bluuebunny/crossref_metadata_2025 huggingface dataset:
Attenuation of the norepinephrine transporter activity and trafficking via interactions with α‐synuclein
Authors: Wersinger Christophe , Jeannotte Alexis , Sidhu Anita
Published: December 2006

Alpha‐synuclein (α‐Syn) has been studied in the context of Parkinson's disease, but its normative role remains elusive. We have shown that α‐Syn regulates the homeostasis of dopaminergic and serotonergic synapses, through trafficking of the dopamine and serotonin transporter, respectively. In the present study we sought to determine if α‐Syn could also modulate noradrenergic signaling, by studying its interactions with the norepinephrine transporter (NET). We co‐transfected Ltk–cells with increasing amounts of α‐Syn DNA and a constant amount of NET DNA, and observed a progressive decrease (68%) in [3H]‐NE uptake in cells co‐transfected with a ratio of 3 : 1 α‐Syn : NET DNA. TheKdof transport did not change, but increasing α‐Syn caused a decrease in theVmaxof the transporter, from 2.27 ± 0.14 to 0.89 ± 0.15 pmol/min/105 cells, with NET expression alone or 4 : 1 ratio of α‐Syn : NET transfection, respectively. Decreases in surface biotinylation and [3H]‐nisoxetine binding kinetics in intact cells revealed that NET cell surface expression was attenuated in correlation to the amount of α‐Syn co‐transfected into cells. The interaction between NET and α‐Syn occurred via the NAC domain of α‐Syn, the region directly responsible for self‐aggregation. These findings are the first to show that α‐Syn has a central role in the homeostasis of noradrenergic neurons. Together with our previous studies on dopamine and serotonin transporters, we propose that a primary physiological role of α‐Syn may be to regulate the homeostasis of monoamines in synapses, through modulatory interactions of the protein with monoaminergic transporters.
Spinal motoneuron synaptic plasticity during the course of an animal model of multiple sclerosis
Authors: Marques K. B. , Santos L. M. B. , Oliveira A. L. R.
Published: December 2006

During the course of experimental autoimmune encephalomyelitis, a massive loss of motor and sensitive function occurs, which has been classically attributed to the demyelination process. In rats, the clinical signs disappear within 5 days following complete tetraplegia, indicating that demyelination might not be the only cause for the rapid evolution of the disease. The present work investigated the occurrence of experimental autoimmune encephalomyelitis‐induced changes of the synaptic covering of spinal motoneurons during exacerbation and after remission. The terminals were typed with transmission electron microscopy as C‐, F‐ and S‐type. Immunohistochemical analysis of synaptophysin, glial fibrillary acidic protein and the microglia/macrophage marker F4/80 were also used in order to draw a correlation between the synaptic changes and the glial reaction. The ultrastructural analysis showed that, during exacerbation, there was a strong retraction of both F‐ and S‐type terminals. In this sense, both the covering as well as the length of the remaining terminals suffered great reductions. However, the retracted terminals rapidly returned to apposition, although the mean length remained shorter. A certain level of sprouting may have occurred as, after remission, the number of F‐terminals was greater than in the control group. The immunohistochemical analysis showed that the peak of synaptic loss was coincident with an increased macro‐ and microglial reaction. Our results suggest that the major changes occurring in the spinal cord network during the time course of the disease may contribute significantly to the origin of the clinical signs as well as help to explain their rapid recovery.
Nicotinic receptor‐mediated enhancement of long‐term potentiation involves activation of metabotropic glutamate receptors and ryanodine‐sensitive calcium stores in the dentate gyrus
Authors: Welsby Philip , Rowan Michael , Anwyl Roger
Published: December 2006

Little is known about the mechanisms underlying the enhancement of long‐term potentiation (LTP) by nicotine. In the present study, the mechanisms of nicotinic enhancement of LTP were investigated in the rat dentate gyrus in vitro. Acute application of nicotine enhanced LTP induction, an action requiring activation of α7 nicotinic acetylcholine receptors (nAChRs), as it was blocked by the nAChR antagonist methyl‐lycaconitine, mimicked by the acetylcholine receptor agonist choline and absent in mutant mice null for α7 nAChR. Nicotinic enhancement of LTP was both dependent on N‐methyl‐d‐aspartate receptor activation, as no LTP was induced in the presence of nicotine and an N‐methyl‐d‐aspartate receptor antagonist, and expressed post‐synaptically, as no change in paired‐pulse ratio accompanied nicotinic enhancement of LTP. The nicotinic‐enhanced component of LTP, unlike control LTP, was dependent on activation of metabotropic glutamate receptors (mGluRs), being inhibited by the group I/II antagonist LY341495 and the mGluR5 antagonist MPEP, and also dependent on influx of Ca via L‐type Ca channels and release from ryanodine (RyR)‐sensitive intracellular stores, being prevented by nifedipine and RyR, respectively. It is suggested that nicotinic activation of the Ca‐permeable α7 nAChRs fills RyR Ca stores and release of Ca from such stores by high‐frequency stimulation via Ca‐induced Ca release and activation of mGluRs induces an additional component of LTP which summates with control LTP. Chronic application of nicotine in vivo also enhanced LTP induction in slices and was dependent on activation of mGluRs and Ca release from RyR‐sensitive intracellular stores, although acutely applied nicotine was not required for such enhanced LTP.
Postnatal switching of NMDA receptor subunits from NR2B to NR2A in rat facial motor neurons
Authors: Xing Guo‐Gang , Wang Rengang , Yang Bo , Zhang Dongxian
Published: December 2006

The subunit composition ofN‐methyl‐d‐aspartate (NMDA) receptors affects their function under normal and pathological conditions. Functional NMDA receptors are expressed in lower motor neurons, but their subunit composition has not been defined. Here, we employed electrophysiology, quantitative PCR, and immunohistochemistry to investigate the subunit composition of NMDA receptors in postnatal motor neurons of the Wistar rat facial nucleus (FN). Whole‐cell patch clamp recordings of acutely dissociated motor neurons from postnatal days 3 and 4 (P3–P4) showed that ifenprodil, a specific antagonist of the NMDA receptor 2B (NR2B) subunit, inhibited 91.62% ± 2.02% of NMDA‐induced current, whereas NVP‐AAM007, a specific antagonist of the NMDA receptor 2A (NR2A) subunit, inhibited much less of the current (16.69% ± 3.28%). Starting from P5, the inhibitory effects of ifenprodil and NVP‐AAM007 gradually decreased and increased, respectively, such that the effect of NVP‐AAM007 exceeded that of ifenprodil by P10. At P14, most of the NMDA‐induced current was inhibited by NVP‐AAM007 (84.59% ± 3.35%). Consistent with this, NR2B mRNA and protein were expressed highly at P3 and then gradually decreased by more than 75% by P14 in FN motor neurons, while NR1 was expressed stably over the same ages. However, NR2A mRNA and protein showed relatively constant levels between P3–P10 and decreased to 45% and 75% of the P3 level, respectively, by P14. Thus, analysis of functional NMDA receptors is critical to revealing subunit switching, which may be an important step in postnatal development of FN motor neurons.
Context‐dependent prefrontal cortex regulation of cocaine self‐administration and reinstatement behaviors in rats
Authors: Di Pietro Nina C. , Black Yolanda D. , Kantak Kathleen M.
Published: December 2006

Evidence of stimulus attribute‐specificity within the prefrontal cortex (PFC) suggests that different prefrontal subregions may contribute to cocaine addiction in functionally distinct ways. Thus, the present study examined the effects of lidocaine‐induced inactivation of two distinct PFC subregions, the prelimbic (PL) or dorsal agranular insular (AId) cortices, on drug‐seeking and drug‐taking behaviors under cocaine maintenance and reinstatement testing conditions in rats trained to self‐administer 1 mg/kg cocaine under a second‐order schedule of drug delivery. Throughout maintenance and reinstatement phases, rats were exposed to conditioned light cues and contextual odor or sound cues. Results showed that PL inactivation during maintenance test sessions significantly reduced drug‐seeking and drug‐taking behaviors, and disrupted patterns of responding in rats exposed to light–sound, but not light–odor, cues. Moreover, lidocaine‐induced inactivation of the PL significantly attenuated drug‐seeking behavior during cue‐induced and cocaine prime‐induced reinstatement in rats exposed to light–sound cues only. In contrast, AId inactivation significantly attenuated cue‐induced reinstatement of drug‐seeking behavior in rats exposed to light–odor cues only. Drug‐seeking and drug‐taking behaviors in these rats were not disrupted during maintenance and cocaine prime‐induced reinstatement testing regardless of the type of contextual cues used. Together, these data suggest that PL and AId subregions play separate yet overlapping roles in regulating cocaine addiction in rats in ways that are dependent on the presence or absence of cocaine and on the types of contextual cues present in the cocaine self‐administration environment.
Activation of class I metabotropic glutamate receptors limits dendritic growth of Purkinje cells in organotypic slice cultures
Authors: Sirzen‐Zelenskaya Alexandra , Zeyse Judith , Kapfhammer Josef P.
Published: December 2006

The development of the dendritic tree of a neuron is a complex process which is thought to be regulated strongly by signals from afferent fibers. We showed previously that the blockade of glutamatergic excitatory neurotransmission has little effect on Purkinje cell dendritic development. We have now studied the effects of glutamate receptor agonists on the development of Purkinje cell dendrites in mouse organotypic slice cultures. The activation of N‐methyl‐d‐aspartate receptors had no major effect on Purkinje cell dendrites and the activation of (RS)‐alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole proprionic acid receptors was strongly excitotoxic so that no analysis of its effects on dendritic development was possible. The activation of metabotropic glutamate receptors led to a very strong inhibition of dendritic growth, resulting in Purkinje cells with very small stubby dendrites. This effect was specific for the activation of class I metabotropic glutamate receptors and could not be reduced by blocking synaptic transmission in the cultures, indicating that it was mediated by receptors present on Purkinje cells. Pharmacological experiments suggest that the signaling pathway involved does not require activation of phospholipase C or protein kinase C. The inhibition of dendritic growth by activation of class I metabotropic glutamate receptor could be a useful negative feedback mechanism for limiting the size of the dendritic tree of Purkinje cells after the establishment of a sufficient number of parallel fiber contacts. This developmental mechanism could protect Purkinje cells from excitotoxic death through excessive release of glutamate from an overload of parallel fiber contacts.
Axonal retraction and regeneration induced byN,N‐diethyldithiocarbamate (DEDTC) in the central nervous system
Authors: Junyent Fèlix , Utrera Juana , Auladell Carme
Published: December 2006

Dithiocarbamates (DTCs), such as disulfiram, have been used in aversion therapy for alcoholism even though an inherent toxicity is induced, which is related mainly to peripheral neuropathy and is associated with behavioural and neurological complications. At anatomical and histopathological levels, DTCs affect structural elements in nervous tissue, such as axonal degeneration and alterations in the cytoskeletal proteins of astrocytes. Therefore, given the axonal effects of DTCs and to gain further insight into axonal growth and axonal pathfinding in the central nervous system (CNS), here we established anin vivoexperimental model of mouse development. Daily intraperitoneal injections ofN,N‐diethyldithiocarbamate (DEDTC), the first metabolite of disulfiram, were given from postnatal day 2 (P2) until P15. From P16 until P30, animals were not treated. Treatment induced considerable physiological alterations, such as growth delay, throughout postnatal development. Moreover, by immunohistochemistry techniques, we observed important alterations in the cytoskeletal glial protein at early stages of postnatal development. At later stages (P15), the immunoreactivity pattern detected by an antibody against axonal neurofilaments (anti‐NF‐H) showed alteration in the axonal distribution pattern followed by drastic axonal loss at P22, data that were corroborated using an anti‐MBP (myelin basic protein) antibody. Using an antibody against the beta amyloid precursor protein (APP), we detected axonal injury. Furthermore, given that we observed axonal re‐growth in adulthood in thein vivomodel presented, we propose that this model would be a good system in which to identify new strategies for inducing regenerative growth in neural diseases in which axonal regeneration is blocked.
Functional dentate gyrus neurogenesis in a rapid kindling seizure model
Authors: Smith Paul D. , McLean Karen J. , Murphy Michael A. , Turnley Ann M. , Cook Mark J.
Published: December 2006

Neurogenesis in the adult mammalian hippocampus resulting in long‐term persistence of new neurons with features of capacity for functional activation is recognized. Many stimuli are capable of increasing the rate of neurogenesis, including seizure activity. Whether these insults result in an increased number of new functionally active neurons over and above the baseline rate of neurogenesis is not known. The rapid electrical amygdala kindling (REAK) model of seizures isolates the effects of seizures alone in the absence of neuronal death and the resulting seizures induce expression of c‐Fos in the vast majority of dentate gyrus (DG) granule cells. C57BL/6 mice were exposed to REAK then injected with bromodeoxyuridine (BrDU) to label dividing cells, then re‐exposed to REAK after a delay period to allow detection of functional activation in new neurons by measurement c‐Fos expression in response to seizures. Adult subgranular zone cells migrated into the DG granule cell layer (GCL), assumed a neuronal phenotype and demonstrated seizure‐dependent responsiveness. Larger absolute numbers of new neurons demonstrating seizure‐dependent activation were found in the GCL of previously kindled mice. Seizures are capable of increasing the number of new neurons with the capacity for functional activation laid down in the postseizure period and incorporated into seizure‐activated circuitry.
Effects of personal familiarity on early neuromagnetic correlates of face perception
Authors: Kloth Nadine , Dobel Christian , Schweinberger Stefan R. , Zwitserlood Pienie , Bölte Jens , Junghöfer Markus
Published: December 2006

This study investigated effects of familiarity and orientation on face processing by means of magnetoencephalography. Participants were presented with photographs of personally familiar, famous and unfamiliar faces in both upright and inverted orientation. They had to decide whether faces were familiar by means of manual yes/no responses. Independent of orientation, we observed a clear modulation of the M170 by familiarity, with personally familiar faces evoking larger amplitudes than unknown faces. The M170 was also sensitive to orientation, with larger amplitudes for inverted than upright faces. Moreover, the M170 exhibited larger amplitudes over the right than over the left hemisphere, but this asymmetry was present for upright faces only. The present data suggest that at least for personally familiar faces, neural correlates of identification start no later than ∼ 170 ms, and underline a special role of the right hemisphere for faces in their typical upright orientation.
Cholinergic modulation in the olfactory bulb influences spontaneous olfactory discrimination in adult rats
Authors: Mandairon Nathalie , Ferretti Casara Jean , Stack Conor M. , Rubin Daniel B. , Cleland Thomas A. , Linster Christiane
Published: December 2006

Cholinergic neuromodulation in the olfactory bulb has been hypothesized to regulate mitral cell molecular receptive ranges and the behavioral discrimination of similar odorants. We tested the effects of cholinergic modulation in the olfactory bulb of cannulated rats by bilaterally infusing cholinergic agents into the olfactory bulbs and measuring the rats' performances on separate spontaneous and motivated odor‐discrimination tasks. Specifically, 6 µL/bulb infusions of vehicle (0.9% saline), the muscarinic antagonist scopolamine (7.6 mm and 38 mm), the nicotinic antagonist mecamylamine hydrochloride (3.8 mm and 19 mm), a combination of both antagonists, or the acetylcholinesterase inhibitor neostigmine (8.7 mm) were made 20 min prior to testing on an olfactory cross‐habituation task or a rewarded, forced‐choice odor‐discrimination task. Spontaneous discrimination between chemically related odorants was abolished when nicotinic receptors were blocked in the olfactory bulb, and enhanced when the efficacy of cholinergic inputs was increased with neostigmine. Blocking muscarinic receptors reduced but did not abolish odor discrimination. Interestingly, no behavioral effects of modulating either nicotinic or muscarinic receptors were observed when rats were trained on a reward‐motivated odor‐discrimination task. Computational modeling of glomerular circuitry demonstrates that known nicotinic cholinergic effects on bulbar neurons suffice to explain these results.
Dynamics and identification of soil microbial populations actively assimilating carbon from 13C‐labelled wheat residue as estimated by DNA‐ and RNA‐SIP techniques
Authors: Bernard Laetitia , Mougel Christophe , Maron Pierre‐Alain , Nowak Virginie , Lévêque Jean , Henault Catherine , Haichar Feth el Zahar , Berge Odile , Marol Christine , Balesdent Jérome , Gibiat Frédéric , Lemanceau Philippe , Ranjard Lionel
Published: December 2006

This work is the first report on the use of DNA‐, RNA‐SIP approaches to elucidate the dynamics and the diversity of bacterial populations actively assimilating C derived from plant residues labelled at more than 90% 13C. Wheat‐residues, were incorporated and incubated into soil microcosms for 28 days. At the end of the incubation time, no more than 55% of the total CO2 released was 13C‐labelled, suggesting the occurrence of an important priming effect process. After 7 days, more than 30% of the whole DNA extracted were labelled, allowing an efficient separation of labelled from unlabelled DNA using density gradient centrifugation. The genetic structure of bacterial community, assessed by Automated Ribosomal Intergenic Spacer Analysis technique, was deduced from the 13C‐ and 12C‐fractions of control and enriched conditions, over the time course of the experiment. Dynamics showed that wheat residues directly induced a rapid and durable stimulation of fresh organic matter (FOM) degrading populations (13C), while specific soil organic matter (SOM) degrading populations (12C) seemed to be indirectly stimulated only at the early time point (t7d). After 14 days of incubations, 16S rRNA clone libraries were elaborated on 12C‐ and 13C‐RNA extracted from enriched microcosms, as well as 12C‐RNA extracted from control condition. Stimulation of the β‐ and γ‐subgroups of proteobacteria, where numerous populations were previously described as r‐strategists or copiotrophic organisms, was recorded in the 13C‐fraction. In the mean time, several phyla like Actinobacteria, Cyanobacteria, Candidate, Gemmatimonadetes and Planctomycetes were only present in 12C fractions. Surprisingly, several sequences affiliated to species characterized as oligotrophic organisms were retrieved in both types of fraction. Trophic relationships between soil bacteria involved in FOM and SOM degradation were discussed on the basis of different hypotheses of Fontaine and colleagues (2003) concerning the mechanisms of the priming effect induction.
Fire persistence traits of plants along a productivity and disturbance gradient in mediterranean shrublands of south‐east Australia
Authors: Pausas Juli G. , Bradstock Ross A.
Published: December 2006

Aim To understand changes in fire persistence traits of plants along a latitudinal gradient, considering the interactions between productivity, community (fuel) structure and fire regime.

Location A gradient in the south of Australia (latitude 33–37° S; longitude 140–143° E), including: Little Desert National Park (VIC), Big Desert Wilderness Park (VIC), Murray‐Sunset National Park (VIC), Danggali Conservation Park (SA) and Tarawi Nature Reserve (NSW).

Methods We selected four areas along a latitudinal gradient for which information on fire history and vegetation was available. Then, we tested to what extent the four selected areas have different climate and different fire regimes. Plant cover values of different life forms provided an indication of the plant community structure and flammability, and the proportion of species with different fire persistence traits (resprouting, seedbank persistence) informed us on the trait selection.

Results Precipitation decreases and temperature increases from south to north. Thus the selected sites represent a gradient from high productivity (low aridity) in the south to low productivity (high aridity) in the north. Fire statistics suggest that fire frequency parallels productivity. There is a tendency for life form dominance and community structure to shift in such a way that fuel connectivity is reduced towards the north. Resprouting species increase and obligate seeders decrease along the fire–productivity gradient.

Main conclusions Changes in plant traits are difficult to understand without simultaneous consideration of both the disturbance and the productivity gradients. In our study area, fire regime and productivity interact in such a way that decreases in productivity imply changes in fuel structure that produce a reduction in fire frequency. Resprouting species are better represented at the high fire–productivity part of the gradient, while obligate seeders are better represented at the opposite end of the gradient. The results also emphasize the importance of considering not only climate changes but also changes in fuel structure to predict future fire regimes.
Study of Heat Flow through Highly Porous Heat Insulators
Authors: Roy Samir , Sundar S.
Published: December 2006

A comprehensive study is done to model flow of heat through heat insulators based on materials with high gas content such as solidified foams (e.g., eXtruded PolyStyrene foams, Expanded PolyStyrene foam), cellular glass, etc. The actual internal cell‐like structure of such an insulator is replicated by regularly shaped gas pockets, which are separated from each other by thin rims of solid materials. The first model focuses on heat flow across the insulator caused by conduction and convection. Subsequently, the effect of radiation is also studied. Several numerical results are presented and computational results are compared with experimentally measured data.
The General Theory of Linear Difference Equations over the Max‐Plus Semi‐Ring
Authors: Joshi Nalini , Ormerod Chris
Published: December 2006

We present the mathematical theory underlying systems of linear difference equations over the max‐plus semi‐ring. The result provides an analog of isomonodromy theory for ultradiscrete Painlevé equations, which are extended cellular automata, and provide evidence for their integrability. Our theory is analogous to that developed by Birkhoff and his school for linear q‐difference equations, but stands independently of the latter. As an example, we derive linear problems in this algebra for ultradiscrete versions of the symmetric PIV equation and show how it is a necessary condition for isomonodromic deformation of a linear system.
Unintended Consequences: Does Aid Promote Arms Races?*
Authors: Collier Paul , Hoeffler Anke
Published: December 2006

Using global data for the period 1960–99, we model military expenditure. Neighbours’ military spending and development aid are important determinants of military expenditure. An implication of the model is that there are regional arms races which are fuelled by aid. Potentially, aid is encouraging a ‘regional public bad’. There may, however, be an offsetting public good effect if military spending deters rebellions. In a simultaneous equation model, we find no deterrence effect of spending on the risk of civil war. Hence, there appears to be no regional public good effect offsetting the public bad arising from a neighbourhood arms race.
Hedonic Price Models for Dynamic Markets*
Authors: Kristofersson Dadi , Rickertsen Kyrre
Published: December 2006

The price of a product depends on its characteristics and will vary in dynamic markets. The model describes a processing firm that bids in an auction for a heterogeneous and perishable input. The reduced form of this model is estimated as an expanded random parameter model that combines a nonlinear hedonic bid function and inverse input demand functions for characteristics. The model was estimated by using 289,405 transactions from the Icelandic fish auctions. Total catch and gut ratio were the main determinants of marginal prices of characteristics, while the price of cod mainly depended on size, gutting and storage.
Factor Utilization and Adjusted Productivity Estimates for the UK*
Authors: Larsen Jens , Neiss Katharine , Shortall Fergal
Published: December 2006

This paper derives series for capital utilization, labour effort and total factor productivity (TFP) for the UK from a general equilibrium model with variable utilization and labour adjustment costs. Capital utilization tracks survey‐based measures closely, but persistent movements in total hours worked mean our labour effort series is not as highly correlated with its comparators. Our estimated TFP series is less cyclical than the traditional Solow residual, although a weighted average of capital utilization and labour effort – aggregate factor utilization – and the Solow residual are not closely related.
Morphometric analysis of facial landmark data to characterize the facial phenotype associated with fetal alcohol syndrome
Authors: Mutsvangwa Tinashe , Douglas Tania S.
Published: December 2006

Procrustes analysis and principal component analysis were applied to stereo‐photogrammetrically obtained landmarks to compare the facial features associated with fetal alcohol syndrome (FAS) in subjects with FAS and normal controls. Two studies were performed; both compared facial landmark data of FAS and normal subjects, but they differed in the number of landmarks chosen. The first study compared landmarks representing palpebral fissure length, upper lip thinness and philtrum smoothness and revealed no significant difference in shape. The second study added to the landmarks used in the first those affected by mid‐face hypoplasia, and revealed significant differences in shape between the two groups, broadly confirming the FAS gestalt reported in the literature. Some disagreement in the characteristic FAS facial shape between our results and those reported in the literature may be due to ethnic variation.
Nicardipine in pre‐eclamptic patients: placental transfer and disposition in breast milk
Authors: Bartels PA , Hanff LM , Mathot RAA , Steegers EAP , Vulto AG , Visser W
Published: December 2006

To assess the safety risks to the fetus and neonate caused by maternal use of nicardipine in pre‐eclamptic patients, we evaluated the placental transfer and the transfer to breast milk after maternal intravenous administration of nicardipine. In ten pre‐eclamptic subjects, nicardipine concentrations of maternal blood (P) and both arterial and venous umbilical cord blood samples (Uarterial and Uvenous) were assessed, and the U/P ratio was calculated as an indication of placental transfer. We found a median transfer of 0.15 (Uarterial/P, range 0.05–0.22) and 0.17 (Uvenous/P, range 0.023–0.22). The highest umbilical cord concentration found after maternal dosage of 4.5 mg/hour was 18 ng/ml, which can be considered as subtherapeutic. Therefore, adverse fetal reactions caused by a direct pharmacological effect of nicardipine are unlikely to occur. Nicardipine levels were determined in 34 breast milk samples of seven women, and were found to be undetectable in 82% of the samples. In six breast milk samples of four different women, nicardipine levels (ranging from 5.1 to 18.5 ng/ml) were detectable during maternal nicardipine dosages ranging from 1 to 6.5 mg/hour. The maximum possible exposure of a neonate to nicardipine was calculated to be less than 300 ng/day, which is an insignificant fraction of therapeutic dosages used in neonates. In conclusion, the exposure of a fetus and neonate to nicardipine through placental transfer and disposition in breast milk expression is low.
Pathways to diagnosis of cervical cancer: screening history, delay in follow up, and smear reading
Authors: Priest P , Sadler L , Peters J , Crengle S , Bethwaite P , Medley G , Jackson R
Published: December 2006

Background  The aim of this study was to determine the most important ways to reduce incidence of and mortality from cervical cancer by a nationally co‐ordinated screening programme.

Design  Descriptive study.

Setting  The New Zealand National Cervical Screening Programme: a nationally organised and co‐ordinated programme.

Sample  Women aged younger than 80 years with histologically proven primary invasive cervical cancer, including microinvasive disease, diagnosed between 1 January 2000 and 30 September 2002. Consent for access to medical records was gained for 371 of 445 eligible women (83%). A total of 359 (81%) of eligible women or their next of kin consented to interview.

Methods  Data on events prior to diagnosis were obtained from routine sources, interview, medical record review and slide reread.

Main outcome measures  Frequency of screening in the 7 years prior to diagnosis, time from abnormal smear or symptoms to appropriate diagnostic confirmation, proportion of negative smears upgraded to high grade on reread.

Results  Half of the 371 participants (83% of 445 eligible women) had not had a screening smear in the 3 years prior to diagnosis, and 80% were defined as inadequately screened. A maximum of 17% of women overall or within any defined subgroup experienced delays in follow up of abnormal smears or bleeding. Only 11% of women overall had had a high‐grade smear, which was originally read as negative.

Conclusions  The most important factor in women’s pathways to a diagnosis of cervical cancer was inadequate screening. While delays in diagnosis could be reduced and laboratory performance improved, priority must be given to improving uptake and frequency of screening.
Specific caspase inhibitor Q‐VD‐OPh prevents neonatal stroke in P7 rat: a role for gender
Authors: Renolleau Sylvain , Fau Sébastien , Goyenvalle Catherine , Joly Luc‐Marie , Chauvier David , Jacotot Etienne , Mariani Jean , Charriaut‐Marlangue Christiane
Published: December 2006

Hypoxia–ischaemia in the developing brain results in brain injury with prominent features of apoptosis. In the present study, a third generation dipeptidyl broad‐spectrum caspase inhibitor, quinoline‐Val‐Asp(Ome)‐CH2‐O‐phenoxy (Q‐VD‐OPh), was tested in a model of unilateral focal ischaemia with reperfusion in 7‐day‐old rats. Q‐VD‐OPh (1 mg/kg, i.p.) reduced cell death, resulting in significant neuroprotection at 48 h of recovery (infarct volume of 12.6 ± 2.8 vs. 24.3 ± 2.2%, p = 0.006). The neuroprotective effects observed at 48 h post‐ischaemia hold up at 21 days of survival time and attenuate neurological dysfunction. Analysis by gender revealed that females were strongly protected (6.7 ± 3.3%, p = 0.006), in contrast to males in which there was no significant effect, when Q‐VD‐OPh was given after clip removal on the left common carotid artery. Immunoblot analysis demonstrated that Q‐VD‐OPh inhibits caspase 3 cleavage into its p17 active form and caspase 1 up‐regulation and cleavage in vivo. Following ischaemia in P7 rats, males and females displayed different time course and pattern of cytochrome c release and active p17 caspase 3 during the first 24 h of recovery. In contrast, no significant difference was observed for caspase 1 expression between genders. These results indicate that ischaemia activates caspases shortly after reperfusion and that the sex of the animal may strongly influences apoptotic pathways in the pathogenesis of neonatal brain injury. The specificity, effectiveness, and reduced toxicity of Q‐VD‐OPh may determine the potential use of peptide‐derived irreversible caspase inhibitors as promising therapeutics.
Enhancing the Effectiveness of Work Groups and Teams
Authors: Kozlowski Steve W.J. , Ilgen Daniel R.
Published: December 2006

Teams of people working together for a common purpose have been a centerpiece of human social organization ever since our ancient ancestors first banded together to hunt game, raise families, and defend their communities. Human history is largely a story of people working together in groups to explore, achieve, and conquer. Yet, the modern concept of work in large organizations that developed in the late 19th and early 20th centuries is largely a tale of work as a collection of individual jobs. A variety of global forces unfolding over the last two decades, however, has pushed organizations worldwide to restructure work around teams, to enable more rapid, flexible, and adaptive responses to the unexpected. This shift in the structure of work has made team effectiveness a salient organizational concern.

Teams touch our lives everyday and their effectiveness is important to well-being across a wide range of societal functions. There is over 50 years of psychological research—literally thousands of studies—focused on understanding and influencing the processes that underlie team effectiveness. Our goal in this monograph is to sift through this voluminous literature to identify what we know, what we think we know, and what we need to know to improve the effectiveness of work groups and teams.

We begin by defining team effectiveness and establishing the conceptual underpinnings of our approach to understanding it. We then turn to our review, which concentrates primarily on topics that have well-developed theoretical and empirical foundations, to ensure that our conclusions and recommendations are on firm footing. Our review begins by focusing on cognitive, motivational/affective, and behavioral team processes—processes that enable team members to combine their resources to resolve task demands and, in so doing, be effective. We then turn our attention to identifying interventions, or “levers,” that can shape or align team processes and thereby provide tools and applications that can improve team effectiveness. Topic-specific conclusions and recommendations are given throughout the review. There is a solid foundation for concluding that there is an emerging science of team effectiveness and that findings from this research foundation provide several means to improve team effectiveness. In the concluding section, we summarize our primary findings to highlight specific research, application, and policy recommendations for enhancing the effectiveness of work groups and teams.
Population Estimation Using Landsat Enhanced Thematic Mapper Imagery
Authors: Wu Changshan , Murray Alan T.
Published: December 2006

An assessment of two groups of approaches for estimating urban population with remote‐sensing information is presented in this article. These approaches, zonal and pixel‐based models, are applied to Landsat Enhanced Thematic Mapper images of a portion of Columbus, Ohio, to generate population estimates. The zonal approach uses impervious surface fraction, spectral radiance, and land‐use/land‐cover classification to derive population estimates. The pixel‐based approach uses impervious surface fraction and spectral radiance to estimate the population of residential areas. To assess robustness, these models were applied to Dayton, Ohio. A comparative study indicates that the models generated promising results in estimating regional population counts. However, zonal regression with spectral radiance produced large errors (76%) for census block groups, whereas other models gave significantly better estimation accuracy. Comparing the performance of the indicators, impervious surface fraction is competitive, and slightly but consistently better than land‐use classification. In comparison with traditional zonal approaches, pixel‐based models give somewhat better estimation accuracy.
Land Absorption in U.S. Metropolitan Areas: Estimates and Projections from Regional Adjustment Models
Authors: Carruthers John I. , Mulligan Gordon F.
Published: December 2006

This article adapts a regional adjustment model to estimate and project the spatial outcome of population and employment growth in U.S. metropolitan areas. The three‐equation multiplicative model of population change, employment change, and land absorption is estimated using three‐stage least squares to account for endogeneity among the dependent variables and contemporaneous correlation across the system of equations. In addition to the core model, alternative specifications are estimated, imposing the initial conditions of size, land availability, and economic structure. The stability of the solutions is then examined using reduced‐form equations estimated via the seemingly unrelated regression equations approach. The results reveal substantive evidence that population and employment growth are jointly determined, of how the two affect the outcome of land development, and, perhaps most importantly, stable and fractionally reasonable estimates at projected equilibrium points. Lastly, the adapted model controlling for the initial condition of land availability is used to project patterns of land consumption at equilibrium in 50 rapid‐growth metropolitan areas.
Melatonin induces neuritogenesis at early stages in N1E‐115 cells through actin rearrangements via activation of protein kinase C and Rho‐associated kinase
Authors: Bellon Alfredo , Ortíz‐López Leonardo , Ramírez‐Rodríguez Gerardo , Antón‐Tay Fernando , Benítez‐King Gloria
Published: December 2006

Abstract:  Melatonin increases neurite formation in N1E‐115 cells through microtubule enlargement elicited by calmodulin antagonism and vimentin intermediate filament reorganization caused by protein kinase C (PKC) activation. Microfilament rearrangement is also a necessary process in growth cone formation during neurite outgrowth. In this work, we studied the effect of melatonin on microfilament rearrangements present at early stages of neurite formation and the possible participation of PKC and the Rho‐associated kinase (ROCK), which is a downstream kinase in the PKC signaling pathway. The results showed that 1 nm melatonin increased both the number of cells with filopodia and with long neurites. Similar results were obtained with the PKC activator phorbol 12‐myristate 13‐acetate (PMA). Both melatonin and PMA increased the quantity of filamentous actin. In contrast, the PKC inhibitor bisindolylmaleimide abolished microfilament organization elicited by either melatonin or PMA, while the Rho inhibitor C3, or the ROCK inhibitor Y27632, abolished the bipolar neurite morphology of N1E‐115 cells. Instead, these inhibitors prompted neurite ramification. ROCK activity measured in whole cell extracts and in N1E‐115 cells was increased in the presence of melatonin and PMA. The results indicate that melatonin increases the number of cells with immature neurites and suggest that these neurites can be susceptible to differentiation by incoming extracellular signals. Data also indicate that PKC and ROCK are involved at initial stages of neurite formation in the mechanism by which melatonin recruits cells for later differentiation.
Melatonin at pharmacological doses enhances human osteoblastic differentiation in vitro and promotes mouse cortical bone formation in vivo
Authors: Satomura Kazuhito , Tobiume Satoru , Tokuyama Reiko , Yamasaki Yasuhumi , Kudoh Keiko , Maeda Eriko , Nagayama Masaru
Published: December 2006

Abstract:  Melatonin is known to regulate a variety of physiological processes including control of circadian rhythms, regulation of seasonal reproductive function, regulation of body temperature, and so forth. Accumulating evidence from in vitro and in vivo experiments using rodent and chicken has also suggested that melatonin may have an influence on skeletal growth and bone formation. However, little is known about the effects of melatonin on human osteoblasts, which thus remains to be elucidated. This study was performed to determine whether melatonin could affect the proliferation and differentiation of human osteoblasts in vitro and to demonstrate the possibility that melatonin could be applied as a pharmaceutical agent to shorten the treatment period of bone fracture, various osteotomies, and bone distraction. Reverse transcription‐polymerase chain reaction and Western blot analysis showed that human osteoblasts expressed melatonin 1a receptor and that its expression levels decreased gradually with the age of the hosts. Melatonin stimulated the proliferation and alkaline phosphatase activity of human osteoblasts in a dose‐dependent manner at the pharmacological concentrations. Melatonin also promotes gene expression of type I collagen, osteopontin, bone sialoprotein, and osteocalcin in a dose‐dependent manner, and stimulated the mineralized matrix formation in vitro. Moreover, intraperitoneal administration of melatonin to mice increased the volume of newly formed cortical bone of femora. These results demonstrated that melatonin directly accelerated the differentiation of osteoblasts of human as well as rodent and chicken and also suggested that melatonin could be applied as a pharmaceutical agent to promote bone regeneration.
Evidence for melatonin synthesis in the rat brain during development
Authors: Jimenez‐Jorge Silvia , Guerrero Juan M. , Jimenez‐Caliani Antonio J. , Naranjo Maria C. , Lardone Patricia J. , Carrillo‐Vico Antonio , Osuna Carmen , Molinero Patrocinio
Published: December 2006

Abstract:  Melatonin production is not restricted to the pineal gland. Several extrapineal sources of this indole such as retina, Harderian gland, and immune system are well documented. Melatonin of pineal origin is not present in the rat at early stages of development. To assess the potential capacity of local melatonin synthesis by the immature brain and to gain insight into the relationship between melatonin production by the brain (without the pineal gland) and pineal gland during rat development, the melatonin content as well as the expression and activity of the melatonin‐synthesizing enzymes, N‐acetyltransferase (NAT) and hydroxyindole‐O‐methyltransferase (HIOMT), were studied at fetal and postnatal stages. Moreover, melatonin‐membrane receptor (MT1) expression was also analyzed. Both, the expression and activity of NAT and HIOMT were found in the brain with significant day/night differences in enzymes activities. Additionally, melatonin content was detected in all stages showing day/night differences depending on the stage of development. The brain nocturnal melatonin content was higher than diurnal content on postnatal day 16 and in adult rats which is in accordance with the pineal melatonin synthesis. To investigate the origin of this brain melatonin, pinealectomized rats were used and we found that the developing brain produced its own melatonin. Also, MT1 expression was detected in brain during development. These results demonstrate that, when the pineal is not yet producing melatonin, there is melatonin synthesis by the brain that could be used as protection from free radical damage and/or could exert some actions through MT1 receptors.
Abortion Opinion Research in Latin America and the Caribbean: A Review of the Literature
Authors: Yam Eileen A. , Dries‐Daffner Ingrid , García Sandra G.
Published: December 2006

Abortion laws in Latin America and the Caribbean (LAC) are highly restrictive and may not reflect public opinion on the issue. This article synthesizes the survey literature on attitudes toward abortion in the region. We searched standard computer indexing services and polled colleagues at regional meetings to identify every methodologically sound quantitative study of abortion opinion in LAC published between 1985 and 2005. Of the 26 studies that met inclusion criteria, none was conducted in the Caribbean, 11 were conducted in Brazil, 11 in Mexico, 3 in Argentina, and 1 in Colombia. The majority of populations surveyed support abortion under a greater number of circumstances than are permitted in their respective countries, particularly in cases of rape and threat to life or health. Future abortion opinion surveys should ask about support for the legality of abortion rather than about abstract acceptance of abortion, and questions should be worded carefully to capture the complexities of the public's views on this issue.
Gender, Migration, Risky Sex, and HIV Infection in China
Authors: Yang Xiushi , Xia Guomei
Published: December 2006

Gender differences in sexual behavior as a consequence of migration have been ignored in both the migration and the HIV literature in China. This study examines differences among temporary migrants in terms of sexual behavior and factors that make female migrants more vulnerable to the risk of acquiring HIV infection. Results suggest that the interplay of migration and gender renders female temporary migrants particularly vulnerable to engaging in casual and commercial sex. Although male temporary migrants do not differ from male nonmigrants in prevalence of casual and commercial sex, the prevalence rates of casual and commercial sex for female temporary migrants are found to be 14 and 80 times those for female nonmigrants, respectively. Female temporary migrants' higher unemployment rate and concentration in the service and entertainment sectors are keys to understanding differences in the prevalence of casual and commercial sex among temporary migrants according to sex. Policy measures to promote female temporary migrants' equal access to employment are urgently needed to improve their economic well‐being and to reduce their risky sexual behavior.
Why Are Infant and Child Mortality Rates Lower in the MCH‐FP Area of Matlab, Bangladesh?
Authors: Hale Lauren , DaVanzo Julie , Razzaque Abdur , Rahman Mizanur
Published: December 2006

Infant and child mortality rates are significantly lower in the Maternal and Child Health‐Family Planning (MCH‐FP) area of Matlab, Bangladesh, than in a comparison area. The two areas are similar in terms of socioeconomic characteristics, but the MCH‐FP area provides better maternal and child health and family planning services, resulting in different reproductive patterns, including lower fertility rates and longer intervals between pregnancies. We use data from the Matlab Demographic Surveillance System for nearly 126,000 singleton live births that occurred between 1982 and 2002 to investigate the extent to which the different reproductive patterns in the MCH‐FP area explain why infant and child mortality rates are lower there. Differences in reproductive patterns account for a small portion (up to 20 percent) of the variation in these rates between the MCH‐FP and comparison areas, suggesting that the majority of the difference is due to the quality of MCH services.