bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell death during development of the cochlear and vestibular ganglia of the chick
Authors: Ard March D. , Morest D. Kent
Published: April 2003

This report documents and quantitates the naturally occurring death of neurons in the cochlear and vestibular ganglia during the normal development of the chick embryo. The data are compared with the amount of cell loss in the cochlear and vestibular nuclei to evaluate the possibility that the death of the neurons in the same sensory pathway may be related to the formation of their connections. Neurons of the cochlear and vestibular ganglia of the chick were counted and their cell bodies measured with light microscopic methods at the beginning of their period of synapse formation, embryonic day 8 (E8), at the end of the period of synapse formation (E14), and again at a more mature stage, post‐hatching day 14 (P14).

The number of neurons declined between E8 and E14 in the cochlear ganglion by 25% (from 11170 to 8353) and in the vestibular ganglion by 24% (from 12687 to 9613). The neuronal population remained relatively stable between E14 and P14. Cell counts at each age were accompanied by morphological descriptions of the neurons and of their synaptic targets in the sensory epithelia of the inner ear. During the period of cell loss the mean diameters of the cell bodies in the cochlear ganglion increased slightly, from 9.5 to 111 μm and reached 17.6 μm at P14, while those in the vestibular ganglion increased from 10.4 to 13.3 μm and reached 20.9 μm at P14. The period of cell loss in the cochlear and vestibular ganglia coincides with the stages in their development when the sensory neurons have already contacted their target cells in the primary sensory nuclei and in the receptor epithelium. It is during this period that the transformation from the immature axonal endings to the definitive types of synapses begins. Thus the present data are consistent with the view that the formation of central as well as peripheral synapses is involved in determining the extent of neuronal death during the development of sensory neurons.
Neurogenesis in the anterior olfactory nucleus and its associated transition areas in the rat brain
Authors: Bayer Shirley A.
Published: April 2003

Neurogenesis in the rat olfactory peduncle was examined with [3H]thymidine autoradiography. Animals in the prenatal groups were the offspring of pregnant females given an injection of [3H]thymidine on two consecutive gestation days. Nine groups of embryos were exposed to [3H]thymidine on embryonic days (E) E13–E14, E14–E15, … E21–E22, respectively. One group of postnatal animals was given four consecutive injections of [3H]thymidine on postnatal days (P) P0‐P3. On P60, the percentage of labeled cells and the proportion of cells originating during either 24 or 48 hr periods were quantified at seven anatomical levels through both the anterior olfactory nucleus and the transition areas. A caudal (older) to rostral (younger) neurogenetic gradient is found both within and between structures in the olfactory peduncle. Neurons in the dorsal, lateral, and ventral‐lateral transition areas are generated mainly between E14 and E19, those in the anterior olfactory nucleus mainly between E15 and E21. Only 3–4% of the neurons in the most anterior pars lateralis and pars dorsalis originate after birth. All parts of the anterior olfactory nucleus show a strong superficial (older) to deep (younger) neurogenetic gradient (the “outside‐in” pattern). In contrast, neurons in the ventral—lateral transition area and in the dorsal transition area originate in a deep to superficial neurogenetic gradient (the “inside‐out” pattern), suggesting that these areas are, in reality, primary olfactory cortex. The lateral transition area is truly “transitional”, showing no neurogenetic gradient along the superficial‐deep plane. The medial transition area originates between E15 and E19 in a center (older) to edge (younger) “sandwich” neurogenetic gradient along the rostrocaudal plane, a pattern apparently unrelated to neurogenetic gradients in other olfactory peduncle structures. These data suggest that characteristic patterns of neurogenesis, namely the “insideout” vs the “outside‐in” gradients, permit the assignment of different structures to cortical vs ganglionic cytoarchitectonic components of the olfactory relay system.
Effect of thyroid deficiency on the regional development of glutaminase, a glutamatergic neuron marker, in the rat brain
Authors: Patel Ambrish J. , Hunt Anthony , Hayashi Masao
Published: April 2003

The effect of thyroid deficiency on the activity of phosphate‐activated glutaminase (the marker for glutamatergic neurons) was studied in different parts of the rat brain at ages 5,10, 15 and 25 days and at day 130 following 102 days of rehabilitation. The brain regions investigated were the cerebral cortex, basal forebrain, hippocampus and cerebellum. During normal development, the activity of glutaminase increased relatively earlier in the cerebral cortex and hippocampus than in the cerebellum, while the absolute value reached a much higher level in the hippocampus than in other brain regions. In the basal forebrain, the developmental pattern of glutaminase was bimodal and the rise in enzyme activity after 15 days coincided with the decrease in the cerebral cortex. These regional developmental changes in glutaminase activity correlated well with known information on the formation of glutamatergic cells and pathways in the brain. Neonatal thyroid deficiency had little effect on the developmental patterns of enzyme activity, the exception being a transient decrease in 10‐day‐old hypothyroid hippocampus. The present results, together with previous findings, indicate that the effect of thyroid hormone on neural maturation is cell‐type specific and the glutamatergic neurons are not the main targets of thyroid hormone action.
The neuro‐endocrine ambiguity of sympathoadrenal cells
Authors: Unsicker K. , Seidl K. , Hofmann H. D.
Published: April 2003

This introductory article presents a survey of the principle cellular constituents of the sympathoadrenal section in the peripheral autonomic nervous system, their development and plasticity and factors that govern the expression of particular morphologic and transmitter phenotypes. The article focuses on results obtained in cell culture studies with isolated chromaffin cells that have permitted the analysis of molecular signals possibly serving as environmental cues during the development of sympathoadrenal cells.
The role of competition in the refinement of the projections of sympathetic neurons to the rat eye during development
Authors: Hill Caryl E. , Vidovic Maria
Published: April 2003

Within the iris, the extent of the nerve plexuses derived from the sympathetic neurons of the superior cervical ganglion (SCG) and the sensory, substance P (SP) neurons of the trigeminal ganglion depend on competition for target tissue derived growth factors. During the postnatal period when these plexuses are initially established, many sympathetic neurons are known to extend transient collateral projections to various targets within the eye. We have investigated the role of neuronal competition in the withdrawal of these transient projections by removing the sensory SP fibres using neonatal capsaicin treatment (50 mg/kg) on days 2, 10 and 17, or day 2 only. At 2, 4 and 7 weeks, fast blue was injected into the anterior chamber or posteriorly into the vitreous to retrogradely label sympathetic neurons in the SCG. Capsaicin treatment resulted in a transient retention of the projections of supernumerary neurons to the eye early during development and a maintenance of the collaterals of some of these sympathetic neurons to adulthood, but only when rats received multiple capsaicin injections. The retention of collaterals in these animals was reflected in an increase in the density of the sympathetic nerve plexus within targets such as the iris. Immunohistochemistry for SP showed that a single injection of capsaicin was less effective than multiple injections in removing the SP‐containing nerve fibres from the iris and in causing long‐lasting changes to the sympathetic projections. We conclude that some form of interaction between different neuronal populations within the eye plays an important role in the refinement of collateral projections of sympathetic neurons, but has no long‐term effect in influencing the final number of neurons which project to the eye.
Evaluation of the effects of inhibition of monoamine oxidase and senescence on methamphetamine‐induced neuronal damage
Authors: Wagner George C. , Walsh Sharon L.
Published: April 2003

The administration of high doses of methamphetamine causes long lasting damage to central dopaminergic and serotonergic neurons through a mechanism known to involve presynaptic, cytoplasmic stores of those transmitters and thought to be dependent upon a free radical reaction. The following studies were designed to determine if differential inhibition of the subtypes of monoamine oxidase would alter the magnitude of the methamphetamine induced neuronal damage. In addition, since monoamine oxidase type B increases with age, the effects of high dose administration of methamphetamine were evaluated in sensescent mice. It was observed that inhibition of monoamine oxidase type A, and to a lesser degree, type B, increased the magnitude of methamphetamine‐induced neuronal damage and that aged mice were more sensitive to the toxic action of methamphetamine. These results are interpreted with respect to the use of monoamine oxidase inhibitors in the treatment of Parkinson's disease.
In vitro screening for anticonvulsant‐induced teratogenesis: Drug alteration of cell adhesivity
Authors: Maguire C. , Regan C.M.
Published: April 2003

Anticonvulsant‐induced alteration in C6 glioma cell adhesivity has been evaluated in two independent in vitro assay systems. A centrifugal shear assay was employed to determine drug‐induced change in cell‐substratum adhesivity. Valproate and clonazepam were found to significantly increase cell‐substratum adhesivity when cells were cultured at concentrations which were within twice their therapeutic plasma level. A second assay evaluated change in affinity for concanavalin A lectin coated surfaces to determine change in cell surface glycoconjugate expression. Valproate and clonazepam and, to a lesser extent, diazepam significantly decreased drug‐exposed C6 glioma cell affinity for concanavalin A lectin coated surfaces. Valproate and clonazepam had approximate IC50 values of 0.75 mM and 75 μM, respectively. These findings are compared and discussed in relation to those obtained with an anti‐proliferative assay which has been suggested to predict teratogen potential.
Short‐ and long‐term effects of combined pre‐ and postnatal ethanol exposure (three trimester equivalency) on the development of myelin and axons in rat optic nerve
Authors: Phillips D.E. , Krueger S.K. , Rydquist J.E.
Published: April 2003

This study evaluated the effects of a combined gestational and 10 day postnatal alcohol exposure (human three trimester equivalency) on the development of myelin and axons in rat optic nerve. Rats were exposed during gestation via liquid diet, then their artificially reared pups were further exposed for 10 postnatal days via an ethanol‐containing diet fed by gastrostomy. Control animals from pair‐fed dams were artificially reared for 10 days on pair‐fed isocaloric diets. Anesthetized animals were perfused with fixative on gestational days (G) 15 and 20 and postnatal days (P) 5, 10, 15, 20, and 90, then optic nerve tissues prepared for electron microscopy. Optic nerve cross‐sectional areas were generally less from G20 through P90 in ethanol exposed animals. Counts of the number of myelinated nerve fibers per unit area and of the numbers of fibers in different stages of myelin development revealed that alcohol exposure caused a delay in myelin acquisition at 10 and 15 days that was compensated for at 20 and 90 days. Myelin thickness as a function of axon diameter was decreased in the alcohol exposed animals from 10 through 90 days, indicating a permanent reduction in the relative thickness of myelin.

These results show that alcohol exposure for all of gestation and 10 postnatal days in the rat (human three trimester equivalency) causes a permanent reduction in myelin thickness along with a delay in myelin acquisition in the optic nerve. Such alterations in developing and adult myelin could help to explain some of the neurological and visual dysfunctions associated with developmental alcohol exposures.
Ontogeny of MAP2 and GFAP antigens in primary cultures of embryonic chick brain. Effect of substratum, oxygen tension, serum and Ara‐C
Authors: Bruinink A. , Reiser P.
Published: April 2003

Brain cells from embryonic chick (stage 28–29) were cultivated for 16 days under serum‐free conditions. Nerve cells were found to mature during the first 7 days in culture, as indicated by the presence and developmental pattern of the relative amount of dendritic‐specific microtubule‐associated protein type 2 (MAP2). Maximal amounts of MAP2 antigen were found to be directly correlated with the number of cells plated out. Astroglia cell proliferation and differentiation, as measured by the amounts of glial fibrillary acidic protein (GFAP), were found to stabilize after a certain astrocyte cell density was reached. Variation in culture plate coating procedure, oxygen tension and addition of serum or of the cytostatic drug Ara‐C were found to differently affect viability and maturation processes of astroglia and of nerve cells. Moreover, optimal culture conditions for long‐term brain cell cultures are described.
Neurotransmitter amino acid levels in rat thalamus and cerebral cortex after cerebellectomy
Authors: Cicirata F. , Meli C. , Castorina C. , Serapide M.F. , Sorrenti V. , Di Giacomo C. , Gambera G. , Vanella A.
Published: April 2003

Glutamate, aspartate, GABA, glycine and taurine levels have been measured in rat thalamus and in cerebral cortex at different time intervals (3rd, 7th, 15th, 30th day) after cerebellectomy. A decrease in glutamate, aspartate and GABA was detected at the 7th day after cerebellectomy in the thalamus and at the 15th day in the cerebral cortex; at the 30th day after cerebellectomy the levels of these amino acids in the thalamus and in the cerebral cortex were observed to have recovered to control values. No statistically significant difference in glycine and taurine levels in the thalamus and in the cerebral cortex after cerebellectomy could be seen. These results show that the functional recovery process after cerebellar injury is associated with a complex modification of amino acid levels in thalamus and in cerebral cortex.
Corpus callosum: Demasculinization via perinatal anti‐androgen
Authors: Fitch Roslyn H. , Cowell Patricia E. , Schrott Lisa M. , Denenberg Victor H.
Published: April 2003

The male rat's corpus callosum is significantly larger than the female's. This dimorphism depends in part on the early presence of testosterone, since postnatal administration of testosterone to female pups enlarges their callosa in adulthood to the size of males. However, castrating males on day 1 is ineffective in reducing (demasculinizing) the size of their callosa as adults. We then addressed the question as to whether testosterone acts prior to day 1 to enlarge the callosa of males. To investigate this hypothesis pregnant rats were administered a non‐steroidal androgen blocker, flutamide, during the last 5 days of pregnancy, while controls received vehicle only. Male pups from flutamide litters were castrated on day 3 to prevent postnatal recovery following clearance of flutamide, while others received sham surgery. Callosal sex differences were found between males and females of control litters, but not between males and females from flutamide litters. The absence of sex effects among flutamide litters was a consequence of small callosal size in flutamide‐castrated males as compared to control males. We concluded that the prenatal production of testosterone in the male rat pup contributes to sexual dimorphism in the callosa of adult rats.
Development of the sensory innervation of muscle spindles in the kitten
Authors: Patak A. , Proske U. , Turner H. , Gregory J.E.
Published: April 2003

This is a report of the changes observed in the pattern of sensory innervation of muscle spindles in hindlimb muscles of kittens during the first four weeks of life. The structural analysis, made on teased, silver‐stained preparations, was complemented by a series of recordings of afferent responses of kitten spindles during ramp‐and‐hold stretches of the muscle. The primary endings of spindles from newborn animals showed a large degree of variability in their branching pattern and branches formed a network across the intrafusal fibres. In older animals there was less variability and lateral branches of stem axons began to encircle the intrafusal fibres. The process of maturation was characterized by a more uniform shape of the endings and more complete, evenly spaced, annulospiral terminals. Recordings of the responses of primary endings of spindles during muscle stretch showed that several features of the adult response were already present in the newborn, although the overall rate of discharge was very much lower. It was concluded that the changes observed in the structure of the sensory endings of kitten spindles did not have clearly identifiable physiological correlates. It appears that an annulospiral shape of the sensory terminals is not a necessary prerequisite for the generation of stretch responses. The predominant factor which appears to determine the responses of spindles to stretch is the maturity of the intrafusal fibres, in particular, the bag2 fibre.
Neuron‐enriched cultures derived from spinal cord of 10‐day‐old chick embryos: Influence of neuropeptides on neuronal survival, proliferation and cholinergic expression
Authors: Kentroti Susan , Vernadakis Antonia
Published: April 2003

The developmental regulation of cell proliferation, survival and cholinergic expression by growth hormone‐releasing hormone (GHRH) and somatostatin (SRIF) was investigated in neuronenriched cultures derived from 10‐day‐old embryonic chick spinal cord. In this study, 3H‐thymidine incorporation into DNA was assessed, using two different applications, in order to determine both cellular proliferation and survival. The rate of neuroblast proliferation in both control and neuropeptide‐treated cultures increased or remained the same up to day 6. However, in neuropeptide‐treated cultures the magnitude of cell proliferation remained at levels higher than those observed in controls through day 6 and was most significant in SRIF‐treated cultures at C4. In all groups, proliferation markedly declined by day 8. Survival of neuronal cells labelled at C4 remained high up to day 12 in all three groups, then drastically declined by day 17. Neuronal survival in the neuropeptide‐treated cultures was also higher than in controls. Cholinergic expression, as assessed by activity of choline acetyltransferase (ChAT), responded differentially to neuropeptide treatment. Cultures treated with GHRH (100 nM) exhibited a long term significant enhancement in ChAT activity throughout the culture period, whereas those treated with SRIF (50 nM) expressed a transient decline in ChAT activity. Videometric analysis showed that both neuropeptides enhanced neuronal aggregation, neuritic arborization and neuritic length. These findings lead us to suggest that GHRH and SRIF may provide neurotrophic signals important not only for neuronal proliferation and survival but also for cholinergic neuronal expression. Furthermore, we propose that GHRH possesses specific cholinotrophic properties, whereas SRIF may act as a general neurotrophic factor.
Effects of polyamine synthesis blockade on neuronal loss and astroglial reaction after transient forebrain ischemia
Authors: Zoli Michele , Zini Isabella , Grimaldi Roberta , Biagini Giuseppe , Agnati Luigi F.
Published: April 2003

Polyamines and ornithine decarboxylase, the polyamine biosynthetic enzyme, have been demonstrated to increase in the early phase of several types of brain lesion. However, their role in the pathogenesis of tissue damage is still debated. In the present paper the effects of treatments with α‐difluoromethylornithine, a suicide inhibitor of ornithine decarboxylase, have been investigated in a model of transient forebrain ischemia. Three treatment schedules were used: α‐difluoromethylornithine treatment was either started 3 hr before and repeated 1 hr after the insult, or started at the time of the insult and continued for 3 or 7 days after post‐ischemic reperfusion. The rats were sacrificed 4 hr, 7 or 40 days after reperfusion, respectively. The acute experiment demonstrated that α‐difluoromethylornithine can reduce the increase of glial fibrillary acidic protein immunoreactivity, an early marker of astroglial reaction, in ischemic striatum. Subchronic and chronic α‐difluoromethylornithine treatments induced a worsening of the morphological outcome of the ischemic lesion. In caudate‐putamen a trend for an increase of the area of neuronal loss was present after both treatments. In the hippocampal formation, a significant increase in the severity of neuronal lesion was observed in the mildly lesioned CA3 field. In addition, other alterations of lesioned tissue were observed in α‐difluoromethylornithine‐treated animals, including increases of non‐neuronal cells at 7 and especially 40 days post‐lesion in striatum and CA3 hippocampal field. In conclusion, present data indicate that ornithine decarboxylase activation after ischemic lesion is a crucial factor for survival of mildly lesioned neurons and proper tissue reaction to the ischemic lesion. The experiment on acute α‐difluoromethylornithine treatment suggests that these effects may be, at least in part, related to putrescine‐induced activation of astroglial cells in the early post‐lesion period.
Gene expression in astrocytes is affected by subculture
Authors: Passaquin Anne‐Catherine , Schreier Wayne A. , de Vellis Jean
Published: April 2003

We have investigated the effects of cell passaging and time in culture on astrocyte morphology, transferrin expression and the expression of two main astrocyte markers, glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS; EC 6.3.1.2). When primary astrocytes were subcultured, giving rise to secondary and tertiary cultures, their morphology changed, regardless of the split ratio used to passage the cells. Correlating with this morphological change, a dramatic increase in the accumulation of GFAP and GS mRNAs was observed after cells had been passaged. This effect was in marked contrast to the moderate increase in the levels of GFAP and GS mRNAs observed over several weeks in primary culture. Hydrocortisone induction of GS gene expression was not affected by cell passage. Transferrin mRNA, which is not normally found in astrocytes in vivo, was expressed at a high level in primary cultures of astrocytes. However, transferring mRNA almost completely disappeared after the second passage. Astrocyte‐conditioned media, or co‐cultures with oligodendrocytes, modified transferrin gene expression. Taken together, these results show that subculturing of primary rat astrocytes leads to a dramatic change in the genetic expression of several proteins and provides a new approach to modify astrocyte differentiation in vitro.
Membrane topology of CLN3, the protein underlying Batten disease
Authors: Mao Qinwen , Foster Brian J , Xia Haibin , Davidson Beverly L
Published: April 2003

Juvenile neuronal ceroid lipofuscinosis, or Batten disease, is an autosomal recessive disorder characterized by progressive loss of motor and cognitive functions, loss of vision, progressively severe seizures, and death. The disease is associated with mutations in the gene CLN3, which encodes a novel 438 amino acid protein, the function of which is currently unknown. Protein secondary structure prediction programs suggest that the CLN3 protein has five to seven membrane‐spanning domains (MSDs). To distinguish among a number of hypothetical models for the membrane topology of CLN3 we used in vitro translation of native, Flag epitope‐labeled and glycosylation site‐mutated CLN3 protein in the presence or absence of canine pancreatic microsomes. These were immunoprecipitated using antibodies specific for Flag or peptide sequences within CLN3 or left untreated. The results indicate that CLN3 contains five MSDs, an extracellular/intraluminal amino‐terminus, and a cytoplasmic carboxy‐terminus.
A new ratiometric fluorescence probe as strong sensor of surface charge of lipid vesicles and micelles
Authors: Singh Yashveer , Gulyani Akash , Bhattacharya Santanu
Published: April 2003

We report on the ability of a new fluorescent probe, 4‐(2‐pyren‐1‐yl‐vinyl) pyridine, 1, to respond to micelles and phospholipid vesicles of different surface charge. The probe gets incorporated into micellar and membranous assemblies and shows a large red‐shift in the fluorescence emission maxima especially when the surface charge of the organized media is anionic. The effect on the photo‐excitation of the probe is very clear and pronounced as it can be easily visualized. The sample color upon photo‐excitation changes from blue to orange/red once the probe experiences negatively charged vesicular or micellar surfaces. These results make the probe molecule useful as a reporter for sensing electrostatic environment in biological membranes and related organized assemblies.
TIP120A associates with unneddylated cullin 1 and regulates its neddylation
Authors: Hwang Ji-Won , Min Kyoeng-Woo , Tamura Taka-aki , Yoon Jong-Bok
Published: April 2003

The cullin‐containing E3 ubiquitin ligases play an important role in regulating the abundance of key proteins involved in cellular processes such as cell cycle and cytokine signaling. We recently identified TIP120A as a cullin‐interacting protein and found that TIP120A functions as a negative regulator of a ubiquitin ligase by interfering with the binding of Skp1 and an F box protein to CUL1. Here we show that TIP120A binds to the unneddylated CUL1 but not the neddylated one. The association of TIP120A with CUL1 requires both the N‐terminal stalk and the C‐terminal globular domain of CUL1. TIP120A efficiently inhibits neddylation of CUL1 but does not affect substrate‐independent ubiquitination by CUL1/Rbx1, implying that it blocks the access of Nedd8 to the conjugation site but does not interfere with the interaction of the ubiquitin‐conjugating enzyme with Rbx1. Our data suggest that the association/dissociation of TIP120A coupled to neddylation/deneddylation of CUL1 may play an important role in assembly and disassembly of Skp1‐Cdc53/cullin‐F box ubiquitin ligases.
Lifetime symptoms of depression in Alzheimer's disease
Authors: Reinhard Heun , Kockler Martin , Ptok Ursula
Published: April 2003

Introduction

Depression is common in Alzheimer's disease (AD). The symptomatology of depression in dementia may differ from depression alone. Consequently, the reports on lifetime depressive symptoms were compared in AD patients and age-matched non-demented participants.

Methods

Seventy-six AD patients, 109 elderly from the general population and their 189 siblings were examined using the Composite International Diagnostic Interview (CIDI). The presence of individual lifetime depressive symptoms was compared between 76 AD patients, 29 AD patients with comorbid depression, and different control groups using χ2 statistics and logistic regression analysis.

Results

Lifetime depressive symptoms were significantly more frequent in 76 AD patients than in 109 age-matched elderly from the general population. These 76 AD patients complained more about thinking and concentration disturbances, and less about depressed mood or appetite disturbance than the 298 non-demented participants matched for the lifetime presence of major depression (MD). In agreement, the 29 patients comorbid for lifetime diagnoses of AD and MD reported less about depressed mood than the 114 age-matched elderly with MD only. Feelings of worthlessness and suicidal ideas were related to the severity of cognitive decline.

Conclusions

AD influences the reports on lifetime depressive symptoms. This may be caused by additional neurodegeneration, by an overlap of symptoms of depression and dementia or by an altered perception of mood disturbances in AD. Further studies should investigate these alternatives.
Relationship between body-mass index and depressive symptoms in patients with major depression
Authors: Berlin Ivan , Lavergne Francis
Published: April 2003

Background

Appetite and weight changes are commonly occurring symptoms of depressive illness. The occurrence of these symptoms may not only be related to depressive mood but may also be related to body weight.

Aim

To examine the relationship between symptoms of depression and body weight.

Methods

Symptoms of depression were assessed by the Montgomery-Asberg depression rating scale (MADRS) in 1694 patients seeking medical help and fulfilling DSM-IV criteria for a major depressive episode. The level of anxiety was evaluated by Covi’s anxiety scale. Body weight was expressed as body-mass index (BMI, kg/m2) and treated both categorically and continuously.

Results

The total MADRS score was not statistically different across the four BMI categories (underweight: 32.3 ± 0.6, normal weight: 30.9 ± 0.2, grade 1: 30.6 ± 0.3, and 2 overweight: 30.6 ± 0.6, P = 0.053 (NS)). In women with BMI ≤ 18.5 kg/m2 MADRS was significantly higher than that in other BMI categories (underweight: 32.4 ± 0.6, normal weight: 30.6 ± 0.2, grade 1: 30.6 ± 0.4, and 2 overweight: 30.6 ± 0.6: P = 0.036). Increasing BMI was related to a linear decrease in symptoms “Reduced appetite” (P < 0.0001) and “Pessimistic thoughts” (P < 0.003). The presence of melancholic or atypical features was not associated with lower or higher BMI, respectively.

Conclusions

In patients with major depression higher body weight is likely to be associated with less reduction in appetite and less pessimistic thoughts.
Basal and exercise‐induced neuroendocrine activation in patients with heart failure and in normal subjects
Authors: Kjær Andreas , Appel Jon , Hildebrandt Per , Petersen Claus Leth
Published: April 2003

Background:

Neuroendocrine activation is a pathophysiological response and an important prognostic marker in patients with chronic heart failure (CHF). Although chronic activation is well described, data on the responsiveness of the hormone systems are more limited. Most previous studies have looked at activation during maximal exercise, whereas we believe that activation at a submaximal level might be more pathophysiologically relevant.

Aim:

To compare exercise‐induced neurohormonal activation between CHF patients and normal subjects using the same relative and submaximal workload.

Subjects:

Twenty‐three newly‐diagnosed CHF patients and 18 age‐ and gender‐matched healthy subjects were exercised at two workloads, which were calculated to correspond to 50 and 75% of each individual's heart rate response.

Results:

In CHF patients, baseline levels of ANP, BNP, AVP, PRA and ET‐1 were elevated compared to healthy subjects. Exercise induced an increase in ANP, A and NA in both CHF patients and in normal subjects, however BNP was only increased in CHF patients and not in normal subjects.

Conclusion:

When CHF patients exercise at the same relative and submaximal level as age‐matched healthy subjects, the relative increases in ANP, A and NA were similar, however, BNP levels only increased in the CHF group.
l-Serine in disease and development
Authors: de KONING Tom J. , SNELL Keith , DURAN Marinus , BERGER Ruud , POLL-THE Bwee-Tien , SURTEES Robert
Published: April 2003

The amino acid l-serine, one of the so-called non-essential amino acids, plays a central role in cellular proliferation. l-Serine is the predominant source of one-carbon groups for the de novo synthesis of purine nucleotides and deoxythymidine monophosphate. It has long been recognized that, in cell cultures, l-serine is a conditional essential amino acid, because it cannot be synthesized in sufficient quantities to meet the cellular demands for its utilization. In recent years, l-serine and the products of its metabolism have been recognized not only to be essential for cell proliferation, but also to be necessary for specific functions in the central nervous system. The findings of altered levels of serine and glycine in patients with psychiatric disorders and the severe neurological abnormalities in patients with defects of l-serine synthesis underscore the importance of l-serine in brain development and function. This paper reviews these recent insights into the role of l-serine and the pathways of l-serine utilization in disease and during development, in particular of the central nervous system.
Troponin C in different insect muscle types: identification of two isoforms in Lethocerus, Drosophila and Anopheles that are specific to asynchronous flight muscle in the adult insect
Authors: QIU Feng , LAKEY Anne , AGIANIAN Bogos , HUTCHINGS Amanda , BUTCHER Geoffrey W. , LABEIT Siegfried , LEONARD Kevin , BULLARD Belinda
Published: April 2003

The indirect flight muscles (IFMs) of Lethocerus (giant water bug) and Drosophila (fruitfly) are asynchronous: oscillatory contractions are produced by periodic stretches in the presence of a Ca2+ concentration that does not fully activate the muscle. The troponin complex on thin filaments regulates contraction in striated muscle. The complex in IFM has subunits that are specific to this muscle type, and stretch activation may act through troponin. Lethocerus and Drosophila have an unusual isoform of the Ca2+-binding subunit of troponin, troponin C (TnC), with a single Ca2+-binding site near the C-terminus (domain IV); this isoform is only in IFMs, together with a minor isoform with an additional Ca2+-binding site in the N-terminal region (domain II). Lethocerus has another TnC isoform in leg muscle which also has two Ca2+-binding sites. Ca2+ binds more strongly to domain IV than to domain II in two-site isoforms. There are four isoforms in Drosophila and Anopheles (malarial mosquito), three of which are also in adult Lethocerus. A larval isoform has not been identified in Lethocerus. Different TnC isoforms are expressed in the embryonic, larval, pupal and adult stages of Drosophila; the expression of the two IFM isoforms is increased in the pupal stage. Immunoelectron microscopy shows the distribution of the major IFM isoform with one Ca2+-binding site is uniform along Lethocerus thin filaments. We suggest that initial activation of IFM is by Ca2+ binding to troponin with the two-site TnC, and full activation is through the action of stretch on the complex with the one-site isoform.
The mitochondria-associated endoplasmic-reticulum subcompartment (MAM fraction) of rat liver contains highly active sphingolipid-specific glycosyltransferases
Authors: ARDAIL Dominique , POPA Iuliana , BODENNEC Jacques , LOUISOT Pierre , SCHMITT Daniel , PORTOUKALIAN Jacques
Published: April 2003

Although most glycosphingolipids (GSLs) are thought to be located in the outer leaflet of the plasma membrane, recent evidence indicates that GSLs and their precursor, ceramide, are also associated with intracellular organelles and, particularly, mitochondria. GSL biosynthesis starts with the formation of ceramide in the endoplasmic reticulum (ER), which is transported by controversial mechanisms to the Golgi apparatus, where stepwise addition of monosaccharides on to ceramides takes place. We now report the presence of GSL-biosynthetic enzymes in a subcompartment of the ER previously characterized and termed ‘mitochondria-associated membrane’ (MAM). MAM is a membrane bridge between the ER and mitochondria that is involved in the biosynthesis and trafficking of phospholipids between the two organelles. Using exogenous acceptors coated on silica gel, we demonstrate the presence of ceramide glucosyltransferase (Cer-Glc-T), glucosylceramide galactosyltransferase and sialyltransferase (SAT) activities in the MAM. Estimation of the marker-enzyme activities showed that glycosyltransferase activities could not be ascribed to cross-contamination of MAM by Golgi membranes. Cer-Glc-T was found to have a marked preference for ceramide bearing phytosphingosine as sphingoid base. SAT activities in MAM led to the synthesis of GM3 ganglioside and small amounts of GD3. GM1 was also synthesized along with GM3 upon incubation of the fraction with exogenous unlabelled GM3, underlying the presence of other sphingolipid-specific glycosyltransferases in MAM. On the basis of our results, we propose MAM as a privileged compartment in providing GSLs for mitochondria.
Specificity of S'1 and S'2 subsites of human tissue kallikrein using the reactive-centre loop of kallistatin: the importance of P'1 and P'2 positions in design of inhibitors
Authors: PIMENTA Daniel C. , FOGAÇA Sandro E. , MELO Robson L. , JULIANO Luiz , JULIANO Maria A.
Published: April 2003

We have demonstrated that the S´1 and S´2 subsites of human tissue kallikrein (hK1) play determinant roles in the recognition and hydrolysis of substrates. The presence of serine at position P´1 and arginine at P´2 resulted in the best substrate, Abz-Ala-Ile-Lys-Phe-Phe-Ser-Arg-Gln-EDDnp, which was derived from the kallistatin reactive-centre loop sequence and quencher groups o-aminobenzoic acid (Abz) and N-(2,4-dinitrophenyl)ethylenediamine (EDDnp). Serine and arginine are also the residues at positions P´1 and P´2 in human kininogen, from which hK1 releases Lys-bradykinin. Several peptide analogues of Abz-Ala-Ile-Lys-Phe-Phe-Ser-Arg-Gln-EDDnp, in which the Ser and Arg residues were substituted with various other amino acids, were synthesized and tested as substrates. Most of them were hydrolysed slowly, although they showed significant binding to hK1, as demonstrated by their competitive inhibition constants (Ki). Using this information, six peptides were designed, synthesized and assayed as inhibitors of hK1. Abz-Lys-Phe-Phe-Pro-Arg-Gln-EDDnp, Abz-Lys-Phe-Arg-Pro-Arg-Gln-EDDnp and acetyl-Lys-Phe-Phe-Pro-Leu-Glu-NH2 inhibited hK1 in the range 20–30 nM (letters in italics denote the d-form of the amino acid). The peptide acetyl-Lys-Phe-Phe-Pro-Leu-Glu-NH2 was a weak inhibitor for other serine proteases, as indicated by the higher Ki values compared with hK1, but this peptide was a potent inhibitor of human plasma kallikrein, which has a Ki value of 8 nM. This result was surprising, since this enzyme is known to be a restricted arginyl-hydrolase. In conclusion, acetyl-Lys-Phe-Phe-Pro-Leu-Glu-NH2 can be used as a leader compound to design specific inhibitors for hK1, plasma kallikrein, or for both at same time, if the inhibition of kinin release is the main goal.
Nonlinear waves and structures in dusty plasmas
Authors: Shukla P. K.
Published: April 2003

Recent laboratory observations conclusively reveal that coherent nonlinear waves and structures (viz., solitons, shocks, Mach cones, voids, vortices, etc.) can be produced in a dusty plasma. Our objective here is to describe the underlying physics, mathematical details, and salient features of dust ion-acoustic as well as dust acoustic solitary and shock waves, dust voids, and dust vortex flows. It is shown that the presence of charged dust grains introduces new features to the nonlinear electrostatic waves and structures. Consideration of the dust charge fluctuation dynamics causes a novel dissipation, which is responsible for the formation of dust ion-acoustic shock waves. Furthermore, the formation of a dust void is associated with double layers and ion holes arising from trapped ion effects. Finally, a nonlinear model for dust vortex flows is presented. It is shown that the dynamics of dust vortex flows in a plasma is governed by a modified Navier–Stokes equation (MNSE), and that possible stationary solutions of the MNSE can be represented as monopolar as well as a row of identical and a row of counter-rotating vortices. The implications of our theoretical results/models to experimental observations of solitary and shock waves as well as of voids and vortices are discussed.
Dependence of burn-in effect on thermal annealing of the GaAs:C base layer in GaInP heterojunction bipolar transistors
Authors: Mimila-Arroyo J. , Cabrera V. , Bland S. W.
Published: April 2003

We investigate in situ thermal annealing of the carbon-doped GaAs base layer in GaInP/GaAs heterojunction bipolar transistors grown by metalorganic chemical vapor deposition in order to eliminate hydrogen incorporation. The influence of the anneal on the carrier transport properties and on the burn-in effect is studied. Results show that the anneal reduces the burn-in effect due to an increase in the emitter minority carrier diffusion length which is caused by passivation of H+ recombination centers in the GaInP emitter layer. However, the anneal also degrades the base minority carrier diffusion length leading to a reduction in the current gain.
Avalanche multiplication due to impact ionization in quantum-well infrared photodetectors: A quantitative approach
Authors: Rehm Robert , Schneider Harald , Walther Martin , Koidl Peter , Weimann Günter
Published: April 2003

We investigate the influence of avalanche multiplication by impact ionization on the photoconductive gain and the noise gain in quantum-well infrared photodetectors (QWIPs). A quantitative method is presented allowing the avalanche multiplication factor M and its field dependence to be determined from the measured photoconductive gain and noise gain. The approach is demonstrated using an In0.30Ga0.70As/GaAs QWIP.
A minimum setup strategy for sequencing PCBs with multi‐slot feeders
Authors: Chen Wei‐Shing , Chyu Chiuh‐Cheng
Published: April 2003

This paper considers the decision problem for a minimum setup strategy of a production system arising in the assembly of printed circuit boards of different types, using a placement machine with multi‐slot feeders. We formulate the problem as a binary linear programming model, and propose a heuristic procedure to find the solution that consists of a board‐assembly sequence, an associated component loading and unloading strategy and a feeder‐assignment plan within reasonable computational effort. Computational results from solving the simulated problem instances by using the heuristic method and the mathematical model are provided and compared. The proposed heuristic procedure can be incorporated into the PCB scheduling optimization software to decrease cycle times and increase overall assembly throughput in a high‐mix, low‐volume PCB manufacturing environment.
Enhancing manufacturing operations effectiveness through knowledge based design
Authors: Chandra Charu , Kumar Sameer
Published: April 2003

Global competition has pushed firms to improve and upgrade their manufacturing operations continuously. Explores the role of knowledge base and learning to facilitate this phenomenon. Developing a knowledge base requires organising knowledge and expertise for a field of inquiry and making it available in formats suitable for users to support and aid various operational, developmental, and organisational functions. Classification and coding form the basis for organising knowledge bases. Classification implies grouping objects into similar classes on the basis of some similarity criteria pertinent to one or more attributes. Learning in the context of classification implies discovering new attributes, bases for grouping and requires frequent updating of the knowledge base. A formal knowledge base makes a firm’s knowledge cumulative and serves an important integrating and coordinating role for the organisation. Presents an example application utilizing classification as a tool for knowledge acquisition in design support activities.
How to choose an ASP: selection guidelines
Authors: Focacci Luisa , Mockler Robert J. , Gartenfeld Marc E. , Dologite Dorothy G.
Published: April 2003

The great promise of software‐as‐a‐service lies in its ability to deliver at a much lower cost and at much greater speed. In the future, software will be delivered in such a way that business customers can pick and choose entire applications or parts of them, paying on a per‐use or subscription basis. To fulfill this need, a new type of business enterprise has arisen, application service providers (ASPs). This paper identifies various success factors, or best practices selection guidelines, potential ASP customers/users should consider when choosing an ASP. These success factors were developed – using experiences of successful ASPs presented in groups based on their underlying business models – from customer requirements, a major driver in the ASP market.
Energy‐dependent degradation: Linkage between ClpX‐catalyzed nucleotide hydrolysis and protein‐substrate processing
Authors: Burton Randall E. , Baker Tania A. , Sauer Robert T.
Published: April 2003

ClpX requires ATP to unfold protein substrates and translocate them into the proteolytic chamber of ClpP for degradation. The steady‐state parameters for hydrolysis of ATP and ATPγS by ClpX were measured with different protein partners and the kinetics of degradation of ssrA‐tagged substrates were determined with both nucleotides. ClpX hydrolyzed ATPγS to ADP and thiophosphate at a rate (6/min) significantly slower than ATP hydrolysis (140/min), but the hydrolysis of both nucleotides was increased by ssrA‐tagged substrates and decreased by ClpP. KM and kcat for hydrolysis of ATP and ATPγS were linearly correlated over a 200‐fold range, suggesting that protein partners largely affect kcat rather than nucleotide binding, indicating that most bound ATP leaves the enzyme by hydrolysis rather than dissociation, and placing an upper limit of ≈15 μM on KD for both nucleotides. Competition studies with ClpX and fluorescently labeled ADP gave inhibition constants for ATPγS (≈2 μM) and ADP (≈3 μM) under the reaction conditions used for steady‐state kinetics. In the absence of Mg2+, where hydrolysis does not occur, the inhibition constant for ATP (≈55 μM) was weaker but very similar to the value for ATPγS (≈45 μM). Compared with ATP, ATPγS supported slow but roughly comparable rates of ClpXP degradation for two Arc‐ssrA substrates and denatured GFP‐ssrA, but not of native GFP‐ssrA. These results show that the processing of protein substrates by ClpX is closely coupled to the maximum rate of nucleotide hydrolysis.
Maximum Bladed Disk Forced Response From Distortion of a Structural Mode
Authors: Kenyon J. A. , Griffin J. H. , Feiner D. M.
Published: April 2003

A method is presented for obtaining maximum bladed disk forced response from distortion of a structural mode. It is shown that maximum response from mode distortion in a bladed disk occurs when the harmonic components of a distorted mode superimpose in a certain manner, causing localization of the mode and strong response in a particular blade. In addition, it is shown that the response of an intentionally mistuned system with maximum response does not change significantly when small random mistuning is added to the system. A method is described for calculating the structural mistuning necessary to obtain the distorted mode that gives maximum response. The theory is validated numerically.
Balancing Selection at the Prion Protein Gene Consistent with Prehistoric Kurulike Epidemics
Authors: Mead Simon , Stumpf Michael P. H. , Whitfield Jerome , Beck Jonathan A. , Poulter Mark , Campbell Tracy , Uphill James B. , Goldstein David , Alpers Michael , Fisher Elizabeth M. C. , Collinge John
Published: April 2003

Kuru is an acquired prion disease largely restricted to the Fore linguistic group of the Papua New Guinea Highlands, which was transmitted during endocannibalistic feasts. Heterozygosity for a common polymorphism in the human prion protein gene (
PRNP
) confers relative resistance to prion diseases. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are, in marked contrast to younger unexposed Fore, predominantly
PRNP
129 heterozygotes. Kuru imposed strong balancing selection on the Fore, essentially eliminating
PRNP
129 homozygotes. Worldwide
PRNP
haplotype diversity and coding allele frequencies suggest that strong balancing selection at this locus occurred during the evolution of modern humans.