Distribution by Scientific Domains
Distribution within Engineering

Kinds of Sons

  • adult son
  • john wiley son
  • wiley son

  • Terms modified by Sons

  • son ltd
  • son ltd.
  • son preference

  • Selected Abstracts

    Impact of Sim1 gene dosage on the development of the paraventricular and supraoptic nuclei of the hypothalamus

    Sabine Michaëlle Duplan
    Abstract The bHLH-PAS transcription SIM1 is required for the development of all neurons of the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Mice with a loss of Sim1 die within a few days of birth, presumably because of the lack of a PVN and SON. In contrast, mice with a decrease of Sim1 survive, are hyperphagic and become obese. The mechanism by which Sim1 controls food intake remains unclear. Here we show that the development of specific PVN and SON cell types is sensitive to Sim1 gene dosage. Sim1 haploinsufficiency reduces the number of vasopressin (AVP)- and oxytocin-producing cells in the PVN by about 50 and 80%, respectively, but does not affect the development of Crh, Trh and Ss neurons. A decrease of AVP-producing cells increases the sensitivity of Sim1 heterozygous mice to chronic dehydration. Moreover, retrograde labelling showed a 70% reduction of PVN neurons projecting to the dorsal vagal complex, raising the possibility that a decrease of these axons contributes to the hyperphagia of Sim1+/, mice. Sim1 haploinsufficiency is thus associated with a decrease of several PVN/SON cell types, which has the potential of affecting distinct homeostatic processes. [source]

    GABA selectively controls the secretory activity of oxytocin neurons in the rat supraoptic nucleus

    Mario Engelmann
    Abstract Recently we reported that a single social defeat experience triggers the release of oxytocin (OXT) from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate the regulatory mechanisms underlying this dissociated release, we exposed male Wistar rats to a 30-min social defeat and monitored release of the inhibitory amino acids gamma amino butyric acid (GABA) and taurine within the hypothalamic supraoptic nucleus (SON) using microdialysis. Social defeat caused a significant increase in the release of both GABA and taurine within the SON (up to 480%; P < 0.01 vs. prestress release). To reveal the physiological significance of centrally released GABA, the specific GABAA -receptor antagonist bicuculline (0.02 mm) was administered into the SON via retrodialysis. This approach caused a significant increase in the release of OXT both within the SON and into the blood under basal conditions and during stress (up to 300 and 200%, respectively; P < 0.05 vs. basal values), without affecting plasma vasopressin. Electrophysiological studies confirmed the selective action of bicuculline on the firing activity of OXT neurons in the SON. Taken together, our data demonstrate that GABA is released within the SON during emotional stress to act as a selective inhibitor of both central and peripheral OXT secretion. [source]

    The effects of nitric oxide on magnocellular neurons could involve multiple indirect cyclic GMP-dependent pathways

    C. M. Vacher
    Abstract Nitric oxide (NO) is known to regulate the release of arginine-vasopressin (AVP) and oxytocin (OT) by the paraventricular nucleus (PVN) and the supraoptic nucleus (SON). The aim of the current study was to identify in these nuclei the NO-producing neurons and the NO-receptive cells in mice. The determination of NO-synthesizing neurons was performed by double immunohistochemistry for the neuronal form of NO synthase (NOS), and AVP or OT. Besides, we visualized the NO-receptive cells by detecting cyclic GMP (cGMP), the major second messenger for NO, by immunohistochemistry on hypothalamus slices. Neuronal NOS was exclusively colocalized with OT in the PVN and the SON, suggesting that NO is mainly synthesized by oxytocinergic neurons in mice. By contrast, cGMP was not observed in magnocellular neurons, but in GABA-, tyrosine hydroxylase- and glutamate-positive fibers, as well as in GFAP-stained cells. The cGMP-immunostaining was abolished by incubating brain slices with a NOS inhibitor (L-NAME). Consequently, we provide the first evidence that NO could regulate the release of AVP and OT indirectly by modulating the activity of the main afferents to magnocellular neurons rather than by acting directly on magnocellular neurons. Moreover, both the NADPH-diaphorase activity and the mean intensity of cGMP-immunofluorescence were increased in monoamine oxidase A knock-out mice (Tg8) compared to control mice (C3H) in both nuclei. This suggests that monoamines could enhance the production of NO, contributing by this way to the fine regulation of AVP and OT release and synthesis. [source]

    Trends in the southern oscillation phenomenon and Australian rainfall and changes in their relationship

    Ramasamy Suppiah
    Abstract An attempt has been made to investigate decadal-scale trends in Australian rainfall and in the southern oscillation index (SOI) and their influence on the relationship between them. Monthly rainfall data from high-quality stations in Australia (from 1900 to 1995), India, Sri Lanka and Tahiti are used. The relationship between the SOI and Australian rainfall is positive, but shows decadal-scale variations during the past century. Although there were extended and severe El Niño events in the early 1990s and in 1997, Australia did not experience the expected severe rainfall deficiencies characteristic of previous events. However, severe drought conditions over eastern Australia were associated with a moderate El Niño event during 2002,03. Long-term fluctuations of March,May (MAM) rainfall show high-frequency variations, but trends during June,August (JJA), September,November (SON) and December,February (DJF) show low-frequency or decadal-scale variations. Trends and multi-decadal fluctuations in all-Australian spring (SON) and summer (DJF) rainfall are strongly dominated by rainfall trend fluctuations in northern and eastern Australia. Austral summer rainfall shows an increasing trend during the 1980s and 1990s, particularly in Queensland and New South Wales, despite the occurrence of extended and severe El Niños. However, some parts of New South Wales and Queensland experienced severe rainfall deficiencies during 2002,03 in conjunction with an El Niño event. The relationship between the SOI and rainfall on the interannual time scale is strong when the SOI and rainfall follow the same direction, but it is weak when they follow opposite directions on a decadal-time scale. The poor correlation during the 1920s and 1930s was due to a slightly increasing trend in the SOI and a stronger decreasing trend in rainfall. A weakening in the relationship between the SOI and rainfall in recent years, after the mid-1970s, is due to a small increase in rainfall in the 1980s and 1990s and a strong decrease in the SOI. Rainfall trends were enhanced (stronger decreases or increases) when the influence of the SOI (or El Niño-southern oscillation (ENSO)) was removed. Enhanced increases and decreases are particularly strong during SON and DJF, when the ENSO phenomenon is at the mature stage and also the influence on Australian rainfall is strong. The increasing trend in rainfall during the 1980s and 1990s in some parts of eastern Australia and the decreasing trend in the SOI result in more rainfall for a given SOI compared with the same SOI during the previous period, i.e. before the mid-1970s. A similar analysis was carried out for two periods, before and after 1972, for Tahiti, India and Sri Lanka. The upward or downward shift in regression lines is very clear during the season, that shows a strong relationship between rainfall and the SOI. Moreover, strengthening or weakening of the relationship between rainfall and the SOI is largely dependent on their multi-decadal variations and trends during the past century. Increases in rainfall during the 1980s and the 1990s and decreases in the SOI have weakened their relationship, both in Australia and India. Such a relationship gives more rainfall for a given SOI after 1973. The pattern was reversed for Sri Lanka, where rainfall during the second intermonsoon season has decreased. Analyses of trends in temperature at Darwin and Tahiti and of rainfall over Australia, India, Tahiti and Sri Lanka suggest a regional-scale change in climate, whereas the SOI reflects a change in the large-scale circulation pattern over the Indo-Pacific region after the mid-1970s. Copyright © 2004 Royal Meteorological Society [source]

    Observed and SST-forced seasonal rainfall variability across tropical America

    Vincent Moron
    Abstract Three experiments starting from different initial conditions have been made with the ECHAM-4 atmospheric General Circulation Model (GCM) integrated at T30 resolution forced with the observed sea-surface temperature (SST) over the period 1960,1994. The tropical America modes of seasonal rainfall anomalies whose time variation is most accurately simulated by the GCM have been searched for using Singular Value Decomposition Analyses (SVDA) and Canonical Correlation Analysis (CCA) between observed and model fields. The leading modes revealed by SVDA and CCA are highly similar, even though the ordering of the modes showed some fluctuation. A first skilful rainfall anomaly mode has weights of the same sign almost everywhere in tropical America, except along the western coast and the sub-tropical margins. This mode appears in all of the four seasons assessed. A second major skilful mode is usually a bipolar north,south (N,S) rainfall anomaly pattern (clear in December,March, DJFM; March,May, MAM; and June,September, JJAS). A large portion of the skill of the first rainfall anomaly mode (same sign anomalies across tropical America except small patches along the western coast) is through variance that is in common with the Southern Oscillation Index (SOI). In addition to forcing from the central/eastern tropical Pacific SST, there also appears a contribution from contrasting SST anomalies in the tropical Atlantic. This rainfall mode is usually a regional portion of a more large-scale mode encompassing at least the whole tropical zone (especially in DJFM, MAM and September,November, SON). Analysis of the relationship of this mode with GCM circulation features reveals that a rainfall deficit (respectively excedent) over the main rainbelt of the tropical America region is associated with strengthening (respectively weakening) of the sub-tropical westerly jet streams, a global warming (respectively cooling) of the tropical atmosphere, an anomalous divergence (respectively convergence) in the lower levels and an anomalous convergence (respectively divergence) in the upper levels over tropical America and in the region of the Atlantic Inter-tropical Convergence Zone (ITCZ). Such global features are not so apparent for the dominant mode of JJAS, even though the correlations with El Niño,Southern Oscillation (ENSO) indicators (as SOI or NINO3 SST index) are as high as for the other seasons. The bipolar N,S rainfall anomaly mode in tropical America is mostly related to anomalous N,S gradient of SST anomalies in the tropical Atlantic. The atmospheric circulation anomalies emphasize changes in 850 hPa meridional winds in the tropical Atlantic. However, there is also interannual variance of this rainfall mode in both the model and observations that is unexplained by tropical Atlantic SSTs, but which is explained by central/eastern tropical Pacific SSTs and, potentially, SSTs from other tropical and extratropical areas. This is especially true in MAM. Some differences in the details of the model and observed teleconnection patterns are noted. Such differences can be used to statistically adjust the model simulations using the CCA or SVDA modes as basis patterns. Both statistical approaches have been applied and the results are consistent between the two. The increase of skill is stronger when temporal correlation (the pattern correlation) between the model and observed pattern is high (low) as for JJAS. The skill is moderate to high around the whole Amazon basin, but remains relatively low inside the Amazon basin, though reliability of the observations themselves may influence this result. Averaged over all the seasons, about 15,35% (35,55%) of the interannual grid-box (regional) seasonal rainfall variance is skilfully simulated from the observed SST forcing. Copyright © 2001 Royal Meteorological Society [source]

    Electrophysiological Identification of the Functional Presynaptic Nerve Terminals on an Isolated Single Vasopressin Neurone of the Rat Supraoptic Nucleus

    T. Ohbuchi
    Release of arginine vasopressin (AVP) and oxytocin from magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) is under the control of glutamate-dependent excitation and GABA-dependent inhibition. The possible role of the synaptic terminals attached to SON neurones has been investigated using whole-cell patch-clamp recording in in vitro rat brain slice preparations. Recent evidence has provided new insights into the repercussions of glial environment modifications on the physiology of MNCs at the synaptic level in the SON. In the present study, excitatory glutamatergic and inhibitory GABAergic synaptic inputs were recorded from an isolated single SON neurone cultured for 12 h, using the whole-cell patch clamp technique. Neurones expressed an AVP-enhanced green fluorescent protein (eGFP) fusion gene in MNCs. In addition, native synaptic terminals attached to a dissociated AVP-eGFP neurone were visualised with synaptic vesicle markers. These results suggest that the function of presynaptic nerve terminals may be evaluated directly in a single AVP-eGFP neurone. These preparations would be helpful in future studies aiming to electrophysiologically distinguish between the functions of synaptic terminals and glial modifications in the SON neurones. [source]

    Interleukin-1, Release in the Supraoptic Nucleus Area During Osmotic Stimulation Requires Neural Function

    J. Y. Summy-Long
    Interleukin (IL)-1, is present throughout the magnocellular neuroendocrine system and co-depletes with oxytocin and vasopressin from the neural lobe during salt-loading. To examine whether IL-1, is released from the dendrites/soma of magnocellular neurones during osmotic stimulation, microdialysis adjacent to the supraoptic nucleus (SON) in conscious rats was combined with immunocapillary electrophoresis and laser-induced fluorescence detection to quantify cytokine in 5-min dialysates collected before (0,180 min; basal), and after (180,240 min), hypertonic saline injected s.c. (1.5 m NaCl). Osmotic release of IL-1, was compared after inhibiting local voltage-gated channels for Na+ (tetrodotoxin) and Ca2+ (cadmium and nickel) or by reducing intracellular Ca2+ stores (thapsigargin). Immunohistochemistry combined with microdialysis was used to localise cytokine sources (IL-1,+) and microglia (OX-42+). Under conditions of microdialysis, the basal release of IL-1,+ in the SON area was measurable and stable (pg/ml; mean ± SEM) from 0,60 min (2.2 ± 0.06), 60,120 min (2.32 ± 0.05) and 120,180 min (2.33 ± 0.06), likely originating locally from activated microglia (OX42+; IL-1,+; ameboid, hypertrophied) and magnocellular neurones expressing IL-1,. In response to osmotic stimulation, IL-1, increased progressively in dialysates of the SON area by a mechanism dependent on intracellular Ca2+ stores sensitive to thapsigargin and, similar to dendritic secretion of oxytocin and vasopressin, required local voltage-gated Na+ and Ca2+ channels for activation by osmoregulatory pathways from the forebrain. During osmotic stimulation, neurally dependent release of IL-1, in the SON area likely upregulates osmosensitive cation currents on magnocellular neurones (observed in vitro by others), to facilitate dendritic release of neurohypophysial hormones. [source]

    Expression of GABAB Receptors in Magnocellular Neurosecretory Cells of Male, Virgin Female and Lactating Rats

    D. S. Richards
    Abstract GABA is one of the key neurotransmitters that regulate the firing activity of neurones in the supraoptic (SON) and paraventricular (PVN) nuclei. In the present study, we used immunohistochemical techniques to study the distribution and subcellular localisation of metabotropic GABAB receptors in magnocellular neurones in the SON and PVN. Robust GABAB receptor immunoreactivity (GABABR; both subunit 1 and subunit 2 of the heterodimer), was observed in the SON and PVN. At the light microcope level, GABABR immonoreactivity displayed a clustered pattern localised both intracytoplasmically and at the plasma membrane. Densitometry analysis indicated that GABABR immunoreactivity was significantly more intense in vasopressin cells than in oxytocin cells, both in male, virgin female and lactating rats, and was denser in males than in virgin females. Light and electron microscope studies indicated that cytoplasmic GABABR was localised in various organelles, including the Golgi, early endosomes and lysosomes, suggesting the cycling of the receptor within the endocytic and trafficking pathways. Some smaller clusters at the level of the cell plasma membrane were apposed to glutamic acid decarboxylase 67 immunoreactive boutons, and appeared to be colocalised with gephyrin, a constituent protein of the postsynaptic density at inhibitory synapses. The presence of GABABR immunoreactivity at synaptic and extrasynaptic sites was supported by electron microscopy. These results provide anatomical evidence for the expression of postsynaptic GABAB receptors in magnocellular neurosecretory cells. [source]

    Glial Limitans Elasticity Subjacent to the Supraoptic Nucleus

    A. K. Salm
    Abstract Two previous studies from our laboratory have indicated that the ventral glial limitans subjacent to the hypothalamic supraoptic nucleus (SON-VGL) undergoes a reversible thinning upon chronic activation of the magnocellular neuroendocrine cells (MNCs) of the supraoptic nucleus (SON). Numerous other studies have shown that MNC somata hypertrophy with activation. One aim of the current study was to understand better how SON-VGL thinning occurs. A second aim was to quantify overall changes of the MNC somata region due to cellular hypertrophy to compare relative changes in dimensions. Here, we undertook a light microscopic stereological investigation of the SON and the subjacent SON-VGL of Nissl stained material under basal and activated conditions. Astrocyte numbers in the underlying SON-VGL remained stable across hydration state as did the overall volume of the SON-VGL and dendritic zone reference area. How these data are consistent with our earlier observations of SON-VGL thinning was resolved by the finding of a highly significant, 30% increase in the mediolateral dimension of the SON-VGL in dehydrated rats. These observations fit well with previous work from our laboratory that demonstrates a reorientation of SON-VGL astrocytes, from vertical to horizontal, which occurs in the activated SON-VGL. We found a significant, approximately 54%, increase in the overall volume of the MNC region of the SON. No significant rostrocaudal lengthening of the SON was detected, although a trend was evident. All the observed changes reversed with rehydration. These data indicate that elasticity of the SON-VGL acts to accommodate the volume expansion of the MNCs and enables the SON-VGL to continue as an interface between the underlying cerebrospinal fluid in the subarachnoid space and the expanded SON above. [source]

    Localization of Transforming Growth Factors, TGF,1 and TGF,3, in Hypothalamic Magnocellular Neurones and the Neurohypophysis

    M. Fèvre-Montange
    Abstract The distribution of transforming growth factor beta (TGF,) in the rat and human hypothalamus and neurohypophysis was investigated by immunocytochemical techniques using rabbit polyclonal antisera against TGF,1 and TGF,3. Colocalization of TGF,1 or TGF,3 and arginine vasopressin (AVP) in the rat hypothalamus was studied by double immunolabelling in light microscopy, while their subcellular localization in the rat neurohypophysis was investigated by immunoelectron microscopy. TGF,1 and TGF,3 immunoreactivity was demonstrated in the cell bodies and processes of neurones in the supraoptic nucleus (SON) and paraventricular nucleus (PVN). The TGF,-immunoreactive cells were more numerous in the SON compared to the PVN. TGF,/AVP double-labelled cells were seen in both nuclei, but some neurones in the SON were labelled for TGF,1 or TGF,3, although not for AVP. In the rat and human neurohypophysis, TGF,3 immunolabelling was more diffuse and stronger than TGF,1 immunolabelling. TGF,1 expression was seen in axonal vesicles and in neurosecretory granules of the axonal endings, while TGF,3 was observed in axonal fibres. Colocalization of TGF,3 or TGF,1 and AVP was observed in some neurosecretory granules, but many were either single-labelled for TGF, or AVP or unlabelled. Our results demonstrate, for the first time, the colocalization of TGF, and neurohypophysial hormones in magnocellular neurones. We suggest that TGF, secreted by the neurohypophysis regulates the proliferation and secretion of certain anterior pituitary cells. [source]

    Ageing and the Diurnal Expression of the mRNAs for Vasopressin and for the V1a and V1b Vasopressin Receptors in the Suprachiasmatic Nucleus of Male Rats

    T. Kalamatianos
    Abstract Changes in the function of neuropeptide synthesizing cells within the suprachiasmatic nucleus (SCN), the site of the predominant circadian pacemaker, may underlie the disturbance of rhythms observed during ageing. Arginine vasopressin (AVP) is synthesized by nearly one-third of SCN neurones in the rat. This peptide has predominantly excitatory actions within the SCN mediated by V1 -type receptors; the extent to which the V1a and/or V1b receptor subtypes are involved in SCN functions remains to be determined. The present study used isotopic in situ hybridization histochemistry to examine the effects of ageing on expression of mRNAs for AVP and V1a in the SCN and for V1b in the SCN and supraoptic nucleus (SON) of male rats kept under a 12 : 12 h light/dark cycle. Analysis of film autoradiographs from young adult (2,3-month-old; n = 40) or aged (19,20-month-old; n = 40) animals, at eight time points across the light/dark cycle, revealed an equivalent pattern and amplitude for the diurnal rhythm of AVP mRNA in the SCN of the young adult and aged groups. Both groups also displayed a significant diurnal rhythm in the expression of V1a receptor mRNA; however, the amplitude of this rhythm was reduced in the aged group, due to increased levels during the light phase and early part of night. Although the expression of V1b mRNA did not display a significant diurnal rhythm within the SCN or SON, persistently elevated levels for V1b mRNA were observed in the aged group at both sites. [source]

    Presynaptic Noradrenergic Regulation of Glutamate Inputs to Hypothalamic Magnocellular Neurones

    C. Boudaba
    Abstract Glutamate and norepinephrine transmitter systems play critical roles in the synaptic control of hypothalamic magnocellular neurones. We recently reported on a norepinephrine-sensitive glutamate circuit within the paraventricular nucleus (PVN) that projects to magnocellular neurones. Here, we present evidence for norepinephrine regulation of glutamate release in the PVN and supraoptic nucleus (SON) via actions on presynaptic terminals. Whole-cell synaptic currents were recorded in magnocellular neurones of the SON and PVN in an acute slice preparation. Bath application of norepinephrine (100 µm) caused a robust, reversible increase in the frequency of spontaneous glutamatergic excitatory postsynaptic currents in 100% of SON neurones (246%) and in 88% of PVN magnocellular neurones (259%). The norepinephrine-induced increase in glutamate release was mediated by activation of both presynaptic ,1 receptors and ,2 receptors, but the ,1 -receptor component was the predominant component of the response. The presynaptic actions of norepinephrine were predominantly, although not completely, resistant to blockade of Na-dependent spikes, implicating a presynaptic terminal locus of action. Interestingly, the spike-dependent component of the response was greater in PVN than in SON magnocellular neurones. This robust presynaptic facilitation of glutamate release by norepinephrine, combined with the known excitatory postsynaptic actions of norepinephrine, activational effects on local glutamate circuits, and inhibitory effects on ,-aminobutyric acid release, indicate a strong excitatory role of norepinephrine in the regulation of oxytocin and vasopressin release during physiological stimulation. [source]

    Nitrogen biomarkers and their fate in soil,

    Wulf Amelung
    Abstract More than 90,% of the nitrogen (N) in soils can be organically bound, but the mechanisms and rates by which it is cycled have eluded researchers. The objective of this research was to contribute to a better understanding of the origin and transformation of soil organic N (SON) by using amino sugars and the enantiomers of amino acids as markers for microbial residues and/or aging processes. Studied samples presented here comprised (1) soil transects across different climates, (2) arable soils with different duration of cropping, and (3) radiocarbon-dated soil profiles. The results suggested that increased microbial alteration of SON temporarily results in a sequestration of N in microbial residues, which are mineralized at later stages of SON decomposition. Microorganisms increasingly sequestered N within intact cell wall residues as frost periods shortened. At a mean annual temperature above 12,15,°C, these residues were mineralized, probably due to limitations in additional substrates. Breaking the grassland for cropping caused rapid SON losses. Microbial residues were decomposed in preference to total N, this effect being enhanced at higher temperatures. Hence, climate and cultivation interactively affected SON dynamics. Nevertheless, not all SON was available to soil microorganisms. In soil profiles, L-aspartic acid and L-lysine slowly converted into their D-form, for lysine even at a similar rate in soils of different microbial activity. Formation of D-aspartate with time was, therefore, induced by microorganisms while that of D-lysine was not. The racemization of the two amino acids indicates that SON not available to microorganisms ages biotically and abiotically. In native soils, the latter is conserved for centuries, despite N deficiency frequently occurring in living terrestrial environments. Climate was not found to affect the fate of old protein constituents in surface soil. When native grassland was broken for cropping, however, old SON constituents had become available to microorganisms and were degraded. Stickstoff-Biomarker und ihre Dynamik im Boden Über 90,% des Stickstoffs im Boden können organisch gebunden sein. Um zu einem besseren Verständnis der Norg -Dynamik im Boden beitragen zu können, analysierte ich Aminozucker und Aminosäure-Enantiomere als Marker für mikrobielle N-Rückstände und/oder Alterungsprozesse von Norg im Boden. Das hier vorgestellte Untersuchungsmaterial umfasste (1) Bodentransekte entlang unterschiedlicher Klimate, (2) Ackerböden mit verschiedener Nutzungsdauer und (3) 14C-datierte Bodenprofile. Die Ergebnisse zeigten, dass mit fortschreitender Umwandlung des Norg mikrobielle N-Rückstände nur vorübergehend im Boden akkumulieren, da sie in späteren Abbauphasen wieder mineralisiert werden. Mikroorganismen bauten zunehmend N in intakte Zellwandrückstände ein, wenn sich die Frostperioden verkürzten. Bei einer Jahresmitteltemperatur über 12,15,°C sank der Beitrag mikrobieller Rückstände zum N-Gehalt, vermutlich weil Mikroorganismen diese mangels anderer Substrate verstärkt mineralisierten. Umbrüche von Gras- zu Ackerland führten zu raschen N-Verlusten. Mikrobielle N-Rückstände wurden bevorzugt abgebaut, ein Effekt, den höhere Temperaturen verstärkten. Demnach steuerte das Klima die Intensität von Nutzungseffekten auf die Norg -Dynamik. Doch nicht der gesamte Norg war für Mikroorganismen zugänglich. Der D-Gehalt von Asparaginsäure und Lysin nahm mit steigendem Alter der organischen Bodensubstanz zu, Lysin racemisierte in den verschiedenen Böden sogar mit gleicher Geschwindigkeit. Anders als die Bildung von D-Asparaginsäure wurde die von Lysin also nicht durch Mikroorganismen beeinflusst. Die Racemisierung der beiden Aminosäuren deutet deshalb darauf hin, dass nicht-bioverfügbare Norg -Bestandteile biotisch und abiotisch im Boden altern. Klimaeinwirkungen auf den Verbleib alter Proteinrückstände ließen sich nicht feststellen. Mit Umbruch von Gras- zu Ackerland erhielten Mikroorganismen allerdings Zugang zu alten Norg -Verbindungen und bauten diese ab. [source]


    MODERN THEOLOGY, Issue 1 2010
    In this article we argue that an immaterialist ontology,a metaphysic that denies the existence of material substance,is more consonant with Christian dogma than any ontology that includes the existence of material substance. We use the philosophy of the famous eighteenth-century Irish immaterialist George Berkeley as a guide while engaging one particularly difficult Christian mystery: the doctrine of the Incarnation of Christ. The goal is to make plausible the claim that, from the analysis of this one example, there are strong reasons for thinking that if one wants to be a Christian one ought to be an immaterialist. [source]

    Characterization of CART neurons in the rat and human hypothalamus

    Carol F. Elias
    Cocaine- and amphetamine-regulated transcript (CART) is a recently described neuropeptide widely expressed in the rat brain. CART mRNA and peptides are found in hypothalamic sites such as the paraventricular nucleus (PVH), the supraoptic nucleus (SON), the lateral hypothalamic area (LHA), the dorsomedial nucleus of the hypothalamus (DMH), the arcuate nucleus (Arc), the periventricular nucleus (Pe), and the ventral premammillary nucleus (PMV). Intracerebroventricular administration of recombinant CART peptide decreases food intake and CART mRNA levels in the Arc are regulated by leptin. Leptin administration induces Fos expression in hypothalamic CART neurons in the PVH, the DMH, the Arc, and the PMV. In the current study, we used double label in situ hybridization histochemistry to investigate the potential direct action of leptin on hypothalamic CART neurons and to define the chemical identity of the hypothalamic CART neurons in the rat brain. We found that CART neurons in the Arc, DMH, and PMV express long form leptin-receptor mRNA, and the suppressor of cytokine signaling-3 (SOCS-3) mRNA after an acute dose of intravenous leptin. We also found that CART neurons in the parvicellular PVH, in the DMH and in the posterior Pe coexpress thyrotropin-releasing hormone (TRH) mRNA. CART neurons in the magnocellular PVH and in the SON coexpress dynorphin (DYN), and CART cell bodies in the LHA and in the posterior Pe coexpress melanin-concentrating hormone (MCH) and glutamic acid decarboxylase (GAD-67) mRNA. In the Arc, a few CART neurons coexpress neurotensin (NT) mRNA. In addition, we examined the distribution of CART immunoreactivity in the human hypothalamus. We found CART cell bodies in the PVH, in the SON, in the LHA, in the Arc (infundibular nucleus) and in the DMH. We also observed CART fibers throughout the hypothalamus, in the bed nucleus of the stria terminalis, and in the amygdala. Our results indicate that leptin directly acts on CART neurons in distinct nuclei of the rat hypothalamus. Furthermore, hypothalamic CART neurons coexpress neuropeptides involved in energy homeostasis, including MCH, TRH, DYN, and NT. The distribution of CART cell bodies and fibers in the human hypothalamus indicates that CART may also play a role in the regulation of energy homeostasis in humans. J. Comp. Neurol. 432:1,19, 2001. © 2001 Wiley-Liss, Inc. [source]

    Cellular sources, targets and actions of constitutive nitric oxide in the magnocellular neurosecretory system of the rat

    Javier E. Stern
    Nitric oxide (NO) is a key activity-dependent modulator of the magnocellular neurosecretory system (MNS) during conditions of high hormonal demand. In addition, recent studies support the presence of a functional consitutive NO tone. The aim of this study was to identify the cellular sources, targets, signalling mechanisms and functional relevance of constitutive NO production within the supraoptic nucleus (SON). Direct visualization of intracellular NO, along with neuronal nitric oxide synthase (nNOS) and cGMP immunohistochemisty, was used to study the cellular sources and targets of NO within the SON, respectively. Our results support the presence of a strong NO basal tone within the SON, and indicate that vasopressin (VP) neurones constitute the major neuronal source and target of basal NO. NO induced-fluorescence and cGMP immunoreactivity (cGMPir) were also found in the glia and microvasculature of the SON, suggesting that they contribute as sources/targets of NO within the SON. cGMPir was also found in association with glutamic acid decarboxylase 67 (GAD67)- and vesicular glutamate transporter 2 (VGLUT2)-positive terminals. Glutamate, acting on NMDA and possibly AMPA receptors, was found to be an important neurotransmitter driving basal NO production within the SON. Finally, electrophysiological recordings obtained from SON neurones in a slice preparation indicated that constitutive NO efficiently restrains ongoing firing activity of these neurones. Furthermore, phasically active (putative VP) and continuously firing neurones appeared to be influenced by NO originating from different sources. The potential roles for basal NO as an autocrine signalling molecule, and one that bridges neuronal,glial,vascular interactions within the MNS are discussed. [source]


    First page of article [source]

    FATHERS, SONS, AND THE STATE: Discipline and Punishment in a Wolof Hinterland

    ABSTRACT This essay builds on fieldwork in rural Senegal to examine three cases in which elder household heads called on gendarmes to physically discipline rebellious youths. These cases, which revolved around harsh acts of corporal punishment, invite inquiry into common assumptions about African families and states. The first assumption is the common dichotomy drawn between African youths, portrayed as modern and menacing, and African elders, portrayed as "traditional" and hence benign. The second assumption is the dichotomy drawn between the African family, conceived as solidary and nurturing, and the African state, conceived as alien and predatory. In examining these cases of discipline and punishment, this essay reveals the ever-shifting power relations that link Wolof household heads, dependent junior males, and state agents, and simultaneously introduces new questions about the morality of farmer,state relations and generational conflict. My analysis reveals the spatial geography of Senegal's youth crisis, which takes different forms in rural and urban locales. The anxiety of rural patriarchs is fed by a fear-mongering media obsessed with youthful anarchy in the cities, and a long-standing political rhetoric about the threat of rural out-migration. Elder men in the countryside, who experience diminishing household authority under neoliberalism, make proactive efforts to keep the urban youth crisis at bay. They seek to augment their domestic power by reestablishing links with a state that has long bolstered patriarchy but whose power is currently in decline. By lending patriarchs their coercive force, gendarmes attempt to accomplish through private, indirect means, what the postcolonial state is unable to do: maintain social order by reining in disruptive youths. The harsh disciplinary measures that gendarmes employ are not alien to Wolof culture, but integral to Wolof conceptions of child rearing. [source]


    ECONOMIC INQUIRY, Issue 4 2009
    Interest in the twin deficits hypothesis fluctuates in tandem with the U.S. current account deficit. Surprisingly though, a statistically robust relationship between budget and trade deficits has been difficult to pin down. We argue that a big part of this difficulty is due to the failure to allow for structural breaks in the series when (either explicitly or implicitly) modeling their time series properties. We show that both series are break stationary (and conditionally heteroskedastic) and argue that while there is no common pattern in the long run, the short-run dynamics reveal a sizeable and fairly persistent positive relationship between budget deficit shocks and current account deficit shocks. (JEL F41, E6, H6) [source]

    The Suffering Mother and the Miserable Son: Organizing Women and Organizing Women's Writing

    Heather Höpfl
    This paper examines the contribution of the writing of Julia Kristeva (1941, ) to post-structuralist ideas about gender in organizations. In particular, it deals with the relationship between her writing and the disciplining of text and, by a parallel movement, with her writings about the body and the regulation of the body. However, it must be said that her writings are ,extremely difficult and complex, and certainly intimidating and inaccessible to the non-specialist' (Lechte 1990, p. 2) but, despite this, Kristeva has come to be considered one of the foremost contemporary French thinkers and her writings have exerted a significant influence on both feminism and postmodernist ideas. Ironically, Kristeva is neither French by birth nor a feminist in the sense that the term is generally understood. Indeed, she has been highly critical of those feminists whom she regards as seeking ,phallic power' (Kristeva 1980, p. 208). [source]

    Ancient Boats, Boat Timbers, and Locked Mortise-and-Tenon Joints from Bronze/Iron-Age Northern Vietnam

    Peter Bellwood
    This paper describes two nautical discoveries buried c.2000 years ago in the Red River alluvial plain, northern Vietnam. One is part of a logboat with a series of empty mortise and locking-peg holes for plank attachment using loose rectangular tenons. The other, from an infant mortuary house, is a series of re-used 4-m-long timbers with exactly the same locked mortise-and-tenon technology. Both finds are interpreted as having belonged to river-boats like those shown on the sides of Heger 1 (Dong Son) bronze drums. Potentially-related technologies from the Mediterranean and China are also discussed. © 2006 The Authors [source]

    The Eternal ,Spirit of the Son': Barth, Florovsky and Torrance on the Filioque

    This article offers an Orthodox response to Barth's defense of the filioque. Florovsky's theology exemplifies how Orthodoxy addresses the concerns underlying Barth's filioque without resort to the filioque. Entailed in the elaboration of Florovsky's Christocentric pneumatology is a critique of other currents in modern Orthodox theology (Florensky, Lossky). Common emphases are noted between Florovsky and T.F. Torrance regarding the consubstantiality and propriety of the Spirit to the Son and the significance of this doctrine for ecclesial life, suggesting a basis for further ecumenical reintegration. [source]

    Justification as Declaration and Deification

    Bruce D. Marshall
    Theological accounts of the way God justifies sinners often struggle to combine forensic or declarative ideas about justification with transformationist ones. Luther seems to have especially steep problems here, not because he fails to think of justification as transformation , indeed deification , but because his forensic claims seem to take back what he says about transformation. Yet in the end Luther shows how forensic and transformationist ideas of even the boldest sort can cohere. At one level the concept of justifying faith as union with Christ extra nos combines the two, but their deeper unity is trinitarian: it lies in the Father's eternal verdict on the work of his incarnate Son, whose death and resurrection win for us the coming of the Spirit. [source]

    The Son's Assumption of a Human Nature: A Call for Clarity

    Kelly M. Kapic
    This article seeks to bring some clarity to the controversial question of whether the Son of God assumed a fallen or unfallen human nature. We briefly survey conflicting historical assessments and continuing perplexity related to this question. Next we argue that much contemporary confusion can only be removed by first noting how John Calvin and Reformation catechisms tended to understand the idea of Jesus' sinlessness. In conclusion, from the vast literature on the subject we outline seven points which may serve contemporary reflection on this question by showing where the two views agree, disagree, or show internal divisions. [source]

    Some Dogmatic Implications of Barth's Understanding of Ebionite and Docetic Christology

    Paul D. Molnar
    This article shows how Barth's understanding of Ebionite andDocetic Christology shaped his trinitarian theology and argues that theologianstoday should learn from Barth in order to avoid the pitfalls of groundingChrist's uniqueness either in experience or in an ideology instead of in Christ himself. The article exhibits how Barth's insights relate to the views of a number of prominent contemporary theologians, illustrating how thesetheologians, in varying ways, actually reach problematic conclusions preciselyto the extent that they do not actually begin their christological reflections with the fact that Jesus is the Son of God simply because he is. [source]

    The Hidden and Triune God

    Robert W. Jenson
    Luther rightly perceived that God is hidden in his presence. The challenge systematically is to integrate discourse about God's hiddenness with a serious trinitarianism. The attempts by Gregory Palamas and Karl Barth to do just this are judged inadequate. A constructive proposal begins by recognizing that God's hiddenness is an impenetrability of his moral agency in his history with us as Father, Son and Holy Spirit, rather than a correlate of God's ontological uniqueness or our creaturely epistemic limitations. God's hiddenness must be thought of in terms of the sheer factuality of God the Father, which limits theodicy; the suffering of the Son, and thus the rejection of idolatry; and the freedom of the Spirit. [source]

    On the Way to a Better Future: Belgium as Transit Country for Trafficking and Smuggling of Unaccompanied Minors1

    Ilse Derluyn
    ABSTRACT During the last decade, irregular border crossings emerged as a new element in international migratory flows, with smuggling and trafficking networks being an essential part. Many people are compelled to use these networks to realize their dream of a better living, and for many this "promised land" is the United Kingdom (UK). Belgium has important sea connections with the UK, and is, therefore, an important migration transit zone, although many migrants are intercepted on Belgian territory during their tempt to reach the UK. Some are unaccompanied or separated children and adolescents, minors travelling without parent(s) or a legal caregiver. This study aims to gain insight about this population of unaccompanied minors travelling to the UK. We use the situation in Zeebrugge, one of Belgium's main ports, as a case study. We analysed 1,093 data files of unaccompanied minors intercepted in Zeebrugge, and carried out participatory observation at the shipping police station. The intercepted unaccompanied minors are mainly male, between 15 and 18 years of age, and from an Asian or Eastern European country. Of the 899 unique persons found in the data files, 113 were intercepted several times. After the interception, the Aliens Office gives the majority (82.9%) an identity document without a requirement to leave Belgium, while 15.3 per cent must leave Belgium immediately or within five days. In 82.9 per cent of the cases, a child protection officer is contacted to make a decision about the situation. In 67.2 per cent of these cases, no child protection measure is taken, and the minor may leave the police station; in 32 per cent of the cases, the minor is transferred to a centre, mostly crisis reception. Almost all unaccompanied minors are convinced they want to reach the UK to create a better livelihood, join a family member, or escape a difficult political situation. Nevertheless, most travel in difficult circumstances; are scared; and lack essential information about life in the UK, their possibilities in Belgium, what will happen if they are transferred to a centre, and so forth. Most minors also do not want to be transferred to a centre, and many , although not all , disappear again from the centres. This study has several implications concerning the kind of decisions taken by the legal authorities, the necessary physical and psycho-social care and the availability of an interpreter and social worker during the interception, the number of reception places and the care in these centres, and the tasks of the legal guardian. Finally, some limitations of the study are mentioned. VERS UN AVENIR MEILLEUR : LA BELGIQUE COMME PAYS DE TRANSIT POUR LA TRAITE ET L'INTRODUCTION CLANDESTINE DE MINEURS NON ACCOMPAGNÉS Au cours de la dernière décennie, le franchissement irrégulier des frontières est apparu comme un nouvel élément des flux migratoires internationaux, dont les réseaux de traite et d'introduction clandestine sont un aspect essentiel. Beaucoup de gens sont forcés d'utiliser ces réseaux pour réaliser leur rêve d'une vie meilleure et pour beaucoup, cette « terre promise », c'est le Royaume-Uni. La Belgique ayant d'importantes liaisons maritimes avec le Royaume-Uni con-stitue de ce fait une importante zone de transit pour les migrations, bien que de nombreux migrants soient interceptés sur le territoire belge alors qu'ils tentent d'atteindre le Royaume-Uni. Certains d'entre eux sont des enfants et des adoles-cents non accompagnés, séparés, des mineurs qui voyagent sans parent(s), sans personne qui en ait la garde juridique. Cette étude vise à mieux connaître cette population de mineurs non accompagnés voyageant en direction du Royaume-Uni. Nous prenons comme cas concret la situation à Zeebrugge, l'un des principaux ports belges. Nous avons analysé 1 093 fichiers de données concernant des mineurs non accompagnés interceptés à Zeebrugge, et nous sommes livrés à une observation participative au poste de police du port. Les mineurs non accompagnés inter-ceptés sont pour la plupart des garçons âgés de quinze à dix-huit ans originaires d'un pays d'Asie ou d'Europe orientale. Sur les 899 personnes trouvées dans les fichiers, 113 ont été interceptées plusieurs fois. Après l'interception, les Ser-vices de l'immigration donnent à la majorité de ces garçons un document d'identité sans obligation de quitter la Belgique, alors que 15,3 pour cent d'entre eux doivent quitter le pays, soit immédiatement soit dans les cinq jours. Dans 82,9 pour cent des cas, un agent de protection de l'enfance est contacté pour prendre une décision quant à la situation. Dans 67,2 pour cent de ces cas, aucune mesure de protection de l'enfant n'est prise et le mineur peut quitter le poste de police. Dans 32 pour cent des cas, le mineur est transféré dans un centre, un lieu d'accueil pour les situations de crise. Presque tous les mineurs non accompagnés sont convaincus de vouloir se rendre au Royaume-Uni pour y gagner leur vie, retrouver un membre de leur famille ou échapper à une situation politique difficile. Pourtant, la plupart de ces mineurs voyagent dans des circonstances difficiles. Ils ont peur. Ils n'ont pas les informations essentielles sur la vie au Royaume-Uni, sur les possibilités qui existent pour eux en Belgique, sur ce qui se passera s'ils sont transférés dans un centre. Beaucoup , mais pas tous , disparaissent de ces centres. Cette étude a diverses implications concernant le genre de décisions que pren-nent les autorités juridiques, les nécessaires soins physiques et psychosociaux pendant l'interception ainsi que la présence d'un interprète et d'un travailleur social, le nombre de places et les soins dans les centres d'accueil, les tâches de la personne qui a la responsabilité légale du mineur. Enfin, certaines limites de cette étude sont évoquées. CON MIRAS A UN MEJOR FUTURO: BÉLGICA COMO PAÍS DE TRÁNSITO DE LA TRATA Y EL TRÁFICO DE MENORES NO ACOMPAÑADOS Durante la última década, los cruces fronterizos irregulares se han convertido en un nuevo elemento de las corrientes migratorias internacionales, siendo un componente esencial de ellas las redes de tráfico y trata de personas. Son muchas las personas que se ven obligadas a recurrir a estas redes para hacer realidad su sueño de una vida mejor y para muchos "la tierra prometida" es el Reino Unido. Bélgica tiene importantes conexiones marítimas con el Reino Unido y, por consi-guiente, es una zona de tránsito de la migración sumamente importante, aunque muchos migrantes son interceptados en territorio belga en su intento por llegar al Reino Unido. Entre las personas interceptadas se encuentran niños y adoles-centes, menores de edad que viajan solos, sin sus padres o tutor legal. Este estudio tiene por objeto comprender cómo esta población de menores no acom-pañados viaja al Reino Unido. Con ese fin, se recurre a un estudio por casos examinando la situación en Zeebrugge, uno de los principales puertos de Bélgica. Se han analizado 1.093 expedientes de menores no acompañados, interceptados en Zeebrugge, y se ha realizado una observación participativa en la estación de policía naval. Los menores no acompañados interceptados eran principalmente varones, entre 15 y 18 años de edad, provenientes de Asia y Europa oriental. De las 899 personas no acompañadas encontradas en los expedientes, 113 habían sido interceptadas varias veces. Tras la intercepción, el Servicio de Inmigración otorga a la mayoría un documento de identidad (82,9 por ciento) sin obligarles a abandonar Bélgica, mientras que el 15,3 por ciento debe salir inmediatamente de Bélgica, o bien en un plazo máximo de cinco días. En el 82,9 por ciento de los casos, se establece contacto con un oficial de la protección de la infancia para que decida en cuanto a la situación del menor. En el 67,2 por ciento de estos casos, no se adopta ninguna medida de protección del menor y éste puede abandonar la estación de policía; y en el 32 por ciento de los casos, se transfiere al menor a un centro de recepción que se ocupa de casos críticos. Prácticamente todos los menores no acompañados tienen la certeza de que llegarán al Reino Unido para tener una mejor vida, reunirse con un familiar, o escapar de la difícil situación política. No obstante, la mayoría viaja en condiciones difí-ciles, tiene miedo y carece de información esencial sobre la vida en el Reino Unido, sobre sus posibilidades en Bélgica, y sobre lo que ocurrirá si son trans-feridos a un centro, etc. La mayoría de estos menores no quiere ser transferida a un centro y muchos, aunque no todos, se escapan de los mismos. Este estudio repercutirá, sin lugar a dudas, en las decisiones que adoptan las autoridades jurídicas, en la atención física y sicosocial necesarias, en la disponi-bilidad de un intérprete o trabajador social durante la intercepción, así como en el número de plazas de acogida y de atención en estos centros, y en las tareas que incumben a todo tutor legal. Finalmente, se enumeran algunas de las limitaciones de este estudio. [source]

    Mission Theology of the Church

    Kirsteen Kim
    This article on the mission theology of the church, a personal perspective by the vice-moderator of CWME, draws on documentation produced by the commission and also responds to the Faith and Order document, The Nature and Mission of the Church. It is based on the trinitarian paradigm of mission referred to as missio Dei, which emphasizes the priority of God's sending activity in the world, by the Son and the Spirit, and the contingency of the church and its mission activities upon that. Therefore, it is concerned with the participation of the church in God's mission to and in the world, and from this perspective, has a particular interest with the actual, empirical church rather than the ideal church, recognizing that the church exists in many different forms in particular social, cultural, economic and political contexts. The article argues that the church is "missionary by its very nature". Both theologically and empirically, it is impossible to separate the church from mission. Indeed mission is the very life of the church and the church is missionary by its very nature the Spirit of Christ breathed into the disciples at the same time as he sent them into the world. The mission theology of the church as it has developed in ecumenical discussion over the 20th and early 21st centuries is discussed in terms of the relationship of the church to the three persons of the Trinity: as foretaste of the kingdom of God; as the body of Christ; and as a movement of the Spirit. The article shows that being in mission is to cross the usual boundaries and bring new perspectives from outside to bear, and this is a never-ending, enriching process. [source]

    Schwarz, Wallace, and Rissanen: Intertwining Themes in Theories of Model Selection

    Aaron D. Lanterman
    Summary Investigators interested in model order estimation have tended to divide themselves into widely separated camps; this survey of the contributions of Schwarz, Wallace, Rissanen, and their coworkers attempts to build bridges between the various viewpoints, illuminating connections which may have previously gone unnoticed and clarifying misconceptions which seem to have propagated in the applied literature. Our tour begins with Schwarz's approximation of Bayesian integrals via Laplace's method. We then introduce the concepts underlying Rissanen's minimum description length principle via a Bayesian scenario with a known prior; this provides the groundwork for understanding his more complex non-Bayesian MDL which employs a "universal" encoding of the integers. Rissanen's method of parameter truncation is contrasted with that employed in various versions of Wallace's minimum message length criteria. Rissanen's more recent notion of stochastic complexity is outlined in terms of Bernardo's information-theoretic derivation of the Jeffreys prior. Résumé Il existe deux courants d'idées tres différents en recberche sur I' ordre de modéles.Ce papier est une revue des contributions de Schwarz, Wallace, Rissanen, et de leurs collaborateurs, Son but est de rapprocher leurs points de vue, d' établir de nouvelles connexions entre certains problémes, et de corriger certaines interprétations erronées qui sont apparues dans la litérature appliquée. Notre revue commence par I' approximation d' intégrales Bayesiennes au moyen de la méthode de Lapace,étudiée par Schwarz. Nous introduisons ensuite le principe de longueur descriptive minimale de Rissanen dans le cadre d' un scénario d' estimation Bayesienne. Ceci permet une nouvelle interpretation de ses méthodes d' estimation basées sur un codage "univasel" des entiers nabuels. Nous comparons la technique de paramétres de Rissanen avec cellcs qu'utilisc Wallace daar sa mtOaic du crib de longueur minimale d'un mtssage. Nous tcrminons cette étude par une présentation de la notion de complexité stochastique de Rissanen et ses connexions avec la distribution de Jeffreys, dont Bernardo a presenté une dérivation basée sur la théorie de l'infaamation. [source]

    Significance of the Grb2 and Son of Sevenless (Sos) Proteins in Human Bladder Cancer Cell Lines

    IUBMB LIFE, Issue 4 2000
    Takafumi Watanabe
    Abstract The epidermal growth factor (EGF) receptor has been suggested to have an important role in tumor initiation and progression of human bladder cancers. Grb2 protein, which is the downstream effector of the EGF receptor, acts as an adaptor protein between the EGF receptor and the Ras guanine-nucleotide exchange factor, son of sevenless (Sos) protein. Sos protein regulates the action of Ras protein by promoting the exchange of GDP for GTP . However, the significance of Grb2 and Sos proteins, which is related to EGF-triggered Ras activation, has not been elucidated in human bladder cancer. The aim of the present study is to clarify the significance of these proteins in human bladder cancer cell lines. In the present study, we used four human bladder cancer cell lines (T24, KU-7, UMUC-2, UMUC-6) and two kinds of cultured normal urothelial cells (HMKU-1, HMKU-2) isolated from patients with no malignancy. We examined the expression of EGF receptor, Grb2, and Sos proteins in these cells by Western blot analysis. Furthermore, the bladder cancer cell lines were subjected to sequence analysis to identify a point mutation in the c-H-ras gene at codon 12. There was no marked difference in the expression of the EGF receptor between human bladder cancer cell lines and cultured normal urothelial cells. On the other hand, expression of Grb2 and Sos proteins was substantially increased in all human bladder cancer cell lines examined in comparison with cultured normal urothelial cells, whether codon 12 of H-ras was mutated or not. These results suggest that the amplification of both Grb2 and SOS proteins plays an important role in the carcinogenesis of human bladder cancer. [source]