EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2003
Jason R. Potas
Abstract Previous research has found that the integrity of a restricted region of the caudal midline medulla (including caudal portions of nucleus raphé obscurus and nucleus raphé pallidus) was critical for vasodepression (hypotension, bradycardia, decreased cardiac contractility) evoked either by haemorrhage or deep pain. In this anatomical tracing study we found that the vasodepressor part of the caudal midline medulla (CMM) receives inputs arising from spinal cord, spinal trigeminal nucleus (SpV) and nucleus of the solitary tract (NTS). Specifically: (i) a spinal,CMM projection arises from neurons of the deep dorsal horn, medial ventral horn and lamina X at all spinal segmental levels, with approximately 60% of the projection originating from the upper cervical spinal cord (C1,C4); (ii) a SpV,CMM projection arises primarily from neurons at the transition between subnucleus caudalis and subnucleus interpolaris; (iii) a NTS,CMM projection arises primarily from neurons in ventrolateral and medial subnuclei. In combination, the specific spinal, SpV and NTS regions which project to the CMM receive the complete range of somatic and visceral afferents known to trigger vasodepression. The role(s) of each specific projection is discussed. [source]

Noxious Somatic Inputs to Hypothalamic-Midbrain Projection Neurones: a Comparison of the Columnar Organisation of Somatic and Visceral Inputs to the Periaqueductal Grey in the Rat

EXPERIMENTAL PHYSIOLOGY, Issue 2 2002
D. M. Parry
The induction of Fos protein was used to localise hypothalamic neurones activated by noxious somatic stimulation. This was combined with retrograde transport of fluorescent latex microspheres from identified ,pressor' and ,depressor' sites in the dorsolateral/lateral or ventrolateral columns of the periaqueductal grey (PAG). Fos-positive neurones were found throughout the rostral hypothalamus. Of those neurones activated by noxious somatic stimuli that projected to the PAG all but one was retrogradely labelled from sites that included the lateral column. Only one neurone was double labelled following injection of tracer at a depressor site in the ventrolateral PAG. This is in marked contrast to visceroresponsive hypothalamic neurones, a larger proportion of which project to the PAG and which, as reported previously, preferentially target depressor sites in the ventrolateral sector. These results are discussed in relation to the roles of the anterior hypothalamus and the different functional columns of the PAG in co-ordinating autonomic and sensory functions in response to nociceptive inputs originating in different peripheral domains. [source]

Germline mutations of the BRCA1-associated ring domain (BARD1) gene in breast and breast/ovarian families negative for BRCA1 and BRCA2 alterations

GENES, CHROMOSOMES AND CANCER, Issue 3 2002
Chiara Ghimenti
BARD1 (BRCA1-associated RING domain) was identified by yeast two-hybrid screening as a protein interacting with BRCA1. Somatic and germline mutations of BARD1 have been detected in sporadic breast, ovarian, and endometrial cancers. The present study represents the first description of BARD1 germline mutations in hereditary breast and breast/ovarian cancer patients. We analyzed the BARD1 gene in 40 families with hereditary breast and breast/ovarian cancer, tested negative for BRCA1 and BRCA2 mutations. A mutational analysis by PCR-SSCP on the coding region and the exon,intron splice boundaries of the BARD1 gene yielded four different germline mutations. A group of 20 patients diagnosed with sporadic breast cancer below the age of 40 was also examined and only one germline mutation was found. A study of loss of heterozygosity at the BARD1 locus in neoplastic tissues from patients with BARD1 germline mutations was carried out. In all cases, we were unable to find any evidence for allelic deletions. The involvement of BARD1 mutations in the susceptibility to hereditary breast and breast/ovarian cancer is discussed. [source]

Depressive symptom patterns in patients with Parkinson's disease and other older adults

JOURNAL OF CLINICAL PSYCHOLOGY, Issue 12 2001
Kristi J. Erdal
Research on depression in Parkinson's disease (PD) has suggested that PD patients experience a qualitatively different depression from that of other older adults, endorsing fewer cognitive symptoms of depression (e.g., guilt, failure) and greater somatic (e.g., poor sleep) and mood symptoms (e.g., sadness, hopelessness); however, this has never been tested directly. In the present study, two PD groups, one with cognitive impairment (PD + CI; n = 26) and one without cognitive impairment (PD; n = 45), and three control groups of older adults were compared on measures of depressive symptomatology. The control groups included a physically disabled group (n = 46), a cognitively impaired group (CI; n = 21), and a healthy group (n = 50). Confirmatory factor analysis verified a four-factor model of depressive symptoms (Cognitive, Mood, Somatic, and Fatigue symptoms). Comparisons revealed that the PD group had a depressive-symptom pattern that was not significantly different from the disabled and healthy groups. The PD + CI group had a symptom pattern that was more similar to the CI group than to the PD group. Implications for the conceptualization of depression in older adults are discussed. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 1559,1569, 2001. [source]

What can humans learn from flies about adenomatous polyposis coli?

BIOESSAYS, Issue 9 2002
Angela I.M. Barth
Somatic or inherited mutations in the adenomatous polyposis coli (APC) gene are a frequent cause of colorectal cancer in humans. APC protein has an important tumor suppression function to reduce cellular levels of the signaling protein ,-catenin and, thereby, inhibit ,-catenin and T-cell-factor-mediated gene expression. In addition, APC protein binds to microtubules in vertebrate cells and localizes to actin-rich adherens junctions in epithelial cells of the fruit fly Drosophila (Fig. 1). Very little is known, however, about the function of these cytoskeletal associations. Recently, Hamada and Bienz have described a potential role for Drosophila E-APC in cellular adhesion,1 which offers new clues to APC function in embryonic development, and potentially colorectal adenoma formation and tumor progression in humans. BioEssays 24:771,774, 2002. © 2002 Wiley Periodicals, Inc. [source]

Female post-reproductive lifespan: a general mammalian trait

BIOLOGICAL REVIEWS, Issue 4 2004
Alan A. Cohen
ABSTRACT Traditional explanations for the evolution of menopause and post-reproductive lifespan in human females have been based on the benefits of maternal or grand-maternal care outweighing the cost of lost reproduction. These explanations assume an evolutionary origin of menopause since human divergence with the most recent common ancestor. In this study, I conduct a literature survey of studies of 42 mammal species from eight orders, showing that post-reproductive lifespan appears to be widespread among mammals. I then propose an alternative to traditional hypotheses: following accepted theories of trade-offs and senescence, I suggest that the cost of extending reproductive lifespan might be relatively high in female mammals. Somatic and reproductive senescence appear to follow separate trajectories, so it is not surprising that the two processes should occur on different schedules. The timing of each process is probably determined by maximization of reproductive performance and survival early in adulthood, with consequent trajectories resulting in a post-reproductive lifespan. The early end of reproduction relative to lifespan may be due to the cost of production and/or maintenance of oocytes, which decline exponentially over time. Oocyte number below a threshold may trigger an end to normal hormonal cycling. [source]

Conceptual background, development, and preliminary data from the unified protocol for transdiagnostic treatment of emotional disorders,

DEPRESSION AND ANXIETY, Issue 10 2010
Zofia A. Wilamowska M.A.
Abstract Anxiety and mood disorders are common, chronic, costly, and characterized by high comorbidity. The development of cognitive behavioral approaches to treating anxiety and mood disorders has left us with highly efficacious treatments that are increasingly widely accepted. The proliferation of treatment manuals targeting single disorders, sometimes with trivial differences among them, leaves the mental health professional with no clear way to choose one manual over another and little chance of ever becoming familiar with most of them, let alone trained to competence in their delivery. Deepening understanding of the nature of emotional disorders reveals that commonalities in etiology and latent structures among these disorders supersedes differences. Based on empirical evidence from the domains of learning, emotional development and regulation, and cognitive science, we have distilled a set of psychological procedures that comprise a unified intervention for emotional disorders. The Unified Protocol (UP) is a transdiagnostic, emotion-focused cognitive behavioral treatment, which emphasizes the adaptive, functional nature of emotions, and seeks to identify and correct maladaptive attempts to regulate emotional experiences, thereby facilitating appropriate processing and extinction of excessive emotional responding to both internal (somatic) and external cues. The treatment components of the UP are briefly outlined. Theory and rationale supporting this new approach are described along with some preliminary evidence supporting its efficacy. Implications for the treatment of emotional disorders using the UP are discussed. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [source]

Little evidence for different phenomenology in poststroke depression

ACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2010
T. B. Cumming
Cumming TB, Churilov L, Skoog I, Blomstrand C, Linden T. Little evidence for different phenomenology in poststroke depression. Objective:, It remains unclear whether mood depressive disorders after stroke have a distinct phenomenology. We evaluated the symptom profile of poststroke depression (PSD) and assessed whether somatic symptoms were reported disproportionately by stroke patients. Method:, The sample was 149 stroke patients at 18 months poststroke and 745 age- and sex-matched general population controls. A comprehensive psychiatric interview was undertaken and depression was diagnosed according to DSM-III-R criteria. Results:, Depressed controls reported more ,inability to feel' (P = 0.002) and ,disturbed sleep' (P = 0.008) than depressed stroke patients. Factor analysis of the 10 depressive symptoms identified two main factors, which appeared to represent somatic and psychological symptoms. There was no difference in scores on these two factors between stroke patients and controls. Conclusion:, Phenomenology of depression at 18 months poststroke is broadly similar but not the same as that described by controls. Somatic symptoms of depression were not over-reported by stroke patients. [source]

Development of the neuromuscular system during asexual propagation in an invertebrate chordate

DEVELOPMENTAL DYNAMICS, Issue 8 2009
Stefano Tiozzo
Abstract Botryllus schlosseri is a colonial ascidian, and the closest relative to vertebrates that can completely regenerate its entire body, including all somatic and germline tissues, using an asexual developmental pathway called blastogenesis. This regenerative potential exhibited by Botryllus and other colonial ascidians does not exist in any other chordate and makes B. schlosseri a promising model to investigate the cellular and molecular basis of regeneration. In this report, we describe postembryonic myogenesis and characterized the development of the neural system during blastogenic development. ,-Tubulin immunoreactivity revealed a high correlation with previous studies on the motor nervous system. The pattern of the serotoninergic system in the adult reflects that observed in solitary ascidians, but in early blastogenesis suggests a morphogenic role of this monoamine. In summary, this study provides the morphological framework to dissect the mechanisms underlying the ability to regenerate entire organ systems as an adult in a chordate model. Developmental Dynamics 238:2081,2094, 2009. © 2009 Wiley-Liss, Inc. [source]

Genome-wide identification of female-enriched genes in zebrafish

DEVELOPMENTAL DYNAMICS, Issue 1 2005
Chaoming Wen
Abstract Characteristic differences in morphology, physiology, and behavior between a male and female are correlated to the differential selection of sex-dependent transcriptomes. By using a cDNA array carrying ,9,000 zebrafish unique genes, we identified a group of genes whose expression are enriched in the female fish. A subset of these genes have been confirmed and further grouped as egg-enriched genes, as both somatic- and egg-enriched genes or as somatic-enriched genes by means of RNA gel blot hybridization. Most importantly, a significant proportion of these genes are either functionally unknown or are novel genes. Thus, future studies of this group of genes will help us greatly to understand more about sex-determination and sex-related physiology and behavior. In addition, comparison of zebrafish female-enriched genes with that in Drosophila, we found that only germline genes are shared between vertebrate and invertebrate, suggesting that the process of oogenesis is highly conserved during the evolution. Developmental Dynamics 232:171,179, 2005. © 2004 Wiley-Liss, Inc. [source]

Transient expression of serotonin 5-HT4 receptors in the mouse developing thalamocortical projections

DEVELOPMENTAL NEUROBIOLOGY, Issue 3 2010
Erin R. Slaten
Abstract The serotonin 5-HT4 receptor (5-HT4 -R) is an unusually complex G-protein coupled receptor that is likely to play important roles in brain development and that may underlie the comorbidity of central and peripheral abnormalities in some developmental disorders. We studied the expression of 5-HT4 -Rs in the developing mouse forebrain at embryonic days 13, 15, 17, and at postnatal days 3 and 14 by using immunohistochemistry, tract tracing, and quantitative RT-PCR. The developing thalamocortical projections transiently expressed 5-HT4 -Rs in the embryonic brain and the 5-HT4 -R expression in the forebrain changed from axonal to somatic around birth. From embryonic days 13,17, the forebrain mRNA levels of the 5-HT4(a) -R and 5-HT4(b) -R splice variants increased nine- and fivefold, respectively, whereas the levels of the 5-HT4(e) -R and 5-HT4(f) -R variants remained relatively low throughout the studied period of embryonic development. These results suggest that during development 5-HT4 -R expression undergoes a dynamic regulation and that this regulation may be important for the normal development of sensory and limbic processing. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2010. [source]

Bilateral optic atrophy following diabetic ketoacidosis

DIABETIC MEDICINE, Issue 5 2000
S. H. Song
Summary Diabetic ketoacidosis (DKA) can result in neuropathic abnormalities of the somatic and the autonomous nervous systems. We report the case of a 50-year-old man with Type 1 diabetes of 20-year duration who after severe DKA lost vision in his right eye and only retain partial vision in his left. This case demonstrates that optic neural tissue is vunerable to haemodynamic and metabolic complications of DKA. [source]

Clinico-pathological features of postural hypotension in diabetic autonomic neuropathy

DIABETIC MEDICINE, Issue 2 2000
K. I. Khawaja
Summary We report the clinico-pathological features and management of a 49-year-old male with a 30-year history of Type 1 diabetes mellitus who had nephropathy (proteinuria 1.81 g/24 h, creatinine 136 ,mol/l), proliferative retinopathy and severe somatic and autonomic neuropathy. A sural nerve biopsy demonstrated marked myelinated fibre loss with unmyelinated fibre degeneration and regeneration combined with extensive endoneurial microangiopathy. The management of the patient's blood pressure problems (supine hypertension) and symptomatic postural hypotension is discussed. [source]

When an epithelium ceases to exist , an ultrastructural study on the fate of the embryonic coelom in Epiperipatus biolleyi (Onychophora, Peripatidae)

ACTA ZOOLOGICA, Issue 3 2004
Georg Mayer
Abstract It is an accepted fact that fusion between the coelomic cavities and the primary body cavity occurs during development in the Arthropoda. However, such a fusion is much disputed in the Onychophora. In order to clarify this subject, the fate of embryonic coelomic cavities has been studied in an onychophoran. Ultrastructural investigations in this paper provide evidence that embryonic coelomic cavities fuse with spaces of the primary body cavity in Epiperipatus biolleyi. During embryogenesis, the somatic and splanchnic portions of the mesoderm separate and the former coelomic linings are transformed into mesenchymatic tissue. The resulting body cavity therefore represents a mixture of primary and secondary (coelomic) body cavities, i.e. the ,mixocoel'. The nephridial anlage is already present, when the ,mixocoel' is formed, although there is no trace of a sacculus yet. The lumen of the nephridial anlage, thus, communicates with the newly formed ,mixocoel'. Accordingly, the lumen of the nephridial sacculus cannot be regarded as a kind of ,persisting coelomic cavity' in E. biolleyi. Our findings support the hypothesis that the ,mixocoel' was already present in the common stem species of the Onychophora and Euarthropoda. [source]

A double-blind, randomized, parallel group study to compare the efficacy, safety and tolerability of slow-release oral morphine versus methadone in opioid-dependent in-patients willing to undergo detoxification

ADDICTION, Issue 9 2009
Ekkehard Madlung-Kratzer
ABSTRACT Aims Evaluation of the efficacy and safety of slow-release oral morphine (SROM) compared with methadone for detoxification from methadone and SROM maintenance treatment. Design Randomized, double-blind, double-dummy, comparative multi-centre study with parallel groups. Setting Three psychiatric hospitals in Austria specializing in in-patient detoxification. Participants Male and female opioid dependents (age > 18 years) willing to undergo detoxification from maintenance therapy in order to reach abstinence. Interventions Abstinence was reached from maintenance treatment by tapered dose reduction of either SROM or methadone over a period of 16 days. Measurements Efficacy analyses were based on the number of patients per treatment group completing the study, as well as on the control of signs and symptoms of withdrawal [measured using Short Opioid Withdrawal Scale (SOWS)] and suppression of opiate craving. In addition, self-reported somatic and psychic symptoms (measured using Symptom Checklist SCL-90-R) were monitored. Findings Of the 208 patients enrolled into the study, 202 were eligible for analysis (SROM: n = 102, methadone: n = 100). Completion rates were 51% in the SROM group and 49% in the methadone group [difference between groups: 2%; 95% confidence interval (CI): ,12% to 16%]. The rate of discontinuation in the study was high mainly because of patients voluntarily withdrawing from treatment. No statistically significant differences between treatment groups were found in terms of signs and symptoms of opiate withdrawal, craving for opiates or self-reported symptoms. SROM and methadone were both well tolerated. Conclusions Detoxification from maintenance treatment with tapered dose reduction of SROM is non-inferior to methadone. [source]

Mortality among opiate users: opioid maintenance therapy, age and causes of death

ADDICTION, Issue 8 2009
Thomas Clausen
ABSTRACT Aims This study investigates how age of opioid users is related to causes of death prior to, during and after opioid maintenance treatment (OMT), and estimates risks of death from various causes in relation to age. Design, setting and participants Data on all opiate dependents in Norway (1997,2003) who applied for and were accepted for OMT (n = 3789) were cross-linked with the Norwegian death register. The total observation time was 10 934 person-years. Findings A total of 213 deaths was recorded. Of these, 73% were subject to autopsy, and causes of death were known for 208 cases: the overall death rate was 1.9%. Deaths were due to drug overdose (54%), somatic (32%) and traumatic causes (14%). Overdose deaths among all age groups were reduced during OMT but age had a differential effect upon risk when out of treatment. Younger opioid users were at greater risk of overdose before entering treatment; older users were at greater risk after leaving treatment. Older OMT patients were at higher risk of both somatic and traumatic deaths, and deaths during OMT were most likely to be due to somatic causes. Conclusions The high rates of overdose prior to and after treatment emphasize the need to provide rapid access to OMT, to retain patients in treatment and to re-enrol patients. The high prevalence among older patients of deaths due to somatic causes has implications for screening, treatment and referral, and may also lead to increased treatment costs. [source]

A review of the acute subjective effects of MDMA/ecstasy

ADDICTION, Issue 7 2006
Chelsea A. Baylen
ABSTRACT Aim Although several relatively recent reviews have summarized the neuropsychiatric effects associated with chronic ecstasy use, there is no published comprehensive review of studies on the acute subjective effects (ASEs) of MDMA/ecstasy. Design The present study reviewed the prevalence, intensity and duration of ASEs collected from 24 studies that provided frequency data on the prevalence of self-reported ecstasy effects and/or provided data on the intensity of ecstasy effects. Findings Although hundreds of ASEs have been reported following MDMA consumption, we identified a subset of effects reported repeatedly by meaningful proportions and large numbers of participants across multiple investigations, most of which were either emotional (e.g. anxiety, depression, closeness, fear, euphoria, calmness) or somatic (e.g. nausea/vomiting, bruxism, muscle aches/headache, sweating, numbness, body temperature changes, fatigue, dizziness, dry mouth, increased energy). Only one sexual ASE (sexual arousal/increased sensual awareness), one cognitive ASE (confused thought), one sensory,perceptual ASE (visual effects/changes in visual perception), one sleep-related ASE (sleeplessness) and one appetite-related ASE (decreased appetite) were reported across five or more investigations. Three factors,number of hours between ingestion and assessment, dose level, and gender,have been associated with the acute subjective experience of MDMA/ecstasy., Conclusions This review provides useful information for clinicians and researchers who want to understand the desirable and undesirable ASEs that may motivate and restrain ecstasy use, for public health advocates who seek to reduce biomedical harms (e.g. fainting, dehydration, shortness of breath, bruxism) associated with recreational use of MDMA/ecstasy, and for educators who wish to design credible prevention messages that neither underestimate nor exaggerate users' experiences of this drug. [source]

REVIEW: Behavioral evidence for the significance of serotoninergic (5-HT) receptors in cocaine addiction

ADDICTION BIOLOGY, Issue 3 2010
gorzata Filip
ABSTRACT Cocaine addiction has somatic, psychological, psychiatric, socio-economic and legal implications in the developed world. Presently, there is no medication approved for the treatment of cocaine addiction. In recent years, data from the literature (pre-clinical studies and clinical trials) have provided several lines of evidence that serotonin (5-HT) and 5-HT receptors play a modulatory role in the mechanisms of action of cocaine. Here we review the contribution of 5-HT receptor subtypes to cocaine sensitization, discrimination, conditioned place preference, self-administration, reinstatement of seeking behavior and withdrawal symptoms in laboratory animals. Additionally, the consequences of chronic cocaine exposure on particular 5-HT receptor-assigned functions in pre-clinical studies are presented. [source]

Intercellular MHC transfer between thymic epithelial and dendritic cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2008
Virginie Millet
Abstract Thymic dendritic cells (DC) and epithelial cells play a major role in central tolerance but their respective roles are still controversial. Epithelial cells have the unique ability to ectopically express peripheral tissue-restricted antigens conferring self-tolerance to tissues. Paradoxically, while negative selection seems to occur for some of these antigens, epithelial cells, contrary to DC, are poor negative selectors. Using a thymic epithelial cell line, we show the functional intercellular transfer of membrane material, including MHC molecules, occurring between epithelial cells. Using somatic and bone marrow chimeras, we show that this transfer occurs efficiently in vivo between epithelial cells and, in a polarized fashion, from epithelial to DC. This novel mode of transfer of MHC-associated, epithelial cell-derived self-antigens onto DC might participate to the process of negative selection in the thymic medulla. [source]

Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004
A. I. Gulyas
Abstract Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) catalyse the hydrolysis of the endocannabinoids anandamide and 2-arachidonoyl glycerol. We investigated their ultrastructural distribution in brain areas where the localization and effects of cannabinoid receptor activation are known. In the hippocampus, FAAH was present in somata and dendrites of principal cells, but not in interneurons. It was located mostly on the membrane surface of intracellular organelles known to store Ca2+ (e.g. mitochondria, smooth endoplasmic reticulum), less frequently on the somatic or dendritic plasma membrane. MGL immunoreactivity was found in axon terminals of granule cells, CA3 pyramidal cells and some interneurons. In the cerebellum, Purkinje cells and their dendrites are intensively immunoreactive for FAAH, together with a sparse axon plexus at the border of the Purkinje cell/granule cell layers. Immunostaining for MGL was complementary, the axons in the molecular layer were intensively labelled leaving the Purkinje cell dendrites blank. FAAH distribution in the amygdala was similar to that of the CB1 cannabinoid receptor: evident signal in neuronal somata and proximal dendrites in the basolateral nucleus, and hardly any labelling in the central nucleus. MGL staining was restricted to axons in the neuropil, with similar relative signal intensities seen for FAAH in different nuclei. Thus, FAAH is primarily a postsynaptic enzyme, whereas MGL is presynaptic. FAAH is associated with membranes of cytoplasmic organelles. The differential compartmentalization of the two enzymes suggests that anandamide and 2-AG signalling may subserve functional roles that are spatially segregated at least at the stage of metabolism. [source]

Cell type-dependent expression of HCN1 in the main olfactory bulb

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2003
Noémi B. Holderith
Abstract In many brain regions, hyperpolarization-activated cationic currents (Ih) are involved in the generation of rhythmic activities, but the role of Ih in olfactory oscillations remains unclear. Knowledge of the cellular and subcellular distributions of hyperpolarization-activated and cyclic nucleotide-gated channel (HCN) subunits is necessary for understanding the role of Ih in olfactory network activities. Using light microscopic immunocytochemistry, we demonstrate strong HCN1 labelling of the glomerular layer and moderate staining of granule cell, internal and external plexiform layers of the rat main olfactory bulb. In the glomerular layer, among many unlabelled neurons, two distinct subpopulations of juxtaglomerular cells are labelled. Approximately 10% of the juxtaglomerular cells strongly express HCN1. These small diameter cells are immunoreactive for GABA and comprise a subpopulation of periglomerular cells. An additional subset of juxtaglomerular cells (, 1%) expresses low levels of HCN1. They are large in diameter, GABA immunonegative but immunopositive for vesicular glutamate transporter 2, characterizing them as external tufted cells. Quantitative immunogold localization revealed that the somatic plasma membranes of periglomerular cells contain approximately four times more HCN1 labelling than those of external tufted cells. Unlike in cortical pyramidal cells, immunogold density for HCN1 does not significantly differ in somatic and dendritic plasma membranes of external tufted cells, indicating that post-synaptic potentials arriving at proximal and distal dendrites are modulated by the same density of Ih. Our results demonstrate a cell type-dependent expression of HCN1 in the olfactory bulb and predict a differential contribution of distinct juxtaglomerular cell types to network oscillations. [source]

Somatic and visceral afferents to the ,vasodepressor region' of the caudal midline medulla in the rat

Postnatal maturation of Na+, K+, 2Cl, cotransporter expression and inhibitory synaptogenesis in the rat hippocampus: an immunocytochemical analysis

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2002
Serge Marty
Abstract GABA, a major inhibitory neurotransmitter, depolarizes hippocampal pyramidal neurons during the first postnatal week. These depolarizations result from an efflux of Cl, through GABAA -gated anion channels. The outward Cl, gradient that provides the driving force for Cl, efflux might be generated and maintained by the Na+, K+, 2Cl, cotransporter (NKCC) that keeps intracellular Cl, concentration above electrochemical equilibrium. The developmental pattern of expression of the cotransporter in the hippocampus is not known. We studied the postnatal distribution pattern of NKCC in the hippocampus using a monoclonal antibody (T4) against a conserved epitope in the C-terminus of the cotransporter molecule. We also examined the temporal relationships between the developmental pattern of NKCC expression and the formation of perisomatic GABAergic synapses. This study was aimed at determining, with antivesicular inhibitory amino acid transporter (VIAAT) antibodies, whether perisomatic GABAergic synapses are formed preferentially at the time when GABA is depolarizing. During the first postnatal week, NKCC immunolabelling was restricted to cell bodies in the pyramidal cell layer and in the strata oriens and radiatum. In contrast, at postnatal day 21 (P21) and in adult animals little or no labelling occurred in cell bodies; instead, a prominent dendritic labelling appeared in both pyramidal and nonpyramidal neurons. The ultrastructural immunogold study in P21 rat hippocampi corroborated the light-microscopy results. In addition, this study revealed that a portion of the silver-intensified colloidal gold particles were located on neuronal plasmalemma, as expected for a functional cotransporter. The formation of inhibitory synapses on perikarya of the pyramidal cell layer was a late process. The density of VIAAT-immunoreactive puncta in the stratum pyramidale at P21 reached four times the P7 value in CA3, and six times the P7 value in CA1. Electron microscopy revealed that the number of synapses per neuronal perikaryal profile in the stratum pyramidale of the CA3 area at P21 was three times higher than at P7, even if a concomitant 20% increase in the area of these neuronal perikaryal profiles occurred. It is concluded that, in hippocampal pyramidal cells, there is a developmental shift in the NKCC localization from a predominantly somatic to a predominantly dendritic location. The presence of NKCC during the first postnatal week is consistent with the hypothesis that this transporter might be involved in the depolarizing effects of GABA. The depolarizing effects of GABA may not be required for the establishment of the majority of GABAergic synapses in the stratum pyramidale, because their number increases after the first postnatal week, when GABA action becomes hyperpolarizing. [source]

The retrograde inhibition of IPSCs in rat cerebellar Purkinje cells is highly sensitive to intracellular Ca2+

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2000
Maike Glitsch
Abstract The Ca2+ -dependent retrograde inhibition of inhibitory postsynaptic currents (depolarization-induced-suppression of inhibition; DSI) was investigated using fura-2 Ca2+ measurements and whole-cell patch-clamp recordings in rat cerebellar Purkinje cells. DSI was studied in cells loaded with different concentrations of the Ca2+ chelators BAPTA and EGTA. A concentration of 40 m m BAPTA was required to significantly interfere with DSI, whereas 10 m m BAPTA was almost ineffective. 40 m m EGTA reduced DSI, but was less effective than 40 m m BAPTA. Ratiometric Ca2+ measurements indicated that the extent of DSI depended critically on the changes in intracellular calcium ([Ca2+]i). The relationship between DSI and peak ,[Ca2+]i could be approximated by a hyperbolic function, with apparent half-saturation concentrations of 200 and 40 n m for dendritic and somatic [Ca2+]i, respectively. It is suggested that DSI is due to somatodendritic exocytosis of a retrograde messenger, and that this exocytosis is highly sensitive to [Ca2+]i. [source]

ON THE EVOLUTION OF DIFFERENTIATED MULTICELLULARITY

EVOLUTION, Issue 2 2009
Martin Willensdorfer
Most conspicuous organisms are multicellular and most multicellular organisms develop somatic cells to perform specific, nonreproductive tasks. The ubiquity of this division of labor suggests that it is highly advantageous. In this article I present a model to study the evolution of specialized cells. The model allows for unicellular and multicellular organisms that may contain somatic (terminally differentiated) cells. Cells contribute additively to a quantitative trait. The fitness of the organism depends on this quantitative trait (via a benefit function), the size of the organism, and the number of somatic cells. The model allows one to determine when somatic cells are advantageous and to calculate the optimum number (or fraction) of reproductive cells. I show that the fraction of reproductive cells is always surprisingly high. If somatic cells are very small, they can outnumber reproductive cells but their biomass is still less than the biomass of reproductive cells. I discuss the biology of primitive multicellular organisms with respect to the model predictions. I find a good agreement and outline how this work can be used to guide further quantitative studies of multicellularity. [source]

The structures of Escherichia coli O-polysaccharide antigens

FEMS MICROBIOLOGY REVIEWS, Issue 3 2006
Roland Stenutz
Abstract Escherichia coli is usually a non-pathogenic member of the human colonic flora. However, certain strains have acquired virulence factors and may cause a variety of infections in humans and in animals. There are three clinical syndromes caused by E. coli: (i) sepsis/meningitis; (ii) urinary tract infection and (iii) diarrhoea. Furthermore the E. coli causing diarrhoea is divided into different ,pathotypes' depending on the type of disease, i.e. (i) enterotoxigenic; (ii) enteropathogenic; (iii) enteroinvasive; (iv) enterohaemorrhagic; (v) enteroaggregative and (vi) diffusely adherent. The serotyping of E. coli based on the somatic (O), flagellar (H) and capsular polysaccharide antigens (K) is used in epidemiology. The different antigens may be unique for a particular serogroup or antigenic determinants may be shared, resulting in cross-reactions with other serogroups of E. coli or even with other members of the family Enterobacteriacea. To establish the uniqueness of a particular serogroup or to identify the presence of common epitopes, a database of the structures of O-antigenic polysaccharides has been created. The E. coli database (ECODAB) contains structures, nuclear magnetic resonance chemical shifts and to some extent cross-reactivity relationships. All fields are searchable. A ranking is produced based on similarity, which facilitates rapid identification of strains that are difficult to serotype (if known) based on classical agglutinating methods. In addition, results pertinent to the biosynthesis of the repeating units of O-antigens are discussed. The ECODAB is accessible to the scientific community at http://www.casper.organ.su.se/ECODAB/. [source]

Somatic Styles of the Early Middle Ages

GENDER & HISTORY, Issue 3 2008
Lynda L. Coon
,Somatic Styles' examines how classical modes of gender played significant roles in carving out competitive arenas between clerical and lay elites, c.600,900 CE. The paper explores the hermeneutical obstacles standing between the contemporary theorist of gender and the complex nature of the early medieval texts under scrutiny. The analysis reconstructs classicising techniques of gender deployed by early medieval churchmen, and it does so in a way that both challenges the stranglehold of the ,one-sex' model on pre-modern understandings of gender and heals the ,rupture' between the ,Ancient' and the ,Dark Age'. Finally, the essay maps early medieval somatic and gendered styles onto an architectural space where lay and consecrated bodies met , a ninth-century monastic basilica. [source]

Generation of mice harboring a Sox6 conditional null allele,

GENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 5 2006
Bogdan Dumitriu
Abstract Sox6 belongs to the family of Sry-related HMG box transcription factors, which determine cell fate and differentiation in various lineages. Sox6 is expressed in several tissues, including cartilage, testis, neuronal, and erythropoietic tissues. Mice lacking Sox6 have revealed critical roles for Sox6 in several of these tissues, but their multiple defects and early lethality has limited studies in specific cell types and in postnatal mice. We show here that we have generated mice harboring a Sox6 conditional null allele (Sox6fl+) by flanking the second coding exon with loxP sites. This allele encodes wildtype Sox6 protein, is expressed normally, and is efficiently converted into a null allele (Sox6fl,) by Cre-mediated recombination in somatic and germ cells. Sox6fl+/fl+ mice are indistinguishable from wildtype mice, and Sox6fl,/fl, mice from Sox6,/, mice. These Sox6 conditional null mice will thus be valuable for further uncovering the roles of Sox6 in various processes in vivo. genesis 44:219,224, 2006. Published 2006 Wiley-Liss, Inc. [source]

Mutations of the Wnt antagonist AXIN2 (Conductin) result in TCF-dependent transcription in medulloblastomas

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2007
Arend Koch
Abstract Medulloblastomas (MBs) represent the most common malignant brain tumors in children. Most MBs develop sporadically in the cerebellum, but their incidence is highly elevated in patients with familial adenomatous polyposis coli. These patients carry germline mutations in the APC tumor suppressor gene. APC is part of a multiprotein complex involved in the Wnt signaling pathway that controls the stability of ,-catenin, the central effector in this cascade. Previous genetic studies in MBs have identified mutations in genes coding for ,-catenin and its partners, APC and AXIN1, which cause activation of Wnt signaling. The pathway is negatively controlled by the tumor suppressor AXIN2 (Conductin), a scaffold protein of this signaling complex. To investigate whether alterations in AXIN2 may also be involved in the pathogenesis of sporadic MBs, we performed a mutational screening of the AXIN2 gene in 116 MB biopsy samples and 11 MB cell lines using single-strand conformation polymorphism and sequencing analysis. One MB displayed a somatic, tumor-specific 2 bp insertion in exon 5, leading to carboxy-terminal truncation of the AXIN2 protein. This tumor biopsy showed nuclear accumulation of ,-catenin protein, indicating an activation of Wnt signaling. In 2 further MB biopsies, mutations were identified in exon 5 (Glu408Lys) and exon 8 (Ser738Phe) of the AXIN2 gene, which are due to predicted germline mutations and rare polymorphisms. mRNA expression analysis in 22 MBs revealed reduced expression of AXIN2 mRNA compared to 8 fetal cerebellar tissues. Promoter hypermethylation could be ruled out as a major cause for transcriptional silencing by bisulfite sequencing. To study the functional role of AXIN2 in MBs, wild-type AXIN2 was overexpressed in MB cell lines in which the Wnt signaling pathway was activated by Wnt-3a. In this assay, AXIN2 inhibited Wnt signaling demonstrated in luciferase reporter assays. In contrast, overexpression of mutated AXIN2 with a deleted C-terminal DIX-domain resulted in an activation of the Wnt signaling pathway. These findings indicate that mutations of AXIN2 can lead to an oncogenic activation of the Wnt pathway in MBs. © 2007 Wiley-Liss, Inc. [source]

The effect of somatic symptom attribution on the prevalence rate of depression and anxiety among nursing home patients

INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2005
Martin Smalbrugge
Abstract The validity of diagnostic psychiatric instruments for depression and anxiety disorders may be compromised among patients with complex physical illness and disability. The objective of this study was to determine the effect on the prevalence rate of depression and anxiety in a nursing home population of attributing somatic symptoms of depression and anxiety to either somatic or psychiatric disorder. Symptoms of major depression (MD), generalized anxiety disorder (GAD) and panic disorder (PD) were measured using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Somatic symptoms of MD, GAD and PD were attributed to somatic causes when the interviewer was not sure about a psychiatric cause. To analyse the effect of this attribution on the prevalence rate of MD, GAD and PD, a sensitivity analysis was undertaken in which symptoms that were attributed to somatic causes were recoded as symptoms attributed to psychiatric disorder. Prevalence rates of MD, GAD and PD were calculated before and after recoding. The prevalence of MD after recoding rose from 7.5% to 8.1%. The prevalence of GAD did not change. The prevalence of PD rose from 1.5% to 1.8%. Attribution of somatic symptoms to either somatic or psychiatric disorder when the interviewer was not sure about a psychiatric cause of the somatic symptoms had only a very modest effect on the prevalence rate of major depression, generalized anxiety disorder and panic disorder in a nursing home population. Copyright © 2005 John Wiley & Sons, Ltd. [source]