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Selected Abstracts


Evidence against a sexual dimorphism in glucose and fatty acid metabolism in skeletal muscle cultures from age-matched men and post-menopausal women

ACTA PHYSIOLOGICA, Issue 3 2009
A. Rune
Abstract Aim:,In vivo whole body differences in glucose/lipid metabolism exist between men and women. Thus, we tested the hypothesis that intrinsic sex differences exist in skeletal muscle gene expression and glucose/lipid metabolism using cultured myotubes. Methods:, Myotube cultures were prepared for gene expression and metabolic studies from vastus lateralis skeletal muscle biopsies obtained from age-matched men (n = 11; 59 ± 2 years) and post-menopausal women (n = 10; 60 ± 1 years). Results:, mRNA expression of several genes involved in glucose and lipid metabolism was higher in skeletal muscle biopsies from female vs. male donors, but unaltered between the sexes in cultured myotubes. Basal and insulin-stimulated glucose uptake, as well as glucose incorporation into glycogen, was similar in myotube cultures derived from male vs. female donors. In males vs. females, insulin increased glucose uptake (1.3 ± 0.1 vs. 1.5 ± 0.1-fold respectively) and incorporation into glycogen (2.3 ± 0.3 vs. 2.0 ± 0.3-fold respectively) to the same extent. Basal fatty acid oxidation and rate of uptake/accumulation was similar between sexes. In response to the 5,AMP-activated protein kinase activator AICAR, lipid oxidation was increased to the same extent in myotubes established from male vs. female donors (1.6 ± 0.6 vs. 2.0 ± 0.3-fold respectively). Moreover, the AICAR-induced rate of uptake/accumulation was similar between sexes. Conclusion:, Differences in metabolic parameters and gene expression profiles between age-matched men and post-menopausal women noted in vivo are not observed in cultured human skeletal muscle cells. Thus, the sexual dimorphism in glucose and lipid metabolism is likely a consequence of systemic whole body factors, rather than intrinsic differences in the skeletal muscle proper. [source]


Forearm vascular and neuroendocrine responses to graded water immersion in humans

ACTA PHYSIOLOGICA, Issue 2 2000
Gabrielsen
The hypothesis that graded expansion of central blood volume by water immersion to the xiphoid process and neck would elicit a graded decrease in forearm vascular resistance was tested. Central venous pressure increased (P < 0.05) by 4.2 ± 0.4 mmHg (mean ± SEM) during xiphoid immersion and by 10.4 ± 0.5 mmHg during neck immersion. Plasma noradrenaline was gradually suppressed (P < 0.05) by 62 ± 8 and 104 ± 11 pg mL,1 during xiphoid and neck immersion, respectively, indicating a graded suppression of sympathetic nervous activity. Plasma concentrations of arginine vasopressin were suppressed by 1.5 ± 0.5 pg mL,1 (P < 0.05) during xiphoid immersion and by 2.0 ± 0.5 pg mL,1 during neck immersion (P < 0.05 vs. xiphoid immersion). Forearm subcutaneous vascular resistance decreased to the same extent by 26 ± 9 and 28 ± 4% (P < 0.05), respectively, during both immersion procedures, whereas forearm skeletal muscle vascular resistance declined only during neck immersion by 27 ± 6% (P < 0.05). In conclusion, graded central blood volume expansion initiated a graded decrease in sympathetic nervous activity and AVP-release. Changes in forearm subcutaneous vascular resistance, however, were not related to the gradual withdrawal of the sympathetic and neuroendocrine vasoconstrictor activity. Forearm skeletal muscle vasodilatation exhibited a more graded response with a detectable decrease only during immersion to the neck. Therefore, the forearm subcutaneous vasodilator response reaches saturation at a lower degree of central volume expansion than that of forearm skeletal muscle. [source]


Differential effects of stress and amphetamine administration on Fos-like protein expression in corticotropin releasing factor-neurons of the rat brain

DEVELOPMENTAL NEUROBIOLOGY, Issue 6 2007
David Rotllant
Abstract Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source]


Activity-dependent regulation of synaptic size in Drosophila neuromuscular junctions

DEVELOPMENTAL NEUROBIOLOGY, Issue 9 2006
Hiroaki Nakayama
Abstract One of the fundamental questions in neural development is how neurons form synapses of the appropriate size for the efficient transfer of information across neural circuits. Here we investigated the mechanisms that bring about the size correlation between synapses and postsynaptic cells during development of Drosophila neuromuscular junctions (NMJs). To do this, we made use of a unique system in which two neighboring muscles (M6 and M7) are innervated by the same neurons. In mature NMJs, synaptic size on M6 is normally larger than that on M7, in accordance with the difference in muscle volume; this ensures the same extent of contraction of both muscles, and we refer to this correspondence as "matching". We found that matching was apparent in larvae 8 h after hatching, but not in newly hatched larvae despite the difference in muscle volume. When sensory inputs were suppressed by the expression of tetanus toxin in sensory neurons, matching did not occur, although synapses were able to grow. Matching was also suppressed by the inhibition of motoneuronal activity. These results suggest that matching is induced by regulating the rate of synaptic growth on M6 and M7 in an experience- and activity-dependent manner. It seems most likely that retrograde signals from the postsynaptic to the presynaptic cell convey the information about muscle cell size. We thus examined whether a candidate of retrograde signaling in NMJs, BMP signaling, is involved inmatching. However, there was no effect on matching inBMP type II receptor gene mutants, suggesting thatother experience-driven mechanisms besides BMP signaling are involved in the proper development of synapses. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source]


Effects of species and habitat positional errors on the performance and interpretation of species distribution models

DIVERSITY AND DISTRIBUTIONS, Issue 4 2009
Patrick E. Osborne
Abstract Aim, A key assumption in species distribution modelling is that both species and environmental data layers contain no positional errors, yet this will rarely be true. This study assesses the effect of introduced positional errors on the performance and interpretation of species distribution models. Location, Baixo Alentejo region of Portugal. Methods, Data on steppe bird occurrence were collected using a random stratified sampling design on a 1-km2 pixel grid. Environmental data were sourced from satellite imagery and digital maps. Error was deliberately introduced into the species data as shifts in a random direction of 0,1, 2,3, 4,5 and 0,5 pixels. Whole habitat layers were shifted by 1 pixel to cause mis-registration, and the cumulative effect of one to three shifted layers investigated. Distribution models were built for three species using three algorithms with three replicates. Test models were compared with controls without errors. Results, Positional errors in the species data led to a drop in model performance (larger errors having larger effects , typically up to 10% drop in area under the curve on average), although not enough for models to be rejected. Model interpretation was more severely affected with inconsistencies in the contributing variables. Errors in the habitat layers had similar although lesser effects. Main conclusions, Models with species positional errors are hard to detect, often statistically good, ecologically plausible and useful for prediction, but interpreting them is dangerous. Mis-registered habitat layers produce smaller effects probably because shifting entire layers does not break down the correlation structure to the same extent as random shifts in individual species observations. Spatial autocorrelation in the habitat layers may protect against species positional errors to some extent but the relationship is complex and requires further work. The key recommendation must be that positional errors should be minimised through careful field design and data processing. [source]


Morphological constancy in spelling: a comparison of children with dyslexia and typically developing children

DYSLEXIA, Issue 3 2008
Derrick C. Bourassa
Abstract The spellings of many English words follow a principle of morphological constancy. For example, musician includes the c of music, even though the pronunciation of this letter changes. With other words, such as explanation and explain, the spellings of morphemes are not retained when affixes are added. We asked whether children with dyslexia use root morphemes to aid their spelling of morphologically complex words. If so, they should sometimes produce misspellings such as ,explaination' for explanation. Our results suggest that children with dyslexia adhere to the principle of morphological constancy to the same extent as typically developing younger children of the same spelling level. In this and other ways, the spellings of older dyslexic children are remarkably similar to those of typical younger children. Copyright © 2008 John Wiley & Sons, Ltd. [source]


Validity of Revised Doppler Echocardiographic Algorithms and Composite Clinical and Angiographic Data in Diagnosis of Diastolic Dysfunction

ECHOCARDIOGRAPHY, Issue 10 2006
Kofo O. Ogunyankin M.D.
Background: Commonly used echocardiographic indices for grading diastolic function predicated on mitral inflow Doppler analysis have a poor diagnostic concordance and discriminatory value. Even when combined with other indices, significant overlap prevents a single group assignment for many subjects. We tested the relative validity of echocardiographic and clinical algorithms for grading diastolic function in patients undergoing cardiac catheterization. Method: Patients (n = 115), had echocardiograms immediately prior to measuring left ventricular (LV) diastolic (pre-A, mean, end-diastolic) pressures. Diastolic function was classified into the traditional four stages, and into three stages using a new classification that obviates the pseudonormal class. Summative clinical and angiographic data were used in a standardized fashion to classify each patient according to the probability for abnormal diastolic function. Measured LV diastolic pressure in each patient was compared with expected diastolic pressures based on the clinical and echocardiographic classifications. Result: The group means of the diastolic pressures were identical in patients stratified by four-stage or three-stage echocardiographic classifications, indicating that both classifications schemes are interchangeable. When severe diastolic dysfunction is diagnosed by the three-stage classification, 88% and 12%, respectively, were clinically classified as high and intermediate probability, and the mean LV pre-A pressures was >12 mmHg (P < 0.005). Conversely, the mean LV pre-A pressure in the clinical low probability or echocardiographic normal groups was <11 mmHg. Conclusion: Use of a standardized clinical algorithm to define the probability of diastolic function identifies patients with elevated LV filing pressure to the same extent as echocardiographic methods. [source]


Has the ECB increased interest rates too soon?

ECONOMIC OUTLOOK, Issue 1 2006
Article first published online: 26 JAN 200
Even though the Eurozone recovery is far from entrenched, the ECB decided to raise interest rates towards the end of 2005 and another hike is expected soon. Those in the ECB who have been looking for a reason to start tightening for some time can point to an inflation rate that remains stubbornly above target as a justification. In this article we find that the price rises of non-energy industrial goods - particularly those for clothing and footwear - have remained very sticky when compared to the deflation seen in countries like the UK. A lack of competitive forces may be an issue - the impact of China and India on goods prices does not seem to be fully feeding through to consumers. And weak productivity in the distribution sector may have prevented retailers from driving down prices to the same extent as in the UK. Does the current ECB action form the start of a prolonged tightening cycle as seen in the US? Despite worries over asset price and credit growth - and here we argue that the ECB's reliance on monetary aggregates as a signal of impending inflation is misguided - there is a possibility that the ECB has acted at the same time that inflation is finally set to subside. Consequently, we expect a "wait and see" approach to further moves, and unless growth comes in much stronger than the 2.2% we expect in 2006, rates should end the year at around 2½%. [source]


Vitamins A1 and A2 in hepatic tissue and subcellular fractions in mink feeding on fish-based diets and exposed to Aroclor 1242

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2002
Anne Käkelä
Abstract Two-month-old female mink were fed diets based on either Baltic herring (Clupea harengus membras) or freshwater smelt (Osmerus eperlanus) for 21 weeks. A portion of the smelt-fed mink were exposed orally to polychlorinated biphenyls (PCBs), Aroclor 1242 (1 mg/d). Retinol (vitamin A1), 3,4-didehydroretinol (vitamin A2), and their different fatty acyl esters were studied in hepatic tissue, microsomes, and cytosol by argentated reversed-phase high-performance liquid chromatography. As a result of Aroclor exposure, concentrations of the fatty acyl esters of vitamins A1 and A2 were about one-tenth and those of unesterified A2 one-fourth those of the control levels. In the fatty acyl esters, percentages of stearates (A1 -18:0 and A2 -18:0) increased at the expense of the other fatty acyl esters. The Aroclor exposure decreased concentrations of alcoholic and esterified forms of the A2 analog more than those of the corresponding A1 analog. In microsomes, Aroclor decreased the alcoholic and esterified vitamin analogs to the same extent (to 9,17%). In the cytosol compared to the control, the concentrations of the vitamin esters fell below 10%, but the alcoholic analogs remained at 30 to 40%. Despite equal dietary supply, in mink fed on Baltic herring, the hepatic levels of vitamin A1 were only about one-third of the values found in the smelt-fed mink. The organochlorines also altered hepatic lipid composition and impaired breeding and kit growth. In the kits of the females fed on Baltic herring, blood hemoglobin was decreased. [source]


Rectal Absorption of Lamotrigine Compressed Tablets

EPILEPSIA, Issue 7 2000
Angela K. Birnbaum
Summary: Purpose: Interruption of oral drug administration poses a significant clinical problem for antiepileptic drugs that have no parenteral formulation. If a drug is absorbed rectally, rectal administration can be a useful alternative when the oral route of administration is not possible. The purpose of this study was to compare the single-dose pharmacokinetics of la-motrigine (LTG) compressed tablets after rectal and oral administration in healthy volunteers. Methods: A single LTG compressed tablet (100 mg) was administered orally and rectally to 12 volunteers in this single-dose, two-period, crossover study with a 2-week washout between doses. For rectal administration, tablets were crushed and suspended in 10 mL of water. Plasma samples were collected from 0 to 120 hr after each dose and analyzed for LTG by an HPLC method developed for this investigation. Results: LTG plasma concentrations were lower after rectal administration versus oral administration. The average area under the curve was 28.90 ± 9.5 ,g/mL/hr after rectal administration and 51.71 ± 19.2 ,g/mL/hr after oral administration. The average maximum LTG concentration was 0.53 ± 0.14 ,g/mL after rectal administration and 1.45 ± 0.35 ,g/mL after oral administration. The relative bioavailability for LTG compressed tablets was 0.63 ± 0.33 for rectal administration. There were no drug-related rashes or serious side effects. Conclusions: LTG suspension prepared from LTG compressed tablets is absorbed rectally, although not to the same extent or rate as when given orally. [source]


Divergence between the Courtship Songs of the Field Crickets Gryllus texensis and Gryllus rubens (Orthoptera, Gryllidae)

ETHOLOGY, Issue 12 2001
Mark J. Fitzpatrick
Acoustic mating signals are often important as both interspecific prezygotic isolating mechanisms and as sexually selected traits in intraspecific mate choice. Here, we investigate the potential for cricket courtship song to act as an isolating mechanism by assessing divergence between the courtship songs of Gryllus texensis and Gryllus rubens, two broadly sympatric cryptic sister species of field crickets with strong prezygotic isolation via the calling song and little or no postzygotic isolation. We found significant species-level differences in the courtship song, but the song has not diverged to the same extent as the calling song, and considerable overlap remains between these two species. Only two related courtship song characters are sufficiently distinct to play a possible role in prezygotic species isolation. [source]


The cytoplasmic tail of invariant chain modulates antigen processing and presentation

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2003

Abstract The MHC class II-associated invariant chain (Ii) has several important functions in antigen presentation. In this study, we have examined the effect of Iip33 expression on endocytic transport and antigen presentation. We find that degradation of both endocytosed antigen and Ii itself is delayed in cells expressing high levels of Ii, whereas a mutant Ii with an altered charge distributionin the cytoplasmic tail was unable to exert this effect. Furthermore, the Ii mutant did not enhance the presentation of an Ii-dependent MHC class II-restricted epitope to the same extent as the wild type. In a parallel study, we investigated the effect of charge in the cytoplasmic tail of Ii. We find that due to exposed negative charges, it promotes endosome fusion events, and we suggest thatthis causes endosomal retention (Nordeng et al., Mol. Biol. Cell 2002). Together, the data reveal an additional property of the Iip33 cytoplasmic tail that contributes to the modulation of antigen processing and presentation. [source]


Altered striatal amino acid neurotransmitter release monitored using microdialysis in R6/1 Huntington transgenic mice

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001
B. NicNiocaill
Abstract Huntington's disease is an autosomal dominant disease which presents with striatal and cortical degeneration causing involuntary movements, dementia and emotional changes. We employed 16-week-old transgenic Huntington mice (R6/1 line developed by Bates and coworkers) that express exon 1 of the mutant human Huntington gene with 115 CAG triplet repeats. At this age, R6/1 mice do not exhibit an overt neurological phenotype nor any striatal neuronal loss. Using microdialysis, we monitored basal and intrastriatal N-methyl d -aspartate (NMDA, 100 µm, 15 min)- and KCl (100 mm, 15 min)-induced increases in local aspartate, glutamate and GABA release in halothane-anaesthetized transgenic mice and wild-type controls. Basal striatal dialysate glutamate levels were reduced by 42% in R6/1 mice whilst aspartate and GABA levels did not differ from those observed in control mice. Intrastriatal NMDA was associated with significantly greater aspartate (at 15 min) and GABA (at 30 min) levels in the R6/1 mice compared to controls, whilst glutamate release rapidly increased to the same extent in both groups. Intrastriatal KCl was associated with enhanced increases (30 min) in local aspartate and glutamate release in the R6/1 mice above those observed in controls whilst the rapid increase (15 min) in GABA release was similar in both groups. The results provide compelling evidence for specific alterations in both basal, as well as NMDA- and KCl-induced, release of striatal amino acid neurotransmitters in this transgenic model of Huntington's disease, even in the absence of manifest neurodegeneration. [source]


The sex-peptide DUP99B is expressed in the male ejaculatory duct and in the cardia of both sexes

FEBS JOURNAL, Issue 21 2003
Albana Rexhepaj
Mating elicits two postmating responses in many insect females: the egg laying rate increases and sexual receptivity is reduced. In Drosophila melanogaster, two peptides of the male genital tract, sex-peptide and DUP99B, elicit these postmating responses when injected into virgin females. Here we show that the gene encoding DUP99B is expressed in the male ejaculatory duct and in the cardia of both sexes. The DUP99B that is synthesized in the ejaculatory duct is transferred, during mating, into the female genital tract. Expression of the gene is first seen in a late pupal stage. Males containing an intact ejaculatory duct, but lacking accessory glands, initiate the two postmating responses in their female partners [Xue, L. & Noll, M. (2000) Proc. Natl Acad. Sci. USA97, 3272,3275]. Although such males synthesize DUP99B in wild-type quantities, they elicit only weak postmating responses in their mating partners. Males lacking the Dup99B gene elicit the two postmating responses to the same extent as wild-type males. These results suggest that both sex-peptide and DUP99B can elicit both responses in vivo. However, sex-peptide seems to play the major role in eliciting the postmating responses, while DUP99B may have specialized for other, as yet unknown, functions. [source]


Identification of two cysteine residues involved in the binding of UDP-GalNAc to UDP-GalNAc:polypeptide N -acetylgalactosaminyltransferase 1 (GalNAc-T1)

FEBS JOURNAL, Issue 17 2002
Mari Tenno
Biosynthesis of mucin-type O-glycans is initiated by a family of UDP-GalNAc:polypeptide N -acetylgalactosaminyltransferases, which contain several conserved cysteine residues among the isozymes. We found that a cysteine-specific reagent, p- chloromercuriphenylsulfonic acid (PCMPS), irreversibly inhibited one of the isozymes (GalNAc-T1). Presence of either UDP-GalNAc or UDP during PCMPS treatment protected GalNAc-T1 from inactivation, to the same extent. This suggests that GalNAc-T1 contains free cysteine residues interacting with the UDP moiety of the sugar donor. For the functional analysis of the cysteine residues, several conserved cysteine residues in GalNAc-T1 were mutated individually to alanine. All of the mutations except one resulted in complete inactivation or a drastic decrease in the activity, of the enzyme. We identified only Cys212 and Cys214, among the conserved cysteine residues in GalNAc-T1, as free cysteine residues, by cysteine-specific labeling of GalNAc-T1. To investigate the role of these two cysteine residues, we generated cysteine to serine mutants (C212S and C214S). The serine mutants were more active than the corresponding alanine mutants (C212A and C214A). Kinetic analysis demonstrated that the affinity of the serine-mutants for UDP-GalNAc was decreased, as compared to the wild type enzyme. The affinity for the acceptor apomucin, on the other hand, was essentially unaffected. The functional importance of the introduced serine residues was further demonstrated by the inhibition of all serine mutant enzymes with diisopropyl fluorophosphate. In addition, the serine mutants were more resistant to modification by PCMPS. Our results indicate that Cys212 and Cys214 are sites of PCMPS modification, and that these cysteine residues are involved in the interaction with the UDP moiety of UDP-GalNAc. [source]


Identification of the epidermal growth factor-like domains of thrombomodulin essential for the acceleration of thrombin-mediated inactivation of single-chain urokinase-type plasminogen activator

FEBS JOURNAL, Issue 21 2001
Ellen A. M. Schenk-Braat
Single-chain urokinase-type plasminogen activator (scu-PA) can be cleaved by thrombin into a virtually inactive form called thrombin-cleaved two-chain urokinase-type plasminogen activator (tcu-PA/T), a process accelerated by thrombomodulin, which contains six epidermal growth factor (EGF)-like domains. In this study, we identified the EGF-like domains of thrombomodulin required for the acceleration of the inactivation of scu-PA by thrombin using various forms of thrombomodulin (TM). scu-PA was treated with thrombin in the absence and presence of full-length rabbit TM (containing EGF1-6), recombinant TM comprising all of the extracellular domains including EGF1-6 (TMLEO) and recombinant TM comprising EGF4-6 plus the interconnecting region between EGF3 and EGF4 (TMEi4-6), and the tcu-PA/T generated was quantitated in each case. Rabbit TM accelerated the inactivation of scu-PA ,,35-fold, while both recombinant forms accelerated it only threefold due to the absence of a critical chondroitin sulfate moiety. Subsequently, TME5-6 was prepared by cyanogen bromide digestion of TMEi4-6. TME5-6 bound to thrombin but did not accelerate the activation of protein C. In contrast, the inactivation of scu-PA by thrombin was accelerated to the same extent as that induced by TMLEO and TMEi4-6. This study demonstrates that, in addition to the chondroitin sulfate moiety, only EGF-like domains 5 and 6 are essential for the acceleration of the inactivation of scu-PA by thrombin. This differs from the domains that are critical for activation of protein C (EGF-like domains i4,6) and thrombin activatable fibrinolysis inhibitor (EGF-like domains 3,6). [source]


Mutation of residues in the coenzyme binding pocket of Dopa decarboxylase

FEBS JOURNAL, Issue 10 2001
Effects on catalytic properties
Residues D271, H192, H302 and N300 of l -3,4-dihydroxyphenylalanine decarboxylase (DDC), a homodimeric pyridoxal 5,-phosphate (PLP) enzyme, were mutated in order to acquire information on the catalytic mechanism. These residues are potential participants in catalysis because they belong to the common PLP-binding structural motif of group I, II and III decarboxylases and other PLP enzymes, and because they are among the putative active-site residues of structural modelled rat liver DDC. The spectroscopic features of the D271E, H192Q, H302Q and N300A mutants as well as their dissociation constants for PLP suggest that substitution of each of these residues causes alteration of the state of the bound coenzyme molecule and of the conformation of aromatic amino acids, possibly in the vicinity of the active site. This supports, but does not prove, the possibility that these residues are located in the coenzyme-binding cleft. Interestingly, mutation of each residue generates an oxidative decarboxylase activity towards l -3,4-dihydroxyphenylalanine (l -Dopa), not inherent in the wild-type in aerobiosis, and reduces the nonoxidative decarboxylase activity of l -Dopa from 3- to 390-fold. The partition ratio between oxidative and nonoxidative decarboxylation ranges from 5.7 × 10,4 for N300A mutant to 946 × 10,4 for H302Q mutant. Unlike wild-type enzyme, the mutants catalyse these two reactions to the same extent either in the presence or absence of O2. In addition, all four mutants exhibit an extremely low level of the oxidative deaminase activity towards serotonin with respect to wild-type. All these findings demonstrate that although D271, H192, H302 and N300 are not essential for catalysis, mutation of these residues alters the nature of catalysis. A possible relationship among the integrity of the PLP cleft, the productive binding of O2 and the transition to a closed conformational state of DDC is discussed. [source]


Limitation of oxygenic photosynthesis and oxygen consumption by phosphate and organic nitrogen in a hypersaline microbial mat: a microsensor study

FEMS MICROBIOLOGY ECOLOGY, Issue 1 2006
Rebecca Ludwig
Abstract Microbial mats are characterized by high primary production but low growth rates, pointing to a limitation of growth by the lack of nutrients or substrates. We identified compounds that instantaneously stimulated photosynthesis rates and oxygen consumption rates in a hypersaline microbial mat by following the short-term response (c. 6 h) of these processes to addition of nutrients, organic and inorganic carbon compounds, using microsensors. Net photosynthesis rates were not stimulated by compound additions. However, both gross photosynthesis and oxygen consumption were substantially stimulated (by a minimum of 25%) by alanine (1 mM) and glutamate (3.5 mM) as well as by phosphate (0.1 mM). A low concentration of ammonium (0.1 mM) did not affect photosynthesis and oxygen consumption, whereas a higher concentration (3.5 mM) decreased both process rates. High concentrations of glycolate (5 mM) and phosphate (1 mM) inhibited gross photosynthesis but not oxygen consumption, leading to a decrease of net photosynthesis. Photosynthesis was not stimulated by addition of inorganic carbon, nor was oxygen consumption stimulated by organic compounds like glycolate (5 mM) or glucose (5 mM), indicating that carbon was efficiently cycled within the mat. Photosynthesis and oxygen consumption were apparently tightly coupled, because stimulations always affected both processes to the same extent, which resulted in unchanged net photosynthesis rates. These findings illustrate that microsensor techniques, due to their ability to quantify all three processes, can clarify community responses to nutrient enrichment studies much better than techniques that solely monitor net fluxes. [source]


Lack of main K+ uptake systems in Saccharomyces cerevisiae cells affects yeast performance in both potassium-sufficient and potassium-limiting conditions

FEMS YEAST RESEARCH, Issue 5 2010
Clara Navarrete
Abstract A new YNB medium containing very low concentrations of alkali metal cations has been developed to carry out experiments to study potassium homoeostasis. Physiological characterization of Saccharomyces cerevisiae BY4741 strain and the corresponding mutant lacking the main potassium uptake systems (trk1 trk2) under potassium nonlimiting and limiting concentrations was performed, and novel important differences between both strains were found. At nonlimiting concentrations of KCl, the two strains had a comparable cell size and potassium content. Nevertheless, mutants were hyperpolarized, had lower pH and extruded fewer protons compared with the BY4741 strain. Upon transfer to K+ -limiting conditions, cells of both strains became hyperpolarized and their cell volume and K+ content diminished; however, the decrease was more relevant in BY4741. In low potassium, trk1 trk2 cells were not able to accomplish the cell cycle to the same extent as in BY4741. Moreover, K+ limitation triggered a high-affinity K+/Rb+ uptake process only in BY4741, with the highest affinity being reached as soon as 30 min after transfer to potassium-limiting conditions. By establishing basic cellular parameters under standard growth conditions, this work aims to establish a basis for the investigation of potassium homoeostasis at the system level. [source]


Modelling the impact of benthic filter-feeders on the composition and biomass of river plankton

FRESHWATER BIOLOGY, Issue 3 2003
J.-P. Descy
SUMMARY 1. The POTAMON model [Everbecq E. et al. (2001) Water Research, 35, 901] has been used to simulate the effect of benthic bivalves (mainly Dreissena polymorpha) on the phytoplankton and zooplankton in a lowland Western European river (the Moselle). Here we use a modified version of the POTAMON model with five categories of phytoplankton (Stephanodiscus, Cyclotella -like, large diatoms, Skeletonema and non-siliceous algae) to model filter-feeding effects of benthic bivalves in the Moselle. Zooplankton has been represented in the model by two categories, Brachionus -like and Keratella -like rotifers. 2. According to density estimates from field surveys (Bachmann V. et al. (1995) Hydroécologie Appliquée, 7, 185, Bachmann V. & Usseglio-Polatera P. (1999) Hydrobiologia, 410, 39), zebra mussel density varied among river stretches, and increased through the year to a maximum in summer. Dreissena filtration rates from the literature were used, and mussels have been assumed to feed on different phytoplankton categories (but less on large and filamentous diatoms) as well as on rotifers. 3. The simulations suggest a significant impact of benthic filter-feeders on potamoplankton and water quality in those stretches where the mussels are abundant, their impact being maximal in summer. Consequently, different plankton groups were not affected to the same extent, depending on their period of development and on indirect effects, such as predation by mussels on herbivorous zooplankton. 4. A daily carbon balance for a typical summer shows the effect of benthic filter-feeders on planktonic and benthic processes: the flux of organic matter to the bottom is greatly enhanced at high mussel density; conversely, production and breakdown of organic carbon in the water column are reduced. Mussel removal would drive the carbon balance of the river toward autotrophy only in the downstream stretches. [source]


Lactate and free glucose in supercooled hatchling Painted Turtles (Chrysemys picta) exposed to natural and semi-natural thermal regimes

FUNCTIONAL ECOLOGY, Issue 3 2005
M. J. PACKARD
Summary 1Hatchlings of the North American Painted Turtle, Chrysemys picta (Schneider 1783) typically spend their first winter of life inside a shallow, terrestrial hibernaculum (the natal nest) where they commonly are exposed for extended periods to ice and cold. Current evidence indicates that turtles withstand such exposure by resisting freezing and becoming supercooled. 2Supercooled hatchlings held at constant temperatures in the laboratory experience circulatory impairment and stagnant hypoxia, and consequently rely on anaerobic metabolism to meet a portion of their energy needs. As a result, lactate accumulates in bodies of supercooled animals. 3The first experiment in the current investigation demonstrated that unfrozen hatchlings exposed to subzero temperatures like those recorded in a natural hibernaculum contained elevated quantities of lactic acid (and free glucose). This finding validates the widespread reliance on laboratory studies to gain insights regarding the physiology of animals overwintering in the field. 4In a second study, hatchling Painted Turtles held for 20 days at ,6 °C contained nearly twice as much lactate as turtles sampled after 10 days at that temperature. Hatchlings held for 10 days at ,6 °C and then for another 10 days at ,3 °C also contained more lactate than turtles sampled after 10 days at ,6 °C, but not as much as the hatchlings that spent 20 days at ,6 °C. Thus, animals held for part of the time at the higher subzero temperature still relied on anaerobic metabolism, but not to the same extent as turtles held continuously at the lower temperature. In contrast, hatchlings held for 10 days at ,6 °C and then for another 10 days at either 0 °C or +3 °C contained no more lactate than control animals that never were exposed to subzero temperatures. Hatchlings exposed for the second 10 days to either 0 °C or +3 °C apparently were able to catabolize or otherwise process all the lactate that was accumulated during the first 10 days of their treatment. 5Free glucose in bodies of hatchlings was elevated in all animals exposed to subzero temperatures, even when the initial exposure was followed by 10 days at temperatures as high as +3 °C. This finding has important implications with regard to the substrate that is used to support intermediary metabolism in supercooled turtles as well as to the metabolic pathways that are used to remove accumulated lactate once body temperature of the turtles rises at least to 0 °C. [source]


Genetic and environmental influences on Anxious/Depression during childhood: a study from the Netherlands Twin Register

GENES, BRAIN AND BEHAVIOR, Issue 8 2005
D. I. Boomsma
For a large sample of twin pairs from the Netherlands Twins Register who were recruited at birth and followed through childhood, we obtained parental ratings of Anxious/Depression (A/D). Maternal ratings were obtained at ages 3 years (for 9025 twin pairs), 5 years (9222 pairs), 7 years (7331 pairs), 10 years (4430 pairs) and 12 years (2363 pairs). For 60,90% of the pairs, father ratings were also available. Multivariate genetic models were used to test for rater-independent and rater-specific assessments of A/D and to determine the genetic and environmental influences on individual differences in A/D at different ages. At all ages, monozygotic twins resembled each other more closely for A/D than dizygotic twins, implying genetic influences on variation in A/D. Opposite sex twin pairs resembled each other to same extent as same-sex dizygotic twins, suggesting that the same genes are expressed in boys and girls. Heritability estimates for rater-independent A/D were high in 3-year olds (76%) and decreased in size as children grew up [60% at age 5, 67% at age 7, 53% at age 10 (60% in boys) and 48% at age 12 years]. The decrease in genetic influences was accompanied by an increase in the influence of the shared family environment [absent at ages 3 and 7, 16% at age 5, 20% at age 10 (5% in boys) and 18% at age 12 years]. The agreement between parental A/D ratings was between 0.5 and 0.7, with somewhat higher correlations for the youngest group. Disagreement in ratings between the parents was not merely the result of unreliability or rater bias. Both the parents provided unique information from their own perspective on the behavior of their children. Significant influences of genetic and shared environmental factors were found for the unique parental views. At all ages, the contribution of shared environmental factors to variation in rater-specific views was higher for father ratings. Also, at all ages except age 12, the heritability estimates for the rater-specific phenotype were higher for mother ratings (59% at age 3 and decreasing to 27% at age 12 years) than for father ratings (between 14 and 29%). Differences between children, even as young as 3 years, in A/D are to a large extent due to genetic differences. As children grow up, the variation in A/D is due in equal parts to genetic and environmental influences. Anxious/Depression, unlike many other common childhood psychopathologies, is influenced by the shared family environment. These findings may provide support for why certain family therapeutic approaches are effective in the A/D spectrum of illnesses. [source]


Estimating monthly surface winds for Scania, southern Sweden, using geostrophic wind (1899,1997)

GEOGRAFISKA ANNALER SERIES A: PHYSICAL GEOGRAPHY, Issue 2 2002
Marie Ekström
Wind direction conditions during the 20th century in Scania, southern Sweden, are investigated using an estimated series of monthly wind vector components (east,west u component and north,south v component). The series is developed from a regression relationship between pairwise (1973 to 1997) monthly averages of 10,m surface wind from Scania and a monthly geostrophic wind, based on mean sea level (MSL) pressure data from the National Center of Atmospheric Research (NCAR). The wind conditions during the 20th century are dominated by winds from southwesterly and westerly directions, particularly during summer and autumn. From the 1980s onwards, increased frequencies of westerly winds are evident in spring and summer; however, similarly large frequencies of westerly winds are also found during the early part of the 20th century. Analysis of the estimated wind series indicates large variation in wind direction during the investigated time period, particularly during 1930 to 1960 when large increases of easterly winds are evident in spring. Increased frequencies of easterly winds were also found in other months during this period but not to the same extent as during the spring season. Thus, the presence of periods with quite different wind characteristics suggests that the overall atmospheric circulation has experienced some shifts in this region during the 20th century. [source]


Surgical treatment of migraine headaches.

HEADACHE, Issue 3 2003
B Guyuron
Plast Reconstr Surg. 2002 Jun;109(7):2183-2189 This prospective study was conducted to investigate the role of removal of corrugator supercilii muscles, transection of the zygomaticotemporal branch of the trigeminal nerve, and temple soft-tissue repositioning in the treatment of migraine headaches. Using the criteria set forth by the International Headache Society, the research team's neurologist evaluated patients with moderate to severe migraine headaches, to confirm the diagnosis. Subsequently, the patients completed a comprehensive migraine headaches questionnaire and the team's plastic surgeon injected 25 units of botulinum toxin type A (Botox) into each corrugator supercilii muscle. The patients were asked to maintain an accurate diary of their migraine headaches and to complete a monthly questionnaire documenting pertinent information related to their headaches. Patients in whom the injection of Botox resulted in complete elimination of the migraine headaches then underwent resection of the corrugator supercilii muscles. Those who experienced only significant improvement underwent transection of the zygomaticotemporal branch of the trigeminal nerve with repositioning of the temple soft tissues, in addition to removal of the corrugator supercilii muscles. Once again, patients kept a detailed postoperative record of their headaches. Of the 29 patients included in the study, 24 were women and five were men, with an average age of 44.9 years (range, 24 to 63 years). Twenty-four of 29 patients (82.8 percent, p < 0.001) reported a positive response to the injection of Botox, 16 (55.2 percent, p < 0.001) observed complete elimination, eight (27.6 percent, p < 0.04) experienced significant improvement (at least 50 percent reduction in intensity or severity), and five (17.2 percent, not significant) did not notice a change in their migraine headaches. Twenty-two of the 24 patients who had a favorable response to the injection of Botox underwent surgery, and 21 (95.5 percent, p < 0.001) observed a postoperative improvement. Ten patients (45.5 percent, p < 0.01) reported elimination of migraine headaches and 11 patients (50.0 percent, p < 0.004) noted a considerable improvement. For the entire surgical group, the average intensity of the migraine headaches reduced from 8.9 to 4.1 on an analogue scale of 1 to 10, and the frequency of migraine headaches changed from an average of 5.2 per month to an average of 0.8 per month. For the group who only experienced an improvement, the intensity fell from 9.0 to 7.5 and the frequency was reduced from 5.6 to 1.0 per month. Only one patient (4.5 percent, not significant) did not notice any change. The follow-up ranged from 222 to 494 days, the average being 347 days. In conclusion, this study confirms the value of surgical treatment of migraine headaches, inasmuch as 21 of 22 patients benefited significantly from the surgery. It is also evident that injection of Botox is an extremely reliable predictor of surgical outcome. Comment: Many small placebo-controlled studies and much anecdotal literature suggests that botulinum toxin may be effective in prevention of migraine, perhaps to the same extent as conventional prophylactic treatment. Larger, randomized clinical trials are underway to resolve this issue. In the meantime, those who believe in the effectiveness of botulinum toxin prophylaxis argue about how it works, that is whether its antinociceptive properties are due to peripheral effects, central or presynaptic effects, or both. Dr. Guyuron's group favors the idea that botulinum toxin interrupts a reflex arc between the central nervous system (CNS) and peripheral musculature, and that after establishing efficacy by low dose botulinum injection in the corrugator supercilii muscles, surgical resection of these muscles results in prolonged and effective prophylaxis. The idea is radical but intriguing and should not be dismissed out of hand. However, a trial is necessary in which both the botulinum toxin injections are blinded with vehicle, and the study of the surgery involves a sham surgery control group with extended long-term follow-up, before these forms of prophylaxis can be recommended to patients. SJT [source]


The Effect of the cag Pathogenicity Island on Binding of Helicobacter pylori to Gastric Epithelial Cells and the Subsequent Induction of Apoptosis

HELICOBACTER, Issue 6 2007
Yutaka Minohara
Abstract Background:,Helicobacter pylori infection leads to gastritis, peptic ulcer, and gastric cancer, in part due to epithelial damage following bacteria binding to the epithelium. Infection with cag pathogenicity island (PAI) bearing strains of H. pylori is associated with increased gastric inflammation and a higher incidence of gastroduodenal diseases. It is now known that various effector molecules are injected into host epithelial cells via a type IV secretion apparatus, resulting in cytoskeletal changes and chemokine secretion. Whether binding of bacteria and subsequent apoptosis of gastric epithelial cells are altered by cag PAI status was examined in this study. Methods:, AGS, Kato III, and N87 human gastric epithelial cell lines were incubated with cag PAI-positive or cag PAI-negative strains of H. pylori in the presence or absence of clarithromycin. Binding was evaluated by flow cytometry and scanning electron microscopy. Apoptosis was assessed by detection of DNA degradation and ELISA detection of exposed histone residues. Results:,cag PAI-negative strains bound to gastric epithelial cells to the same extent as cag PAI-positive strains. Both cag PAI-positive and cag PAI-negative strains induced apoptosis. However, cag PAI-positive strains induced higher levels of DNA degradation. Incubation with clarithromycin inactivated H. pylori but did not affect binding. However, pretreatment with clarithromycin decreased infection-induced apoptosis. Conclusions:,cag PAI status did not affect binding of bacteria to gastric epithelial cells but cag PAI-positive H. pylori induced apoptosis more rapidly than cag PAI-negative mutant strains, suggesting that H. pylori binding and subsequent apoptosis are differentially regulated with regard to bacterial properties. [source]


Transamination by Polymeric Enzyme Mimics

HELVETICA CHIMICA ACTA, Issue 11 2003
Wenjun Zhou
Pyridoxamine was linked to a series of polyethylenimines (PEIs) with Mn=600, 1800, 10,000, and 60,000, both simply permethylated and with additional attached dodecyl chains. They were examined in the transamination of pyruvic acid and of phenylpyruvic acid, and showed MichaelisMenten behavior. The values of k2 and of KM determined showed only small variations with polymer size. Thus, the previously reported strong advantage of pyridoxamines attached to the Mn=60,000 PEI, relative to simple pyridoxamine alone, is seen to almost the same extent with the smaller PEIs. [source]


Alcohol-induced alterations in hepatic microtubule dynamics can be explained by impaired histone deacetylase 6 function,

HEPATOLOGY, Issue 5 2008
Blythe D. Shepard
We have been using polarized, hepatic WIF-B cells to examine ethanol-induced liver injury. These cells polarize in culture and maintain numerous liver-specific activities including the ability to metabolize alcohol. Previously, we found that microtubules were more highly acetylated and more stable in ethanol-treated WIF-B cells and that increased microtubule acetylation required ethanol metabolism and was likely mediated by acetaldehyde. This study was aimed at identifying the mechanism responsible for increased microtubule acetylation. We examined the expression of two known microtubule deacetylases, histone deacetylase 6 (HDAC6) and Sirtuin T2 (SirT2), in WIF-B cells. Immunoblotting, immunofluorescence microscopy, and assays using the SirT2 inhibitor nicotinamide revealed that WIF-B cells do not express SirT2. In contrast, HDAC6 was highly expressed in WIF-B cells. Addition of trichostatin A (TSA), an HDAC6 inhibitor, induced microtubule acetylation to the same extent as in ethanol-treated cells (approximately threefold). Although immunofluorescence labeling revealed that HDAC6 distribution did not change in ethanol-treated cells, immunoblotting showed HDAC6 protein levels slightly decreased. HDAC6 solubility was increased in nocodazole-treated cells, suggesting impaired microtubule binding. Direct microtubule binding assays confirmed this hypothesis. The decreased microtubule binding was partially prevented by 4-methyl pyrazole, indicating the effect was in part mediated by acetaldehyde. Interestingly, HDAC6 from ethanol-treated cells was able to bind and deacetylate exogenous tubulin to the same extent as control, suggesting that ethanol-induced tubulin modifications prevented HDAC6 binding to endogenous microtubules. Conclusion: We propose that lower HDAC6 levels combined with decreased microtubule binding lead to increased tubulin acetylation in ethanol-treated cells. (HEPATOLOGY 2008.) [source]


Measurement of racial life events in schizophrenia: development of a new schedule , a pilot study

INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2001
Dinesh Bhugra
Abstract The relationship between stressors and the onset of psychosis is well described in the literature. However, for minority ethnic groups in the UK the impact of racism and racial life events has not been studied to the same extent. In this paper we describe the development of a semi-structured interview , Racial Life Events Schedule (RALES) , in order to measure racial life events as well as continuing difficulties attributable to racial discrimination. The interview was piloted on 12 African-Caribbean and eight Asian patients presenting with first onset schizophrenia. The interview was useful in eliciting racial events but overall there were no differences between patients and community controls. We believe that this schedule is useful for understanding racial events in the individual's personal and cultural context. The development and the schedule are described in this paper. Copyright © 2001 Whurr Publishers Ltd. [source]


Cross-cultural study on adult age-group differences in the recall of the literal and interpretive meanings of narrative text1

JAPANESE PSYCHOLOGICAL RESEARCH, Issue 2 2006
AYA HOSOKAWA
Abstract:, This study examined cultural and age differences in the recall of the literal and interpretive meanings of narrative text. Twenty Japanese younger adults (age: M = 21.05, SD = 1.02), 20 Japanese older adults (age: M = 66.95, SD = 1.71), 20 American younger adults (age M = 21.7, SD = 1.76), and 16 American older adults (age M = 69.56, SD = 3.43) participated in this study. One story rich in both literal and interpretive content was used as a stimulus text for two recall tasks, to retell and interpret the story. The response task order was counterbalanced across the participants for each group. When asked to retell a story as close to the original as possible, the younger adults in both of the two cultural groups recalled more of the literal propositions than did the older adults. Both older and younger adults in the two cultural groups recalled more of the main ideas relative to the details; however, when asked to interpret the same story, more older than younger adults represented deep and synthetic representations of the story's interpretive meanings in the Japanese group. The interpretive responses by both the older and younger adults were almost to the same extent on depth; however, the younger adults' responses were slightly higher on synthesis in the American group. These interpretive patterns stem from cultural background. [source]


Lack of Interaction between Extreme High-Temperature Events at Vegetative and Reproductive Growth Stages in Wheat

JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 3 2003
B. Wollenweber
Abstract Increased climatic variability and more frequent episodes of extreme conditions may result in crops being exposed to more than one extreme temperature event in a single growing season and could decrease crop yields to the same extent as changes in mean temperature. The developmental stage of the crop exposed to increased temperatures will determine the severity of possible damage experienced by the plant. It is not known whether or not the damaging effects of heat episodes occurring at different phenological stages are additive. In the present study, the interaction of high-temperature events applied at the stages of double ridges and anthesis in Triticum aestivum (L.) cv. Chablis was investigated. Biomass accumulation of control plants and that of plants experiencing high temperatures during the double-ridge stage were similar and were reduced by 40 % when plants were subjected to a heat event at anthesis. Grain number on the main and side tillers declined by 41 %, and individual grain weight declined by 45 % with heat stress applied at the double-ridge stage and anthesis or at anthesis alone. The harvest index was reduced from 0.53 to 0.33. Nitrogen contents in leaves were reduced by 10 % at the double-ridge stage and by 25 % at anthesis. The maximum rates of CO2 assimilation increased with heat stress at the double-ridge stage and higher rates were maintained throughout the growing season. The results clearly indicate that an extreme heat event at the double-ridge stage does not affect subsequent growth or the response of wheat to heat stress at anthesis. [source]