linear relationships were observed between the Pb concentrations in the roots and leaves and the Pb treatment concentrations in the sediments in A. ilicifolius but not in K. obovata. The proline concentration increased in both mangrove species at Day 49, especially in A. ilicifolius, but no changes were observed at Day 1. The tolerant species K. obovata tended to acclimate to metal stress by restricting the translocation of toxic metals and by increasing and/or maintaining high superoxide dismutase (SOD) activity, minimizing lipid peroxidation, and exhibiting prolonged unaltered growth (49 days) under Pb treatment. The non-tolerant species, A. ilicifolius, did not acclimate to metal stress, its leaves were seriously damaged with significant increased MDA content, and its SOD activity was decreased. An increase of endogenous jasmonic acid concentration was observed only in K. obovata, both at Day 1 and at Day 49, which suggests that this hormone plays an important role in metal tolerance under short-term and long-term metal treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

Is anaerobic digestion effective for the removal of organic micropollutants and biological activities from sewage sludge?

PubMed

Gonzalez-Gil, L; Papa, M; Feretti, D; Ceretti, E; Mazzoleni, G; Steimberg, N; Pedrazzani, R; Bertanza, G; Lema, J M; Carballa, M

2016-10-01

The occurrence of emerging organic micropollutants (OMPs) in sewage sludge has been widely reported; nevertheless, their fate during sludge treatment remains unclear. The objective of this work was to study the fate of OMPs during mesophilic and thermophilic anaerobic digestion (AD), the most common processes used for sludge stabilization, by using raw sewage sludge without spiking OMPs. Moreover, the results of analytical chemistry were complemented with biological assays in order to verify the possible adverse effects (estrogenic and genotoxic) on the environment and human health in view of an agricultural (re)use of digested sludge. Musk fragrances (AHTN, HHCB), ibuprofen (IBP) and triclosan (TCS) were the most abundant compounds detected in sewage sludge. In general, the efficiency of the AD process was not dependent on operational parameters but compound-specific: some OMPs were highly biotransformed (e.g. sulfamethoxazole and naproxen), while others were only slightly affected (e.g. IBP and TCS) or even unaltered (e.g. AHTN and HHCB). The MCF-7 assay evidenced that estrogenicity removal was driven by temperature. The Ames test did not show point mutation in Salmonella typhimurium while the Comet test exhibited a genotoxic effect on human leukocytes attenuated by AD. This study highlights the importance of combining chemical analysis and biological activities in order to establish appropriate operational strategies for a safer disposal of sewage sludge. Actually, it was demonstrated that temperature has an insignificant effect on the disappearance of the parent compounds while it is crucial to decrease estrogenicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mass spectrometry–based relative quantification of proteins in precatalytic and catalytically active spliceosomes by metabolic labeling (SILAC), chemical labeling (iTRAQ), and label-free spectral count

PubMed Central

Schmidt, Carla; Grønborg, Mads; Deckert, Jochen; Bessonov, Sergey; Conrad, Thomas; Lührmann, Reinhard; Urlaub, Henning

2014-01-01

The spliceosome undergoes major changes in protein and RNA composition during pre-mRNA splicing. Knowing the proteins—and their respective quantities—at each spliceosomal assembly stage is critical for understanding the molecular mechanisms and regulation of splicing. Here, we applied three independent mass spectrometry (MS)–based approaches for quantification of these proteins: (1) metabolic labeling by SILAC, (2) chemical labeling by iTRAQ, and (3) label-free spectral count for quantification of the protein composition of the human spliceosomal precatalytic B and catalytic C complexes. In total we were able to quantify 157 proteins by at least two of the three approaches. Our quantification shows that only a very small subset of spliceosomal proteins (the U5 and U2 Sm proteins, a subset of U5 snRNP-specific proteins, and the U2 snRNP-specific proteins U2A′ and U2B′′) remains unaltered upon transition from the B to the C complex. The MS-based quantification approaches classify the majority of proteins as dynamically associated specifically with the B or the C complex. In terms of experimental procedure and the methodical aspect of this work, we show that metabolically labeled spliceosomes are functionally active in terms of their assembly and splicing kinetics and can be utilized for quantitative studies. Moreover, we obtain consistent quantification results from all three methods, including the relatively straightforward and inexpensive label-free spectral count technique. PMID:24448447

Effects of a submarine eruption on the performance of two brown seaweeds

NASA Astrophysics Data System (ADS)

Betancor, Séfora; Tuya, Fernando; Gil-Díaz, Teba; Figueroa, Félix L.; Haroun, Ricardo

2014-03-01

World oceans are becoming more acidic as a consequence of CO2 anthropogenic emissions, with multiple physiological and ecological implications. So far, our understanding is mainly limited to some species through in vitro experimentation. In this study, we took advantage of a recent submarine eruption (from October 2011 to March 2012) at ~ 1 nautical mile offshore El Hierro Island (Canary Islands, central east Atlantic) to determine whether altered physical-chemical conditions, mainly sudden natural ocean acidification, affected the morphology, photosynthesis (in situ Chl-a fluorescence) and physiological performance (photo-protective mechanisms and oxidative stress) of the conspicuous brown seaweeds Padina pavonica-a species with carbonate deposition - and Lobophora variegata-a species without carbonate on thallus surfaces - , both with similar morphology. Seaweeds were sampled twice: November 2011 (eruptive phase with a pH drop of ca. 1.22 units relative to standard conditions) and March 2012 (post-eruptive phase with a pH of ca. 8.23), on two intertidal locations adjacent to the eruption and at a control location. P. pavonica showed decalcification and loss of photo-protective compounds and antioxidant activity at locations affected by the eruption, behaving as a sun-adapted species during lowered pH conditions. At the same time, L. variegata suffered a decrease in photo-protective compounds and antioxidant activity during the volcanic event, but its photosynthetic performance remained unaltered. These results reinforce the idea that calcareous seaweeds, as a whole, are more sensitive than non-calcareous seaweeds to alter their performance under scenarios of reduced pH.

Weathering of pyrogenic organic matter induces fungal oxidative enzyme response in single culture inoculation experiments.

PubMed

Gibson, Christy; Berry, Timothy D; Wang, Ruzhen; Spencer, Julie A; Johnston, Cliff T; Jiang, Yong; Bird, Jeffrey A; Filley, Timothy R

2016-02-01

The addition of pyrogenic organic matter (PyOM), the aromatic carbon-rich product of the incomplete combustion of plant biomass or fossil fuels, to soil can influence the rate of microbial metabolism of native soil carbon. The interaction of soil heterotrophs with PyOM may be governed by the surficial chemical and physical properties of PyOM that evolve with environmental exposure. We present results of a 36-day laboratory incubation investigating the interaction of a common white-rot fungus, Trametes versicolor, with three forms of 13 C-enriched (2.08 atom% 13 C) PyOM derived from Pinus ponderosa (450 °C): one freshly produced, and two artificially weathered (254 nm, UV light-water treatment and water-leaching alone). Analysis (FTIR, XPS) of the UV-weathered PyOM showed increased aliphatic C-H content and oxidation of aromatic carbon relative to both the original and water-leached PyOM. The addition of both weathered forms of PyOM stimulated (positively primed) fungal respiration of the growth media, while the unaltered PyOM mildly inhibited (negatively primed) respiration. Artificial weathering resulted in higher oxidative (laccase and peroxidase) enzyme activity than unaltered PyOM, possibly the result of a diminished capacity to bind reactive substrates and extracellular enzymes after weathering. However, and contrary to expectations, simple water-leached weathering resulted in a relatively higher enzyme activity and respiration than that of UV-weathering. The 13 C content of respired CO 2 indicated negligible fungal oxidation of PyOM for all treatments, demonstrating the overall low microbial reactivity of this high temperature PyOM. The increased enzymatic and positive priming response of T. versicolor to weathered PyOM highlights the importance of weathering-induced chemistry in controlling PyOM-microbe-soil carbon interactions.

Estimation of unaltered daily mean streamflow at ungaged streams of New York, excluding Long Island, water years 1961-2010

USGS Publications Warehouse

Gazoorian, Christopher L.

2015-01-01

A graphical user interface, with an integrated spreadsheet summary report, has been developed to estimate and display the daily mean streamflows and statistics and to evaluate different water management or water withdrawal scenarios with the estimated monthly data. This package of regression equations, U.S. Geological Survey streamgage data, and spreadsheet application produces an interactive tool to estimate an unaltered daily streamflow hydrograph and streamflow statistics at ungaged sites in New York. Among other uses, the New York Streamflow Estimation Tool can assist water managers with permitting water withdrawals, implementing habitat protection, estimating contaminant loads, or determining the potential affect from chemical spills.

CUDC-907 in relapsed/refractory diffuse large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase I trial.

PubMed

Oki, Yasuhiro; Kelly, Kevin R; Flinn, Ian; Patel, Manish R; Gharavi, Robert; Ma, Anna; Parker, Jefferson; Hafeez, Amir; Tuck, David; Younes, Anas

2017-11-01

CUDC-907 is a first-in-class, oral small molecule inhibitor of both HDAC (class I and II) and PI3K (class Iα, β, and δ) enzymes, with demonstrated anti-tumor activity in multiple pre-clinical models, including MYC-driven ones. In this report, we present the safety and preliminary activity results of CUDC-907, with and without rituximab, in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), with a particular focus on those with MYC-altered disease. Thirty-seven DLBCL patients were enrolled, 14 with confirmed MYC-altered disease. Twenty-five patients received monotherapy treatment, and 12 received the combination of CUDC-907 with rituximab. CUDC-907 monotherapy and combination demonstrated similar safety profiles consisting primarily of Grade 1/2 hematologic and gastrointestinal events. The most frequently reported Grade ≥3 treatment-related events were thrombocytopenia, neutropenia, diarrhea, fatigue, and anemia. Eleven responses (5 complete responses and 6 partial responses) were reported, for a response rate of 37% (11 out of 30) in evaluable patients [30% (11 out of 37) including all patients]. The objective response rate in evaluable MYC-altered DLBCL patients was 64% (7 out of 11; 4 complete responses and 3 partial responses), while it was 29% (2 out of 7) in MYC unaltered, and 17% (2 out of 12) in those with unknown MYC status. Median duration of response was 11.2 months overall; 13.6 months in MYC-altered patients, 6.0 months in MYC unaltered, and 7.8 months in those with MYC status unknown. The tolerable safety profile and encouraging evidence of durable anti-tumor activity, particularly in MYC-altered patients, support the continued development of CUDC-907 in these populations of high unmet need. ( clinicaltrials.gov identifier: 01742988 ). Copyright© Ferrata Storti Foundation.

Metal-free catalysis of persulfate activation and organic-pollutant degradation by nitrogen-doped graphene and aminated graphene.

PubMed

Chen, Hao; Carroll, Kenneth C

2016-08-01

We evaluated three types of functionalized, graphene-based materials for activating persulfate (PS) and removing (i.e., sorption and oxidation) sulfamethoxazole (SMX) as a model emerging contaminant. Although advanced oxidative water treatment requires PS activation, activation requires energy or chemical inputs, and toxic substances are contained in many catalysts. Graphene-based materials were examined herein as an alternative to metal-based catalysts. Results show that nitrogen-doped graphene (N-GP) and aminated graphene (NH2-GP) can effectively activate PS. Overall, PS activation by graphene oxide was not observed in this study. N-GP (50 mg L(-1)) can rapidly activate PS (1 mM) to remove >99.9% SMX within 3 h, and NH2-GP (50 mg L(-1)) activated PS (1 mM) can also remove 50% SMX within 10 h. SMX sorption and total removal was greater for N-GP, which suggests oxidation was enhanced by increasing proximity to PS activation sites. Increasing pH enhanced the N-GP catalytic ability, and >99.9% SMX removal time decreased from 3 h to 1 h when pH increased from 3 to 9. However, the PS catalytic ability was inhibited at pH 9 for NH2-GP. Increases in ionic strength (100 mM NaCl or Na2SO4) and addition of radical scavengers (500 mM ethanol) both had negligible impacts on SMX removal. With bicarbonate addition (100 mM), while the catalytic ability of N-GP remained unaltered, NH2-GP catalytic ability was inhibited completely. Humic acid (250 mg L(-1)) was partially effective in inhibiting SMX removal in both N-GP and NH2-GP systems. These results have implications for elucidating oxidant catalysis mechanisms, and they quantify the ability of functionalization of graphene with hetero-atom doping to effectively catalyze PS for water treatment of organic pollutants including emerging contaminants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomechanical comparison between bicortical pin and monocortical screw/polymethylmethacrylate constructs in the cadaveric canine cervical vertebral column.

PubMed

Hettlich, Bianca F; Allen, Matthew J; Pascetta, Daniel; Fosgate, Geoffrey T; Litsky, Alan S

2013-08-01

To compare biomechanical stiffness of cadaveric canine cervical spine constructs stabilized with bicortical stainless steel pins and polymethylmethacrylate (PMMA), monocortical stainless steel screws with PMMA, or monocortical titanium screws with PMMA. Biomechanical cadaver study. Eighteen canine cervical vertebral columns (C2-C7) were collected from skeletally mature dogs (weighing 22-32 kg). Specimens were radiographed and examined by dual energy X-ray absorptiometry. Stiffness of the unaltered C4-C5 intervertebral motion unit was measured in extension, flexion and lateral bending using non-destructive 4-point bend testing. Specimens were then stabilized by (1) bicortical stainless steel pins/PMMA, (2) monocortical stainless steel screws/PMMA, or (3) monocortical titanium screws/PMMA. Mechanical testing was repeated and stiffness data from unaltered specimens and the 3 treatment groups were compared. All 3 surgical methods significantly increased stiffness of the C4-C5 motion unit compared with the unaltered specimen (P < .001 for all treatments), but stiffness was not significantly different among the 3 fixation groups (P = .578). In this model, monocortical screw fixation (with stainless steel or titanium screws) was biomechanically equivalent to bicortical fixation. © Copyright 2013 by The American College of Veterinary Surgeons.

Absence of Intracellular Ion Channels TPC1 and TPC2 Leads to Mature-Onset Obesity in Male Mice, Due to Impaired Lipid Availability for Thermogenesis in Brown Adipose Tissue

PubMed Central

Lear, Pamela V.; González-Touceda, David; Porteiro Couto, Begoña; Viaño, Patricia; Guymer, Vanessa; Remzova, Elena; Tunn, Ruth; Chalasani, Annapurna; García-Caballero, Tomás; Hargreaves, Iain P.; Tynan, Patricia W.; Christian, Helen C.; Nogueiras, Rubén

2015-01-01

Intracellular calcium-permeable channels have been implicated in thermogenic function of murine brown and brite/beige adipocytes, respectively transient receptor potential melastin-8 and transient receptor potential vanilloid-4. Because the endo-lysosomal two-pore channels (TPCs) have also been ascribed with metabolic functionality, we studied the effect of simultaneously knocking out TPC1 and TPC2 on body composition and energy balance in male mice fed a chow diet. Compared with wild-type mice, TPC1 and TPC2 double knockout (Tpcn1/2−/−) animals had a higher respiratory quotient and became obese between 6 and 9 months of age. Although food intake was unaltered, interscapular brown adipose tissue (BAT) maximal temperature and lean-mass adjusted oxygen consumption were lower in Tpcn1/2−/− than in wild type mice. Phosphorylated hormone-sensitive lipase expression, lipid density and expression of β-adrenergic receptors were also lower in Tpcn1/2−/− BAT, whereas mitochondrial respiratory chain function and uncoupling protein-1 expression remained intact. We conclude that Tpcn1/2−/− mice show mature-onset obesity due to reduced lipid availability and use, and a defect in β-adrenergic receptor signaling, leading to impaired thermogenic activity, in BAT. PMID:25545384

Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice.

PubMed

Rozhdestvensky, Timofey S; Robeck, Thomas; Galiveti, Chenna R; Raabe, Carsten A; Seeger, Birte; Wolters, Anna; Gubar, Leonid V; Brosius, Jürgen; Skryabin, Boris V

2016-02-05

Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans and growth retardation in mice exhibiting ~15% postnatal lethality in C57BL/6 background. Here we analysed a knock-in mouse containing a 5'HPRT-LoxP-Neo(R) cassette (5'LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScr(p-/m5'LoxP)), we observed compensation of growth retardation and postnatal lethality. Genomic methylation pattern and expression of protein-coding genes remained unaltered at the PWS-locus of PWScr(p-/m5'LoxP) mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScr(p-/m5'LoxP) mice expressed Snord116 in brain areas similar to wild type animals. Our results suggest that the lack of PWScr RNA expression in certain brain areas could be a primary cause of the growth retardation phenotype in mice. We propose that activation of disease-associated genes on imprinted regions could lead to general therapeutic strategies in associated diseases.

Peroxisome Proliferator-Activated Receptor-γ Ligands Alter Breast Cancer Cell Motility through Modulation of the Plasminogen Activator System

PubMed Central

Carter, Jennifer C.; Church, Frank C.

2011-01-01

We investigated peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands effect on cell motility and the plasminogen activator system using normal MCF-10A and malignant MCF-10CA1 cell lines. Ciglitazone reduced both wound-induced migration and chemotaxis. However, the effect was not reversed with pretreatment of cells with the PPAR-γ-specific antagonist GW9662. Immunoblot analysis of conditioned media showed ciglitazone decreased plasminogen activator inhibitor-1 (PAI-1) in both cell lines; this effect was also unaltered by PPAR-γ antagonism. Alternatively, treatment with the ω-6 fatty acid arachidonic acid (ArA), but not the ω-3 fatty acid docosahexanoic acid, increased both MCF-10A cell migration and cell surface uPA activity. Pretreatment with a PPAR-γ antagonist reversed these effects, suggesting that ArA mediates its effect on cell motility and uPA activity through PPAR-γ activation. Collectively, the data suggest PPAR-γ ligands have a differential effect on normal and malignant cell migration and the plasminogen activation system, resulting from PPAR-γ-dependent and PPAR-γ-independent effects. PMID:22131991

Alteration Effects at Gale and Gusev Craters

NASA Image and Video Library

2015-12-17

This graph shows the ratio of concentrations of several elements in four different pairs of targets examined by Alpha Particle X-ray Spectrometer (APXS) instruments on NASA Mars rovers Curiosity and Spirit. For each pair of targets, one shows evidence of mineral alteration and the other is an unaltered counterpart. The first three pairs (with ratios shown by green, blue and red lines) are targets in Gale Crater analyzed by Curiosity's APXS. The fourth pair (with ratio shown by the black line) is in Gusev Crater and was analyzed by Spirit's APXS. Similar profiles are observed, suggesting the possibility of related formation processes. As with examples of silica enrichment found by Curiosity, the origin of high-silica nodular deposits found by Spirit also remains unresolved: Either acidic weathering or silica addition could be responsible. It is clear, however, that liquid water was involved in either alteration scenario. http://photojournal.jpl.nasa.gov/catalog/PIA20276

Detailed analysis of petroleum hydrocarbon attenuation in biopiles by high-performance liquid chromatography followed by comprehensive two-dimensional gas chromatography.

PubMed

Mao, Debin; Lookman, Richard; Van De Weghe, Hendrik; Van Look, Dirk; Vanermen, Guido; De Brucker, Nicole; Diels, Ludo

2009-02-27

Enhanced bioremediation of petroleum hydrocarbons in two biopiles was quantified by high-performance liquid chromatography (HPLC) followed by comprehensive two-dimensional gas chromatography (GCXGC). The attenuation of 34 defined hydrocarbon classes was calculated by HPLC-GCXGC analysis of representative biopile samples at start-up and after 18 weeks of biopile operation. In general, a-cyclic alkanes were most efficiently removed from the biopiles, followed by monoaromatic hydrocarbons. Cycloalkanes and polycyclic aromatic hydrocarbons (PAHs) were more resistant to degradation. A-cyclic biomarkers farnesane, trimethyl-C13, norpristane, pristane and phytane dropped to only about 10% of their initial concentrations. On the other hand, C29-C31 hopane concentrations remained almost unaltered after 18 weeks of biopile operation, confirming their resistance to biodegradation. They are thus reliable indicators to estimate attenuation potential of petroleum hydrocarbons in biopile processed soils.

Opposite effects of cannabis and cocaine on performance monitoring.

PubMed

Spronk, Desirée B; Verkes, Robbert J; Cools, Roshan; Franke, Barbara; Van Wel, Janelle H P; Ramaekers, Johannes G; De Bruijn, Ellen R A

2016-07-01

Drug use is often associated with risky and unsafe behavior. However, the acute effects of cocaine and cannabis on performance monitoring processes have not been systematically investigated. The aim of the current study was to investigate how administration of these drugs alters performance monitoring processes, as reflected in the error-related negativity (ERN), the error positivity (Pe) and post-error slowing. A double-blind placebo-controlled randomized three-way crossover design was used. Sixty-one subjects completed a Flanker task while EEG measures were obtained. Subjects showed diminished ERN and Pe amplitudes after cannabis administration and increased ERN and Pe amplitudes after administration of cocaine. Neither drug affected post-error slowing. These results demonstrate diametrically opposing effects on the early and late phases of performance monitoring of the two most commonly used illicit drugs of abuse. Conversely, the behavioral adaptation phase of performance monitoring remained unaltered by the drugs. Copyright © 2016. Published by Elsevier B.V.

Effects of chronic administration of nicotine on storage and synthesis of noradrenaline in rat brain

PubMed Central

Bhagat, B.

1970-01-01

1. Chronic administration of nicotine (0·5 mg/kg, subcutaneously four times a day, 5 days a week, for 6 weeks) did not affect the growth rate and water intake in rats. In these animals food intake was normal for the first 5 weeks, but was significantly increased during the sixth week of treatment. 2. Nicotine administration increased the blood pressure of rats from 120 mm Hg to 151 mm Hg. 3. The concentrations of endogenous noradrenaline, dopamine, 5-hydroxytryptamine and acetylcholine in the brain remained unaltered. However, chronic treatment with nicotine increased the turnover rate of noradrenaline. Initial accumulation of 3H-noradrenaline was also significantly increased. 4. It is concluded from these studies that changes in the turnover of cerebral noradrenaline caused by chronic administration rather than changes in the concentration of noradrenaline may be an important factor in nicotine-induced behavioural changes. PMID:5413293

Imaging mitochondrial flux in single cells with a FRET sensor for pyruvate.

PubMed

San Martín, Alejandro; Ceballo, Sebastián; Baeza-Lehnert, Felipe; Lerchundi, Rodrigo; Valdebenito, Rocío; Contreras-Baeza, Yasna; Alegría, Karin; Barros, L Felipe

2014-01-01

Mitochondrial flux is currently accessible at low resolution. Here we introduce a genetically-encoded FRET sensor for pyruvate, and methods for quantitative measurement of pyruvate transport, pyruvate production and mitochondrial pyruvate consumption in intact individual cells at high temporal resolution. In HEK293 cells, neurons and astrocytes, mitochondrial pyruvate uptake was saturated at physiological levels, showing that the metabolic rate is determined by intrinsic properties of the organelle and not by substrate availability. The potential of the sensor was further demonstrated in neurons, where mitochondrial flux was found to rise by 300% within seconds of a calcium transient triggered by a short theta burst, while glucose levels remained unaltered. In contrast, astrocytic mitochondria were insensitive to a similar calcium transient elicited by extracellular ATP. We expect the improved resolution provided by the pyruvate sensor will be of practical interest for basic and applied researchers interested in mitochondrial function.

A Solution-Doped Polymer Semiconductor:Insulator Blend for Thermoelectrics.

PubMed

Kiefer, David; Yu, Liyang; Fransson, Erik; Gómez, Andrés; Primetzhofer, Daniel; Amassian, Aram; Campoy-Quiles, Mariano; Müller, Christian

2017-01-01

Poly(ethylene oxide) is demonstrated to be a suitable matrix polymer for the solution-doped conjugated polymer poly(3-hexylthiophene). The polarity of the insulator combined with carefully chosen processing conditions permits the fabrication of tens of micrometer-thick films that feature a fine distribution of the F4TCNQ dopant:semiconductor complex. Changes in electrical conductivity from 0.1 to 0.3 S cm -1 and Seebeck coefficient from 100 to 60 μV K -1 upon addition of the insulator correlate with an increase in doping efficiency from 20% to 40% for heavily doped ternary blends. An invariant bulk thermal conductivity of about 0.3 W m -1 K -1 gives rise to a thermoelectric Figure of merit ZT ∼ 10 -4 that remains unaltered for an insulator content of more than 60 wt%. Free-standing, mechanically robust tapes illustrate the versatility of the developed dopant:semiconductor:insulator ternary blends.

Cholera toxin structure, gene regulation and pathophysiological and immunological aspects.

PubMed

Sánchez, J; Holmgren, J

2008-05-01

Many notions regarding the function, structure and regulation of cholera toxin expression have remained essentially unaltered in the last 15 years. At the same time, recent findings have generated additional perspectives. For example, the cholera toxin genes are now known to be carried by a non-lytic bacteriophage, a previously unsuspected condition. Understanding of how the expression of cholera toxin genes is controlled by the bacterium at the molecular level has advanced significantly and relationships with cell-density-associated (quorum-sensing) responses have recently been discovered. Regarding the cell intoxication process, the mode of entry and intracellular transport of cholera toxin are becoming clearer. In the immunological field, the strong oral immunogenicity of the non-toxic B subunit of cholera toxin (CTB) has been exploited in the development of a now widely licensed oral cholera vaccine. Additionally, CTB has been shown to induce tolerance against co-administered (linked) foreign antigens in some autoimmune and allergic diseases.

Dehydration rate determines the degree of membrane damage and desiccation tolerance in bryophytes.

PubMed

Cruz de Carvalho, Ricardo; Catalá, Myriam; Branquinho, Cristina; Marques da Silva, Jorge; Barreno, Eva

2017-03-01

Desiccation tolerant (DT) organisms are able to withstand an extended loss of body water and rapidly resume metabolism upon rehydration. This ability, however, is strongly dependent on a slow dehydration rate. Fast dehydration affects membrane integrity leading to intracellular solute leakage upon rehydration and thereby impairs metabolism recovery. We test the hypothesis that the increased cell membrane damage and membrane permeability observed under fast dehydration, compared with slow dehydration, is related to an increase in lipid peroxidation. Our results reject this hypothesis because following rehydration lipid peroxidation remains unaltered, a fact that could be due to the high increase of NO upon rehydration. However, in fast-dried samples we found a strong signal of red autofluorescence upon rehydration, which correlates with an increase in ROS production and with membrane leakage, particularly the case of phenolics. This could be used as a bioindicator of oxidative stress and membrane damage. © 2016 Scandinavian Plant Physiology Society.

A large iris-like expansion of a mechanosensitive channel protein induced by membrane tension

NASA Technical Reports Server (NTRS)

Betanzos, Monica; Chiang, Chien-Sung; Guy, H. Robert; Sukharev, Sergei

2002-01-01

MscL, a bacterial mechanosensitive channel of large conductance, is the first structurally characterized mechanosensor protein. Molecular models of its gating mechanisms are tested here. Disulfide crosslinking shows that M1 transmembrane alpha-helices in MscL of resting Escherichia coli are arranged similarly to those in the crystal structure of MscL from Mycobacterium tuberculosis. An expanded conformation was trapped in osmotically shocked cells by the specific bridging between Cys 20 and Cys 36 of adjacent M1 helices. These bridges stabilized the open channel. Disulfide bonds engineered between the M1 and M2 helices of adjacent subunits (Cys 32-Cys 81) do not prevent channel gating. These findings support gating models in which interactions between M1 and M2 of adjacent subunits remain unaltered while their tilts simultaneously increase. The MscL barrel, therefore, undergoes a large concerted iris-like expansion and flattening when perturbed by membrane tension.

Imaging Mitochondrial Flux in Single Cells with a FRET Sensor for Pyruvate

PubMed Central

Baeza-Lehnert, Felipe; Lerchundi, Rodrigo; Valdebenito, Rocío; Contreras-Baeza, Yasna; Alegría, Karin; Barros, L. Felipe

2014-01-01

Mitochondrial flux is currently accessible at low resolution. Here we introduce a genetically-encoded FRET sensor for pyruvate, and methods for quantitative measurement of pyruvate transport, pyruvate production and mitochondrial pyruvate consumption in intact individual cells at high temporal resolution. In HEK293 cells, neurons and astrocytes, mitochondrial pyruvate uptake was saturated at physiological levels, showing that the metabolic rate is determined by intrinsic properties of the organelle and not by substrate availability. The potential of the sensor was further demonstrated in neurons, where mitochondrial flux was found to rise by 300% within seconds of a calcium transient triggered by a short theta burst, while glucose levels remained unaltered. In contrast, astrocytic mitochondria were insensitive to a similar calcium transient elicited by extracellular ATP. We expect the improved resolution provided by the pyruvate sensor will be of practical interest for basic and applied researchers interested in mitochondrial function. PMID:24465702

The significance of direct sunlight and polarized skylight in the ant's celestial system of navigation.

PubMed

Wehner, Rüdiger; Müller, Martin

2006-08-15

As textbook knowledge has it, bees and ants use polarized skylight as a backup cue whenever the main compass cue, the sun, is obscured by clouds. Here we show, by employing a unique experimental paradigm, that the celestial compass system of desert ants, Cataglyphis, relies predominantly on polarized skylight. If ants experience only parts of the polarization pattern during training but the full pattern in a subsequent test situation, they systematically deviate from their true homeward courses, with the systematics depending on what parts of the skylight patterns have been presented during training. This "signature" of the polarization compass remains unaltered, even if the ants can simultaneously experience the sun, which, if presented alone, enables the ants to select their true homeward courses. Information provided by direct sunlight and polarized skylight is picked up by different parts of the ant's compound eyes and is channeled into two rather separate systems of navigation.

Dendritic spine dynamics leading to spine elimination after repeated inductions of LTD

PubMed Central

Hasegawa, Sho; Sakuragi, Shigeo; Tominaga-Yoshino, Keiko; Ogura, Akihiko

2015-01-01

Memory is fixed solidly by repetition. However, the cellular mechanism underlying this repetition-dependent memory consolidation/reconsolidation remains unclear. In our previous study using stable slice cultures of the rodent hippocampus, we found long-lasting synaptic enhancement/suppression coupled with synapse formation/elimination after repeated inductions of chemical LTP/LTD, respectively. We proposed these phenomena as useful model systems for analyzing repetition-dependent memory consolidation. Recently, we analyzed the dynamics of dendritic spines during development of the enhancement, and found that the spines increased in number following characteristic stochastic processes. The current study investigates spine dynamics during the development of the suppression. We found that the rate of spine retraction increased immediately leaving that of spine generation unaltered. Spine elimination occurred independent of the pre-existing spine density on the dendritic segment. In terms of elimination, mushroom-type spines were not necessarily more stable than stubby-type and thin-type spines. PMID:25573377

Moving house: long-term dynamics of corticosterone secretion are unaltered in translocated populations of a rare reptile (the tuatara, Sphenodon punctatus).

PubMed

Anderson, Lindsay E; Cree, Alison; Towns, David R; Nelson, Nicola J

2015-01-01

Translocations are an important conservation tool used to restore at-risk species to their historical range. Unavoidable procedures during translocations, such as habitat disturbance, capture, handling, processing, captivity, transport and release to a novel environment, have the potential to be stressful for most species. In this study, we examined acute and chronic stress (through the measurement of the glucocorticoid corticosterone) in a rare reptile (the tuatara, Sphenodon punctatus). We found that: (i) the acute corticosterone response remains elevated during the initial translocation process but is not amplified by cumulative stressors; and (ii) the long-term dynamics of corticosterone secretion are similar in translocated and source populations. Taken together, our results show that translocated tuatara are generally resistant to cumulative acute stressors and show no hormonal sign of chronic stress. Translocation efforts in tuatara afford the potential to reduce extinction risk and restore natural ecosystems.

Modification of Lightweight Aggregates' Microstructure by Used Motor Oil Addition.

PubMed

Franus, Małgorzata; Jozefaciuk, Grzegorz; Bandura, Lidia; Lamorski, Krzysztof; Hajnos, Mieczysław; Franus, Wojciech

2016-10-18

An admixture of lightweight aggregate substrates (beidellitic clay containing 10 wt % of natural clinoptilolite or Na-P1 zeolite) with used motor oil (1 wt %-8 wt %) caused marked changes in the aggregates' microstructure, measured by a combination of mercury porosimetry (MIP), microtomography (MT), and scanning electron microscopy. Maximum porosity was produced at low (1%-2%) oil concentrations and it dropped at higher concentrations, opposite to the aggregates' bulk density. Average pore radii, measured by MIP, decreased with an increasing oil concentration, whereas larger (MT) pore sizes tended to increase. Fractal dimension, derived from MIP data, changed similarly to the MIP pore radius, while that derived from MT remained unaltered. Solid phase density, measured by helium pycnometry, initially dropped slightly and then increased with the amount of oil added, which was most probably connected to changes in the formation of extremely small closed pores that were not available for He atoms.

Bilateral somatosensory evoked potentials following intermittent theta-burst repetitive transcranial magnetic stimulation.

PubMed

Premji, Azra; Ziluk, Angela; Nelson, Aimee J

2010-08-05

Intermittent theta-burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation that may alter cortical excitability in the primary somatosensory cortex (SI). The present study investigated the effects of iTBS on subcortical and early cortical somatosensory evoked potentials (SEPs) recorded over left, iTBS stimulated SI and the right-hemisphere non-stimulated SI. SEPs were recorded before and at 5, 15, and 25 minutes following iTBS. Compared to pre-iTBS, the amplitude of cortical potential N20/P25 was significantly increased for 5 minutes from non-stimulated SI and for 15 to 25 minutes from stimulated SI. Subcortical potentials recorded bilaterally remained unaltered following iTBS. We conclude that iTBS increases the cortical excitability of SI bilaterally and does not alter thalamocortical afferent input to SI. ITBS may provide one avenue to induce cortical plasticity in the somatosensory cortex.

Modification of Lightweight Aggregates’ Microstructure by Used Motor Oil Addition

PubMed Central

Franus, Małgorzata; Jozefaciuk, Grzegorz; Bandura, Lidia; Lamorski, Krzysztof; Hajnos, Mieczysław; Franus, Wojciech

2016-01-01

An admixture of lightweight aggregate substrates (beidellitic clay containing 10 wt % of natural clinoptilolite or Na-P1 zeolite) with used motor oil (1 wt %–8 wt %) caused marked changes in the aggregates’ microstructure, measured by a combination of mercury porosimetry (MIP), microtomography (MT), and scanning electron microscopy. Maximum porosity was produced at low (1%–2%) oil concentrations and it dropped at higher concentrations, opposite to the aggregates’ bulk density. Average pore radii, measured by MIP, decreased with an increasing oil concentration, whereas larger (MT) pore sizes tended to increase. Fractal dimension, derived from MIP data, changed similarly to the MIP pore radius, while that derived from MT remained unaltered. Solid phase density, measured by helium pycnometry, initially dropped slightly and then increased with the amount of oil added, which was most probably connected to changes in the formation of extremely small closed pores that were not available for He atoms. PMID:28773964

Effects of initial-state nucleon shadowing on the elliptic flow of thermal photons

NASA Astrophysics Data System (ADS)

Dasgupta, Pingal; Chatterjee, Rupa; Singh, Sushant K.; Alam, Jan-e.

2018-03-01

Recently the effect of nucleon shadowing on the Monte Carlo-Glauber initial condition was studied and its role on the centrality dependence of elliptic flow (v2) and fluctuations in initial eccentricity for different colliding nuclei were explored. It was found that the results with shadowing effects are closer to the QCD-based dynamical model as well as to the experimental data. Inspired by this outcome, in this work we study the transverse momentum (pT) spectra and elliptic flow of thermal photons for Au +Au collisions at the BNL Relativisitic Heavy Ion Collider and Pb +Pb collisions at the CERN Large Hadron Collider by incorporating the shadowing effects in deducing the initial energy density profile required to solve the relativistic hydrodynamical equations. We find that the thermal photon spectra remain almost unaltered; however, the elliptic flow of photons is found to be enhanced significantly due to shadowing effects.

Proteomic analysis in giant axonal neuropathy: new insights into disease mechanisms.

PubMed

Mussche, Silke; De Paepe, Boel; Smet, Joél; Devreese, Katrien; Lissens, Willy; Rasic, Vedrana Milic; Murnane, Matthew; Devreese, Bart; Van Coster, Rudy

2012-08-01

Giant axonal neuropathy (GAN) is a progressive hereditary disease that affects the peripheral and central nervous systems. It is characterized morphologically by aggregates of intermediate filaments in different tissues. Mutations have been reported in the gene that codes for gigaxonin. Nevertheless, the underlying molecular mechanism remains obscure. Cell lines from 4 GAN patients and 4 controls were analyzed by iTRAQ. Among the dysregulated proteins were ribosomal protein L29, ribosomal protein L37, galectin-1, glia-derived nexin, and aminopeptidase N. Also, nuclear proteins linked to formin-binding proteins were found to be dysregulated. Although the major role of gigaxonin is reported to be degradation of cytoskeleton-associated proteins, the amount of 76 structural cytoskeletal proteins was unaltered. Several of the dysregulated proteins play a role in cytoskeletal reorganization. Based on these findings, we speculate that disturbed cytoskeletal regulation is responsible for formation of aggregates of intermediate filaments. Copyright © 2012 Wiley Periodicals, Inc.

The surface stability and morphology of tobermorite 11 Å from first principles

NASA Astrophysics Data System (ADS)

Mutisya, Sylvia M.; Miranda, Caetano R.

2018-06-01

Tobermorite minerals are important in many industrial processes typically occurring in hydrous environment. Their functionality is therefore governed in various aspects by their morphology and surface stability/reactivity. Here, we present the results of the surface energies and morphology of normal tobermorite 11 Å in a water vapor environment investigated by employing first principles atomistic thermodynamic calculations. For the low index tobermorite surfaces studied, the calculated surface energies fall within a narrow range (0.41-0.97 J/m2) with the (0 0 4) surface being the most stable. The equilibrium morphology is a thin pseudohexagonal plate elongated along the b axis. The hydrated surfaces are more stable at high water vapor chemical potentials with the stability enhanced as the water partial pressures are varied from ambient to supercritical hydrothermal conditions. Increasing the water vapor chemical potential gives rise to a smaller size of the tobermorite crystal, with the equilibrium morphology remaining unaltered.

Mud Volcanoes in the Martian Lowlands: Potential Windows to Fluid-Rich Samples from Depth

NASA Technical Reports Server (NTRS)

Oehler, Dorothy Z.; Allen, Carlton C.

2009-01-01

The regional setting of the Chryse-Acidalia area augurs well for a fluid-rich subsurface, accumulation of diverse rock types reflecting the wide catchment area, astrobiological prospectivity, and mud volcanism. This latter provides a mechanism for transporting samples from relatively great depth to the surface. Since mud volcanoes are not associated with extreme heat or shock pressures, materials they transport to the surface are likely to be relatively unaltered; thus such materials could contain interpretable remnants of potential martian life (e.g., organic chemical biomarkers, mineral biosignatures, or structural remains) as well as unmetamorphosed rock samples. None of the previous landings on Mars was located in an area with features identified as potential mud volcanoes (Fig. 3), but some of these features may offer targets for future missions aimed at sampling deep fluid-rich strata with potential habitable zones.

The classical and quantum dynamics of molecular spins on graphene.

PubMed

Cervetti, Christian; Rettori, Angelo; Pini, Maria Gloria; Cornia, Andrea; Repollés, Ana; Luis, Fernando; Dressel, Martin; Rauschenbach, Stephan; Kern, Klaus; Burghard, Marko; Bogani, Lapo

2016-02-01

Controlling the dynamics of spins on surfaces is pivotal to the design of spintronic and quantum computing devices. Proposed schemes involve the interaction of spins with graphene to enable surface-state spintronics and electrical spin manipulation. However, the influence of the graphene environment on the spin systems has yet to be unravelled. Here we explore the spin-graphene interaction by studying the classical and quantum dynamics of molecular magnets on graphene. Whereas the static spin response remains unaltered, the quantum spin dynamics and associated selection rules are profoundly modulated. The couplings to graphene phonons, to other spins, and to Dirac fermions are quantified using a newly developed model. Coupling to Dirac electrons introduces a dominant quantum relaxation channel that, by driving the spins over Villain's threshold, gives rise to fully coherent, resonant spin tunnelling. Our findings provide fundamental insight into the interaction between spins and graphene, establishing the basis for electrical spin manipulation in graphene nanodevices.

The classical and quantum dynamics of molecular spins on graphene

NASA Astrophysics Data System (ADS)

Cervetti, Christian; Rettori, Angelo; Pini, Maria Gloria; Cornia, Andrea; Repollés, Ana; Luis, Fernando; Dressel, Martin; Rauschenbach, Stephan; Kern, Klaus; Burghard, Marko; Bogani, Lapo

2016-02-01

Controlling the dynamics of spins on surfaces is pivotal to the design of spintronic and quantum computing devices. Proposed schemes involve the interaction of spins with graphene to enable surface-state spintronics and electrical spin manipulation. However, the influence of the graphene environment on the spin systems has yet to be unravelled. Here we explore the spin-graphene interaction by studying the classical and quantum dynamics of molecular magnets on graphene. Whereas the static spin response remains unaltered, the quantum spin dynamics and associated selection rules are profoundly modulated. The couplings to graphene phonons, to other spins, and to Dirac fermions are quantified using a newly developed model. Coupling to Dirac electrons introduces a dominant quantum relaxation channel that, by driving the spins over Villain’s threshold, gives rise to fully coherent, resonant spin tunnelling. Our findings provide fundamental insight into the interaction between spins and graphene, establishing the basis for electrical spin manipulation in graphene nanodevices.

In Vivo Physiological Experiments in the Random Positioning Macine: A Study on the Rat Intestinal Transit

NASA Astrophysics Data System (ADS)

Peana, A. T.; Marzocco, S.; Bianco, G.; Autore, G.; Pinto, A.; Pippia, P.

2008-06-01

The aim of this work is to evaluate the rat intestinal transit as well as the expression of enzymes involved in this process and in gastrointestinal homeostasis as ciclooxygenase (COX-1 and COX-2), the inducibile isoform of nitric oxide synthase (iNOS), ICAM-1 and heat shock proteins HSP70 and HSP90. The modeled microgravity conditions were performed utilizing a three-dimensional clinostat, the Random Positioning Machine (RPM). Our results indicate that modeled microgravity significantly reduce rat intestinal transit. Western blot analysis on small intestine tissues of RPM rats reveals a significant increase in iNOS expression, a significant reduction in COX-2 levels, while COX-1 expression remains unaltered, and a significant increase in ICAM-1 and HSP 70 expression. Also a significant increase in HSP 90 stomach expression indicates a strong effect of simulated low g on gastrointestinal homeostasis.

Influence of crystal habit on trimethoprim suspension formulation.

PubMed

Tiwary, A K; Panpalia, G M

1999-02-01

The role of crystal habit in influencing the physical stability and pharmacokinetics of trimethoprim suspensions was examined. Different habits for trimethoprim (TMP) were obtained by recrystallizing the commercial sample (PD) utilizing solvent-change precipitation method. Four distinct habits (microscopic observation) belonging to the same polymorphic state (DSC studies) were selected for studies. Preformulation and formulation studies were carried out on suspension dosage forms containing these crystals. The freshly prepared suspensions were also evaluated for their pharmacokinetic behaviour on healthy human volunteers using a cross over study. Variation of crystallization conditions produces different habits of TMP. Among the different crystal habits exhibiting same polymorphic state, the most anisometric crystal showed best physical stability in terms of sedimentation volume and redispersibility. However, habit did not significantly affect the extent of TMP excreted in urine. Modification of surface morphology without significantly altering the polymorphic state can be utilized for improving physical stability of TMP suspensions. However, the pharmacokinetic profile remains unaltered.

A Solution‐Doped Polymer Semiconductor:Insulator Blend for Thermoelectrics

PubMed Central

Kiefer, David; Yu, Liyang; Fransson, Erik; Gómez, Andrés; Primetzhofer, Daniel; Amassian, Aram; Campoy‐Quiles, Mariano

2016-01-01

Poly(ethylene oxide) is demonstrated to be a suitable matrix polymer for the solution‐doped conjugated polymer poly(3‐hexylthiophene). The polarity of the insulator combined with carefully chosen processing conditions permits the fabrication of tens of micrometer‐thick films that feature a fine distribution of the F4TCNQ dopant:semiconductor complex. Changes in electrical conductivity from 0.1 to 0.3 S cm−1 and Seebeck coefficient from 100 to 60 μV K−1 upon addition of the insulator correlate with an increase in doping efficiency from 20% to 40% for heavily doped ternary blends. An invariant bulk thermal conductivity of about 0.3 W m−1 K−1 gives rise to a thermoelectric Figure of merit ZT ∼ 10−4 that remains unaltered for an insulator content of more than 60 wt%. Free‐standing, mechanically robust tapes illustrate the versatility of the developed dopant:semiconductor:insulator ternary blends. PMID:28105396

ESR spectrum of Cr(V) with 2,3-dioxynaphthalene in a liquid crystal

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

Novosadov, N.A.; Mukhtarov, A.S.; Usmanov, Z.I.

1987-01-01

Research has previously been reported on the complex formed by Cr(V) with 2,3-dioxynaphthalene (I) in solution in DMFA. An open question remaining is the mutual orientation of the molecular symmetry axes and the magnetic ones. The authors give results on the complex formed by Cr(V) with I obtained by ESR in 4-methoxy-benzylidene-n-4'-butylaniline (MBBA). The ESR spectrum of Cr(V) with I in the nematic phase of MBBA is a strong line due to /sup 52/Cr with g = 1.978 and four weak lines due to /sup 53/Cr at the natural content with HFI constant a* = 11.8 x 10/sup -4/ T;more » when the MBBA is converted to the isotropic phase, the observed HFI constant from /sup 53/Cr increases to 18 x 10/sup -4/ T, while the g factor is unaltered.« less

Nanoscale control of oxide interface conduction in graphene-complex-oxide heterostructures

NASA Astrophysics Data System (ADS)

Huang, Mengchen; Ryu, Sangwoo; Ghahari, Fereshte; Jnawali, Giriraj; Ravichandran, Jayakanth; Irvin, Patrick; Kim, Philip; Eom, Chang-Beom; Levy, Jeremy

2014-03-01

Graphene is a promising material for high-speed optoelectronic devices such as THz modulators and detectors. Recently, broadband THz emission and detection can be achieved with nanostructures at the LaAlO3/SrTiO3 interface [2]. We have mechanically exfoliated single layer and multilayer graphene on top of 3.4 unit cell LaAlO3/SrTiO3 and successfully sketched nanowires in the 2DEG underneath graphene using conductive AFM lithgraphy [3]. Raman and AFM investigations confirm that the graphene quality and surface morphology remain unaltered by the writing process. These first experimental demonstrations of integrating graphene and LaAlO3/SrTiO3 are promising for future DC-THz photonic applications. We gratefully acknowledge support for this work from ONR (N00014-13-1-0806), NSF(DMR-1124131, DMR-1104191), and AFOSR (FA9550-12-1-0342).

Supercritical Carbon Dioxide Extraction of Coronene in the Presence of Perchlorate for In Situ Chemical Analysis of Martian Regolith.

PubMed

McCaig, Heather C; Stockton, Amanda; Crilly, Candice; Chung, Shirley; Kanik, Isik; Lin, Ying; Zhong, Fang

2016-09-01

The analysis of the organic compounds present in the martian regolith is essential for understanding the history and habitability of Mars, as well as studying the signs of possible extant or extinct life. To date, pyrolysis, the only technique that has been used to extract organic compounds from the martian regolith, has not enabled the detection of unaltered native martian organics. The elevated temperatures required for pyrolysis extraction can cause native martian organics to react with perchlorate salts in the regolith and possibly result in the chlorohydrocarbons that have been detected by in situ instruments. Supercritical carbon dioxide (SCCO2) extraction is an alternative to pyrolysis that may be capable of delivering unaltered native organic species to an in situ detector. In this study, we report the SCCO2 extraction of unaltered coronene, a representative polycyclic aromatic hydrocarbon (PAH), from martian regolith simulants, in the presence of 3 parts per thousand (ppth) sodium perchlorate. PAHs are a class of nonpolar molecules of astrobiological interest and are delivered to the martian surface by meteoritic infall. We also determined that the extraction efficiency of coronene was unaffected by the presence of perchlorate on the regolith simulant, and that no sodium perchlorate was extracted by SCCO2. This indicates that SCCO2 extraction can provide de-salted samples that could be directly delivered to a variety of in situ detectors. SCCO2 was also used to extract trace native fluorescent organic compounds from the martian regolith simulant JSC Mars-1, providing further evidence that SCCO2 extraction may provide an alternative to pyrolysis to enable the delivery of unaltered native organic compounds to an in situ detector on a future Mars rover. Biomarkers-Carbon dioxide-In situ measurement-Mars-Search for Mars' organics. Astrobiology 16, 703-714.

Peroxidized mineral oil increases the oxidant status of culture media and inhibits in vitro porcine embryo development.

PubMed

Martinez, C A; Nohalez, A; Ceron, J J; Rubio, C P; Roca, J; Cuello, C; Rodriguez-Martinez, H; Martinez, E A; Gil, M A

2017-11-01

The use of oils with undetected alterations is a long-recognized problem for in vitro embryo production systems. Since peroxides in oils have been associated with reduced embryo production outcomes, our goals were (1) to evaluate the effects of a batch of mineral oil (MO) that was suspected to be altered on the in vitro production of pig embryos and (2) to determine oil peroxide values throughout culture and the transfer of oxidant agents from oil to culture media. Sunflower oil, which has a completely different chemical composition than MO but a higher oxidative status, and unaltered MO were used as controls. Oocyte maturation, fertilization and embryo development were affected differently depending on the oil overlay used. While the suspected MO was not able to sustain in vitro maturation and fertilization, the oocytes incubated in the presence of sunflower oil were matured and fertilized similarly to those of the unaltered MO group. Moreover, the cleavage rate of presumed zygotes cultured under the suspected MO was severely reduced compared with those cultured under the other oils, and none of the cleaved embryos developed to the blastocyst stage. Although the cleavage rates in the sunflower oil and unaltered MO groups were similar, embryos cultured under sunflower oil also failed to develop to the blastocyst stage. Our results revealed that the suspected MO and sunflower oil had similar levels of peroxides and that these levels were much higher than those of the unaltered MO. The total oxidant status was higher in media incubated under peroxidized oils than in fresh media or media incubated without an oil overlay or under unaltered MO, indicating that oxidant agents were transferred to the incubation media. However, unlike the sunflower oil group, the culture media incubated under the suspected MO had high levels of total oxidant status and low levels of hydrogen peroxide and reactive oxygen species, suggesting the presence of other unknown oxidant agents in that oil. These results indicate that a peroxidized MO overlay dramatically decreases embryo production outcomes. This decrease could be associated with the higher peroxide values of the oil but cannot be explained by the levels of hydrogen peroxide and reactive oxygen species transferred from the oil to the culture media. It is likely that different oxidant agent(s) and/or other toxic compounds present in the peroxidized MO are responsible for its damaging effects on oocytes and embryos. Copyright © 2017 Elsevier Inc. All rights reserved.

Graphene Quantum Dot-Aerogel: From Nanoscopic to Macroscopic Fluorescent Materials. Sensing Polyaromatic Compounds in Water.

PubMed

Martín-Pacheco, Ana; Del Río Castillo, Antonio Esaú; Martín, Cristina; Herrero, María Antonia; Merino, Sonia; García Fierro, José Luis; Díez-Barra, Enrique; Vázquez, Ester

2018-05-30

Fluorescence based on quantum confinement is a property restricted to the nanoscopic range. The incorporation of nanoparticles in a three-dimensional polymeric network could afford macroscopic scaffolds that show nanoscopic properties. Moreover, if these scaffolds are based on strong bonds, the stability of the resulting materials can be preserved, thus enhancing their final applications. We report for the first time the preparation of a graphene quantum dot (GQD) composite based on a cationic covalent network. This new material has unusual features: (i) the final composite remains stable after several swelling-deswelling cycles, thus demonstrating strong interactions between GQDs and the polymeric material, and therefore it could be used as a portable system. (ii) Fluorescence emission in the composite and in solution is quasi-independent to the excitation wavelength. (iii) However, and in contrast to the behavior observed in GQD solutions, the fluorescence of the composite remains unaltered over a wide pH range and in the presence of different ions commonly found in tap water. (iv) Fluorescence quenching is only observed as a consequence of molecules that bear aromatic systems, and this could be applied to the preparation of in situ water sensors.

Remotely-sensed detection of effects of extreme droughts on gross primary production.

PubMed

Vicca, Sara; Balzarolo, Manuela; Filella, Iolanda; Granier, André; Herbst, Mathias; Knohl, Alexander; Longdoz, Bernard; Mund, Martina; Nagy, Zoltan; Pintér, Krisztina; Rambal, Serge; Verbesselt, Jan; Verger, Aleixandre; Zeileis, Achim; Zhang, Chao; Peñuelas, Josep

2016-06-15

Severe droughts strongly impact photosynthesis (GPP), and satellite imagery has yet to demonstrate its ability to detect drought effects. Especially changes in vegetation functioning when vegetation state remains unaltered (no browning or defoliation) pose a challenge to satellite-derived indicators. We evaluated the performance of different satellite indicators to detect strong drought effects on GPP in a beech forest in France (Hesse), where vegetation state remained largely unaffected while GPP decreased substantially. We compared the results with three additional sites: a Mediterranean holm oak forest (Puéchabon), a temperate beech forest (Hainich), and a semi-arid grassland (Bugacpuszta). In Hesse, a three-year reduction in GPP following drought was detected only by the Enhanced Vegetation Index (EVI). The Photochemical Reflectance Index (PRI) also detected this drought effect, but only after normalization for absorbed light. In Puéchabon normalized PRI outperformed the other indicators, while the short-term drought effect in Hainich was not detected by any tested indicator. In contrast, most indicators, but not PRI, captured the drought effects in Bugacpuszta. Hence, PRI improved detection of drought effects on GPP in forests and we propose that PRI normalized for absorbed light is considered in future algorithms to estimate GPP from space.

A static organization in a dynamic context--A qualitative study of changes in working conditions for Swedish engine officers.

PubMed

Lundh, Monica; Rydstedt, Leif W

2016-07-01

During the last decades the shipping industry has undergone rapid technical developments and experienced hard economic conditions and increased striving for profitability. This has led to reduced staffing and changes in task performance, which has been reported to increase workload for the remaining seafarers. The working conditions on board have a number of distinct and in many ways unique characteristics, which makes the job demands and resources for seafarers unique in several ways. The purpose of this study was to assess how engine room staff perceives how these major technical and organizational changes in the shipping industry have affected job demands as well as resources. The study compiled individual interviews and focus groups interviews with engine crew members where they were asked to elaborate on the psychosocial work environment and the major changes in the working conditions on board. Engine crew describes a work situation where they feel a lack of resources. The content of the work has changed, staffing has been reduced, new tasks are being added but the organization of the crew and the design of the work place remains unaltered. Copyright © 2016 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Anorectal function and morphology in patients with sporadic proctalgia fugax.

PubMed

Eckardt, V F; Dodt, O; Kanzler, G; Bernhard, G

1996-07-01

The pathophysiology of sporadic proctalgia fugax remains unknown. This study investigates whether patients with this syndrome exhibit alterations in anal function and morphology. Eighteen patients with sporadic proctalgia fugax and 18 sex-matched and age-matched healthy controls were studied. Manometric studies investigated anal resting and squeeze pressures, the rectoanal inhibitory reflex, rectal compliance, and smooth muscle response to edrophonium chloride administration. External and internal sphincter thickness was measured endosonographically. Patients had slightly higher (P = 0.0291) anal resting pressures (65.5 +/- 11.4 mmHg) than controls (56 +/- 9.9 mmHg). However, anal squeeze pressure, sphincter relaxation during rectal distention, and rectal compliance were similar in both groups, and no alterations were detected in external and internal anal sphincter thickness. Edrophonium chloride administration was followed by sharp postrelaxation contractions in two patients, whereas anal function remained unaltered in controls. Acute episodes of proctalgia, which occurred in two patients while under study, were associated with a rise in anal resting tone and an increase in slow wave amplitude. In the resting state, patients with proctalgia fugax have normal anorectal function and morphology. However, they may exhibit a motor abnormality of the anal smooth muscle during an acute attack.

Mechanical-physical experimental tests on lime mortars and bricks reinforced with hemp

NASA Astrophysics Data System (ADS)

Formisano, Antonio; Dessı, Enzo; Landolfo, Raffaele

2017-11-01

Hemp is an agricultural product used for various applications. In the Civil Engineering field, only a limited use of this natural material, called the "green pig" since exploitation of all its constituent parts is allowed, has been done. For this reason, in the paper an experimental activity on lime mortars and bricks reinforced with hemp components has been performed. Compression and bending tests have been carried out on specimens manufactured with hemp shives and fibres, respectively. The achieved results have shown that hemp products change the failure modes from brittle to ductile, leaving basically unaltered the strength capacity of reinforced specimens with respect to unreinforced ones.

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

Diallo, S. O.; Zhang, Q.; O'Neill, H.

Here we present a pressure-dependence study of the dynamics of lysozyme protein powder immersed in deuterated , α-trehalose environment via quasielastic neutron scattering (QENS). The goal is to assess the baroprotective benefits of trehalose on biomolecules by comparing the findings with those of a trehalose-free reference study. While the mean-square displacement of the trehalose-free protein (hydrated to d D₂O ≃40 w%) as a whole, is reduced by increasing pressure, the actual observable relaxation dynamics in the picoseconds to nanoseconds time range remains largely unaffected by pressure up to the maximum investigated pressure of 2.78(2) Kbar. Our observation is independent ofmore » whether or not the protein is mixed with the deuterated sugar. This suggests that the hydrated protein s conformational states at atmospheric pressure remain unaltered by hydrostatic pressures, below 2.78 Kbar. We also found the QENS response to be totally recoverable after ambient pressure conditions are restored. Small-angle neutron diffraction measurements confirm that the protein-protein correlation remains undisturbed.We observe, however, a clear narrowing of the QENS response as the temperature is decreased from 290 to 230 K in both cases, which we parametrize using the Kohlrausch-Williams-Watts stretched exponential model. Finally, only the fraction of protons that are immobile on the accessible time window of the instrument, referred to as the elastic incoherent structure factor, is observably sensitive to pressure, increasing only marginally but systematically with increasing pressure.« less

Quantum Dot/Siloxane Composite Film Exceptionally Stable against Oxidation under Heat and Moisture.

PubMed

Kim, Hwea Yoon; Yoon, Da-Eun; Jang, Junho; Lee, Daewon; Choi, Gwang-Mun; Chang, Joon Ha; Lee, Jeong Yong; Lee, Doh C; Bae, Byeong-Soo

2016-12-21

We report on the fabrication of a siloxane-encapsulated quantum dot (QD) film (QD-silox film), which exhibits stable emission intensity for over 1 month even at elevated temperature and humidity. QD-silox films are solidified via free radical addition reaction between oligosiloxane resin and ligand molecules on QDs. We prepare the QD-oligosiloxane resin by sol-gel condensation reaction of silane precursors with QDs blended in the precursor solution, forgoing ligand-exchange of QDs. The resulting QD-oligosiloxane resin remains optically clear after 40 days of storage, in contrast to other QD-containing resins which turn turbid and ultimately form sediments. QDs also disperse uniformly in the QD-silox film, whose photoluminescence (PL) quantum yield (QY) remains nearly unaltered under harsh conditions; for example, 85 °C/5% relative humidity (RH), 85 °C/85% RH, strongly acidic, and strongly basic environments for 40 days. The QD-silox film appears to remain equally emissive even after being immersed into boiling water (100 °C). Interestingly, the PL QY of the QD-silox film noticeably increases when the film is exposed to a moist environment, which opens a new, facile avenue to curing dimmed QD-containing films. Given its excellent stability, we envision that the QD-silox film is best suited in display applications, particularly as a PL-type down-conversion layer.

Detection and mapping of hydrothermally altered rocks in the vicinity of the Comstock Lode, Virginia Range, Nevada, using enhanced Landsat images

USGS Publications Warehouse

Ashley, Roger P.; Goetz, A.F.H.; Rowan, L.C.; Abrams, M.J.

1979-01-01

The Virginia Range, immediately southeast of Reno, Nev., consists mainly of flows, breccias, and turfs of Miocene age. Most of these volcanic rocks are of intermediate composition; rhyodacite is the most common rock type. Basalt, rhyolite and rhyolite tuff, and tuffaceous sedimentary rocks of Miocene and Pliocene age also cover substantial areas in the range. Pre-Tertiary metasedimentary, metavolcanic, and granitic rocks are exposed in scattered inliers, mostly along the southern and eastern margins of the range. Several large areas and many small areas within the volcanic pile were subjected to hydrothermal alteration during and after the period of intermediate volcanic activity. Economic precious metal mineralization is spatially and temporally associated with the hydrothermal alteration in several areas. The most important deposit is the Comstock Lode, which produced 192 million troy ounces of silver and 8.3 million troy ounces of gold from epithermal veins (Bonham, 1969). The hydrothermally altered rocks include silicified, advanced argillic, montmorillonite-bearing argillic, and propylitic types. The first three types typically contain pyrite, and some propylitic rocks contain pyrite as well. Supergene oxidation of these pyritic rocks produces limonitic bleached rocks. The term 'limonite,' as used here, refers to any combination of the minerals hematite, goethite, and Jarosite. Where vegetation cover is sparse to moderate, these limonitic rocks are readily identified on Landsat images enhanced by the color-ratio composite technique developed by Rowan and others (1974), so the altered areas can be mapped. About 30 percent tree cover (here mainly pinyon pine) is sufficient to change the spectral signature of individual picture elements (pixels) enough so that limonitic materials can no longer be uniquely identified. As in all other areas where this technique has been applied, limonitic unaltered rocks with intermediate to high albedos have the same appearance on the color-ratio composite as limonitic altered rocks. This problem represents the most important limitation to the use of enhanced Landsat images for detection and mapping of hydrothermally altered rocks. Reflectance spectra of altered and unaltered rocks taken in the field in the Virginia Range show that most altered rocks have a conspicuous absorption band near 2.2 ?m produced by clay minerals or alunite, whereas unaltered rocks have no features in this spectral region. Thus spectral information for selected bands in the 1.1-2.5 ?m region may allow discrimination between limonitic altered and limonitic unaltered rocks (Rowan and others, 1977; Abrams and others, 1977; Rowan and Abrams, 1978). Another potential limitation is loss of spectral information on slopes with low effective sun angle. Although a minor problem in the Virginia Range, loss of information sufficient to preclude identification of limonitic altered rocks occurs with effective sun angle lower than 20-25 degrees. Thus, even at moderate latitudes substantial parts of areas with high topographic relief may be lost to observation.

Feedforward neural control of toe walking in humans.

PubMed

Lorentzen, Jakob; Willerslev-Olsen, Maria; Hüche Larsen, Helle; Svane, Christian; Forman, Christian; Frisk, Rasmus; Farmer, Simon Francis; Kersting, Uwe; Nielsen, Jens Bo

2018-03-23

Activation of ankle muscles at ground contact during toe walking is unaltered when sensory feedback is blocked or the ground is suddenly dropped. Responses in the soleus muscle to transcranial magnetic stimulation, but not peripheral nerve stimulation, are facilitated at ground contact during toe walking. We argue that toe walking is supported by feedforward control at ground contact. Toe walking requires careful control of the ankle muscles in order to absorb the impact of ground contact and maintain a stable position of the joint. The present study aimed to clarify the peripheral and central neural mechanisms involved. Fifteen healthy adults walked on a treadmill (3.0 km h -1 ). Tibialis anterior (TA) and soleus (Sol) EMG, knee and ankle joint angles, and gastrocnemius-soleus muscle fascicle lengths were recorded. Peripheral and central contributions to the EMG activity were assessed by afferent blockade, H-reflex testing, transcranial magnetic brain stimulation (TMS) and sudden unloading of the planter flexor muscle-tendon complex. Sol EMG activity started prior to ground contact and remained high throughout stance. TA EMG activity, which is normally seen around ground contact during heel strike walking, was absent. Although stretch of the Achilles tendon-muscle complex was observed after ground contact, this was not associated with lengthening of the ankle plantar flexor muscle fascicles. Sol EMG around ground contact was not affected by ischaemic blockade of large-diameter sensory afferents, or the sudden removal of ground support shortly after toe contact. Soleus motor-evoked potentials elicited by TMS were facilitated immediately after ground contact, whereas Sol H-reflexes were not. These findings indicate that at the crucial time of ankle stabilization following ground contact, toe walking is governed by centrally mediated motor drive rather than sensory driven reflex mechanisms. These findings have implications for our understanding of the control of human gait during voluntary toe walking. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Male and female voices activate distinct regions in the male brain.

PubMed

Sokhi, Dilraj S; Hunter, Michael D; Wilkinson, Iain D; Woodruff, Peter W R

2005-09-01

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions.

Influence of neonatal and adult hyperthyroidism on behavior and biosynthetic capacity for norepinephrine, dopamine and 5-hydroxytryptamine in rat brain.

PubMed

Rastogi, R B; Singhal, R L

1976-09-01

In neonatal rats, administration of l-triiodothyronine (10 mug/100 g/day) for 30 days presented signs of hyperthyroidism which included accelerated development of a variety of physical and behavioral characteristics accompanying maturation. The spontaneous motor activity was increased by 69%. Exposure of developing rats to thyroid hormone significantly increased the endogenous concentration of striatal tyrosine and the activity of tyrosine hydroxylase as well as the levels of dopamine in several brain regions. The concentration of striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid, the chief metabolites of dopamine, was also increased and the magnitude of change was greater than the rise in dopamine. Despite increases in the activity of tyrosine hydroxylase and the availability of the substrate tyrosine, the steady-state levels of norepinephrine remained unaltered in various regions of brain except in cerebellum. Futhermore, neonatal hyperthyroidism significantly increased the levels of midbrain tryptophan and tryptophan hydroxylase activity but produced no change in 5-hydroxytryptamine levels of several discrete brain regions, except hypothalamus and cerebellum where its concentration was slightly decreased. However, the 5-hydroxyindoleacetic acid levels were enhanced in hypothalamus, ponsmedulla, midbrain, striatum and hippocampus. The elevated levels of 5-hydroxyindoleacetic acid did not seem to be due to increased intraneuronal deamination of 5-hydroxytryptamine since monoamine oxidase activity was not affected in cerebral cortex and midbrain of hyperthyroid rats. The data demonstrate that hyperthyroidism significantly increased the synthesis as well as the utilization of catecholamines and 5-hydroxytryptamine in maturing brain. Since the mature brain is known to respond differently to thyroid hormone action than does the developing brain, the effect of L-triiodothyronine treatment on various putative neurohumors also was examined in adult rats. Whereas administration of l-triiodothyronine (10 mug/100 g/day) for 30 days to 120-day-old rats increased the levels of tyrosine by 23% and of tryptophan by 43%, no appreciable change was noted in tryptophan hydroxylase activity. In contrast to neonatal hyperthyroidism, excess of thyroid hormone in adult rats failed to produce any change in motor activity and tended to decrease striatal tyrosine hydroxylase activity only slightly. The concentration of dopamine remained unchanged in all regions of the brain except in midbrain where it rose by 19%. Whereas norepinephrine concentration was altered in hypothalamus, pons-medulla and midbrain, the levels of 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, were significantly decreased in striatum and cerebellum. Since dopaminergic and noradrenergic neurons are the critical components of the motor system, the possibility exists that elevated behavioral activity in young L-triiodothyronine-treated animals might be associated with increased turnover of catecholamines in neuronal tissue.

Effects of Igneous Intrusion on Microporosity and Gas Adsorption Capacity of Coals in the Haizi Mine, China

PubMed Central

2014-01-01

This paper describes the effects of igneous intrusions on pore structure and adsorption capacity of the Permian coals in the Huaibei Coalfield, China. Twelve coal samples were obtained at different distances from a ~120 m extremely thick sill. Comparisons were made between unaltered and heat-affected coals using geochemical data, pore-fracture characteristics, and adsorption properties. Thermal alteration occurs down to ~1.3 × sill thickness. Approaching the sill, the vitrinite reflectance (R o) increased from 2.30% to 2.78%, forming devolatilization vacuoles and a fine mosaic texture. Volatile matter (VM) decreased from 17.6% to 10.0% and the moisture decreased from 3.0% to 1.6%. With decreasing distance to the sill, the micropore volumes initially increased from 0.0054 cm3/g to a maximum of 0.0146 cm3/g and then decreased to 0.0079 cm3/g. The results show that the thermal evolution of the sill obviously changed the coal geochemistry and increased the micropore volume and adsorption capacity of heat-affected coal (60–160 m from the sill) compared with the unaltered coals. The trap effect of the sill prevented the high-pressure gas from being released, forming gas pocket. Mining activities near the sill created a low pressure zone leading to the rapid accumulation of methane and gas outbursts in the Haizi Mine. PMID:24723841

Soil-plant-microbial relations in hydrothermally altered soils of Northern California

USGS Publications Warehouse

Blecker, S.W.; Stillings, L.L.; DeCrappeo, N.M.; Ippolito, J.A.

2014-01-01

Soils developed on relict hydrothermally altered soils throughout the Western USA present unique opportunities to study the role of geology on above and belowground biotic activity and composition. Soil and vegetation samples were taken at three unaltered andesite and three hydrothermally altered (acid-sulfate) sites located in and around Lassen VolcanicNational Park in northeastern California. In addition, three different types of disturbed areas (clearcut, thinned, and pipeline) were sampled in acid-sulfate altered sites. Soils were sampled (0–15 cm) in mid-summer 2010 from both under-canopy and between-canopy areas within each of the sites. Soils were analyzed for numerous physical and chemical properties along with soil enzyme assays, C and N mineralization potential, microbial biomass-C and C-substrate utilization. Field vegetation measurements consisted of canopy cover by life form (tree, shrub, forb, and grass), tree and shrub density, and above-ground net primary productivity of the understory. Overall, parameters at the clearcut sites were more similar to the unaltered sites, while parameters at the thinned and pipeline sites were more similar to the altered sites. We employed principal components analysis (PCA) to develop two soil quality indices (SQI) to help quantify the differences among the sites: one based on the correlation between soil parameters and canopy cover, and the second based on six sub-indices. Soil quality indices developed in these systems could provide a means for monitoring and identifying key relations between the vegetation, soils, and microorganisms.

Diagenesis Along Fractures in an Eolian Sandstone, Gale Crater, Mars

NASA Technical Reports Server (NTRS)

Ming, D. W.; Yen, A. S.; Rampe, E. B.; Grotzinger, J. P.; Blake, D. F.; Bristow, T. F.; Chipera, S. J.; Downs, R.; Morris, R. V.; Morrison, S. M.;

[The effect of enzymatic treatment using proteases on properties of persistent sodium current in CA1 pyramidal neurons of rat hippocampus].

PubMed

Lun'ko, O O; Isaiev, D S; Maxymiuk, O P; Kryshtal', O O; Isaieva, O V

2014-01-01

We investigated the effect of proteases, widely used for neuron isolation in electrophysiological studies, on the amplitude and kinetic characteristics of persistent sodium current (I(NaP)) in hippocampal CA1 pyramidal neurons. Properties of I(NaP) were studied on neurons isolated by mechanical treatment (control group) and by mechanical and enzymatic treatment using pronase E (from Streptomyces griseus) or protease type XXIII (from Aspergillus oryzae). We show that in neurons isolated with pronase E kinetic of activation and density of I(NaP) was unaltered. Enzymatic treatment with protease type XXIII did not alter I(NaP) activation but result in significant decrease in I(NaP) density. Our data indicates that enzymatic treatment using pronase E for neuron isolation is preferable for investigation of I(NaP).

Energy deficit does not affect immune responses of experimentally infected pacu (Piaractus mesopotamicus).

PubMed

Gimbo, Rodrigo Y; Fávero, Gisele C; Franco Montoya, Luz N; Urbinati, Elisabeth C

2015-04-01

We investigated if the energy deficit following a 30-day starvation period could affect the ability of fish to mount immune responses after experimental exposure to Aeromonas hydrophila. Fish were submitted to two feeding strategies during 30 days: starvation and continuously feeding. Fish were then sampled to allow for the assessment of baseline metabolic and immune system indicators, were next intraperitonially inoculated with A. hydrophila, and finally were sampled at 3 and 24 h after the challenge. The respiratory activity of leukocytes was lower in starved fish at baseline, increasing after bacterial inoculation to levels similar to those seen among fed fish. Levels of serum lysozyme were higher in starved fish at baseline. The same response profile was observed 3 h after inoculation, but among fed fish, these levels increased to values similar to those of starved fish 24 h after infection. Among starved fish, lysozyme concentration did not change over the course of the experiment. The serum ACH activity was lower in starved fish at baseline and increased after bacterial inoculation in both fish groups. Baseline levels of blood glucose of starved fish were lower than those of fed fish and increased 3 h after bacterial inoculation in both fish groups, decreasing in both groups at 24 h after inoculation. Baseline liver glycogen levels were similar in both fish groups and higher than at 3 and 24 h after inoculation. Three hours after bacterial inoculation, liver glycogen was less reduced in fed fish. Baseline levels of blood triglycerides were lower in starved fish and the profile remained unchanged 3 h after inoculation. There was a gradual decrease in fed fish, and the levels of starved fish remained unchanged throughout the observation period. Blood glycerol levels at baseline were higher in starved fish than in fed fish and remained unaltered at 3 h after inoculation. However those levels increased at 24 h. In fed fish there was a gradual increase of glycerol levels up to 24 h after bacterial inoculation. Baseline liver lipid levels of starved fish were lower and this difference in the response profile remained unchanged 3 and 24 h after inoculation. The liver lipid levels of starved fish decreased after inoculation, and remained unchanged in fed fish. As observed in liver lipid, muscle lipid levels of starved fish were lower than in fed fish, throughout the experiment. Starved fish levels remained unchanged; however fed fish levels decreased 24 h after bacterial inoculation. Levels of cortisol were higher in starved fish at baseline and increased in both fish groups 3 h after bacterial inoculation, reaching intermediary levels 24 h after inoculation. Our results show that in pacu, although mounting an immune response triggered after bacterial exposure is an energy-expensive process, fish under energetic deficit status were able to display protection against infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Magnetic fields are causing small, but significant changes of the radiochromic EBT3 film response to 6 MV photons

NASA Astrophysics Data System (ADS)

Delfs, Björn; Schoenfeld, Andreas A.; Poppinga, Daniela; Kapsch, Ralf-Peter; Jiang, Ping; Harder, Dietrich; Poppe, Björn; Khee Looe, Hui

2018-02-01

The optical density (OD) of EBT3 radiochromic films (Ashland Specialty Ingredients, Bridgewater, NJ, USA) exposed to absorbed doses to water up to D  =  20 Gy in magnetic fields of B  =  0.35 and 1.42 T was measured in the three colour channels of an Epson Expression 10000XL flatbed scanner. A 7 cm wide water phantom with fixed film holder was placed between the pole shoes of a constant-current electromagnet with variable field strength and was irradiated by a 6 MV photon beam whose axis was directed at right angles with the field lines. The doses at the film position at water depth 5 cm were measured with a calibrated ionization chamber when the magnet was switched off and were converted to the doses in presence of the magnetic field via the monitor units and by a Monte Carlo-calculated correction accounting for the slight change of the depth dose curves in magnetic fields. In the presence of the 0.35 and 1.42 T fields small negative changes of the OD values at given absorbed doses to water occurred and just significantly exceeded the uncertainty margin given by the stochastic and the uncorrected systematic deviations. This change can be described by a  +2.1% change of the dose values needed to produce a given optical density in the presence of a 1.42 T field. The thereby modified OD versus D function remained unchanged irrespective of whether the original short film side—the preference direction of the monomer crystals of the film—was directed parallel or orthogonal to the magnetic field. The ‘orientation effect’, the difference between the optical densities measured in the ‘portrait’ or ‘landscape’ film positions on the scanner bed caused by the reflection of polarised light in the scanner’s mirror system, remained unaltered after EBT3 film exposure in magnetic fields. An independent optical bench investigation of EBT3 films exposed to doses of 10 and 20 Gy at 0.35 and 1.42 T showed that the direction of the electric vector of polarised light experiencing the largest transmission through EBT3 films remained unaltered after film exposure in the magnetic fields. The observed small modification of the OD versus D curve of the radiochromic film EBT3 in the range up to 20 Gy and 1.42 T, hardly exceeding the experimental uncertainty margin, numerically confirms other recent studies on EBT3 film. A stronger magnetic field effect had been observed with the previous product EBT2 exposed to 60Co gamma radiation at 0.35 T.

Magnetic fields are causing small, but significant changes of the radiochromic EBT3 film response to 6 MV photons.

PubMed

Delfs, Björn; Schoenfeld, Andreas A; Poppinga, Daniela; Kapsch, Ralf-Peter; Jiang, Ping; Harder, Dietrich; Poppe, Björn; Looe, Hui Khee

2018-01-31

The optical density (OD) of EBT3 radiochromic films (Ashland Specialty Ingredients, Bridgewater, NJ, USA) exposed to absorbed doses to water up to D  =  20 Gy in magnetic fields of B  =  0.35 and 1.42 T was measured in the three colour channels of an Epson Expression 10000XL flatbed scanner. A 7 cm wide water phantom with fixed film holder was placed between the pole shoes of a constant-current electromagnet with variable field strength and was irradiated by a 6 MV photon beam whose axis was directed at right angles with the field lines. The doses at the film position at water depth 5 cm were measured with a calibrated ionization chamber when the magnet was switched off and were converted to the doses in presence of the magnetic field via the monitor units and by a Monte Carlo-calculated correction accounting for the slight change of the depth dose curves in magnetic fields. In the presence of the 0.35 and 1.42 T fields small negative changes of the OD values at given absorbed doses to water occurred and just significantly exceeded the uncertainty margin given by the stochastic and the uncorrected systematic deviations. This change can be described by a  +2.1% change of the dose values needed to produce a given optical density in the presence of a 1.42 T field. The thereby modified OD versus D function remained unchanged irrespective of whether the original short film side-the preference direction of the monomer crystals of the film-was directed parallel or orthogonal to the magnetic field. The 'orientation effect', the difference between the optical densities measured in the 'portrait' or 'landscape' film positions on the scanner bed caused by the reflection of polarised light in the scanner's mirror system, remained unaltered after EBT3 film exposure in magnetic fields. An independent optical bench investigation of EBT3 films exposed to doses of 10 and 20 Gy at 0.35 and 1.42 T showed that the direction of the electric vector of polarised light experiencing the largest transmission through EBT3 films remained unaltered after film exposure in the magnetic fields. The observed small modification of the OD versus D curve of the radiochromic film EBT3 in the range up to 20 Gy and 1.42 T, hardly exceeding the experimental uncertainty margin, numerically confirms other recent studies on EBT3 film. A stronger magnetic field effect had been observed with the previous product EBT2 exposed to 60 Co gamma radiation at 0.35 T.

Acute stress alters autonomic modulation during sleep in women approaching menopause.

PubMed

de Zambotti, Massimiliano; Sugarbaker, David; Trinder, John; Colrain, Ian M; Baker, Fiona C

2016-04-01

Hot flashes, hormones, and psychosocial factors contribute to insomnia risk in the context of the menopausal transition. Stress is a well-recognized factor implicated in the pathophysiology of insomnia; however the impact of stress on sleep and sleep-related processes in perimenopausal women remains largely unknown. We investigated the effect of an acute experimental stress (impending Trier Social Stress Task in the morning) on pre-sleep measures of cortisol and autonomic arousal in perimenopausal women with and without insomnia that developed in the context of the menopausal transition. In addition, we assessed the macro- and micro-structure of sleep and autonomic functioning during sleep. Following adaptation to the laboratory, twenty two women with (age: 50.4 ± 3.2 years) and eighteen women without (age: 48.5 ± 2.3 years) insomnia had two randomized in-lab overnight recordings: baseline and stress nights. Anticipation of the task resulted in higher pre-sleep salivary cortisol levels and perceived tension, faster heart rate and lower vagal activity, based on heart rate variability measures, in both groups of women. The effect of the stress manipulation on the autonomic nervous system extended into the first 4 h of the night in both groups. However, vagal tone recovered 4-6 h into the stress night in controls but not in the insomnia group. Sleep macrostructure was largely unaltered by the stress, apart from a delayed latency to REM sleep in both groups. Quantitative analysis of non-rapid eye movement sleep microstructure revealed greater electroencephalographic (EEG) power in the beta1 range (15-≤23 Hz), reflecting greater EEG arousal during sleep, on the stress night compared to baseline, in the insomnia group. Hot flash frequency remained similar on both nights for both groups. These results show that pre-sleep stress impacts autonomic nervous system functioning before and during sleep in perimenopausal women with and without insomnia. Findings also indicate that women with insomnia had increased EEG arousal and lacked recovery in vagal activity across the stress night suggesting a greater sensitivity to stress in this group. Copyright © 2015 Elsevier Ltd. All rights reserved.

β-adrenergic Receptor Blocker ICI 118,551 Selectively Increases Intermediate-Conductance Calcium-Activated Potassium Channel (IKCa )-Mediated Relaxations in Rat Main Mesenteric Artery.

PubMed

Ozkan, Melike Hacer; Uma, Serdar

2018-06-01

Endothelial IK C a and/or SK C a channels play an important role in the control of vascular tone by participating in endothelium-dependent relaxation. Whether β-AR antagonists, mainly used in hypertension, affect endothelial K C a channel function is unknown. In this study, we examined the effect of the β2-AR antagonist and inverse agonist ICI 118,551 on the IK C a /SK C a channel activity by assessing functional relaxation responses to several agonists that stimulate these channels. Mesenteric arterial rings isolated from male Sprague Dawley mounted to organ baths. Acetylcholine elicited IK C a - and SK C a -mediated relaxations that were abolished by TRAM-34 and apamin, respectively. ICI 118,551, which did not dilate the arteries per se, increased the IK C a -mediated relaxations, whereas SK C a -mediated relaxations remained unaltered. Same potentiating effect was also detected on the IK C a -mediated relaxations to carbachol and A23187, but not to NS309. Neither acetylcholine-induced nitric oxide-mediated relaxations nor SNP relaxations changed with ICI 118,551. The PKA inhibitor KT-5720, the selective β2-AR agonist salbutamol, the selective β2-AR antagonist butoxamine, the non-selective β-AR antagonist propranolol, and the inverse agonists carvedilol or nadolol failed to affect the IK C a -mediated relaxations. ICI 118,551-induced increase was not reversed by salbutamol or propranolol as well. Besides, low potassium-induced relaxations in endothelium-removed arteries remained the same in the presence of ICI 118,551. These data demonstrate a previously unrecognized action of ICI 118,551, the ability to potentiate endothelial IK C a channel-mediated vasodilation, through a mechanism independent of β2-AR antagonistic or inverse agonistic action. Instead, the enhancement of acetylcholine relaxation seems likely to occur by a mechanism secondary to endothelial calcium increase. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Monitoring Cell Proliferation by Dye Dilution: Considerations for Probe Selection

PubMed Central

Tario, Joseph D.; Conway, Alexis N.; Muirhead, Katharine A.; Wallace, Paul K.

2018-01-01

In the third edition of this series, we described protocols for labeling cell populations with tracking dyes, and addressed issues to be considered when combining two different tracking dyes with other phenotypic and viability probes for the assessment of cytotoxic effector activity and regulatory T cell functions. We summarized key characteristics of and differences between general protein and membrane labeling dyes, discussed determination of optimal staining concentrations, and provided detailed labeling protocols for both dye types. Examples of the advantages of two color cell tracking were provided in the form of protocols for: (a) independent enumeration of viable effector and target cells in a direct cytotoxicity assay; and (b) an in vitro suppression assay for simultaneous proliferation monitoring of effector and regulatory T cells. The number of commercially available fluorescent cell tracking dyes has expanded significantly since the last edition, with new suppliers and/or new spectral properties being added at least annually. In this fourth edition, we describe evaluations to be performed by the supplier and/or user when characterizing a new cell tracking dye and by the user when selecting one for use in multicolor proliferation monitoring. These include methods for: Assessment of the dye’s spectral profile on the laboratory’s flow cytometer(s) to optimize compatibility with other employed fluorochromes and minimize compensation problems;Evaluating the effect of labeling on cell growth rate;Testing the fidelity with which dye dilution reports cell division;Determining the maximum number of generations to be included when using dye dilution profiles to estimate fold population expansion or frequency of responder cells; andVerifying that relevant cell functions (e.g., effector activity) remain unaltered by tracking dye labeling. PMID:29071683

Immunosuppression after Sepsis: Systemic Inflammation and Sepsis Induce a Loss of Naïve T-Cells but No Enduring Cell-Autonomous Defects in T-Cell Function

PubMed Central

Markwart, Robby; Condotta, Stephanie A.; Requardt, Robert P.; Borken, Farina; Schubert, Katja; Weigel, Cynthia; Bauer, Michael; Griffith, Thomas S.; Förster, Martin; Brunkhorst, Frank M.; Badovinac, Vladimir P.; Rubio, Ignacio

2014-01-01

Sepsis describes the life-threatening systemic inflammatory response (SIRS) of an organism to an infection and is the leading cause of mortality on intensive care units (ICU) worldwide. An acute episode of sepsis is characterized by the extensive release of cytokines and other mediators resulting in a dysregulated immune response leading to organ damage and/or death. This initial pro-inflammatory burst often transits into a state of immune suppression characterised by loss of immune cells and T-cell dysfunction at later disease stages in sepsis survivors. However, despite these appreciations, the precise nature of the evoked defect in T-cell immunity in post-acute phases of SIRS remains unknown. Here we present an in-depth functional analysis of T-cell function in post-acute SIRS/sepsis. We document that T-cell function is not compromised on a per cell basis in experimental rodent models of infection-free SIRS (LPS or CpG) or septic peritonitis. Transgenic antigen-specific T-cells feature an unaltered cytokine response if challenged in vivo and ex vivo with cognate antigens. Isolated CD4+/CD8+ T-cells from post-acute septic animals do not exhibit defects in T-cell receptor-mediated activation at the the level of receptor-proximal signalling, activation marker upregulation or expansion. However, SIRS/sepsis induced transient lymphopenia and gave rise to an environment of immune attenuation at post acute disease stages. Thus, systemic inflammation has an acute impact on T-cell numbers and adaptive immunity, but does not cause major cell-autonomous enduring functional defects in T-cells. PMID:25541945

Heart-rate reduction by If-channel inhibition with ivabradine restores collateral artery growth in hypercholesterolemic atherosclerosis.

PubMed

Schirmer, Stephan H; Degen, Achim; Baumhäkel, Magnus; Custodis, Florian; Schuh, Lisa; Kohlhaas, Michael; Friedrich, Erik; Bahlmann, Ferdinand; Kappl, Reinhard; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

2012-05-01

Collateral arteries protect tissue from ischaemia. Heart rate correlates with vascular events in patients with arterial obstructive disease. Here, we tested the effect of heart-rate reduction (HRR) on collateral artery growth. The I(f)-channel inhibitor ivabradine reduced heart rate by 11% in wild-type and 15% in apolipoprotein E (ApoE)(-/-) mice and restored endothelium-dependent relaxation in aortic rings of ApoE(-/-) mice. Microsphere perfusion and angiographies demonstrated that ivabradine did not change hindlimb perfusion in wild-type mice but improved perfusion in ApoE(-/-) mice from 40.5 ± 15.8-60.2 ± 18.5% ligated/unligated hindlimb. Heart rate reduction (13%) with metoprolol failed to improve endothelial function and perfusion. Protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS, and eNOS activity were increased in collateral tissue following ivabradine treatment of ApoE(-/-) mice. Co-treatment with nitric oxide-inhibitor N (G)-nitro-L-arginine methyl ester abolished the effects of ivabradine on arteriogenesis. Following ivabradine, classical inflammatory cytokine expression was lowered in ApoE(-/-) circulating mononuclear cells and in plasma, but unaltered in collateral-containing hindlimb tissue, where numbers of perivascular macrophages also remained unchanged. However, ivabradine reduced expression of anti-arteriogenic cytokines CXCL10and CXCL11 and of smooth muscle cell markers smoothelin and desmin in ApoE(-/-) hindlimb tissue. Endothelial nitric oxide synthase and inflammatory cytokine expression were unchanged in wild-type mice. Ivabradine did not affect cytokine production in HUVECs and THP1 mononuclear cells and had no effect on the membrane potential of HUVECs in patch-clamp experiments. Ivabradine-induced HRR stimulates adaptive collateral artery growth. Important contributing mechanisms include improved endothelial function, eNOS activity, and modulation of inflammatory cytokine gene expression.

The Tyrosine Phosphatase STEP Is Involved in Age-Related Memory Decline.

PubMed

Castonguay, David; Dufort-Gervais, Julien; Ménard, Caroline; Chatterjee, Manavi; Quirion, Rémi; Bontempi, Bruno; Schneider, Jay S; Arnsten, Amy F T; Nairn, Angus C; Norris, Christopher M; Ferland, Guylaine; Bézard, Erwan; Gaudreau, Pierrette; Lombroso, Paul J; Brouillette, Jonathan

2018-04-02

Cognitive disabilities that occur with age represent a growing and expensive health problem. Age-associated memory deficits are observed across many species, but the underlying molecular mechanisms remain to be fully identified. Here, we report elevations in the levels and activity of the striatal-enriched phosphatase (STEP) in the hippocampus of aged memory-impaired mice and rats, in aged rhesus monkeys, and in people diagnosed with amnestic mild cognitive impairment (aMCI). The accumulation of STEP with aging is related to dysfunction of the ubiquitin-proteasome system that normally leads to the degradation of STEP. Higher level of active STEP is linked to enhanced dephosphorylation of its substrates GluN2B and ERK1/2, CREB inactivation, and a decrease in total levels of GluN2B and brain-derived neurotrophic factor (BDNF). These molecular events are reversed in aged STEP knockout and heterozygous mice, which perform similarly to young control mice in the Morris water maze (MWM) and Y-maze tasks. In addition, administration of the STEP inhibitor TC-2153 to old rats significantly improved performance in a delayed alternation T-maze memory task. In contrast, viral-mediated STEP overexpression in the hippocampus is sufficient to induce memory impairment in the MWM and Y-maze tests, and these cognitive deficits are reversed by STEP inhibition. In old LOU/C/Jall rats, a model of healthy aging with preserved memory capacities, levels of STEP and GluN2B are stable, and phosphorylation of GluN2B and ERK1/2 is unaltered. Altogether, these data suggest that elevated levels of STEP that appear with advancing age in several species contribute to the cognitive declines associated with aging. Copyright © 2018 Elsevier Ltd. All rights reserved.

Alpha-Tocopherol Supplementation Restricts Aluminium- and Ethanol-Induced Oxidative Damage in Rat Brain but Fails to Protect Against Neurobehavioral Damage.

PubMed

Nayak, Prasunpriya; Sharma, Shiv Bhushan; Chowdary, N V S

2018-04-05

The concurrent presence of oxidative stress (OS) and aluminium exposure is an inducer of neurodegenerative changes. Aluminium can augment OS in a pro-oxidant dominant condition. Antioxidative property of α-tocopherol may be useful in restricting these degenerative changes in the brain. OS parameters are tested in frontal cortex (FC), hippocampus (HC), and cerebellum (CL) of α-tocopherol-supplemented (5 IU/day) male Wistar rats exposed to aluminium (10 mg Al/Kg/day; "Al"), ethanol (0.6 g ethanol/Kg/day; "Et"), and both ("Al-Et") and vehicle-treated control ("C") for 4 weeks. The α-tocopherol supplementation restricted regional alterations of reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase. Accordingly, the regional superoxide and peroxide handling capacities (SPHC) also remain unaltered. Al-Et group demonstrated significant elevation in the lipid peroxidation level in FC and CL regions compared to the group C; similar elevations in lipid peroxidation were noted in all the tested brain regions of Al group. Likewise, declines in glutathione reductase activity were noted in HC (versus Et group) and CL (versus Al and Et groups) of Al-Et group. Interestingly, changes in behavioral patterns of all the treatment groups are comparable while differing from that of the control group. Significant difference with group C is observed during first through fourth weeks, third to fourth weeks, and second to third weeks in terms of spontaneous motor activity, Rota Rod performance, and Hebb-Williams maze performance, respectively. Hence, the current dose and duration of α-tocopherol supplementation failed to provide full protection against the aluminium-induced neurodegeneration; nevertheless, it could provide only partial protection toward aluminium-induced augmentation of OS in specific brain regions.

A time course study on prothrombotic parameters and their modulation by anti-platelet drugs in hyperlipidemic hamsters.

PubMed

Singh, Vishal; Jain, Manish; Prakash, Prem; Misra, Ankita; Khanna, Vivek; Tiwari, Rajiv Lochan; Keshari, Ravi Shankar; Singh, Shivendra; Dikshit, Madhu; Barthwal, Manoj Kumar

2011-06-01

The present study was undertaken to assess the chronology of major pathological events associated with high cholesterol (HC) diet and their modulation by anti-platelet drugs. Male Golden Syrian hamsters were fed HC diet up to 90 days. Plasma lipid, glucose and coagulation parameters (commercial kits), platelet activation (whole blood aggregation and static adhesion), endothelial dysfunction (aortic ring vasoreactivity), splenocyte TNF-α, IFN-γ and iNOS mRNA transcripts (RT-PCR), and ferric chloride (time to occlusion) induced thrombosis were monitored at 15, 30, 60, and 90 days after HC feeding and compared with normolipidemic hamsters. A significant increase in plasma lipid levels was observed at 15 days of HC feeding, but other parameters remain unaltered. Enhanced ADP, collagen, and thrombin-induced platelet aggregation, splenocyte TNF-α expression along with endothelial dysfunction were observed from 30 to 90 days of HC feeding. Platelet adhesion on collagen-/fibrinogen-coated surface and IFN-γ expression were augmented only after 60 days, while enhanced iNOS expression, reduction in thrombin time, and potentiation of ferric chloride-induced thrombosis was observed only at 90 days of HC feeding. Thus, pathological changes induced by HC diet depend on the duration and extent of hyperlipidemia. Moreover, hamsters treated with anti-platelet drugs aspirin (5 mg/kg) or clopidogrel (10 mg/kg) along with HC feeding exhibited reduction in platelet activation as well as subsequent changes observed in the abovementioned parameters following HC feeding. Since reduction in TNF-α was associated with reversion in endothelial dysfunction and prothrombotic state, the role of platelets is implicated in the pathological changes associated with HC feeding.

Fasting Increases Human Skeletal Muscle Net Phenylalanine Release and This Is Associated with Decreased mTOR Signaling

PubMed Central

Vendelbo, Mikkel Holm; Møller, Andreas Buch; Christensen, Britt; Nellemann, Birgitte; Clasen, Berthil Frederik Forrest; Nair, K. Sreekumaran; Jørgensen, Jens Otto Lunde; Jessen, Niels; Møller, Niels

2014-01-01

Aim Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR), a key regulator of cell growth. Methods Eight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days. Results Fasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation. Conclusions Our results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth. PMID:25020061

Biology, status, and management of the yellowstone cutthroat trout

USGS Publications Warehouse

Gresswell, R.E.

2011-01-01

Yellowstone cutthroat trout Oncorhynchus clarkii bouvieri were historically distributed in the Yellowstone River drainage (Montana and Wyoming) and the Snake River drainage (Wyoming, Idaho, Utah, Nevada, and probably Washington). Individual populations evolved distinct life history characteristics in response to the diverse environments in which they were isolated after the last glaciation. Anthropogenic activities have resulted in a substantial decline (42% of the historical range is currently occupied; 28% is occupied by core [genetically unaltered] populations), but the number of extant populations, especially in headwater streams, has precluded listing of this taxon under the Endangered Species Act. Primary threats to persistence of Yellowstone cutthroat trout include (1) invasive species, resulting in hybridization, predation, disease, and interspecific competition; (2) habitat degradation from human activities such as agricultural practices, water diversions, grazing, dam construction, mineral extraction, grazing, timber harvest, and road construction; and (3) climate change, including an escalating risk of drought, wildfire, winter flooding, and rising temperatures. Extirpation of individual populations or assemblages has led to increasing isolation and fragmentation of remaining groups, which in turn raises susceptibility to the demographic influences of disturbance (both human and stochastic) and genetic factors. Primary conservation strategies include (1) preventing risks associated with invasive species by isolating populations of Yellowstone cutthroat trout and (2) connecting occupied habitats (where possible) to preserve metapopulation function and the expression of multiple life histories. Because persistence of isolated populations may be greater in the short term, current management is focused on isolating individual populations and restoring habitats; however, this approach implies that humans will act as dispersal agents if a population is extirpated because of stochastic events. ?? American Fisheries Society 2011.

Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson's disease mutation G2019S.

PubMed

Li, Xianting; Patel, Jyoti C; Wang, Jing; Avshalumov, Marat V; Nicholson, Charles; Buxbaum, Joseph D; Elder, Gregory A; Rice, Margaret E; Yue, Zhenyu

2010-02-03

PARK8/LRRK2 (leucine-rich repeat kinase 2) was recently identified as a causative gene for autosomal dominant Parkinson's disease (PD), with LRRK2 mutation G2019S linked to the most frequent familial form of PD. Emerging in vitro evidence indicates that aberrant enzymatic activity of LRRK2 protein carrying this mutation can cause neurotoxicity. However, the physiological and pathophysiological functions of LRRK2 in vivo remain elusive. Here we characterize two bacterial artificial chromosome (BAC) transgenic mouse strains overexpressing LRRK2 wild-type (Wt) or mutant G2019S. Transgenic LRRK2-Wt mice had elevated striatal dopamine (DA) release with unaltered DA uptake or tissue content. Consistent with this result, LRRK2-Wt mice were hyperactive and showed enhanced performance in motor function tests. These results suggest a role for LRRK2 in striatal DA transmission and the consequent motor function. In contrast, LRRK2-G2019S mice showed an age-dependent decrease in striatal DA content, as well as decreased striatal DA release and uptake. Despite increased brain kinase activity, LRRK2-G2019S overexpression was not associated with loss of DAergic neurons in substantia nigra or degeneration of nigrostriatal terminals at 12 months. Our results thus reveal a pivotal role for LRRK2 in regulating striatal DA transmission and consequent control of motor function. The PD-associated mutation G2019S may exert pathogenic effects by impairing these functions of LRRK2. Our LRRK2 BAC transgenic mice, therefore, could provide a useful model for understanding early PD pathological events.

Mineral chemistry and shrimp U-Pb Geochronology of mesoproterozoic polycrase-titanite veins in the sullivan Pb-Zn-Ag Deposit, British Columbia

USGS Publications Warehouse

Slack, J.F.; Aleinikoff, J.N.; Belkin, H.E.; Fanning, C.M.; Ransom, P.W.

2008-01-01

Small polycrase-titanite veins 0.1-2 mm thick cut the tourmalinite feeder zone in the deep footwall of the Sullivan Pb-Zn-Ag deposit, southeastern British Columbia. Unaltered, euhedral crystals of polycrase and titanite 50-100 ??m in diameter are variably replaced by a finer-grained alteration-induced assemblage composed of anhedral polycrase and titanite with local calcite, albite, epidote, allanite, and thorite or uranothorite (or both). Average compositions of the unaltered and altered polycrase, as determined by electron-microprobe analysis, are (Y0.38 REE0.49 Th0.10 Ca0.04 Pb0.03 Fe0.01U0.01) (Ti1.48 Nb0.54 W0.04 Ta0.02)O6 and (Y0.42 REE0.32 Th0.15 U0.06 Ca0.04 Pb0.01 Fe0.01) (Ti1.57 Nb0.44 W0.04 Ta0.02)O6, respectively. The unaltered titanite has, in some areas, appreciable F (to 0.15 apfu), Y (to 0.40 apfu), and Nb (to 0.13 apfu). SHRIMP U-Pb geochronology of eight grains of unaltered polycrase yields a weighted 207Pb/206Pb age of 1413 ?? 4 Ma (2??) that is interpreted to be the age of vein formation. This age is 50-60 m.y. younger than the ca. 1470 Ma age of synsedimentary Pb-Zn-Ag mineralization in the Sullivan deposit, which is based on combined geological and geochronological data. SHRIMP ages for altered polycrase and titanite suggest later growth of minerals during the ???1370-1320 Ma East Kootenay and ???1150-1050 Ma Grenvillian orogenies. The 1413 ?? 4 Ma age for the unaltered polycrase in the veins records a previously unrecognized post-ore (1370 Ma) mineralizing event in the Sullivan deposit and vicinity. The SHRIMP U-Pb age of the polycrase and high concentrations of REE, Y, Ti, Nb, and Th in the veins, together with elevated F in titanite and the absence of associated sulfides, suggest transport of these high-field-strength elements (HFSE) by F-rich and S-poor hydrothermal fluids unrelated to the fluids that formed the older Fe-Pb-Zn-Ag sulfide ores of the Sullivan deposit. Fluids containing abundant REE, HFSE, and F may have been derived from a geochemically specialized magma such as those that form alkaline granites, pegmatites, or carbonatites. In an alternative model. preferred here, these fluids were associated with a rift-related, crustal metasomatic event in the region. Determination of a Mesoproterozoic age for the polycrase-titanite veins establishes the first known occurrence of pre-Grenvillian REE-rich mineralization in the Belt-Purcell basin.

Sarcomeric protein modification during adrenergic stress enhances cross-bridge kinetics and cardiac output

PubMed Central

Gresham, Kenneth S.; Mamidi, Ranganath; Li, Jiayang; Kwak, Hyerin

2017-01-01

Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on posttranslational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine, IPE) for 14 days using implantable osmotic pumps. In addition to significant cardiac hypertrophy and increased maximal ventricular pressure, IPE treatment accelerated pressure development and relaxation (74% increase in dP/dtmax and 14% decrease in τ), resulting in a 52% increase in cardiac output compared with saline (SAL)-treated mice. Accelerated pressure development was maintained when accounting for changes in heart rate and preload, suggesting that myocardial adaptations contribute to enhanced ventricular contractility. Ventricular myocardium isolated from IPE-treated mice displayed a significant reduction in troponin I (TnI) and myosin-binding protein C (MyBP-C) expression and a concomitant increase in the phosphorylation levels of the remaining TnI and MyBP-C protein compared with myocardium isolated from saline-treated control mice. Skinned myocardium isolated from IPE-treated mice displayed a significant acceleration in the rate of cross-bridge (XB) detachment (46% increase) and an enhanced magnitude of XB recruitment (43% increase) at submaximal Ca2+ activation compared with SAL-treated mice but unaltered myofilament Ca2+ sensitivity of force generation. These findings demonstrate that sarcomeric protein modifications during neurohormonal stress are molecular adaptations that enhance in vivo ventricular contractility through accelerated XB kinetics to increase cardiac output. NEW & NOTEWORTHY Posttranslational modifications to sarcomeric regulatory proteins provide a mechanism to modulate cardiac function in response to stress. In this study, we demonstrate that neurohormonal stress produces modifications to myosin-binding protein C and troponin I, including a reduction in protein expression within the sarcomere and increased phosphorylation of the remaining protein, which serve to enhance cross-bridge kinetics and increase cardiac output. These findings highlight the importance of sarcomeric regulatory protein modifications in modulating ventricular function during cardiac stress. PMID:27909224

Sarcomeric protein modification during adrenergic stress enhances cross-bridge kinetics and cardiac output.

PubMed

Gresham, Kenneth S; Mamidi, Ranganath; Li, Jiayang; Kwak, Hyerin; Stelzer, Julian E

2017-03-01

Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on posttranslational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine, IPE) for 14 days using implantable osmotic pumps. In addition to significant cardiac hypertrophy and increased maximal ventricular pressure, IPE treatment accelerated pressure development and relaxation (74% increase in dP/d t max and 14% decrease in τ), resulting in a 52% increase in cardiac output compared with saline (SAL)-treated mice. Accelerated pressure development was maintained when accounting for changes in heart rate and preload, suggesting that myocardial adaptations contribute to enhanced ventricular contractility. Ventricular myocardium isolated from IPE-treated mice displayed a significant reduction in troponin I (TnI) and myosin-binding protein C (MyBP-C) expression and a concomitant increase in the phosphorylation levels of the remaining TnI and MyBP-C protein compared with myocardium isolated from saline-treated control mice. Skinned myocardium isolated from IPE-treated mice displayed a significant acceleration in the rate of cross-bridge (XB) detachment (46% increase) and an enhanced magnitude of XB recruitment (43% increase) at submaximal Ca 2+ activation compared with SAL-treated mice but unaltered myofilament Ca 2+ sensitivity of force generation. These findings demonstrate that sarcomeric protein modifications during neurohormonal stress are molecular adaptations that enhance in vivo ventricular contractility through accelerated XB kinetics to increase cardiac output. NEW & NOTEWORTHY Posttranslational modifications to sarcomeric regulatory proteins provide a mechanism to modulate cardiac function in response to stress. In this study, we demonstrate that neurohormonal stress produces modifications to myosin-binding protein C and troponin I, including a reduction in protein expression within the sarcomere and increased phosphorylation of the remaining protein, which serve to enhance cross-bridge kinetics and increase cardiac output. These findings highlight the importance of sarcomeric regulatory protein modifications in modulating ventricular function during cardiac stress. Copyright © 2017 the American Physiological Society.

The healthy heart race: a short-duration, hands-on activity in cardiovascular physiology for museums and science festivals.

PubMed

Pressley, Thomas A; Limson, Melvin; Byse, Miranda; Matyas, Marsha Lakes

2011-09-01

The "Healthy Heart Race" activity provides a hands-on demonstration of cardiovascular function suitable for lay audiences. It was field tested during the United States of America Science and Engineering Festival held in Washington, DC, in October 2010. The basic equipment for the activity consisted of lengths of plastic tubing, a hand pump, collection containers, clamps, and simulated blood prepared by tinting water with red food coloring. Student participants were first asked to experience the effort required to pump through an unaltered tube. A presenter then applied a strong clamp that pinched each tube downstream from the pump, and students were asked to pump against the increased resistance. The students' observations were then used as the basis for discussions of atherosclerosis and coronary heart disease with the presenters. Distribution of informative postcards during the 2 days of the festival indicated that at least 2,500 students completed the Healthy Heart Race activity. Our experiences to date suggest that the Healthy Heart Race activity can be accomplished effectively in the high-volume, high-distraction environment of a science fair or museum.

Regional brain blood flow and cerebral hemispheric oxygen consumption during acute hypoxaemia in the llama fetus

PubMed Central

Llanos, Aníbal J; Riquelme, Raquel A; Sanhueza, Emilia M; Herrera, Emilio; Cabello, Gertrudis; Giussani, Dino A; Parer, Julian T

2002-01-01

Unlike fetal animals of lowland species, the llama fetus does not increase its cerebral blood flow during an episode of acute hypoxaemia. This study tested the hypothesis that the fetal llama brain maintains cerebral hemispheric O2 consumption by increasing cerebral O2 extraction rather than decreasing cerebral oxygen utilisation during acute hypoxaemia. Six llama fetuses were surgically instrumented under general anaesthesia at 217 days of gestation (term ca 350 days) with vascular and amniotic catheters in order to carry out cardiorespiratory studies. Following a control period of 1 h, the llama fetuses underwent 3 × 20 min episodes of progressive hypoxaemia, induced by maternal inhalational hypoxia. During basal conditions and during each of the 20 min of hypoxaemia, fetal cerebral blood flow was measured with radioactive microspheres, cerebral oxygen extraction was calculated, and fetal cerebral hemispheric O2 consumption was determined by the modified Fick principle. During hypoxaemia, fetal arterial O2 tension and fetal pH decreased progressively from 24 ± 1 to 20 ± 1 Torr and from 7.36 ± 0.01 to 7.33 ± 0.01, respectively, during the first 20 min episode, to 16 ± 1 Torr and 7.25 ± 0.05 during the second 20 min episode and to 14 ± 1 Torr and 7.21 ± 0.04 during the final 20 min episode. Fetal arterial partial pressure of CO2 (Pa,CO2, 42 ± 2 Torr) remained unaltered from baseline throughout the experiment. Fetal cerebral hemispheric blood flow and cerebral hemispheric oxygen extraction were unaltered from baseline during progressive hypoxaemia. In contrast, a progressive fall in fetal cerebral hemispheric oxygen consumption occurred during the hypoxaemic challenge. In conclusion, these data do not support the hypothesis that the fetal llama brain maintains cerebral hemispheric O2 consumption by increasing cerebral hemispheric O2 extraction. Rather, the data show that in the llama fetus, a reduction in cerebral hemispheric metabolism occurs during acute hypoxaemia. PMID:11826180

Porcine proximal tubular cells (LLC-PK1) are able to tolerate high levels of lithium chloride in vitro: assessment of the influence of 1-20 mM LiCl on cell death and alterations in cell biology and biochemistry.

PubMed

Lucas, Kirsten C; Hart, David A; Becker, Rolf W

2010-01-25

Lithium, a prophylactic drug for the treatment of bipolar disorder, is prescribed with caution due to its side effects, including renal damage. In this study porcine LLC-PK1 renal tubular cells were used to establish the direct toxicity of lithium on proximal cells and gain insights into the molecular mechanisms involved. In the presence of LiCl, cell proliferation exhibited insignificant decreases in a concentration-dependent manner, but once confluent, constant cell numbers were observed. Cell cycle studies indicated a small dose-dependent accumulation of cells in the G2/M stage after 24 h, as well as an increase in cells in the G0/G1 phase after treatment with 1-10 mM LiCl, but not at 20 mM LiCl. No evidence of apoptosis was observed based on cell morphology or DNA fragmentation studies, or evidence of protein expression changes for Bax, Bcl-2, and p53 proteins using immunocytochemistry. In addition caspases 3, 8 and 9 activity remained unaltered between control and lithium-treated cultures. To conclude, exposure to high concentrations of lithium did not result in overt toxic effects to LLC-PK1 renal cells, although LiCl did alter some aspects of cell behaviour, which could potentially influence function over time.

Hepatitis E virus persists in the presence of a type III interferon response.

PubMed

Yin, Xin; Li, Xinlei; Ambardekar, Charuta; Hu, Zhimin; Lhomme, Sébastien; Feng, Zongdi

2017-05-01

The RIG-I-like RNA helicase (RLR)-mediated interferon (IFN) response plays a pivotal role in the hepatic antiviral immunity. The hepatitis A virus (HAV) and the hepatitis C virus (HCV) counter this response by encoding a viral protease that cleaves the mitochondria antiviral signaling protein (MAVS), a common signaling adaptor for RLRs. However, a third hepatotropic RNA virus, the hepatitis E virus (HEV), does not appear to encode a functional protease yet persists in infected cells. We investigated HEV-induced IFN responses in human hepatoma cells and primary human hepatocytes. HEV infection resulted in persistent virus replication despite poor spread. This was companied by a type III IFN response that upregulated multiple IFN-stimulated genes (ISGs), but type I IFNs were barely detected. Blocking type III IFN production or signaling resulted in reduced ISG expression and enhanced HEV replication. Unlike HAV and HCV, HEV did not cleave MAVS; MAVS protein size, mitochondrial localization, and function remained unaltered in HEV-replicating cells. Depletion of MAVS or MDA5, and to a less extent RIG-I, also diminished IFN production and increased HEV replication. Furthermore, persistent activation of the JAK/STAT signaling rendered infected cells refractory to exogenous IFN treatment, and depletion of MAVS or the receptor for type III IFNs restored the IFN responsiveness. Collectively, these results indicate that unlike other hepatotropic RNA viruses, HEV does not target MAVS and its persistence is associated with continuous production of type III IFNs.

Satellite bulk tropospheric temperatures as a metric for climate sensitivity

NASA Astrophysics Data System (ADS)

Christy, John R.; McNider, Richard T.

2017-11-01

We identify and remove the main natural perturbations (e.g. volcanic activity, ENSOs) from the global mean lower tropospheric temperatures ( T LT ) over January 1979 - June 2017 to estimate the underlying, potentially human-forced trend. The unaltered value is +0.155 K dec-1 while the adjusted trend is +0.096 K dec-1, related primarily to the removal of volcanic cooling in the early part of the record. This is essentially the same value we determined in 1994 (+0.09 K dec-1, Christy and McNider, 1994) using only 15 years of data. If the warming rate of +0.096 K dec-1 represents the net T LT response to increasing greenhouse radiative forcings, this implies that the T LT tropospheric transient climate response (Δ T LT at the time CO2 doubles) is +1.10 ± 0.26 K which is about half of the average of the IPCC AR5 climate models of 2.31 ± 0.20 K. Assuming that the net remaining unknown internal and external natural forcing over this period is near zero, the mismatch since 1979 between observations and CMIP-5 model values suggests that excessive sensitivity to enhanced radiative forcing in the models can be appreciable. The tropical region is mainly responsible for this discrepancy suggesting processes that are the likely sources of the extra sensitivity are (a) the parameterized hydrology of the deep atmosphere, (b) the parameterized heat-partitioning at the oceanatmosphere interface and/or (c) unknown natural variations.

A Novel 3D Label-Free Monitoring System of hES-Derived Cardiomyocyte Clusters: A Step Forward to In Vitro Cardiotoxicity Testing

PubMed Central

Jahnke, Heinz-Georg; Steel, Daniella; Fleischer, Stephan; Seidel, Diana; Kurz, Randy; Vinz, Silvia; Dahlenborg, Kerstin; Sartipy, Peter; Robitzki, Andrea A.

2013-01-01

Unexpected adverse effects on the cardiovascular system remain a major challenge in the development of novel active pharmaceutical ingredients (API). To overcome the current limitations of animal-based in vitro and in vivo test systems, stem cell derived human cardiomyocyte clusters (hCMC) offer the opportunity for highly predictable pre-clinical testing. The three-dimensional structure of hCMC appears more representative of tissue milieu than traditional monolayer cell culture. However, there is a lack of long-term, real time monitoring systems for tissue-like cardiac material. To address this issue, we have developed a microcavity array (MCA)-based label-free monitoring system that eliminates the need for critical hCMC adhesion and outgrowth steps. In contrast, feasible field potential derived action potential recording is possible immediately after positioning within the microcavity. Moreover, this approach allows extended observation of adverse effects on hCMC. For the first time, we describe herein the monitoring of hCMC over 35 days while preserving the hCMC structure and electrophysiological characteristics. Furthermore, we demonstrated the sensitive detection and quantification of adverse API effects using E4031, doxorubicin, and noradrenaline directly on unaltered 3D cultures. The MCA system provides multi-parameter analysis capabilities incorporating field potential recording, impedance spectroscopy, and optical read-outs on individual clusters giving a comprehensive insight into induced cellular alterations within a complex cardiac culture over days or even weeks. PMID:23861955

Preservation of renal blood flow by the antioxidant EUK-134 in LPS-treated pigs.

PubMed

Magder, Sheldon; Parthenis, Dimitrios G; Ghouleh, Imad Al

2015-03-25

Sepsis is associated with an increase in reactive oxygen species (ROS), however, the precise role of ROS in the septic process remains unknown. We hypothesized that treatment with EUK-134 (manganese-3-methoxy N,N'-bis(salicyclidene)ethylene-diamine chloride), a compound with superoxide dismutase and catalase activity, attenuates the vascular manifestations of sepsis in vivo. Pigs were instrumented to measure cardiac output and blood flow in renal, superior mesenteric and femoral arteries, and portal vein. Animals were treated with saline (control), lipopolysaccharide (LPS; 10 µg·kg-1·h-1), EUK-134, or EUK-134 plus LPS. Results show that an LPS-induced increase in pulmonary artery pressure (PAP) as well as a trend towards lower blood pressure (BP) were both attenuated by EUK-134. Renal blood flow decreased with LPS whereas superior mesenteric, portal and femoral flows did not change. Importantly, EUK-134 decreased the LPS-induced fall in renal blood flow and this was associated with a corresponding decrease in LPS-induced protein nitrotyrosinylation in the kidney. PO2, pH, base excess and systemic vascular resistance fell with LPS and were unaltered by EUK-134. EUK-134 also had no effect on LPS-associated increase in CO. Interestingly, EUK-134 alone resulted in higher CO, BP, PAP, mean circulatory filling pressure, and portal flow than controls. Taken together, these data support a protective role for EUK-134 in the renal circulation in sepsis.

Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice

PubMed Central

Rozhdestvensky, Timofey S.; Robeck, Thomas; Galiveti, Chenna R.; Raabe, Carsten A.; Seeger, Birte; Wolters, Anna; Gubar, Leonid V.; Brosius, Jürgen; Skryabin, Boris V.

2016-01-01

Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans and growth retardation in mice exhibiting ~15% postnatal lethality in C57BL/6 background. Here we analysed a knock-in mouse containing a 5′HPRT-LoxP-NeoR cassette (5′LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScrp−/m5′LoxP), we observed compensation of growth retardation and postnatal lethality. Genomic methylation pattern and expression of protein-coding genes remained unaltered at the PWS-locus of PWScrp−/m5′LoxP mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScrp−/m5′LoxP mice expressed Snord116 in brain areas similar to wild type animals. Our results suggest that the lack of PWScr RNA expression in certain brain areas could be a primary cause of the growth retardation phenotype in mice. We propose that activation of disease-associated genes on imprinted regions could lead to general therapeutic strategies in associated diseases. PMID:26848093

MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils

PubMed Central

Campo, Vanina A.; Patenaude, Anne-Marie; Kaden, Svenja; Horb, Lori; Firka, Daniel; Jiricny, Josef; Di Noia, Javier M.

2013-01-01

The mammalian antibody repertoire is shaped by somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) loci of B lymphocytes. SHM and CSR are triggered by non-canonical, error-prone processing of G/U mismatches generated by activation-induced deaminase (AID). In birds, AID does not trigger SHM, but it triggers Ig gene conversion (GC), a ‘homeologous’ recombination process involving the Ig variable region and proximal pseudogenes. Because recombination fidelity is controlled by the mismatch repair (MMR) system, we investigated whether MMR affects GC in the chicken B cell line DT40. We show here that Msh6−/− and Pms2−/− DT40 cells display cell cycle defects, including genomic re-replication. However, although IgVλ GC tracts in MMR-deficient cells were slightly longer than in normal cells, Ig GC frequency, donor choice or the number of mutations per sequence remained unaltered. The finding that the avian MMR system, unlike that of mammals, does not seem to contribute towards the processing of G/U mismatches in vitro could explain why MMR is unable to initiate Ig GC in this species, despite initiating SHM and CSR in mammalian cells. Moreover, as MMR does not counteract or govern Ig GC, we report a rare example of ‘homeologous’ recombination insensitive to MMR. PMID:23314153

High-pressure dynamics of hydrated protein in bioprotective trehalose environment

DOE PAGES

Diallo, S. O.; Zhang, Q.; O'Neill, H.; ...

2014-10-30

Here we present a pressure-dependence study of the dynamics of lysozyme protein powder immersed in deuterated , α-trehalose environment via quasielastic neutron scattering (QENS). The goal is to assess the baroprotective benefits of trehalose on biomolecules by comparing the findings with those of a trehalose-free reference study. While the mean-square displacement of the trehalose-free protein (hydrated to d D₂O ≃40 w%) as a whole, is reduced by increasing pressure, the actual observable relaxation dynamics in the picoseconds to nanoseconds time range remains largely unaffected by pressure up to the maximum investigated pressure of 2.78(2) Kbar. Our observation is independent ofmore » whether or not the protein is mixed with the deuterated sugar. This suggests that the hydrated protein s conformational states at atmospheric pressure remain unaltered by hydrostatic pressures, below 2.78 Kbar. We also found the QENS response to be totally recoverable after ambient pressure conditions are restored. Small-angle neutron diffraction measurements confirm that the protein-protein correlation remains undisturbed.We observe, however, a clear narrowing of the QENS response as the temperature is decreased from 290 to 230 K in both cases, which we parametrize using the Kohlrausch-Williams-Watts stretched exponential model. Finally, only the fraction of protons that are immobile on the accessible time window of the instrument, referred to as the elastic incoherent structure factor, is observably sensitive to pressure, increasing only marginally but systematically with increasing pressure.« less

High-pressure dynamics of hydrated protein in bioprotective trehalose environment

NASA Astrophysics Data System (ADS)

Diallo, S. O.; Zhang, Q.; O'Neill, H.; Mamontov, E.

2014-10-01

We present a pressure-dependence study of the dynamics of lysozyme protein powder immersed in deuterated α ,α -trehalose environment via quasielastic neutron scattering (QENS). The goal is to assess the baroprotective benefits of trehalose on biomolecules by comparing the findings with those of a trehalose-free reference study. While the mean-square displacement of the trehalose-free protein (hydrated to dD2O≃ 40 w%) as a whole, is reduced by increasing pressure, the actual observable relaxation dynamics in the picoseconds to nanoseconds time range remains largely unaffected by pressure—up to the maximum investigated pressure of 2.78(2) Kbar. Our observation is independent of whether or not the protein is mixed with the deuterated sugar. This suggests that the hydrated protein's conformational states at atmospheric pressure remain unaltered by hydrostatic pressures, below 2.78 Kbar. We also found the QENS response to be totally recoverable after ambient pressure conditions are restored. Small-angle neutron diffraction measurements confirm that the protein-protein correlation remains undisturbed. We observe, however, a clear narrowing of the QENS response as the temperature is decreased from 290 to 230 K in both cases, which we parametrize using the Kohlrausch-Williams-Watts stretched exponential model. Only the fraction of protons that are immobile on the accessible time window of the instrument, referred to as the elastic incoherent structure factor, is observably sensitive to pressure, increasing only marginally but systematically with increasing pressure.

Cytarabine and daunorubicin for the treatment of acute myeloid leukemia.

PubMed

Murphy, Tracy; Yee, Karen W L

2017-11-01

Acute myeloid leukemia (AML) is the most common acute forms of leukemia in adults. It has a poor long-term survival with a high relapse rate and at relapse, is commonly resistant to available therapies. The current combination of daunorubicin (DNR) for three days and cytarabine (Ara-C) as a continuous infusion for seven days, more commonly known as '3 + 7' has remained essentially unaltered over the last forty-four years and remains the standard induction regimen internationally. Areas covered: This paper will briefly review clinically important trials related to '3 + 7'. Somatic mutations in AML that are linked to chemoresistance to '3 + 7'will be discussed. Other topics covered include the novel ratiometric agent containing daunorubicin and cytarabine, CPX-351, and midostaurin in FLT3 mutated AML. Expert opinion: '3 + 7' continues to be the backbone of therapy for AML. However, genetic risk stratification should be used to determine patients who are unlikely to respond to standard intensive chemotherapy and hence, should be enrolled onto a clinical trial upfront. This will facilitate development of newer effective treatment strategies in AML. Patients with mutations that are associated with chemoresistance should be offered therapies which may circumvent or overcome these pathways.

Remotely-sensed detection of effects of extreme droughts on gross primary production

PubMed Central

Vicca, Sara; Balzarolo, Manuela; Filella, Iolanda; Granier, André; Herbst, Mathias; Knohl, Alexander; Longdoz, Bernard; Mund, Martina; Nagy, Zoltan; Pintér, Krisztina; Rambal, Serge; Verbesselt, Jan; Verger, Aleixandre; Zeileis, Achim; Zhang, Chao; Peñuelas, Josep

2016-01-01

Severe droughts strongly impact photosynthesis (GPP), and satellite imagery has yet to demonstrate its ability to detect drought effects. Especially changes in vegetation functioning when vegetation state remains unaltered (no browning or defoliation) pose a challenge to satellite-derived indicators. We evaluated the performance of different satellite indicators to detect strong drought effects on GPP in a beech forest in France (Hesse), where vegetation state remained largely unaffected while GPP decreased substantially. We compared the results with three additional sites: a Mediterranean holm oak forest (Puéchabon), a temperate beech forest (Hainich), and a semi-arid grassland (Bugacpuszta). In Hesse, a three-year reduction in GPP following drought was detected only by the Enhanced Vegetation Index (EVI). The Photochemical Reflectance Index (PRI) also detected this drought effect, but only after normalization for absorbed light. In Puéchabon normalized PRI outperformed the other indicators, while the short-term drought effect in Hainich was not detected by any tested indicator. In contrast, most indicators, but not PRI, captured the drought effects in Bugacpuszta. Hence, PRI improved detection of drought effects on GPP in forests and we propose that PRI normalized for absorbed light is considered in future algorithms to estimate GPP from space. PMID:27301671

Correlation of Tc17 cells at early stages after allogeneic hematopoietic stem cell transplantation with acute graft-versus-host disease.

PubMed

Wang, Ling; Zhao, Peng; Song, Lingling; Yan, Fahong; Shi, Chunlei; Li, Ying; Han, Mingzhe; Lan, Ketao

2016-12-01

Acute graft-versus-host disease (aGVHD) is associated with an immune dysregulation usually mediated by T lymphocytes. Recently, IL-17-producing T cells including Th17 and Tc17 cells have been implicated in immune-related diseases. However, their roles in aGVHD remain uncertain. In the study, we analyzed IL-17-producing cell recovery and association with the occurrence of aGVHD. While Th17 cells steadily recovered, Tc17 cell numbers remained unaltered during the first 3months after transplantation. Occurrence of aGVHD was correlated with increased level of Tc17 cells at the second months after allo-SCT. Interestingly, Tc17 cells were negatively associated with CD4 + CD25 + FOXP3 + regulatory T (Treg) cells, which was an important prognostic predictor in patients with aGVHD. In addition, we found that Tc17 numbers increased as the increased concentrations of TGF-β and IL-6, which are known to drive Th17 polarization. These finding supported that Tc17 subset is involved in the immunopathology of aGVHD. Blocking the abnormally increased number of Tc17 may be a reasonable therapeutic strategy for aGVHD. Copyright © 2016 Elsevier B.V. All rights reserved.

Differential expression of ryanodine receptor isoforms after spinal cord injury.

PubMed

Pelisch, Nicolas; Gomes, Cynthia; Nally, Jacqueline M; Petruska, Jeffrey C; Stirling, David P

2017-11-01

Ryanodine receptors (RyRs) are highly conductive intracellular Ca 2+ release channels and are widely expressed in many tissues, including the central nervous system. RyRs have been implicated in intracellular Ca 2+ overload which can drive secondary damage following traumatic injury to the spinal cord (SCI), but the spatiotemporal expression of the three isoforms of RyRs (RyR1-3) after SCI remains unknown. Here, we analyzed the gene and protein expression of RyR isoforms in the murine lumbar dorsal root ganglion (DRG) and the spinal cord lesion site at 1, 2 and 7 d after a mild contusion SCI. Quantitative RT PCR analysis revealed that RyR3 was significantly increased in lumbar DRGs and at the lesion site at 1 and 2 d post contusion compared to sham (laminectomy only) controls. Additionally, RyR2 expression was increased at 1 d post injury within the lesion site. RyR2 and -3 protein expression was localized to lumbar DRG neurons and their spinal projections within the lesion site acutely after SCI. In contrast, RyR1 expression within the DRG and lesion site remained unaltered following trauma. Our study shows that SCI initiates acute differential expression of RyR isoforms in DRG and spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

(How) Can We Use Satellite Data to Estimate Effects of Extreme Drought on Photosynthesis?

NASA Astrophysics Data System (ADS)

Vicca, S.; Balzarolo, M.; Filella, I.; Granier, A.; Herbst, M.; Knohl, A.; Longdoz, B.; Mund, M.; Nagy, Z.; Pintér, K.; Rambal, S.; Verbesselt, J.; Verger, A.; Zeileis, A.; Zhang, C.; Penuelas, J.

2017-12-01

Severe droughts can strongly impact photosynthesis (GPP), but the tool best suited for large-scale and long-term monitoring, satellite imagery, has yet to prove its ability to detect drought effects on GPP. Especially changes in vegetation functioning when vegetation state remains unaltered (no browning or defoliation) pose a challenge to satellite-derived indicators. We evaluated the performance of different satellite indicators to detect effect of a strong drought (that started during the European heatwave of 2003) on GPP in a beech forest in France (Hesse). While vegetation state remained largely unaffected by the drought, Eddy Covariance data revealed a substantial decrease in GPP and GPP recovered only after about three years. This three-year reduction in GPP was, however not detected by severaly commonly used reflectance indices (like NDVI and FAPAR) or by MODIS GPP product. Only he Enhanced Vegetation Index (EVI) and the Photochemical Reflectance Index (PRI) detected the drought effect, but the PRI only after normalization for absorbed light. These results were compared to a two other forests where a severe drought event had affected GPP and these data confirmed that especially the PRI normalized for absorbed light provides useful information about vegetation functioning that is not captured by other remote sensing indicators under test.

Evolution of dominance in sporophytic self-incompatibility systems: I. Genetic load and coevolution of levels of dominance in pollen and pistil.

PubMed

Llaurens, Violaine; Billiard, Sylvain; Castric, Vincent; Vekemans, Xavier

2009-09-01

Recent theoretical advances have suggested that various forms of balancing selection may promote the evolution of dominance through an increase of the proportion of heterozygote genotypes. We test whether dominance can evolve in the sporophytic self-incompatibility (SSI) system in plants. SSI prevents mating between individuals expressing identical SI phenotypes by recognition of pollen by pistils, which avoids selfing and inbreeding depression. SI phenotypes depend on a complex network of dominance relationships between alleles at the self-incompatibility locus (S-locus). Empirical studies suggest that these relationships are not random, but the exact evolutionary processes shaping these relationships remain unclear. We investigate the expected patterns of dominance under the hypothesis that dominance is a direct target of natural selection. We follow the fate of a mutant allele at the S-locus whose dominance relationships are changed but whose specificity remains unaltered. We show that strict codominance is not evolutionarily stable in SSI, and that inbreeding depression due to deleterious mutations linked or unlinked to the S-locus exerts strong constraints on changes in relative levels of dominance in pollen and pistil. Our results provide a general adaptive explanation for most patterns of dominance relationships empirically observed in natural plant populations.

Nippostrongylus brasiliensis: infection induces upregulation of acetylcholinesterase activity on rat intestinal epithelial cells.

PubMed

Russell, W S; Henson, S M; Hussein, A S; Tippins, J R; Selkirk, M E

2000-12-01

Expression of cholines terases and muscarinic acetylcholine receptors in the jejunal mucosa has been investigated during infection of rats with the nematode parasite Nippostrongylus brasiliensis. Selective expression of m3 receptors was observed on epithelial cells from uninfected rats and animals 7 days postinfection, and saturation binding with [(3)H]quinuclidinyl benzilate indicated that receptor expression on cell membranes was unaltered by infection. Butyrylcholinesterase was highly expressed in mucosal epithelia, but acetylcholinesterase was present at low levels in uninfected animals. In contrast, discrete foci of intense acetylcholinesterase activity were observed on the basement membrane of intestinal epithelial cells in animals infected with N. brasiliensis. This was demonstrated to be due to upregulation of expression of endogenous enzyme, which peaked at Day 10 postinfection and subsequently declined to preinfection levels. It is suggested that this occurs in response to hyper-activation of the enteric nervous system as a result of infection, and may benefit the host by limiting excessive fluid secretion due to cholinergic stimulation. Copyright 2000 Academic Press.

Removal of acutely hazardous pharmaceuticals from water using multi-template imprinted polymer adsorbent.

PubMed

Venkatesh, Avinash; Chopra, Nikita; Krupadam, Reddithota J

2014-05-01

Molecularly imprinted polymer adsorbent has been prepared to remove a group of recalcitrant and acutely hazardous (p-type) chemicals from water and wastewaters. The polymer adsorbent exhibited twofold higher adsorption capacity than the commercially used polystyrene divinylbenzene resin (XAD) and powdered activated carbon adsorbents. Higher adsorption capacity of the polymer adsorbent was explained on the basis of high specific surface area formed during molecular imprinting process. Freundlich isotherms drawn showed that the adsorption of p-type chemicals onto polymer adsorbent was kinetically faster than the other reference adsorbents. Matrix effect on adsorption of p-type chemicals was minimal, and also polymer adsorbent was amenable to regeneration by washing with water/methanol (3:1, v/v) solution. The polymer adsorbent was unaltered in its adsorption capacity up to 10 cycles of adsorption and desorption, which will be more desirable in cost reduction of treatment compared with single-time-use activated carbon.

Allelopathy of Bracken Fern (Pteridium arachnoideum): New Evidence from Green Fronds, Litter, and Soil

PubMed Central

Juliano Gualtieri, Sonia Cristina; Rodrigues-Filho, Edson; Macías, Francisco Antonio

2016-01-01

The neotropical bracken fern Pteridium arachnoideum (Kaulf.) Maxon. (Dennstaedtiaceae) is described as an aggressive pioneer plant species. It invades abandoned or newly burned areas and represents a management challenge at these invaded sites. Native to the Atlantic Forest and Cerrado (Tropical Savanna) Brazilian biomes, P. arachnoideum has nevertheless become very problematic in these conservation hotspots. Despite some reports suggesting a possible role of allelopathy in this plant’s dominance, until now there has been little evidence of isolated and individually identified compounds with phytotoxic activities present in its tissues or in the surrounding environment. Thus, the aim of this study was to investigate the allelopathic potential of P. arachnoideum by isolating and identifying any secondary metabolites with phytotoxic activity in its tissues, litter, and soil. Bioguided phytochemical investigation led to the isolation and identification of the proanthocyanidin selligueain A as the major secondary compound in the green fronds and litter of this fern. It is produced by P. arachnoideum in its green fronds, remains unaltered during the senescence process, and is the major secondary compound present in litter. Selligueain A showed phytotoxic activity against the selected target species sesame (Sesamum indicum) early development. In particular, the compound inhibited root and stem growth, and root metaxylem cell size but did not affect chlorophyll content. This compound can be considered as an allelochemical because it is present in the soil under P. arachnoideum patches as one of the major compounds in the soil solution. This is the first report of the presence of selligueain A in any member of the Dennstaedtiaceae family and the first time an isolated and identified allelochemical produced by members of the Pteridium species complex has been described. This evidence of selligueain A as a putative allelochemical of P. arachnoideum reinforces the role of allelopathy in the dominance processes of this plant in the areas where it occurs. PMID:27552161

Activation of sorbitol pathway in metabolic syndrome and increased susceptibility to cataract in Wistar-Obese rats

PubMed Central

Giridharan, Nappan Veettil

2012-01-01

Purpose Obesity is a major public health problem worldwide, and of late, epidemiological studies indicate a preponderance of cataracts under obesity conditions. Although cataract is a multifactorial disorder and various biochemical mechanisms have been proposed, the influence of obesity on cataractogenesis has yet to be investigated. In such a scenario, a suitable animal model that develops cataract following the onset of obesity will be a welcome tool for biomedical research. Therefore, we investigated the molecular and biochemical basis for predisposition to cataract in the obese mutant rat models established in our institute because 15%–20% of these rats develop cataracts spontaneously as they reach 12–15 months of age. Methods We analyzed the major biochemical pathways in the normal lenses of different age groups of our obese mutant rat strains, Wistar/Obese (WNIN/Ob) and WNIN/GR-Ob, the former with euglycemia and the latter with an additional impaired glucose tolerance trait. In addition, sorbitol levels were estimated in the cataractous lenses of the obese rats. Results Except for the polyol pathway, all the principal pathways of the lens remained unaltered. Therefore, sorbitol levels were found to be high in the normal eye lenses of obese rats (WNIN/Ob and WNIN/GR-Ob) compared to their lean controls from three months of age onwards. Between WNIN/Ob and WNIN/GR-Ob, the levels of sorbitol were higher in the latter, suggesting a synergistic effect of impaired glucose tolerance along with obesity in the activation of the sorbitol pathway. Either way, an elevated sorbitol pathway seemed to be the predisposing factor responsible for cataract formation in these mutant rats. Conclusions Activation of the sorbitol pathway indeed enhances the risk of cataract development in conditions such as metabolic syndrome. These rat models thus may be valuable tools for investigating obesity-associated cataract and for developing intervention strategies, based on these findings. PMID:22393276

Activation of sorbitol pathway in metabolic syndrome and increased susceptibility to cataract in Wistar-Obese rats.

PubMed

Reddy, Paduru Yadagiri; Giridharan, Nappan Veettil; Reddy, Geereddy Bhanuprakash

2012-01-01

Obesity is a major public health problem worldwide, and of late, epidemiological studies indicate a preponderance of cataracts under obesity conditions. Although cataract is a multifactorial disorder and various biochemical mechanisms have been proposed, the influence of obesity on cataractogenesis has yet to be investigated. In such a scenario, a suitable animal model that develops cataract following the onset of obesity will be a welcome tool for biomedical research. Therefore, we investigated the molecular and biochemical basis for predisposition to cataract in the obese mutant rat models established in our institute because 15%-20% of these rats develop cataracts spontaneously as they reach 12-15 months of age. We analyzed the major biochemical pathways in the normal lenses of different age groups of our obese mutant rat strains, Wistar/Obese (WNIN/Ob) and WNIN/GR-Ob, the former with euglycemia and the latter with an additional impaired glucose tolerance trait. In addition, sorbitol levels were estimated in the cataractous lenses of the obese rats. Except for the polyol pathway, all the principal pathways of the lens remained unaltered. Therefore, sorbitol levels were found to be high in the normal eye lenses of obese rats (WNIN/Ob and WNIN/GR-Ob) compared to their lean controls from three months of age onwards. Between WNIN/Ob and WNIN/GR-Ob, the levels of sorbitol were higher in the latter, suggesting a synergistic effect of impaired glucose tolerance along with obesity in the activation of the sorbitol pathway. Either way, an elevated sorbitol pathway seemed to be the predisposing factor responsible for cataract formation in these mutant rats. Activation of the sorbitol pathway indeed enhances the risk of cataract development in conditions such as metabolic syndrome. These rat models thus may be valuable tools for investigating obesity-associated cataract and for developing intervention strategies, based on these findings.

Activation of M1 muscarinic receptors triggers transmitter release from rat sympathetic neurons through an inhibition of M-type K+ channels.

PubMed

Lechner, Stefan G; Mayer, Martina; Boehm, Stefan

2003-12-15

Acetylcholine has long been known to excite sympathetic neurons via M1 muscarinic receptors through an inhibition of M-currents. Nevertheless, it remained controversial whether activation of muscarinic receptors is also sufficient to trigger noradrenaline release from sympathetic neurons. In primary cultures of rat superior cervical ganglia, the muscarinic agonist oxotremorine M inhibited M-currents with half-maximal effects at 1 microM and induced the release of previously incorporated [3H]noradrenaline with half-maximal effects at 10 microM. This latter action was not affected by the nicotinic antagonist mecamylamine which, however, abolished currents through nicotinic receptors elicited by high oxotremorine M concentrations. Ablation of the signalling cascades linked to inhibitory G proteins by pertussis toxin potentiated the release stimulating effect of oxotremorine M, and the half-maximal concentration required to stimulate noradrenaline release was decreased to 3 microM. Pirenzepine antagonized the inhibition of M-currents and the induction of release by oxotremorine M with identical apparent affinity, and both effects were abolished by the muscarinic toxin 7. These results indicate that one muscarinic receptor subtype, namely M1, mediates these two effects. Retigabine, which enhances M-currents, abolished the release induced by oxotremorine M, but left electrically induced release unaltered. Moreover, retigabine shifted the voltage-dependent activation of M-currents by about 20 mV to more negative potentials and caused 20 mV hyperpolarisations of the membrane potential. In the absence of retigabine, oxotremorine M depolarised the neurons and elicited action potential discharges in 8 of 23 neurons; in its presence, oxotremorine M still caused equal depolarisations, but always failed to trigger action potentials. Action potential waveforms caused by current injection were not affected by retigabine. These results indicate that the inhibition of M-currents is the basis for the stimulation of transmitter release from sympathetic neurons via M1 muscarinic receptors.

Optimal Solution Volume for Luminal Preservation: A Preclinical Study in Porcine Intestinal Preservation.

PubMed

Oltean, M; Papurica, M; Jiga, L; Hoinoiu, B; Glameanu, C; Bresler, A; Patrut, G; Grigorie, R; Ionac, M; Hellström, M

2016-03-01

Rodent studies suggest that luminal solutions alleviate the mucosal injury and prolong intestinal preservation but concerns exist that excessive volumes of luminal fluid may promote tissue edema. Differences in size, structure, and metabolism between rats and humans require studies in large animals before clinical use. Intestinal procurement was performed in 7 pigs. After perfusion with histidine-tryptophan-ketoglutarate (HTK), 40-cm-long segments were cut and filled with 13.5% polyethylene glycol (PEG) 3350 solution as follows: V0 (controls, none), V1 (0.5 mL/cm), V2 (1 mL/cm), V3 (1.5 mL/cm), and V4 (2 mL/cm). Tissue and luminal solutions were sampled after 8, 14, and 24 hours of cold storage (CS). Preservation injury (Chiu score), the apical membrane (ZO-1, brush-border maltase activity), and the electrolyte content in the luminal solution were studied. In control intestines, 8-hour CS in HTK solution resulted in minimal mucosal changes (grade 1) that progressed to significant subepithelial edema (grade 3) by 24 hours. During this time, a gradual loss in ZO-1 was recorded, whereas maltase activity remained unaltered. Moreover, variable degrees of submucosal edema were observed. Luminal introduction of high volumes (2 mL/mL) of PEG solution accelerated the development of the subepithelial edema and submucosal edema, leading to worse histology. However, ZO-1 was preserved better over time than in control intestines (no luminal solution). Maltase activity was reduced in intestines receiving luminal preservation. Luminal sodium content decreased in time and did not differ between groups. This PEG solution protects the apical membrane and the tight-junction proteins but may favor water absorption and tissue (submucosal) edema, and luminal volumes >2 mL/cm may result in worse intestinal morphology. Copyright © 2016 Elsevier Inc. All rights reserved.

Calpain activity in fast, slow, transforming, and regenerating skeletal muscles of rat.

PubMed

Sultan, K R; Dittrich, B T; Pette, D

2000-09-01

Fiber-type transitions in adult skeletal muscle induced by chronic low-frequency stimulation (CLFS) encompass coordinated exchanges of myofibrillar protein isoforms. CLFS-induced elevations in cytosolic Ca(2+) could activate proteases, especially calpains, the major Ca(2+)-regulated cytosolic proteases. Calpain activity determined by a fluorogenic substrate in the presence of unaltered endogenous calpastatin activities increased twofold in low-frequency-stimulated extensor digitorum longus (EDL) muscle, reaching a level intermediate between normal fast- and slow-twitch muscles. micro- and m-calpains were delineated by a calpain-specific zymographical assay that assessed total activities independent of calpastatin and distinguished between native and processed calpains. Contrary to normal EDL, structure-bound, namely myofibrillar and microsomal calpains, were abundant in soleus muscle. However, the fast-to-slow conversion of EDL was accompanied by an early translocation of cytosolic micro-calpain, suggesting that myofibrillar and microsomal micro-calpain was responsible for the twofold increase in activity and thus involved in controlled proteolysis during fiber transformation. This is in contrast to muscle regeneration where m-calpain translocation predominated. Taken together, we suggest that translocation is an important step in the control of calpain activity in skeletal muscle in vivo.

Mechanism of neem limonoids-induced cell death in cancer: role of oxidative phosphorylation

PubMed Central

Yadav, Neelu; Kumar, Sandeep; Kumar, Rahul; Srivastava, Pragya; Sun, Leimin; Rapali, Peter; Marlowe, Timothy; Schneider, Andrea; Inigo, Joseph; O’Malley, Jordan; Londonkar, Ramesh; Gogada, Raghu; Chaudhary, Ajay; Yadava, Nagendra; Chandra, Dhyan

2016-01-01

We have previously reported that neem limonoids (neem) induce multiple cancer cell death pathways. Here we dissect the underlying mechanisms of neem-induced apoptotic cell death in cancer. We observed that neem-induced caspase activation does not require Bax/Bak channel-mediated mitochondrial outer membrane permeabilization, permeability transition pore, and mitochondrial fragmentation. Neem enhanced mitochondrial DNA and mitochondrial biomass. While oxidative phosphorylation (OXPHOS) Complex-I activity was decreased, the activities of other OXPHOS complexes including Complex-II and -IV were unaltered. Increased reactive oxygen species (ROS) levels were associated with an increase in mitochondrial biomass and apoptosis upon neem exposure. Complex-I deficiency due to the loss of Ndufa1-encoded MWFE protein inhibited neem-induced caspase activation and apoptosis, but cell death induction was enhanced. Complex II-deficiency due to the loss of succinate dehydrogenase complex subunit C (SDHC) robustly decreased caspase activation, apoptosis, and cell death. Additionally, the ablation of Complexes-I, -III, -IV, and -V together did not inhibit caspase activation. Together, we demonstrate that neem limonoids target OXPHOS system to induce cancer cell death, which does not require upregulation or activation of proapoptotic Bcl-2 family proteins. PMID:26627937

Protection of host cells by complement regulators.

PubMed

Schmidt, Christoph Q; Lambris, John D; Ricklin, Daniel

2016-11-01

The complement cascade is an ancient immune-surveillance system that not only provides protection from pathogen invasion but has also evolved to participate in physiological processes to maintain tissue homeostasis. The alternative pathway (AP) of complement activation is the evolutionarily oldest part of this innate immune cascade. It is unique in that it is continuously activated at a low level and arbitrarily probes foreign, modified-self, and also unaltered self-structures. This indiscriminate activation necessitates the presence of preformed regulators on autologous surfaces to spare self-cells from the undirected nature of AP activation. Although the other two canonical complement activation routes, the classical and lectin pathways, initiate the cascade more specifically through pattern recognition, their activity still needs to be tightly controlled to avoid excessive reactivity. It is the perpetual duty of complement regulators to protect the self from damage inflicted by inadequate complement activation. Here, we review the role of complement regulators as preformed mediators of defense, explain their common and specialized functions, and discuss selected cases in which alterations in complement regulators lead to disease. Finally, rational engineering approaches using natural complement inhibitors as potential therapeutics are highlighted. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mechanism of neem limonoids-induced cell death in cancer: Role of oxidative phosphorylation.

PubMed

Yadav, Neelu; Kumar, Sandeep; Kumar, Rahul; Srivastava, Pragya; Sun, Leimin; Rapali, Peter; Marlowe, Timothy; Schneider, Andrea; Inigo, Joseph R; O'Malley, Jordan; Londonkar, Ramesh; Gogada, Raghu; Chaudhary, Ajay K; Yadava, Nagendra; Chandra, Dhyan

2016-01-01

We have previously reported that neem limonoids (neem) induce multiple cancer cell death pathways. Here we dissect the underlying mechanisms of neem-induced apoptotic cell death in cancer. We observed that neem-induced caspase activation does not require Bax/Bak channel-mediated mitochondrial outer membrane permeabilization, permeability transition pore, and mitochondrial fragmentation. Neem enhanced mitochondrial DNA and mitochondrial biomass. While oxidative phosphorylation (OXPHOS) Complex-I activity was decreased, the activities of other OXPHOS complexes including Complex-II and -IV were unaltered. Increased reactive oxygen species (ROS) levels were associated with an increase in mitochondrial biomass and apoptosis upon neem exposure. Complex-I deficiency due to the loss of Ndufa1-encoded MWFE protein inhibited neem-induced caspase activation and apoptosis, but cell death induction was enhanced. Complex II-deficiency due to the loss of succinate dehydrogenase complex subunit C (SDHC) robustly decreased caspase activation, apoptosis, and cell death. Additionally, the ablation of Complexes-I, -III, -IV, and -V together did not inhibit caspase activation. Together, we demonstrate that neem limonoids target OXPHOS system to induce cancer cell death, which does not require upregulation or activation of proapoptotic Bcl-2 family proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

Bone marrow-specific knock-in of a non-activatable Ikkα kinase mutant influences haematopoiesis but not atherosclerosis in Apoe-deficient mice.

PubMed

Tilstam, Pathricia V; Gijbels, Marion J; Habbeddine, Mohamed; Cudejko, Céline; Asare, Yaw; Theelen, Wendy; Zhou, Baixue; Döring, Yvonne; Drechsler, Maik; Pawig, Lukas; Simsekyilmaz, Sakine; Koenen, Rory R; de Winther, Menno P J; Lawrence, Toby; Bernhagen, Jürgen; Zernecke, Alma; Weber, Christian; Noels, Heidi

2014-01-01

The Ikkα kinase, a subunit of the NF-κB-activating IKK complex, has emerged as an important regulator of inflammatory gene expression. However, the role of Ikkα-mediated phosphorylation in haematopoiesis and atherogenesis remains unexplored. In this study, we investigated the effect of a bone marrow (BM)-specific activation-resistant Ikkα mutant knock-in on haematopoiesis and atherosclerosis in mice. Apolipoprotein E (Apoe)-deficient mice were transplanted with BM carrying an activation-resistant Ikkα gene (Ikkα(AA/AA)Apoe(-/-) ) or with Ikkα(+/+)Apoe(-/-) BM as control and were fed a high-cholesterol diet for 8 or 13 weeks. Interestingly, haematopoietic profiling by flow cytometry revealed a significant decrease in B-cells, regulatory T-cells and effector memory T-cells in Ikkα(AA/AA)Apoe(-/-) BM-chimeras, whereas the naive T-cell population was increased. Surprisingly, no differences were observed in the size, stage or cellular composition of atherosclerotic lesions in the aorta and aortic root of Ikkα(AA/AA)Apoe(-/-) vs Ikkα(+/+)Apoe(-/-) BM-transplanted mice, as shown by histological and immunofluorescent stainings. Necrotic core sizes, apoptosis, and intracellular lipid deposits in aortic root lesions were unaltered. In vitro, BM-derived macrophages from Ikkα(AA/AA)Apoe(-/-) vs Ikkα(+/+)Apoe(-/-) mice did not show significant differences in the uptake of oxidized low-density lipoproteins (oxLDL), and, with the exception of Il-12, the secretion of inflammatory proteins in conditions of Tnf-α or oxLDL stimulation was not significantly altered. Furthermore, serum levels of inflammatory proteins as measured with a cytokine bead array were comparable. Our data reveal an important and previously unrecognized role of haematopoietic Ikkα kinase activation in the homeostasis of B-cells and regulatory T-cells. However, transplantation of Ikkα(AA) mutant BM did not affect atherosclerosis in Apoe(-/-) mice. This suggests that the diverse functions of Ikkα in haematopoietic cells may counterbalance each other or may not be strong enough to influence atherogenesis, and reveals that targeting haematopoietic Ikkα kinase activity alone does not represent a therapeutic approach.

Modulation of neurosteroid potentiation by protein kinases at synaptic- and extrasynaptic-type GABAA receptors

PubMed Central

Adams, Joanna M.; Thomas, Philip; Smart, Trevor G.

2015-01-01

GABAA receptors are important for inhibition in the CNS where neurosteroids and protein kinases are potent endogenous modulators. Acting individually, these can either enhance or depress receptor function, dependent upon the type of neurosteroid or kinase and the receptor subunit combination. However, in vivo, these modulators probably act in concert to fine-tune GABAA receptor activity and thus inhibition, although how this is achieved remains unclear. Therefore, we investigated the relationship between these modulators at synaptic-type α1β3γ2L and extrasynaptic-type α4β3δ GABAA receptors using electrophysiology. For α1β3γ2L, potentiation of GABA responses by tetrahydro-deoxycorticosterone was reduced after inhibiting protein kinase C, and enhanced following its activation, suggesting this kinase regulates neurosteroid modulation. In comparison, neurosteroid potentiation was reduced at α1β3S408A,S409Aγ2L receptors, and unaltered by PKC inhibitors or activators, indicating that phosphorylation of β3 subunits is important for regulating neurosteroid activity. To determine whether extrasynaptic-type GABAA receptors were similarly modulated, α4β3δ and α4β3S408A,S409Aδ receptors were investigated. Neurosteroid potentiation was reduced at both receptors by the kinase inhibitor staurosporine. By contrast, neurosteroid-mediated potentiation at α4S443Aβ3S408A,S409Aδ receptors was unaffected by protein kinase inhibition, strongly suggesting that phosphorylation of α4 and β3 subunits is required for regulating neurosteroid activity at extrasynaptic receptors. Western blot analyses revealed that neurosteroids increased phosphorylation of β3S408,S409 implying that a reciprocal pathway exists for neurosteroids to modulate phosphorylation of GABAA receptors. Overall, these findings provide important insight into the regulation of GABAA receptors in vivo, and into the mechanisms by which GABAergic inhibitory transmission may be simultaneously tuned by two endogenous neuromodulators. This article is part of the Special Issue entitled ‘GABAergic Signaling in Health and Disease’. PMID:25278033

Interaction of toxic azo dyes with heme protein: biophysical insights into the binding aspect of the food additive amaranth with human hemoglobin.

PubMed

Basu, Anirban; Kumar, Gopinatha Suresh

2015-05-30

A biophysical study on the interaction of the food colorant amaranth with hemoglobin was undertaken. Spectrophotometric and spectrofluorimetric studies proposed for an intimate binding interaction between the dye and the protein. The dye quenched the fluorescence of the protein remarkably and the mechanism of quenching was found to be static in nature. Synchronous fluorescence studies suggested that the polarity around the tryptophan residues was altered in the presence of amaranth whereas the polarity around tyrosine residues remained largely unaltered. 3D fluorescence, FTIR and circular dichroism results suggested that the binding reaction caused conformational changes in hemoglobin. The negative far-UV CD bands exhibited a significantly large decrease in magnitude in the presence of amaranth. From calorimetry studies it was established that the binding was driven by a large positive entropic contribution and a small but favorable enthalpy change. Copyright © 2015 Elsevier B.V. All rights reserved.

Water Vapor Adsorption on Biomass Based Carbons under Post-Combustion CO2 Capture Conditions: Effect of Post-Treatment

PubMed Central

Querejeta, Nausika; Plaza, Marta G.; Rubiera, Fernando; Pevida, Covadonga

2016-01-01

The effect of post-treatment upon the H2O adsorption performance of biomass-based carbons was studied under post-combustion CO2 capture conditions. Oxygen surface functionalities were partially replaced through heat treatment, acid washing, and wet impregnation with amines. The surface chemistry of the final carbon is strongly affected by the type of post-treatment: acid treatment introduces a greater amount of oxygen whereas it is substantially reduced after thermal treatment. The porous texture of the carbons is also influenced by post-treatment: the wider pore volume is somewhat reduced, while narrow microporosity remains unaltered only after acid treatment. Despite heat treatment leading to a reduction in the number of oxygen surface groups, water vapor adsorption was enhanced in the higher pressure range. On the other hand acid treatment and wet impregnation with amines reduce the total water vapor uptake thus being more suitable for post-combustion CO2 capture applications. PMID:28773488

Characterization of a Torulaspora delbrueckii diploid strain with optimized performance in sweet and frozen sweet dough.

PubMed

Hernández-López, Maria José; Pallotti, Claudia; Andreu, Pasqual; Aguilera, Jaime; Prieto, José Antonio; Randez-Gil, Francisca

2007-05-01

Torulaspora delbrueckii is a baker's yeast that is highly tolerant to freeze-thaw stress, making it suitable for frozen dough technology. The T. delbrueckii strain PYCC5321, isolated from traditional bread dough, combines this tolerance with a high degree of ionic and osmotic stress resistance. However, the industrial use of this strain for frozen and sweet frozen baking is hampered by its small cell size, which causes clogging problems at the filtering stage. Here, we report the construction of a stable diploid strain of T. delbrueckii PYCC5321, which we named Td21-2n. The new strain was more than 2.7-fold bigger than their haploid counterpart, whereas biomass yield, stress resistance and sweet dough leavening ability were found to be similar in both strains. Moreover, the gassing power of the diploid after dough freezing also remained unaltered. Thus, Td21-2n meets the requirements necessary for industrial production and is suitable for application in frozen sweet baking products.

Temporal Variation of HCO+ 1_0 Galactic Absorption Lines Toward NRAO 150 and BL Lac

NASA Astrophysics Data System (ADS)

Han, Junghwan; Yun, Youngjoo; Park, Yong-Sun

2017-12-01

We present observations of HCO^+ 1-0 absorption lines toward two extragalactic compact radio sources, NRAO 150 and BL Lac with the Korean VLBI Network in order to investigate their time variation over 20 years by Galactic foreground clouds. It is found that the line shape of -17 km s^{-1} component changed marginally during 1993-1998 period and has remained unaltered thereafter for NRAO 150. Its behavior is different from that of H_2CO 1_{10}-1_{11}, suggesting chemical differentiation on ˜ 20 AU scale, the smallest ever seen. On the other hand, BL Lac exhibits little temporal variation for the HCO^+ and H_2CO lines. Our observation also suggests that Korea VLBI Network performs reliably in the spectrum mode in that the shapes of the new HCO^+ 1-0 spectra are in good agreement with the previous ones to an accuracy of a few percent except the time varying component toward NRAO 150.

Ereptiospiration.

PubMed

Woolley, Christine; Garcia, Antonio A; Santello, Marco

2017-04-12

Pure coconut oil, lanolin, and acetaminophen were vaporized at rates of 1-50 mg/min, using a porous network exhibiting a temperature gradient from 5000 to 5500 K/mm, without incurring noticeable chemical changes due to combustion, oxidation, or other thermally-induced chemical structural changes. The newly coined term "ereptiospiration" is used here to describe this combination of thermal transpiration at high temperature gradients since the process can force the creation of thermal aerosols by rapid heating in a localized zone. Experimental data were generated for these materials using two different supports for metering the materials to the battery powered coil: namely, a stainless steel fiber bundle and a 3-D printed steel cartridge. Heating coconut oil, lanolin, or acetaminophen in a beaker to lower temperatures than those achieved at the surface of the coil showed noticeable and rapid degradation in the samples, while visual and olfactory observations for ereptiospiration showed no noticeable degradation in lanolin and coconut oil while HPLC chromatograms along with visual observation confirm that within the limit of detection, acetaminophen remains chemically unaltered by ereptiospiration.

The effect of partial rostral hemimandibulectomy on mandibular mobility and temporomandibular joint morphology in the dog.

PubMed

Umphlet, R C; Johnson, A L; Eurell, J C; Losonsky, J

1988-01-01

Partial rostral hemimandibulectomy was performed in 10 adult dogs. The temporomandibular joints (TMJs) were examined radiographically and tomographically before surgery, and mandibular stability was evaluated before and immediately after surgery. Radiographic, tomographic, and hemimandibular mobility assessments were made again at months 3 and 6. The TMJs were examined grossly and histologically in five dogs euthanatized at month 3 and in five dogs euthanatized at month 6. Statistically significant hemimandibular instability (p less than 0.05) persisted in all subjects throughout the study. The radiographic appearance of the joints remained unaltered; however, space asymmetry was identified in postoperative tomograms of three dogs at month 3 and four dogs at month 6. The TMJs were grossly normal at necropsy. Histologically, there were degenerative changes in articular cartilage and subchondral bone in all of the joints. The authors conclude that partial rostral hemimandibulectomy causes TMJ degeneration, as a consequence of hemimandibular instability or abnormal loading, or both.

Chemical and microscopic characterization of outer seed coats of fossil and extant water plants

NASA Astrophysics Data System (ADS)

van Bergen, P. F.; Goñi, M.; Collinson, M. E.; Barrie, P. J.; Damsté, J. S. Sinninghe; De Leeuw, J. W.

1994-09-01

Sclerotic outer seed coat layers (testae) of three fossil and two extant water plant species were analyzed using scanning electron and light microscopy in addition to Curie-point pyrolysis, solid state 13C NMR, and CuO oxidation. Comparison between the chemical results from the fossil and extant samples reveals that the original resistant constituents in the sclerotic testae are native lignin-celluloses which are transformed to polyphenol macromolecules recognized in the fossil samples. The combination of microscopic and chemical data provides new insights regarding the early diagenetic processes by which lignin-cellulose-containing plant remains may have been transformed. In particular, the unaltered morphology in combination with major chemical modifications is used as the basis to postulate the timing and nature of lignin transformations. The combination of pyrolysis, solid state 13C NMR, and CuO oxidation is shown to be a powerful tool to characterize the chemical structure of testae of fossil and extant water plants.

Information encoded in non-native states drives substrate-chaperone pairing.

PubMed

Mapa, Koyeli; Tiwari, Satyam; Kumar, Vignesh; Jayaraj, Gopal Gunanathan; Maiti, Souvik

2012-09-05

Many proteins refold in vitro through kinetic folding intermediates that are believed to be by-products of native-state centric evolution. These intermediates are postulated to play only minor roles, if any, in vivo because they lack any information related to translation-associated vectorial folding. We demonstrate that refolding intermediate of a test protein, generated in vitro, is able to find its cognate chaperone, from the whole complement of Escherichia coli soluble chaperones. Cognate chaperone-binding uniquely alters the conformation of non-native substrate. Importantly, precise chaperone targeting of substrates are maintained as long as physiological molar ratios of chaperones remain unaltered. Using a library of different chaperone substrates, we demonstrate that kinetically trapped refolding intermediates contain sufficient structural features for precise targeting to cognate chaperones. We posit that evolution favors sequences that, in addition to coding for a functional native state, encode folding intermediates with higher affinity for cognate chaperones than noncognate ones. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dengue virus in bats from southeastern Mexico.

PubMed

Sotomayor-Bonilla, Jesús; Chaves, Andrea; Rico-Chávez, Oscar; Rostal, Melinda K; Ojeda-Flores, Rafael; Salas-Rojas, Mónica; Aguilar-Setien, Álvaro; Ibáñez-Bernal, Sergio; Barbachano-Guerrero, Arturo; Gutiérrez-Espeleta, Gustavo; Aguilar-Faisal, J Leopoldo; Aguirre, A Alonso; Daszak, Peter; Suzán, Gerardo

2014-07-01

To identify the relationship between landscape use and dengue virus (DENV) occurrence in bats, we investigated the presence of DENV from anthropogenically changed and unaltered landscapes in two Biosphere Reserves: Calakmul (Campeche) and Montes Azules (Chiapas) in southern Mexico. Spleen samples of 146 bats, belonging to 16 species, were tested for four DENV serotypes with standard reverse transcriptase polymerase chain reaction (RT-PCR) protocols. Six bats (4.1%) tested positive for DENV-2: four bats in Calakmul (two Glossophaga soricina, one Artibeus jamaicensis, and one A. lituratus) and two bats in Montes Azules (both A. lituratus). No effect of anthropogenic disturbance on the occurrence of DENV was detected; however, all three RT-PCR-positive bat species are considered abundant species in the Neotropics and well-adapted to disturbed habitats. To our knowledge, this study is the first study conducted in southeastern Mexico to identify DENV-2 in bats by a widely accepted RT-PCR protocol. The role that bats play on DENV's ecology remains undetermined. © The American Society of Tropical Medicine and Hygiene.

Detection and mapping of mineralized areas in the Cortez-Uinta Belt, Utah-Nevada, using computer-enhanced ERTS imagery

NASA Technical Reports Server (NTRS)

Rowan, L. C. (Principal Investigator)

1976-01-01

The author has identified the following significant results. Mineralogical differences between hydrothermally altered rocks and most unaltered rocks in south central Nevada cause visible and near infrared (0.45-2.4 micron) spectral reflectance differences which can be used to discriminate broad categories of rocks in multispectral images. The most important mineralogical differences are the increased abundance of goethite, hematite, jarosite, alunite, montmorillonite, and kaolinite in the altered zones. Because of the wavelength positions and widths of the LANDSAT MSS bands, these spectral differences are not apparent in individual or color infrared composite MSS images. The technique developed to enhance these subtle spectral differences combines ratioing of the MSS bands and contrast stretching. Field evaluation of color-ratio composite shows that, after exclusion of alluvial areas, approximately 80% of the green and brown color patterns are related to hydrothermal alteration. The remaining 20% consists mainly of pink hematitic crystallized tuff and tan or red ferruginous shale and siltstone.

The intermediate filament network protein, vimentin, is required for parvoviral infection.

PubMed

Fay, Nikta; Panté, Nelly

2013-09-01

Intermediate filaments (IFs) have recently been shown to serve novel roles during infection by many viruses. Here we have begun to study the role of IFs during the early steps of infection by the parvovirus minute virus of mice (MVM). We found that during early infection with MVM, after endosomal escape, the vimentin IF network was considerably altered, yielding collapsed immunofluorescence staining near the nuclear periphery. Furthermore, we found that vimentin plays an important role in the life cycle of MVM. The number of cells, which successfully replicated MVM, was reduced in infected cells in which the vimentin network was genetically or pharmacologically modified; viral endocytosis, however, remained unaltered. Perinuclear accumulation of MVM-containing vesicles was reduced in cells lacking vimentin. Our data suggests that vimentin is required for the MVM life cycle, presenting possibly a dual role: (1) following MVM escape from endosomes and (2) during endosomal trafficking of MVM. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

The significance of direct sunlight and polarized skylight in the ant’s celestial system of navigation

PubMed Central

Wehner, Rüdiger; Müller, Martin

2006-01-01

As textbook knowledge has it, bees and ants use polarized skylight as a backup cue whenever the main compass cue, the sun, is obscured by clouds. Here we show, by employing a unique experimental paradigm, that the celestial compass system of desert ants, Cataglyphis, relies predominantly on polarized skylight. If ants experience only parts of the polarization pattern during training but the full pattern in a subsequent test situation, they systematically deviate from their true homeward courses, with the systematics depending on what parts of the skylight patterns have been presented during training. This “signature” of the polarization compass remains unaltered, even if the ants can simultaneously experience the sun, which, if presented alone, enables the ants to select their true homeward courses. Information provided by direct sunlight and polarized skylight is picked up by different parts of the ant’s compound eyes and is channeled into two rather separate systems of navigation. PMID:16888039

Volitional Weight-Lifting in Rats Promotes Adaptation via Performance and Muscle Morphology prior to Gains in Muscle Mass

PubMed Central

Rader, Erik P; Miller, G Roger; Chetlin, Robert D; Wirth, Oliver; Baker, Brent A

2014-01-01

Investigation of volitional animal models of resistance training has been instrumental in our understanding of adaptive training. However, these studies have lacked reactive force measurements, a precise performance measure, and morphological analysis at a distinct phase of training – when initial strength gains precede muscle hypertrophy. Our aim was to expose rats to one month of training (70 or 700 g load) on a custom-designed weight-lifting apparatus for analysis of reactive forces and muscle morphology prior to muscle hypertrophy. Exclusively following 700 g load training, forces increased by 21% whereas muscle masses remained unaltered. For soleus (SOL) and tibialis anterior (TA) muscles, 700 g load training increased muscle fiber number per unit area by ∼20% and decreased muscle fiber area by ∼20%. Additionally, number of muscle fibers per section increased by 18% for SOL muscles. These results establish that distinct morphological alterations accompany early strength gains in a volitional animal model of load-dependent adaptive resistance training. PMID:25392697

Constructing a generalized network design model to study air distribution in ventilation networks in subway with a single-track tunnel

NASA Astrophysics Data System (ADS)

Lugin, IV

2018-03-01

In focus are the features of construction of the generalized design model for the network method to study air distribution in ventilation system in subway with the single-track tunnel. The generalizations, assumptions and simplifications included in the model are specified. The air distribution is calculated with regard to the influence of topology and air resistances of the ventilation network sections. The author studies two variants of the subway line: half-open and closed with dead end on the both sides. It is found that the total air exchange at a subway station depends on the station location within the line. The operating mode of fans remains unaltered in this case. The article shows that elimination of air leakage in the station ventilation room allows an increase in the air flow rate by 7–8% at the same energy consumption by fans. The influence of the stop of a train in the tunnel on the air distribution is illustrated.

Optimized protocol for combined PALM-dSTORM imaging.

PubMed

Glushonkov, O; Réal, E; Boutant, E; Mély, Y; Didier, P

2018-06-08

Multi-colour super-resolution localization microscopy is an efficient technique to study a variety of intracellular processes, including protein-protein interactions. This technique requires specific labels that display transition between fluorescent and non-fluorescent states under given conditions. For the most commonly used label types, photoactivatable fluorescent proteins and organic fluorophores, these conditions are different, making experiments that combine both labels difficult. Here, we demonstrate that changing the standard imaging buffer of thiols/oxygen scavenging system, used for organic fluorophores, to the commercial mounting medium Vectashield increased the number of photons emitted by the fluorescent protein mEos2 and enhanced the photoconversion rate between its green and red forms. In addition, the photophysical properties of organic fluorophores remained unaltered with respect to the standard imaging buffer. The use of Vectashield together with our optimized protocol for correction of sample drift and chromatic aberrations enabled us to perform two-colour 3D super-resolution imaging of the nucleolus and resolve its three compartments.

Evaluations of Silica Aerogel-Based Flexible Blanket as Passive Thermal Control Element for Spacecraft Applications

NASA Astrophysics Data System (ADS)

Hasan, Mohammed Adnan; Rashmi, S.; Esther, A. Carmel Mary; Bhavanisankar, Prudhivi Yashwantkumar; Sherikar, Baburao N.; Sridhara, N.; Dey, Arjun

2018-03-01

The feasibility of utilizing commercially available silica aerogel-based flexible composite blankets as passive thermal control element in applications such as extraterrestrial environments is investigated. Differential scanning calorimetry showed that aerogel blanket was thermally stable over - 150 to 126 °C. The outgassing behavior, e.g., total mass loss, collected volatile condensable materials, water vapor regained and recovered mass loss, was within acceptable range recommended for the space applications. ASTM tension and tear tests confirmed the material's mechanical integrity. The thermo-optical properties remained nearly unaltered in simulated space environmental tests such as relative humidity, thermal cycling and thermo-vacuum tests and confirmed the space worthiness of the aerogel. Aluminized Kapton stitched or anchored to the blanket could be used to control the optical transparency of the aerogel. These outcomes highlight the potential of commercial aerogel composite blankets as passive thermal control element in spacecraft. Structural and chemical characterization of the material was also done using scanning electron microscopy, Fourier transform infrared spectroscopy and x-ray photoelectron spectroscopy.

Experience-Dependent Rewiring of Specific Inhibitory Connections in Adult Neocortex

PubMed Central

Kätzel, Dennis; Miesenböck, Gero

2014-01-01

Although neocortical connectivity is remarkably stereotyped, the abundance of some wiring motifs varies greatly between cortical areas. To examine if regional wiring differences represent functional adaptations, we have used optogenetic raster stimulation to map the laminar distribution of GABAergic interneurons providing inhibition to pyramidal cells in layer 2/3 (L2/3) of adult mouse barrel cortex during sensory deprivation and recovery. Whisker trimming caused large, motif-specific changes in inhibitory synaptic connectivity: ascending inhibition from deep layers 4 and 5 was attenuated to 20%–45% of baseline, whereas inhibition from superficial layers remained stable (L2/3) or increased moderately (L1). The principal mechanism of deprivation-induced plasticity was motif-specific changes in inhibitory-to-excitatory connection probabilities; the strengths of extant connections were left unaltered. Whisker regrowth restored the original balance of inhibition from deep and superficial layers. Targeted, reversible modifications of specific inhibitory wiring motifs thus contribute to the adaptive remodeling of cortical circuits. PMID:24586113

Dengue Virus in Bats from Southeastern Mexico

PubMed Central

Sotomayor-Bonilla, Jesús; Chaves, Andrea; Rico-Chávez, Oscar; Rostal, Melinda K.; Ojeda-Flores, Rafael; Salas-Rojas, Mónica; Aguilar-Setien, Álvaro; Ibáñez-Bernal, Sergio; Barbachano-Guerrero, Arturo; Gutiérrez-Espeleta, Gustavo; Aguilar-Faisal, J. Leopoldo; Aguirre, A. Alonso; Daszak, Peter; Suzán, Gerardo

2014-01-01

To identify the relationship between landscape use and dengue virus (DENV) occurrence in bats, we investigated the presence of DENV from anthropogenically changed and unaltered landscapes in two Biosphere Reserves: Calakmul (Campeche) and Montes Azules (Chiapas) in southern Mexico. Spleen samples of 146 bats, belonging to 16 species, were tested for four DENV serotypes with standard reverse transcriptase polymerase chain reaction (RT-PCR) protocols. Six bats (4.1%) tested positive for DENV-2: four bats in Calakmul (two Glossophaga soricina, one Artibeus jamaicensis, and one A. lituratus) and two bats in Montes Azules (both A. lituratus). No effect of anthropogenic disturbance on the occurrence of DENV was detected; however, all three RT-PCR–positive bat species are considered abundant species in the Neotropics and well-adapted to disturbed habitats. To our knowledge, this study is the first study conducted in southeastern Mexico to identify DENV-2 in bats by a widely accepted RT-PCR protocol. The role that bats play on DENV's ecology remains undetermined. PMID:24752688

Hydroxyapatite with Permanent Electrical Polarization: Preparation, Characterization, and Response against Inorganic Adsorbates.

PubMed

Rivas, Manuel; Del Valle, Luis J; Armelin, Elaine; Bertran, Oscar; Turon, Pau; Puiggalí, Jordi; Alemán, Carlos

2018-04-16

Permanently polarized hydroxyapatite (HAp) particles have been prepared by applying a constant DC of 500 V at 1000 °C for 1 h to the sintered mineral. This process causes important chemical changes, as the formation of OH - defects (vacancies), the disappearance of hydrogenophosphate ions at the mineral surface layer, and structural variations reflected by the increment of the crystallinity. As a consequence, the electrochemical properties and electrical conductivity of the polarized mineral increase noticeably compared with as-prepared and sintered samples. Moreover, these increments remain practically unaltered after several months. In addition, permanent polarization favours significantly the ability of HAp to adsorb inorganic bioadsorbates in comparison with as-prepared and sintered samples. The adsorbates cause a significant increment of the electrochemical stability and electrical conductivity with respect to bare polarized HAp, which may have many implications for biomedical applications of permanently polarized HAp. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acetylation of barnyardgrass starch with acetic anhydride under iodine catalysis.

PubMed

Bartz, Josiane; Goebel, Jorge Tiago; Giovanaz, Marcos Antônio; Zavareze, Elessandra da Rosa; Schirmer, Manoel Artigas; Dias, Alvaro Renato Guerra

2015-07-01

Barnyardgrass (Echinochloa crus-galli) is an invasive plant that is difficult to control and is found in abundance as part of the waste of the paddy industry. In this study, barnyardgrass starch was extracted and studied to obtain a novel starch with potential food and non-food applications. We report some of the physicochemical, functional and morphological properties as well as the effect of modifying this starch with acetic anhydride by catalysis with 1, 5 or 10mM of iodine. The extent of the introduction of acetyl groups increased with increasing iodine levels as catalyst. The shape of the granules remained unaltered, but there were low levels of surface corrosion and the overall relative crystallinity decreased. The pasting temperature, enthalpy and other gelatinisation temperatures were reduced by the modification. There was an increase in the viscosity of the pastes, except for the peak viscosity, which was strongly reduced in 10mM iodine. Copyright © 2015 Elsevier Ltd. All rights reserved.

The classical and quantum dynamics of molecular spins on graphene

PubMed Central

Cervetti, Christian; Rettori, Angelo; Pini, Maria Gloria; Cornia, Andrea; Repollés, Ana; Luis, Fernando; Dressel, Martin; Rauschenbach, Stephan; Kern, Klaus; Burghard, Marko; Bogani, Lapo

2015-01-01

Controlling the dynamics of spins on surfaces is pivotal to the design of spintronic1 and quantum computing2 devices. Proposed schemes involve the interaction of spins with graphene to enable surface-state spintronics3,4, and electrical spin-manipulation4-11. However, the influence of the graphene environment on the spin systems has yet to be unraveled12. Here we explore the spin-graphene interaction by studying the classical and quantum dynamics of molecular magnets13 on graphene. While the static spin response remains unaltered, the quantum spin dynamics and associated selection rules are profoundly modulated. The couplings to graphene phonons, to other spins, and to Dirac fermions are quantified using a newly-developed model. Coupling to Dirac electrons introduces a dominant quantum-relaxation channel that, by driving the spins over Villain’s threshold, gives rise to fully-coherent, resonant spin tunneling. Our findings provide fundamental insight into the interaction between spins and graphene, establishing the basis for electrical spin-manipulation in graphene nanodevices. PMID:26641019

Stability of cavitation structures in a thin liquid layer.

PubMed

Wu, Pengfei; Bai, Lixin; Lin, Weijun; Yan, Jiuchun

2017-09-01

The inception and evolution of acoustic cavitation structures in thin liquid layers under different conditions and perturbations are investigated experimentally with high speed photography. The stability and characterization of cavitation structures are quantified by image analysis methods. It is found that cavitation structures (shape of bubble cloud and number of bubbles) are stable under unaltered experimental conditions, and the cavitation bubble cloud will return to the original structure and remain stable even in the face of large perturbations. When the experimental conditions are altered (for example, acoustic intensity, cavitation nuclei, boundary), the cavitation structures will vary correspondingly. Further analysis implies that the stability of cavitation structures is closely related to the number of bubbles in the cavitation bubble cloud. There are two mechanisms acting simultaneously in the cavitation bubble cloud evolution, one "bubble production" and the other "bubble disappearance". We propose that the two mechanisms acting together constitute the most likely explanation for the stability of cavitation structures and their transformation. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of hemicholinium and bretylium on the release of autonomic transmitters in the isolated sino-atrial node

PubMed Central

Appel, W. C.; Vincenzi, F. F.

1970-01-01

1. In the isolated, spontaneously beating, sino-atrial node of the rabbit selective electrical excitation of intranodal autonomic nerve fibres results in a biphasic chronotropic response. This chronotropic response (negative followed by positive chronotropism) is due to the release of the autonomic transmitters (acetylcholine and noradrenaline, respectively) from intranodal nerve fibres. 2. In the presence of 2 × 10-4 g/ml hemicholinium, the negative chronotropic (cholinergic) response is abolished while the positive chronotropic (adrenergic) response is unaltered. 3. In the presence of 5 × 10-6 g/ml bretylium, the positive chronotropic response is abolished while the negative chronotropic response is little affected. 4. After blockade of the negative chronotropic response by hemicholinium, bretylium abolishes the remaining positive chronotropic response. The effect of bretylium is not altered in the presence of hemicholinium. 5. Considering currently accepted mechanisms of action for hemicholinium and bretylium, the results of these experiments do not lend support to the cholinergic link hypothesis of adrenergic neuro-effector transmission. PMID:5492897

Effects of hemicholinium and bretylium on the release of autonomic transmitters in the isolated sino-atrial node.

PubMed

Appel, W C; Vincenzi, F F

1970-10-01

1. In the isolated, spontaneously beating, sino-atrial node of the rabbit selective electrical excitation of intranodal autonomic nerve fibres results in a biphasic chronotropic response. This chronotropic response (negative followed by positive chronotropism) is due to the release of the autonomic transmitters (acetylcholine and noradrenaline, respectively) from intranodal nerve fibres.2. In the presence of 2 x 10(-4) g/ml hemicholinium, the negative chronotropic (cholinergic) response is abolished while the positive chronotropic (adrenergic) response is unaltered.3. In the presence of 5 x 10(-6) g/ml bretylium, the positive chronotropic response is abolished while the negative chronotropic response is little affected.4. After blockade of the negative chronotropic response by hemicholinium, bretylium abolishes the remaining positive chronotropic response. The effect of bretylium is not altered in the presence of hemicholinium.5. Considering currently accepted mechanisms of action for hemicholinium and bretylium, the results of these experiments do not lend support to the cholinergic link hypothesis of adrenergic neuro-effector transmission.

Can rodents conceive hyperbolic spaces?

PubMed Central

Urdapilleta, Eugenio; Troiani, Francesca; Stella, Federico; Treves, Alessandro

2015-01-01

The grid cells discovered in the rodent medial entorhinal cortex have been proposed to provide a metric for Euclidean space, possibly even hardwired in the embryo. Yet, one class of models describing the formation of grid unit selectivity is entirely based on developmental self-organization, and as such it predicts that the metric it expresses should reflect the environment to which the animal has adapted. We show that, according to self-organizing models, if raised in a non-Euclidean hyperbolic cage rats should be able to form hyperbolic grids. For a given range of grid spacing relative to the radius of negative curvature of the hyperbolic surface, such grids are predicted to appear as multi-peaked firing maps, in which each peak has seven neighbours instead of the Euclidean six, a prediction that can be tested in experiments. We thus demonstrate that a useful universal neuronal metric, in the sense of a multi-scale ruler and compass that remain unaltered when changing environments, can be extended to other than the standard Euclidean plane. PMID:25948611

Error-dependent modulation of speech-induced auditory suppression for pitch-shifted voice feedback.

PubMed

Behroozmand, Roozbeh; Larson, Charles R

2011-06-06

The motor-driven predictions about expected sensory feedback (efference copies) have been proposed to play an important role in recognition of sensory consequences of self-produced motor actions. In the auditory system, this effect was suggested to result in suppression of sensory neural responses to self-produced voices that are predicted by the efference copies during vocal production in comparison with passive listening to the playback of the identical self-vocalizations. In the present study, event-related potentials (ERPs) were recorded in response to upward pitch shift stimuli (PSS) with five different magnitudes (0, +50, +100, +200 and +400 cents) at voice onset during active vocal production and passive listening to the playback. Results indicated that the suppression of the N1 component during vocal production was largest for unaltered voice feedback (PSS: 0 cents), became smaller as the magnitude of PSS increased to 200 cents, and was almost completely eliminated in response to 400 cents stimuli. Findings of the present study suggest that the brain utilizes the motor predictions (efference copies) to determine the source of incoming stimuli and maximally suppresses the auditory responses to unaltered feedback of self-vocalizations. The reduction of suppression for 50, 100 and 200 cents and its elimination for 400 cents pitch-shifted voice auditory feedback support the idea that motor-driven suppression of voice feedback leads to distinctly different sensory neural processing of self vs. non-self vocalizations. This characteristic may enable the audio-vocal system to more effectively detect and correct for unexpected errors in the feedback of self-produced voice pitch compared with externally-generated sounds.

An insight into the hepatocellular death induced by amphetamines, individually and in combination: the involvement of necrosis and apoptosis.

PubMed

Dias da Silva, Diana; Carmo, Helena; Lynch, Adam; Silva, Elisabete

2013-12-01

The liver is a vulnerable target for amphetamine toxicity, but the mechanisms involved in the drug's hepatotoxicity remain poorly understood. The purpose of the current research was to characterize the mode of death elicited by four amphetamines and to evaluate whether their combination triggered similar mechanisms in immortalized human HepG2 cells. The obtained data revealed a time- and temperature-dependent mortality of HepG2 cells exposed to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy; 1.3 mM), methamphetamine (3 mM), 4-methylthioamphetamine (0.5 mM) and D-amphetamine (1.7 mM), alone or combined (1.6 mM mixture). At physiological temperature (37 °C), 24-h exposures caused HepG2 death preferentially by apoptosis, while a rise to 40.5 °C favoured necrosis. ATP levels remained unaltered when the drugs where tested at normothermia, but incubation at 40.5 °C provoked marked ATP depletion for all treatments. Further investigations on the apoptotic mechanisms triggered by the drugs (alone or combined) showed a decline in BCL-2 and BCL- XL mRNA levels, with concurrent upregulation of BAX, BIM, PUMA and BID genes. Elevation of Bax, cleaved Bid, Puma, Bak and Bim protein levels was also seen. To the best of our knowledge, Puma, Bim and Bak have never been linked with the toxicity induced by amphetamines. Time-dependent caspase-3/-7 activation, but not mitochondrial membrane potential (∆ψm) disruption, also mediated amphetamine-induced apoptosis. The cell dismantling was confirmed by poly(ADP-ribose)polymerase proteolysis. Overall, for all evaluated parameters, no relevant differences were detected between individual amphetamines and the mixture (all tested at equieffective cytotoxic concentrations), suggesting that the mode of action of the amphetamines in combination does not deviate from the mode of action of the drugs individually, when eliciting HepG2 cell death.

Preliminary report of 48-hours Atosiban administration in spontaneous preterm labor - Doppler blood flow assessment of placental and fetal circulation.

PubMed

Grzesiak, Mariusz; Wilczynski, Jan

2013-01-01

The aims were to investigate whether there are any changes in placental and fetal circulation during Atosiban tocolysis within the first 48 hours of therapy. Detailed Doppler evaluation of placental and fetal circulation was performed prior to Atosiban administration and thereafter at 24 and 48 hours. Maternal heart rate and the pulsatility index (PI) in both uterine arteries (R-UtA, L-UtA) were assessed. Fetal heart rate (FHR), the resistance (RI) and pulsatility index (PI) of umbilical (UA) and middle cerebral artery (MCA) were measured. Additionally cerebroplacental ratio was calculated. E-wave/A-wave ratio (E/A) for atrioventricular valves, the myocardial performance index (MPI) and shortening fraction (SF) for both ventricles were calculated for both ventricles independently. To determine changes over time in all study variables analysis of variance (ANOVA) for repeated measurements followed by Tukey-Kramer's post hoc test was used. The effects of additional clinical covariates were checked. Maternal heart rate and blood flow in (R-UtA/L-UtA) were not altered significantly during Atosiban administration. No significant changes in FHR as well as Doppler parameters (RI, PI, PSV) in UA and MCA were recorded after 24/48 hours of tocolytic treatment. The mean values of cerebroplacental ratio (CPR) remained unaltered during treatment. Detailed evaluation of fetal cardiac function parameters (E/A, SF, MPI) calculated independently for both ventricles, revealed no significant changes over the time. To our best knowledge this study has been first evaluation of placental and fetal circulation with assessment of cardiac hemodynamic function during 48-hours administration of Atosiban. This kind of tocolysis treatment seems not to alter uterine nor fetal arterial blood flow pattern seriously. Hemodynamic cardiac activity in fetuses has remained unaffected. We cannot conclude definitely that there are absolutely no changes in the fetal hemodynamic condition due to Atosiban. Further studies should be performed to verify its possible influence on fetal venous blood flow.

Extremely elevated room-temperature kinetic isotope effects quantify the critical role of barrier width in enzymatic C-H activation.

PubMed

Hu, Shenshen; Sharma, Sudhir C; Scouras, Alexander D; Soudackov, Alexander V; Carr, Cody A Marcus; Hammes-Schiffer, Sharon; Alber, Tom; Klinman, Judith P

2014-06-11

The enzyme soybean lipoxygenase (SLO) has served as a prototype for hydrogen-tunneling reactions, as a result of its unusual kinetic isotope effects (KIEs) and their temperature dependencies. Using a synergy of kinetic, structural, and theoretical studies, we show how the interplay between donor-acceptor distance and active-site flexibility leads to catalytic behavior previously predicted by quantum tunneling theory. Modification of the size of two hydrophobic residues by site-specific mutagenesis in SLO reduces the reaction rate 10(4)-fold and is accompanied by an enormous and unprecedented room-temperature KIE. Fitting of the kinetic data to a non-adiabatic model implicates an expansion of the active site that cannot be compensated by donor-acceptor distance sampling. A 1.7 Å resolution X-ray structure of the double mutant further indicates an unaltered backbone conformation, almost identical side-chain conformations, and a significantly enlarged active-site cavity. These findings show the compelling property of room-temperature hydrogen tunneling within a biological context and demonstrate the very high sensitivity of such tunneling to barrier width.

Stability of dronabinol capsules when stored frozen, refrigerated, or at room temperature.

PubMed

Wempe, Michael F; Oldland, Alan; Stolpman, Nancy; Kiser, Tyree H

2016-07-15

Results of a study to determine the 90-day stability of dronabinol capsules stored under various temperature conditions are reported. High-performance liquid chromatography (HPLC) with ultraviolet (UV) detection was used to assess the stability of dronabinol capsules (synthetic delta-9-tetrahydrocannabinol [Δ9-THC] mixed with high-grade sesame oil and other inactive ingredients and encapsulated as soft gelatin capsules) that were frozen, refrigerated, or kept at room temperature for three months. The dronabinol capsules remained in the original foil-sealed blister packs until preparation for HPLC-UV assessment. The primary endpoint was the percentage of the initial Δ9-THC concentration remaining at multiple designated time points. The secondary aim was to perform forced-degradation studies under acidic conditions to demonstrate that the HPLC-UV method used was stability indicating. The appearance of the dronabinol capsules remained unaltered during frozen, cold, or room-temperature storage. Regardless of storage condition, the percentage of the initial Δ9-THC content remaining was greater than 97% for all evaluated samples at all time points over the three-month study. These experimental data indicate that the product packaging and the sesame oil used to formulate dronabinol capsules efficiently protect Δ9-THC from oxidative degradation to cannabinol; this suggests that pharmacies can store dronabinol capsules in nonrefrigerated automated dispensing systems, with a capsule expiration date of 90 days after removal from the refrigerator. Dronabinol capsules may be stored at room temperature in their original packaging for up to three months without compromising capsule appearance and with minimal reduction in Δ9-THC concentration. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Resilience of norovirus GII.4 to freezing and thawing: implications for virus infectivity.

PubMed

Richards, Gary P; Watson, Michael A; Meade, Gloria K; Hovan, Gregory L; Kingsley, David H

2012-12-01

Genogroup II.4 norovirus (NoV) remains the predominant NoV strain in food- and water-borne outbreaks. Capsid integrity as well as viral RNA persistence were determined for GII.4 NoV by real-time RT-PCR after 1-14 freeze/thaw (F/T) cycles (-80 °C/+22 °C) or after -80 °C storage for up to 120 days. In both cases, capsid integrity and viral RNA titers remained stable. RNase was exogenously added after 1-14 F/T cycles, but did not alter the amount of genomic NoV RNA detected, indicating that capsids remained intact. Presumptive NoV infectivity was evaluated in functional studies by a porcine gastric mucin binding assay. Viruses frozen and thawed up to 14× bound similarly to porcine mucin, suggesting no reduction in virus infectivity. Overall, this study shows that a) NoV particles retain their integrity for at least 14 F/T cycles, b) long-term (120 day) frozen storage does not decrease NoV RNA titers, and c) capsid binding to receptor-like glycoprotein moieties remains unaltered after 14 F/T cycles. This work indicates that freezing and thawing of foods or beverages would not be a practical processing intervention to reduce NoV contamination. Likewise, repeated freezing and thawing, as might be encountered during winter months, is not expected to inactivate NoV in the environment. Results do show that laboratory samples destined for molecular biological analyses or for use as positive controls may be repeatedly frozen and thawed without any anticipated reduction in NoV RNA titers. This study documents the cryostability of NoV capsids and RNA to freezing and thawing and to the possible retention of virus infectivity.

Circadian wheel-running activity during withdrawal from chronic intermittent ethanol exposure in mice

PubMed Central

Logan, Ryan W.; Seggio, Joseph A.; Robinson, Stacy L.; Richard, Gregory R.; Rosenwasser, Alan M.

2010-01-01

Alcohol withdrawal is associated with affective-behavioral disturbances in both human alcoholics and in animal models. In general, these phenomena are potentiated by increased alcohol exposure duration and by prior withdrawal episodes. Previous studies have also reported locomotor hypoactivity during ethanol withdrawal in rats and mice, but only in novel test environments, not in the home-cage. In the present study, we examined the effects of withdrawal from chronic intermittent ethanol (CIE) vapor exposure on the level and circadian periodicity of wheel-running activity in C57BL/6J mice. CIE treatment resulted in reductions in wheel-running activity relative to plain-air controls that persisted for about one week after withdrawal. Analysis of circadian waveforms indicated that reduced activity occurred throughout the night phase, but that daily activity patterns were otherwise unaltered. CIE failed to alter free-running circadian period or phase in animals maintained under constant darkness. These results show that ethanol withdrawal can result in locomotor hypoactivity even in the habitual, home-cage environment, and suggest that withdrawal-related reductions in wheel-running activity may reflect the specific motivational significance of this behavior. PMID:20682191

Beetroot juice supplementation reduces whole body oxygen consumption but does not improve indices of mitochondrial efficiency in human skeletal muscle.

PubMed

Whitfield, J; Ludzki, A; Heigenhauser, G J F; Senden, J M G; Verdijk, L B; van Loon, L J C; Spriet, L L; Holloway, G P

2016-01-15

Oral consumption of nitrate (NO3(-)) in beetroot juice has been shown to decrease the oxygen cost of submaximal exercise; however, the mechanism of action remains unresolved. We supplemented recreationally active males with beetroot juice to determine if this altered mitochondrial bioenergetics. Despite reduced submaximal exercise oxygen consumption, measures of mitochondrial coupling and respiratory efficiency were not altered in muscle. In contrast, rates of mitochondrial hydrogen peroxide (H2O2) emission were increased in the absence of markers of lipid or protein oxidative damage. These results suggest that improvements in mitochondrial oxidative metabolism are not the cause of beetroot juice-mediated improvements in whole body oxygen consumption. Ingestion of sodium nitrate (NO3(-)) simultaneously reduces whole body oxygen consumption (V̇O2) during submaximal exercise while improving mitochondrial efficiency, suggesting a causal link. Consumption of beetroot juice (BRJ) elicits similar decreases in V̇O2 but potential effects on the mitochondria remain unknown. Therefore we examined the effects of 7-day supplementation with BRJ (280 ml day(-1), ∼26 mmol NO3(-)) in young active males (n = 10) who had muscle biopsies taken before and after supplementation for assessments of mitochondrial bioenergetics. Subjects performed 20 min of cycling (10 min at 50% and 70% V̇O2 peak) 48 h before 'Pre' (baseline) and 'Post' (day 5 of supplementation) biopsies. Whole body V̇O2 decreased (P < 0.05) by ∼3% at 70% V̇O2 peak following supplementation. Mitochondrial respiration in permeabilized muscle fibres showed no change in leak respiration, the content of proteins associated with uncoupling (UCP3, ANT1, ANT2), maximal substrate-supported respiration, or ADP sensitivity (apparent Km). In addition, isolated subsarcolemmal and intermyofibrillar mitochondria showed unaltered assessments of mitochondrial efficiency, including ADP consumed/oxygen consumed (P/O ratio), respiratory control ratios and membrane potential determined fluorometrically using Safranine-O. In contrast, rates of mitochondrial hydrogen peroxide (H2O2) emission were increased following BRJ. Therefore, in contrast to sodium nitrate, BRJ supplementation does not alter key parameters of mitochondrial efficiency. This occurred despite a decrease in exercise V̇O2, suggesting that the ergogenic effects of BRJ ingestion are not due to a change in mitochondrial coupling or efficiency. It remains to be determined if increased mitochondrial H2O2 contributes to this response. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Urinary and plasma oxalate during ingestion of pure ascorbic acid: a re-evaluation.

PubMed

Fituri, N; Allawi, N; Bentley, M; Costello, J

1983-01-01

Daily ingestion of 8 g of pure ascorbic acid by 8 normal subjects for 7 days did not, in contrast to previous reports in the literature, significantly alter urinary or plasma oxalate during or after ingestion. When urine with raised ascorbate values was heated at 100 degrees C for 30 min, a significant increase in urinary oxalate concentration was observed. Plasma ascorbate reached a mean value during ingestion of 3.3 mg/100 ml. Urinary citrate excretion significantly decreased during the first 4 days of ascorbic acid ingestion; however, the urinary inhibitory activity of calcium oxalate crystal growth was not significantly altered. Urinary and serum urate as well as urinary calcium and magnesium were unaltered by ingestion of the vitamin supplement.

5. Photograph of a photograph in possession of Rock Island ...

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

5. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. WEST ELEVATION IN UNALTERED CONDITION. ORIGINALLY PUBLISHED 1898. - Rock Island Arsenal, Building No. 280, Sylvan Drive, Rock Island, Rock Island County, IL

Major Cys protease activities are not essential for senescence in individually darkened Arabidopsis leaves.

PubMed

Pružinská, Adriana; Shindo, Takayuki; Niessen, Sherry; Kaschani, Farnusch; Tóth, Réka; Millar, A Harvey; van der Hoorn, Renier A L

2017-01-06

Papain-like Cys Proteases (PLCPs) and Vacuolar Processing Enzymes (VPEs) are amongst the most highly expressed proteases during leaf senescence in Arabidopsis. Using activity-based protein profiling (ABPP), a method that enables detection of active enzymes within a complex sample using chemical probes, the activities of PLCPs and VPEs were investigated in individually darkened leaves of Arabidopsis, and their role in senescence was tested in null mutants. ABPP and mass spectrometry revealed an increased activity of several PLCPs, particularly RD21A and AALP. By contrast, despite increased VPE transcript levels, active VPE decreased in individually darkened leaves. Eight protease knock-out lines and two protease over expressing lines were subjected to senescence phenotype analysis to determine the importance of individual protease activities to senescence. Unexpectedly, despite the absence of dominating PLCP activities in these plants, the rubisco and chlorophyll decline in individually darkened leaves and the onset of whole plant senescence were unaltered. However, a significant delay in progression of whole plant senescence was observed in aalp-1 and rd21A-1/aalp-1 mutants, visible in the reduced number of senescent leaves. Major Cys protease activities are not essential for dark-induced and developmental senescence and only a knock out line lacking AALP shows a slight but significant delay in plant senescence.

Virus-mediated swapping of zolpidem-insensitive with zolpidem-sensitive GABA(A) receptors in cortical pyramidal cells.

PubMed

Sumegi, Mate; Fukazawa, Yugo; Matsui, Ko; Lorincz, Andrea; Eyre, Mark D; Nusser, Zoltan; Shigemoto, Ryuichi

2012-04-01

Recently developed pharmacogenetic and optogenetic approaches, with their own advantages and disadvantages, have become indispensable tools in modern neuroscience. Here, we employed a previously described knock-in mouse line (GABA(A)Rγ2(77I)lox) in which the γ2 subunit of the GABA(A) receptor (GABA(A)R) was mutated to become zolpidem insensitive (γ2(77I)) and used viral vectors to swap γ2(77I) with wild-type, zolpidem-sensitive γ2 subunits (γ2(77F)). The verification of unaltered density and subcellular distribution of the virally introduced γ2 subunits requires their selective labelling. For this we generated six N- and six C-terminal-tagged γ2 subunits, with which cortical cultures of GABA(A)Rγ2(−/−) mice were transduced using lentiviruses. We found that the N-terminal AU1 tag resulted in excellent immunodetection and unimpaired synaptic localization. Unaltered kinetic properties of the AU1-tagged γ2 ((AU1)γ2(77F)) channels were demonstrated with whole-cell patch-clamp recordings of spontaneous IPSCs from cultured cells. Next, we carried out stereotaxic injections of lenti- and adeno-associated viruses containing Cre-recombinase and the (AU1)γ2(77F) subunit (Cre-2A-(AU1)γ2(77F)) into the neocortex of GABA(A)Rγ2(77I)lox mice. Light microscopic immunofluorescence and electron microscopic freeze-fracture replica immunogold labelling demonstrated the efficient immunodetection of the AU1 tag and the normal enrichment of the (AU1)γ2(77F) subunits in perisomatic GABAergic synapses. In line with this,miniature and action potential-evoked IPSCs whole-cell recorded from transduced cells had unaltered amplitudes, kinetics and restored zolpidem sensitivity. Our results obtained with a wide range of structural and functional verification methods reveal unaltered subcellular distributions and functional properties of γ2(77I) and (AU1)γ2(77F) GABA(A)Rs in cortical pyramidal cells. This transgenic–viral pharmacogenetic approach has the advantage that it does not require any extrinsic protein that might endow some unforeseen alterations of the genetically modified cells. In addition, this virus-based approach opens up the possibility of modifying multiple cell types in distinct brain regions and performing alternative recombination-based intersectional genetic manipulations.

Discrimination of hydrothermally altered rocks along the Battle Mountain-Eureka, Nevada, mineral belt using Landsat images

USGS Publications Warehouse

Krohn, M. Dennis; Abrams, Michael J.; Rowan, Lawrence C.

1978-01-01

Landsat Multispectral Scanner (MSS) images of the northwestern part of the Battle Mountain-Eureki, Nevada mineral belt were evaluated for distinguishing hydrothermally altered rocks associated with porphyry copper and disseminated gold deposits. Detection of altered rocks from Landsat is based on the distinctive spectral reflectance of limonite present at coatings on weathered surfaces Some altered rocks are visible as bleached areas in individual MSS bands; however, they cannot be consistently distinguished from unaltered rocks with high albedo nor from bright areas resulting .from topographic slope. Black-and-white ratio images were generated to subdue .topographic effects, and three ratio images were composited in color to portray spectral radiance differences, forming an image known as a color-ratio composite (CRC). The optimum CRC image for this area has MSS 4/5 as blue, MSS 4/6 as yellow, and MSS 6/7 as magenta, and differs in two respects from most CRC images of arid areas. First, as a result of the increased vegetation cover in the study area, MSS 5/6 was replaced by MSS 4/6 as the yellow layer. Second, 70 mm positive transparencies were replaced by large format images (64 cm), thereby improving the internal registration of the CRC image and the effective spatial resolution. The pattern of limonitic rocks depicted in the CRC closely agrees with the mapped pattern of the alteration zones at the Copper Canyon and Copper Basin porphyry copper deposits. Certain west-facing topographic slopes in the altered areas are depicted as unaltered in the CRC, apparently due to atmospheric scattering, and illustrate the need for atmospheric correction. The disseminated gold deposits at Gold Acres and Tenabo are poorly represented in the CRC because of the general absence of limonite on these deposits. The presence of unaltered limonitic sedimentary and volcanic rocks is the largest obstacle to discriminating altered areas within the mineral belt. Reflectance spectra, made in situ and in the laboratory indicate differences between altered and unaltered rocks in the Spectra region between 1.1 ?m and 2.5 ?m. Such differences may be detectable by a remote scanner with a longer wavelength range than current Landsat MSS (0.6 ?m-1.1 ?m).

Lipophilization of somatostatin analog RC-160 with long chain fatty acid improves its anti-proliferative activity on human oral carcinoma cells in vitro.

PubMed

Dasgupta, P; Singh, A T; Mukherjee, R

2000-03-01

Oral cancer which comprises about 40% of total cancers in India, has one of the lowest relative survival rates of all cancers. Epidermal growth factor (EGF) has been known to play a role in the proliferation/malignant transformation of oral neoplasms. Since, the somatostatin analog RC-160 is reported to be a potent inhibitor of EGF stimulated cell proliferation, its anti-proliferative activity in the human oral carcinoma cell line KB was investigated, in this study. RC-160 was found to potently inhibit EGF-induced proliferation in KB cells in vitro, suggesting a therapeutic potential of the same in oral carcinoma. However, the therapeutic potential of RC-160 is limited by its short serum half life. To overcome this limitation, fatty acids namely butanoic acid and myristic acid individually were coupled to RC-160. The lipophilized derivatives of RC-160 were synthesized, purified and characterized. The anti-proliferative activity of lipophilized derivatives of RC-160 on KB cells was evaluated in vitro. Myristoyl-RC-160 (0.75 nM) inhibited the growth of KB cells at a 10-fold lower concentration relative to RC-160 (8.8 nM) and at a 100-fold lower concentration relative to butanoyl-RC-160 (0.83 microM) (p<0.001). The affinity of RC-160 towards somatostatin receptors remains unaltered by lipophilization. The signaling pathways underlying the antineoplastic activity of these lipopeptides are similar to RC-160, and do not involve the stimulation of a protein tyrosine phosphatase or a serine threonine phosphatase 1A and 2A. The anti-proliferative activity of the lipopeptides was found to be mediated by somatostatin receptors and correlates with the inhibition of protein tyrosine kinase activity and decrease in intracellular cAMP levels. Myristoyl-RC-160 displayed significantly greater resistance towards trypsin and serum degradation than RC-160 (p<0.01). These findings demonstrate that RC-160 can inhibit the growth of oral cancer cells in vitro. Lipophilization of RC-160 with long chain fatty acids like myristic acid improves its stability and anti-proliferative activity, in human oral carcinoma cells in vitro, thereby enhancing the scope of improving its therapeutic index.

Hepatitis D virus replication is sensed by MDA5 and induces IFN-β/λ responses in hepatocytes.

PubMed

Zhang, Zhenfeng; Filzmayer, Christina; Ni, Yi; Sültmann, Holger; Mutz, Pascal; Hiet, Marie-Sophie; Vondran, Florian W R; Bartenschlager, Ralf; Urban, Stephan

2018-07-01

Hepatitis B virus (HBV) and D virus (HDV) co-infections cause the most severe form of viral hepatitis. HDV induces an innate immune response, but it is unknown how the host cell senses HDV and if this defense affects HDV replication. We aim to characterize interferon (IFN) activation by HDV, identify the responsible sensor and evaluate the effect of IFN on HDV replication. HDV and HBV susceptible hepatoma cell lines and primary human hepatocytes (PHH) were used for infection studies. Viral markers and cellular gene expression were analyzed at different time points after infection. Pattern recognition receptors (PRRs) required for HDV-mediated IFN activation and the impact on HDV replication were studied using stable knock-down or overexpression of the PRRs. Microarray analysis revealed that HDV but not HBV infection activated a broad range of interferon stimulated genes (ISGs) in HepG2 NTCP cells. HDV strongly activated IFN-β and IFN-λ in cell lines and PHH. HDV induced IFN levels remained unaltered upon RIG-I (DDX58) or TLR3 knock-down, but were almost completely abolished upon MDA5 (IFIH1) depletion. Conversely, overexpression of MDA5 but not RIG-I and TLR3 in HuH7.5 NTCP cells partially restored ISG induction. During long-term infection, IFN levels gradually diminished in both HepG2 NTCP and HepaRG NTCP cell lines. MDA5 depletion had little effect on HDV replication despite dampening HDV-induced IFN response. Moreover, treatment with type I or type III IFNs did not abolish HDV replication. Active replication of HDV induces an IFN-β/λ response, which is predominantly mediated by MDA5. This IFN response and exogenous IFN treatment have only a moderate effect on HDV replication in vitro indicating the adaption of HDV replication to an IFN-activated state. In contrast to hepatitis B virus, infection with hepatitis D virus induces a strong IFN-β/λ response in innate immune competent cell lines. MDA5 is the key sensor for the recognition of hepatitis D virus replicative intermediates. An IFN-activated state did not prevent hepatitis D virus replication in vitro, indicating that hepatitis D virus is resistant to self-induced innate immune responses and therapeutic IFN treatment. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Lithospheric and Asthenospheric Contributions to Post-Collisional Volcanism in the Lesser Caucasus Mts (Armenia)

NASA Astrophysics Data System (ADS)

Sugden, P.; Savov, I. P.; Wilson, M.; Meliksetian, K.; Navasardyan, G.

2017-12-01

Continental collision zones remain the most enigmatic tectonic setting for volcanic activity on earth. The Lesser Caucasus Mts are host to widespread and unique intraplate volcanism, associated with the active Arabia-Eurasia continental collision. Volcanic products range from alkali basalts to rhyolites (including extensive ignimbrites), and occur as basaltic lava flow fields, large composite and shield volcanoes, and regions of distributed (mostly monogenetic) volcanism. Geomorphology, archaeology, and historical accounts suggest volcanic activity has extended in to the Holocene-historical period. The high quality of the exposures and the diversity of unaltered rock types makes Armenia an ideal natural laboratory for studying the sources of magmatism in an active continental collision zone. For the first time, we will present the mineral chemistry (ol, px, amph), whole rock major and trace element, and Sr-Nd isotope compositions of volcanic rocks from southernmost Armenia- namely the Gegham, Vardenis and Syunik volcanic highlands. We compare our dataset with the composition of post-collisional volcanic rocks elsewhere in the Arabia-Eurasia collision zone. Samples from S. Armenia are more mafic, more alkaline and more K2O rich. All volcanic rocks show negative HFSE anomalies and LILE and LREE enrichments reminiscent of continental volcanic arc settings. However, volcanic rocks in Southern Armenia are further enriched in some of the most incompatible trace elements, most notably LREE, Sr and P, and have higher La/Yb, Th/Yb, Ta/Yb, and more variable Th/Nb. Volcanic rocks from Eastern Anatolia and N. Armenia have Sr-Nd isotope compositions similar to those of the Mesozoic volcanic arc (87Sr/86Sr 0.7034-0.7045; 143Nd/144Nd 0.5128-0.5129), whereas samples from S. Armenia deviate towards more enriched compositions resembling a typical EM-I type reservoir (87Sr/86Sr 0.7041- 0.7047; 143Nd/144Nd 0.5127-0.5128). We argue that these distinctive geochemical characteristics result from the addition of an enriched lithospheric component to a ubiquitous subduction-modified baseline asthenospheric mantle. This EM-I like component may be characteristic for not only intraplate hotspot volcanoes but also to collisional and arc settings.

Indirect suppression of photosynthesis on individual leaves by arthropod herbivory

PubMed Central

Nabity, Paul D.; Zavala, Jorge A.; DeLucia, Evan H.

2009-01-01

Background Herbivory reduces leaf area, disrupts the function of leaves, and ultimately alters yield and productivity. Herbivore damage to foliage typically is assessed in the field by measuring the amount of leaf tissue removed and disrupted. This approach assumes the remaining tissues are unaltered, and plant photosynthesis and water balance function normally. However, recent application of thermal and fluorescent imaging technologies revealed that alterations to photosynthesis and transpiration propagate into remaining undamaged leaf tissue. Scope and Conclusions This review briefly examines the indirect effects of herbivory on photosynthesis, measured by gas exchange or chlorophyll fluorescence, and identifies four mechanisms contributing to the indirect suppression of photosynthesis in remaining leaf tissues: severed vasculature, altered sink demand, defence-induced autotoxicity, and defence-induced down-regulation of photosynthesis. We review the chlorophyll fluorescence and thermal imaging techniques used to gather layers of spatial data and discuss methods for compiling these layers to achieve greater insight into mechanisms contributing to the indirect suppression of photosynthesis. We also elaborate on a few herbivore-induced gene-regulating mechanisms which modulate photosynthesis and discuss the difficult nature of measuring spatial heterogeneity when combining fluorescence imaging and gas exchange technology. Although few studies have characterized herbivore-induced indirect effects on photosynthesis at the leaf level, an emerging literature suggests that the loss of photosynthetic capacity following herbivory may be greater than direct loss of photosynthetic tissues. Depending on the damage guild, ignoring the indirect suppression of photosynthesis by arthropods and other organisms may lead to an underestimate of their physiological and ecological impacts. PMID:18660492

3. Photograph of a photograph in possession of Rock Island ...

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

3. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. NORTH ELEVATION IN UNALTERED CONDITION. DATED NOVEMBER 21, 1944. - Rock Island Arsenal, Building No. 103, Rodman Avenue & First Street, Rock Island, Rock Island County, IL

3. Photograph of a photograph in possession of Rock Island ...

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

3. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. SOUTH ELEVATION IN UNALTERED CONDITION. DATED MARCH 19, 1945. - Rock Island Arsenal, Building No. 61, Rodman Avenue & First Street, Rock Island, Rock Island County, IL

4. Photograph of a photograph in possession of Rock Island ...

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

4. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. NORTH ELEVATION IN UNALTERED CONDITION. DATED NOVEMBER 21, 1944. - Rock Island Arsenal, Building No. 109, Rodman Avenue & Fourth Street, Rock Island, Rock Island County, IL

40 CFR 300.400 - General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... unaltered form, or altered solely through naturally occurring processes or phenomena, from a location where... federal agency, and a state or political subdivision operating pursuant to a contract or cooperative... or political subdivision operating pursuant to a contract or cooperative agreement under CERCLA...

Inducing self-selected human engagement in robotic locomotion training.

PubMed

Collins, Steven H; Jackson, Rachel W

2013-06-01

Stroke leads to severe mobility impairments for millions of individuals each year. Functional outcomes can be improved through manual treadmill therapy, but high costs limit patient exposure and, thereby, outcomes. Robotic gait training could increase the viable duration and frequency of training sessions, but robotic approaches employed thus far have been less effective than manual therapy. These shortcomings may relate to subconscious energy-minimizing drives, which might cause patients to engage less actively in therapy when provided with corrective robotic assistance. We have devised a new method for gait rehabilitation that harnesses, rather than fights, least-effort tendencies. Therapeutic goals, such as increased use of the paretic limb, are made easier than the patient's nominal gait through selective assistance from a robotic platform. We performed a pilot test on a healthy subject (N = 1) in which altered self-selected stride length was induced using a tethered robotic ankle-foot orthosis. The subject first walked on a treadmill while wearing the orthosis with and without assistance at unaltered and voluntarily altered stride length. Voluntarily increasing stride length by 5% increased metabolic energy cost by 4%. Robotic assistance decreased energy cost at both unaltered and voluntarily increased stride lengths, by 6% and 8% respectively. We then performed a test in which the robotic system continually monitored stride length and provided more assistance if the subject's stride length approached a target increase. This adaptive assistance protocol caused the subject to slowly adjust their gait patterns towards the target, leading to a 4% increase in stride length. Metabolic energy consumption was simultaneously reduced by 5%. These results suggest that selective-assistance protocols based on targets relevant to rehabilitation might lead patients to self-select desirable gait patterns during robotic gait training sessions, possibly facilitating better adherence and outcomes.

Predicting the biological condition of streams: Use of geospatial indicators of natural and anthropogenic characteristics of watersheds

USGS Publications Warehouse

Carlisle, D.M.; Falcone, J.; Meador, M.R.

2009-01-01

We developed and evaluated empirical models to predict biological condition of wadeable streams in a large portion of the eastern USA, with the ultimate goal of prediction for unsampled basins. Previous work had classified (i.e., altered vs. unaltered) the biological condition of 920 streams based on a biological assessment of macroinvertebrate assemblages. Predictor variables were limited to widely available geospatial data, which included land cover, topography, climate, soils, societal infrastructure, and potential hydrologic modification. We compared the accuracy of predictions of biological condition class based on models with continuous and binary responses. We also evaluated the relative importance of specific groups and individual predictor variables, as well as the relationships between the most important predictors and biological condition. Prediction accuracy and the relative importance of predictor variables were different for two subregions for which models were created. Predictive accuracy in the highlands region improved by including predictors that represented both natural and human activities. Riparian land cover and road-stream intersections were the most important predictors. In contrast, predictive accuracy in the lowlands region was best for models limited to predictors representing natural factors, including basin topography and soil properties. Partial dependence plots revealed complex and nonlinear relationships between specific predictors and the probability of biological alteration. We demonstrate a potential application of the model by predicting biological condition in 552 unsampled basins across an ecoregion in southeastern Wisconsin (USA). Estimates of the likelihood of biological condition of unsampled streams could be a valuable tool for screening large numbers of basins to focus targeted monitoring of potentially unaltered or altered stream segments. ?? Springer Science+Business Media B.V. 2008.

Error-dependent modulation of speech-induced auditory suppression for pitch-shifted voice feedback

PubMed Central

2011-01-01

Background The motor-driven predictions about expected sensory feedback (efference copies) have been proposed to play an important role in recognition of sensory consequences of self-produced motor actions. In the auditory system, this effect was suggested to result in suppression of sensory neural responses to self-produced voices that are predicted by the efference copies during vocal production in comparison with passive listening to the playback of the identical self-vocalizations. In the present study, event-related potentials (ERPs) were recorded in response to upward pitch shift stimuli (PSS) with five different magnitudes (0, +50, +100, +200 and +400 cents) at voice onset during active vocal production and passive listening to the playback. Results Results indicated that the suppression of the N1 component during vocal production was largest for unaltered voice feedback (PSS: 0 cents), became smaller as the magnitude of PSS increased to 200 cents, and was almost completely eliminated in response to 400 cents stimuli. Conclusions Findings of the present study suggest that the brain utilizes the motor predictions (efference copies) to determine the source of incoming stimuli and maximally suppresses the auditory responses to unaltered feedback of self-vocalizations. The reduction of suppression for 50, 100 and 200 cents and its elimination for 400 cents pitch-shifted voice auditory feedback support the idea that motor-driven suppression of voice feedback leads to distinctly different sensory neural processing of self vs. non-self vocalizations. This characteristic may enable the audio-vocal system to more effectively detect and correct for unexpected errors in the feedback of self-produced voice pitch compared with externally-generated sounds. PMID:21645406

Effect of an acute intraluminal administration of capsaicin on oesophageal motor pattern in GORD patients with ineffective oesophageal motility.

PubMed

Grossi, L; Cappello, G; Marzio, L

2006-08-01

Ineffective oesophageal motility (IOM) is a functional disorder affecting about 50% of gastro-oesophageal reflux disease (GORD) patients. This disease in a severe form limits the clearing ability of the oesophagus and is considered one of the predictive factors for poorer GORD resolution. Capsaicin, the active compound of red pepper, exerts a prokinetic effect on oesophageal motility in healthy subjects by increasing the amplitude of body waves, even if no evidence exists on its possible role in situations of reduced motility. The aim of the study was to evaluate the effect of an acute administration of capsaicin on the oesophageal motor pattern in a group of GORD patients affected by severe IOM. Twelve GORD patients with severe IOM received an intra-oesophageal administration of 2 mL of a red pepper-olive oil mixture and 2 mL of olive oil alone serving as a control during a stationary manometry. The motor patterns of the oesophageal body and lower oesophageal sphincter (LOS) were analysed at baseline and after the infusion of the two stimuli. The administration of capsaicin induced a significant improvement in oesophageal body contractility when compared with baseline. The velocity of propagation of waves and the LOS basal tone remained unchanged. The motor pattern was unaltered by the administration of olive oil alone. An acute administration of capsaicin seems to improve the motor performance of the oesophageal body in patients with ineffective motility. Whether this could represent the basis for further therapeutic approaches of GORD patients needs further study.

Prednisolone reduces experimental arthritis, and inflammatory tissue destruction in SCID mice infected with Borrelia burgdorferi.

PubMed

Hurtenbach, U; Böggemeyer, E; Stehle, T; Museteanu, C; Del Pozo, E; Simon, M M

1996-05-01

Glucocorticosteroids (GC) are widely used as anti-inflammatory agents. The effects of Prednisolone on the development of Borrelia (B.) burgdorferi-induced clinical arthritis and organ inflammation was studied in severe combined immunodeficiency (SCID) mice. The drug was administered orally at a dose of 3, 10 and 30 mg/kg, starting shortly before experimental infection of the mice. A dose dependent inhibition of arthritic joint swelling was observed. Full protection was obtained with 30 mg/kg until 21 days after infection, subsequently, mild joint swelling developed but progression and severity of the disease was considerably less than in the other treated as well as in the untreated mice. Inhibition of clinical arthritis coincided with reduction of inflammatory cell infiltration in the joints, liver and muscle. Prednisolone was ineffective when application was initiated after arthritis was fully developed, i.e., 22 days after infection. Since the activated endothelium plays a critical role in development of inflammatory lesions, the expression of the cellular adhesion molecules (CAMs) E-selectin, P-selectin, ICAM-1 and VCAM-1 was determined in vitro using the bEnd3 endothelial cell line. Stimulation with a sonicated B. burgdorferi preparation in the presence of the water-soluble compound Prednisolone-21-hemisuccinate considerably reduced expression of ICAM-1, and marginally also of E-selectin, whereas the level of P-selectin and VCAM-1 remained unaltered. Thus, downregulation of ICAM-1 might be a critical factor in Prednisolone-mediated inhibition of B. burgdorferi-induced inflammation; the flare up of the disease after the initial protection indicates that additional therapy, e.g. with antibiotics, is necessary.

Effect of silver nanoparticles on the metabolic rate, hematological response, and survival of juvenile white shrimp Litopenaeus vannamei.

PubMed

Juarez-Moreno, Karla; Mejía-Ruiz, Claudio Humberto; Díaz, Fernando; Reyna-Verdugo, Horacio; Re, Ana Denisse; Vazquez-Felix, Edgar F; Sánchez-Castrejón, Edna; Mota-Morales, Josué D; Pestryakov, Alexey; Bogdanchikova, Nina

2017-02-01

White spot syndrome virus (WSSV) is highly lethal and contagious in shrimps; its outbreaks causes an economic crisis for aquaculture. Several attempts have been made to treat this disease; however, to date, there is no effective cure. Because of their antimicrobial activities, silver nanoparticles (AgNPs) are the most studied nanomaterial. Although the antiviral properties of AgNPs have been studied, their antiviral effect against viral infection in aquaculture has not been reported. The AgNPs tested herein are coated with polyvinylpyrrolidone (PVP) and possess multiple international certifications for their use in veterinary and human applications. The aim of this work was to evaluate the survival rate of juvenile white shrimps (Litopenaeus vannamei) after the intramuscular administration of AgNPs. For this, different concentrations of metallic AgNPs and PVP alone were injected into the organisms. After 96 h of administration, shrimp survival was more than 90% for all treatments. The oxygen consumption routine rate and total hemocyte count remained unaltered after AgNP injection, reflecting no stress caused. We evaluated whether AgNPs had an antiviral effect in shrimps infected with WSSV. The results revealed that the survival rate of WSSV-infected shrimps after AgNP administration was 80%, whereas the survival rate of untreated organisms was only 10% 96 h after infection. These results open up the possibility to explore the potential use of AgNPs as antiviral agents for the treatment of diseases in aquaculture organisms, particularly the WSSV in shrimp culture. Copyright © 2016 Elsevier Ltd. All rights reserved.

Revisiting the human polypeptide GalNAc-T1 and T13 paralogs

PubMed Central

Festari, María Florencia; Trajtenberg, Felipe; Berois, Nora; Pantano, Sergio; Revoredo, Leslie; Kong, Yun; Solari-Saquieres, Patricia; Narimatsu, Yoshiki; Freire, Teresa; Bay, Sylvie; Robello, Carlos; Bénard, Jean; Gerken, Thomas A; Clausen, Henrik; Osinaga, Eduardo

2017-01-01

Polypeptide GalNAc-transferases (GalNAc-Ts) constitute a family of 20 human glycosyltransferases (comprising 9 subfamilies), which initiate mucin-type O-glycosylation. The O-glycoproteome is thought to be differentially regulated via the different substrate specificities and expression patterns of each GalNAc-T isoforms. Here, we present a comprehensive in vitro analysis of the peptide substrate specificity of GalNAc-T13, showing that it essentially overlaps with the ubiquitous expressed GalNAc-T1 isoform found in the same subfamily as T13. We have also identified and partially characterized nine splice variants of GalNAc-T13, which add further complexity to the GalNAc-T family. Two variants with changes in their lectin domains were characterized by in vitro glycosylation assays, and one (Δ39Ex9) was inactive while the second one (Ex10b) had essentially unaltered activity. We used reverse transcription-polymerase chain reaction analysis of human neuroblastoma cell lines, normal brain and a small panel of neuroblastoma tumors to demonstrate that several splice variants (Ex10b, ΔEx9, ΔEx2-7 and ΔEx6/8-39bpEx9) were highly expressed in tumor cell lines compared with normal brain, although the functional implications remain to be unveiled. In summary, the GalNAc-T13 isoform is predicted to function similarly to GalNAc-T1 against peptide substrates in vivo, in contrast to a prior report, but is unique by being selectively expressed in the brain. PMID:27913570

Seawater 234U/238U recorded by modern and fossil corals

NASA Astrophysics Data System (ADS)

Chutcharavan, Peter M.; Dutton, Andrea; Ellwood, Michael J.

2018-03-01

U-series dating of corals is a crucial tool for generating absolute chronologies of Late Quaternary sea-level change and calibrating the radiocarbon timescale. Unfortunately, coralline aragonite is susceptible to post-depositional alteration of its primary geochemistry. One screening technique used to identify unaltered corals relies on the back-calculation of initial 234U/238U activity (δ234Ui) at the time of coral growth and implicitly assumes that seawater δ234U has remained constant during the Late Quaternary. Here, we test this assumption using the most comprehensive compilation to date of coral U-series measurements. Unlike previous compilations, this study normalizes U-series measurements to the same decay constants and corrects for offsets in interlaboratory calibrations, thus reducing systematic biases between reported δ234U values. Using this approach, we reassess (a) the value of modern seawater δ234U, and (b) the evolution of seawater δ234U over the last deglaciation. Modern coral δ234U values (145.0 ± 1.5‰) agree with previous measurements of seawater and modern corals only once the data have been normalized. Additionally, fossil corals in the surface ocean display δ234Ui values that are ∼5-7‰ lower during the last glacial maximum regardless of site, taxon, or diagenetic setting. We conclude that physical weathering of U-bearing minerals exposed during ice sheet retreat drives the increase in δ234U observed in the oceans, a mechanism that is consistent with the interpretation of the seawater Pb-isotope signal over the same timescale.

Natural flow regimes, nonnative fishes, and native fish persistence in arid-land river systems.

PubMed

Propst, David L; Gido, Keith B; Stefferud, Jerome A

2008-07-01

Escalating demands for water have led to substantial modifications of river systems in arid regions, which coupled with the widespread invasion of nonnative organisms, have increased the vulnerability of native aquatic species to extirpation. Whereas a number of studies have evaluated the role of modified flow regimes and nonnative species on native aquatic assemblages, few have been conducted where the compounding effects of modified flow regimes and established nonnatives do not confound interpretations, particularly at spatial and temporal scales that are relevant to conservation of species at a range-wide level. By evaluating a 19-year data set across six sites in the relatively unaltered upper Gila River basin, New Mexico, USA, we tested how natural flow regimes and presence of nonnative species affected long-term stability of native fish assemblages. Overall, we found that native fish density was greatest during a wet period at the beginning of our study and declined during a dry period near the end of the study. Nonnative fishes, particularly predators, generally responded in opposite directions to these climatic cycles. Our data suggested that chronic presence of nonnative fishes, coupled with naturally low flows reduced abundance of individual species and compromised persistence of native fish assemblages. We also found that a natural flow regime alone was unlikely to ensure persistence of native fish assemblages. Rather, active management that maintains natural flow regimes while concurrently suppressing or excluding nonnative fishes from remaining native fish strongholds is critical to conservation of native fish assemblages in a system, such as the upper Gila River drainage, with comparatively little anthropogenic modification.

Full-length cellular β-secretase has a trimeric subunit stoichiometry, and its sulfur-rich transmembrane interaction site modulates cytosolic copper compartmentalization.

PubMed

Liebsch, Filip; Aurousseau, Mark R P; Bethge, Tobias; McGuire, Hugo; Scolari, Silvia; Herrmann, Andreas; Blunck, Rikard; Bowie, Derek; Multhaup, Gerd

2017-08-11

The β-secretase (BACE1) initiates processing of the amyloid precursor protein (APP) into Aβ peptides, which have been implicated as central players in the pathology of Alzheimer disease. BACE1 has been described as a copper-binding protein and its oligomeric state as being monomeric, dimeric, and/or multimeric, but the native cellular stoichiometry has remained elusive. Here, by using single-molecule fluorescence and in vitro cross-linking experiments with photo-activatable unnatural amino acids, we show that full-length BACE1, independently of its subcellular localization, exists as trimers in human cells. We found that trimerization requires the BACE1 transmembrane sequences (TMSs) and cytoplasmic domains, with residues Ala 463 and Cys 466 buried within the trimer interface of the sulfur-rich core of the TMSs. Our 3D model predicts that the sulfur-rich core of the trimeric BACE1 TMS is accessible to metal ions, but copper ions did not trigger trimerization. The results of functional assays of endogenous BACE1 suggest that it has a role in intracellular copper compartmentalization by transferring cytosolic copper to intracellular compartments, while leaving the overall cellular copper concentration unaltered. Adding to existing physiological models, our results provide novel insight into the atypical interactions between copper and BACE1 and into its non-enzymatic activities. In conclusion, therapeutic Alzheimer disease prevention strategies aimed at decreasing BACE1 protein levels should be regarded with caution, because adverse effects in copper homeostasis may occur. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of Co Addition on the Microstructure, Martensitic Transformation and Shape Memory Behavior of Fe-Mn-Si Alloys

NASA Astrophysics Data System (ADS)

Maji, Bikas C.; Krishnan, Madangopal; Sujata, M.; Gouthama; Ray, Ranjit K.

2013-01-01

The effect of Co addition has been studied in Fe-30Mn-6Si- xCo ( x = 0 to 9 wt pct) shape memory alloys in terms of their microstructure, martensitic transformation and shape recovery. Microstructural investigations reveal that in Fe-Mn-Si-Co alloys, the microstructure remains single-phase austenite (γ) up to 5 pct Co and beyond that becomes two-phase comprising γ and off-stoichiometric (Fe,Co)5Mn3Si2 intermetallic π-phases. The forward γ-ɛ martensite transformation start temperature ( M S) decreases with the addition of Co up to 5 pct, and alloys containing more than 5 pct Co, show slightly higher M S possibly on account of two-phase microstructure. Unlike M S, the ɛ-γ reverse transformation start temperature ( A S) has been found to remain almost unaltered by Co addition. In general, addition of Co to Fe-Mn-Si alloys deteriorates shape recovery due to decreasing resistance to plastic yielding concomitant with the formation of stress induced ɛ martensite. However, there is an improvement in shape recovery beyond 5 pct Co addition, possibly due to the strengthening effect arising from the presence of (Fe,Co)5Mn3Si2 precipitates within the two-phase microstructure and due to higher amount of stress induced ɛ martensite.

Spinoculation Enhances HBV Infection in NTCP-Reconstituted Hepatocytes.

PubMed

Yan, Ran; Zhang, Yongmei; Cai, Dawei; Liu, Yuanjie; Cuconati, Andrea; Guo, Haitao

2015-01-01

Hepatitis B virus (HBV) infection and its sequelae remain a major public health burden, but both HBV basic research and the development of antiviral therapeutics have been hindered by the lack of an efficient in vitro infection system. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the HBV receptor. We herein report that we established a NTCP-complemented HepG2 cell line (HepG2-NTCP12) that supports HBV infection, albeit at a low infectivity level following the reported infection procedures. In our attempts to optimize the infection conditions, we found that the centrifugation of HepG2-NTCP12 cells during HBV inoculation (termed "spinoculation") significantly enhanced the virus infectivity. Moreover, the infection level gradually increased with accelerated speed of spinoculation up to 1,000g tested. However, the enhancement of HBV infection was not significantly dependent upon the duration of centrifugation. Furthermore, covalently closed circular (ccc) DNA was detected in infected cells under optimized infection condition by conventional Southern blot, suggesting a successful establishment of HBV infection after spinoculation. Finally, the parental HepG2 cells remained uninfected under HBV spinoculation, and HBV entry inhibitors targeting NTCP blocked HBV infection when cells were spinoculated, suggesting the authentic virus entry mechanism is unaltered under centrifugal inoculation. Our data suggest that spinoculation could serve as a standard protocol for enhancing the efficiency of HBV infection in vitro.

Spinoculation Enhances HBV Infection in NTCP-Reconstituted Hepatocytes

PubMed Central

Yan, Ran; Zhang, Yongmei; Cai, Dawei; Liu, Yuanjie; Cuconati, Andrea; Guo, Haitao

2015-01-01

Hepatitis B virus (HBV) infection and its sequelae remain a major public health burden, but both HBV basic research and the development of antiviral therapeutics have been hindered by the lack of an efficient in vitro infection system. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the HBV receptor. We herein report that we established a NTCP-complemented HepG2 cell line (HepG2-NTCP12) that supports HBV infection, albeit at a low infectivity level following the reported infection procedures. In our attempts to optimize the infection conditions, we found that the centrifugation of HepG2-NTCP12 cells during HBV inoculation (termed “spinoculation”) significantly enhanced the virus infectivity. Moreover, the infection level gradually increased with accelerated speed of spinoculation up to 1,000g tested. However, the enhancement of HBV infection was not significantly dependent upon the duration of centrifugation. Furthermore, covalently closed circular (ccc) DNA was detected in infected cells under optimized infection condition by conventional Southern blot, suggesting a successful establishment of HBV infection after spinoculation. Finally, the parental HepG2 cells remained uninfected under HBV spinoculation, and HBV entry inhibitors targeting NTCP blocked HBV infection when cells were spinoculated, suggesting the authentic virus entry mechanism is unaltered under centrifugal inoculation. Our data suggest that spinoculation could serve as a standard protocol for enhancing the efficiency of HBV infection in vitro. PMID:26070202

Alaska goose populations: Past, present and future

USGS Publications Warehouse

King, James G.; Derksen, Dirk V.

1986-01-01

Many people think Alaska remains a pristine wilderness and that wildlife populations are still at prehistoric levels. This very likely is not true for the 11 species and subspecies of geese that nest in Alaska. Large, widely dispersed populations of geese were observed near the turn of the century. Even in the early 1970s, it was estimated that Alaskan habitats were used by 915,000 nesting and 100,000 additional migrating geese each year (King and Lensink 1971). Since then the Alaskan populations of most of these species have declined, some to dramatically low levels (Raveling 1984), even though habitats within the state have remained largely unaltered by man.The U.S. has treaties with Canada, Mexico, Japan and the Soviet Union to protect geese and other shared migratory birds, confirming international concern for the welfare of this resource. Cooperative research on Alaskan geese during the past several decades has given understanding of their migration corridors, staging and wintering habitats, and the principle places where they are hunted, thereby providing information needed to develop effective management plans. The only attempt to re-introduce geese in Alaska has been in the Aleutian Islands. Other opportunities exist.It is our intent here to: (1) review the historic and current status and important habitats of geese that occur in Alaska; (2) identify existing and potential threats to these populations; and (3) offer alternative management approaches for geese in Alaska.

The glass ceiling in Irish healthcare: a nursing perspective.

PubMed

Tracey, Catherine

2006-01-01

The purpose of this study is to describe and explore from the perspectives of top-level nurses holding the formal position of director of nursing their perceptions and interpretations of their experiences in the Irish healthcare system. This paper presents some findings from a nation-wide study, which is qualitative in approach using grounded theory methodology. Semi-structured interviews were conducted with 50 directors of nursing representing general and psychiatric nursing. The study in this paper was conducted in the context of a changing healthcare system, which emphasises the flattening of organisational pyramids. However, this study's findings indicate that, while structures might be changing, behaviours remain unaltered. In particular, the medicine nursing power base remains unchanged, while the power shift between nursing and general management continues to widen in favour of general management. Research in this paper shows that directors of nursing who chose to participate in this study may have different perceptions of experiences from those who chose not to participate. In the paper the reality is neither medicine nor general management, individually or collectively, are going to share or devolve power and influence to nursing. This study's findings indicate that nursing needs to confront this power imbalance. Nursing needs to take the first steps towards shattering the glass ceiling by really examining its own behaviours, in maintaining the status quo, in the traditional balance of power.

Altered small intestinal absorptive enzyme activities in leptin-deficient obese mice: influence of bowel resection.

PubMed

Kiely, James M; Noh, Jae H; Svatek, Carol L; Pitt, Henry A; Swartz-Basile, Deborah A

2006-07-01

Residual bowel increases absorption after massive small bowel resection. Leptin affects intestinal adaptation, carbohydrate, peptide, and lipid handling. Sucrase, peptidase, and acyl coenzyme A:monoacylglycerol acyltransferase (MGAT) are involved in carbohydrate, protein, and lipid absorption. We hypothesized that leptin-deficient obese mice would have altered absorptive enzymes compared with controls before and after small bowel resection. Sucrase, peptidase (aminopeptidase N [ApN], dipeptidyl peptidase IV [DPPIV]), and MGAT activities were determined from lean control (C57BL/6J, n = 16) and leptin-deficient (Lep(ob), n = 16) mice small bowel before and after 50% resection. Ileal sucrase activity was greater in obese mice before and after resection. Jejunal ApN and DPPIV activities were lower for obese mice before resection; ileal ApN activity was unaltered after resection for both strains. Resection increased DPPIV activity in both strains. Jejunal MGAT in obese mice decreased postresection. In both strains, ileal MGAT activity decreased after resection, and obese mice had greater activity in remnant ileum. After small bowel resection, leptin-deficient mice have increased sucrase activity and diminished ileal ApN, DPPIV, and MGAT activity compared with controls. Therefore, we conclude that leptin deficiency alters intestinal enzyme activity in unresected animals and after small bowel resection. Altered handling of carbohydrate, protein, and lipid may contribute to obesity and diabetes in leptin-deficient mice.

8. Photograph of a photograph in possession of Rock Island ...

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

8. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. SOUTH ELEVATON IN UNALTERED CONDITION. ORIGINALLY PUBLISHED 1898. - Rock Island Arsenal, Building No. 68, Rodman Avenue between Fourth Street & East Avenue, Rock Island, Rock Island County, IL

10. Photograph of a photograph in possession of Rock Island ...

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

10. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. SOUTH AND WEST ELEVATIONS IN UNALTERED CONDITION. DATED APRIL 18, 1941. - Rock Island Arsenal, Building No. 56, North Avenue & East Avenue, Rock Island, Rock Island County, IL

SPAWNING SUCCESS OF FATHEAD MINNOWS ON SELECTED ARTIFICIAL SUBSTRATES

EPA Science Inventory

Spawning success of fathead minnows (Pimephales promelas) on six different substrates was tested and evaluated. Egg adhesiveness was equally good on cement-asbestos tile and sand-coated stainless steel substrates, but was poor on unaltered stainless steel, shot-peened stainless s...

[Co-adaptation of enzymatic systems of cells and blood supply in smooth muscle tumors of the corpus uteri].

PubMed

Lazaarev, A F; Avbalian, A M; Bobrov, I P; Klimachev, V V; Mischenko, E V

2008-01-01

We investigated co-adaptation of enzymatic systems of cells using data on activity of NAD(Ph)-dependent enzymes and AgNOR proteins of vascular endothelium vis-a-vis angiogenesis in benign and malignant smooth muscle tumors of the corpus uteri. Overall metabolic activity (NAD-H2 diaphorase) was found to directly correlate with angiogenesis and endothelial vessel proliferation (r = 0.76 and 0.84, respectively). SDH-regulated oxidation in the main metabolic succession of a tricarbonic acid cycle depended on blood supply and endothelial vessel proliferation (r = 0.84 and 0.92, respectively; p = 0.04). A similar relationship was shown for anaerobic glycolysis of SDH (LDH content), on the one hand, and blood supply and endothelial vessel proliferation(r = 0.57 and 0.70, respectively; p = 0.02), on the other. Hence, metabolic profile varied in unaltered myometrium and tumor with variable cellular density and peculiar extracellular matrix. The highest levels of metabolic activity with NAD(Ph)-dependent enzyme co-adaptation was observed in sarcomas which were also characterized by the highest vascular density for endothelial proliferation.

CATION EXCHANGE BETWEEN CELLS AND PLASMA OF MAMMALIAN BLOOD

PubMed Central

Sheppard, C. W.; Martin, W. R.; Beyl, Gertrude

1951-01-01

Sodium and potassium exchange has been studied in the blood of the sheep, dog, cow, and man. The potassium exchange rate in human cells is practically unaltered by increasing the plasma potassium concentration approximately threefold. Comparing the results in different species the exchange rate for potassium shows a rough correlation with the intracellular amount of the element. Expressed in per cent of the cellular content sodium tends to exchange more rapidly than potassium. In three instances the specific activity curves deviate from the simple exponential behavior of a two compartment system. In the exchange of potassium in canine blood the deviation is caused by the presence of a rapidly exchanging fraction in the buffy coat cells. Such an effect does not account for the inhomogeneity of sodium exchange in human blood. PMID:14824508

bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship.

PubMed

Strasser, A; Harris, A W; Cory, S

1991-11-29

Early death is the fate of most developing T lymphocytes. Because bcl-2 can promote cell survival, we tested its impact in mice expressing an E mu-bcl-2 transgene within the T lymphoid compartment. The T cells showed remarkably sustained viability and some spontaneous differentiation in vitro. They also resisted killing by lymphotoxic agents. Although total T cell numbers and the rate of thymic involution were unaltered, the response to immunization was enhanced, consistent with reduced death of activated T cells. No T cells reactive with self-superantigens appeared in the lymph nodes, but an excess was found in the thymus. These observations, together with previous findings on B cells, suggest that modulated bcl-2 expression is a determinant of life and death in normal lymphocytes.

Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble [(3,5,5-trimethylhexanoyl)ferrocene].

PubMed

Lykkesfeldt, Jens; Morgan, Evan; Christen, Stephan; Skovgaard, Lene Theil; Moos, Torben

2007-01-01

Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month-old rats following supplementation with the lipophilic iron derivative [(3,5,5-trimethylhexanoyl)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of alpha- and gamma-tocopherols and glutathione (GSH) were also higher. In contrast, the brain displayed unaltered levels of the tocopherols and GSH. Malondialdehyde (MDA) level was also higher in the cerebrospinal fluid (CSF) and the liver but not in the brain. In old rats, the absence of an increase in iron concentration in the brain was reflected by unaltered concentrations of GSH, tocopherols, and MDA as compared to that in untreated rats. In the aging liver, concentrations of GSH and MDA increased with TMHF treatment. Morphological studies revealed unaltered levels of iron, ferritin, heme oxygenase-1 (HO-1), nitrotyrosine (NT), or MDA in the brains of both young and old rats treated with TMHF. In contrast, TMHF treatment increased the level of HO-1 in Kupffer cells, NT in hepatic endothelial cells, and MDA and ferritin in hepatocytes. Although these results demonstrated an increase in the biochemical markers of oxidative stress and damage in response to increasing concentrations of iron in the liver, they also demonstrated that the brain is well protected against dietary iron overload by using iron in a lipid-soluble formulation.

Paclitaxel-induced painful neuropathy is associated with changes in mitochondrial bioenergetics, glycolysis, and an energy deficit in dorsal root ganglia neurons

PubMed Central

Duggett, Natalie A.; Griffiths, Lisa A.; Flatters, Sarah J.L.

2017-01-01

Abstract Painful neuropathy is the major dose-limiting side effect of paclitaxel chemotherapy. Mitochondrial dysfunction and adenosine triphosphate (ATP) deficit have previously been shown in peripheral nerves of paclitaxel-treated rats, but the effects of paclitaxel in the dorsal root ganglia (DRGs) have not been explored. The aim of this study was to determine the bioenergetic status of DRG neurons following paclitaxel exposure in vitro and in vivo. Utilising isolated DRG neurons, we measured respiratory function under basal conditions and at maximal capacity, glycolytic function, and Adenosine diphosphate (ADP)/ATP levels at 3 key behavioural timepoints; prior to pain onset (day 7), peak pain severity and pain resolution. At day 7, maximal respiration and spare reserve capacity were significantly decreased in DRG neurons from paclitaxel-treated rats. This was accompanied by decreased basal ATP levels and unaltered ADP levels. At peak pain severity, respiratory function was unaltered, yet glycolytic function was significantly increased. Reduced ATP and unaltered ADP levels were also observed at the peak pain timepoint. All these effects in DRG neurons had dissipated by the pain resolution timepoint. None of these paclitaxel-evoked changes could be replicated from in vitro paclitaxel exposure to naive DRG neurons, demonstrating the impact of in vivo exposure and the importance of in vivo models. These data demonstrate the nature of mitochondrial dysfunction evoked by in vivo paclitaxel in the DRG for the first time. Furthermore, we have identified paclitaxel-evoked changes in the bioenergetics of DRG neurons, which result in a persistent energy deficit that is causal to the development and maintenance of paclitaxel-induced pain. PMID:28541258

Soil Communities Promote Temporal Stability and Species Asynchrony in Experimental Grassland Communities

PubMed Central

Pellkofer, Sarah; van der Heijden, Marcel G. A.; Schmid, Bernhard; Wagg, Cameron

2016-01-01

Background Over the past two decades many studies have demonstrated that plant species diversity promotes primary productivity and stability in grassland ecosystems. Additionally, soil community characteristics have also been shown to influence the productivity and composition of plant communities, yet little is known about whether soil communities also play a role in stabilizing the productivity of an ecosystem. Methodology/Principal Findings Here we use microcosms to assess the effects of the presence of soil communities on plant community dynamics and stability over a one-year time span. Microcosms were filled with sterilized soil and inoculated with either unaltered field soil or field soil sterilized to eliminate the naturally occurring soil biota. Eliminating the naturally occurring soil biota not only resulted in lower plant productivity, and reduced plant species diversity, and evenness, but also destabilized the net aboveground productivity of the plant communities over time, which was largely driven by changes in abundance of the dominant grass Lolium perenne. In contrast, the grass and legumes contributed more to net aboveground productivity of the plant communities in microcosms where soil biota had been inoculated. Additionally, the forbs exhibited compensatory dynamics with grasses and legumes, thus lowering temporal variation in productivity in microcosms that received the unaltered soil inocula. Overall, asynchrony among plant species was higher in microcosms where an unaltered soil community had been inoculated, which lead to higher temporal stability in community productivity. Conclusions/Significance Our results suggest that soil communities increase plant species asynchrony and stabilize plant community productivity by equalizing the performance among competing plant species through potential antagonistic and facilitative effects on individual plant species. PMID:26829481

Florida Bay: A history of recent ecological changes

USGS Publications Warehouse

Fourqurean, J.W.; Robblee, M.B.

1999-01-01

Florida Bay is a unique subtropical estuary at the southern tip of the Florida peninsula. Recent ecological changes (seagrass die-off, algal blooms, increased turbidity) to the Florida Bay ecosystem have focused the attention of the public, commercial interests, scientists, and resource managers on the factors influencing the structure and function of Florida Bay. Restoring Florida Bay to some historic condition is the goal of resource managers, but what is not clear is what an anthropogenically-unaltered Florida Bay would look like. While there is general consensus that human activities have contributed to the changes occurring in the Florida Bay ecosystem, a high degree of natural system variability has made elucidation of the links between human activity and Florida Bay dynamics difficult. Paleoecological analyses, examination of long-term datasets, and directed measurements of aspects of the ecology of Florida Bay all contribute to our understanding of the behavior of the bay, and allow quantification of the magnitude of the recent ecological changes with respect to historical variability of the system.

Alkyne- and 1,6-elimination- succinimidyl carbonate - terminated heterobifunctional poly(ethylene glycol) for reversible "Click" PEGylation.

PubMed

Xie, Yumei; Duan, Shaofeng; Forrest, M Laird

2010-01-01

A new heterobifunctional (succinimidyl carbonate, SC)-activated poly(ethylene glycol) (PEG) with a reversible 1,6-elimination linker and a terminal alkyne for "click" chemistry was synthesized with high efficiency and low polydispersity. The α-alkyne-ω-hydroxyl PEG was first prepared using trimethylsilyl-2-propargyl alcohol as an initiator for ring-opening polymerization of ethylene oxide followed by mild deprotection with tetrabutylammonium fluoride. The hydroxy end was then modified with diglycolic anhydride to generate α-alkyne-ω-carboxylic acid PEG. The reversible 1, 6-elimination linker was introduced by conjugation of a hydroxymethyl phenol followed by activation with N,N'-disuccinimidyl carbonate to generate the heterobifunctional α-alkyne-ω-SC PEG. The terminal alkyne is available for "click" conjugation to azido ligands via 1,3-dipolar cycloaddition, and the succinimidyl carbonate will form a reversible conjugate to amines (e.g. in proteins) that can release the unaltered amine after base or enzyme catalyzed cleavage of the 1,6-linker.

Application of micro-Raman spectroscopy for fight against terrorism and smuggling

NASA Astrophysics Data System (ADS)

Almaviva, Salvatore; Botti, Sabina; Palucci, Antonio; Puiu, Adriana; Schnürer, Frank; Schweikert, Wenka; Romolo, Francesco Saverio

2014-04-01

We report the results of Raman measurements on some common military explosives and explosives precursors deposited on clothing fabrics, both synthetic and natural, in concentration comparable to those obtained from a single fingerprint or mixed with similar harmless substances to detect illegal compounds for smuggling activities. Raman spectra were obtained using an integrated portable Raman system equipped with an optical microscope and a 785-nm laser in an analysis of <1 min. The spectral features of each illicit substance have been identified and distinguished from those belonging to the substrate fabric or from the interfering compound. Our results show that the application of Raman spectroscopy (RS) with a microscope-based portable apparatus can provide interpretable Raman spectra for a fast, in-situ analysis, directly from explosive particles of some μ, despite the contribution of the substrate, leaving the sample completely unaltered for further, more specific, and propedeutic laboratory analysis. We also show how the RS is suitable for detecting illegal compounds mixed with harmless substances for smuggling purposes or for counterfeiting activities.

7. Photograph of a photograph in possession of Rock Island ...

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

7. Photograph of a photograph in possession of Rock Island Arsenal Historical Office. WEST AND SOUTH ELEVATIONS, IN UNALTERED CONDITION. PROBABLY TAKEN ABOUT 1910. - Rock Island Arsenal, Building No. 60, Rodman Avenue between Gillespie Avenue & First Street, Rock Island, Rock Island County, IL

Valuing ecosystem services of an impacted waterway in the Southwestern US

EPA Science Inventory

While many studies of ecosystem services focus on unaltered areas such as wilderness, management insight is also needed for those more impacted. This case study values ecosystem services of the Santa Cruz River, an effluent-dominated waterway in southern Arizona. Wastewater treat...

Reducing the negative effects of media exposure on body image: Testing the effectiveness of subvertising and disclaimer labels.

PubMed

Frederick, David A; Sandhu, Gaganjyot; Scott, Terri; Akbari, Yasmin

2016-06-01

Body image activists have proposed adding disclaimer labels to digitally altered media as a way to promote positive body image. Another approach advocated by activists is to alter advertisements through subvertising (adding social commentary to the image to undermine the message of the advertisement). We examined if body image could be enhanced by attaching Photoshop disclaimers or subvertising to thin-ideal media images of swimsuit models. In Study 1 (N=1268), adult women exposed to disclaimers or subvertising did not report higher body state satisfaction or lower drive for thinness than women exposed to unaltered images. In Study 2 (N=820), adult women who were exposed to disclaimers or subvertising did not report higher state body satisfaction or lower state social appearance comparisons than women exposed to unaltered images or to no images. These results raise questions about the effectiveness of disclaimers and subvertising for promoting body satisfaction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Triiodothyronine Acutely Stimulates Glucose Transport into L6 Muscle Cells Without Increasing Surface GLUT4, GLUT1, or GLUT3

PubMed Central

Teixeira, Silvania Silva; Tamrakar, Akhilesh K.; Goulart-Silva, Francemilson; Serrano-Nascimento, Caroline; Klip, Amira

2012-01-01

Background Thyroid hormones (THs) act genomically to stimulate glucose transport by elevating glucose transporter (Slc2a) expression and glucose utilization by cells. However, nongenomic effects of THs are now emerging. Here, we assess how triiodothyronine (T3) acutely affects glucose transport and the content of GLUT4, GLUT1, and GLUT3 at the surface of muscle cells, and possible interactions between T3 and insulin action. Methods Differentiated L6 myotubes transfected with myc-tagged Slc2a4 (L6-GLUT4myc) or Slc2a1 (L6-GLUT1myc) and wild-type L6 myotubes were studied in the following conditions: control, hypothyroid (Tx), Tx plus T3, Tx plus insulin, and Tx plus insulin and T3. Results Glucose uptake and GLUT4 content at the cell surface decreased in the Tx group relative to controls. T3 treatment for 30 minutes increased glucose transport into L6-GLUT4myc cells without altering surface GLUT4 content, which increased only thereafter. The total amount of GLUT4 protein remained unchanged among the groups studied. The surface GLUT1 content of L6-GLUT1myc cells also remained unaltered after T3 treatment; however, in these cells glucose transport was not stimulated by T3. In wild-type L6 cells, although T3 treatment increased the total amount of GLUT3, it did not change the surface GLUT3 content. Moreover, within 30 minutes, T3 stimulation of glucose uptake was additive to that of insulin in L6-GLUT4myc cells. As expected, insulin elevated surface GLUT4 content and glucose uptake. However, interestingly, surface GLUT4 content remained unchanged or even dropped with T3 plus insulin. Conclusions These data reveal that T3 rapidly increases glucose uptake in L6-GLUT4myc cells, which, at least for 30 minutes, did not depend on an increment in GLUT4 at the cell surface yet potentiates insulin action. We propose that this rapid T3 effect involves activation of GLUT4 transporters at the cell surface, but cannot discount the involvement of an unknown GLUT. PMID:22663547

Unipedal Postural Balance and Countermovement Jumps After a Warm-up and Plyometric Training Session: A Randomized Controlled Trial.

PubMed

Romero-Franco, Natalia; Jiménez-Reyes, Pedro

2015-11-01

The purpose of this study was to analyze the immediate effects of a plyometric training protocol on unipedal postural balance and countermovement jumps. In addition, we analyzed the effects of a warm-up on these parameters. Thirty-two amateur male sprinters (24.9 ± 4.1 years; 72.3 ± 10.7 kg; 1.78 ± 0.05 m; 22.6 ± 3.3 kg·m) were randomly sorted into a control group (n = 16) (they did not perform any physical activity) and a plyometric training group (n = 16) (they performed a 15-minute warm-up and a high-intensity plyometric protocol consisting of 10 sets of 15 vertical jumps). Before and after the warm-up, and immediately after and 5 minutes after the plyometric protocol, all athletes indicated the perceived exertion on calf and quad regions on a scale from 0 (no exertion) to 10 (maximum exertion). They also carried out a maximum countermovement jump and a unipedal postural balance test (athletes would remain as still as possible for 15 seconds in a left leg and right leg support stance). Results showed that, in the plyometric group, length and velocity of center-of-pressure movement in right leg support stance increased compared with baseline (p = 0.001 and p = 0.004, respectively) and to the control group (p = 0.035 and p = 0.029, respectively) immediately after the plyometric protocol. In addition, the countermovement jump height decreased right after the plyometric protocol (p < 0.001). The perceived exertion on calf and quad regions increased after the plyometry (p < 0.001). Five minutes later, these parameters remained deteriorated despite a slight recovery (length: p = 0.044; velocity: p = 0.05; countermovement jump height: p < 0.001; local exertion: p < 0.001). Data also showed that countermovement jump height improved after the warm-up (p = 0.021), but unipedal postural balance remained unaltered. As a conclusion, high-intensity plyometric exercises blunt unipedal postural balance and countermovement jump performance. The deterioration lasts at least 5 minutes, which may influence future exercises in the training session. Coaches should plan the training routine according to the immediate effects of plyometry on postural balance and vertical jumps, which play a role in injury prevention and sports performance.

Rapid presumptive identification of the Mycobacterium tuberculosis-bovis complex by radiometric determination of heat stable urease

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

Gandy, J.H.; Pruden, E.L.; Cox, F.R.

1983-12-01

Simple and rapid Bactec methodologies for the determination of neat (unaltered) and heat stable urease activity of mycobacteria are presented. Clinical isolates (63) and stock cultures (32)--consisting of: M. tuberculosis (19), M. bovis (5), M. kansasii (15), M. marinum (4), M. simiae (3), M. scrofulaceum (16), M. gordonae (6), M. szulgai (6), M. flavescens (1), M. gastri (1), M. intracellulare (6), M. fortuitum-chelonei complex (12), and M. smegmatis (1)--were tested for neat urease activity by Bactec radiometry. Mycobacterial isolates (50-100 mg wet weight) were incubated at 35 degrees C for 30 minutes with microCi14C-urea. Urease-positive mycobacteria gave Bactec growth indexmore » (GI) values greater than 100 units, whereas urease-negative species gave values less than 10 GI units. Eighty-three isolates possessing neat urease activity were heated at 80 degrees C for 30 minutes followed by incubation at 35 degrees C for 30 minutes with 1 microCi14C-urea. Mycobacterium tuberculosis-bovis complex demonstrated heat-stable urease activity (GI more than 130 units) and could be distinguished from mycobacteria other than tuberculosis (MOTT), which gave GI values equal to or less than 40 units.« less

Effects of bis(guanylhydrazones) on the activity and expression of ornithine decarboxylase.

PubMed Central

Nikula, P; Alhonen-Hongisto, L; Jänne, J

1985-01-01

Derivatives of glyoxal bis(guanylhydrazone) (GBG), such as methylglyoxal bis(guanylhydrazone) and ethylglyoxal bis(guanylhydrazone), are potent inhibitors of S-adenosylmethionine decarboxylase (EC 4.1.1.50), the key enzyme required for the synthesis of spermidine and spermine. These compounds, but not the parent compound, induce a massive accumulation of putrescine, partly by blocking the conversion of putrescine into spermidine, but also by strikingly stimulating ornithine decarboxylase (ODC; EC 4.1.1.17) activity. The mechanism of the stimulation of ODC activity and enhanced accumulation of the enzyme protein apparently involved a distinct stabilization of the enzyme against intracellular degradation. However, although the parent compound GBG also stabilized ODC, it powerfully inhibited the enzyme activity and the accumulation of immunoreactive protein in cultured L1210 leukaemia cells. Kinetic considerations indicated that, in addition to the stabilization, all three compounds, GBG in particular, inhibited the expression of ODC. It is unlikely that the decreased rate of synthesis of ODC was attributable to almost unaltered amounts of mRNA in drug-treated cells, thus supporting the view that especially GBG apparently depressed the expression of ODC at some post-transcriptional level. Images PMID:4062886

Direct covalent attachment of small peptide antigens to enzyme-linked immunosorbent assay plates using radiation and carbodiimide activation.

PubMed

Dagenais, P; Desprez, B; Albert, J; Escher, E

1994-10-01

Direct adsorption of small peptide antigens to unaltered, commercially available polystyrene surfaces may be too weak to permit suitable assay by ELISA. We therefore developed a simple method for the covalent attachment of small, potentially single epitope antigens to polystyrene surfaces. Chemical activation of polystyrene plates with carbodiimide considerably improves the total and covalent attachment of radioactive octapeptides. The covalent attachment was demonstrated by washing with hot detergent. A 3.5 Mrad gamma-irradiation of plates also increases total binding, particularly in combination with chemical activation. The covalent attachment presumably occurs through formation and chemical activation of carboxylate functions on the polystyrene surface which form amide bonds with peptides. ELISA test was performed with CGRP and successive smaller CGRP fragments. Covalent attachment of C-terminal peptide fragments as detection antigens allows optimal recognition and sensitivity even for hexapeptides, while decapeptide antigens were already poorly recognized using a conventional antigen plating technique. Repetitive detergent washes and/or prolonged storage of plates with covalently bound antigens did not reduce their ELISA sensitivity. The method with storage and reutilization capacities that we present here will be useful for the development of preplated antibody screening test.

Lawsonite Microstructures and Fabric Development at the Slab-Mantle Interface

NASA Astrophysics Data System (ADS)

Fornash, K.; Whitney, D.; Teyssier, C. P.; Seaton, N. C.

2016-12-01

Lawsonite is of critical importance to element and water cycling in subduction zones because it has a high H2O content, is stable at high pressures, and is a significant reservoir for trace elements in HP/LT rocks. In addition, the presence, abundance, and crystallographic orientation of lawsonite can affect the deformation and rheological behavior of subducted oceanic crust and sediments, and may influence the seismic properties of subducted slabs. The scarcity of unaltered lawsonite in HP/LT rocks exhumed to the Earth's surface, particularly in eclogite, however, has prevented an understanding of the deformation behavior of lawsonite and the factors controlling the development of fabrics in lawsonite, which are important for understanding the effects of lawsonite on the physical properties of subducted slabs. One of the few places in the world with unaltered lawsonite in eclogite and blueschist facies rocks is the Sivrihisar Massif, Turkey, which contains a coherent sequence of lawsonite-bearing metabasaltic and metasedimentary rocks that were metamorphosed and deformed at the slab-mantle interface (45 - 80 km), and therefore provide an opportunity to systematically compare lawsonite fabrics in rocks with different modal amounts of rheologically significant minerals (e.g., glaucophane, omphacite, quartz), integrated with information about lawsonite crystal size, compositional zoning patterns, shape, and twinning. Studies to date of lawsonite CPO from natural lawsonite-bearing rocks have resulted in two patterns: one is characterized by a concentration of [001] axes parallel to lineation and the other is characterized by a concentration of [001] axes perpendicular to foliation. We have documented the first type in metabasalt and the second in quartzite, but other researchers have documented both types in metabasalt. Regardless of variations in lawsonite CPO or rock type, omphacite and glaucophane CPO remain consistent. Quartz c-axis patterns vary in eclogite- and blueschist-facies quartzite, although lawsonite CPO in quartzite does not vary. Samples in which lawsonite is polycrystalline or occurs as aggregates, tends to yield more diffuse patterns. Ongoing research investigates the controls on lawsonite CPO, and their consequences for subduction processes.

Treatment of Venous Aortorenal Bypass Graft Aneurysm Using a Stent-Graft

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

Novotny, Jiri, E-mail: jino@medicon.cz; Peregrin, Jan H.; Stribrna, Jarmila

2010-02-15

We present the case of a 77-year-old male patient who had undergone a bilateral venous aortorenal bypass graft 30 years previously. Thirteen years previously, the patient was shown to have a decrease in renal function, with mild shrinking of both kidneys; additionally, a stenosis was found in the left proximal anastomosis. At the most recent follow-up visit (1 year previously), ultrasound revealed an aneurysm (42 mm in diameter) of the left renal bypass graft; the finding was confirmed by CT angiography. A significant ostial stenosis of the left renal bypass graft was also confirmed. It was decided to place amore » self-expandable stent-graft into the aneurysm while also attempting to dilate the stenosis. Proximal endoleak after stent-graft placement necessitated the implantation of another, balloon-expandable stent-graft into the bypass graft ostium. Postprocedural angiography and follow-up by CT angiography at 3 months confirmed good patency of the stent-grafts and complete thrombosis of the aneurysmal sac, with preserved kidney perfusion. Renal function remained unaltered, while the hypertension is better controlled.« less

Three-Dimensional, Laminar Flow Past a Short, Surface-Mounted Cylinder

NASA Astrophysics Data System (ADS)

Liakos, Anastasios; Malamataris, Nikolaos

2016-11-01

The topology and evolution of three-dimensional flow past a cylinder of slenderness ratio SR = 1 mounted in a wind tunnel is examined for 0 . 1 <= Re <= 325 (based on the diameter of the cylinder) where steady-state solutions have been obtained. Direct numerical simulations were computed using an in-house parallel finite element code. Results indicate that symmetry breaking occurs at Re = 1 , while the first prominent structure is a horseshoe vortex downstream from the cylinder. At Re = 150 , two foci are observed, indicating the formation of two tornadolike vortices downstream. Concurrently, another horseshoe vortex is formed upstream from the cylinder. For higher Reynolds numbers, the flow downstream is segmented to upper and lower parts, whereas the topology of the flow on the solid boundaries remains unaltered. Pressure distributions show that pressure, the key physical parameter in the flow, decreases everywhere except immediately upstream from the cylinder. In addition, creation of critical points from saddle-node-type bifurcations occur when the streamwise component of the pressure gradient changes sign. Finally, at Re = 325 , an additional horseshoe vorrtex is formed at the wake of the cylinder

Proteomic analysis of upland rice (Oryza sativa L.) exposed to intermittent water deficit.

PubMed

Rabello, Fernanda R; Villeth, Gabriela R C; Rabello, Aline R; Rangel, Paulo H N; Guimarães, Cleber M; Huergo, Luciano F; Souza, Emanuel M; Pedrosa, Fabio O; Ferreira, Márcio E; Mehta, Angela

2014-06-01

Rice is the most important crop consumed all over the world. In Brazil, irrigated rice covers 50 % of the rice producing area and is responsible for 75 % of the national production. Upland rice covers most of the remaining area, and is therefore, a very important production system in the country. In the present study, we have used the drought tolerant upland rice variety Três Meses Antigo to investigate the proteomic changes that occur during drought stress. Plants were submitted to drought by the reposition of 50 % of the water lost daily. Twenty days after the beginning of the drought stress period, leaves were harvested and used for protein extraction. The 2D maps obtained from treated and control plants revealed 408 reproducible spots, 44 of which were identified by mass spectrometry, including 15 differential proteins. Several unaltered proteins were also identified (39 spots) and were mainly involved in photosynthesis. Taken together, the results obtained suggest that the tolerant upland rice up-regulates anti-oxidant and energy production related proteins in order to cope with water deficit.

The E2 glycoprotein of classical swine fever virus is a virulence determinant in swine.

PubMed

Risatti, G R; Borca, M V; Kutish, G F; Lu, Z; Holinka, L G; French, R A; Tulman, E R; Rock, D L

2005-03-01

To identify genetic determinants of classical swine fever virus (CSFV) virulence and host range, chimeras of the highly pathogenic Brescia strain and the attenuated vaccine strain CS were constructed and evaluated for viral virulence in swine. Upon initial screening, only chimeras 138.8v and 337.14v, the only chimeras containing the E2 glycoprotein of CS, were attenuated in swine despite exhibiting unaltered growth characteristics in primary porcine macrophage cell cultures. Additional viral chimeras were constructed to confirm the role of E2 in virulence. Chimeric virus 319.1v, which contained only the CS E2 glycoprotein in the Brescia background, was markedly attenuated in pigs, exhibiting significantly decreased virus replication in tonsils, a transient viremia, limited generalization of infection, and decreased virus shedding. Chimeras encoding all Brescia structural proteins in a CS genetic background remained attenuated, indicating that additional mutations outside the structural region are important for CS vaccine virus attenuation. These results demonstrate that CS E2 alone is sufficient for attenuating Brescia, indicating a significant role for the CSFV E2 glycoprotein in swine virulence.

Detection and mapping of mineralized areas in the Cortez-Uinta Belt, Utah-Nevada, using computer-enhanced ERTS imagery

NASA Technical Reports Server (NTRS)

Rowan, L. C. (Principal Investigator)

1976-01-01

The author has identified the following significant results. Preliminary analysis indicates that mineralogical differences between altered rocks and most unaltered rocks in south-central Nevada cause visible and near infrared spectral reflectance differences, which can be used to discriminate these broad categories of rocks in multispectral images. The most important mineralogical differences are the increased abundance of goethite, hematite, and jarosite, and the presence of alunite, montmorillonite, and kaolinite in the altered rock. The technique to enhance subtle spectral differences combines ratioing of the MSS bands and contrast stretching. The stretched ratio values are used to produce black and white images that depict materials according to spectral reflectance; rationing minimizes the influence of topography and overall albedo on the grouping of spectrally similar materials. Field evaluation of color-ratio composite shows that, excluding alluvial areas, approximately 80 percent of the green and brown color patterns are related to hydrothermal alternation. The remaining 20 percent consists mainly of pink hematitic crystallized tuff, a result of vapor phase crystallization, and of tan and red ferruginous shale and siltstone.

A Thermochromic Superhydrophobic Surface

PubMed Central

Cataldi, Pietro; Bayer, Ilker S.; Cingolani, Roberto; Marras, Sergio; Chellali, Ryad; Athanassiou, Athanassia

2016-01-01

Highly enhanced solid-state thermochromism is observed in regioregular poly(3-hexylthiophene), P3HT, when deposited on a superhydrophobic polymer-SiO2 nanocomposite coating. The conformal P3HT coating on the nanocomposite surface does not alter or reduce superhydrophicity while maintaining its reversible enhanced thermochromism. The polymeric matrix of the superhydrophobic surface is comprised of a blend of poly(vinylidene fluoride-co-hexafluoropropylene) copolymer and an acrylic adhesive. Based on detailed X-ray diffraction measurements, this long-lasting, repeatable and hysteresis-free thermochromic effect is attributed to the enhancement of the Bragg peak associated with the d-spacing of interchain directional packing (100) which remains unaltered during several heating-cooling cycles. We propose that the superhydrophobic surface confines π–π interchain stacking in P3HT with uniform d-spacing into its nanostructured texture resulting in better packing and reduction in face-on orientation. The rapid response of the system to sudden temperature changes is also demonstrated by water droplet impact and bounce back on heated surfaces. This effect can be exploited for embedded thin film temperature sensors for metal coatings. PMID:27301422

Multifunctional Magnetic and Upconverting Nanobeads as Dual Modal Imaging Tools.

PubMed

Materia, Maria Elena; Pernia Leal, Manuel; Scotto, Marco; Balakrishnan, Preethi Bala; Kumar Avugadda, Sahitya; García-Martín, María L; Cohen, Bruce E; Chan, Emory M; Pellegrino, Teresa

2017-11-15

We report the fabrication of aqueous multimodal imaging nanocomposites based on superparamagnetic nanoparticles (MNPs) and two different sizes of photoluminescent upconverting nanoparticles (UCNPs). The controlled and simultaneous incorporation of both types of nanoparticles (NPs) was obtained by controlling the solvent composition and the addition rate of the destabilizing solvent. The magnetic properties of the MNPs remained unaltered after their encapsulation into the polymeric beads as shown by the T2 relaxivity measurements. The UCNPs maintain photoluminescent properties even when embedded with the MNPs into the polymer bead. Moreover, the light emitted by the magnetic and upconverting nanobeads (MUCNBs) under NIR excitation (λ exc = 980 nm) was clearly observed through different thicknesses of agarose gel or through a mouse skin layer. The comparison with magnetic and luminescent nanobeads based on red-emitting quantum dots (QDs) demonstrated that while the QD-based beads show significant autofluorescence background from the skin, the signal obtained by the MUCNBs allows a decrease in this background. In summary, these results indicate that MUCNBs are good magnetic and optical probes for in vivo multimodal imaging sensors.

Enhancing water stress tolerance improves fitness in biological control strains of Lactobacillus plantarum in plant environments

PubMed Central

Daranas, Núria; Badosa, Esther; Francés, Jesús; Montesinos, Emilio

2018-01-01

Lactobacillus plantarum strains PM411 and TC92 can efficiently control bacterial plant diseases, but their fitness on the plant surface is limited under unfavourable low relative humidity (RH) conditions. To increase tolerance of these strains to water stress, an adaptive strategy was used consisting of hyperosmotic and acidic conditions during growth. Adapted cells had higher survival rates under desiccation than non-adapted cells. Transcript levels and patterns of general stress-related genes increased immediately after the combined-stress adaptation treatment, and remained unaltered or repressed during the desiccation challenge. However, there were differences between strains in the transcription patterns that were in agreement with a better performance of adapted cells of PM411 than TC92 in plant surfaces under low RH environmental conditions. The combined-stress adaptation treatment increased the survival of PM411 cells consistently in different plant hosts in the greenhouse and under field conditions. Stress-adapted cells of PM411 had similar biocontrol potential against bacterial plant pathogens than non-adapted cells, but with less variability within experiments. PMID:29304187

Biomethanation of vegetable market waste in an anaerobic baffled reactor: Effect of effluent recirculation and carbon mass balance analysis.

PubMed

Gulhane, Madhuri; Khardenavis, Anshuman A; Karia, Sneha; Pandit, Prabhakar; Kanade, Gajanan S; Lokhande, Satish; Vaidya, Atul N; Purohit, Hemant J

2016-09-01

In the present study, feasibility of biomethanation of vegetable market waste in a 4-chambered anaerobic baffled reactor (ABR) was investigated at 30d hydraulic retention time and organic loading rate of 0.5gVS/L/d for one year. Indicators of process stability viz., butyrate/acetate and propionate/acetate ratios were consistent with phase separation in the different chambers, which remained unaltered even during recirculation of effluent. Chemical oxygen demand (COD) and volatile solids (VS) removal efficiencies were observed to be consistently high (above 90%). Corresponding biogas and methane yields of 0.7-0.8L/g VS added/d and 0.42-52L/g VS added/d respectively were among the highest reported in case of AD of vegetable waste in an ABR. Process efficiency of the ABR for vegetable waste methanation, which is indicated by carbon recovery factor showed that, nearly 96.7% of the input carbon considered for mass balance was accounted for in the product. Copyright © 2016 Elsevier Ltd. All rights reserved.

Copolymers enhance selective bacterial community colonization for potential root zone applications.

PubMed

Pham, Vy T H; Murugaraj, Pandiyan; Mathes, Falko; Tan, Boon K; Truong, Vi Khanh; Murphy, Daniel V; Mainwaring, David E

2017-11-21

Managing the impact of anthropogenic and climate induced stress on plant growth remains a challenge. Here we show that polymeric hydrogels, which maintain their hydrous state, can be designed to exploit functional interactions with soil microorganisms. This microbial enhancement may mitigate biotic and abiotic stresses limiting productivity. The presence of mannan chains within synthetic polyacrylic acid (PAA) enhanced the dynamics and selectivity of bacterial ingress in model microbial systems and soil microcosms. Pseudomonas fluorescens exhibiting high mannan binding adhesins showed higher ingress and localised microcolonies throughout the polymeric network. In contrast, ingress of Bacillus subtilis, lacking adhesins, was unaltered by mannan showing motility comparable to bulk liquids. Incubation within microcosms of an agricultural soil yielded hydrogel populations significantly increased from the corresponding soil. Bacterial diversity was markedly higher in mannan containing hydrogels compared to both control polymer and soil, indicating enhanced selectivity towards microbial families that contain plant beneficial species. Here we propose functional polymers applied to the potential root zone which can positively influence rhizobacteria colonization and potentially plant growth as a new approach to stress tolerance.

Genetically induced cell death in bulge stem cells reveals their redundancy for hair and epidermal regeneration.

PubMed

Driskell, Iwona; Oeztuerk-Winder, Feride; Humphreys, Peter; Frye, Michaela

2015-03-01

Adult mammalian epidermis contains multiple stem cell populations in which quiescent and more proliferative stem and progenitor populations coexist. However, the precise interrelation of these populations in homeostasis remains unclear. Here, we blocked the contribution of quiescent keratin 19 (K19)-expressing bulge stem cells to hair follicle formation through genetic ablation of the essential histone methyltransferase Setd8 that is required for the maintenance of adult skin. Deletion of Setd8 eliminated the contribution of bulge cells to hair follicle regeneration through inhibition of cell division and induction of cell death, but the growth and morphology of hair follicles were unaffected. Furthermore, ablation of Setd8 in the hair follicle bulge blocked the contribution of K19-postive stem cells to wounded epidermis, but the wound healing process was unaltered. Our data indicate that quiescent bulge stem cells are dispensable for hair follicle regeneration and epidermal injury in the short term and support the hypothesis that quiescent and cycling stem cell populations are equipotent. © 2014 AlphaMed Press.

Flow in Rotating Serpentine Coolant Passages With Skewed Trip Strips

NASA Technical Reports Server (NTRS)

Tse, David G.N.; Steuber, Gary

1996-01-01

Laser velocimetry was utilized to map the velocity field in serpentine turbine blade cooling passages with skewed trip strips. The measurements were obtained at Reynolds and Rotation numbers of 25,000 and 0.24 to assess the influence of trips, passage curvature and Coriolis force on the flow field. The interaction of the secondary flows induced by skewed trips with the passage rotation produces a swirling vortex and a corner recirculation zone. With trips skewed at +45 deg, the secondary flows remain unaltered as the cross-flow proceeds from the passage to the turn. However, the flow characteristics at these locations differ when trips are skewed at -45 deg. Changes in the flow structure are expected to augment heat transfer, in agreement with the heat transfer measurements of Johnson, et al. The present results show that trips are skewed at -45 deg in the outward flow passage and trips are skewed at +45 deg in the inward flow passage maximize heat transfer. Details of the present measurements were related to the heat transfer measurements of Johnson, et al. to relate fluid flow and heat transfer measurements.

Impact of α-amylase during breadmaking on in vitro kinetics of starch hydrolysis and glycaemic index of enriched bread with bran.

PubMed

Sanz-Penella, Juan Mario; Laparra, José Moisés; Haros, Monika

2014-09-01

Nowadays, the use of enzymes has become a common practice in the bakery industry, as they can improve dough quality and texture of final product. However, the use of α-amylases could have a negative effect in the glycaemic load of product, due to the released sugars from the starch hydrolysis that are not used by yeasts during the fermentation process. This study evaluated the effect of the addition of α-amylase in bakery products with bran on in vitro kinetics of starch hydrolysis. The use of flour with a high degree of extraction or high bran amount could decrease the GI even with the inclusion of α-amylase in the formulation. It should be taken into account the amount of bran and α-amylase when formulating breads in order to obtain products with lower GI than white bread. However, the fact that kinetics of starch hydrolysis remained unaltered indicates that the use of α-amylase in bread-making processes could provide technological advantages improving quality of breads without markedly changes in their glycaemic index.

Development of a pericardial acellular matrix biomaterial: biochemical and mechanical effects of cell extraction.

PubMed

Courtman, D W; Pereira, C A; Kashef, V; McComb, D; Lee, J M; Wilson, G J

1994-06-01

There is evidence to suggest that the cellular components of homografts and bioprosthetic xenografts may contribute to calcification or immunogenic reactions. A four-step detergent and enzymatic extraction process has been developed to remove cellular components from bovine pericardial tissue. The process results in an acellular matrix material consisting primarily of elastin, insoluble collagen, and tightly bound glycosaminoglycans. Light and electron microscopy confirmed that nearly all cellular constituents are removed without ultrastructural evidence of damage to fibrous components. Collagen denaturation temperatures remained unaltered. Biochemical analysis confirmed the retention of collagen and elastin and some differential extraction of glycosaminoglycans. Low strain rate fracture testing and high strain rate viscoelastic characterization showed that, with the exception of slightly increased stress relaxation, the mechanical properties of the fresh tissue were preserved in the pericardial acellular matrix. Crosslinking of the material in glutaraldehyde or poly(glycidyl ether) produced mechanical changes consistent with the same treatments of fresh tissue. The pericardial acellular matrix is a promising approach to the production of biomaterials for heart valve or cardiovascular patching applications.

Amino acid racemization in amber-entombed insects: implications for DNA preservation

NASA Technical Reports Server (NTRS)

Bada, J. L.; Wang, X. S.; Poinar, H. N.; Paabo, S.; Poinar, G. O.

1994-01-01

DNA depurination and amino acid racemization take place at similar rates in aqueous solution at neutral pH. This relationship suggests that amino acid racemization may be useful in accessing the extent of DNA chain breakage in ancient biological remains. To test this suggestion, we have investigated the amino acids in insects entombed in fossilized tree resins ranging in age from <100 years to 130 million years. The amino acids present in 40 to 130 million year old amber-entombed insects resemble those in a modern fly and are probably the most ancient, unaltered amino acids found so far on Earth. In comparison to other geochemical environments on the surface of the Earth, the amino acid racemization rate in amber insect inclusions is retarded by a factor of >10(4). These results suggest that in amber insect inclusions DNA depurination rates would also likely be retarded in comparison to aqueous solution measurements, and thus DNA fragments containing many hundreds of base pairs should be preserved. This conclusion is consistent with the reported successful retrieval of DNA sequences from amber-entombed organisms.

Biochemical bases for environmental adaptation in goldfish (Carassius auratus L. ): resistance to ammonia

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

Schenone, G.; Arillo, A.; Margiocco, C.

1982-10-01

Goldfish specimens were exposed for 24-48 hr to 20, 40, 600, and 2500 micrograms N/liter unionized ammonia (UIA). This treatment causes, in the brain, increases in total ammonia, glutamine, lactate, and succinate and decreases in glutamate, glucidic stores, total NADH, and ATP. Most of these effects have already been reported in ammonia-treated trout. It is therefore suggested that the cerebral biochemical mechanisms of ammonia toxicity in these two species are fundamentally the same. The most important metabolic alterations, however, appear for UIA concentrations which are higher than those necessary to produce the same effects in trout, in accordance with themore » greater resistance of goldfish to ammonia. Some of the physiological-biochemical adaptations which are at the root of this phenomenon have been pointed out and discussed. In the liver of the ammonia-treated goldfish total ammonia, glutamine, glutamate, and succinate all increase, while lactate, glycine, and taurine decrease; liver glucidic stores remain unaltered. These results indicate a difference in the metabolic responses of goldfish and trout liver.« less

Differentiated norepinephrine spillover in human skeletal muscle.

PubMed

Karlsson, A K; Elam, M; Lönnroth, P; Sullivan, L; Friberg, P

1997-07-01

Most neurophysiological studies have shown similar sympathetic outflow to arm and leg. However, some direct microneurographic recordings indicate differentiated sympathetic outflow to limbs both at rest and during mental stress. Hence, differentiated levels of norepinephrine (NE) spillover could prevail. By steady-state infusion of [3H]NE and body composition determination by dual-energy X-ray absorptiometry-scan, we simultaneously assessed arm and leg NE spillover related to 100 g tissue and total limb weight. NE spillover was lower in leg than arm (0.26 vs. 1.51 pmol.min-1.100 g-1, P < 0.05), and the difference remained when expressed as a function of total limb weight (66 vs. 137 pmol/min, P < 0.05). Fractional extraction of [3H]NE was similar in arm and leg. Neuronal uptake blockade by desipramine was more effective in leg than arm; fractional extraction in leg decreased by 32% (P < 0.05) but was unaltered in arm. Thus a lower NE spillover was observed from leg than arm, possibly reflecting a lower sympathetic outflow and a more neuronally dependent reuptake.

Do saw palmetto extracts block human alpha1-adrenoceptor subtypes in vivo?

PubMed

Goepel, M; Dinh, L; Mitchell, A; Schäfers, R F; Rübben, H; Michel, M C

2001-02-15

To test whether saw palmetto extracts, which act as alpha1-adrenoceptor antagonists in vitro, also do so in vivo in man. In a placebo-controlled, double-blind, four-way cross-over study 12 healthy young men were treated with three different saw palmetto extract preparations (320 mg o.d.) for 8 days each. On the last day, before and 2, 4 and 6 hr after drug intake blood pressure and heart rate were determined and blood samples obtained, which were used in an ex vivo radioreceptor assay with cloned human alpha1-adrenoceptor subtypes. Saw palmetto extract treatment did not result in alpha1-adrenoceptor subtype occupancy in the radioreceptor assay. Although the saw palmetto extracts caused minor reductions of supine blood pressure, they did not affect blood pressure during orthostatic stress testing and did not alter heart rate under either condition. Moreover, plasma catecholamines remained largely unaltered. Despite their alpha1-adrenoceptor antagonist effects in vitro, therapeutically used doses of saw palmetto extracts do not cause alpha1-adrenoceptor antagonism in man in vivo. Copyright 2001 Wiley-Liss, Inc.

Mass Spectrometric Imaging Using Laser Ablation and Solvent Capture by Aspiration (LASCA)

NASA Astrophysics Data System (ADS)

Brauer, Jonathan I.; Beech, Iwona B.; Sunner, Jan

2015-09-01

A novel interface for ambient, laser ablation-based mass spectrometric imaging (MSI) referred to as laser ablation and solvent capture by aspiration (LASCA) is presented and its performance demonstrated using selected, unaltered biological materials. LASCA employs a pulsed 2.94 μm laser beam for specimen ablation. Ablated materials in the laser plumes are collected on a hanging solvent droplet with electric field-enhanced trapping, followed by aspiration of droplets and remaining plume material in the form of a coarse aerosol into a collection capillary. The gas and liquid phases are subsequently separated in a 10 μL-volume separatory funnel, and the solution is analyzed with electrospray ionization in a high mass resolution Q-ToF mass spectrometer. The LASCA system separates the sampling and ionization steps in MSI and combines high efficiencies of laser plume sampling and of electrospray ionization (ESI) with high mass resolution MS. Up to 2000 different compounds are detected from a single ablation spot (pixel). Using the LASCA platform, rapid (6 s per pixel), high sensitivity, high mass-resolution ambient imaging of "as-received" biological material is achieved routinely and reproducibly.

The IPA and the American Psychoanalytic Association: a perspective on the regional association agreement.

PubMed

Wallerstein, R S

1998-06-01

Ever since 1938 the American Psychoanalytic Association has had a special autonomous relationship within the IPA accorded to no other component organisation. This Regional Association status has had two main features: (1) total internal control over training standards and membership criteria, with no accountability to the IPA; and (2) an 'exclusive franchise', so that the IPA was barred from recognising any other component within the United States. This unique Regional Association status reflected the resolution at the time (1938) of the long-standing controversy between the IPA and the American over the issue of 'lay analysis', and remained unaltered for half a century until, with the resolution of the 3 1/2-year long law-suit against the American (and secondarily against the IPA) in 1988, the Regional Association agreement was modified (but not totally abrogated) by the American's giving up the 'exclusive franchise' aspect (thus permitting IPA recognition of psychoanalytic groups in the US organised outside the American), but still retaining its internal full control over training and membership. The meanings and consequences for psychoanalysis of this special status of the American are explored.

Effect of some blocking drugs on the pressor response to physostigmine in the rat

PubMed Central

Gokhale, S. D.; Gulati, O. D.; Joshi, N. Y.

1963-01-01

Bretylium and guanethidine blocked the pressor effect of physostigmine and potentiated the responses to adrenaline and noradrenaline on the blood pressure of the rat. Morphine and atropine in small doses blocked the pressor effect of physostigmine without interfering with the actions of adrenaline and noradrenaline. Chlorpromazine in small doses (0.5 to 2.5 mg/kg) blocked the pressor effect of physostigmine and potentiated the responses to noradrenaline whilst those to adrenaline remained unaltered. 3,6-Di(3-diethylaminopropoxy)pyridazine di(methiodide) (Win 4981) blocked the pressor effect of physostigmine and, in its early stages, this block was partially reversed by choline chloride. N-Diethylaminoethyl-N-isopentyl-N'N'-diisopropylurea (P-286), in a dose that reduced the effect of dimethylphenylpiperazinium, had no effect on the pressor response to physostigmine or on the responses to adrenaline and noradrenaline. Hexamethonium, even in large doses (100 mg/kg), only blocked partially the effect of physostigmine while mecamylamine produced a complete block; the responses to adrenaline and noradrenaline were potentiated in both instances. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:14081658

Spiral waves in driven strongly coupled Yukawa systems

NASA Astrophysics Data System (ADS)

Kumar, Sandeep; Das, Amita

2018-06-01

Spiral wave formations are ubiquitous in nature. In the present paper, the excitation of spiral waves in the context of driven two-dimensional dusty plasma (Yukawa system) has been demonstrated at particle level using molecular-dynamics simulations. The interaction amidst dust particles is modeled by the Yukawa potential to take account of the shielding of dust charges by the lighter electron and ion species. The spatiotemporal evolution of these spiral waves has been characterized as a function of the frequency and amplitude of the driving force and dust neutral collisions. The effect of strong coupling has been studied, which shows that the excited spiral wave structures get clearer as the medium gets more strongly coupled. The radial propagation speed of the spiral wave is observed to remain unaltered with the coupling parameter. However, it is found to depend on the screening parameter of the dust medium and decreases when it is increased. In the crystalline phase (with screening parameter κ >0.58 ), the spiral wavefronts are shown to be hexagonal in shape. This shows that the radial propagation speed depends on the interparticle spacing.

Neuromuscular blockade of slow twitch muscle fibres elevates muscle oxygen uptake and energy turnover during submaximal exercise in humans.

PubMed

Krustrup, Peter; Secher, Niels H; Relu, Mihai U; Hellsten, Ylva; Söderlund, Karin; Bangsbo, Jens

2008-12-15

We tested the hypothesis that a greater activation of fast-twitch (FT) fibres during dynamic exercise leads to a higher muscle oxygen uptake (VO2 ) and energy turnover as well as a slower muscle on-kinetics. Subjects performed one-legged knee-extensor exercise for 10 min at an intensity of 30 W without (CON) and with (CUR) arterial injections of the non-depolarizing neuromuscular blocking agent cisatracurium. In CUR, creatine phosphate (CP) was unaltered in slow twitch (ST) fibres and decreased (P < 0.05) by 28% in FT fibres, whereas in CON, CP decreased (P < 0.05) by 33% and 23% in ST and FT fibres, respectively. From 127 s of exercise, muscle VO2 was higher (P < 0.05) in CUR compared to CON (425 +/- 25 (+/- S.E.M.) versus 332 +/- 30 ml min(-1)) and remained higher (P < 0.05) throughout exercise. Using monoexponential fitting, the time constant of the exercise-induced muscle VO2 response was slower (P < 0.05) in CUR than in CON (55 +/- 6 versus 33 +/- 5 s). During CUR and CON, muscle homogenate CP was lowered (P < 0.05) by 32 and 35%, respectively, and also muscle lactate production was similar in CUR and CON (37.8 +/- 4.1 versus 35.2 +/- 6.2 mmol). Estimated total muscle ATP turnover was 19% higher (P < 0.05) in CUR than in CON (1196 +/- 90 versus 1011 +/- 59 mmol) and true mechanical efficiency was lower (P < 0.05) in CUR than in CON (26.2 +/- 2.0 versus 30.9 +/- 1.5%). In conclusion, the present findings provide evidence that FT fibres are less efficient than ST fibres in vivo at a contraction frequency of 1 Hz, and that the muscle VO2 kinetics is slowed by FT fibre activation.

Effects of TORC1 Inhibition during the Early and Established Phases of Polycystic Kidney Disease

PubMed Central

Ta, Michelle H. T.; Schwensen, Kristina G.; Foster, Sheryl; Korgaonkar, Mayuresh; Ozimek-Kulik, Justyna E.; Phillips, Jacqueline K.; Peduto, Anthony; Rangan, Gopala K.

2016-01-01

The disease-modifying effects of target of rapamycin complex 1 (TORC1) inhibitors during different stages of polycystic kidney disease (PKD) are not well defined. In this study, male Lewis Polycystic Kidney Disease (LPK) rats (a genetic ortholog of human NPHP9, phenotypically characterised by diffuse distal nephron cystic growth) and Lewis controls received either vehicle (V) or sirolimus (S, 0.2 mg/kg by intraperitoneal injection 5 days per week) during the early (postnatal weeks 3 to 10) or late stages of disease (weeks 10 to 20). In early-stage disease, sirolimus reduced kidney enlargement (by 63%), slowed the rate of increase in total kidney volume (TKV) in serial MRI by 78.2% (LPK+V: 132.3±59.7 vs. LPK+S: 28.8±12.0% per week) but only partly reduced the percentage renal cyst area (by 19%) and did not affect the decline in endogenous creatinine clearance (CrCl) in LPK rats. In late-stage disease, sirolimus reduced kidney enlargement (by 22%) and the rate of increase in TKV by 71.8% (LPK+V: 13.1±6.6 vs. LPK+S: 3.7±3.7% per week) but the percentage renal cyst area was unaltered, and the CrCl only marginally better. Sirolimus reduced renal TORC1 activation but not TORC2, NF-κB DNA binding activity, CCL2 or TNFα expression, and abnormalities in cilia ultrastructure, hypertension and cardiac disease were also not improved. Thus, the relative treatment efficacy of TORC1 inhibition on kidney enlargement was consistent at all disease stages, but the absolute effect was determined by the timing of drug initiation. Furthermore, cystic microarchitecture, renal function and cardiac disease remain abnormal with TORC1 inhibition, indicating that additional approaches to normalise cellular dedifferentiation, inflammation and hypertension are required to completely arrest the progression of PKDs. PMID:27723777

Organic Matter Responses to Radiation under Lunar Conditions

PubMed Central

Matthewman, Richard; Crawford, Ian A.; Jones, Adrian P.; Joy, Katherine H.

2016-01-01

Abstract Large bodies, such as the Moon, that have remained relatively unaltered for long periods of time have the potential to preserve a record of organic chemical processes from early in the history of the Solar System. A record of volatiles and impactors may be preserved in buried lunar regolith layers that have been capped by protective lava flows. Of particular interest is the possible preservation of prebiotic organic materials delivered by ejected fragments of other bodies, including those originating from the surface of early Earth. Lava flow layers would shield the underlying regolith and any carbon-bearing materials within them from most of the effects of space weathering, but the encapsulated organic materials would still be subject to irradiation before they were buried by regolith formation and capped with lava. We have performed a study to simulate the effects of solar radiation on a variety of organic materials mixed with lunar and meteorite analog substrates. A fluence of ∼3 × 1013 protons cm−2 at 4–13 MeV, intended to be representative of solar energetic particles, has little detectable effect on low-molecular-weight (≤C30) hydrocarbon structures that can be used to indicate biological activity (biomarkers) or the high-molecular-weight hydrocarbon polymer poly(styrene-co-divinylbenzene), and has little apparent effect on a selection of amino acids (≤C9). Inevitably, more lengthy durations of exposure to solar energetic particles may have more deleterious effects, and rapid burial and encapsulation will always be more favorable to organic preservation. Our data indicate that biomarker compounds that may be used to infer biological activity on their parent planet can be relatively resistant to the effects of radiation and may have a high preservation potential in paleoregolith layers on the Moon. Key Words: Radiation—Moon—Regolith—Amino acids—Biomarkers. Astrobiology 16, 900–912. PMID:27870583

Molecular Mechanism of MART-1+/A*0201+ Human Melanoma Resistance to Specific CTL-Killing Despite Functional Tumor-CTL Interaction

PubMed Central

Jazirehi, Ali R.; Baritaki, Stavroula; Koya, Richard C.; Bonavida, Benjamin; Economou, James S.

2014-01-01

Durable responses in metastatic melanoma patients remain generally difficult to achieve. Adoptive cell therapy with ex vivo engineered lymphocytes expressing high affinity T cell receptors TCRα/β for the melanoma antigen MART-127-35/HLA A*0201 (recognized by F5 cytotoxic T lymphocytes [F5 CTLs]) has been found to benefit certain patients. However, many other patients are inherently unresponsive and/or relapse for unknown reasons. To analyze the basis for the acquired-resistance and strategies to reverse it, we established F5 CTLresistant (R) human melanoma clones from relatively sensitive parental lines under selective F5 CTL pressure. Surface MART-127-35/HLA-A*0201 in these clones was unaltered and F5 CTLs recognized and interacted with them similarly to the parental lines. Nevertheless, the R clones were resistant to F5 CTL killing, exhibited hyperactivation of the NF-κB survival pathway, and overexpression of the anti-apoptotic genes Bcl-2, Bcl-xL and Mcl-1. Sensitivity to F5 CTL-killing could be increased by pharmacological inhibition of the NF-κB pathway, Bcl-2 family members, or the proteasome, the latter of which reduced NF-κB activity and diminished anti-apoptotic gene expression. Specific gene-silencing (by siRNA) confirmed the protective role of anti-apoptotic factors by reversing R clone resistance. Together, our findings suggest that long-term immunotherapy may impose a selection for the development of resistant cells that are unresponsive to highly avid and specific melanoma-reactive CTLs, despite maintaining expression of functional peptide:MHC complexes, due to activation of anti-apoptotic signaling pathways. Though unresponsive to CTL, our results argue that resistant cells can be re-sensitized to immunotherapy with co-administration of targeted inhibitors to anti-apoptotic survival pathways. PMID:21159666

Caveolin-1 knockout mice exhibit impaired induction of mGluR-dependent long-term depression at CA3-CA1 synapses.

PubMed

Takayasu, Yukihiro; Takeuchi, Koichi; Kumari, Ranju; Bennett, Michael V L; Zukin, R Suzanne; Francesconi, Anna

2010-12-14

Group I metabotropic glutamate receptors (mGluR1/5) are important to synaptic circuitry formation during development and to forms of activity-dependent synaptic plasticity. Dysregulation of mGluR1/5 signaling is implicated in some disorders of neurodevelopment, including fragile X syndrome, the most common inherited form of intellectual disabilities and leading cause of autism. Site(s) in the intracellular loops of mGluR1/5 directly bind caveolin-1, an adaptor protein that associates with membrane rafts. Caveolin-1 is the main coat component of caveolae and organizes macromolecular signaling complexes with effector proteins and membrane receptors. We report that long-term depression (LTD) elicited by a single application of the group I mGluR selective agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) was markedly attenuated at Schaffer collateral-CA1 synapses of mice lacking caveolin-1 (Cav1(-/-)), as assessed by field recording. In contrast, multiple applications of DHPG produced LTD comparable to that in WT mice. Passive membrane properties, basal glutamatergic transmission and NMDA receptor (NMDAR)-dependent LTD were unaltered. The remaining LTD was reduced by anisomycin, an inhibitor of protein synthesis, by U0126, an inhibitor of MEK1/2 kinases, and by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), suggesting mediation by the same mechanisms as in WT. mGluR1/5-dependent activation (phosphorylation) of MEK and extracellular signal-regulated kinase (ERK1/2) was altered in Cav1(-/-) mice; basal phosphorylation was increased, but a single application of DHPG had no further effect, and after DHPG, phosphorylation was similar in WT and Cav1(-/-) mice. Taken together, our findings suggest that caveolin-1 is required for normal coupling of mGluR1/5 to downstream signaling cascades and induction of mGluR-LTD.

Modulation of gastric contractions in response to tachykinins and bethanechol by extrinsic nerves.

PubMed

Holzer-Petsche, U

1991-08-01

1. Extrinsic reflexes elicited by changes in gastric wall tension play an important role in regulating gastric tone. The present study investigated whether such reflexes modulate gastric contractions induced by close arterially administered neurokinin A (NKA), substance P (SP), SP-methylester and bethancehol in anaesthetized rats. 2. Reflex pathways were acutely interrupted by either subdiaphragmatic vagotomy or prevertebral ganglionectomy. C-fibre afferent nerve activity was abolished by pretreating rats with capsaicin 10 to 16 days before the experiments. 3. The order of potency in inducing gastric contractions was NKA greater than SP greater than bethanechol. SP-methylester was markedly less effective than SP and its effects did not fit sigmoid dose-response curves (DRCs). The maximal responses to NKA, SP, and bethanechol were similar, whilst the DRC for SP was significantly flatter than those for NKA or bethanechol. Pretreatment of the rats with the peptidase inhibitors phosphoramidon or captopril did not increase the contractile response to SP. 4. Prevertebral ganglionectomy had no significant effect on the DRCs for SP and NKA, whereas vagotomy shifted the DRCs for all three test substances to the left. 5. Capsaicin pretreatment did not change the DRC for NKA in rats with intact vagus but shifted that for bethanechol to the left. The leftward of the DRC for NKA caused by vagotomy was prevented in capsaicin-pretreated rats whereas the vagotomy-induced shift of the DRC for bethanechol remained unaltered. The shift of the DRC for SP seen in response to vagotomy was only slightly reduced by capsaicin pretreatment. 6. These data may be interpreted as demonstrating two neuronal mechanisms for modulating drug-induced gastric contractions. First, the contractions themselves activate a vago-vagal negative feedback involving capsaicin-sensitive afferents. Second, NKA, and to a lesser degree SP, seem to induce a nonvagal non-splanchnic mechanism which via capsaicin-sensitive afferent neurones reinforces tachykinininduced gastric contractions.

T cell protein tyrosine phosphatase (TCPTP) deficiency in muscle does not alter insulin signalling and glucose homeostasis in mice.

PubMed

Loh, K; Merry, T L; Galic, S; Wu, B J; Watt, M J; Zhang, S; Zhang, Z-Y; Neel, B G; Tiganis, T

2012-02-01

Insulin activates insulin receptor protein tyrosine kinase and downstream phosphatidylinositol-3-kinase (PI3K)/Akt signalling in muscle to promote glucose uptake. The insulin receptor can serve as a substrate for the protein tyrosine phosphatase (PTP) 1B and T cell protein tyrosine phosphatase (TCPTP), which share a striking 74% sequence identity in their catalytic domains. PTP1B is a validated therapeutic target for the alleviation of insulin resistance in type 2 diabetes. PTP1B dephosphorylates the insulin receptor in liver and muscle to regulate glucose homeostasis, whereas TCPTP regulates insulin receptor signalling and gluconeogenesis in the liver. In this study we assessed for the first time the role of TCPTP in the regulation of insulin receptor signalling in muscle. We generated muscle-specific TCPTP-deficient (Mck-Cre;Ptpn2(lox/lox)) mice (Mck, also known as Ckm) and assessed the impact on glucose homeostasis and muscle insulin receptor signalling in chow-fed versus high-fat-fed mice. Blood glucose and insulin levels, insulin and glucose tolerance, and insulin-induced muscle insulin receptor activation and downstream PI3K/Akt signalling remained unaltered in chow-fed Mck-Cre;Ptpn2(lox/lox) versus Ptpn2(lox/lox) mice. In addition, body weight, adiposity, energy expenditure, insulin sensitivity and glucose homeostasis were not altered in high-fat-fed Mck-Cre;Ptpn2(lox/lox) versus Ptpn2(lox/lox) mice. These results indicate that TCPTP deficiency in muscle has no effect on insulin signalling and glucose homeostasis, and does not prevent high-fat diet-induced insulin resistance. Thus, despite their high degree of sequence identity, PTP1B and TCPTP contribute differentially to insulin receptor regulation in muscle. Our results are consistent with the notion that these two highly related PTPs make distinct contributions to insulin receptor regulation in different tissues.

A point mutation in the human Slo1 channel that impairs its sensitivity to omega-3 docosahexaenoic acid

PubMed Central

Xu, Rong; Hou, Shangwei; Heinemann, Stefan H.; Tian, Yutao

2013-01-01

Long-chain polyunsaturated omega-3 fatty acids such as docosahexaenoic acid (DHA) at nanomolar concentrations reversibly activate human large-conductance Ca2+- and voltage-gated K+ (Slo1 BK) channels containing auxiliary β1 or β4 subunits in cell-free patches. Here we examined the action of DHA on the Slo1 channel without any auxiliary subunit and sought to elucidate the biophysical mechanism and the molecular determinants of the DHA sensitivity. Measurements of ionic currents through human Slo1 (hSlo1) channels reveal that the stimulatory effect of DHA does not require activation of the voltage or Ca2+ sensors. Unlike gating of the hSlo1 channel, that of the Drosophila melanogaster Slo1 (dSlo1) channel is unaltered by DHA. Our mutagenesis study based on the differential responses of human and dSlo1 channels to DHA pinpoints that Y318 near the cytoplasmic end of S6 in the hSlo1 channel is a critical determinant of the stimulatory action of DHA. The mutation Y318S in hSlo1, which replaces Y with S as found in dSlo1, greatly diminishes the channel’s response to DHA with a 22-carbon chain whether β1 or β4 is absent or present. However, the responses to α-linolenic acid, an omegea-3 fatty acid with an 18-carbon chain, and to arachidonic acid, an omega-6 fatty acid with a 20-carbon chain, remain unaffected by the mutation. Y318 in the S6 segment of hSlo1 is thus an important determinant of the electrophysiological response of the channel to DHA. Furthermore, the mutation Y318S may prove to be useful in dissecting out the complex lipid-mediated modulation of Slo1 BK channels. PMID:24127525

Formula for the Removal and Remediation of Polychlorinated Biphenyls in Painted Structures

NASA Technical Reports Server (NTRS)

Quinn, Jacqueline; Loftin, Kathleen; Geiger, Cherie

2010-01-01

An activated metal treatment system (AMTS) removes and destroys polychlorinated biphenyls (PCBs) found in painted structures or within the binding or caulking material on structures. It may be applied using a "paint-on and wipe-off" process that leaves the structure PCB-free and virtually unaltered in physical form. AMTS is used in conjunction with a solvent solution capable of donating hydrogen atoms. AMTS as a treatment technology has two functions: first, to extract PCBs from the material, and second, to degrade the extracted PCBs. The process for removing PCBs from structures is accomplished as an independent step to the degradation process. The goal is to extract the PCBs out of the paint, without destroying the paint, and to partition the PCBs into an environmentally friendly solvent. The research to date indicates this can be accomplished within the first 24 hours of AMTS contact with the paint. PCBs are extremely hydrophobic and prefer to be in the AMTS over the hardened paint or binder material. The solvent selected must be used to open, but not to destroy, the paint s polymeric lattice structure, allowing pathways for PCB movement out of the paint and into the solvent. A number of solvent systems were tested and are available for use within the AMTS. The second process of the AMTS is the degradation or dehalogenation of the PCBs. The solvent selection for this process is limited to solvents that are capable of donating a hydrogen atom to the PCB structure. Additional AMTS formulation properties that must be addressed for each site-specific application include viscosity and stability. The AMTS must be thick enough to remain where it is applied. Several thickening agents have been tested. Adding a stabilizing agent ensures that the AMTS will not evaporate and leave unprotected, activated metal exposed. During AMTS formulation testing, a number of reagents were evaluated to ensure the rate of dehalogenation was not inhibited by its addition to the system.

Differential modulation of ammonia excretion, Rhesus glycoproteins and ion-regulation in common carp (Cyprinus carpio) following individual and combined exposure to waterborne copper and ammonia.

PubMed

Sinha, Amit Kumar; Kapotwe, Mumba; Dabi, Shambel Boki; Montes, Caroline da Silva; Shrivastava, Jyotsna; Blust, Ronny; De Boeck, Gudrun

2016-01-01

The main objective of this study was to understand the mode of interaction between waterborne copper (Cu) and high environmental ammonia (HEA) exposure on freshwater fish, and how they influence the toxicity of each other when present together. For this purpose, individual and combined effects of Cu and HEA were examined on selected physiological and ion-regulatory processes and changes at transcript level in the common carp (Cyprinus carpio). Juvenile carp were exposed to 2.6μM Cu (25% of the 96h LC50value) and to 0.65mM ammonia (25% of the 96h LC50value) singly and as a mixture for 12h, 24h, 48h, 84h and 180h. Responses such as ammonia (Jamm) and urea (Jurea) excretion rate, plasma ammonia and urea, plasma ions (Na(+), Cl(-) and K(+)), muscle water content (MWC) as well as branchial Na(+)/K(+)-ATPase (NKA) and H(+)-ATPase activity, and branchial mRNA expression of NKA, H(+)-ATPase, Na(+)/H(+) exchanger (NHE-3) and Rhesus (Rh) glycoproteins were investigated under experimental conditions. Results show that Jamm was inhibited during Cu exposure, while HEA exposed fish were able to increase excretion efficiently. In the combined exposure, Jamm remained at the control levels indicating that Cu and HEA abolished each other's effect. Expression of Rhcg (Rhcg-a and Rhcg-b) mRNA was upregulated during HEA, thereby facilitated ammonia efflux out of gills. On the contrary, Rhcg-a transcript level declined following Cu exposure which might account for Cu induced Jamm inhibition. Likewise, Rhcg-a was also down-regulated in Cu-HEA co-exposed fish whilst a temporary increment was noted for Rhch-b. Fish exposed to HEA displayed pronounced up-regulation in NKA expression and activity and stable plasma ion levels. In both the Cu exposure alone and combined Cu-HEA exposure, ion-osmo homeostasis was adversely affected, exemplified by the significant reduction in plasma [Na(+)] and [Cl(-)], and elevated plasma [K(+)], along with an elevation in MWC. These changes were accompanied by a decline in NKA activity. Gill H(+)-ATPase mRNA levels and activities were not affected by either Cu or HEA or both. Likewise, NHE-3 expression remained unaltered but tended to be numerically higher during HEA exposure. Overall, these data suggest that at equitoxic concentrations (25% of 96h LC50), the individual effect of Cu is more harmful while HEA induces quicker adaptive responses. Our findings also denote a competitive mode of interaction, exemplified by the inhibition of HEA -mediated adaptive responses in the presence of Cu. Copyright © 2015 Elsevier B.V. All rights reserved.

32 CFR 807.1 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION SALE TO THE PUBLIC § 807.1 General requirements. (a) Unaltered Air Force publications and forms will be made available to the public with or without charge, subject to the requirements of this part. Base Chiefs of...

Substrate Shuttling Between Active Sites of Uroporphyrinogen Decarboxylase in Not Required to Generate Coproporphyrinogen

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

Phillips, J.; Warby, C; Whitby, F

2009-01-01

Uroporphyrinogen decarboxylase (URO-D; EC 4.1.1.37), the fifth enzyme of the heme biosynthetic pathway, is required for the production of heme, vitamin B12, siroheme, and chlorophyll precursors. URO-D catalyzes the sequential decarboxylation of four acetate side chains in the pyrrole groups of uroporphyrinogen to produce coproporphyrinogen. URO-D is a stable homodimer, with the active-site clefts of the two subunits adjacent to each other. It has been hypothesized that the two catalytic centers interact functionally, perhaps by shuttling of reaction intermediates between subunits. We tested this hypothesis by construction of a single-chain protein (single-chain URO-D) in which the two subunits were connectedmore » by a flexible linker. The crystal structure of this protein was shown to be superimposable with wild-type activity and to have comparable catalytic activity. Mutations that impaired one or the other of the two active sites of single-chain URO-D resulted in approximately half of wild-type activity. The distributions of reaction intermediates were the same for mutant and wild-type sequences and were unaltered in a competition experiment using I and III isomer substrates. These observations indicate that communication between active sites is not required for enzyme function and suggest that the dimeric structure of URO-D is required to achieve conformational stability and to create a large active-site cleft.« less

Integration of a 'proton antenna' facilitates transport activity of the monocarboxylate transporter MCT4.

PubMed

Noor, Sina Ibne; Pouyssegur, Jacques; Deitmer, Joachim W; Becker, Holger M

2017-01-01

Monocarboxylate transporters (MCTs) mediate the proton-coupled transport of high-energy metabolites like lactate and pyruvate and are expressed in nearly every mammalian tissue. We have shown previously that transport activity of MCT4 is enhanced by carbonic anhydrase II (CAII), which has been suggested to function as a 'proton antenna' for the transporter. In the present study, we tested whether creation of an endogenous proton antenna by introduction of a cluster of histidine residues into the C-terminal tail of MCT4 (MCT4-6xHis) could facilitate MCT4 transport activity when heterologously expressed in Xenopus oocytes. Our results show that integration of six histidines into the C-terminal tail does indeed increase transport activity of MCT4 to the same extent as did coexpression of MCT4-WT with CAII. Transport activity of MCT4-6xHis could be further enhanced by coexpression with extracellular CAIV, but not with intracellular CAII. Injection of an antibody against the histidine cluster into MCT4-expressing oocytes decreased transport activity of MCT4-6xHis, while leaving activity of MCT4-WT unaltered. Taken together, these findings suggest that transport activity of the proton-coupled monocarboxylate transporter MCT4 can be facilitated by integration of an endogenous proton antenna into the transporter's C-terminal tail. © 2016 Federation of European Biochemical Societies.

Chronophin regulates active vitamin B6 levels and transcriptomic features of glioblastoma cell lines cultured under non-adherent, serum-free conditions.

PubMed

Schulze, Markus; Hutterer, Maria; Sabo, Anja; Hoja, Sabine; Lorenz, Julia; Rothhammer-Hampl, Tanja; Herold-Mende, Christel; Floßbach, Lucia; Monoranu, Camelia; Riemenschneider, Markus J

2018-05-03

The phosphatase chronophin (CIN/PDXP) has been shown to be an important regulator of glioma cell migration and invasion. It has two known substrates: p-Ser3-cofilin, the phosphorylated form of the actin binding protein cofilin, and pyridoxal 5'-phosphate, the active form of vitamin B6. Phosphoregulation of cofilin, among other functions, plays an important role in cell migration, whereas active vitamin B6 is a cofactor for more than one hundred enzymatic reactions. The role of CIN has yet only been examined in glioblastoma cell line models derived under serum culture conditions. We found that CIN is highly expressed in cells cultured under non-adherent, serum-free conditions that are thought to better mimic the in vivo situation. Furthermore, the substrates of CIN, p-Ser3-cofilin and active vitamin B6, were significantly reduced as compared to cell lines cultured in serum-containing medium. To further examine its molecular role we stably knocked down the CIN protein with two different shRNA hairpins in the glioblastoma cell lines NCH421k and NCH644. Both cell lines did not show any significant alterations in proliferation but expression of differentiation markers (such as GFAP or TUBB3) was increased in the knockdown cell lines. In addition, colony formation was significantly impaired in NCH644. Of note, in both cell lines CIN knockdown increased active vitamin B6 levels with vitamin B6 being known to be important for S-adenosylmethionine biosynthesis. Nevertheless, global histone and DNA methylation remained unaltered as was chemoresistance towards temozolomide. To further elucidate the role of phosphocofilin in glioblastoma cells we applied inhibitors for ROCK1/2 and LIMK1/2 to our model. LIMK- and ROCK-inhibitor treatment alone was not toxic for glioblastoma cells. However, it had profound, but antagonistic effects in NCH421k and NCH644 under chemotherapy. In non-adherent glioblastoma cell lines cultured in serum-free medium, chronophin knockdown induces phenotypic changes, e.g. in colony formation and transcription, but these are highly dependent on the cellular background. The same is true for phenotypes observed after treatment with inhibitors for kinases regulating cofilin phosphorylation (ROCKs and LIMKs). Targeting the cofilin phosphorylation pathway might therefore not be a straightforward therapeutic option in glioblastoma.

Further characterization of a highly attenuated Yersinia pestis CO92 mutant deleted for the genes encoding Braun lipoprotein and plasminogen activator protease in murine alveolar and primary human macrophages.

PubMed

van Lier, Christina J; Tiner, Bethany L; Chauhan, Sadhana; Motin, Vladimir L; Fitts, Eric C; Huante, Matthew B; Endsley, Janice J; Ponnusamy, Duraisamy; Sha, Jian; Chopra, Ashok K

2015-03-01

We recently characterized the Δlpp Δpla double in-frame deletion mutant of Yersinia pestis CO92 molecularly, biologically, and immunologically. While Braun lipoprotein (Lpp) activates toll-like receptor-2 to initiate an inflammatory cascade, plasminogen activator (Pla) protease facilitates bacterial dissemination in the host. The Δlpp Δpla double mutant was highly attenuated in evoking bubonic and pneumonic plague, was rapidly cleared from mouse organs, and generated humoral and cell-mediated immune responses to provide subsequent protection to mice against a lethal challenge dose of wild-type (WT) CO92. Here, we further characterized the Δlpp Δpla double mutant in two murine macrophage cell lines as well as in primary human monocyte-derived macrophages to gauge its potential as a live-attenuated vaccine candidate. We first demonstrated that the Δpla single and the Δlpp Δpla double mutant were unable to survive efficiently in murine and human macrophages, unlike WT CO92. We observed that the levels of Pla and its associated protease activity were not affected in the Δlpp single mutant, and, likewise, deletion of the pla gene from WT CO92 did not alter Lpp levels. Further, our study revealed that both Lpp and Pla contributed to the intracellular survival of WT CO92 via different mechanisms. Importantly, the ability of the Δlpp Δpla double mutant to be phagocytized by macrophages, to stimulate production of tumor necrosis factor-α and interleukin-6, and to activate the nitric oxide killing pathways of the host cells remained unaltered when compared to the WT CO92-infected macrophages. Finally, macrophages infected with either the WT CO92 or the Δlpp Δpla double mutant were equally efficient in their uptake of zymosan particles as determined by flow cytometric analysis. Overall, our data indicated that although the Δlpp Δpla double mutant of Y. pestis CO92 was highly attenuated, it retained the ability to elicit innate and subsequent acquired immune responses in the host similar to that of WT CO92, which are highly desirable in a live-attenuated vaccine candidate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Muscular activation during reverse and non-reverse chewing cycles in unilateral posterior crossbite.

PubMed

Piancino, Maria Grazia; Farina, Dario; Talpone, Francesca; Merlo, Andrea; Bracco, Pietro

2009-04-01

The aim of this study was to characterize the kinematics and masseter muscle activation in unilateral posterior crossbite. Eighty-two children (8.6 +/- 1.3 yr of age) with unilateral posterior crossbite and 12 children (8.9 +/- 0.6 yr of age) with normal occlusion were selected for the study. Electromyography (EMG) and kinematics were concurrently recorded during mastication of a soft bolus and a hard bolus. The percentage of reverse cycles in the group of patients was 59.0 +/- 33.1% (soft bolus) and 69.7 +/- 29.7% (hard bolus) when chewing on the crossbite side. When chewing on the non-affected side, the number of reverse cycles was 16.7 +/- 24.5% (soft bolus) and 16.7 +/- 22.3% (hard bolus). The reverse cycles on the crossbite side were narrower with respect to the cycles on the non-affected side. Although both types of cycles in patients resulted in lower EMG activity of the masseter of the crossbite side than of the contralateral masseter, the activity of the non-affected side was larger for reverse than for non-reverse cycles. It was concluded that when chewing on the crossbite side, the masseter activity is reduced on the mastication side (crossbite) and is unaltered (non-reverse cycles) or increased (reverse) on the non-affected side.

S-nitrosylation of GAD65 is implicated in decreased GAD activity and oxygen-induced seizures.

PubMed

Gasier, Heath G; Demchenko, Ivan T; Tatro, Lynn G; Piantadosi, Claude A

2017-07-13

Breathing oxygen at partial pressures ≥2.5 atmospheres absolute, which can occur in diving and hyperbaric oxygen (HBO 2 ) therapy, can rapidly become toxic to the central nervous system (CNS). This neurotoxicity culminates in generalized EEG epileptiform discharges, tonic-clonic convulsions and ultimately death. Increased production of neuronal nitric oxide (NO) has been implicated in eliciting hyperoxic seizures by altering the equilibrium between glutamatergic and GABAergic synaptic transmission. Inhibition of glutamic acid decarboxylase (GAD) activity in HBO 2 promotes this imbalance; however, the mechanisms by which this occurs is unknown. Therefore, we conducted a series of experiments using mice, a species that is highly susceptible to CNS oxygen toxicity, to explore the possibility that NO modulates GABA metabolism. Mice were exposed to 100% oxygen at 4 ATA for various durations, and brain GAD and GABA transaminase (GABA-T) activity, as well as S-nitrosylation of GAD65 and GAD67 were determined. HBO 2 inhibited GAD activity by 50% and this was negatively correlated with S-nitrosylation of GAD65, whereas GABA-T activity and S-nitrosylation of GAD67 were unaltered. These results suggest a new mechanism by which NO alters GABA metabolism, leading to neuroexcitation and seizures in HBO 2 . Published by Elsevier B.V.

Osmolality and respiratory regulation in humans: respiratory compensation for hyperchloremic metabolic acidosis is absent after infusion of hypertonic saline in healthy volunteers.

PubMed

Moen, Vibeke; Brudin, Lars; Rundgren, Mats; Irestedt, Lars

2014-10-01

Several animal studies show that changes in plasma osmolality may influence ventilation. Respiratory depression caused by increased plasma osmolality is interpreted as inhibition of water-dependent thermoregulation because conservation of body fluid predominates at the cost of increased core temperature. Respiratory alkalosis, on the other hand, is associated with a decrease in plasma osmolality and strong ion difference (SID) during human pregnancy. We investigated the hypothesis that osmolality would influence ventilation, so that increased osmolality will decrease ventilation and decreased osmolality will stimulate ventilation in both men and women. Our study participants were healthy volunteers of both sexes (ASA physical status I). Ten men (mean 28 years; range 20-40) and 9 women (mean 33 years; range 22-43) were included. All women participated in both the follicular and luteal phases of the menstrual cycle. Hyperosmolality was induced by IV infusion of hypertonic saline 3%, and hypoosmolality by drinking tap water. Arterial blood samples were collected for analysis of electrolytes, osmolality, and blood gases. Sensitivity to CO2 was determined by rebreathing tests performed before and after the fluid-loading procedures. Infusion of hypertonic saline caused hyperchloremic metabolic acidosis with decreased SID in all subjects. Analysis of pooled data showed absence of respiratory compensation. Baseline arterial PCO2 (PaCO2) mean (SD) 37.8 (2.9) mm Hg remained unaltered, with lowest PaCO2 37.8 (2.9) mm Hg after 100 minutes, P = 0.70, causing a decrease in pH from mean (SD) 7.42 (0.02) to 7.38 (0.02), P < 0.001. Metabolic acidosis was also observed during water loading. Pooled results show that PaCO2 decreased from 38.2 (3.3) mm Hg at baseline to 35.7 (2.8) mm Hg after 80 minutes of drinking water, P = 0.002, and pH remained unaltered: pH 7.43 (0.02) at baseline to pH 7.42 (0.02), P = 0.14, mean difference (confidence interval) = pH -0.007 (-0.017 to 0.003). Our results indicate that osmolality has an influence on ventilation. Respiratory compensation for hyperchloremic metabolic acidosis was suppressed during hyperosmolality. Water loading caused a decrease in plasma osmolality and metabolic acidosis, and although the decrease in SID was smaller compared with salt loading, the expected respiratory compensation was observed. Ventilation was also stimulated in men, therefore independently of progesterone levels. We propose that the influence of osmolality on ventilation consists mainly as depression in conditions of hyperosmolality and that this depression is absent during hypoosmolality.

Context-Conditioned Generalization in Adaptation to Distorted Speech

ERIC Educational Resources Information Center

Dahan, Delphine; Mead, Rebecca L.

2010-01-01

People were trained to decode noise-vocoded speech by hearing monosyllabic stimuli in distorted and unaltered forms. When later presented with different stimuli, listeners were able to successfully generalize their experience. However, generalization was modulated by the degree to which testing stimuli resembled training stimuli: Testing stimuli's…

Habitat selection is unaltered after severe insect infestation: Concerns for forest-dependent species

Treesearch

Claire A. Zugmeyer; John L. Koprowski

2009-01-01

Severe disturbance may alter or eliminate important habitat structure that helps preserve food caches of foodhoarding species. Recent recolonization of an insect-damaged forest by the endangered Mt. Graham red squirrel (Tamiasciurus hudsonicus grahamensis) provided an opportunity to examine habitat selection for midden (cache) sites following...

USE OF FLUORESCENT POLYCYLIC AROMATIC HYDROCARBON PROBES IN STUDYING THE IMPACT OF COLLOIDS ON POLLUTANT TRANSPORT IN GROUNDWATER

EPA Science Inventory

A fluorescence-quenching method was developed to assess the hydrophobic organic pollutant binding potential of organic colloids (OC) in unaltered natural waters. This method allows (1) direct assessment of the importance of OC-enhanced pollutant transport for environmental sam- p...

Immortalized Parkinson's disease lymphocytes have enhanced mitochondrial respiratory activity

PubMed Central

Annesley, Sarah J.; Lay, Sui T.; De Piazza, Shawn W.; Sanislav, Oana; Hammersley, Eleanor; Allan, Claire Y.; Francione, Lisa M.; Bui, Minh Q.; Chen, Zhi-Ping; Ngoei, Kevin R. W.; Tassone, Flora; Kemp, Bruce E.; Storey, Elsdon; Evans, Andrew; Loesch, Danuta Z.

2016-01-01

ABSTRACT In combination with studies of post-mortem Parkinson's disease (PD) brains, pharmacological and genetic models of PD have suggested that two fundamental interacting cellular processes are impaired – proteostasis and mitochondrial respiration. We have re-examined the role of mitochondrial dysfunction in lymphoblasts isolated from individuals with idiopathic PD and an age-matched control group. As previously reported for various PD cell types, the production of reactive oxygen species (ROS) by PD lymphoblasts was significantly elevated. However, this was not due to an impairment of mitochondrial respiration, as is often assumed. Instead, basal mitochondrial respiration and ATP synthesis are dramatically elevated in PD lymphoblasts. The mitochondrial mass, genome copy number and membrane potential were unaltered, but the expression of indicative respiratory complex proteins was also elevated. This explains the increased oxygen consumption rates by each of the respiratory complexes in experimentally uncoupled mitochondria of iPD cells. However, it was not attributable to increased activity of the stress- and energy-sensing protein kinase AMPK, a regulator of mitochondrial biogenesis and activity. The respiratory differences between iPD and control cells were sufficiently dramatic as to provide a potentially sensitive and reliable biomarker of the disease state, unaffected by disease duration (time since diagnosis) or clinical severity. Lymphoblasts from control and PD individuals thus occupy two distinct, quasi-stable steady states; a ‘normal’ and a ‘hyperactive’ state characterized by two different metabolic rates. The apparent stability of the ‘hyperactive’ state in patient-derived lymphoblasts in the face of patient ageing, ongoing disease and mounting disease severity suggests an early, permanent switch to an alternative metabolic steady state. With its associated, elevated ROS production, the ‘hyperactive’ state might not cause pathology to cells that are rapidly turned over, but brain cells might accumulate long-term damage leading ultimately to neurodegeneration and the loss of mitochondrial function observed post-mortem. Whether the ‘hyperactive’ state in lymphoblasts is a biomarker specifically of PD or more generally of neurodegenerative disease remains to be determined. PMID:27638668

Mutation of cysteine 111 in Dopa decarboxylase leads to active site perturbation.

PubMed Central

Dominici, P.; Moore, P. S.; Castellani, S.; Bertoldi, M.; Voltattorni, C. B.

1997-01-01

Cysteine 111 in Dopa decarboxylase (DDC) has been replaced by alanine or serine by site-directed mutagenesis. Compared to the wild-type enzyme, the resultant C111A and C111S mutant enzymes exhibit Kcat values of about 50% and 15%, respectively, at pH 6.8, while the K(m) values remain relatively unaltered for L-3,4-dihydroxyphenylalanine (L-Dopa) and L-5-hydroxytryptophan (L-5-HTP). While a significant decrease of the 280 nm optically active band present in the wild type is observed in mutant DDCs, their visible co-enzyme absorption and CD spectra are similar to those of the wild type. With respect to the wild type, the Cys-111-->Ala mutant displays a reduced affinity for pyridoxal 5'-phosphate (PLP), slower kinetics of reconstitution to holoenzyme, a decreased ability to anchor the external aldimine formed between D-Dopa and the bound co-enzyme, and a decreased efficiency of energy transfer between tryptophan residue(s) and reduced PLP. Values of pKa and pKb for the groups involved in catalysis were determined for the wild-type and the C111A mutant enzymes. The mutant showed a decrease in both pK values by about 1 pH unit, resulting in a shift of the pH of the maximum velocity from 7.2 (wild-type) to 6.2 (mutant). This change in maximum velocity is mirrored by a similar shift in the spectrophotometrically determined pK value of the 420-->390 nm transition of the external aldimine. These results demonstrate that the sulfhydryl group of Cys-111 is catalytically nonessential and provide strong support for previous suggestion that this residue is located at or near the PLP binding site (Dominici P, Maras B, Mei G, Borri Voltattorni C. 1991. Eur J Biochem 201:393-397). Moreover, our findings provide evidence that Cys-111 has a structural role in PLP binding and suggest that this residue is required for maintenance of proper active-site conformation. PMID:9300500

The taste of KCl - What a difference a sugar makes.

PubMed

Ben Abu, Natalie; Harries, Daniel; Voet, Hillary; Niv, Masha Y

2018-07-30

Dramatic increase in NaCl consumption lead to sodium intake beyond health guidelines. KCl substitution helps reduce sodium intake but results in a bitter-metallic off-taste. Two disaccharides, trehalose and sucrose, were tested in order to untangle the chemical (increase in effective concentration of KCl due to sugar addition) from the sensory effects. The bitter-metallic taste of KCl was reduced by these sugars, while saltiness was enhanced or unaltered. The perceived sweetness of sugar, regardless of its type and concentration, was an important factor in KCl taste modulation. Though KCl was previously shown to increase the chemical activity of trehalose but not of sucrose, we found that it suppressed the perceived sweetness of both sugars. Therefore, sensory integration was the dominant factor in the tested KCl-sugar combinations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Luteinizing hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active.

PubMed

Kanamarlapudi, Venkateswarlu; Gordon, Uma D; López Bernal, Andrés

2016-06-01

Polycystic ovarian syndrome (PCOS) is associated with anovulatory infertility. Luteinizing hormone/chorionic gonadotrophin receptor (LHCGR), which is critical for ovulation, has been suggested to be expressed prematurely in the ovarian follicles of women with PCOS. This study aimed to analyse the expression and activity of LHCGR in ovarian granulosa cells from PCOS patients and the involvement of ARF6 small GTPase in LHCGR internalization. Granulosa cells (GC) isolated from follicular fluid collected during oocyte retrieval from normal women (n = 19) and women with PCOS (n = 17) were used to study differences in LHCGR protein expression and activity between normal and PCOS patients. LHCGR expression is up-regulated in GC from PCOS women. LHCGR in PCOS GC is functionally active, as shown by increased cAMP production upon human gonadotrophin (HCG)-stimulation. Moreover, ARF6 is highly expressed in GC from PCOS patients and HCG-stimulation increases the concentrations of active ARF6. The inhibition of ARF6 activation attenuates HCG-induced LHCGR internalization in both normal and PCOS GC, indicating that there are no alterations in LHCGR internalisation in GC from PCOS. In conclusion, the expression and activation of LHCGR and ARF6 are up-regulated in GC from PCOS women but the mechanism of agonist-induced LHCGR internalization is unaltered. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Ghrelin Causes a Decline in GABA Release by Reducing Fatty Acid Oxidation in Cortex.

PubMed

Mir, Joan Francesc; Zagmutt, Sebastián; Lichtenstein, Mathieu P; García-Villoria, Judit; Weber, Minéia; Gracia, Ana; Fabriàs, Gemma; Casas, Josefina; López, Miguel; Casals, Núria; Ribes, Antònia; Suñol, Cristina; Herrero, Laura; Serra, Dolors

2018-02-02

Lipid metabolism, specifically fatty acid oxidation (FAO) mediated by carnitine palmitoyltransferase (CPT) 1A, has been described to be an important actor of ghrelin action in hypothalamus. However, it is not known whether CPT1A and FAO mediate the effect of ghrelin on the cortex. Here, we show that ghrelin produces a differential effect on CPT1 activity and γ-aminobutyric acid (GABA) metabolism in the hypothalamus and cortex of mice. In the hypothalamus, ghrelin enhances CPT1A activity while GABA transaminase (GABAT) activity, a key enzyme in GABA shunt metabolism, is unaltered. However, in cortex CPT1A activity and GABAT activity are reduced after ghrelin treatment. Furthermore, in primary cortical neurons, ghrelin reduces GABA release through a CPT1A reduction. By using CPT1A floxed mice, we have observed that genetic ablation of CPT1A recapitulates the effect of ghrelin on GABA release in cortical neurons, inducing reductions in mitochondrial oxygen consumption, cell content of citrate and α-ketoglutarate, and GABA shunt enzyme activity. Taken together, these observations indicate that ghrelin-induced changes in CPT1A activity modulate mitochondrial function, yielding changes in GABA metabolism. This evidence suggests that the action of ghrelin on GABA release is region specific within the brain, providing a basis for differential effects of ghrelin in the central nervous system.

Effect of Frustration on Brain Activation Pattern in Subjects with Different Temperament

PubMed Central

Bierzynska, Maria; Bielecki, Maksymilian; Marchewka, Artur; Debowska, Weronika; Duszyk, Anna; Zajkowski, Wojciech; Falkiewicz, Marcel; Nowicka, Anna; Strelau, Jan; Kossut, Malgorzata

2016-01-01

In spite of the prevalence of frustration in everyday life, very few neuroimaging studies were focused on this emotional state. In the current study we aimed to examine effects of frustration on brain activity while performing a well-learned task in participants with low and high tolerance for arousal. Prior to the functional magnetic resonance imaging session, the subjects underwent 2 weeks of Braille reading training. Frustration induction was obtained by using a novel highly difficult tactile task based on discrimination of Braille-like raised dots patterns and negative feedback. Effectiveness of this procedure has been confirmed in a pilot study using galvanic skin response and questionnaires. Brain activation pattern during tactile discrimination task before and after frustration were compared directly. Results revealed changes in brain activity in structures mostly reported in acute stress studies: striatum, cingulate cortex, insula, middle frontal gyrus and precuneus and in structures engaged in tactile Braille discrimination: SI and SII. Temperament type affected activation pattern. Subjects with low tolerance for arousal showed higher activation in the posterior cingulate gyrus, precuneus, and inferior parietal lobule than high reactivity group. Even though performance in the discrimination trials following frustration was unaltered, we observed increased activity of primary and secondary somatosensory cortex processing the tactile information. We interpret this effect as an indicator of additional involvement required to counteract the effects of frustration. PMID:26793136

Effect of Frustration on Brain Activation Pattern in Subjects with Different Temperament.

PubMed

Bierzynska, Maria; Bielecki, Maksymilian; Marchewka, Artur; Debowska, Weronika; Duszyk, Anna; Zajkowski, Wojciech; Falkiewicz, Marcel; Nowicka, Anna; Strelau, Jan; Kossut, Malgorzata

2015-01-01

In spite of the prevalence of frustration in everyday life, very few neuroimaging studies were focused on this emotional state. In the current study we aimed to examine effects of frustration on brain activity while performing a well-learned task in participants with low and high tolerance for arousal. Prior to the functional magnetic resonance imaging session, the subjects underwent 2 weeks of Braille reading training. Frustration induction was obtained by using a novel highly difficult tactile task based on discrimination of Braille-like raised dots patterns and negative feedback. Effectiveness of this procedure has been confirmed in a pilot study using galvanic skin response and questionnaires. Brain activation pattern during tactile discrimination task before and after frustration were compared directly. Results revealed changes in brain activity in structures mostly reported in acute stress studies: striatum, cingulate cortex, insula, middle frontal gyrus and precuneus and in structures engaged in tactile Braille discrimination: SI and SII. Temperament type affected activation pattern. Subjects with low tolerance for arousal showed higher activation in the posterior cingulate gyrus, precuneus, and inferior parietal lobule than high reactivity group. Even though performance in the discrimination trials following frustration was unaltered, we observed increased activity of primary and secondary somatosensory cortex processing the tactile information. We interpret this effect as an indicator of additional involvement required to counteract the effects of frustration.

Brassinosteroids Improve Quality of Summer Tea (Camellia sinensis L.) by Balancing Biosynthesis of Polyphenols and Amino Acids.

PubMed

Li, Xin; Ahammed, Golam J; Li, Zhi-Xin; Zhang, Lan; Wei, Ji-Peng; Shen, Chen; Yan, Peng; Zhang, Li-Ping; Han, Wen-Yan

2016-01-01

Summer grown green tea is less popular due to bitterness and high astringency, which are attributed to high levels of tea polyphenols (TP) and low levels of amino acids (AA) in tea leaves (Camellia sinensis L.). Brassinosteroids (BRs), a group of steroidal plant hormones can regulate primary and secondary metabolism in a range of plant species under both normal and stress conditions. However, specific effects of BRs on the photosynthesis of tea plants and the quality of summer green tea are largely unknown. Here we show that 24-epibrassinolide (EBR), a bioactive BR, promoted photosynthesis in tea plants in a concentration-dependent manner. Stimulation in photosynthesis by EBR resulted in an increased summer tea yield. Although all tested concentrations (0.01, 0.05, 0.1, 0.5, and 1.0 ppm) of EBR increased concentrations of TP and AA, a moderate concentration (0.5 ppm) caused the highest decrease in TP to AA ratio, an important feature of quality tea. Time-course analysis using 0.5 ppm EBR as foliar spray revealed that TP or AA concentration increased as early as 3 h after EBR application, reaching the highest peak at 24 h and that remained more or less stable. Importantly, such changes in TP and AA concentration by EBR resulted in a remarkably decreased but stable TP to AA ratio at 24 h and onward. Furthermore, concentrations of catechins and theanine increased, while that of caffeine remained unaltered following treatment with EBR. EBR improved activity of phenylalanine ammonia-lyase (PAL) and glutamine: 2-oxoglutarate aminotransferase (GOGAT) enzymes involved in catechins and theanine biosynthesis, respectively. Transcript analysis revealed that transcript levels of CsPAL and CsGS peaked as early as 6 h, while that of CsGOGAT peaked at 12 h following application of EBR, implying that EBR increased the concentration of TP and AA by inducing their biosynthesis. These results suggest a positive role of BR in enhancing green tea quality, which might have potential implication in improving quality of summer tea.

Brassinosteroids Improve Quality of Summer Tea (Camellia sinensis L.) by Balancing Biosynthesis of Polyphenols and Amino Acids

PubMed Central

Li, Xin; Ahammed, Golam J.; Li, Zhi-Xin; Zhang, Lan; Wei, Ji-Peng; Shen, Chen; Yan, Peng; Zhang, Li-Ping; Han, Wen-Yan

2016-01-01

Summer grown green tea is less popular due to bitterness and high astringency, which are attributed to high levels of tea polyphenols (TP) and low levels of amino acids (AA) in tea leaves (Camellia sinensis L.). Brassinosteroids (BRs), a group of steroidal plant hormones can regulate primary and secondary metabolism in a range of plant species under both normal and stress conditions. However, specific effects of BRs on the photosynthesis of tea plants and the quality of summer green tea are largely unknown. Here we show that 24-epibrassinolide (EBR), a bioactive BR, promoted photosynthesis in tea plants in a concentration-dependent manner. Stimulation in photosynthesis by EBR resulted in an increased summer tea yield. Although all tested concentrations (0.01, 0.05, 0.1, 0.5, and 1.0 ppm) of EBR increased concentrations of TP and AA, a moderate concentration (0.5 ppm) caused the highest decrease in TP to AA ratio, an important feature of quality tea. Time-course analysis using 0.5 ppm EBR as foliar spray revealed that TP or AA concentration increased as early as 3 h after EBR application, reaching the highest peak at 24 h and that remained more or less stable. Importantly, such changes in TP and AA concentration by EBR resulted in a remarkably decreased but stable TP to AA ratio at 24 h and onward. Furthermore, concentrations of catechins and theanine increased, while that of caffeine remained unaltered following treatment with EBR. EBR improved activity of phenylalanine ammonia-lyase (PAL) and glutamine: 2-oxoglutarate aminotransferase (GOGAT) enzymes involved in catechins and theanine biosynthesis, respectively. Transcript analysis revealed that transcript levels of CsPAL and CsGS peaked as early as 6 h, while that of CsGOGAT peaked at 12 h following application of EBR, implying that EBR increased the concentration of TP and AA by inducing their biosynthesis. These results suggest a positive role of BR in enhancing green tea quality, which might have potential implication in improving quality of summer tea. PMID:27625668

Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load

PubMed Central

Walsh, Lauren K.; Restaino, Robert M.; Neuringer, Martha; Manrique, Camila; Padilla, Jaume

2017-01-01

Postprandial hyperglycemia leads to a transient impairment in endothelial function; however, the mechanisms remain largely unknown. Previous work in cell culture models demonstrate that high glucose results in endoplasmic reticulum (ER) stress and, in animal studies, ER stress has been implicated as a cause of endothelial dysfunction. Herein we tested the hypothesis that acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500mg), a chemical chaperone known to alleviate ER stress, would prevent hyperglycemia-induced endothelial dysfunction. In 12 young healthy subjects (seven men, five women), brachial artery flow-mediated dilation (FMD) was assessed at baseline, 1 hour, and 2 hours post an oral glucose challenge. Subjects were tested on two separate visits in a single-blind randomized crossover design: after oral ingestion of TUDCA or placebo capsules. FMD was reduced from baseline during hyperglycemia under the placebo condition (−32% at 1 hr and −28% at 2 hr post oral glucose load; p<0.05 from baseline) but not under the TUDCA condition (−4% at 1 hr and +0.3% at 2 hr post oral glucose load; p>0.05 from baseline). Postprandial plasma glucose and insulin were not altered by TUDCA ingestion. Plasma oxidative stress markers 3-nitrotyrosine and TBARs remained unaltered throughout the oral glucose challenge in both conditions. These results suggest that hyperglycemia-induced endothelial dysfunction can be mitigated by oral administration of TUDCA, thus supporting the hypothesis that ER stress may contribute to endothelial dysfunction during postprandial hyperglycemia. PMID:27503949

Elephant grass, sugarcane, and rice bran in diets for confined sheep.

PubMed

Cutrim, Darley Oliveira; Alves, Kaliandra Souza; Oliveira, Luis Rennan Sampaio; da Conceição dos Santos, Rozilda; da Mata, Vanessa Jaqueline Veloso; do Carmo, Danilo Moreira; Gomes, Daiany Iris; Mezzomo, Rafael; de Carvalho, Francisco Fernando Ramos

2012-12-01

We aimed to evaluate the effects of diets, based on elephant grass or sugarcane as roughage and corn meal or rice bran as energy concentrate, on performance and body composition in terms of diet intake and digestibility. A total of 30 Santa Ines crossbreds (SIC), castrated male sheep with 19.8 ± 2.0 kg initial body weight (BW) were used. Six animals were slaughtered at the onset of the experiment to estimate the initial body composition for the other animals. The remaining 24 animals were distributed in a completely randomized 2 × 2 factorial design, with four treatments (two roughages and two concentrates) and six replicates. The sheep were slaughtered when they reached 30.0 kg BW. Elephant grass diets provided higher intake and digestibility than sugarcane diets for the following contents: dry matter (DM), organic matter (OM), crude protein (CP), neutral detergent fibre, minerals, total carbohydrates (TC), and total digestible nutrients (TDN). Among the concentrates, corn meal diets were associated with higher intakes than rice bran diets for the following contents: DM, OM, CP, TC, and TDN. Animals from all of the treatments exhibited low average daily weight gain and low protein and high fat and energy body levels. Sugarcane and rice bran can be used as ingredients in diets for sheep with low weight gain potential. Regardless of roughage or concentrate types used in diets for confined SIC sheep, performance and body composition remained unaltered.

Citraturic response to oral citric acid load

NASA Technical Reports Server (NTRS)

Sakhaee, K.; Alpern, R.; Poindexter, J.; Pak, C. Y.

1992-01-01

It is possible that some orally administered citrate may appear in urine by escaping oxidation in vivo. To determine whether this mechanism contributes to the citraturic response to potassium citrate, we measured serum and urinary citrate for 4 hours after a single oral load of citric acid (40 mEq.) in 6 normal subjects. Since citric acid does not alter acid-base balance, the effect of absorbed citrate could be isolated from that of alkali load. Serum citrate concentration increased significantly (p less than 0.05) 30 minutes after a single oral dose of citric acid and remained significantly elevated for 3 hours after citric acid load. Commensurate with this change, urinary citrate excretion peaked at 2 hours and gradually decreased during the next 2 hours after citric acid load. In contrast, serum and urinary citrate remained unaltered following the control load (no drug). Differences of the citratemic and citraturic effects between phases were significant (p less than 0.05) at 2 and 3 hours. Urinary pH, carbon dioxide pressure, bicarbonate, total carbon dioxide and ammonium did not change at any time after citric acid load, and did not differ between the 2 phases. No significant difference was noted in serum electrolytes, arterialized venous pH and carbon dioxide pressure at any time after citric acid load and between the 2 phases. Thus, the citraturic and citratemic effects of oral citric acid are largely accountable by provision of absorbed citrate, which has escaped in vivo degradation.

Behavioral consequences of exposure to a high fat diet during the post-weaning period in rats.

PubMed

Rabasa, Cristina; Winsa-Jörnulf, Julia; Vogel, Heike; Babaei, Carina S; Askevik, Kaisa; Dickson, Suzanne L

2016-09-01

We explored the impact of exposure to an obesogenic diet (High Fat-High Sucrose; HFS) during the post-weaning period on sweet preference and behaviors linked to reward and anxiety. All rats were fed chow. In addition a HFS-transient group had access to this diet for 10days from post-natal (PN) day 22 and a HFS-continuous group continued access until adult. Behavioral tests were conducted immediately after PN 32 (adolescence) or after PN 60 (adult) and included: the condition place preference (CPP) test for chocolate, sugar and saccharin preference (anhedonia), the elevated plus maze (anxiety-like behavior) and the locomotor response to quinpirole in the open field. Behavior was unaltered in adult rats in the HFS-transient group, suggesting that a short exposure to this obesogenic food does not induce long-term effects in food preferences, reward perception and value of palatable food, anxiety or locomotor activity. Nevertheless, rats that continued to have access to HFS ate less chocolate during CPP training and consumed less saccharin and sucrose when tested in adolescence, effects that were attenuated when these rats became adult. Moreover, behavioral effects linked to transient HFS exposure in adolescence were not sustained if the rats did not remain on that diet until adult. Collectively our data demonstrate that exposure to fat and sucrose in adolescence can induce immediate reward hypofunction after only 10days on the diet. Moreover, this effect is attenuated when the diet is extended until the adult period, and completely reversed when the HFS diet is removed. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.