bluuebunny/crossref_metadata_2025 huggingface dataset:
Density, habitat use and activity patterns of ocelots (Leopardus pardalis) in the Atlantic Forest of Misiones, Argentina
Authors: Di Bitetti M. S. , Paviolo A. , De Angelo C.
Published: May 2006

Camera‐trap surveys were carried out at two different sites within the Atlantic Forest of Misiones province, Argentina, to study the density, habitat use and activity patterns of ocelots. At Urugua‐í Provincial Park, 17 different individuals were captured (nine females, six males, two of unknown sex) during a 3‐month‐long survey (34 camera stations, 1409 trap days). At Iguazú National Park, 34 different individuals were trapped (20 adult females, nine adult males, two subadult females and three of unknown sex) during the survey (39 sampling stations, 1631 trap days). Population density estimates (±se) for Urugua‐í, in an area of between 150 and 259 km2 (depending on the buffer used to estimate the area effectively sampled), range from 7.7±1.4 to 13.4±2.6 individuals × 100 km−2, whereas at Iguazú, in an area of between 275 and 428 km2, a population density of between 12.8±2.7 and 20.0±4.2 individuals × 100 km−2 was estimated. Minimum observed range estimates for individuals with >3 capture sites range from 3.19 to 37.09 km2 for four males and from 4.17 to 7.11 km2 for three females, but underestimate the true home range size. Ocelots were captured more frequently along old roads than on new trails opened with machetes. Ocelots were captured more frequently at night than during the day and reduce their use of roads and trails during the week previous to and during full moon nights, a behavior previously reported for Amazonian ocelots. Population density estimates for ocelots in the Upper Paraná Atlantic Forest ecoregion are lower than those at other neotropical sites. The whole Green Corridor contains a population of about 1280 individuals. This estimate should bring our attention to the larger cats (pumas and jaguars) that live at lower population densities because the future of their local populations is compromised if protected areas are not urgently created and properly managed.
Stable isotope evidence (δ13C, δ18O) for winter feeding on seaweed by Neolithic sheep of Scotland
Authors: Balasse M. , Tresset A. , Ambrose S. H.
Published: May 2006

The antiquity of the use of seaweed to feed domestic animals was investigated through carbon (δ13C) and oxygen (δ18O) isotope analysis of tooth enamel bioapatite. The analysis was performed on sheep and cattle teeth from two Neolithic sites in Orkney (Scotland). At the Knap of Howar, c. 3600 bc, carbon isotopes reflect grazing on terrestrial plants throughout the year for both sheep and cattle, with no contribution of seaweed to their diet. At the Holm of Papa Westray North (HPWN), c. 3000 bc, significant contribution of seaweed to the sheep diet during winter is indicated by bioapatite δ13C values as high as −5.7‰, far outside of the range of values expected for the feeding on terrestrial C3 plants, and δ18O values higher than expected during winter, possibly caused by ingestion of oceanic water with seaweed. Ingestion of seaweed by sheep at HPWN might have been necessitated by severe reduction of pastures during winter. Results suggest that sheep ingested fresh seaweed rather than dry fodder, perhaps directly on the shore as sheep do nowadays on North Ronaldsay. A significant difference between the two populations is the exclusive reliance on seaweed by the North Ronaldsay sheep, which have developed physiological adaptations to this diet. Contribution of seaweed to the sheep winter diet at HPWN might have been a first step towards this adaptation.
Growth and age determination of African savanna elephants
Authors: Shrader A. M. , Ferreira S. M. , McElveen M. E. , Lee P. C. , Moss C. J. , Van Aarde R.J.
Published: May 2006

Understanding the population dynamics of savanna elephants depends on estimating population parameters such as the age at first reproduction, calving interval and age‐specific survival rates. The generation of these parameters, however, relies on the ability to accurately determine the age of individuals, but a reliable age estimation technique for free‐ranging elephants is presently not available. Shoulder heights of elephants were measured in 10 populations in five countries across southern and eastern Africa. Data included shoulder height measurements from two populations where the age of each individual was known (i.e. Addo Elephant National Park, South Africa and Amboseli National Park, Kenya). From the known‐age data, Von Bertalanffy growth functions were constructed for both male and female elephants. Savanna elephants were found to attain similar asymptotic shoulder heights in the 10 populations, while individuals in the two known‐age populations grew at the same rate. The Von Bertalanffy growth curves allowed for the accurate age estimation of females up to 15 years of age and males up to 36 years of age. The results indicate that shoulder height can serve as an indicator of chronological age for elephants below 15 years of age for females and 36 years of age for males. Ages derived from these growth curves can then be used to generate age‐specific population variables, which will help assess the demographic status of savanna elephant populations across Africa.
Probability‐independent and ‐dependent ERPs reflecting visual change detection
Authors: Kimura Motohiro , Katayama Jun'ichi , Murohashi Harumitsu
Published: May 2006

In ERP studies, two posterior components with different polarities have been identified as ERP correlates of visual change detection. To compare these components in terms of sensitivity to the preceding stimulus sequence, two peripheral stimuli of different colors (red and blue) were presented with equal (50:50) or different probabilities (20:80 or 80:20), while 12 participants performed shape discrimination at a central location. A posterior positivity at around 90–140 ms was observed with similar amplitude to all stimuli immediately preceded by a different stimulus. In contrast, a posterior negativity at around 140–180 ms was observed to increase in amplitude with increasing number of preceding different stimuli. These results suggest the existence of probability‐independent and ‐dependent change processing in the human visual system. The functional significance is discussed in terms of memory‐based comparison and stimulus‐specific refractoriness.
Fast optical imaging of frontal cortex during active and passive oddball tasks
Authors: Low Kathy A. , Leaver Echo , Kramer Arthur F. , Fabiani Monica , Gratton Gabriele
Published: May 2006

This study used the high spatial and temporal resolution of the event‐related optical signal (EROS) to investigate the timing of neuronal activity in frontal cortex during auditory target detection and passive oddball tasks. Activation in right middle frontal gyrus (MFG) peaked approximately 350 ms following rare target tones. This corresponded closely to the latency of the simultaneously recorded electrical P3 component. In addition, we found activation in left lateral MFG peaking at approximately 130 ms following tone onset for conditions that may have required response inhibition. These results correspond with activation patterns observed in similar fMRI studies, but provide temporal tags for the activated locations. These data may help bridge the gap between electrophysiological and hemodynamic measures of target detection and contribute to our understanding of the spatiotemporal dynamics of brain activity during target processing.
Habituation of auditory evoked potentials in intracranial and extracranial recordings
Authors: Rosburg Timm , Trautner Peter , Boutros Nashaat N. , Korzyukov Oleg A. , Schaller Carlo , Elger Christian Erich , Kurthen Martin
Published: May 2006

Effects of stimulus repetition are investigated in short‐term habituation experiments. In these experiments, trains of stimuli are applied with longer intervals of no stimulation between the trains. In scalp recordings, an amplitude and latency decrease of the auditory N100 is usually observed at the beginning of the train. This contrasts to a recent finding with intracranial recordings, exhibiting an effect on N100 amplitude, but not on its latency. In the current study, P50 and N100 were simultaneously recorded intra‐ and extracranially in epilepsy patients. The amplitudes of P50 and N100 decreased in both recordings, whereas the P50 latency was not significantly affected. A latency decrease was revealed for the extracranially recorded N100, but not for the intracranial N100. This dissociation between the intracranial and scalp recordings might be explained by a different sensitivity of the two measurements for N100 generators.
When does size not matter? Effects of stimulus size on affective modulation
Authors: De Cesarei Andrea , Codispoti Maurizio
Published: May 2006

Motivationally relevant stimuli have been shown to receive prioritized processing compared to neutral stimuli at distinct processing stages. This effect has been related to the evolutionary importance of rapidly detecting dangers and potential rewards and has been shown to be modulated by the distance between an organism and a faced stimulus. Similarly, recent studies showed degrees of emotional modulation of autonomic responses and subjective arousal ratings depending on stimulus size. In the present study, affective modulation of pictures presented in different sizes was investigated by measuring event‐related potentials during a two‐choice categorization task. Results showed significant emotional modulation across all sizes at both earlier and later stages of processing. Moreover, affective modulation of earlier processes was reduced in smaller compared to larger sizes, whereas no changes in affective modulation were observed at later stages.
Task‐dependent exogenous cuing effects depend on cue modality
Authors: Van der Lubbe Robh.J. , Havik Maarten M. , Bekker Evelijne M. , Postma Albert
Published: May 2006

Task‐dependent exogenous cuing effects on reaction time in detection and discrimination tasks have been ascribed to delayed withdrawal of attention in discrimination tasks. Alternatively, these differences may be due to cue‐induced response inhibition in detection tasks. Unimodal and crossmodal versions of the Posner paradigm were examined with short cue–target intervals. Targets above or below fixation required either detection or discrimination responses. Cuing effects were determined for the target‐elicited P1 component and for the lateralized readiness potential (LRP). Task‐dependent cuing effects on reaction time were found in the unimodal but not in the crossmodal version, but not for the P1 component. The LRP data indicated that inhibition of return in the unimodal detection task had a premotoric locus. These findings suggest that inhibition in the unimodal detection task resulted from speeded motor inhibition triggered by the visual cue.
An event‐related potential study of supramodal attentional control and crossmodal attention effects
Authors: Green Jessica J. , McDonald John J.
Published: May 2006

We conducted two audiovisual experiments to determine whether event‐related potential (ERP) components elicited by attention‐directing cues reflect supramodal attentional control. Symbolic visual cues were used to direct attention prior to auditory targets in Experiment 1, and symbolic auditory cues were used to direct attention prior to visual targets in Experiment 2. Different patterns of cue ERPs were found in the two experiments. A frontal negativity called the ADAN was absent in Experiment 2, which indicates that this component does not reflect supramodal attentional control. A posterior positivity called the LDAP was observed in both experiments but was focused more posteriorly over the occipital scalp in Experiment 2. This component appears to reflect multiple processes, including visual processes involved in location marking and target preparation as well as supramodal processes involved in attentional control.
Preattentive timing of empty intervals is from marker offset to onset
Authors: Tse Chun‐Yu , Penney Trevor B.
Published: May 2006

The internal marker hypothesis explains the superior timing performance for empty intervals over filled intervals by assuming that timing an empty interval starts from the offset of the first marker stimulus and stops at the onset of the second marker stimulus. Other models suggest that timing an empty interval is from first marker onset to second marker onset. We used an electrophysiological measure of preattentive change detection, the mismatch negativity (MMN), to examine processing of empty intervals. Participants watched a silent movie while a stream of auditory stimuli demarcating empty intervals was presented in the background. Most intervals were of the same duration (standards), but shorter intervals (deviants) were presented occasionally also. The pattern of MMN amplitudes obtained across five deviant conditions indicated that preattentive timing of empty intervals occurred from marker offset to onset.
Uterine rupture and labour after a previous low transverse caesarean section
Authors: Turner MJA , Agnew G , Langan H
Published: May 2006

This study reviewed all cases of complete uterine rupture (UR) in pregnancy during the decade 1993–2002. In 69 412 deliveries, 5320 women had a single prior caesarean section. Of these, 4021 had a trial of labour and 3129 (77.8%) delivered vaginally. In nine (0.22%) cases, the previous transverse scar ruptured during labour. None of these nine ruptures resulted in maternal or fetal death, peripartum hysterectomy or fetal morbidity. In our practice, a trial of labour in women with a previous low transverse caesarean is associated with a high rate of vaginal delivery and a low rate of UR.
Predicting the impact of in vitro fertilisation and other forms of assisted conception on perinatal and infant mortality in England and Wales: examining the role of multiplicity
Authors: Oakley L , Doyle P
Published: May 2006

The increased risk of perinatal and infant mortality observed among in vitro fertilisation (IVF) births and other assisted conception births is thought to be largely attributable to multiplicity. Using mortality statistics and estimates of the proportion of births following infertility treatment, we predicted the excess stillbirths and infant deaths associated with twins and higher order births resulting from assisted conception in England and Wales. According to our results, approximately 73 deaths could have been avoided in 2001 if all IVF infants had been born as singletons or as naturally occurring monozygotic twins, equating to a population attributable risk fraction of around 1% for perinatal and infant deaths. If we include all types of assisted conception, this figure was estimated to be around 4% of deaths—more than 220 perinatal and infant deaths in 2001. We confirm the public health importance of multiple births associated with assisted conception.
Late miscarriage and preterm birth after treatment with clindamycin: a randomised consent design study according to Zelen
Authors: Larsson P‐G , Fåhraeus L , Carlsson B , Jakobsson T , Forsum U ,   the premature study group of the Southeast Health Care Region of Sweden
Published: May 2006

Objective  To screen for bacterial vaginosis (BV) and to investigate the effect of treatment with vaginal clindamycin in order to observe the effect on late miscarriage and delivery prior to 37 completed weeks (primary outcome).

Design  Randomised consent design for clinical trials according to Zelen.

Setting  Southeast region of Sweden.

Population  A total of 9025 women were screened in early pregnancy.

Methods  A total of 819 women with a Nugent score of 6 and above were considered to have BV and treated according to Zelen allocation. The incidence of late miscarriage and spontaneous (noniatrogenic) preterm birth was assessed.

Main outcome measures  Late miscarriage and spontaneous preterm delivery before 37 weeks.

Results  Therapy with vaginal clindamycin had no significant impact on the incidence of spontaneous preterm delivery prior to 37 completed weeks; OR 0.90, 95% CI 0.40–2.02 (primary outcome variable). However, only 1 of 11 women in the treatment group versus 5 of 12 in the control group delivered prior to 33 completed weeks; OR 0.14, 95% CI 0.02–0.95. Treatment was associated with 32 days longer gestation for the 23 participants who had late miscarriage or spontaneous preterm birth (P= 0.024, Mann–Whitney U test) and significantly fewer infants had a birthweight below 2500 g (secondary outcome). A follow up of infants born preterm 4 years postnatally indicated that extending gestational age did not increase the number of sequelae.

Conclusions  Clindamycin vaginal cream therapy was associated with significantly prolonged gestation and reduced cost of neonatal care in women with BV. Early screening for BV and treatment with clindamycin saved approximately €27 per woman.
Regimens of misoprostol with mifepristone for early medical abortion: a randomised trial
Authors: Shannon C , Wiebe E , Jacot F , Guilbert E , Dunn S , Sheldon WR , Winikoff B
Published: May 2006

Objective  To compare the efficacy, adverse effects and acceptability of the three most common misoprostol regimens used with mifepristone for medical abortion.

Design  Randomised nonblinded trial.

Setting  Three clinics associated with major research universities in Canada; two in major urban areas and one in a periurban area.

Population  Women of reproductive age.

Methods  Consenting women presenting for abortion services with gestations less than 56 days and who met inclusion criteria were given 200 mg mifepristone orally and then randomised into three misoprostol study groups: (group I) 400 micrograms of oral misoprostol, (group II) 600 micrograms of oral misoprostol, and (group III) 800 micrograms of vaginal misoprostol. Misoprostol was self‐administered at home 24–48 hours following mifepristone, and participants were instructed to take a second similar misoprostol dose at 24 hours after the initial dose if bleeding was less than a normal menstrual period.

Main outcome measures  Successful abortion without surgery was 94.1%, with no significant differences across the three study groups (94.7% in group I, 93.4% in group II, and 94.3% in group III; P= 0.975).

Results  Efficacy and adverse effects did not differ significantly across the three study groups. Pain increased significantly across the study and the gestational age groups and was associated with lower acceptability.

Conclusions  There appears to be a range of safe and effective options for early medical abortion with mifepristone including a choice between oral and vaginal administration of misoprostol.
Antenatal fear of childbirth and its association with subsequent caesarean section and experience of childbirth
Authors: Waldenström U , Hildingsson I , Ryding EL
Published: May 2006

Objective  To investigate the prevalence of fear of childbirth in a nationwide sample and its association with subsequent rates of caesarean section and overall experience of childbirth.

Design  A prospective study using between‐group comparisons.

Setting  About 600 antenatal clinics in Sweden.

Sample  A total of 2662 women recruited at their first visit to an antenatal clinic during three predetermined weeks spread over 1 year.

Methods  Postal questionnaires at 16 weeks of gestation (mean) and 2 months postpartum. Women with fear of childbirth, defined as ‘very negative’ feelings when thinking about the delivery in second trimester and/or having undergone counselling because of fear of childbirth later in pregnancy, were compared with those in the reference group without these characteristics.

Main outcome measures  Elective and emergency caesarean section and overall childbirth experience.

Results  In total 97 women (3.6%) had very negative feelings and about half of them subsequently underwent counselling. In addition, 193 women (7.2%) who initially had more positive feelings underwent counselling later in pregnancy. In women who underwent counselling, fear of childbirth was associated with a three to six times higher rate of elective caesarean sections but not with higher rates of emergency caesarean section or negative childbirth experience. Very negative feelings without counselling were not associated with an increased caesarean section rate but were associated with a negative birth experience.

Conclusions  At least 10% of pregnant women in Sweden suffer from fear of childbirth. Fear of childbirth in combination with counselling may increase the rate of elective caesarean sections, whereas fear without treatment may have a negative impact on the subsequent experience of childbirth.
Routine ultrasound examination at 12 or 18 gestational weeks for prenatal detection of major congenital heart malformations? A randomised controlled trial comprising 36 299 fetuses
Authors: Westin M , Saltvedt S , Bergman G , Kublickas M , Almström H , Grunewald C , Valentin L
Published: May 2006

Objective  To compare the rate of prenatal diagnosis of heart malformations between two policies of screening for heart malformations.

Design  Randomised controlled trial.

Setting  Six university hospitals, two district general hospitals.

Sample  A total of 39 572 unselected pregnancies randomised to either policy.

Methods  The 12‐week policy implied one routine scan at 12 weeks including measurement of nuchal translucency (NT), and the 18‐week policy implied one routine scan at 18 weeks. Fetal anatomy was scrutinised using the same check‐list in both groups, and in both groups, indications for fetal echocardiography were ultrasound findings of any fetal anomaly, including abnormal four‐chamber view, or other risk factors for heart malformation. In the 12‐week scan group, NT ≥3.5 mm was also an indication for fetal echocardiography.

Main outcome measure  Prenatal diagnosis of major congenital heart malformation.

Results  In the 12‐week scan group, 7 (11%) of 61 major heart malformations were prenatally diagnosed versus 9 (15%) of 60 in the 18‐week scan group (P= 0.60). In four (6.6%) women in the 12‐week scan group, the routine scan was the starting point for investigations resulting in a prenatal diagnosis versus in 9 (15%) women in the 18‐week scan group (P= 0.15). The diagnosis was made ≤22 weeks in 5% (3/61) of the cases in the 12‐week scan group versus in 15% (9/60) in the 18‐week scan group (P= 0.08).

Conclusions  The prenatal detection rate of major heart malformations was low with both policies. The 18‐week scan policy seemed to be superior to the 12‐week scan policy, although the differences in prenatal detection rates were not statistically significant.
Detection of malformations in chromosomally normal fetuses by routine ultrasound at 12 or 18 weeks of gestation—a randomised controlled trial in 39 572 pregnancies
Authors: Saltvedt S , Almström H , Kublickas M , Valentin L , Grunewald C
Published: May 2006

Objective  To compare the antenatal detection rate of malformations in chromosomally normal fetuses between a strategy of offering one routine ultrasound examination at 12 gestational weeks (gws) and a strategy of offering one routine examination at 18 gws.

Design  Randomised controlled trial.

Setting  Multicentre trial including eight hospitals.

Population  A total of 39 572 unselected pregnant women.

Methods  Women were randomised either to one routine ultrasound scan at 12 (12–14) gws including nuchal translucency (NT) measurement or to one routine scan at 18 (15–22) gws. Anomaly screening was performed in both groups following a check‐list. A repeat scan was offered in the 12‐week scan group if the fetal anatomy could not be adequately seen at 12–14 gws or if NT was ≥3.5 mm in a fetus with normal or unknown chromosomes.

Main outcome measures  Antenatal detection rate of malformed fetuses.

Results  The antenatal detection rate of fetuses with a major malformation was 38% (66/176) in the 12‐week scan group and 47% (72/152) in the 18‐week scan group (P= 0.06). The corresponding figures for detection at <22 gws were 30% (53/176) and 40% (61/152) (P= 0.07). In the 12‐week scan group, 69% of fetuses with a lethal anomaly were detected at a scan at 12–14 gws.

Conclusions  None of the two strategies for prenatal diagnosis is clearly superior to the other. The 12‐week strategy has the advantage that most lethal malformations will be detected at <15 gws, enabling earlier pregnancy termination. The 18‐week strategy seems to be associated with a slightly higher detection rate of major malformations, although the difference was not statistically significant.
Tomoregulin‐2 is found extensively in plaques in Alzheimer's disease brain
Authors: Siegel Donald A. , Davies Peter , Dobrenis Kostantin , Huang May
Published: May 2006

Tomoregulin (TR)2 is a transmembrane protein predominantly expressed in brain. It has a unique extracellular domain, containing epidermal growth factor‐like and follistatin‐like modules. The ectodomain is released from the cell surface, and thought to function as a neurotrophic factor and dendritogenic agent. During CNS development and in the neuronal storage disease GM2 gangliosidosis, which is characterized by ectopic dendrites, the TR2 ectodomain is present in neuronal nuclei where it may function in dendrite initiation. Data presented here demonstrate that TR2 is found extensively in Alzheimer's disease (AD) plaques. Confocal microscopy shows that TR2 is present throughout plaques. Interestingly, TR2 is absent from plaques in the presenilin‐1/amyloid precursor protein mouse model of AD. From these data, and what is known about TR2, it is hypothesized that TR2 may participate in amyloid plaque formation and contribute to the pathogenesis of AD. The human TR2 gene is located on chromosome 2q32.3, near a locus linked to Parkinson's disease. TR2 is reported to be a trophic factor for dopaminergic mesencephalic neurons.
Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stress
Authors: Muqit Miratul M. K. , Abou‐Sleiman Patrick M. , Saurin Adrian T. , Harvey Kirsten , Gandhi Sonia , Deas Emma , Eaton Simon , Payne Smith Martin D. , Venner Kerrie , Matilla Antoni , Healy Daniel G. , Gilks William P. , Lees Andrew J. , Holton Janice , Revesz Tamas , Parker Peter J. , Harvey Robert J. , Wood Nicholas W. , Latchman David S.
Published: May 2006

Following our identification of PTEN‐induced putative kinase 1 (PINK1) gene mutations in PARK6‐linked Parkinson's disease (PD), we have recently reported that PINK1 protein localizes to Lewy bodies (LBs) in PD brains. We have used a cellular model system of LBs, namely induction of aggresomes, to determine how a mitochondrial protein, such as PINK1, can localize to aggregates. Using specific polyclonal antibodies, we firstly demonstrated that human PINK1 was cleaved and localized to mitochondria. We demonstrated that, on proteasome inhibition with MG‐132, PINK1 and other mitochondrial proteins localized to aggresomes. Ultrastructural studies revealed that the mechanism was linked to the recruitment of intact mitochondria to the aggresome. Fractionation studies of lysates showed that PINK1 cleavage was enhanced by proteasomal stress in vitro and correlated with increased expression of the processed PINK1 protein in PD brain. These observations provide valuable insights into the mechanisms of LB formation in PD that should lead to a better understanding of PD pathogenesis.
Biochemical and biological characterization of a neuroendocrine‐associated phosphatase
Authors: Wang Jiz‐Yuh , Lin Chia‐Hua , Yang Chi‐Hwa , Tan Tse‐Hua , Chen Yi‐Rong
Published: May 2006

The biochemical and biological properties of a novel neuroendocrine‐associated phosphatase (NEAP) were characterized. NEAP had a sequence characteristic of a dual‐specificity phosphatase (DSP), and was preferentially expressed in neuroendocrine cells/tissues as well as in skeletal muscle and heart. Expression of NEAP was up‐regulated in nerve growth factor (NGF)‐treated, differentiated PC12 cells. NEAP was cytosolic and did not apparently have effects against extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase activated by various stimuli. Although NEAP and MAPK phosphatase (MPK)‐1 showed similar phosphatase activity towardsp‐nitro phenylphosphate (pNPP), in contrast to MKP‐1, NEAP did not dephosphorylate JNK and p38‐MAPKin vitro. Overexpression of NEAP, but not the C152S mutant, in PC12 cells suppressed NGF‐induced phosphorylation of the p85 subunit of phosphatidylinositol 3‐kinase (PI3K) and Akt activation. Overexpression of NEAP also suppressed neurite outgrowth induced by NGF and sensitized PC12 cells to cisplatin‐induced apoptosis. Suppression of NEAP by RNA interference enhanced NGF‐induced neurite outgrowth and Akt activation. Our results indicated that, unlike other DSPs, down‐regulation of conventional MAPKs was not the major function of NEAP. Furthermore, NEAP might be involved in neuronal differentiation via regulation of the PI3K/Akt signaling.
Tissue Inhibitor of Metalloproteinase‐2 (TIMP‐2) expression is regulated by multiple neural differentiation signals
Authors: Jaworski Diane M. , Pérez‐Martínez Leonor
Published: May 2006

Neuronal differentiation requires exquisitely timed cell cycle arrest for progenitors to acquire an appropriate neuronal cell fate and is achieved by communication between soluble signals, such as growth factors and extracellular matrix molecules. Here we report that the expression of TIMP‐2, a matrix metalloproteinase inhibitor, is up‐regulated by signals that control proliferation (bFGF and EGF) and differentiation (retinoic acid and NGF) in neural progenitor and neuroblastoma cell lines. TIMP‐2 expression coincides with the appearance of neurofilament‐positive neurons, indicating that TIMP‐2 may play a role in neurogenesis. The up‐regulation of TIMP‐2 expression by proliferate signals suggests a role in the transition from proliferation to neuronal differentiation. Live labeling experiments demonstrate TIMP‐2 expression only on α3 integrin‐positive cells. Thus, TIMP‐2 function may be mediated via interaction with integrin receptor(s). We propose that TIMP‐2 represents a component of the neurogenic signaling cascade induced by mitogenic stimuli that may withdraw progenitor cells from the cell cycle permitting their terminal neuronal differentiation.
Increased calcitonin gene‐related peptide in neuroma and invading macrophages is involved in the up‐regulation of interleukin‐6 and thermal hyperalgesia in a rat model of mononeuropathy
Authors: Ma Weiya , Quirion Remi
Published: May 2006

The pain related peptide, calcitonin gene‐related peptide (CGRP), plays an important role in inflammatory pain and immune responses. However, its role in neuropathic pain is not established. Following nerve injury, CGRP and pro‐inflammatory interleukin‐6 (IL‐6) are increased in injured nerves. The aim of this study was to determine if CGRP in injured nerves is involved in the up‐regulation of IL‐6 and in the maintenance of neuropathic pain. Perineural injection of a neutralizing IL‐6 antiserum or CGRP receptor antagonists (CGRP8‐37 and BIBN4096BS) effectively attenuated thermal hyperalgesia 4 weeks after partial sciatic nerve ligation. Perineural CGRP antagonists also dramatically reduced IL‐6 level in injured nerves. CGRP release from injured sites was dramatically increased and CGRP immunoreactivity was localized in both neuroma and invading macrophages. CGRP receptor markers (CRLR and RAMP1) were expressed in invading macrophages. Both CGRP antagonists significantly reduced IL‐6 release from injured nerve explants. In cell cultures derived from injured nerves, CGRP concentration‐dependently increased IL‐6 release, an effect also blocked by CGRP antagonists. Taken together, these data show that increased levels of CGRP in injured neuroma and invading macrophages are involved in the up‐regulation of IL‐6 in macrophages as well as in the maintenance of neuropathic pain.
Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells
Authors: Cao Fang , Hata Ryuji , Zhu Pengxiang , Ma Yong‐Jie , Tanaka Junya , Hanakawa Yasushi , Hashimoto Koji , Niinobe Michio , Yoshikawa Kazuaki , Sakanaka Masahiro
Published: May 2006

To investigate the effects of suppressors of cytokine signaling 3 (SOCS3) on neural stem cell fate, stem cells were infected with an adenoviral vector expressing SOCS3. Three days later, western blot analysis and immunocytochemical analysis revealed that the protein level of MAP2 and the number of MAP2‐positive cells were significantly increased in SOCS3‐transfected cells, whereas the protein level of GFAP and the number of GFAP‐positive cells were significantly decreased. Furthermore, promoter assay revealed a significant reduction in the transcriptional level of signal transducer and activator of transcription 3 (Stat3) in the transfected cells. In addition, the mRNA levels of Notch family member (notch1) and inhibitory basic helix‐loop‐helix (bHLH) factors (hes5 and id3) were significantly up‐regulated 1 day after overexpression of SOCS3. Three days after transfection, the mRNA level of hes5 was significantly decreased, whereas that of notch1 was still up‐regulated. Moreover, all of SOCS3‐positive cells expressed Nestin protein but did not express MAP2 or GFAP proteins. These data indicate that overexpression of SOCS3 induced neurogenesis and inhibited astrogliogenesis in neural stem cells. Our data also show that SOCS3 promoted maintenance of neural stem cells.
Sodium channel β4 subunit: down‐regulation and possible involvement in neuritic degeneration in Huntington's disease transgenic mice
Authors: Oyama Fumitaka , Miyazaki Haruko , Sakamoto Naoaki , Becquet Celine , Machida Yoko , Kaneko Kumi , Uchikawa Chiharu , Suzuki Taishi , Kurosawa Masaru , Ikeda Tetsurou , Tamaoka Akira , Sakurai Takashi , Nukina Nobuyuki
Published: May 2006

Sodium channel β4 is a very recently identified auxiliary subunit of the voltage‐gated sodium channels. To find the primarily affected gene in Huntington's disease (HD) pathogenesis, we profiled HD transgenic mice using a high‐density oligonucleotide array and identified β4 as an expressed sequence tag (EST) that was significantly down‐regulated in the striatum of HD model mice and patients. Reduction in β4 started at a presymptomatic stage in HD mice, whereas other voltage‐gated ion channel subunits were decreased later. In contrast, spinal cord neurons, which generate only negligible levels of expanded polyglutamine aggregates, maintained normal levels of β4 expression even at the symptomatic stage. Overexpression of β4 induced neurite outgrowth in Neuro2a cells, and caused a thickening of dendrites and increased density of dendritic spines in hippocampal primary neurons, indicating that β4 modulates neurite outgrowth activities. These results suggest that down‐regulation of β4 may lead to abnormalities of sodium channel and neurite degeneration in the striatum of HD transgenic mice and patients with HD.
Olfactory receptors and signalling elements in the Grueneberg ganglion
Authors: Fleischer Jörg , Schwarzenbacher Karin , Besser Stefanie , Hass Nicole , Breer Heinz
Published: May 2006

The Grueneberg ganglion (GG) is a cluster of neurones present in the vestibule of the anterior nasal cavity. Although its function is still elusive, recent studies have shown that cells of the GG transcribe the gene encoding the olfactory marker protein (OMP) and project their axons to glomeruli of the olfactory bulb, suggesting that they may have a chemosensory function. Chemosensory responsiveness of olfactory neurones in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO) is based on the expression of either odorant receptors or vomeronasal putative pheromone receptors. To scrutinize its presumptive olfactory nature, the GG was assessed for receptor expression by extensive RT–PCR analyses, leading to the identification of a distinct vomeronasal receptor which was expressed in the majority of OMP‐positive GG neurones. Along with this receptor, these cells expressed the G proteins Go and Gi, both of which are also present in sensory neurones of the vomeronasal organ. Odorant receptors were expressed by very few cells during prenatal and perinatal stages; a similar number of cells expressed adenylyl cyclase type III and Golf/s, characteristic signalling elements of the main olfactory system. The findings of the study support the notion that the GG is in fact a subunit of the complex olfactory system, comprising cells with either a VNO‐like or a MOE‐like phenotype. Moreover, expression of a vomeronasal receptor indicates that the GG might serve to detect pheromones.
Increase of proliferating oligodendroglial progenitors in the adult mouse brain upon Sonic hedgehog delivery in the lateral ventricle
Authors: Loulier Karine , Ruat Martial , Traiffort Elisabeth
Published: May 2006

Sonic hedgehog signaling is required for the maintenance of stem cell niches in the postnatal subventricular zone and the proliferation of neural progenitors in the mature hippocampus. We show here that delivery of Sonic hedgehog protein into the lateral ventricle of adult mice increases cell proliferation in the corpus callosum and cerebral cortex. In this latter area, the number of neural progenitors expressing the proteoglycan NG2 is enhanced 2 days after the injection. In both areas, mRNA up‐regulation of the transcriptional target gene Patched was observed in cells expressing the oligodendroglial transcription factor Olig1. Twenty‐six days following the adenovirus‐mediated delivery of Sonic hedgehog into the lateral ventricle, newly generated cells in the cerebral cortex and in the corpus callosum are influenced towards the initial steps of oligodendrogenesis, as indicated by a 50% increase in the number of cells expressing the oligodendroglial marker DM20. Our experiments demonstrate that the number of oligodendrocyte precursor cells in the cerebral cortex and corpus callosum can be increased upon delivery of Sonic hedgehog proteins and highlight the potential capacity of the adult brain to mobilize a pool of premyelinating cells.
Balance of purines may determine life or death of retinal ganglion cells as A3 adenosine receptors prevent loss following P2X7 receptor stimulation
Authors: Zhang Xiulan , Zhang Mei , Laties Alan M. , Mitchell Claire H.
Published: May 2006

The purines ATP and adenosine can act as a coordinated team of transmitters. As extracellular adenosine is frequently derived from the enzymatic dephosphorylation of released ATP, the distinct actions of the two purines can be synchronized. In retinal ganglion cells (RGCs), stimulation of the P2X7 receptor for ATP leads to increased intracellular Ca2+ and death. Here we define the contrasting effects of adenosine and identify protective actions mediated by the A3 receptor. Adenosine attenuated the rise in Ca2+ produced by the P2X7 agonist 3′‐O‐(4‐benzoylbenzoyl)ATP (BzATP). Adenosine was also neuroprotective, increasing the survival of ganglion cells exposed to BzATP. The A3 adenosine receptor agonist 2‐chloro‐N6‐(3‐iodobenzyl)‐adenosine‐5′‐N‐methyluronimide (Cl‐IB‐MECA) mimicked the inhibition of the Ca2+ rise, whereas the A3 antagonist 3‐Ethyl‐5‐benzyl‐2‐methyl‐4‐phenylethynyl‐6‐phenyl‐1,4‐(±)‐dihydropyridine‐3,5‐dicarboxylate (MRS‐1191) reduced the protective effects of adenosine. Both Cl‐IB‐MECA and a second A3 receptor agonist IB‐MECA reduced the cell loss triggered by BzATP. The actions of BzATP were mimicked by ATPγS, but not by ATP. In summary, adenosine can stop the rise in Ca2+ and cell death resulting from stimulation of the P2X7 receptor on RGCs, with the A3 adenosine receptor contributing to this protection. Hydrolysis of ATP into adenosine and perhaps inosine shifts the balance of purinergic action from that of death to the preservation of life.
Phosphorylation of dystrophin Dp71d by Ca2+/calmodulin‐dependent protein kinase II modulates the Dp71d nuclear localization in PC12 cells
Authors: Calderilla‐Barbosa Luis , Ortega Arturo , Cisneros Bulmaro
Published: May 2006

We have shown that the splicing isoform of Dp71 (Dp71d) localizes to the nucleus of PC12 cells, an established cell line derived from a rat pheochromocytoma; however, the mechanisms governing its nuclear localization are unknown. As protein phosphorylation modulates the nuclear import of proteins, and as Dp71d presents several potential sites for phosphorylation, we analyzed whether Dp71d is phosphorylated in PC12 cells and the role of phosphorylation on its nuclear localization. We demonstrated that Dp71d is phosphorylated under basal conditions at serine and threonine residues by endogenous protein kinases. Dp71d phosphorylation was activated by 2‐O‐tetradecanoyl phorbol 13‐acetate (TPA), but this effect was blocked by EGTA. Supporting the role of intracellular calcium on Dp71d phosphorylation, we observed that the stimulation of calcium influx by cell depolarization increased Dp71d phosphorylation, and that the calcium‐calmodulin inhibitor N‐(6‐aminohexyl)‐1‐naphthalenesulfonamide (W‐7) blocked such induction. The blocking action of bisindolylmaleimide I (Bis I), a specific inhibitor for Ca2+/diacylglicerol‐dependent protein kinase (PKC), on Dp71d phosphorylation suggested the participation of PKC in this event. In addition, transfection experiments with Ca2+/calmodulin‐dependent protein kinase II (CaMKII) expression vectors as well as the use of KN‐62, a CaMKII‐specific inhibitor, demonstrated that CaMKII is also involved in Dp71d phosphorylation. Stimulation of Dp71d phosphorylation by cell depolarization and/or the overexpression of CaMKII favored the Dp71d nuclear accumulation. Overall, our results indicate that CAMKII‐mediated Dp71d phosphorylation modulates its nuclear localization.
Mouse brains deficient in neuronal PDGF receptor‐β develop normally but are vulnerable to injury
Authors: Ishii Yoko , Oya Takeshi , Zheng Lianshun , Gao Zhiyang , Kawaguchi Makoto , Sabit Hemragul , Matsushima Takako , Tokunaga Ayano , Ishizawa Shin , Hori Etsuro , Nabeshima Yo‐ichi , Sasaoka Toshikuni , Fujimori Toshihiko , Mori Hisashi , Sasahara Masakiyo
Published: May 2006

Platelet‐derived growth factors (PDGFs) and PDGF receptors (PDGFRs) are widely expressed in the mammalian CNS, though their functional significance remains unclear. The corresponding null‐knockout mutations are lethal. Here, we developed novel mutant mice in which the gene encoding the β subunit of PDGFR (PDGFR‐β) was genetically deleted in CNS neurons to elucidate the role of PDGFR‐β, particularly in the post‐natal stage. Our mutant mice reached adulthood without apparent anatomical defects. In the mutant brain, immunohistochemical analyses showed that PDGFR‐β detected in neurons and in the cells in the subventricular zone of the lateral ventricle in wild‐type mice was depleted, but PDGFR‐β detected in blood vessels remained unaffected. The cerebral damage after cryogenic injury was severely exacerbated in the mutants compared with controls. Furthermore, TdT‐mediated dUTP‐biotin nick end labeling (TUNEL)‐positive neuronal cell death and lesion formation in the cerebral hemisphere were extensively exacerbated in our mutant mice after direct injection of NMDA without altered NMDA receptor expression. Our results clearly demonstrate that PDGFR‐β expressed in neurons protects them from cryogenic injury and NMDA‐induced excitotoxicity.
GATA‐3 regulates the transcriptional activity of tyrosine hydroxylase by interacting with CREB
Authors: Hong Seok Jong , Huh Youngbuhm , Chae Han , Hong Sunghoi , Lardaro Thomas , Kim Kwang‐Soo
Published: May 2006

The zinc finger transcription factor GATA‐3 is a master regulator of type 2 T‐helper cell development. Interestingly, in GATA‐3–/– mice, noradrenaline (NA) deficiency is a proximal cause of embryonic lethality. However, neither the role of GATA‐3 nor its target gene(s) in the nervous system were known. Here, we report that forced expression of GATA‐3 resulted in an increased number of tyrosine hydroxylase (TH) expressing neurons in primary neural crest stem cell (NCSC) culture. We also found that GATA‐3 transactivates the promoter function of TH via specific upstream sequences, a domain of the TH promoter residing at −61 to −39 bp. Surprisingly, this domain does not contain GATA‐3 binding sites but possesses a binding motif, a cAMP response element (CRE), for the transcription factor, CREB. In addition, we found that site‐directed mutation of this CRE almost completely abolished transactivation of the TH promoter by GATA‐3. Furthermore, protein–protein interaction assays showed that GATA‐3 is able to physically interact with CREB in vitro as well as in vivo. Based on these results, we propose that GATA‐3 may regulate TH gene transcription via a novel and distinct protein–protein interaction, and directly contributes to NA phenotype specification.
Ten polymorphic microsatellite loci for the endangered Buena Vista Lake shrew (Sorex ornatus relictus)
Authors: MALDONADO JESÚS E. , LEONARD JENNIFER , MIRANDA GUSTAVO A. , ORTEGA JORGE , WAYNE ROBERT K. , AGUILERA RENATO J.
Published: May 2006

The ornate shrew (Sorex ornatus) is restricted to the vanishing wetlands of California, USA and Baja California, Mexico. Several subspecies of ornate shrews are considered ‘mammal species of special concern’ in California by the Department of Fish and Game, and one (Sorex ornatus relictus) has recently been listed as endangered. Populations of shrews around Buena Vista Lake have been diminished or extirpated due to habitat deterioration and human development. In order to study the patterns of genetic variation in isolated populations of Buena Vista Lake shrews, we developed 10 polymorphic microsatellite loci. There were 6–27 alleles per locus, and the loci had heterozygosity values that ranged from 20 to 80%. In addition, we screened 20 different populations of S. ornatus, eight species within two subfamilies of shrews (Soricinae and Crocidurinae), as well as in a mole (Talpidae, Neurotrichus gibbsii), to determine if these loci could be informative in other species as well.
Characterization of microsatellite DNA markers in a critically endangered species, Mekong giant catfish, Pangasianodon gigas
Authors: NGAMSIRI T. , OHASHI Y. , SUKUMASAVIN N. , NAKAJIMA M. , NA‐NAKORN U. , TANIGUCHI N.
Published: May 2006

Microsatellite DNA markers for a critically endangered Mekong giant catfish (Pangasianodon gigas Roberts and Vidthayanon, 1991) were developed from fin clips collected from captive fish using (GT)15 probe. The number of alleles per locus ranged from two to four. The expected heterozygosities ranged from 0.13 to 0.68. Also, these primers were successfully amplified in four closely related species, Pangasius bocourti, Pangasius conchophilus, Pangasius larnaudii and Pangasius sanitwongsei with the number of alleles per locus ranged from 1 to 13, 1 to 16, 1 to 12 and 1 to 4, respectively. These markers should prove to be very useful for the evaluation of genetic diversity for this species and other related Pangasius species.
Isolation and characterization of polymorphic microsatellites in a Yangtze River fish, brass gudgeon (Coreius heterodon Bleeker)
Authors: LIAO XIAOLIN , ZHU BIN , YU XIAOMU , TAN DEQING , CHANG JIANBO , TONG JINGOU
Published: May 2006

The brass gudgeon (Coreius heterodon) is a fish of economic importance in the Yangtze River. From a (GATA)n‐enriched genomic library, 25 microsatellites were developed by employing the fast isolation by AFLP of sequences containing repeats (FIASCO) protocol. Nine loci exhibited polymorphism with two to 12 alleles (mean 3.9 alleles/locus) in a test population, and observed heterozygosity ranged from 0.1111 to 0.9630 (mean 0.4426). Three of the nine loci showed polymorphism in a congeneric species, the largemouth bronze gudgeon Coreius guichenoti. These loci should provide sufficient level of genetic diversity to evaluate the fine‐scale population structure of C. heterodon.