bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological Characteristics and Distributions of σ and Phencyclidine Receptors in the Animal Kingdom
Authors: Vu Tuan H. , Weissman Arthur D. , London Edythe D. 
Published: October 2006

Abstract:The phylogenetic distributions ofσ‐ and phencyclidine receptors in neural tissues of 13 species and the pharmacological characteristics of these receptors in whole sea anemone and neural tissues of the guinea pig, chicken, and frog were studied. Specific binding of [3H]haloperidol and [3H]N‐[1‐(2‐thienyl)cyclohexyl]‐3,4‐piperidine, ligands that bind with high affinity to σ‐ and phencyclidine receptors, respectively, was detected in all organisms examined. The order of potencies of various ligands to inhibit 1 nM [3H]haloperidol binding in brains of frogs and guinea pigs or 1 nM [3H]N‐[1‐(2‐thienyl)cyclohexyl]‐3,4–piperidine in chicken or guinea pig brain homogenates was very similar. However, the characteristics and stereospecificity of binding of the two radioligands in sea anemone were different than in higher organisms. The results suggest that σ– and phencyclidine binding sites are evolutionarily old, as the characteristics of the two sites are well preserved over a range of vertebrate phyla.
Marked Regional Heterogeniety of 125I‐Bolton Hunter Substance P Binding and Substance P‐Induced Activation of Phospholipase C in Astrocyte Cultures from the Embryonic or Newborn Rat
Authors: Beaujouan J. C. , de Montety M. C. Daguet , Torrens Y. , Saffroy M. , Dietl M. , Glowinski J. 
Published: October 2006

Abstract:The specific binding of 125‐Bolton Hunter substance P (125I‐BHSP) was estimated on 4‐ to 5‐week‐old primary cultures of astrocytes from several brain structures and the spinal cord of 16‐day‐old embryonic or newborn rats. In both cases, high levels of binding of 125I‐BHSP were found on intact astrocytes from the brainstem, but this binding was low or negligible on cells from the cerebral cortex, striatum, hypothalamus, and mesencephalon. In addition, hippocampal astrocytes from newborn rats were also devoid of 125I‐BHSP binding sites, while a binding of 125I‐BHSP (half that of brainstem cells) was observed on astrocytes from the cerebellum and spinal cord. It was also shown that this regional heterogeneity in 125I‐BHSP binding was not linked to differences in the inactivation of the ligand, cell plating density. or eventual cell contaminants. Five‐day‐old cultures from 16‐day‐old embryos were used to estimate 125I‐BHSP binding on neuron‐enriched cultures. Specific 125I‐BHSP binding was found on cells from the brainstem, mesencephalon, and hypothalamus, but neurons from the cerebral cortex or the striatum contained low or negligible amounts of 125I‐BHSP binding sites. Competition studies using tachykinins and SP analogues indicated that 125I‐BHSP binding sites on brainstem astrocytes (16‐day‐old embryos) have the pharmacological profile expected for NK1 binding sites. SP (1 μM) stimulated phosphoinositide breakdown in cells rich in 125I‐BHSP binding sites (brainstem) but not in those devoid of 125I‐BHSP binding (striatum). These results are discussed in light of previous observations that have shown the presence of 125I‐BHSP binding sites on astrocytes from different brain structures of the mouse.
Modulation of γ‐Aminobutyric Acid Release in Cerebral Cortex by Fluoride, Phorbol Ester, and Phosphodiesterase Inhibitors: Differential Sensitivity of Acetylcholine Release to Fluoride and K+ Channel Blockers
Authors: Gardiner I. M. , de Belleroche J. 
Published: October 2006

Abstract:In this study we have used fluoride as a tool to investigate the involvement of G protein‐coupled effector systems in the regulation of the depolarization‐induced release of γ‐aminobutyric acid (GABA) from rat cerebral cortex. To distinguish among the activating effects of NaF on G proteins linked to different effectors, such as adenylate cyclase, polyphosphoinositide phospholipase C, and K+ channels, agents specific to these effectors have been used in parallel. NaF induced a marked dose‐dependent facilitation of the K+‐evoked release of [14C]GABA, with an EC50 of 1.26 mM, increasing release by 103% at 5 mM NaF. No effect on basal release was seen up to 3 mM NaF, and no modulation of [3H]acetylcholine (ACh) release was seen up to 5 mM NaF. Phorbol 12,13‐diacetate (PDA) produced a similar dose‐dependent facilitation of the K+‐evoked release of [14C]GABA, potentiating the release of [14C]GABA by 50% at 10 μM PDA. The phosphodiesterase inhibitors, 3‐isobutyl‐1‐methylxanthine (IBMX) and theophylline, inhibited the K+‐evoked release of [14C]GABA, and IBMX reversed the NaF facilitation of GABA release in a dose‐dependent manner (pA2 2.57). The K+ channel blocker (IA current) tetrahydroaminoacridine (THA), which markedly inhibits the K+‐evoked release of [14C]GABA, also reversed the NaF facilitatory effect, but the release of [3H]ACh was less sensitive to the inhibitory effect of THA. On the other hand, the K+ channel blocker, tetraethylammonium, which has no effect on the release of [14C]GABA, caused a significant facilitation of K+‐evoked release of [3H]ACh. From these studies, it is concluded that GABA release in cerebral cortex is subject to regulation by G protein‐linked effector systems that are distinct from those affecting the release of [3H]ACh in cerebral cortex.
Immunological Evidence for the Requirement of Sepiapterin Reductase for Tetrahydrobiopterin Biosynthesis in Brain
Authors: Levine Robert A. , Kapatos Gregory , Kaufman Seymour , Milstien Sheldon 
Published: October 2006

Abstract:Specific antibodies to sepiapterin reductase were used to investigate its involvement in de novo (6R)‐5,6,7,8‐tetrahydrobiopterin (BH4) biosynthesis in rat brain. Antisepiapterin reductase (anti‐SR) serum totally inhibited NADPH‐dependent sepiapterin reductase activity in supernatants from discrete rat brain areas and liver. The anti‐SR serum also inhibited the conversion of 7,8‐dihydroneopterin triphosphate to BH4 in rat brain extracts. The inhibition was accompanied by a concentration‐dependent increase in the formation of 6‐lactoyltetrahydropterin (6LPH4), a proposed intermediate in BH4 biosynthesis. In addition, anti‐SR serum was used to characterize the distribution and molecular properties of sepiapterin reductase in rat tissues. Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis followed by Western blotting indicated that there was a single polypeptide with the same molecular weight (28,000) as that of the subunit of pure sepiapterin reductase present in all tissues examined except for liver, where an immunoreactive protein of higher molecular weight (30,500) also was detected. Two‐dimensional gel electrophoresis of rat striatum and liver demonstrated that the isoelectric point of sepiapterin reductase from both tissues was 6.16 and that the higher molecular weight immunoreactive material in liver had an isoelectric point of 7.06. Our studies with specific anti‐SR serum confirmed the results of previous studies using chemical inhibitors of sepiapterin reductase, which suggested that sepiapterin reductase activity was essential for BH4 biosynthesis in the CNS and that 6LPH4 could be a precursor of BH4.
Neuroblastoma Differentiation Involves the Expression of Two Isoforms of the α‐Subunit of Go
Authors: Brabet Philippe , Pantaloni Colette , Rodriguez Marc , Martinez Jean , Bockaert Joël , Homburger Vincent 
Published: October 2006

Abstract:The regulation of GTP‐binding proteins (G proteins) was examined during the course of differentiation of neuroblastoma N1E‐115 cells. N1E‐115 cell membranes possess three Bordetella pertussis toxin (PTX) substrates assigned to α‐subunits (Gα) of Go (a G protein of unknown function) and “Gi (a G protein inhibitory to adenylate cyclase)‐like” proteins and one substrate of Vibrio cholerae toxin corresponding to an α‐subunit of Gs (a G protein stimulatory to adenylate cyclase). In undifferentiated cells, only one form of Goα was found, having a pI of 5.8. Goα content increased by approximately twofold from the undifferentiated state to 96 h of cell differentiation. This is mainly due to the appearance of another Goα form having a pI of 5.55. Both Goα isoforms have similar sizes on sodium dodecyl sulfate‐polyacrylamide gels, are recognized by polyclonal antibodies to bovine brain Goα, are ADP‐ribosylated by PTX, and are covalently myristylated in whole N1E‐115 cells. In addition, immunofluorescent staining of N1E‐115 cells with Goα antibodies revealed that association of Goα with the plasma membrane appears to coincide with the expression of the most acidic isoform and morphological cell differentiation. In contrast, the levels of both Giα and Gsα did not significantly change, whereas that of the common β‐subunit increased by ∼ 30% over the same period. These results demonstrate specific regulation of the expression of Goα during neuronal differentiation.
PACAP and C2‐ceramide generate different AP‐1 complexes through a MAP‐kinase‐dependent pathway: involvement of c‐Fos in PACAP‐induced Bcl‐2 expression
Authors: Aubert Nicolas , Falluel‐Morel Anthony , Vaudry David , Xifro Xavier , Rodriguez‐Alvarez José , Fisch Cécile , De Jouffrey Stéphane , Lebigot Jean‐François , Fournier Alain , Vaudry Hubert , Gonzalez Bruno J. 
Published: October 2006

AbstractThe neuropeptide pituitary adenylate cyclase‐activating polypeptide (PACAP) inhibits C2‐ceramide‐induced cell death through blockade of the mitochondrial apoptotic pathway in rat cerebellar granule neurones. However, the gene induction processes and transcription factors involved in the anti‐apoptotic effect of PACAP remain unknown. Here, we show that PACAP and C2‐ceramide activate activator protein‐1 (AP‐1) DNA binding in a dose‐ and time‐dependent manner, but generate different AP‐1 dimers. Thus, PACAP increased the proportion of c‐Fos and Jun D while C2‐ceramide increased c‐Jun and reduced c‐Fos in AP‐1 complexes. In addition, PACAP strongly activated c‐Fos gene expression while C2‐ceramide markedly increased c‐Jun phosphorylation. The effect of PACAP on c‐Fos expression was blocked by the mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MEK) inhibitor, U0126, while phosphorylation of c‐Jun induced by C2‐ceramide was abrogated by the protein phosphatase 2A (PP2A) inhibitor, okadaic acid. Transfection of immature granule cells with c‐Fos siRNA, which strongly reduced basal and PACAP‐stimulated levels of the protein, totally prevented the stimulatory effect of PACAP on Bcl‐2 expression. The present study demonstrates that AP‐1 complexes containing c‐Fos mediate the effect of PACAP on Bcl‐2 gene expression in cerebellar granule neurones. Our data also indicate that different AP‐1 dimers are associated with the pro‐apoptotic effect of C2‐ceramide and the anti‐apoptotic effect of PACAP.
Differential chemokine response of fibroblast subtypes to complement C1q
Authors: Verardi S. , Page R. C. , Ammons W. F. , Bordin S. 
Published: October 2006

Background and Objective:  The pathogenesis of periodontitis includes an inappropriate activation of the classical complement cascade (C′) with accumulation of inflammatory C′ products in fluids and tissues. Our hypothesis is that in vivo the C′ product, C1q, may act as a regulatory component of the innate immune response of distinct matrix fibroblasts to the inflammatory environment. This study analyzed the C1q induction of pro‐inflammatory cytokine secretion in fibroblast subtypes derived from distinct periodontal tissues, and identified a mechanism of the cell response.Material and Methods:  Primary human gingival fibroblast, periodontal ligament fibroblast, and granulation tissue fibroblast cultures were treated for 24 h with C1q. Protein arrays assessed the secretory profile of constitutive and C1q‐inducible pro‐inflammatory cytokines, and enzyme‐linked immunosorbent assays were used to quantify the kinetics of each inducible cytokine.Results:  Granulation tissue fibroblast cultures were unresponsive to C1q challenge. In contrast, periodontal ligament fibroblasts responded with a release of monocyte chemoattractant protein (MCP)‐1, interleukin‐6, interleukin‐8, and macrophage inflammatory protein (MIP)‐1β higher than the basal level by 8.2‐, 7.0‐, 3.8‐, and 7.2‐fold, respectively. Human gingival fibroblast cultures increased secretion of these chemokines by 5.2‐, 4.5‐, 3.0‐, and 9.8‐fold, respectively. Inhibitor studies revealed that C1q‐inducible release of chemokines by the human gingival fibroblast and periodontal ligament cultures was contingent upon p38 mitogen‐activated protein kinase activity.Conclusion:  The ability of C1q to stimulate secretion of pro‐inflammatory chemokines depends upon which specific fibroblast subtype is involved. Targeting C1q‐activated intracellular signaling pathways may be an effective means to inhibit the production of chemokines that promote inflammatory cell infiltration into gingival and periodontal ligament tissues.
A Standard Penicillinase Preparation
Authors: Liebmann A. J. , McQuarrie E. B. , Perlstein D. 
Published: October 2006

(1) Standardization of penicillinase has been made possible by the method for its assay.
(2) A purified, dried and sterile penicillinase has been found to be a penicillin-inactivator superior to Clarase for the penicillin sterility test.
(3) Preliminary studies show this penicillinase preparation may be used for inactivating penicillin in exudates of body fluids.
Precipitation and Agglutination Tests with the Hemolytic Streptococcus. Titration of "M" and "T" Anti-Bodies in Human Sera
Authors: Thomas Ruth Alida 
Published: October 2006

While "M" and "T" antibodies can be demonstrated in low titre in human sera, an almost complete absence of specificity seems to indicate an apparent lack of correlation with current or past streptococcal illness. In the present study, agglutination and precipitation tests on patient's sera, using known "T" and "M" antigens, appear to have little value in determining the antigenic relationship of the streptococci involved in infection. Moreover, no correlation could be shown between the amounts of "M" antibody and of "T" antibody present in the different sera.
It is obvious that further work is needed. With a greater degree of purification of "M" and "T" and the elimination of non-specific substances, it may ultimately be possible to demonstrate the development of significant type-specific antibodies in human sera.
Penicillin in Iodized Oil for Instillation Into the Lungs
Authors: Romansky Monroe J. , Dugan David J. , Rittman George E. 
Published: October 2006

(1) A suspension of calcium penicillin in 40 per cent. iodized oil produces a stable mixture which has been instilled in the lungs of 12 patients without adverse effect and has maintained penicillin in the lung for a minimum of 24 hours, after a single instillation.
(2) The penicillin iodized oil has maintained its potency for 60 days at ice box, room and 37° C. temperatures.
An Adjustable Resistance with Linear Response to Air Flow for Respiration Experiments
Authors: Silverman Leslie , Rao M. N. 
Published: October 2006

A simple easily adjustable linear response resistance apparatus is described. The resistance unit contains a glass filter cloth, the effective area of which is adjusted by a mercury column.
The resistance of the unit can be adjusted from 0.1 to 1.0 millimeters of water per liter of air flow per minute. The resistance can be easily increased or decreased during the progress of an experiment. The mercury hazard during inspiration was evaluated and not found significant for experiments of one hour.
Architecture of the Human Lung
Authors: Weibel Ewald R. , Gomez Domingo M. 
Published: October 2006

An attempt has been made to define quantitatively the architecture of airways and blood vessels of the human lung. For this purpose five normal lungs from individuals aged 8 to 74 years were subjected to a dimensional analysis by several methods of measurement based on statistical principles.
The elements of the "respiratory zone" may be regarded as randomly distributed in the lung. There are essentially the same number of alveoli (300 million), alveolar ducts (14 million), and capillary segments (280 billion) in all lungs. The dimensions of these architectural elements are shown to depend mainly on the size of the lung. The effect on these dimensions of such functional variables as the degree of inflation of the lung or of the filling of capillaries with blood are discussed.
The alveolar and alveolar-capillary surface areas, which are of importance in the analysis of gas exchange between air and blood, are found to increase with the size of the lung. In our material, both varied in the range of 40 to 80 square meters.
The elements of the conductive zone of the lung show a polar orientation. The airways have, on the average, 23 generations of dichotomous branching; the pulmonary arteries reach the precapillaries after about 28 generations. The average diameters of the airway and blood-vessel elements at each generation appear to follow the laws of "best" dimensions. The functional significance of this finding is discussed.
It is suggested that morphometric studies conducted according to this general model may be useful in the anatomical description of other organs.
Planetary Contamination I: The Problem and the Agreements
Authors: Horowitz N. H. , Sharp R. P. , Davies R. W. 
Published: October 2006

The sterility requirements for landed spacecraft tentatively adopted in the COSPAR resolution of 1964 are so severe as to pose a major obstacle to planetary exploration. This by itself would not justify modification of the requirements, since preservation of the biological integrity of Mars is essential for proper exploration of the planet. However, when the physical and biological assumptions underlying the COSPAR recommendations are compared with actual conditions on Mars, as established by recent observations, it becomes apparent that the COSPAR assumptions are unrealistic in important respects. Specifically, the belief that eolian erosion on Mars can effect the release of spores trapped in the interior of solids in periods of time that are short compared with the time scale of the unmanned space program is unsupported by either observation or theory. On the contrary, the analysis suggests that rates of eolian erosion on Mars are very low. Similarly, present knowledge of the Martian environment opposes the view that terrestrial microorganisms would readily contaminate the planet. The combination of dryness, lack of oxygen, and high ultraviolet flux makes the surface of Mars peculiarly unsuitable for the multiplication of terrestrial organisms. Recent studies give little support to the proposal that significant areas of geothermal activity exist on Mars.
These various findings suggest that the COSPAR-recommended constraints could be substantially relaxed without compromising to any significant degree the biological condition of Mars. In particular, a distinction needs to be made between microorganisms trapped in solids and those on exposed surfaces of landed spacecraft. Surface sterility is an unconditional requirement, in the sense that it is imposed by considerations unrelated to the nature of the Martian environment. Sterilization of the interior of solids to the extreme level recommended by COSPAR, however, is based on the assumption that entrapped organisms constitute a substantial hazard to the ecology of Mars. This assumption now seems unjustified, and the need for a high degree of interior sterility is doubtful. Current spacecraft-sterilization policies should be revised accordingly.
Sounder Thinking Through Clearer Writing
Authors: Woodford F. Peter 
Published: October 2006

Bad scientific writing involves more than stylistic inelegance: it is often the outward and visible form of an inward confusion of thought. The scientific literature at its present standard distorts rather than forms the graduate student's view of scientific knowledge and thought, and corrupts his ability to write, to read, and to think.
Strong educational measures are needed to effect reform. I advocate a course on scientific writing as an essential feature in every scientist's training. Such a course delves deep into the philosophy and method of science if it deals with logic, precision, and clarity; on how these qualities can be achieved in writing; and on how such achievement strengthens the corresponding faculties in thinking.
Hydride Complexes
Authors: Chatt Joseph 
Published: October 2006

Hydride complexes of transition metals were virtually unknown 12 years ago, but they have now been found to lie at the root of many interesting catalytic chemical reactions, some of which were used in industry even before the unique properties of hydride complexes, which formed their basis, had been realized.
This article surveys the history, preparations, important properties, and reactions of hydride complexes, surveys their part in important catalytic industrial processes, and speculates about their possible role in the biological fixation of nitrogen.
The Discovery of America
Authors: Martin Paul S. 
Published: October 2006

I propose a new scenario for the discovery of America. By analogy with other successful animal invasions, one may assume that the discovery of the New World triggered a human population explosion. The invading hunters attained their highest population density along a front that swept from Canada to the Gulf of Mexico in 350 years, and on to the tip of South America in roughly 1000 years. A sharp drop in human population soon followed as major prey animals declined to extinction.
Possible values for the model include an average frontal depth of 160 kilometers, an average population density of 0.4 person per square kilometer on the front and of 0.04 person per square kilometer behind the front, and an average rate of frontal advance of 16 kilometers per year. For the first two centuries the maximum rate of growth may have equaled the historic maximum of 3.4 percent annually. During the episode of faunal extinctions, the population of North America need not have exceeded 600,000 people at any one time.

The model generates a population sufficiently large to overkill a biomass of Pleistocene large animals averaging 9 metric tons per square kilometer (50 animal units per section) or 2.3 × 10
8
metric tons in the hemisphere. It requires that on the front one person in four destroy one animal unit (450 kilograms) per week, or 26 percent of the biomass of an average section in 1 year in any one region. Extinction would occur within a decade. There was insufficient time for the fauna to learn defensive behaviors, or for more than a few kill sites to be buried and preserved for the archeologist. Should the model survive future findings, it will mean that the extinction chronology of the Pleistocene megafauna can be used to map the spread of
Homo sapiens
throughout the New World.