bluuebunny/crossref_metadata_2025 huggingface dataset:
EBAG9 Adds a New Layer of Control on Large Dense-Core Vesicle Exocytosis via Interaction with Snapin
Authors: Rüder Constantin , Reimer Tatiana , Delgado-Martinez Ignacio , Hermosilla Ricardo , Engelsberg Arne , Nehring Ralf , Dörken Bernd , Rehm Armin
Published: January 2005

Regulated exocytosis is subject to several modulatory steps that include phosphorylation events and transient protein–protein interactions. The estrogen receptor-binding fragment-associated gene9 (EBAG9) gene product was recently identified as a modulator of tumor-associated O-linked glycan expression in nonneuronal cells; however, this molecule is expressed physiologically in essentially all mammalian tissues. Particular interest has developed toward this molecule because in some human tumor entities high expression levels correlated with clinical prognosis. To gain insight into the cellular function of EBAG9, we scored for interaction partners by using the yeast two-hybrid system. Here, we demonstrate that EBAG9 interacts with Snapin, which is likely to be a modulator of Synaptotagmin-associated regulated exocytosis. Strengthening of this interaction inhibited regulated secretion of neuropeptide Y from PC12 cells, whereas evoked neurotransmitter release from hippocampal neurons remained unaltered. Mechanistically, EBAG9 decreased phosphorylation of Snapin; subsequently, association of Snapin with synaptosome-associated protein of 25 kDa (SNAP25) and SNAP23 was diminished. We suggest that the occurrence of SNAP23, Snapin, and EBAG9 also in nonneuronal cells might extend the modulatory role of EBAG9 to a broad range of secretory cells. The conjunction between EBAG9 and Snapin adds an additional layer of control on exocytosis processes; in addition, mechanistic evidence is provided that inhibition of phosphorylation has a regulatory function in exocytosis.
Isolation and Transcription Profiling of Purified Uncultured Human Stromal Stem Cells: Alteration of Gene Expression after In Vitro Cell Culture
Authors: Boquest Andrew C. , Shahdadfar Aboulghassem , Frønsdal Katrine , Sigurjonsson Olafur , Tunheim Siv H. , Collas Philippe , Brinchmann Jan E.
Published: January 2005

Stromal stem cells proliferate in vitro and may be differentiated along several lineages. Freshly isolated, these cells have been too few or insufficiently pure to be thoroughly characterized. Here, we have isolated two populations of CD45-CD34+CD105+ cells from human adipose tissue which could be separated based on expression of CD31. Compared with CD31+ cells, CD31- cells overexpressed transcripts associated with cell cycle quiescence and stemness, and transcripts involved in the biology of cartilage, bone, fat, muscle, and neural tissues. In contrast, CD31+ cells overexpressed transcripts associated with endothelium and the major histocompatibility complex class II complex. Clones of CD31- cells could be expanded in vitro and differentiated into cells with characteristics of bone, fat, and neural-like tissue. On culture, transcripts associated with cell cycle quiescence, stemness, certain cytokines and organ specific genes were down-regulated, whereas transcripts associated with signal transduction, cell adhesion, and cytoskeletal components were up-regulated. CD31+ cells did not proliferate in vitro. CD45-CD34+CD105+CD31- cells from human adipose tissue have stromal stem cell properties which may make them useful for tissue engineering.
Normal, bound and nonbound testosterone levels in normally ageing men: results from the Massachusetts Male Ageing Study
Authors: Mohr Beth A. , Guay Andre T. , O'Donnell Amy B. , McKinlay John B.
Published: January 2005

Objective  There is little consensus on what androgen levels are ‘normal’ for healthy, ageing men. Using data from the Massachusetts Male Ageing Study (MMAS), we estimated age‐specific, normal androgen levels for men aged 40–79 years while accounting for health status and behavioural factors known to influence hormone levels.

Design  Prospective, observational study.

Patients  Community‐based random sample of men aged 40–79 years: n = 1677 men studied at T1 (1987–1989), n = 1031 at T2 (1995–1997) and n = 631 at T3 (2002–2004), for a total of 3339 observations. The average number of years between the T1 and T2 interviews was 8·8 (range 7·1–10·4 years) and 6·4 (range 5·6–7·9 years) between T2 and T3.

Measurements  Serum total testosterone (T) and sex hormone‐binding globulin (SHBG) were measured on nonfasting blood samples collected within 4 h of subject's awakening. Free and bio‐available T were calculated from T and SHBG using the Södergard equation. Trained interviewers administered an in‐home questionnaire of health, medication and lifestyle. Participants were considered apparently healthy if all of the following were met: (i) absence of self‐reported chronic disease (diabetes, heart disease, high blood pressure, cancer, ulcer); (ii) not on prescription medication believed to affect hormone levels; (iii) body mass index (BMI) not exceeding 29 kg/m2; (iv) alcohol consumption less than or equal to six drinks/day; and (v) nonsmoking.

Results  Chronic disease and high BMI significantly decreased whereas smoking tended to increase total, free and bio‐available T concentrations. Apparently healthy men had significantly higher median hormone concentrations at most time points than did not apparently healthy men. Due to the opposite effects of smoking and the other components of the definition, apparently healthy men were compared to nonsmoking, apparently unhealthy men. The former group had significantly higher androgen levels (Wilcoxon rank‐sum P‐values ranged from 0·01 to 0·0001) for all hormones at all interviews. Ninety‐five percent of apparently healthy men in their 40s, 50s, 60s and 70s would be expected to have total T in the range (2·5–97·5th percentile): 8·7–31·7, 7·5–30·4, 6·8–29·8 and 5·4–28·4 nm (251–914, 216–876, 196–859, 156–818 ng/dl), respectively.

Conclusions  Age, health and lifestyle factors impact androgen levels and should be accounted for in calculations of normal reference ranges. We propose the following age‐specific thresholds, below which a man is considered to have an abnormally low total T: 8·7, 7·5, 6·8 and 5·4 nm (251, 216, 196 and 156 ng/dl) for men in their 40s, 50s, 60s and 70s, respectively. These cutoffs correspond to the 2·5th percentile in our data; thus, approximately 2·5% of men aged 40–79 years would have abnormally low T levels based on hormone levels alone.
The effects of five‐year growth hormone replacement therapy on muscle strength in elderly hypopituitary patients
Authors: Götherström Galina , Bengtsson Bengt‐Åke , Sunnerhagen Katharina Stibrant , Johannsson Gudmundur , Svensson Johan
Published: January 2005

Objective  Little is known of the long‐term effects of GH replacement therapy on muscle strength in elderly adults with adult onset GH deficiency (GHD). In this study, the effects of 5 years of GH replacement therapy on muscle function were determined in adults over 60 years of age with adult onset GHD.

Design  A prospective, open‐label, single‐centre study.

Patients  Twenty‐six (12 male and 14 female) consecutive hypopituitary adults with adult onset GHD, mean age 65·0 (range 61–74) years.

Measurements  Upper leg muscle strength was measured using a Kin‐Com dynamometer. Right and left handgrip strength were measured using an electronic grip force instrument.

Results  The mean insulin‐like growth factor‐I (IGF‐I) SD score increased from −1·10 at baseline to 1·21 at end of the study. Body weight was unchanged during the 5‐year study. A sustained increase in lean body mass and a sustained reduction of body fat was observed as measured using dual‐energy X‐ray absorptiometry (DEXA). The GH replacement therapy induced a sustained increase in isometric (60°) knee flexor strength. After statistical correction for age and sex variables using observed/predicted value ratios, a sustained increase was also observed in concentric knee flexor strength at an angular velocity of 60°/s, concentric knee extensor strength at 60°/s and 180°/s, and peak right handgrip strength. At baseline, knee flexor strength was 90–96% of predicted, knee extensor strength was 85–87% of predicted, and hand‐grip strength was 74–80% of predicted values. At study end, knee flexor strength was 98–106% of predicted, knee extensor strength was 90–100% of predicted, and hand‐grip strength was 80–87% of predicted values.

Conclusion  Elderly patients with adult onset GH deficiency had decreased baseline muscle strength also after correction for age and sex. The 5‐year GH replacement therapy normalized knee flexor strength and improved, but did not fully normalize, knee extensor strength and handgrip strength.
Misunderstandings about illness and treatment among patients with type 2 diabetes
Authors: Holmström Inger M. , Rosenqvist Urban
Published: January 2005

Aims.  This paper reports a study whose aim was to describe the misunderstandings that Swedish patients with type 2 diabetes have about their illness and treatment.

Background.  It is well known that patients with type 2 diabetes need extensive support and education to learn to manage and live with their illness. However, a Swedish survey has shown that only 34% of these patients had good metabolic control. Despite intensive education and support, misunderstandings about both the illness and treatment seem to be common. Furthermore, patients are currently complaining that health care services sometimes obstruct rather than support self‐care and learning.

Methods.  We videotaped 18 authentic encounters between a patient with diabetes and a physician, or a diabetes nurse. Patients then viewed the video and reflected on what took place during the consultation. Video‐recordings and transcribed reflections were analysed thematically.

Results.  Five themes emerged from the analysis: (a) Type 2 diabetes is not ‘real diabetes’; (b) Complications – horror visions or suppression; (c) Self‐monitoring of blood glucose and medication is a routine, not a learning tool; (d) Diet – the important thing is to reduce fat and (e) ‘Physical exercise is good, they tell us’. Four of the 18 patients showed no misunderstandings. Misunderstandings of diabetes and its treatment were thus common and numerous, despite regular checkups and good access to care. The patients adhered to prescribed regimens but did not know why they performed many routines or how they could benefit from them.

Conclusion.  The results show that misunderstandings of illness and treatment were common. We suggest that diabetes educators should base their education on this variation of understanding, using a phenomenological approach to learning. Reflecting on this kind of varied experiences can be a powerful tool to help people to move from ‘novice to expert’ and apply basic routines to new situations.
Health visiting and refugee families: issues in professional practice
Authors: Drennan Vari M. , Joseph Judy
Published: January 2005

Aim.  This paper reports on the perceptions of experienced health visitors working with refugee families in Inner London.

Background.  Women who are refugees and asylum seekers in the United Kingdom are more likely to experience depression than either non‐refugee women or male asylum seekers. Health visitors provide a universal public health service to all women on the birth of a child, or with children aged under five, and as such are well placed to identify emotional and mental health problems of women who are refugees. Despite successive waves of refugees to the United Kingdom in the 20th century, there are no empirical studies of health visiting practice with this vulnerable group. There is also no body of evidence to inform the practice of health visitors new to working with asylum seekers and refugees.

Methods.  An exploratory study was undertaken in Inner London in 2001. Semi‐structured interviews were conducted with a purposive sample of 13 health visitors experienced in working with women and families who are refugees.

Findings.  A range of structural challenges was identified that mediated against the development of a health‐promoting relationship between health visitors and refugee women. With refugee families, who were living in temporary accommodation, health visitors were prioritizing basic needs that had to be addressed: in addition, they prioritized the needs of children before those of women. Health visitors were aware of the emotional needs of women and had strategies for addressing these with women in more settled circumstances. Health visitors considered themselves ill‐prepared to deal with the complexities of working with women in these situations.

Conclusions.  This study identifies issues for further exploration, not least from the perspective of refugee women receiving health visiting services. Health visitors in countries receiving refugee women are framing their work with these women in ways that reflect Maslow's theory of a hierarchy of needs. This study suggests ways that public health nursing practice could be improved, and identifies issues for further study.
Worker reproduction in the antFormica fusca
Authors: Helanterä H. , Sundström L.
Published: January 2005

We studied the kin conflict over male parentage in the antFormica fusca. The conflict arises because each worker and queen is most related to her own sons and is thus predicted to lay eggs. Microsatellite analysis of eggs revealed that workers laid eggs in more than half the queenright experimental nests. Nevertheless, almost exclusively diploid offspring were reared in the presence of a queen. This also occurred when worker‐laid haploid male eggs were experimentally introduced in to the nests. Because our experimental setup allowed us to exclude the possibility of queen policing, we conclude that worker laid eggs are removed by other workers, either as a response to their parentage or gender. Our results suggest that worker reproduction inF. fuscais ultimately an interplay of conflicts over male parentage and sex allocation and that both worker and self policing have roles as proximate mechanisms of resolution.
Potential fitness benefits from mate selection in the Atlantic cod (Gadus morhua)
Authors: Rudolfsen G. , Figenschou L. , Folstad I. , Nordeide J. T. , Søreng E.
Published: January 2005

Little evidence of benefits from female mate choice has been found when males provide no parental care or resources. Yet, good genes models of sexual selection suggest that elaborated male sexual characters are reliable signals of mate quality and that the offspring of males with elaborate sexual ornaments will perform better than those of males with less elaborate ornaments. We used cod (Gadus morhua L.), an externally fertilizing species where males provide nothing but sperm, to examine the potential of optimal mate selection with respect to offspring survival. By applying in vitro fertilizations, we crossed eight females with nine males in all possible combinations and reared each of the 72 sib groups. We found that offspring survival was dependent on which female was mated with which male and that optimal mate selection has the potential to increase mean offspring survival from 31.9 to 55.6% (a 74% increase). However, the size of the male sexual ornaments and sperm quality (i.e. sperm velocity and sperm density) could not predict offspring survival. Thus, even if there may be large fitness benefits of mate selection, we might not yet have identified the male characteristics generating high offspring survival.
Estimation of effective population size and detection of a recent population decline coinciding with habitat fragmentation in a ground beetle
Authors: Keller I. , Excoffier L. , Largiadèr C. R.
Published: January 2005

We assess the impact of habitat fragmentation on the effective size (Ne) of local populations of the flightless ground beetleCarabus violaceusin a small (<25 ha) and a large (>80 ha) forest fragment separated by a highway.Newas estimated based on the temporal variation of allele frequencies at 13 microsatellite loci using two different methods. In the smaller fragment,Neestimates ranged between 59 and a few hundred, whereas values between 190 and positive infinity were estimated for the larger fragment. In both samples, we detected a signal of population decline, which was stronger in the small fragment. The estimated time of onset of thisNereduction was consistent with the hypothesis that recent road constructions have divided a continuous population into several isolated subpopulations. In the small fragment,Neof the local population may be so small that its long‐term persistence is endangered.
The evolution of repeated mating under sexual conflict
Authors: Härdling R. , Kaitala A.
Published: January 2005

In insects, repeated mating by females may have direct effects on female fecundity, fertility, and longevity. In addition, a female's remating rate affects her fitness through mortality costs of male harassment and ecological risks of mating such as predation. We analyse a model where these female fitness factors are put into their life‐history context, and traded against each other, while accounting for limitations because of mate availability. We solve analytically for the condition when female multiple mating will evolve. We show that the probability that a female mates with a courting male decreases with increases in population density. The extent of conflict between the sexes thus automatically becomes larger at higher densities. However, because at higher densities females meet males at a higher rate, the resulting ESS female remating rate is independent of population density. The female remating probability is in conflict with male adaptations that increase male mating rate by persuading or forcing females to mate, and also in conflict with male adaptations for protecting the own sperm from being removed by future female mates. We show that the relative importance of these conflicts depends on population density.
Co‐evolution of male and female reproductive characters across the Scathophagidae (Diptera)
Authors: Minder A. M. , Hosken D. J. , Ward P. I.
Published: January 2005

Sperm morphometry is extremely variable across species, but a general adaptive explanation for this diversity is lacking. As sperm must function within the female, variation in sperm form may be associated with variation in female reproductive tract morphology. We investigated this and other potential evolutionary associations between male and female reproductive characters across the Scathophagidae. Sperm length was positively associated with the length of the spermathecal (sperm store) ducts, indicating correlated evolution between the two. No association was found between sperm length and spermathecal size. However, the size of the spermathecae was positively associated with testis size indicating co‐evolution between male investment in sperm production and female sperm storage capacity. Furthermore, species with a higher degree of polyandry (larger testes) had longer spermathecal ducts. However, no associations between sperm length or length variation and testis size were found which suggests greater sperm competitionsensu strictodoes not select for longer sperm.
Mutation and the experimental evolution of outcrossing in Caenorhabditis elegans
Authors: Cutter A. D.
Published: January 2005

An understanding of the forces that contribute to the phylogenetically widespread phenomenon of sexual reproduction has posed a longstanding problem in evolutionary biology. Mutational theories contend that sex can be maintained when the deleterious mutation rate is sufficiently high, although empirical evidence is equivocal and experimental studies are rare. To test the influence of mutation on the evolution of obligate outcrossing, I introduced a genetic polymorphism for breeding system into populations of the nematode Caenorhabditis elegans with high‐ and low‐mutation rate genetic backgrounds and tracked the change in frequency of females, hermaphrodites, and males over approximately 21 generations. Hermaphrodites invaded all populations, regardless of mutational background. However, experimental populations with elevated mutation rates experienced more outcrossing and greater retention of females. This provides experimental evidence consistent with deleterious mutational explanations for the evolution of sex in principle, but the action of other processes is required to explain the evolution of sex in entirety.
Genetic and environmental effects on secondary sex traits in guppies (Poecilia reticulata)
Authors: Hughes K. A. , Rodd F. H. , Reznick D. N.
Published: January 2005

Male guppies (Poecilia reticulata) exhibit extreme phenotypic and genetic variability for several traits that are important to male fitness, and several lines of evidence suggest that resource level affects phenotypic expression of these traits in nature. We tested the hypothesis that genetic variation for male secondary sex traits could be maintained by genotype‐specific effects of variable resource levels (genotype–environment interaction). To do this, we measured genetic variation and covariation under two environmental conditions – relatively low and relatively high food availability. We found high levels of genetic variation for most traits, but we only found a significant G × E interaction across food levels for one trait (body size) for one population. The across‐environment correlations for size were large and positive, indicating that the reaction norms for size did not cross. We also found that male colour pattern elements had nearly an order of magnitude more genetic variation than did male size. Heritability estimates indicated that Y‐linked genes are responsible for some of the genetic variation in male size and colour traits. We discuss implications of these results for theories of the maintenance of genetic variation in male secondary sexual traits in guppies.
Mechanisms of constraints: the contributions of selection and genetic variance to the maintenance of cotyledon number in wild radish
Authors: Conner J. K. , Agrawal A. A.
Published: January 2005

The evolutionary mechanisms underlying the maintenance of invariant traits are poorly understood, partly because the lack of variance makes these mechanisms difficult to study. Although the number of cotyledons that plant species produce is highly canalized, populations of plants frequently contain individuals with abnormal cotyledon numbers. In a garden study with 1857 wild radish plants from 75 paternal half‐sibling families, 89 (almost 5%) had cotyledon numbers less or greater than two. We found evidence for direct selection on cotyledon number, but no evidence for additive genetic variation for cotyledon number. In spite of the very large sample size, our power to detect variation and selection was hampered by the small number of individuals (10) producing more than two cotyledons. Thus, our results provide support for both a lack of genetic variation and selection as reasons for the current lack of variation in wild radish cotyledon number.
Evidence for bilateral control of skilled movements: ipsilateral skilled forelimb reaching deficits and functional recovery in rats follow motor cortex and lateral frontal cortex lesions
Authors: Gonzalez Claudia L. R. , Gharbawie Omar A. , Williams Preston T. , Kleim Jeffrey A. , Kolb Bryan , Whishaw Ian Q.
Published: January 2005

Unilateral damage to cortical areas in the frontal cortex produces sensorimotor deficits on the side contralateral to the lesion. Although there are anecdotal reports of bilateral deficits after stroke in humans and in experimental animals, little is known of the effects of unilateral lesions on the same side of the body. The objective of the present study was to make a systematic examination of the motor skills of the ipsilateral forelimb after frontal cortex lesions to either the motor cortex by devascularization of the surface blood vessels (pial stroke), or to the lateral cortex by electrocoagulation of the distal branches of the middle cerebral artery (MCA stroke). Plastic processes in the intact hemisphere were documented using Golgi–Cox dendritic analysis and by intracortical microstimulation analysis. Although tests of reflexive responses in forelimb placing identified a contralateral motor impairment following both cortical lesions, quantitative and qualitative measures of skilled reaching identified a severe ipsilateral impairment from which recovery was substantial but incomplete. Golgi‐impregnated pyramidal cells in the forelimb area showed an increase in dendritic length and branching. Electrophysiological mapping showed normal size forelimb representations in the lesioned rats relative to control animals. The finding of an enduring ipsilateral impairment in skilled movement is consistent with a large but more anecdotal literature in rats, nonhuman primates and humans, and suggests that plastic changes in the intact hemisphere are related to that hemisphere's contribution to skilled movement.
Differential effects of prolonged high frequency stimulation and of excitotoxic lesion of the subthalamic nucleus on dopamine denervation‐induced cellular defects in the rat striatum and globus pallidus
Authors: Bacci Jean‐Jacques , Absi El Hadi , Manrique Christine , Baunez Christelle , Salin Pascal , Kerkerian‐Le Goff Lydia
Published: January 2005

This study examined the effects of prolonged (4 days) high frequency stimulation (HFS) of the subthalamic nucleus (STN), in comparison with those of STN lesion, on the dopamine denervation‐mediated cellular changes in the basal ganglia in a Wistar rat model of Parkinson's disease. STN HFS counteracted the dopamine lesion‐induced increase in GAD67 mRNA expression in the output structures of the basal ganglia, as shown previously after STN lesion, providing cellular support for the similar antiparkinsonian benefits produced by the two surgical procedures. The dopamine denervation‐induced increase in GAD67 mRNA levels in the globus pallidus was partially antagonized after HFS and totally reversed after ibotenate‐induced STN lesion. The overexpression of striatal enkephalin mRNA tended to be further increased by HFS but was antagonized by STN lesion. The decrease in striatal substance P mRNA levels was affected neither by STN HFS nor lesion. As STN HFS for two hours was previously found not to interfere with the effects of dopamine lesion in the globus pallidus and striatum, the present data provide strong evidence that the effects of STN surgery in these structures involve long‐term adaptive processes and that the rearrangements mediated by HFS and lesion are, at least in part, different.
Functional dissociation between serotonergic pathways in dorsal and ventral hippocampus in psychotomimetic drug‐induced locomotor hyperactivity and prepulse inhibition in rats
Authors: Kusljic Snezana , Van Den Buuse Maarten
Published: January 2005

Altered hippocampal function and brain serotonin activity are implicated in the development and symptoms of schizophrenia. We have previously shown that lesions of the median raphe nucleus, but not the dorsal raphe nucleus, produced a marked enhancement of locomotor hyperactivity induced by phencyclidine and disruption of prepulse inhibition. The dorsal and ventral hippocampus receive serotonin projections predominantly from the median raphe nucleus and dorsal raphe nucleus, respectively. Therefore, we investigated the effect of local lesions of serotonin projections into the dorsal and ventral hippocampus on psychotomimetic drug‐induced locomotor hyperactivity and prepulse inhibition. Male Sprague–Dawley rats were anaesthetized with pentobarbitone and stereotaxically microinjected with 5 µg of the serotonergic neurotoxin 5,7‐dihydroxytryptamine into either the dorsal or the ventral hippocampus. Two weeks after surgery, dorsal hippocampus‐lesioned rats showed a 100% enhancement of the locomotor hyperactivity caused by phencyclidine treatment and a slight but significant reduction of the effect of amphetamine. Prepulse inhibition was significantly disrupted in lesioned rats and serotonin levels in the dorsal hippocampus were reduced by 80%. Rats with lesions of the ventral hippocampus showed 85% depletion of serotonin and partial disruption of prepulse inhibition, but no significant changes in the effect of phencyclidine or amphetamine. These results suggest that serotonin projections from the median raphe nucleus to the dorsal hippocampus play an important role in locomotor hyperactivity and prepulse inhibition in rats, animal models of aspects of schizophrenia. This suggests that these serotonin projections may be involved in the pathophysiology of schizophrenia symptomology.
Presynaptic localization of an AMPA‐type glutamate receptor in corticostriatal and thalamostriatal axon terminals
Authors: Fujiyama Fumino , Kuramoto Eriko , Okamoto Keiko , Hioki Hiroyuki , Furuta Takahiro , Zhou Ligang , Nomura Sakashi , Kaneko Takeshi
Published: January 2005

The neostriatum is known to receive glutamatergic projections from the cerebral cortex and thalamic nuclei. Vesicular glutamate transporters 1 and 2 (VGluT1 and VGluT2) are located on axon terminals of corticostriatal and thalamostriatal afferents, respectively, whereas VGluT3 is found in axon terminals of cholinergic interneurons in the neostriatum. In the present study, the postsynaptic localization of ionotropic glutamate receptors was examined in rat neostriatum by the postembedding immunogold method for double labelling of VGluT and glutamate receptors. Immunoreactive gold particles for AMPA receptor subunits GluR1 and GluR2/3 were frequently found not only on postsynaptic but also on presynaptic profiles immunopositive for VGluT1 and VGluT2 in the neostriatum, and GluR4‐immunoreactive particles were observed on postsynaptic and presynaptic profiles positive for VGluT1. Quantitative analysis revealed that 27–45% of GluR1‐, GluR2‐, GluR2/3‐ and GluR4‐immunopositive particles found in VGluT1‐ or VGluT2‐positive synaptic structures in the neostriatum were associated with the presynaptic profiles of VGluT‐positive axons. In contrast, VGluT‐positive presynaptic profiles in the neostriatum showed almost no immunoreactivity for NMDA receptor subunits NR1 or NR2A/B. Furthermore, almost no GluR2/3‐immunopositive particles were observed in presynaptic profiles of VGluT3‐positive (cholinergic) terminals that made asymmetric synapses in the neostriatum, or in those of VGluT1‐ or VGluT2‐positive terminals in the neocortex. The present results indicate that AMPA receptor subunits but not NMDA receptor subunits are located on axon terminals of corticostriatal and thalamostriatal afferents, and suggest that glutamate released from these axon terminals controls the activity of the terminals through the presynaptic AMPA autoreceptors.
Transient expression of secretin in serotoninergic neurons of mouse brain during development
Authors: Lossi Laura , Bottarelli Lorena , Candusso Maria Elena , Leiter Andrew B. , Rindi Guido , Merighi Adalberto
Published: January 2005

Existence of the gastro‐intestinal peptide secretin in the CNS has been a matter of debate, and contrasting results have been reported, altogether indicating that the CNS is not a major site of production of this peptide. A thorough analysis was conducted in brain of transgenic mice in which the expression of the early region of simian virus 40 large T antigen (Tag) is under control of the rat secretin gene promoter. We studied Tag expression in the brains of E14–P90 transgenic mice as well as secretin mRNA and protein expression in transgenic and control CD1 mice at corresponding developmental stages. We show here a perfect correspondence of Tag and secretin mRNA expression in the mesencephalon of transgenic and normal mice between E14 and birth. In embryos, Tag is also expressed in the spinal cord, as well as in several areas of the peripheral nervous system. Localization of Tag in P0–P90 animals becomes restricted to a single compact cellular mass in mesencephalon at the level of the dorsal raphe, raphe magnus and lateral paragigantocellular nuclei. Neurons of these nuclei display secretin mRNA from E14 to birth, in both control CD1 and transgenic mice. Approximately half of these secretin‐expressing neurons are immunoreactive for serotonin (5HT) and/or tryptophan hydroxylase. These results demonstrate that the secretin gene is transiently expressed in mouse serotoninergic mesencephalic neurons during development. In addition our data suggest a trophic role for secretin on neurons known to be involved in multiple superior functions in the normal brain, and lost in neurodegenerative disorders.
Elevation of the level and activity of acid ceramidase in Alzheimer's disease brain
Authors: Huang Yu , Tanimukai Hitoshi , Liu Fei , Iqbal Khalid , Grundke‐Iqbal Inge , Gong Cheng‐Xin
Published: January 2005

Protein glycosylation modifies the processing of several key proteins involved in the molecular pathogenesis of Alzheimer's disease (AD). Aberrant glycosylation of tau and down‐regulation of sialyltransferase in AD brain suggest a possible dysregulation of protein glycosylation that may play a role in AD. We therefore isolated major glycoproteins from AD brain by using lectin‐affinity chromatographies and ion‐exchange chromatography and further separated them using SDS‐polyacylamide gel electrophoresis. Mass spectrometry analysis of 11 isolated glycoproteins led to their identification as: neuronal cell adhesion molecule, β‐globin, IgM heavy chain VH1 region precursor, contactin precursor, dipeptidylpeptidase VI, CD81 partner 3, prenylcysteine lyase, adipocyte plasma‐associated protein, acid ceramidase and two novel proteins. We found that the level and activity of acid ceramidase (AC), one of the major identified human brain glycoproteins, were significantly elevated in AD brain. Immunohistochemical staining indicated that AC was located mainly in the cell bodies of neurons and colocalized with neurofibrillary tangles. Our findings suggest that AC might play a role in controlling neuronal apoptosis and that AC‐mediated signalling pathways might be involved in the molecular mechanism of AD.
Robust and powerful serial correlation tests with new robust estimates in ARX models
Authors: Duchesne Pierre
Published: January 2005

Abstract.  We consider robust serial correlation tests in autoregressive models with exogenous variables (ARX). Since the least squares estimators are not robust when outliers are present, a new family of estimators is introduced, called residual autocovariances for ARX (RA‐ARX). They provide resistant estimators that are less sensible to abnormal observations in the output variable of the dynamic model. Such ‘bad’ observations could be due to unexpected phenomena such as economic crisis or equipment failure in engineering, among others. We show that the new robust estimators are consistent and we can consider robust and powerful tests of serial correlation in ARX models based on these estimators. The new one‐sided tests of serial correlation are obtained in extending Hong's (1996) approach in a framework resistant to outliers. They are based on a weighted sum of robust squared residual autocorrelations and on any robust and n1/2‐consistent estimators. Our approach generalizes Li's (1988) test statistic, that can be interpreted as a test using the truncated uniform kernel. However, many kernels deliver a higher power. This is confirmed in a simulation study, where we investigate the finite sample properties of the new robust serial correlation tests in comparison to some commonly used robust and non‐robust tests.
Outlier Detection And Estimation In NonLinear Time Series
Authors: Battaglia Francesco , Orfei Lia
Published: January 2005

Abstract. The problem of identifying the time location and estimating the amplitude of outliers in nonlinear time series is addressed. A model‐based method is proposed for detecting the presence of additive or innovational outliers when the series is generated by a general nonlinear model. We use this method for identifying and estimating outliers in bilinear, self‐exciting threshold autoregressive and exponential autoregressive models. A simulation study is performed to test the proposed procedures and comparing them with the methods based on linear models and linear interpolators. Finally, our results are applied for detecting outliers in the Canadian lynx trappings and in the sunspot numbers data.
A case–control study to investigate an association between adverse pregnancy outcome and periodontal disease
Authors: Moore S. , Randhawa M. , Ide M.
Published: January 2005

Objectives: The aim of this case–control study was to ascertain if women who experienced a preterm (or premature) birth had any differences in periodontal disease severity compared with women who delivered at term.

Material and Methods: Subjects were recruited postpartum. Case subjects delivered a baby before 37 weeks of gestation whereas control subjects gave birth at or around term. A questionnaire was administered by a Research Midwife, designed to collect demographic information, pregnancy outcome variables and information on other factors which may influence health in pregnancy. A periodontal examination was then performed at the bedside.

Results: Demographic variables were similar between case and control subjects. There was a higher proportion of case subjects who reported smoking. There were no differences in oral hygiene, bleeding on probing or loss of attachment; however, control subjects had a higher proportion of periodontal pockets probing 5 mm or greater.

Conclusions: There was no association between the severity of periodontal disease and pregnancy outcome in this population.
Expression of the receptor of advanced glycation end products in gingival tissues of type 2 diabetes patients with chronic periodontal disease: a study utilizing immunohistochemistry and RT‐PCR
Authors: Katz J. , Bhattacharyya I. , Farkhondeh‐Kish F. , Perez F. M. , Caudle R. M. , Heft M. W.
Published: January 2005

Objectives: Relationship between diabetes and periodontal disease is well established. It has been shown that advanced glycation end‐products (AGEs) might exert noxious effects on gingival tissues through its receptor. Evidence for the role of receptors of AGE (RAGE) in periodontal disease was verified in a murine model for diabetes. However, the presence of RAGE in human gingival tissues has not been demonstrated previously. In this study we demonstrate the presence of RAGE in human periodontium in patients with chronic periodontitis with and without type 2 diabetes.

Material and Methods: Gingival biopsies from eight patients with both type 2 diabetes and chronic periodontitis and 14 healthy control subjects with chronic periodontitis were immunohistochemically stained for RAGE. Five samples from the study groups and four controls were subjected to reverse transcriptase coupled to polymerase chain reaction (RT‐PCR) for quantitative determination of mRNA for RAGE.

Results: On immunohistochemistry, positive staining for RAGE was seen in the endothelium and the basal and spinous layer of the inflamed gingival epithelium in both type 2 diabetes and non‐diabetes tissue with no statistically significant difference between both groups. RT‐PCR, however, showed a 50% increase in mRNA for RAGE in the gingiva of diabetic patients when compared with controls (p<0.05).

Conclusions: Although there was no change in the staining intensity for RAGE between both groups, the increase in the mRNA for RAGE in the type 2 diabetes gingival epithelium may indicate a possible involvement of this receptor in the periodontal destruction in type 2 diabetes.
Filament end‐rounding quality in electric toothbrushes
Authors: Meyer‐Lueckel H. , Rieben A. S. , Kielbassa A. M.
Published: January 2005

Objectives: A good quality of filament tips is desirable to protect both gingiva and dental hard tissues. The aim of the present study was to compare the end‐rounding quality of the filaments in 15 electric toothbrushes (Rowenta dentaclip® ZH‐07, dentaclip® ZH 010, rotaclip® ZH‐11; Blend‐a‐dent Wellenprofil 2000 hart, Wellenprofil 2000 mittel‐weich, Medic for kids; Broxo®; UltraSonex™; Krups 548, Waterpik® BH‐4U; Butler Gum®; Dr. Best e‐Flex3; Oral‐B® (EB3, EB 17‐8, Plak Control Kids)).

Material and Methods: From each brand five brushes were chosen randomly. Five tufts were selected from each brush and studied with a scanning electron microscope (× 45) at a viewing angle of 45°. The filament tips were numbered from top left to bottom right and selected filaments were judged by a well‐trained, blinded second examiner according to the Silverstone & Featherstone method.

Results: Nine of the 15 brands examined showed a high (“acceptable”: >89%), four products a medium (76–84%) and two a bad (34–38%) end‐rounding quality.

Conclusion: A good quality of filament tips is claimed by the dental profession to protect both gingiva and dental hard tissues from abrasion. This could be observed for 13 of the 15 brands examined.
Three different rinsing times and inhibition of plaque accumulation with chlorhexidine
Authors: Van der Weijden G. A. , Timmerman M. F. , Novotny A. G. A. , Rosema N. A. M. , Verkerk A. A. J.
Published: January 2005

Aim: This study assessed the plaque inhibiting effect of a 0.2% chlorhexidine (CHX) solution (Corsodyl®) with three different rinsing times following a 72 h non‐brushing period.

Material and Methods: The clinical investigation was a single‐blind, randomised study involving 90 volunteer students (40 male and 50 female, mean age 23.2 years). Subjects were randomly allocated to one of three groups for which the protocol only differed with respect to the duration of rinsing. At the start of the trial, all participants received a dental prophylaxis to remove all plaque deposits. Subjects refrained from all mechanical oral hygiene procedures, but rinsed two times per day for the allocated duration with CHX mouth rinse over a period of 72 h. The chlorhexidine preparation was of 0.2% concentration used at a dose of 10 ml for either 15, 30 or 60 s. After 72 h, the Quigley & Hein plaque index (PI) from all volunteers was recorded at six sites per tooth. All participants received a questionnaire to evaluate their perception of rinsing duration.

Results: After 72 h, the mean whole‐mouth PI was 1.33, 1.18 and 1.24, respectively, for the 15, 30 and 60 s rinsing group. The difference in plaque scores between the three groups was not statistically significant. Results from the questionnaire showed a significant difference between the groups for their perception of rinsing duration.

Conclusions: No significant difference was observed in the level of plaque after 72 h of non‐brushing whether the subjects rinsed for 15, 30 or 60 s with 0.2% chlorhexidine.
Social and biological early life influences on severity of dental caries in children aged 6 years
Authors: Peres Marco Aurélio , Latorre Maria do Rosário Dias de Oliveira , Sheiham Aubrey , Peres Karen Glazer , Barros Fernando C. , Hernandez Pedro Gonzales , Maas Angela Maria Nunes , Romano Ana Regina , Victora Cesar Gomes
Published: January 2005

Abstract – Objective: To investigate the relationship between social and biological conditions experienced in very early life and dental caries in children aged 6 years.

Methods: The design was a dental caries cross‐sectional study nested in a birth cohort study started in Pelotas, Brazil, in 1993. The cross‐sectional study was carried out in 1999. A random sample of 400 6‐year‐old children was selected from among 5249 live births in 1993. The World Health Organization (1997) criteria were used to diagnose dental caries. Results from the oral health study were linked to the data concerning perinatal and childhood health and illnesses and family social conditions collected at birth, 1, 3, 6 and 12 months, and in the sixth year of life. Dental caries was the outcome measured at two levels of severity (very low: dmft ≤ 1; high: dmft ≥ 4). Unconditional univariate and multiple logistic regression analysis were performed.

Results: Self‐employed and employees/unemployed, fathers with <8 years of education at time child was born, child's height deficit for age at 12 months; child who did not attend day care centre in sixth year of life; brushing teeth less than once a day, and children with sweet consumption of at least once a day at 6 years were risk factors for high dental caries after controlling for possible confounders.

Conclusions: Harmful social and biological risk factors accumulated in early life contributed to the development of a high level of dental caries in childhood.
Antidepressant xerogenic medications and restoration rates
Authors: Brad Rindal D. , Rush William A. , Peters Dawn , Maupomé Gerardo
Published: January 2005

Abstract –  Objectives:  This report examines the association between xerogenic antidepressant medication use and dental restorations (a proxy for dental caries).

Methods:  Data for this study was collected from the electronic databases of two large dental group practices associated with two managed care organizations. The population examined was at least 55‐year‐old on the reference date and had at least 48 months of concurrent dental, medical and pharmacy coverage. We identified 915 individuals whose only exposure to a xerogenic medication was to an antidepressant. This group was compared with a group not on any medications and to a group on medications without any known xerostomic side effect.

Results:  Poisson regression was used to compare restoration occurrence and restoration rates among the three groups. The antidepressant medication and the no xerogenic medication groups were more likely to have restorations than the no medication group but there was no difference in restoration rates between the two medication groups. The mean restoration rates were significantly different between the three groups with the antidepressant group having the highest restoration rate. The no xerogenic group also had a higher rate than the no medication group but not as high as the antidepressant group rate.

Conclusions:  This study provides objective quantification of the long‐term effects that anti‐depressant medications have on restoration use.
V-ATPase B1-subunit promoter drives expression of EGFP in intercalated cells of kidney, clear cells of epididymis and airway cells of lung in transgenic mice
Authors: Miller R. Lance , Zhang Ping , Smith Maren , Beaulieu Valerie , Păunescu Teodor G. , Brown Dennis , Breton Sylvie , Nelson Raoul D.
Published: January 2005

The kidney, epididymis, and lungs are complex organs with considerable epithelial cell heterogeneity. This has limited the characterization of pathophysiological transport processes that are specific for each cell type in these epithelia. The purpose of the present study was to develop new tools to study cell-specific gene and protein expression in such complex tissues and organs. We report the production of a transgenic mouse that expresses enhanced green fluorescent protein (EGFP) in a subset of epithelial cells that express the B1 subunit of vacuolar H+-ATPase (V-ATPase) and are actively involved in proton transport. A 6.5-kb portion of the V-ATPase B1 promoter was used to drive expression of EGFP. In two founders, quantitative real-time RT-PCR demonstrated expression of EGFP in kidney, epididymis, and lung. Immunofluorescence labeling using antibodies against the B1 and E subunits of V-ATPase and against carbonic anhydrase type II (CAII) revealed specific EGFP expression in all renal type A and type B intercalated cells, some renal connecting tubule cells, all epididymal narrow and clear cells, and some nonciliated airway epithelial cells. No EGFP expression was detected in collecting duct principal cells (identified using an anti-AQP2 antibody) or epididymal principal cells (negative for V-ATPase or CAII). This EGFP-expressing mouse model should prove useful in future studies of gene and protein expression and their physiological and/or developmental regulation in distinct cell types that can now be separated using fluorescence-assisted microdissection, fluorescence-activated cell sorting, and laser capture microdissection.