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Acute and subchronic effects of clozapine on licking in rats: tolerance to disruptive effects on number of licks, but no tolerance to rhythm slowing.

In order to assess the effects of the atypical neuroleptic clozapine on orolingual competence in rats, tongue function was measured by quantitating the rhythm of tongue movements after acute (1.0, 3.0, 6.0 mg/kg) or subchronic intraperitoneal treatment (1.5, 3.0, 4.5 mg/kg, each dose for at least 7 days) with the drug. Thirsty rats were trained to lick water from a force-sensing disk by thrusting the tongue through a 12-mm-diameter hole to strike the horizontal disk located 5 mm below the hole. Number of licks in 2 min and rhythm of tongue movements (as determined by Fourier analysis of the force-time signal) were each dose dependently reduced in the acute dose-effect phase of the study. In the subchronic study number of licks exhibited tolerance, but the slowing of lick rhythm did not show tolerance. An acute dose range of the serotonin antagonist ritanserin (0.5, 1.0, 2.0, 4.0 mg/kg) was also studied in the same rats. Ritanserin had no effect on any of the measures of orolingual function. The clozapine result was replicated in a second study using younger, drug naive rats. The results for clozapine were contrasted with previous reports indicating that haloperidol has little effect on lick rhythm. Additional discussion evaluated the possible contribution of neurotransmitter receptors on motor neurons of the hypoglossal nucleus to the observed rhythm slowing induced by clozapine.

Animals↗

Salt tolerance and glycerol accumulation of a respiration-deficient mutant isolated from the petite-negative, salt-tolerant yeast Zygosaccharomyces rouxii.

A respiration-deficient (RD) mutant was isolated from the petite-negative, salt-tolerant yeast Zygosaccharomyces rouxii. One strain among sixteen glycerol-non-utilizing mutants exhibited vigorous liberation of CO2 but no uptake of O2. Furthermore, this strain lacked cytochrome aa3 and had a reduced level of cytochrome b. The few mitochondria found in cells of this strain contained few or no cristae. Salt tolerance and intracellular accumulation of glycerol by the RD strain were almost equal to that of the wild-type strain in media containing NaCl up to 2.5 M. In media with more than 3 M NaCl, the growth of the RD mutant was retarded and the intracellular accumulation of glycerol was depressed in spite of ample production.

Adaptation, Biological↗

Short-term efficacy of apraclonidine hydrochloride added to maximum-tolerated medical therapy for glaucoma. Apraclonidine Maximum-Tolerated Medical Therapy Study Group.

PURPOSE: We determined whether the addition of topical apraclonidine hydrochloride to eyes that are receiving maximal medical therapy but still have inadequate intraocular pressure control and that are scheduled to undergo surgery could adequately decrease intraocular pressure, postponing the need for further intervention. METHODS: We performed a prospective, 90-day, multicentered, placebo-controlled, double-masked parallel study. We enrolled one eye each of 174 glaucoma patients with inadequate intraocular pressure control who were on maximally tolerated medical therapy. We continued to administer maximum medical therapy for glaucoma. Study medications were either apraclonidine hydrochloride 0.5% or placebo (apraclonidine's vehicle). Patients were instructed to take the study medication every eight hours. We measured intraocular pressure, change in intraocular pressure from baseline, and the number of eyes requiring surgery after the addition of study medication. RESULTS: Fifty-two (60%) of 86 patients treated with apraclonidine maintained adequate intraocular pressure control throughout the study and avoided surgery, compared with 28 (32%) of 88 patients treated with placebo (P < .001). Apraclonidine treatment resulted in significantly more patients attaining an additional 20% reduction or more in intraocular pressure from baseline and an intraocular pressure less than or equal to 20 mm Hg (P < .05). The most common ocular complication was conjunctival hyperemia (11 of 86 patients, 12.8%). The most frequent nonocular problem was dry mouth (four patients, 4.7%). CONCLUSION: Apraclonidine appeared to be safe in all eyes and efficacious in some eyes. It significantly lowered intraocular pressure when used in combination with maximally tolerated medical therapy, which delayed or prevented further glaucoma surgery for at least 90 days in 52 (60%) of 86 treated patients.

Adrenergic alpha-Agonists↗

Glyphosate-tolerant corn: the composition and feeding value of grain from glyphosate-tolerant corn is equivalent to that of conventional corn (Zea mays L.).

Glyphosate-tolerant (Roundup Ready) corn line GA21 has been developed by genetic modification to tolerate glyphosate, the active ingredient in Roundup herbicide. The purpose of this study was to evaluate the compositional and nutritional safety of corn line GA21 compared to that of conventional corn. Compositional analyses were conducted to measure proximate, fiber, amino acid, fatty acid, and mineral contents of grain and proximate, fiber, and mineral contents of forage collected from 16 field sites over two growing seasons. The nutritional safety of corn line GA21 was evaluated in a poultry feeding study conducted with 2-day old, rapidly growing broiler chickens, at a dietary concentration of 50-60% w/w. Compositional analysis results showed that, except for a few minor differences that are unlikely to be of biological significance, the grain and forage of GA21 corn were comparable in their composition to that of the control corn line and to conventional corn. Results from the poultry feeding study showed that there were no differences in growth, feed efficiency, adjusted feed efficiency, and fat pad weights between chickens fed with GA21 grain or with parental control grain. These data taken together demonstrate that Roundup Ready corn is as safe and nutritious as conventional corn for food and feed use.

Amino Acids↗

Transfer of the yeast salt tolerance gene HAL1 to Cucumis melo L. cultivars and in vitro evaluation of salt tolerance.

An Agrobacterium-mediated gene transfer method for production of transgenic melon plants has been optimized. The HAL1 gene, an halotolerance gene isolated from yeast, was inserted in a chimaeric construct and joined to two marker genes: a selectable-neomycin phosphotransferase-II (nptII)-, and a reporter-beta-glucuronidase (gus)-. The entire construct was introduced into commercial cultivars of melon. Transformants were selected for their ability to grow on media containing kanamycin. Transformation was confirmed by GUS assays, PCR analysis and Southern hybridization. Transformation efficiency depended on the cultivar, selection scheme used and the induction of vir-genes by the addition of acetosyringone during the cocultivation period. The highest transformation frequency, 3% of the total number of explants cocultivated, was obtained with cotyledonary explants of cv. 'Pharo'. Although at a lower frequency (1.3%), we have also succeeded in the transformation of leaf explants. A loss of genetic material was detected in some plants, and results are in accordance with the directional model of T-DNA transfer. In vitro cultured shoots from transgenic populations carrying the HAL1 gene were evaluated for salt tolerance on shoot growth medium containing 10 gl-1 NaCl. Although root and vegetative growth were reduced, transgenic HAL1-positive plants consistently showed a higher level of tolerance than control HAL1-negative plants.

Acetophenones↗

More than zero tolerance? Burnout and tolerance for patient aggression amongst mental health nurses in China and the UK.

OBJECTIVE: The aim of the study was to examine attitudes toward patient aggressive behaviour amongst mental health nurses in China and the UK and the relationship between these attitudes and burnout. The UK government policy of 'zero tolerance' of patient aggression may conflict with practitioner attitudes and could potentially increase the risk of aggression occurring. METHOD: Two surveys of mental health nurses were conducted, one in the People's Republic of China and one in the UK using the Perceptions of Aggression Scale (POAS). The UK sample also completed the Maslach Burnout Inventory (MBI). RESULTS: Some nurses in both groups agreed that patient aggression could sometimes have positive benefits. A sense of personal accomplishment at work (MBI) was significantly associated with a tendency to endorse positive statements about aggression. DISCUSSION: Nurses seem to have a complex set of attitudes toward this issue that do not simply equate with 'zero tolerance'.

Aggression↗

Salt tolerance-related protein STO binds to a Myb transcription factor homologue and confers salt tolerance in Arabidopsis.

Regulating the intracellular Na+/K+ ratio is an essential process for salinity tolerance. The yeast mutant, can, which is deficient in calcineurin, can not grow on medium containing Na+ because it is unable to regulate the intracellular Na+/K+ ratio. Expression of the STO gene of Arabidopsis thaliana in the can mutant complements the salt-sensitive phenotype. A protein of Arabidopsis, an H-protein promoter binding factor (HPPBF-1), that binds to STO protein was isolated. HPPBF-1 cDNA has a sequence encoding a Myb DNA binding-motif and its gene expression is induced by salt stress. Furthermore, HPPBF-1 protein is localized in the nucleus. Although, the expression level of STO is not induced under salt-stress conditions, overexpression of STO in a transgenic Arabidopsis plant gave it a higher salt tolerance than was observed in the wild type. When STO transgenic plants and wild-type plants were subjected to salt stress, root growth was increased by 33-70% in the transgenic plants under salt stress. These results suggest that STO is involved in salt-stress responses in Arabidopsis.

Adaptation, Physiological↗

Salinity tolerance of 'Valencia' orange trees on rootstocks with contrasting salt tolerance is not improved by moderate shade.

The effects of shading in combination with salinity treatments were studied in citrus trees on two rootstocks with contrasting salt tolerance to determine if shading could reduce the negative effects of salinity stress. Well-nourished 2-year-old 'Valencia' orange trees grafted on Cleopatra mandarin (Cleo, relatively salt tolerant) or Carrizo citrange (Carr, relatively salt sensitive), were grown either under a 50% shade cloth or left unshaded in full sunlight. Half the trees received no salinity treatment and half were salinized with 50 mM Cl- during two 9 week salinity periods in the spring and autumn interrupted by an 11 week rainy period. The shade treatment reduced midday leaf temperature and leaf-to-air vapour pressure deficit regardless of salinity treatments. In non-salinized trees, shade increased midday CO2 assimilation rate (A(CO2)) and stomatal conductance, but had no effect on leaf transpiration (E(lf)). Shade also increased leaf chlorophyll and photosynthetic water use efficiency (A(CO2)/E(lf)) in leaves on both rootstocks and increased total plant dry weight in Cleo. The salinity treatment reduced leaf growth and leaf gas exchange parameters. Shade decreased Cl- concentrations in leaves of salinized Carr trees, but had no effect on leaf or root Cl- of trees on Cleo. There were no significant differences in leaf gas exchange parameters of shaded and unshaded salinized plants but the growth reduction from salinity stress was actually greater for shaded than for unshaded trees. Shaded trees on both rootstocks had higher leaf Na+ than unshaded trees after the first salinity period, and this shade-induced elevated leaf Na+ persisted after the second salinity period in trees on Carr. Thus, shading did not alleviate the negative effects of salinity on growth and Na+ accumulation.

Carbon Dioxide↗

Photosynthesis and photoassimilate transport during root hypoxia in Melaleuca cajuputi, a flood-tolerant species, and in Eucalyptus camaldulensis, a moderately flood-tolerant species.

We compared the photosynthetic and photoassimilate transport responses of Melaleuca cajuputi Powell seedlings to root hypoxia with those of Eucalyptus camaldulensis Dehnh. Control and hypoxia treated roots were maintained in a nutrient solution through which air or nitrogen was bubbled. Under root hypoxic conditions, seedlings of M. cajuputi, a flood-tolerant species, maintained height growth, whereas seedlings of E. camaldulensis, a moderately flood-tolerant species, showed markedly decreased height growth compared with control seedlings. Root hypoxia caused decreases in whole-plant biomass, photosynthetic rate and stomatal conductance in E. camaldulensis, but not in M. cajuputi. Photoassimilate transport to roots decreased significantly in E. camaldulensis seedlings 4 days after treatment and starch accumulated in mature leaves. Photoassimilate supply to hypoxic roots of E. camaldulensis seedlings was, thus, limited by reduced photoassimilate transport rather than by reduced photosynthesis. In contrast, M. cajuputi seedlings showed sustained photoassimilate transport to hypoxic roots and persistent photosynthesis, which together provided a substantial photoassimilate supply to the roots. Sucrose accumulated in hypoxic E. camaldulensis roots, but not in hypoxic M. cajuputi roots. A stable, low sucrose concentration in hypoxic roots would let M. cajuputi seedlings prolong photoassimilate transport to the roots. Photoassimilate partitioning among the water-soluble carbohydrates, starch and structural carbohydrates within the roots was unaffected by root hypoxia in E. camaldulensis, but in M. cajuputi, partitioning was shifted somewhat from structural carbohydrates to water-soluble carbohydrates. This suggests that M. cajuputi seedlings are able to increase photoassimilate utilization in metabolism and sustain energy production under root hypoxic conditions.

Alcohol Dehydrogenase↗

Influence of Protoplasmic Water Loss on the Control of Protein Synthesis in the Desiccation-Tolerant Moss Tortula ruralis: Ramifications for a Repair-Based Mechanism of Desiccation Tolerance.

Desiccation tolerance of the moss Tortula ruralis is characterized by a desiccation-induced change in gene expression that becomes evident upon rehydration. As reported earlier, this change in gene expression is apparently brought about by a change in the control of translation and does not include a major shift in mRNA abundance. A full qualitative and quantitative analysis of the alteration in gene expression, which is characterized by the loss of (or greater than fivefold decrease in) the synthesis of 25 hydration (h) proteins and initiation (or greater than fivefold increase) of the synthesis of 74 rehydration (r) proteins, is given in this report. Exposure to a desiccating atmosphere, for times that result in varying levels of water loss, enabled the determination that the control of synthesis of r proteins is different from the control of synthesis of h proteins. The r and h protein synthesis responses are internally coordinate, however. Similarly, the return to normal levels of h protein synthesis differs from that of the r proteins. The return to normal synthetic levels for all h proteins is synchronous, but the rate of loss of r protein synthesis varies with each individual r protein. Run-off translation of polysomes isolated from gametophytes during the drying phase demonstrates that there are no novel mRNAs recruited and no particular mRNA is favored for translation during desiccation. These findings add credence to the argument that translational control is the major component of the desiccation-induced alteration in gene expression in this plant, as discussed. Aspects of the response of protein synthesis to desiccation are consistent with the hypothesis that T. ruralis exhibits a repair-based mechanism of desiccation tolerance.

Journal Article↗

Poplar metal tolerance protein 1 confers zinc tolerance and is an oligomeric vacuolar zinc transporter with an essential leucine zipper motif.

Cation diffusion facilitator (CDF) proteins are a recently discovered family of cation efflux transporters that might play an essential role in metal homeostasis and tolerance. Here, we describe the identification, characterization, and localization of PtdMTP1, a member of the CDF family from the hybrid poplar Populus trichocarpa x Populus deltoides. PtdMTP1 is expressed constitutively and ubiquitously, although at low levels. Heterologous expression in yeast showed that PtdMTP1 was able to complement the hypersensitivity of mutant strains to Zn but not to other metals, including Cd, Co, Mn, and Ni. PtdMTP1 fused to green fluorescent protein localized to the vacuolar membrane both in yeast and in plant cells, consistent with a function of PtdMTP1 in zinc sequestration. Overexpression of PtdMTP1 in Arabidopsis confers Zn tolerance. We show that PtdMTP1, when expressed in yeast and Arabidopsis, forms homooligomers, a novel feature of CDF members. Oligomer formation is disrupted by reducing agents, indicating possible disulfide bridge formation. PtdMTP1 also contains a conserved Leu zipper motif. Although not necessary for oligomer formation, Leu residues within this motif are required for PtdMTP1 functional activity.

Adaptation, Physiological↗

Contribution of dps to acid stress tolerance and oxidative stress tolerance in Escherichia coli O157:H7.

An Escherichia coli O157:H7 dps::nptI mutant (FRIK 47991) was generated, and its survival was compared to that of the parent in HCl (synthetic gastric fluid, pH 1.8) and hydrogen peroxide (15 mM) challenges. The survival of the mutant in log phase (5-h culture) was significantly impaired (4-log(10)-CFU/ml reduction) compared to that of the parent strain (ca. 1.0-log(10)-CFU/ml reduction) after a standard 3-h acid challenge. Early-stationary-phase cells (12-h culture) of the mutant decreased by ca. 4 log(10) CFU/ml while the parent strain decreased by approximately 2 log(10) CFU/ml. No significant differences in the survival of late-stationary-phase cells (24-h culture) between the parent strain and the mutant were observed, although numbers of the parent strain declined less in the initial 1 h of acid challenge. FRIK 47991 was more sensitive to hydrogen peroxide challenge than was the parent strain, although survival improved in stationary phase. Complementation of the mutant with a functional dps gene restored acid and hydrogen peroxide tolerance to levels equal to or greater than those exhibited by the parent strain. These results demonstrate that decreases in survival were from the absence of Dps or a protein regulated by Dps. The results from this study establish that Dps contributes to acid tolerance in E. coli O157:H7 and confirm the importance of Dps in oxidative stress protection.

Animals↗

Aquaporin expression correlates with freeze tolerance in baker's yeast, and overexpression improves freeze tolerance in industrial strains.

Little information is available about the precise mechanisms and determinants of freeze resistance in baker's yeast, Saccharomyces cerevisiae. Genomewide gene expression analysis and Northern analysis of different freeze-resistant and freeze-sensitive strains have now revealed a correlation between freeze resistance and the aquaporin genes AQY1 and AQY2. Deletion of these genes in a laboratory strain rendered yeast cells more sensitive to freezing, while overexpression of the respective genes, as well as heterologous expression of the human aquaporin gene hAQP1, improved freeze tolerance. These findings support a role for plasma membrane water transport activity in determination of freeze tolerance in yeast. This appears to be the first clear physiological function identified for microbial aquaporins. We suggest that a rapid, osmotically driven efflux of water during the freezing process reduces intracellular ice crystal formation and resulting cell damage. Aquaporin overexpression also improved maintenance of the viability of industrial yeast strains, both in cell suspensions and in small doughs stored frozen or submitted to freeze-thaw cycles. Furthermore, an aquaporin overexpression transformant could be selected based on its improved freeze-thaw resistance without the need for a selectable marker gene. Since aquaporin overexpression does not seem to affect the growth and fermentation characteristics of yeast, these results open new perspectives for the successful development of freeze-resistant baker's yeast strains for use in frozen dough applications.

Aquaporin 1↗

Dehydration tolerance in wood frogs: a new perspective on development of amphibian freeze tolerance.

Wood frogs, Rana sylvatica, tolerate the loss of 50-60% of total body water during experimental dehydration. The rate of water loss for unprotected frogs is the same whether animals are frozen (at -2 degrees C) or unfrozen (at 1 degrees C) but is greatly reduced when frogs are frozen under a protective layer of moss. Dehydrational death could occur in as little as 7-9 days for unprotected animals; this indicates the importance for winter survival of selecting well-protected and damp hibernation sites. Prior dehydration affected the cooling and freezing properties of frogs, reducing supercooling point and the amount of ice formed after 24 h at -2 degrees C and acting synergistically with freezing exposure in stimulating cryoprotectant synthesis. Analysis of the effects of controlled dehydration at 5 degrees C showed that changes in body water content alone (without freezing) stimulated liver glycogenolysis and the export of high concentrations of glucose into blood and other organs. Autumn-collected frogs dehydrated to 50% of total body water lost showed glucose levels of 165-1,409 nmol/mg protein in different organs, increases of 9- to 313-fold compared with control values and reaching final levels very similar to those induced by freezing exposure. The data support the proposal that various adaptations for natural freeze tolerance may have been derived from preexisting mechanisms for dealing with water stress in amphibians and that cell volume change may be one of the signals involved in triggering and sustaining molecular adaptations (e.g., cryoprotectant output) that support freezing survival.

Adaptation, Physiological↗

Organic solvent tolerance of halophilic archaea, Haloarcula strains: effects of NaCl concentration on the tolerance and polar lipid composition.

Strains of halophilic archaea, Haloarcula vallismortis and two Haloarcula strains OHF-1 and OHF-2, showed high tolerance to organic solvents at high media NaCl concentrations. For example, the lowest log Pow of the solvent which allowed growth (log Pow is the common logarithm of the partition coefficient of a given solvent in a mixture of n-octanol and water) for H. vallismortis was 5.1 at 20% NaCl and 4.4 at 30% NaCl. The solvent tolerance of Haloarcula argentinensis, on the other hand, was not affected by the NaCl concentration. Cells of strains OHF-1 and OHF-2 were of triangular or irregular morphology but became spherical in cultures in NaCl media overlaid with cyclohexane (log Pow=3.4), but returned to the triangular shape when the organic solvent evaporated from the medium. When cells of strains OHF-1, OHF-2, and H. argentinensis were grown in NaCl media in the presence of n-decane, they contained less phosphatidylglycerol and more phosphatidylglycerosulfate and phosphatidylglycerophosphate methyl ester than when grown without added n-decane. When the solvent was removed from the media after cultivation, the levels of these compounds returned to their initial ones.

Cell Proliferation↗

[Assessment of the somatotropic function of the hypophysis in patients with hypophyseal nanism and gonadal dysgenesis by using the insulin-tolerance and arginine-tolerance tests].

With the aid of insulin-tolerance and arginine tolerance tests (ITT and ATT, respectively) somatotropic function of the hypophysis was assessed in 18 patients with hypophyseal nanism and in 12--with gonad dysgenesis. A marked delay in development and a premature exhaustion of the STH secretion was noted in the patients wiht hypophyseal nanism. In patients with gonad dysgenesis the STH secretion was somewhat redeced during the ITT. A change in the STH secretion was accompanied by a parallel depression of insulin secretion during the ATT. Patients with hypophyseal nanism displayed a correlation between the extent of growth delay and the value of the STH secretion during the ITT (R=0.6, P smaller than 0.05).

Adolescent↗

Tolerance to tolerances: some thoughts on the 1979 American National Standard recommendations for prescription ophthalmic lenses.

The 1979 revision of the ANSI Z80.1 Ophthalmic Lens Standards resulted in rather significant changes affecting three areas of ophthalmic lens requirements: 1) central refractive characteristics, 2) prismatic characterstics, and 3) factors relating to the magnification properties of lenses. Based primarily on what an optical laboratory could consistently produce, the ANSI Ophthalmic Lens Sub-committee decided to widen some of the tolerances over those expressed in previous revisions. This paper attempts to show how these new tolerances relate to certain aspects of patient sensitivity to errors induced by ophthalmic lenses conforming with the new revision.

Eyeglasses↗

[Methods and clinical significance of an oral tolerance test of essential trace element, especially an oral zinc tolerance test].

Oral administration of zinc (zinc tolerance test) was performed in 6 healthy adults, 11 patients with chronic hepatitis and 17 patients with liver cirrhosis to evaluate the ability of the digestive organs in patients with chronic hepatic diseases to absorb zinc. That is 300 mg of zinc sulfate powder (ZnSO4 7H2O)--equivalent to 68 mg of zinc--was dissolved in 200 ml of physiological saline solution, and the subjects received oral administration of the solution in a fasting condition during the early morning. The mean levels of serum Zn (ppm) at 0, 1, 2, and 3 hours after the test dose of ZnSO4 were 0.8 +/- 0.06, 1.66 +/- 0.21, 2.73 +/- 0.22 and 2.53 +/- 0.33 in cirrhotic patients, respectively. In most subjects, serum Zn levels peaked at 2 or 3 ours. The increase in serum Zn at 60 minutes during the base line Zn tolerance test was similar in patients and controls. The area under the curve was also significantly decreased in cirrhotic patients. These results will confirm the presence of diminished absorption by the intestinal tract in patients with liver cirrhosis.

Administration, Oral↗