bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockade of neuropeptide Y2 receptors and suppression of NPY's anti‐epileptic actions in the rat hippocampal slice by BIIE0246
Authors: Bahh Bouchaïb El , Cao Jeffrey Q , Beck‐Sickinger Annette G , Colmers William F
Published: January 2005

Neuropeptide Y (NPY) has been shown to suppress synaptic excitation in rat hippocampus by a presynaptic action. The Y2 (Y2R) and the Y5 (Y5R) receptors have both been implicated in this action. We used the non‐peptide, Y2R‐selective antagonist, BIIE0246, to test the hypothesis that the Y2R mediates both the presynaptic inhibitory and anti‐epileptic actions of NPY in rat hippocampus in vitro.

NPY and the Y2R‐selective agonist, [ahx5‐24]NPY, both inhibited the population excitatory postsynaptic potential (pEPSP) evoked in area CA1 by stratum radiatum stimulation in a concentration‐dependent manner. BIIE0246 suppressed the inhibitory effects of both agonists, suppressing the maximal inhibition without causing a change in the agonist EC50, in a manner inconsistent with competitive antagonism.

BIIE0246 washed out from hippocampal slices extremely slowly. Application of agonist at high concentrations (1–3 μM) for prolonged periods did not alter the rate of washout, but did partially overcome the antagonism, inconsistent with an insurmountable antagonism by BIIE0246.

In the stimulus train‐induced bursting (STIB) model of ictal activity in hippocampal slices, both NPY and [ahx5‐24]NPY inhibited primary afterdischarge (1°AD) activity. BIIE0246 (100 nM) completely suppressed the actions of NPY and [ahx5‐24]NPY in this model. In contrast, the potent Y5R‐selective agonist, Ala31Aib32NPY, affected neither 1°AD activity in the presence of BIIE0246, nor, by itself, even the pEPSP in CA1.

BIIE0246 potently suppresses NPY actions in rat hippocampus, suggesting a dominant role for Y2R there. The apparently insurmountable antagonism observed may result from the lipophilic nature of the antagonist.

British Journal of Pharmacology (2002) 136, 502–509; doi:10.1038/sj.bjp.0704751
Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide‐ and kinin‐dependent mechanism
Authors: Xu Biao , Xiao‐hong Li , Lin Gao , Queen Lindsay , Ferro Albert
Published: January 2005

We investigated the nitric oxide (NO) dependence of vasorelaxation in response to different calcium channel blockers (CCB), in rabbit femoral artery in vivo.

Anaesthetized rabbits underwent femoral artery ligation, and blood from the proximal artery was returned distal to the ligature through a constant infusion pump. The effects of local injection of CCB on perfusion pressure and plasma nitrite+nitrate (NOx, which reflects local NO biosynthesis) concentration in this system were determined.

Intra‐arterial verapamil, nifedipine or amlodipine 10 μmol kg−1 each reduced perfusion pressure. Pre‐treatment with intra‐arterial NG‐nitro‐L‐arginine methyl ester (L‐NAME, a NO synthase inhibitor) 1 μmol kg−1 did not affect responses to verapamil or nifedipine, but attenuated the reduction in perfusion pressure to amlodipine, from 33.2±2.1% to 22.5±1.6% (P=0.002).

Intra‐arterial amlodipine  –  unlike verapamil or nifedipine  –  increased femoral venous NOx, from 9.1±0.4 μM to 14.1±0.5 μM (P=0.005).

The bradykinin B2 receptor antagonist HOE 140, 30 mg kg−1, attenuated the reduction in perfusion pressure and abolished the rise in venous NOx concentration, following intra‐arterial amlodipine.

Amlodipine potently inhibited serum angiotensin converting‐enzyme (ACE) activity in vitro, as effectively as enalapril at similar concentrations.

These results suggest that the vasorelaxant effects of nifedipine and verapamil are NO‐independent, whereas those of amlodipine are partly NO‐dependent, in rabbit femoral artery in vivo. This effect of amlodipine occurs through B2 receptor activation, and may be related to an increase in local bradykinin through inhibition of ACE.

British Journal of Pharmacology (2002) 136, 375–382; doi:10.1038/sj.bjp.0704753
Enhancement of delayed‐rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones
Authors: Olschewski Andrea , Wolff Matthias , Bräu Michael E , Hempelmann Gunter , Vogel Werner , Safronov Boris V
Published: January 2005

Combining the patch‐clamp recordings in slice preparation with the ‘entire soma isolation’ method we studied action of several local anaesthetics on delayed‐rectifier K+ currents in spinal dorsal horn neurones.

Bupivacaine, lidocaine and mepivacaine at low concentrations (1–100 μM) enhanced delayed‐rectifier K+ current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 μM). In isolated somata 0.1–10 μM bupivacaine enhanced delayed‐rectifier K+ current by shifting its steady‐state activation characteristic and the voltage‐dependence of the activation time constant to more negative potentials by 10–20 mV.

Detailed analysis has revealed that bupivacaine also increased the maximum delayed‐rectifier K+ conductance by changing the open probability, rather than the unitary conductance, of the channel.

It is concluded that local anaesthetics show a dual effect on delayed‐rectifier K+ currents by potentiating them at low concentrations and partially suppressing at high concentrations. The phenomenon observed demonstrated the complex action of local anaesthetics during spinal and epidural anaesthesia, which is not restricted to a suppression of Na+ conductance only.

British Journal of Pharmacology (2002) 136, 540–549; doi:10.1038/sj.bjp.0704754
Pre‐ and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons
Authors: Cheng Gong , Kendig Joan J
Published: January 2005

A common anaesthetic endpoint, prevention of withdrawal from a noxious stimulus, is determined primarily in spinal cord, where glycine is an important inhibitory transmitter. To define pre‐ and postsynaptic anaesthetic actions at glycinergic snyapses, the effects of volatile anaesthetic agents on spontaneous and evoked glycinergic currents in spinal cord motor neurons from 6 – 14‐day old rats was investigated.

The volatile anaesthetic agents enflurane, isoflurane and halothane significantly increased the frequency of glycinergic mIPSCs, enflurane to 190.4% of control±22.0 (mean±s.e.m., n=7, P<0.01), isoflurane to 199.0%±28.8 (n=7, P<0.05) and halothane to 198.2%±19.5 (n=7, P<0.01). However without TTX, isoflurane and halothane had no significant effect and enflurane decreased sIPSC frequency to 42.5% of control±12.4 (n=6, P<0.01). All the anaesthetics prolonged the decay time constant (τ) of both spontaneous and glycine‐evoked currents without increasing amplitude. With TTX total charge transfer was increased; without TTX charge transfer was unchanged (isoflurane and halothane) or decreased (enflurane).

Enflurane‐induced mIPSC frequency increases were not significantly affected by Cd2+ (50 μM), thapsigargin (1 – 5 μM), or KB‐R7943 (5 μM). KB‐R7943 and thapsigargin together abolished the enflurane‐induced increase in mIPSC frequency.

There are opposing facilitatory and inhibitory actions of volatile anaesthetics on glycine release dependent on calcium homeostatic mechanisms and sodium channels respectively. Under normal conditions (no TTX) the absolute amount of glycinergic inhibition does not increase. The contribution of glycinergic inhibition to anaesthesia may depend on its duration rather than its absolute magnitude.

British Journal of Pharmacology (2002) 136, 673–684; doi:10.1038/sj.bjp.0704760
Comparison of the expression of calcitonin receptor‐like receptor (CRLR) and receptor activity modifying proteins (RAMPs) with CGRP and adrenomedullin binding in cell lines
Authors: Choksi Tejal , Hay Debbie L , Legon Stephen , Poyner David R , Hagner Stefanie , Bloom Stephen R , Smith David M
Published: January 2005

The calcitonin receptor‐like receptor (CRLR) and specific receptor activity modifying proteins (RAMPs) together form receptors for calcitonin gene‐related peptide (CGRP) and/or adrenomedullin in transfected cells.

There is less evidence that innate CGRP and adrenomedullin receptors are formed by CRLR/RAMP combinations. We therefore examined whether CGRP and/or adrenomedullin binding correlated with CRLR and RAMP mRNA expression in human and rat cell lines known to express these receptors. Specific human or rat CRLR antibodies were used to examine the presence of CRLR in these cells.

We confirmed CGRP subtype 1 receptor (CGRP1) pharmacology in SK‐N‐MC neuroblastoma cells. L6 myoblast cells expressed both CGRP1 and adrenomedullin receptors whereas Rat‐2 fibroblasts expressed only adrenomedullin receptors. In contrast we could not confirm CGRP2 receptor pharmacology for Col‐29 colonic epithelial cells, which, instead were CGRP1‐like in this study.

L6, SK‐N‐MC and Col‐29 cells expressed mRNA for RAMP1 and RAMP2 but Rat‐2 fibroblasts had only RAMP2. No cell line had detectable RAMP3 mRNA.

SK‐N‐MC, Col‐29 and Rat‐2 fibroblast cells expressed CRLR mRNA. By contrast, CRLR mRNA was undetectable by Northern analysis in one source of L6 cells. Conversely, a different source of L6 cells had mRNA for CRLR. All of the cell lines expressed CRLR protein. Thus, circumstances where CRLR mRNA is apparently absent by Northern analysis do not exclude the presence of this receptor.

These data strongly support CRLR, together with appropriate RAMPs as binding sites for CGRP and adrenomedullin in cultured cells.

British Journal of Pharmacology (2002) 136, 784–792; doi:10.1038/sj.bjp.0704761
Elevated mean arterial pressure in the ovariectomized rat was normalized by ETA receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis
Authors: Mercier Isabelle , Pham‐Dang Mylan , Clement Robert , Gosselin Hugues , Colombo Federico , Rouleau Jean‐Lucien , Calderone Angelino
Published: January 2005

The influence of menopause on ventricular function and remodelling remains undefined. The following study examined the effect of ovariectomy on ventricular contractility, cardiac hypertrophy and extracellular matrix protein expression.

Elevated circulating levels of the vasoconstrictor endothelin‐1 have been reported in post‐menopausal women. Moreover, endothelin‐1 has been shown to influence blood pressure, ventricular function and cardiac remodelling. In this regard, the potential pathophysiological role of endothelin‐1 in the ovariectomized rat was assessed via the administration of the selective endothelinA receptor (ETA) antagonist BMS‐182874.

In 3 and 6 week ovariectomized female Sprague – Dawley rats, uterus atrophy was associated with a significant increase in mean arterial pressure, and left ventricular systolic pressure, as compared to sham. By contrast, right ventricular contractile indices were normal in the ovariectomized rat. Despite increased systolic load, left ventricular hypertrophy was not evident, prepro‐atrial natriuretic peptide (prepro‐ANP) mRNA levels and collagen protein content were similar to sham.

The treatment of ovariectomized rats with BMS‐182874 (60 mg kg−1 per day) did not reverse uterus atrophy. However, BMS‐182874 normalized mean arterial pressure, and left ventricular systolic pressure in the ovariectomized rat.

Thus, despite elevated blood pressure, ovariectomized rats were not associated with either cardiac hypertrophy or fibrosis. Lastly, endothelin‐1, acting via the stimulation of the ETA receptor represents an integral mechanism implicated in the increase of mean arterial pressure following ovariectomy.

British Journal of Pharmacology (2002) 136, 685–692; doi:10.1038/sj.bjp.0704765
The anti‐epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA‐ and glycine‐gated currents
Authors: Rigo J‐M , Hans G , Nguyen L , Rocher V , Belachew S , Malgrange B , Leprince P , Moonen G , Selak I , Matagne A , Klitgaard H
Published: January 2005

In this studyin vitroandin vivoapproaches were combined in order to investigate if the anti‐epileptic mechanism(s) of action of levetiracetam (LEV; Keppra®) may involve modulation of inhibitory neurotransmission.

GABA‐ and glycine‐gated currents were studiedin vitrousing whole‐cell patch‐clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessedin vivoin sound‐susceptible mice. The effect of LEV was compared with reference anti‐epileptic drugs (AEDs): carbamazepine, phenytoin, valproate, clonazepam, phenobarbital and ethosuximide.

LEV contrasted the reference AEDs by an absence of any direct effect on glycine‐gated currents. At high concentrations, beyond therapeutic relevance, it induced a small reduction in the peak amplitude and a prolongation of the decay phase of GABA‐gated currents. A similar action on GABA‐elicited currents was observed with the reference AEDs, except ethosuximide.

These minor direct effects contrasted with a potent ability of LEV (EC50=1 – 10 μM) to reverse the inhibitory effects of the negative allosteric modulators zinc and β‐carbolines on both GABAAand glycine receptor‐mediated responses.

Clonazepam, phenobarbital and valproate showed a similar ability to reverse the inhibition of β‐carbolines on GABA‐gated currents. Blockade of zinc inhibition of GABA responses was observed with clonazepam and ethosuximide. Phenytoin was the only AED together with LEV that inhibited the antagonism of zinc on glycine‐gated currents and only clonazepam and phenobarbital inhibited the action of DMCM.

LEV (17 mg kg−1) produced a potent suppression of sound‐induced clonic convulsions in mice. This protective effect was significantly abolished by co‐administration of the β‐carboline FG 7142, from a dose of 5 mg kg−1. In contrast, the benzodiazepine receptor antagonist flumazenil (up to 10 mg kg−1) was without any effect on the protection afforded by LEV.

The results of the present study suggest that a novel ability to oppose the action of negative modulators on the two main inhibitory ionotropic receptors may be of relevance for the anti‐epileptic mechanism(s) of action of LEV.

British Journal of Pharmacology(2002)136, 659–672; doi:10.1038/sj.bjp.0704766
Docosahexaenoic acid potentiates interleukin‐1β induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vascular smooth muscle cells
Authors: Hirafuji Masahiko , Machida Takuji , Tsunoda Marito , Miyamoto Atsushi , Minami Masaru
Published: January 2005

The effect of docosahexaenoic acid (DHA) on nitric oxide (NO) production and inducible NO synthase (iNOS) expression induced by interleukin (IL)‐1β, and whether the effect of DHA is related to its effect on mitogen‐activated protein kinase (MAPK) activation were investigated in cultured rat vascular smooth muscle cells (VSMCs).

DHA and eicosapentaenoic acid (EPA), although less potent, increased the NO production induced by IL‐1β (3 ng ml−1) in a concentration‐dependent manner (3–30 μM) Arachidonic acid had no significant effect. The stimulatory effect of DHA (30 μM) on the NO production was more obvious at lower concentrations of IL‐1β.

IL‐1β induced iNOS protein and mRNA expressions, which were significantly potentiated by DHA. EPA (30 μM) had a tendency to increase the iNOS protein and mRNA expressions, but arachidonic acid had no effect.

IL‐1β‐induced iNOS protein expression was significantly inhibited by PD 98059 (10 μM), a selective inhibitor of p44/42 MAPK kinase, both in the absence and the presence of DHA. SB 203580 (10 μM), a selective inhibitor of p38 MAPK activity, had no significant effect, although had a tendency to inhibit slightly.

IL‐1β increased the phosphorylation of p44/42 MAPK, while it did not apparently increase the phosphorylation of p38 MAPK. DHA significantly potentiated the IL‐1β‐induced phosphorylation of p44/42 MAPK, while it had no significant effect on the phosphorylation of p38 MAPK.

These results suggest that DHA increases NO production by potentiating iNOS expression induced by IL‐1β through mechanism involving p44/42 MAPK signalling cascade in rat VSMCs. The present study may contribute to the understanding of basic mechanisms underlying the beneficial effects of DHA on various cardiovascular disorders.

British Journal of Pharmacology (2002) 136, 613–619; doi:10.1038/sj.bjp.0704768
Oncostatin M stimulates proliferation, induces collagen production and inhibits apoptosis of human lung fibroblasts
Authors: Scaffidi Amelia K , Mutsaers Steven E , Moodley Yuben P , McAnulty Robin J , Laurent Geoffrey J , Thompson Philip J , Knight Darryl A
Published: January 2005

Oncostatin M (OSM), a member of the interleukin‐6 (IL‐6) cytokine family, acts on a variety of cells and elicits diversified biological responses, suggesting potential roles in the regulation of cell survival, differentiation and proliferation.

We have examined the effect of OSM on the regulation of human lung fibroblast proliferation, collagen production and spontaneous apoptosis. The proliferative effects of OSM (0.5 – 100 ng ml−1) were assessed using a MTS assay as well as [3H]‐thymidine incorporation and cell counts at 24 and 48 h. Hydroxyproline was measured as an index of procollagen production by high pressure liquid chromotography (HPLC). Apoptosis was determined by annexin staining.

OSM enhanced the mitotic activity of lung fibroblasts in a time and dose dependent manner. Maximum proliferation of 57% above control was observed after incubation for 48 h with 2 ng ml−1 OSM (P<0.05).

Incubation with the mitogen activated protein kinase (MAPK) kinase inhibitor, PD98059 or the tyrosine kinase inhibitor, genestein both significantly reduced the mitogenic effect of OSM (P<0.05).

In contrast, proliferation in response to OSM was not regulated by induction of cyclo‐oxygenase and subsequent prostaglandin E2 (PGE2) release or by IL‐6.

OSM also stimulated fibroblasts to synthesize pro‐collagen by a maximum of 35% above control levels after 48 h (P<0.05).

OSM significantly inhibited the spontaneous apoptosis of fibroblasts at 24 and 48 h.

These results provide evidence that OSM has pro‐fibrotic properties and suggest that it may play a role in normal lung wound repair and fibrosis.

British Journal of Pharmacology (2002) 136, 793–801; doi:10.1038/sj.bjp.0704769
Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sarcolemmal KATP channels
Authors: Lawrence C L , Rainbow R D , Davies N W , Standen N B
Published: January 2005

We have investigated the effects of the sulphonylurea, glimepiride, currently used to treat type 2 diabetes, on ATP‐sensitive K+ (KATP) currents of rat cardiac myocytes and on their cloned constituents Kir6.2 and SUR2A expressed in HEK 293 cells.

Glimepiride blocked pinacidil‐activated whole‐cell KATP currents of cardiac myocytes with an IC50 of 6.8 nM, comparable to the potency of glibenclamide in these cells. Glimepiride blocked KATP channels formed by co‐expression of Kir6.2/SUR2A subunits in HEK 293 cells in outside‐out excised patches with a similar IC50 of 6.2 nM.

Glimepiride was much less effective at blocking KATP currents activated by either metabolic inhibition (MI) with CN− and iodoacetate or by the KATP channel opener diazoxide in the presence of inhibitors of F0/F1‐ATPase (oligomycin) and creatine kinase (DNFB). Thus 10 μM glimepiride blocked pinacidil‐activated currents by >99%, MI‐activated currents by 70% and diazoxide‐activated currents by 82%.

In inside‐out patches from HEK 293 cells expressing the cloned KATP channel subunits Kir6.2/SUR2A, increasing the concentration of ADP (1 – 100 μM), in the presence of 100 nM glimepiride, lead to significant increases in Kir6.2/SUR2A channel activity. However, over the range tested, ADP did not affect cloned KATP channel activity in the presence of 100 nM glibenclamide. These results are consistent with the suggestion that ADP reduces glimepiride block of KATP channels.

Our results show that glimepiride is a potent blocker of native cardiac KATP channels activated by pinacidil and blocks cloned Kir6.2/SUR2A channels activated by ATP depletion with similar potency. However, glimepiride is much less effective when KATP channels are activated by MI and this may reflect a reduction in glimepiride block by increased intracellular ADP.

British Journal of Pharmacology (2002) 136, 746–752; doi:10.1038/sj.bjp.0704770
Characterization of an organometallic xenon complex using NMR and IR spectroscopy
Authors: Ball Graham E. , Darwish Tamim A. , Geftakis Spili , George Michael W. , Lawes Douglas J. , Portius Peter , Rourke Jonathan P.
Published: January 2005

Photolysis of Re(
i
PrCp)(CO)
2
(PF
3
) in liquid or supercritical Xe yields two new compounds [Re(
i
PrCp)(CO)
2
Xe and Re(
i
PrCp)(CO)(PF
3
)Xe]. Re(
i
PrCp)(CO)(PF
3
)Xe has been characterized by NMR and IR spectroscopies. The compound is an organometallic Xe complex that has been characterized by using NMR spectroscopy and is shown to be longer-lived than other organometallic Xe complexes by IR spectroscopy.
19
F,
31
P, and
129
Xe chemical shifts have been determined. The
129
Xe chemical shift of Re(
i
PrCp)(CO)(PF
3
)Xe, δ –6,179, is a Xe shift that is significantly shielded, on the order of 1,000 ppm, with respect to free Xe. The coupling constants between coordinated
129
Xe and both the
19
F and
31
P nuclei present have been extracted, confirming the identity of the compound. Observed line widths give a lower limit to the lifetime of the coordinated Xe of 27 ms at 163 K.
Drosophila
neuropeptide F and its receptor, NPFR1, define a signaling pathway that acutely modulates alcohol sensitivity
Authors: Wen Tieqiao , Parrish Clayton A. , Xu Dan , Wu Qi , Shen Ping
Published: January 2005

Alcohol is likely to affect neurons nonselectively, and the understanding of its action in the CNS requires elucidation of underlying neuronal circuits and associated cellular processes. We have identified a
Drosophila
signaling system, comprising neurons expressing neuropeptide F (NPF, a homolog of mammalian neuropeptide Y) and its receptor, NPFR1, that acutely mediates sensitivity to ethanol sedation. Flies deficient in NPF/NPFR1 signaling showed decreased alcohol sensitivity, whereas those overexpressing NPF exhibited the opposite phenotype. Furthermore, controlled functional disruption of NPF or NPFR1 neurons in adults rapidly confers resistance to ethanol sedation. Finally, the NPF/NPFR1 system selectively mediates sedation by ethanol vapor but not diethyl ether, indicating that the observed NPF/NPFR1 activity reflects a specialized response to alcohol sedation rather than a general response to intoxication by sedative agents. Together, our results provide the molecular and neural basis for the strikingly similar alcohol-responsive behaviors between flies and mammals.
Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment
Authors: Maxwell Kara N. , Fisher Edward A. , Breslow Jan L.
Published: January 2005

Proprotein convertase subtilisin kexin 9 (PCSK9) is a member of the subtilisin serine protease family with an important role in cholesterol metabolism. PCSK9 expression is regulated by dietary cholesterol in mice and cellular sterol levels in cell culture via the sterol regulatory element binding protein transcription factors, and mutations in PCSK9 are associated with a form of autosomal dominant hypercholesterolemia. Overexpression of PCSK9 in mice leads to increased total and low-density lipoprotein (LDL) cholesterol levels because of a decrease in hepatic LDL receptor (LDLR) protein with normal mRNA levels. To study the mechanism, PCSK9 was overexpressed in human hepatoma cells, HepG2, by adenovirus. Overexpression of PCSK9 in HepG2 cells caused a decrease in whole-cell and cell-surface LDLR levels. PCSK9 overexpression had no effect on LDLR synthesis but caused a dramatic increase in the degradation of the mature LDLR and a lesser increase in the degradation of the precursor LDLR. In contrast, overexpression of a catalytically inactive mutant PCSK9 prevented the degradation of the mature LDLR; whereas increased degradation of the precursor LDLR still occurred. The PCSK9-induced degradation of the LDLR was not affected by inhibitors of the proteasome, lysosomal cysteine proteases, aspartic acid proteases, or metalloproteases. The PCSK9-induced degradation of the LDLR was shown to require transport out of the endoplasmic reticulum. These results indicate that overexpression of PCSK9 induces the degradation of the LDLR by a nonproteasomal mechanism in a post-endoplasmic reticulum compartment.
Demographic dynamics and kinship in anthropological populations
Authors: Hammel E. A.
Published: January 2005

Changes in fertility and mortality affect the size of surviving sibling sets and thus numbers of surviving kin. Because the genealogical generations specifying kinship relations are not temporal cohorts and most plausible demographic changes in anthropological populations are period shocks, the effect of such shocks on kin counts are complex. Shocks increasing fertility or decreasing mortality produce larger numbers of kin per ego and decrease the inequality of the distribution of kin and vice versa. Effects are more diffuse at more distant collateral ranges. Effects are stronger the more intense the shock and the longer its duration. Kinship distributions return to their initial state after the shock and as the original age structure of the population is ergodically reattained. Alternating shocks produce more complex patterns. Implications of these outcomes are that opportunities for political networking and consolidation by means of kinship are altered by demographic instabilities, as are the dynamics of kin selection. This analysis is limited for simplicity to unilineal agnatic reckoning of kin.
Institutions, incentives and the future of fisheries
Authors: Hilborn Ray , Orensanz J. M. (Lobo) , Parma Ana M.
Published: January 2005

Fisheries around the world are managed with a broad range of institutional structures. Some of these have been quite disastrous, whereas others have proven both biologically and economically successful. Unsuccessful systems have generally involved either open access, attempts at top–down control with poor ability to monitor and implement regulations, or reliance on consensus. Successful systems range from local cooperatives to strong governmental control, to various forms of property rights, but usually involve institutional systems that provide incentives to individual operators that lead to behaviour consistent with conservation.
Regime, phase and paradigm shifts: making community ecology the basic science for fisheries
Authors: Mangel Marc , Levin Phillip S.
Published: January 2005

Modern fishery science, which began in 1957 with Beverton and Holt, is
ca
. 50 years old. At its inception, fishery science was limited by a nineteenth century mechanistic worldview and by computational technology; thus, the relatively simple equations of population ecology became the fundamental ecological science underlying fisheries. The time has come for this to change and for community ecology to become the fundamental ecological science underlying fisheries. This point will be illustrated with two examples. First, when viewed from a community perspective, excess production must be considered in the context of biomass left for predators. We argue that this is a better measure of the effects of fisheries than spawning biomass per recruit. Second, we shall analyse a simple, but still multi–species, model for fishery management that considers the alternatives of harvest regulations, inshore marine protected areas and offshore marine protected areas. Population or community perspectives lead to very different predictions about the efficacy of reserves.
Extinction, survival or recovery of large predatory fishes
Authors: Myers Ransom A. , Worm Boris
Published: January 2005

Large predatory fishes have long played an important role in marine ecosystems and fisheries. Overexploitation, however, is gradually diminishing this role. Recent estimates indicate that exploitation has depleted large predatory fish communities worldwide by at least 90% over the past 50–100 years. We demonstrate that these declines are general, independent of methodology, and even higher for sensitive species such as sharks. We also attempt to predict the future prospects of large predatory fishes. (i) An analysis of maximum reproductive rates predicts the collapse and extinction of sensitive species under current levels of fishing mortality. Sensitive species occur in marine habitats worldwide and have to be considered in most management situations. (ii) We show that to ensure the survival of sensitive species in the northwest Atlantic fishing mortality has to be reduced by 40–80%. (iii) We show that rapid recovery of community biomass and diversity usually occurs when fishing mortality is reduced. However, recovery is more variable for single species, often because of the influence of species interactions. We conclude that management of multi–species fisheries needs to be tailored to the most sensitive, rather than the more robust species. This requires reductions in fishing effort, reduction in bycatch mortality and protection of key areas to initiate recovery of severely depleted communities.
The estimation of potential yield and stock status using life–history parameters
Authors: Beddington J. R. , Kirkwood G. P.
Published: January 2005

Using life–history invariants, this paper develops techniques that allow the estimation of maximum sustainable yield and the fishing mortality rate that produces the maximum yield from estimates of the growth parameters, the length at first capture and the steepness of the stock recruitment relationship. This allows sustainable yields and fishing capacity to be estimated from sparse data, such as those available for developing country fisheries.
Phylogenetic trends in the abundance and distribution of pit organs of elasmobranchs
Authors: Peach M. B. , Rouse G. W.
Published: January 2005

Pit organs (free neuromasts of the mechanosensory lateral line system) are distributed over the skin of elasmobranchs. To investigate phylogenetic trends in the distribution and abundance of pit organs, 12 relevant morphological characters were added to an existing matrix of morphological data (plus two additional end terminals), which was then re‐analysed using cladistic parsimony methods (paup* 4.0b10). Character transformations were traced onto the most parsimonious phylogenetic trees. The results suggest the following interpretations. First, the distinctive overlapping denticles covering the pit organs in many sharks are a derived feature; plesiomorphic elasmobranchs have pit organs in open slits, with widely spaced accessory denticles. Second, the number of pit organs on the ventral surface of rays has been reduced during evolution, and third, spiracular pit organs have changed position or have been lost on several occasions in elasmobranch evolution. The concentrated‐changes test inmacclade(version 4.05) was used to investigate the association between a pelagic lifestyle and loss of spiracular pit organs (the only character transformation that occurred more than once within pelagic taxa). Depending on the choice of tree, the association was either nonsignificant atP = 0.06 or significant atP < 0.05. Future studies, using species within more restricted elasmobranch clades, are needed to resolve this issue.
A short personal memoir
Authors: Hubback Judith
Published: January 2005

Abstract:  The history of the formation of the different analytical psychology groups in Britain is briefly described to illustrate the recurring splitting that has taken place throughout the development of the profession of analytical psychology. The author discusses her role as editor of the Journal of Analytical Psychology.
An immunohistochemical study of the extracellular matrix of the tarsal plate in the upper eyelid in human beings
Authors: Milz Stefan , Neufang Joerg , Higashiyama Ichiro , Putz Reinhard , Benjamin Michael
Published: January 2005

The superior tarsus is a plate of tissue that stiffens the upper eyelid, gives it support and determines its form. The purpose of the present study was to relate the composition of its extracellular matrix to its function and to report regional differences that may influence the activity of its Meibomian glands. Fourteen methanol‐fixed specimens were cryosectioned for immunohistochemistry and labelled with a panel of monoclonal antibodies against a wide range of collagens, glycosaminoglycans and proteoglycans. Labelling was detected with avidin–biotin–peroxidase. A further six specimens were formalin‐fixed for routine histology. The tarsal plate immunolabelled strongly for types I, III and VI collagen and for aggrecan, versican, tenascin, cartilage oligomeric matrix protein (COMP) together with a variety of glycosaminoglycans (notably chondroitin 6 sulphate). A region of strong labelling for aggrecan, dermatan sulphate and chondroitin 6 sulphate immediately surrounded the Meibomian glands. The site of labelling corresponded to a layer of acellular and amorphous matrix seen histologically that we have termed the ‘territorial matrix’. The results suggested that the tarsal plate is a specialized connective tissue that is neither purely fibrous nor cartilaginous, yet has an aggrecan content that probably contributes to its stiffness. Its unique character highlights the challenge in choosing an ideal mechanical substitute. As patients with rheumatoid arthritis often have problems relating to tear film deficiency, the ability of aggrecan or COMP to act as autoantigens may be significant. An immune reaction directed against these molecules could alter tarsal gland function by interfering with the interaction between the glands and their territorial matrix.
Quantification of N‐CAM and N‐cadherin expression in axotomized and crushed rat sciatic nerve
Authors: Thornton M. R. , Mantovani C. , Birchall M. A. , Terenghi G.
Published: January 2005

Adhesion molecules are important in supporting axonal regeneration. Qualitative studies have described increased expression of neural cell adhesion molecule (NCAM) and N‐cadherin in models of nerve injury allowing active regeneration. In this study we have used quantitative immunohistochemistry to compare expression of NCAM and N‐cadherin after nerve injury either with active regeneration (crush) into the distal stump or without (axotomy and capping). Quantification was performed 15 days after axotomy in proximal and distal stumps. Quantification after crush either proximal, distal or within the crushed area was performed at 2, 7, 15 and 30 days after injury. Axotomy induced increases in expression in proximal stumps between two and three times those in uninjured nerves for both molecules. In distal stumps, N‐cadherin levels increased seven‐fold, yet NCAM levels did not exceed control values. After crush, NCAM immunoreactivity increased in the crushed area and distal stump in contrast to axotomy and NCAM‐positive axons co‐localized with PGP9.5. N‐cadherin levels in the distal stump increased above control levels, but the magnitude of the increase seen after crush was different to those seen after axotomy. In conclusion, increased expression of adhesion molecules, particularly NCAM, in the distal stump of injured nerves is dependent upon the presence of regenerating axons.
Evaluation of the mouse TgTP6.3 tauGFP transgene as a lineage marker in chimeras
Authors: MacKay Gillian E. , Keighren Margaret A. , Wilson Linda , Pratt Thomas , Flockhart Jean H. , Mason John O. , Price David J. , West John D.
Published: January 2005

The mouse TgTP6.3 transgene, encoding a tauGFP fusion protein, is becoming widely used but has yet to be fully characterized and evaluated as suitable lineage marker. The aim of the present study was to investigate the phenotype of TgTP6.3+/+ homozygotes and TgTP6.3+/– hemizygotes, characterize the expression of the TgTP6.3 transgene in different tissues and critically evaluate its use as a lineage marker. TgTP6.3+/+ homozygotes died between embryonic day 14.5 and weaning, whereas TgTP6.3+/– hemizygotes were mostly viable and fertile but smaller than non‐transgenic siblings. TgTP6.3 expression began in the late two‐cell stage, persisted in most fetal and adult tissues and was uniformly expressed in many (but not all) tissues. TgTP6.3+/– cells were readily identified in many chimeric tissues and their contribution appeared to be quantitatively and spatially normal. Overall, tauGFP expression in hemizygous TgTP6.3+/– cells fulfils the main criteria of a good lineage marker for many tissues. It provides a useful lineage marker, which should be particularly suitable for axons, blood vessels and pre‐implantation embryos.
Anatomics: the intersection of anatomy and bioinformatics
Authors: Bard Jonathan B. L.
Published: January 2005

Computational resources are now using the tissue names of the major model organisms so that tissue‐associated data can be archived in and retrieved from databases on the basis of developing and adult anatomy. For this to be done, the set of tissues in that organism (its anatome) has to be organized in a way that is computer‐comprehensible. Indeed, such formalization is a necessary part of what is becoming known as systems biology, in which explanations of high‐level biological phenomena are not only sought in terms of lower‐level events, but are articulated within a computational framework. Lists of tissue names alone, however, turn out to be inadequate for this formalization because tissue organization is essentially hierarchical and thus cannot easily be put into tables, the natural format of relational databases. The solution now adopted is to organize the anatomy of each organism as a hierarchy of tissue names and linking relationships (e.g. the tibia is PART OF the leg, the tibia IS‐A bone) within what are known as ontologies. In these, a unique ID is assigned to each tissue and this can be used within, for example, gene‐expression databases to link data to tissue organization, and also used to query other data sources (interoperability), while inferences about the anatomy can be made within the ontology on the basis of the relationships. There are now about 15 such anatomical ontologies, many of which are linked to organism databases; these ontologies are now publicly available at the Open Biological Ontologies website (http://obo.sourceforge.net) from where they can be freely downloaded and viewed using standard tools. This review considers how anatomy is formalized within ontologies, together with the problems that have had to be solved for this to be done. It is suggested that the appropriate term for the analysis, computer formulation and use of the anatome is anatomics.
Role of gamma interferon and T cells in congenital Toxoplasma transmission
Authors: Abou‐Bacar A. , Pfaff A. W. , Letscher‐Bru V. , Filisetti D. , Rajapakse R. , Antoni E. , Villard O. , Klein J.‐P. , Candolfi E.
Published: January 2005

In the BALB/c mouse model, primary infection with Toxoplasma gondii during the second third of gestation leads to a high percentage of infected foetuses. However, immunity induced by infection contracted before pregnancy prevents parasites from crossing the placenta and completely protects the foetuses, as well as the pregnant women. In order to clarify the roles of CD4+, CD8+T lymphocytes and IFN‐γ in this protection, pregnant BALB/c mice were treated with depleting monoclonal antibodies against CD4, CD8, IFN‐γ, or control antibody. Only the foetuses of the groups treated with anti‐CD8 and anti‐IFN‐γ antibodies developed congenital toxoplasmosis. The maternal production of IFN‐γ was depressed in the mice depleted of CD4 and CD8 cells (P < 0·001). Determination of the blood parasite load demonstrated that materno‐foetal transmission of T. gondii correlates with maternal parasitaemia. Together, these results show that CD8+T lymphocytes and IFN‐γ play an important role in protection against congenital toxoplasmosis during reinfection.
Immune‐mediated alteration in gut physiology and its role in host defence in nematode infection
Authors: Khan W. I. , Collins S. M.
Published: January 2005

Activation of the mucosal immune system of the gastrointestinal tract in nematode infection results in altered intestinal physiology, which includes changes in intestinal motility and mucus production. These changes are considered to be under direct immunological control rather than a non‐specific consequence of the inflammatory reaction to the infective agent. However, little is known about the immunological basis for the changes in intestinal physiology accompanying nematode infection, or the precise role of these changes in host defence, which remains an important area to explore. In this review we describe the mechanisms by which the immune response to nematode infection influences the changes in two major cells of intestinal physiology, namely smooth muscle and goblet cells, and how these changes in intestinal physiology contribute to the host defence.

Data clearly demonstrate that the T helper (Th) 2 type immune response generated by nematode infection plays an important role in the development of infection‐induced intestinal muscle hypercontractility and goblet cell hyperplasia and that these immune‐mediated changes in intestinal physiology are associated with worm expulsion. These observations strongly suggest that intestinal muscle contractility, goblet cell hyperplasia and worm expulsion share a common immunological basis and may be causally related. These data not only provide insights into host defence in nematode infection in the context of muscle function and goblet cell response, but also have broad implications in elucidating the pathophysiology of a wide range of gastrointestinal disorders associated with altered gut physiology.
Association of autoantibodies against small nuclear ribonucleoproteins (snRNPs) with symptomatic Toxocara canis infestation
Authors: Obwaller Andreas , Duchêne Michael , Walochnik Julia , Wiedermann Gerhard , Auer Herbert , Aspöck Horst
Published: January 2005

Several studies have demonstrated the occurrence of autoantibodies in the course of infestations with helminth parasites and a number of target proteins have been identified. Sera from patients suffering from toxocarosis, a disease caused by the parasitic roundworm Toxocara canis, and from healthy individuals were tested for autoantibodies by immunofluorescence and immunoblot assays using HEp‐2 cells as antigen. A considerable proportion of the sera from patients with toxocarosis‐associated symptoms were autoantibody‐positive, with a speckled staining pattern in the immunofluorescence test (62%) and with anti‐snRNP reactivity in the immunoblot assay (98%). In contrast, significantly fewer sera from asymptomatic individuals scored positive in these assays (18% in the immunofluorescence test, P < 0·005; 24% in the immunoblot, P < 0·005). Although the causative link between Toxocara infestation and the occurrence of autoantibodies is still unclear, our results show that increased amounts of autoantibodies are associated with clinical symptoms of inflammation. Thus a serum test for autoantibodies in toxocarosis patients might be a valuable gatekeeper assay for the decision for or against anti‐inflammatory treatment.
Identification of tropomyosin, paramyosin and apolipophorin/vitellogenin as three major allergens of the sheep scab mite, Psoroptes ovis
Authors: Huntley J. F. , Machell J. , Nisbet A. J. , Van Den Broek A. , Chua K. Y. , Cheong N. , Hales B. J. , Thomas W. R.
Published: January 2005

Analysis by one‐dimensional (1‐D) SDS‐PAGE/Western blotting of whole mite extract (larval and adult stages) with sheep sera taken 0–84 days after infection with the sheep scab mite, Psoroptes ovis revealed a progressive IgE antibody response, with a dominant high molecular weight allergen (MW 180 kDa) detected early during infection. Further analysis by two‐dimensional (2‐D) SDS‐PAGE/Western blotting with post‐infection sera, revealed a more complex picture with numerous (> 20) IgE reactive spots. Trypsin digest and Maldi‐ToF analyses of these spots identified two house dust mite allergen homologues, namely tropomyosin (Der p 10) and paramyosin (Der p 11), and analysis of a third spot indicated an apolipoprotein‐like IgE reactive protein (Der p 14). Further 1‐D and 2‐D SDS/Western blotting, with specific antibodies to the house dust mite allergens Der p 10, 11, and to the IgE reactive peptide of the high molecular weight house dust mite allergen, Der p 14 (vitellogenin/apolipophorin), provided firm evidence for the presence of these three allergens in extracts of the Psoroptes mite. These studies show for the first time that homologues of the house dust mite 10, 11 and 14 group allergens are represented as immunodominant allergens of the sheep scab mite, and may represent important vaccine candidates.
Immunization with a tetramer derivative of an anti‐inflammatory pentapeptide produced by Entamoeba histolytica protects gerbils (Meriones unguiculatus) against experimental amoebic abscess of the liver
Authors: Giménez‐Scherer Juan Antonio , Cárdenas Guadalupe , López‐Osuna Martha , Velázquez Juan Raymundo , Rico Guadalupe , Isibasi Armando , Maldonado Ma. del Carmen , Morales Ma. Esther , Fernández‐Diez Jorge , Kretschmer Roberto R.
Published: January 2005

Axenically grown Entamoeba histolytica produces a pentapeptide (Met‐Gln‐Cys‐Asn‐Ser) with several anti‐inflammatory properties, including the inhibition of human monocyte locomotion (Monocyte Locomotion Inhibitory Factor (MLIF)). A construct displays the same effects as the native material. It remains to be seen if MLIF is used, or even produced in vivo by the tissue‐invading parasite. If MLIF were to be relevant in invasive amoebiasis, immunizing against it could diminish this parasite advantage and prevent lesions. KLH‐linked MLIF mixed with Freund's adjuvant was too aggressive an immunizing material to answer this question. However, immunization with a tetramer of MLIF (but not a scrambled version of MLIF) around a lysine core (MLIF–MAPS), that displays increased antigenicity, yet lacks excessive innate immunity activation, completely protects gerbils against amoebic abscess of the liver caused by the intraportal injection of virulent E. histolytica. Liver abscesses caused by Listeria monocytogenes were not prevented. Invasive E. histolytica may produce the parent protein of MLIF in vivo, and if appropriately cleaved, it may play a role in invasive amoebiasis. MLIF may join new vaccination strategies against amoebiasis.