Krill faecal pellets drive hidden pulses of particulate organic carbon in the marginal ice zone.

The biological carbon pump drives a flux of particulate organic carbon (POC) through the ocean and affects atmospheric levels of carbon dioxide. Short term, episodic flux events are hard to capture with current observational techniques and may thus be underrepresented in POC flux estimates. We model the potential hidden flux of POC originating from Antarctic krill, whose swarming behaviour could result in a major conduit of carbon to depth through their rapid exploitation of phytoplankton blooms and bulk egestion of rapidly sinking faecal pellets (FPs). Our model results suggest a seasonal krill FP export flux of 0.039 GT C across the Southern Ocean marginal ice zone, corresponding to 17-61% (mean 35%) of current satellite-derived export estimates for this zone. The magnitude of our conservatively estimated flux highlights the important role of large, swarming macrozooplankton in POC export and, the need to incorporate such processes more mechanistically to improve model projections.

Purification from rat liver of a novel constitutively expressed member of the aldo-keto reductase 7 family that is widely distributed in extrahepatic tissues.

Antiserum raised against human aflatoxin B(1) aldehyde reductase 1 (hAFAR1) has been used to identify a previously unrecognized rat aldo-keto reductase (AKR). This novel enzyme is designated rat aflatoxin B(1) aldehyde reductase 2 (rAFAR2) and it characteristically migrates faster during SDS/PAGE than does the archetypal ethoxyquin-inducible rAFAR protein (now called rAFAR1). Significantly, rAFAR2 is essentially unreactive with polyclonal antibodies raised against rAFAR1. Besides its distinct electrophoretic and immunochemical properties, rAFAR2 appears to be regulated differently from rAFAR1 as it is expressed in most rat tissues and does not appear to be induced by ethoxyquin. Multiple forms of rAFAR2 have been identified. Anion-exchange chromatography on Q-Sepharose, followed by adsorption chromatography on columns of Matrex Orange A and Cibacron Blue, have been employed to purify rAFAR2 from rat liver cytosol. The Q-Sepharose chromatography step resulted in the resolution of rAFAR2 into three peaks of AKR activity, two of which were purified and shown to be capable of catalysing the reduction of 2-carboxybenzaldehyde, succinic semialdehyde, 4-nitrobenzaldehyde and 9,10-phenathrenequinone. The two most highly purified rAFAR2-containing preparations eluted from the Cibacron Blue column were 91 and 98% homogeneous. Analysis of these by SDS/PAGE indicated that the least anionic (peak CBA5) comprised a polypeptide of 37.0 kDa, whereas the most anionic (peak CBA6) contained two closely migrating polypeptides of 36.8 and 37.0 kDa; by contrast, in the present study, rAFAR1 was estimated by SDS/PAGE to be composed of 38.0 kDa subunits. Final purification of the 37 kDa polypeptide in CBA5 and CBA6 was accomplished by reversed-phase HPLC. Partial proteolysis of the two preparations of the 37 kDa polypeptide with Staphylococcus aureus V8 protease yielded fragments of identical size, suggesting that they represent the product of a single gene. Furthermore, the peptide maps from CBA5 and CBA6 differed substantially from that yielded by rAFAR1, indicating that they are genetically distinct from the inducible reductase. A peptide generated by CNBr digestion of the 37 kDa polypeptide from CBA6 was shown by Edman degradation to share 88% sequence identity with residues Tyr(168)-Leu(183) of rAFAR1. This provides evidence that the rat protein identified by its cross-reactivity with anti-hAFAR1 serum is an additional member of the AKR7 family.

Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members.

Complementary DNA clones encoding human aflatoxin B(1) aldehyde reductase (AKR7A2), aldehyde reductase (AKR1A1), aldose reductase (AKR1B1), dihydrodiol dehydrogenase 1 (AKR1C1) and chlordecone reductase (AKR1C4) have been expressed in Escherichia coli. These members of the aldo-keto reductase (AKR) superfamily have been purified from E. coli as recombinant proteins. The recently identified AKR7A2 was shown to differ from the AKR1 isoenzymes in being able to catalyse the reduction of 2-carboxybenzaldehyde. Also, AKR7A2 was found to exhibit a narrow substrate specificity, with activity being restricted to succinic semialdehyde (SSA), 2-nitrobenzaldehyde, pyridine-2-aldehyde, isatin, 1,2-naphthoquinone (1,2-NQ) and 9,10-phenanthrenequinone. In contrast, AKR1A1 reduces a broad spectrum of carbonyl-containing compounds, displaying highest specific activity for SSA, 4-carboxybenzaldehyde, 4-nitrobenzaldehyde, pyridine-3-aldehyde, pyridine-4-aldehyde, 4-hydroxynonenal, phenylglyoxal, methylglyoxal, 2,3-hexanedione, 1, 2-NQ, 16-ketoestrone and d-glucuronic acid. Comparison between the kinetic properties of AKR7A2 and AKR1A1 showed that both recombinant enzymes exhibited roughly similar k(cat)/K(m) values for SSA, 1,2-NQ and 16-ketoestrone. Many of the compounds which are substrates for AKR1A1 also serve as substrates for AKR1B1, though the latter enzyme was shown to display a specific activity significantly less than that of AKR1A1 for most of the aromatic and aliphatic aldehydes studied. Neither AKR1C1 nor AKR1C4 was found to possess high reductase activity towards aliphatic aldehydes, aromatic aldehydes, aldoses or dicarbonyls. However, unlike AKR1A1 and AKR1B1, both AKR1C1 and AKR1C4 were able to catalyse the oxidation of 1-acenaphthenol and, in addition, AKR1C4 could oxidize di- and tri-hydroxylated bile acids. Specific antibodies raised against AKR7A2, AKR1A1, AKR1B1, AKR1C1 and AKR1C4 have been used to show the presence of all of the reductases in human hepatic cytosol; the levels of AKR1B1 and AKR1C1 were markedly elevated in livers with alcohol-associated injury, and indeed AKR1B1 was only detectable in livers with evidence of alcoholic liver disease. Western blotting of extracts from brain, heart, kidney, liver, lung, prostate, skeletal muscle, small intestine, spleen and testis showed that AKR7A2 is present in all of the organs examined, and AKR1B1 is similarly widely distributed in human tissues. These experiments revealed however, that the expression of AKR1A1 is restricted primarily to brain, kidney, liver and small intestine. The AKR1C family members proved not to be as widely expressed as the other reductases, with AKR1C1 being observed in only kidney, liver and testis, and AKR1C4 being found in liver alone. As human kidney is a rich source of AKR, the isoenzymes in this organ have been studied further. Anion-exchange chromatography of human renal cytosol on Q-Sepharose allowed resolution of AKR1A1, AKR1B1, AKR1C1 and AKR7A2, as identified by substrate specificity and Western blotting. Immunohistochemistry of human kidney demonstrated that AKR7A2 is expressed in a similar fashion to the AKR1 family members in proximal and distal convoluted renal tubules. Furthermore, both AKR7A2 and AKR1 members were expressed in renal carcinoma cells, suggesting that these groups of isoenzymes may be engaged in related physiological functions.

HIV positive tests at Coronial Services in Victoria 1989-1996: lessons for HIV surveillance.

Results of routine testing at other sites can supplement surveillance of the HIV epidemic in Australia which is largely based upon voluntary testing. Since 1989, systematic onsite HIV testing has been undertaken on all bodies taken to the Victorian Institute of Forensic Medicine (VIFM). Information was collected on all cases of HIV infection detected at VIFM between 1989 and 1996, and matched to surveillance databases. In 8 years, 75 people were diagnosed with HIV; all except one were male. The age range was 14-70 years, mean 37.4 years. The major causes of death were suicide 35%, AIDS 21%, drug toxicity 16%, natural causes 12% and injury 7%. The major exposure categories were male homosexual 51%, male bisexual 11%, homosexual/bisexual IDU 16%, IDU other 8%, and haemophiliac 7%. For only two was exposure information unavailable. Seropositivity for anti-HCV and HBsAg was 37% and 11% respectively. The deceased was recorded as having HIV/AIDS on the police report in 73% of cases, and at least 90% of subjects had been diagnosed with HIV prior to their death. The study suggests there is relatively little undiagnosed HIV infection in Victoria, that HIV infection has not moved outside traditional risk groups, and that many tests for HIV are undertaken using false namecodes. Many patients could not be matched on the HIV/AIDS databases, identifying a problem with HIV surveillance systems in Victoria, and the need to capture all information on HIV positives detected at VIFM.

Molecular cloning, expression and catalytic activity of a human AKR7 member of the aldo-keto reductase superfamily: evidence that the major 2-carboxybenzaldehyde reductase from human liver is a homologue of rat aflatoxin B1-aldehyde reductase.

The masking of charged amino or carboxy groups by N-phthalidylation and O-phthalidylation has been used to improve the absorption of many drugs, including ampicillin and 5-fluorouracil. Following absorption of such prodrugs, the phthalidyl group is hydrolysed to release 2-carboxybenzaldehyde (2-CBA) and the pharmaceutically active compound; in humans, 2-CBA is further metabolized to 2-hydroxymethylbenzoic acid by reduction of the aldehyde group. In the present work, the enzyme responsible for the reduction of 2-CBA in humans is identified as a homologue of rat aflatoxin B1-aldehyde reductase (rAFAR). This novel human aldo-keto reductase (AKR) has been cloned from a liver cDNA library, and together with the rat protein, establishes the AKR7 family of the AKR superfamily. Unlike its rat homologue, human AFAR (hAFAR) appears to be constitutively expressed in human liver, and is widely expressed in extrahepatic tissues. The deduced human and rat protein sequences share 78% identity and 87% similarity. Although the two AKR7 proteins are predicted to possess distinct secondary structural features which distinguish them from the prototypic AKR1 family of AKRs, the catalytic- and NADPH-binding residues appear to be conserved in both families. Certain of the predicted structural features of the AKR7 family members are shared with the AKR6 beta-subunits of voltage-gated K+-channels. In addition to reducing the dialdehydic form of aflatoxin B1-8,9-dihydrodiol, hAFAR shows high affinity for the gamma-aminobutyric acid metabolite succinic semialdehyde (SSA) which is structurally related to 2-CBA, suggesting that hAFAR could function as both a SSA reductase and a 2-CBA reductase in vivo. This hypothesis is supported in part by the finding that the major peak of 2-CBA reductase activity in human liver co-purifies with hAFAR protein.

Actions of A-131701, a novel, selective antagonist for alpha-1A compared with alpha-1B adrenoceptors on intraurethral and blood pressure responses in conscious dogs and a pharmacodynamic assessment of in vivo prostatic selectivity.

A-131701 (3-[2-((3aR,9bR)-cis-6-methoxy-2,3,3a,4,5,9b, hexahydro-[1H]-benz[e]isoindol-2-yl)ethyl]pyrido [3',4': 4,5]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione) is a novel compound previously shown to be selective for alpha-1a sites compared with alpha-1b adrenoceptors in radioligand binding studies and isolated tissue bioassays and to block canine urethral pressure (IUP) responses to exogenous alpha-1 adrenergic agonists to a greater extent than blood pressure responses. In conscious dogs in which IUP and mean arterial blood pressure (MABP) responses were measured periodically up to 24 hr, A-131701 blocked phenylephrine (PHE)-induced increases in IUP to a greater extent than MABP responses, and the blockade of the IUP effects of PHE was significantly different from control for up to 12 hr after doses greater than 0.3 mg/kg p.o., whereas blood pressure effects were of a lesser extent and duration. In addition to the weak antagonism of PHE-induced blood pressure responses, A-131701 also exhibited minimal effects on basal blood pressure in the dog, unlike terazosin, doxazosin or tamsulosin. Pharmacokinetic analysis of plasma samples from dogs indicated that A-131701 had a half-life of 0.4 to 0.8 hr and a bioavailability of 30 to 50% in dogs. Somewhat longer half-lives were observed in rat and monkey, with bioavailability values in the 25 to 30% range. Evidence of nonlinearity of pharmacokinetics was obtained in dogs and monkeys. Pharmacodynamic analysis revealed differences between A-131701 and nonselective alpha-1 adrenoceptor antagonists in selectivity for prostatic versus vascular alpha-1 adrenoceptors based on either extent or duration of blockade, which were either similar to or superior to compounds such as tamsulosin or REC 15/2739. These data demonstrate that A-131701 selectively blocks canine prostatic alpha-1 adrenoceptors for prolonged periods compared with MABP responses in vivo. Therefore, A-131701 should have clinical utility in the pharmacotherapy of benign prostatic hyperplasia.

Children's perceptions of asthma: establishing normality.

This qualitative research study explores children's perceptions of having asthma. The research methodology utilized a grounded theory approach. The study aimed to identify the beliefs and attitudes held by asthmatic children regarding their illness and to consider how this influences their asthma management. Ten asthmatic children, boys and girls, aged between 9 and 12 years, were interviewed. The transcribed interviews were analysed using the constant comparative method. Analysis revealed four major categories and a core variable identified as 'establishing normality'. These themes influenced each child's appraisal and response to having asthma. The findings show that their concern to establish normality and to be 'normal' does have benefits, but in some circumstances also encourages the acceptance of suboptimal control.

Development of an introductory course in child protection.

The maltreatment of children is a significant public health and social problem. Healthcare professionals have a crucial role to play working with other agencies to protect children from abuse and neglect. The need for training, support and clinical supervision in this work has been identified. This article discusses the collaborative work that led to the establishment of an introductory course in child protection (English National Board 970) at one school of nursing and midwifery and outlines the benefits of undertaking such a course. The course has attracted participants from a range of healthcare settings and has proved to be well evaluated and oversubscribed. Practitioners have returned to their work setting with increased awareness of child maltreatment and an understanding of the need for a proactive approach to child protection.

[3H]R-terazosin binds selectively to alpha1-adrenoceptors over alpha2-adrenoceptors - comparison with racemic [3H]terazosin and [3H]prazosin.

Most tissue sources for adrenoceptors contain a mixed population of alpha1- and/or alpha2-adrenoceptor subtypes; thus studies using non-specific radioligands are complicated by receptor heterogeneity. The examination of alpha1-adrenoceptor radioligand binding by radiolabeled terazosin and its enantiomers was simplified by using mouse fibroblast cells, which are thymidine kinase mutant (LTK-), transfected with cloned alpha1a-, alpha1b-, and alpha1d-adrenoceptor subtypes. [3H]Terazosin and its enantiomers were equipotent at the alpha1b-adrenoceptor. [3H]R-Terazosin was significantly less potent than [3H]terazosin and [3H]S-terazosin at the alpha1a- and the alpha1d-adrenoceptors. Using tissue derived alpha-adrenoceptors prepared in cold 25 mM glycyl-glycine buffer, [3H]prazosin, [3H]terazosin and [3H]S-terazosin bound to two sites in the rat neonatal lung preparation consistent with the presence of both alpha1- and alpha2B-adrenoceptors. The relative binding potencies of these radioligands at these two sites correlated with low affinity binding to the alpha2B-adrenoceptor and high affinity binding to an alpha1-adrenoceptor. [3H]R-Terazosin, on the other hand, bound to a single site in the rat neonatal lung membrane preparation, most likely an alpha1-adrenoceptor. Thus, [3H]R-terazosin may be useful as a selective alpha1-adrenoceptor radioligand for establishing the functional role of adrenoceptors in tissues expressing multiple subtypes.

Fit for whose purpose? The contextual forces underpinning the provision of nurse education in the UK.

This paper explores the implications of the contextual forces currently underpinning nurse education. It challenges the notion of a model of education which is principally founded on the concept of 'fitness for purpose'. Open acknowledgement is made that the driving forces impacting on the purchasers and providers of nurse education are different, and may be in conflict. The central tenet of this debate is based upon a growing awareness that the notion of practitioners being fit for purpose is increasingly being dictated and articulated by local purchasers. Their views may reflect financial expedience and short-term goals, arguably to the detriment of a longer term vision. Tensions also exist between purchasers' locally driven agendas and the reality that practitioners receive a nationally and internationally recognized qualification. The importance of manpower planning is also central to the debate. Solutions are offered which consider guidelines offered by a range of recent policy documents. Their contribution to the debate is assessed. Recommendations are made which recognize the need to equip practitioners with skills that have currency at point of registration, but argue that dominance must be given to the longer term goals of the educational enterprise.

Is the quest for evidence-based care detrimental to children's nursing?

Evidence-based care and the expanded role of the nurse are inexorably linked. Facets of this are found in every specialist area of nursing. Children's nurses are no exception and they have proved their commitment to family-centred care over a period of many years. However, within the ranks of nurse educationalists now employed by the universities and not the NHS new tensions have emerged. The research-led ethos of the universities demands that nurses demonstrate expertise in the field of scientific enquiry. Although the philosophy of caring and research are not incongruent, there exists the potential that family empowerment may take a back seat to academic prowess. This article examines the background to this dilemma.

Effects of selective and nonselective alpha-1-adrenoceptor antagonists on intraurethral and arterial pressures in intact conscious dogs.

In this study, we used a novel conscious dog model to evaluate the uroselectivity of selected alpha 1-antagonists either approved for human use or in clinical development for the treatment of symptomatic benign prostatic hyperplasia (BPH) and compared those results to their in vitro binding and functional affinities at alpha 1A, alpha 1B and alpha 1D receptor subtypes. Conscious dogs were instrumented acutely with a balloon catheter for the measurement of changes in prostatic intraurethral pressure (IUP) and chronically with implantable telemetry devices for the measurement of arterial pressure. The pressor effects of the alpha 1-agonist phenylephrine (PE) on IUP and mean arterial pressure (MAP) were compared before and at various time points after oral doses of either terazosin, doxazosin, tamsulosin or Rec 15/2739 (SB 216469). At submaximal doses, terazosin and doxazosin blocked PE-induced increases in MAP to a greater extent than increases in IUP. Tamsulosin blocked both parameters equally at the lowest and highest doses; however, at the intermediate dose, IUP was blocked more than MAP. Rec 15/2739 at each dose always blocked IUP to a greater extent than MAP. While the in vivo uroselectivity of these agents was predicted by radioligand binding and in vitro functional selectivity for the alpha 1A subtype over alpha 1B and alpha 1D subtypes, results from conscious dog experiments indicate that estimates of in vivo uroselectivity also depend upon dose and the time after administration. Our conscious canine model provides the basis for frequent and repeated evaluation of uroselectivity parameters over many hours, thus providing a pharmacological profile of compound effects perhaps more relevant to clinical practice.

Regulation of glutathione S-transferases and aldehyde reductase by chemoprotectors: studies of mechanisms responsible for inducible resistance to aflatoxin B1.

A number of xenobiotics, including the synthetic antioxidant ethoxyquin, inhibit aflatoxin B1 (AFB1)-induced hepatocarcinogenesis in the rat. Two detoxification enzymes that mediate ethoxyquin-induced chemoprotection against AFB1 have been identified by protein purification: a glutathione S-transferase (GST) Yc2 subunit with at least 100-fold greater activity towards AFB1-8,9-epoxide than previously studied transferases, and a unique aldehyde reductase with activity towards the dialdehydic form of AFB1-8,9-dihydrodiol. Molecular cloning has revealed that the Yc2 subunit is a class alpha GST and that the aflatoxin-metabolizing aldehyde reductase (AFAR) is a distant member of the aldo-keto reductase superfamily. Enzyme assay and western blotting have shown that many chemoprotectors, such as ethoxyquin, butylated hydroxyanisole, butylated hydroxytoluene, oltipraz and indole-3-carbinol, that inhibit AFB1-mediated hepatocarcinogenesis induce both GST Yc2 and AFAR. However, western blotting suggests that these enzymes are not always coordinately regulated, as treatment with phenobarbital and beta-naphthoflavone results in differences in the relative increase in hepatic GST Yc2 and AFAR. These findings indicate that GST Yc2 and AFAR represent important resistance mechanisms against AFB1 in the rat. This conclusion is supported by the observation that GST Yc2 and AFAR are overexpressed in rat liver preneoplastic nodules, which display pleiotropic drug resistance.

Differential effects of 2,4-dithiobiuret on the synthesis and release of acetylcholine and dopamine from rat pheochromocytoma (PC12) cells.

Chronic administration of 2,4-dithiobiuret (DTB), causes delayed-onset neuromuscular weakness in rats. This effect results from inhibition of quantal release of acetylcholine (ACh) from motor nerve terminals. The effects of noncholinergic neurotransmission are unknown. The purpose of the present study was to examine the presynaptic mechanisms involved in DTB-induced inhibition of ACh release, particularly, the specificity of action of DTB for cholinergic secretion. Differentiated pheochromocytoma (PC12) cells were used to compare the effects of DTB on the content and release of ACh and dopamine (DA) using neurochemical techniques. At concentrations of 50 to 1000 microM, DTB had little or no effect on [3H]choline uptake or on the spontaneous release of endogenous or [3H]ACh, but caused a significant decrease in release of endogenous or [3H]ACh elicited by depolarization with elevated extracellular [K+]. DTB reduced evoked release of ACh without altering cellular levels of ACh or choline, suggesting that DTB acts directly on mechanisms involved in ACh release. These alterations occurred without prominent alterations in [Ca2+]i as measured by fluorescence microscopy of individual PC12 cells loaded with fura-2. Moreover, DTB did not affect the increase of [Ca2+]i of PC12 cells in response to KCl-induced depolarization. alpha-Latrotoxin-stimulated release of ACh was not inhibited by DTB. DTB-induced suppression of depolarization-evoked release of [3H]ACh was associated with an increased level of [3H]ACh in the vesicular pool although the cytosolic pool was unaffected. High concentrations of DTB also reduced depolarization-evoked release of DA and inhibited DA synthesis resulting in a decrease in the readily releasable pool of DA. These effects occurred at higher concentrations and after longer exposures to DTB than were necessary to alter ACh release. Inasmuch as DA synthesis in the PC12 cell has been shown to be modulated by ACh release, this effect on DA release may reflect a consequence of the diminished release of ACh. These results suggest that DTB alters the release of ACh by interrupting either the mobilization and/or release of the vesicular pool of ACh.

Actions of terazosin and its enantiomers at subtypes of alpha 1- and alpha 2-adrenoceptors in vitro.

Terazosin and its enantiomers, antagonists of alpha 1-adrenoceptors, were studied in radioligand binding and functional assays to determine relative potencies at subtypes of alpha 1- and alpha 2-adrenoceptors in vitro. The racemic compound and its enantiomers showed high and apparently equal affinity for subtypes of alpha 1-adrenoceptors with Kl values in the low nanomolar range, and showed potent antagonism of alpha 1-adrenoceptors in isolated tissues, with the enantiomers approximately equipotent to the racemate at each alpha 1-adrenoceptor subtype. At alpha 2b sites, R(+) terazosin bound less potently than either the S(-) enantiomer or racemate. R(+) terazosin was also less potent than the S(-) enantiomer or the racemate at rat atrial alpha 2B receptors. These agents were not significantly different in their potencies at alpha 2a or alpha 2A sites. Since the high affinity for alpha 2B sites of quinazoline-type alpha-adrenoceptor antagonists has been used to differentiate alpha 2-adrenoceptor subtypes, the low affinity of R(+) terazosin for these sites was unexpected. Because terazosin or its enantiomers are approximately equipotent at alpha 1-adrenoceptor subtypes, the lower potency of R(+) terazosin at alpha 2B receptors indicates a somewhat greater selectivity for alpha 1-compared to alpha 2B adrenoceptor subtypes. The possible pharmacological significance of this observation is discussed.

Behavioral phenotype in children with Turner syndrome.

Compared Child Behavior Checklist results in 103 girls with Turner syndrome (TS) ages 7 to 13 years and 52 age-matched normal girls. Subjects with TS were part of a national study in Canada to evaluate growth hormone therapy in TS. Present data were obtained at baseline. Girls with TS scored below the comparison group in Total Social Competence (p < .0001), and above it in Total Behavior Problems (p < .05), Social (p < .0001), and Attention Problems (p < .001) scales. Item analysis revealed that subjects with TS were more immature, hyperactive, and nervous, and had poorer peer relations, greater difficulty at schooling, and more problems concentrating. In children with TS, height was correlated with social competence while karyotypes involving structural abnormalities of the X chromosome were associated with more behavior problems than a missing X or mosaicism.

A member of a novel family of yeast 'zn-finger' proteins mediates the transition from stationary phase to cell proliferation.

The cloning and molecular characterization of the GCS1 gene from the budding yeast Saccharomyces cerevisiae show that stationary phase is in fact a unique developmental state, with requirements to resume cell proliferation that can be distinct from those for maintenance of proliferation. Deletion of the GCS1 gene products a novel phenotype: stationary-phase mutant cells do not resume proliferation at a restrictive temperature of 15 degrees C, but mutant cells lacking Gcs1p that are proliferating at the permissive temperature of 29 degrees C continue to proliferate after transfer to 15 degrees C as long as nutrients are available. The GCS1 gene sequence predicts a 39 kDa polypeptide with a novel 'Zn-finger' motif. A point mutation within the finger motif produces a phenotype that mimics that of deletion of the GCS1 gene, showing that the finger motif is essential for full Gcs1p activity. Gcs1p and the products of two newly identified genes, SPS18 and GLO3, constitute a family of novel Zn-finger proteins.

Mitochondrial DNA loss by yeast reentry-mutant cells conditionally unable to proliferate from stationary phase.

Double-mutant cells of the budding yeast Saccharomyces cerevisiae harboring the gcs1-1 and sed1-1 mutations are conditionally defective (cold-sensitive) only for reentry into the mitotic cycle from stationary phase. If already proliferating at the permissive temperature (29 degrees C), these reentry-mutant cells continue to proliferate when transferred to the restrictive temperature of 14 degrees C, but under these conditions reentry-mutant cells lose mitochondrial DNA (mtDNA). In addition, upon exhaustion of the nutrient supply at 14 degrees C, these reentry-mutant cells entered stationary phase at a decreased cell concentration and did not accumulate the reserve carbohydrates trehalose and glycogen. Both of these deficiencies were due to the loss of mtDNA, as shown by the responses of wild-type cells also lacking mtDNA. Mitochondrial status did not affect other aspects of the reentry-mutant phenotype. Although mitochondrial activity and the accumulation of carbohydrate reserves are typical features of cells in stationary phase, the reentry-mutant phenotype reveals that neither entry into nor exit from stationary phase need involve mitochondrial function.

Chlorpromazine and the lateralisation of the perception of emotion.

In a double-blind design, sixteen volunteer students were administered 50 mg of chlorpromazine or a placebo in tablet form on separate occasions, two hours prior to testing. The test was a lexical decision paradigm involving unilateral presentation of pairs of neutral, positive and negative emotional words and nonwords to the left or right visual fields. Reaction time to identify words and nonwords was recorded. Neutral stimuli were processed faster in the left hemisphere, while negative stimuli were processed faster in the right hemisphere. Chlorpromazine improved speed of response for neutral stimuli presented to the right hemisphere and for affective stimuli presented to the left hemisphere. Thus chlorpromazine seems to benefit right hemisphere processing of nonaffective stimuli and benefit left hemisphere processing of affective stimuli. Chlorpromazine appeared to have a different impact on neutral and affective words, and on the right and the left hemispheres. The general effect of chlorpromazine was to reduce lateralisation. It was suggested that this occurred because chlorpromazine blocked dopamine and possibly other neurotransmitters.