Do benzodiazepine receptors mediate the anticonflict action of pentobarbital?

The effects of the benzodiazepine antagonist CGS 8216 (2-phenylpyrazolo[4,3-c]quinoline-3(5H)-one) were examined in a thirsty rat conflict test in the presence and absence of pentobarbital. CGS 8216 (2.5-10 mg/kg i.p.) did not affect nonpunished responding, but doses of 5 and 10 mg/kg significantly reduced the rate of punished responding (i.e., the number of 3 second drinking episodes in a "shock" contingency). However, a dose of CGS 8216 which did not significantly alter punished responding (2.5 mg/kg) antagonized the anticonflict actions of pentobarbital. These observations suggest that while high doses of CGS 8216 may elicit an "anxiogenic" response in rodents, lower doses of CGS 8216 antagonize the anticonflict actions of a compound which has been shown to enhance benzodiazepine affinity in vitro. These data imply that the anticonflict actions of pentobarbital may be mediated through benzodiazepine receptors.     

Glutamate receptors: the cause or cure in perinatal white matter injury?

Glutamate toxicity from hypoxia-ischaemia during the perinatal period causes white matter injury that can result in long-term motor and intellectual disability. Blocking ionotropic glutamate receptors (GluRs) has been shown to inhibit oligodendrocyte injury in vitro, but GluR antagonists have not yet proven helpful in clinical studies. The opposite approach of activating GluRs on developing oligodendrocytes shows promise in experimental studies on rodents as reported by Jartzie et al., in this issue. Group I metabotropic glutamate receptors (mGluRs) are expressed transiently on developing oligodendrocytes in humans during the perinatal period, and the blood-brain-barrier permeable agonist of group I mGluRs, 1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD), reduces white matter damage significantly in a rat model of perinatal hypoxia-ischaemia. The results suggest drugs activating this class of GluRs could provide a new therapeutic approach for preventing cerebral palsy and other neurological consequences of diffuse white matter injury in premature infants.     

Watching soap opera in the diaspora: cultural proximity or critical proximity?

Abstract

This paper focused on an area of transnational Arabic television, which has attracted little scholarly attention: soap operas and their consumption among women in the Arab diaspora. Focus groups with Arab audiences in London revealed the significant role that soap operas play in sustaining a gendered critical and reflexive proximity to the Arab world. The paper shows that soap opera viewing provides female audiences in the diaspora with opportunities to reflect on their own gender identities as distant from hegemonic discourses of gender in their region of origin but as proximate to a moral set of values they associate with this same region. This was especially, but not exclusively, the case with young women born in the diaspora.     

Mangroves: obligate or facultative halophytes? A review

Salinity plays significant roles in regulating the growth and distribution of mangroves, and the salt tolerance mechanisms of mangroves have been the focus of research for several decades. There are contradictory views regarding the relationship between mangroves and salt: (1) Mangroves are facultative halophytes, i.e. freshwater is a physiological requirement and salt water is an ecological requirement for mangroves because they are capable of growing in freshwater. The former prevents excess respiratory losses while the latter prevents invasion and competition from non-halophytes. (2) Mangroves are obligate halophytes, i.e. salt is necessary for their growth. Mangroves cannot survive in freshwater permanently and salt water is a physiological requirement. Up to now, mangroves are usually considered as facultative halophytes. In this review, we provided five lines of evidence to evaluate these two contradictory views: (1) the results of laboratory culture experiments and field investigations; (2) the viviparous nature of mangroves; (3) the salt accumulation of mangroves under freshwater or low salinity; (4) the effect of salinity on the photosynthetic rate and in vitro enzyme activities, and (5) the effects of salinity fluctuation on mangrove growth and physiology. Contrary to widely accepted view, our evaluations of the aforementioned evidence suggest that mangroves are obligate halophytes. Mangroves can grow in freshwater for a limited time by drawing upon the nutrients and salt reserves in their hypocotyls while prolonged culture in freshwater is fatal to them. Mangroves have the ability to absorb Na⁺ and Cl⁻ rapidly and preferentially under low-salinity conditions. Not all of the enzymes in mangroves are sensitive to salt. In fact, the activities of some enzymes are even stimulated by low or moderate salinity. Plants grown under constant salinity in a laboratory setting are unlikely to behave in the same way as those in their natural habitat with fluctuating salinity. Thus, studies on the effects of freshwater or low salinity and salinity fluctuation on mangroves, as well as the physiological mechanisms that allow maintenance of function under fluctuating salinity conditions should be strengthened in future research.     

Multiple Vacuoles in Plant Cells: Rule or Exception?

It is generally accepted that plant cells can contain multiple vacuoles with different functions, for example lytic vacuoles with lysosome-like properties and protein storage vacuoles for reserve accumulation. Recent data call into question the generality of this theory. In this study, we review the published evidence for the existence of multiple vacuoles. We conclude that the multivacuole hypothesis is valid for a number of cases, but care should be taken before assuming that it applies universally.     

Corticosteroid receptors in lymphocytes: a possible marker of brain involution?

A similarity has recently been found between the regulation of corticosteroid receptors in brain and in lymphoid tissue. We have studied the regulation of corticosteroid receptors in human mononuclear leukocytes as a possible marker of brain involution. Type I corticosteroid receptors are down regulated by excess of mineralocorticoids (primary and secondary hyperaldosteronism, pseudohyperaldosteronism) and of glucocorticoids (Cushing's syndrome). Type II corticosteroid receptors are not reduced by excess of endogenous corticostiroids (Cushing's syndrome). In normal adults there is a direct significant correlation between plasma cortisol and Type I and between plasma cortisol and Type II receptors in mononuclear leukocytes, while in Cushing's syndrome the correlation is inverse between plasma cortisol at 8 a.m. and Type II receptors. In an aged population the mean numbers of Type I and of Type II receptors are lower and plasma cortisol is higher than in adult controls, but the increase of plasma cortisol is not followed by a clinical picture of hypercorticism. Corticosteroid Type I and Type II receptors are inversely correlated with age. After dexamethasone suppression (1 mg at 11 p.m.) Type I receptors always decrease in controls while the response of Type II is not homogeneous. In an aged group of patients, both receptors are reduced by dexamethasone. We conclude that the decrease with age of corticosteroid receptors is possibly related to a physiological involution of corticosteroid receptors and that this reduction does increase plasma cortisol concentration, without affecting the glucocorticoid effector mechanism.     

Nitrite in nitric oxide biology: cause or consequence? A systems-based review

All life requires nitrogen compounds. Nitrite is such a compound that is naturally occurring in nature and biology. Over the years, the pharmacological stance on nitrite has undergone a surprising metamorphosis, from a vilified substance that generates carcinogenic nitrosamines in the stomach to a life-saving drug that liberates a protective agent (nitric oxide or NO) during hypoxic events. Nitrite has been investigated as a vasodilator in mammals for over 125 years and is a known by-product of organic nitrate metabolism. There has been a recent rediscovery of some of the vasodilator actions of nitrite in physiology along with novel discoveries which render nitrite a fundamental molecule in biology. Until recently nitrite was thought to be an inert oxidative breakdown product of endogenous NO synthesis but the past few years have focused on the reduction of nitrite back to NO in the circulation as a possible mechanism for hypoxic vasodilatation. Nitrite has evolved into an endogenous signaling molecule and regulator of gene expression that may not only serve as a diagnostic marker but also find its role as a potential therapeutic agent of cardiovascular disease. These data therefore warrant a reevaluation on the fate and metabolism of nitrite in biological systems. This review serves to encompass the history and recent evolution of nitrite, the compartment-specific metabolism of nitrite and its role in plasma as a biomarker for disease, the role of nitrite as a potential regulator of NO homeostasis, and the future of nitrite-based research.     

Supportive or information-processing functions of the mature protoplasmic astrocyte in the mammalian CNS? A critical appraisal

It has been proposed that astrocytes should no longer be viewed purely as support cells for neurons, such as providing a constant environment and metabolic substrates, but that they should also be viewed as being involved in affecting synaptic activity in an active way and, therefore, an integral part of the information-processing properties of the brain. This essay discusses the possible differences between a support and an instructive role, and concludes that any distinction has to be blurred. In view of this, and a brief overview of the nature of the data, the new evidence seems insufficient to conclude that the physiological roles of mature astrocytes go beyond a general support role. I propose a model of mature protoplasmic astrocyte function that is drawn from the most recent data on their structure, the domain concept and their syncytial characteristics, of an independent rather than integrative functioning of the ends of each process where the activities that affect synaptic activity and blood vessel diameter will be concentrated.     

Wnt Signaling in Remyelination in Multiple Sclerosis: Friend or Foe?

Myelination is critical to normal functioning of the vertebrate nervous system. In demyelinating diseases such as multiple sclerosis, oligodendrocytes, the myelinating cells in the central nervous system, are targeted, resulting in myelin loss, axonal damage, and severe functional impairment. While spontaneous remyelination has been proven a failure in multiple sclerosis, understanding the molecular mechanism underlying oligodendrocyte biology, myelination, and remyelination becomes crucial. To date, a series of signaling pathways in regulating oligodendrocyte development and remyelination have been suggested and, among them, the Wnt/β-catenin/Tcf pathway has been considered a negative factor in the myelinating process. However, this notion has been challenged by recent studies, which showed a pro-myelinating effect of this pathway. This review summarizes the current contradictory concepts concerning the role of the Wnt pathway in the oligodendrocyte development and remyelination process, attempts to address the potential mechanism underlying this controversy, and recommends caution in targeting the Wnt pathway as a potential demyelinating therapy.     

Signalling shortcuts: cell-surface receptors in the nucleus?

Do cell-surface growth-factor receptors and their ligands accumulate in the nucleoplasm under physiological conditions? And, if so, how do they get there and what function do they serve in this location? Recent advances have provided tantalizing hints to the answers to these questions, and hold the key to identifying a new mode of signal transduction.     

Neuropeptides in the pineal gland? A critical immunocytochemical study

In an attempt to localize components of the renin angiotensin-system in the pineal gland of rats, immunocytochemical studies using the PAP-technique were performed with antisera against angiotensin I, angiotensin II and angiotensinogen. The staining pattern thus obtained was not only the same for the three antisera, but was also identical to that shown for many other peptide-antisera in the literature. In those studies, the immunocytochemical staining had been ascribed to a distinct pineal cell population or to cell processes. However, by examining adjacent semithin and ultrathin sections by immunocytochemistry and electron microscopy, respectively, we could identify the extracellular perivascular compartment and its flocculent material as the site of staining. This unexpected localization and the observation of "immunoreactivity" of some preimmunesera in the same compartment as well as several additional findings and arguments are taken to suggest that likelihood of "pseudopositive" immunostaining, typical for the pineal gland.     

Can aging be programmed? A critical literature review

The evolution of the aging process has long been a biological riddle, because it is difficult to explain the evolution of a trait that has apparently no benefit to the individual. Over 60 years ago, Medawar realized that the force of natural selection declines with chronological age because of unavoidable environmental risks. This forms the basis of the mainstream view that aging arises as a consequence of a declining selection pressure to maintain the physiological functioning of living beings forever. Over recent years, however, a number of articles have appeared that nevertheless propose the existence of specific aging genes; that is, that the aging process is genetically programmed. If this view were correct, it would have serious implications for experiments to understand and postpone aging. Therefore, we studied in detail various specific proposals why aging should be programmed. We find that not a single one withstands close scrutiny of its assumptions or simulation results. Nonprogrammed aging theories based on the insight of Medawar (as further developed by Hamilton and Charlesworth) are still the best explanation for the evolution of the aging process. We hope that this analysis helps to clarify the problems associated with the idea of programmed aging.     

Is the functional interaction between adenosine A2A receptors and metabotropic glutamate 5 receptors a general mechanism in the brain? Differences and similarities between the striatum and the hippocampus

The aim of the present paper was to examine, in a comparative way, the occurrence and the mechanisms of the interactions between adenosine A_2A receptors (A_2ARs) and metabotropic glutamate 5 receptors (mGlu5Rs) in the hippocampus and the striatum. In rat hippocampal and corticostriatal slices, combined ineffective doses of the mGlu5R agonist 2-chloro-5-hydroxyphenylglycine (CHPG) and the A_2AR agonist CGS 21680 synergistically reduced the slope of excitatory postsynaptic field potentials (fEPSPs) recorded in CA1 and the amplitude of field potentials (FPs) recorded in the dorsomedial striatum. The cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway appeared to be involved in the effects of CGS 21680 in corticostriatal but not in hippocampal slices. In both areas, a postsynaptic locus of interaction appeared more likely. N-methyl-D-aspartate (NMDA) reduced the fEPSP slope and FP amplitude in hippocampal and corticostriatal slices, respectively. Such an effect was significantly potentiated by CHPG in both areas. Interestingly, the A_2AR antagonist ZM 241385 significantly reduced the NMDA-potentiating effect of CHPG. In primary cultures of rat hippocampal and striatal neurons (ED 17, DIV 14), CHPG significantly potentiated NMDA-induced lactate dehydrogenase (LDH) release. Again, such an effect was prevented by ZM 241385. Our results show that A_2A and mGlu5 receptors functionally interact both in the hippocampus and in the striatum, even though different mechanisms seem to be involved in the two areas. The ability of A_2ARs to control mGlu5R-dependent effects may thus be a general feature of A_2ARs in different brain regions (irrespective of their density) and may represent an additional target for the development of therapeutic strategies against neurological disorders.     

Multiple or multiphasic uptake mechanisms in plants?

Abstract Borstlap (1983) has alleged that (a) there are no abrupt changes in curves for the concentration dependence of solute uptake in plants, and (b) many such uptake isotherms may be described by the sum of two Michaelis-Menten terms and a linear term. These claims are considered in detail in connection with the recent finding (Nandi, Pant & Nissen, 1987) that phosphate uptake by corn roots increased more rapidly within the higher phases, i.e. at high external phosphate concentrations, but also levelled off faster than predicted from Michaelis-Menten kinetics. Similar deviations are, in retrospect, also found for uptake of other solutes and result in fewer phases at high external solute concentrations. The simplified and strikingly similar multiphasic patterns in the present paper show that (a) the abrupt changes in published isotherms are not due to error in the data, and (b) uptake isotherms cannot be adequately represented by the sum of two Michaelis-Menten terms and a linear term, or by similar continuous functions, if sufficiently detailed and precise data are used. These findings are not consistent with the existence of multiple uptake mechanisms, including free diffusion, in the plasmalemma. Uptake occurs instead by a single, multiphasic mechanism for each solute or group of related solutes. The similarities in the multiphasic patterns indicate, furthermore, that influx of the various solutes may be coupled.     

Multiple Hsp70 Isoforms in the Eukaryotic Cytosol: Mere Redundancy or Functional Specificity?

Hsp70 molecular chaperones play a variety of functions in every organism, cell type and organelle, and their activities have been implicated in a number of human pathologies, ranging from cancer to neurodegenerative diseases. The functions, regulations and structure of Hsp70s were intensively studied for about three decades, yet much still remains to be learned about these essential folding enzymes. Genome sequencing efforts revealed that most genomes contain multiple members of the Hsp70 family, some of which co-exist in the same cellular compartment. For example, the human cytosol and nucleus contain six highly homologous Hsp70 proteins while the yeast Saccharomyces cerevisiae contains four canonical Hsp70s and three fungal-specific ribosome-associated and specialized Hsp70s. The reasons and significance of the requirement for multiple Hsp70s is still a subject of debate. It has been postulated for a long time that these Hsp70 isoforms are functionally redundant and differ only by their spatio-temporal expression patterns. However, several studies in yeast and higher eukaryotic organisms challenged this widely accepted idea by demonstrating functional specificity among Hsp70 isoforms. Another element of complexity is brought about by specific cofactors, such as Hsp40s or nucleotide exchange factors that modulate the activity of Hsp70s and their binding to client proteins. Hence, a dynamic network of chaperone/co-chaperone interactions has evolved in each organism to efficiently take advantage of the multiple cellular roles Hsp70s can play. We summarize here our current knowledge of the functions and regulations of these molecular chaperones, and shed light on the known functional specificities among isoforms.