bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired Time Perception in Patients with Chronic Headache
Authors: Isler Hansreudi , Solomon Seymour , Spielman Arthur J. , Wittlieb‐Verpoort Elke
Published: June 2005

SYNOPSIS

The retrospective estimation of duration of an event appears to depend upon the amount of information processed within a given interval. Little information processing leads to under‐estimation of duration while an increase in the amount of information processed raises the duration estimate of the interval. During chronic recurring headache, patients usually exhibit automatic responses directed toward avoiding stress in general and sensory stimulation in particular. This reduction of information processing would be expected to lead to under‐estimation of duration of the headache. When headache free, the estimates of duration should increase. These hypotheses were tested in three experiments. In the first experiment, 38 patients with primary headache (migraine, muscle contraction, or mixed headaches) were asked to estimate the duration of a respiratory biofeedback session. Patients with headache at the time of the session gave significantly lower estimates of the duration of the session than patients without headache. The second experiment was similar to the first, but used electromyographic (EMG) biofeedback in 44 patients. Those patients with headache again tended to underestimate the du ration of the biofeedback session to a greater degree than patients without symptoms. A third experiment with 23 primary headache patients showed a tendency to overestimate the duration of a reading task during headache free intervals as compared with 30 normal controls. The perceived shortened duration of an experience during headache may have clinical implications. Normal time perspective, which usually shortens the subjective duration of previous events, may be enhanced by this additional bias. The perception of much shorter intervals between past drug intake and headache relief would tend to create the impression of loss of drug efficiency for the present headache, leading to increased frequency and dosage of medication. The misperceived shortening of the latencies of therapeutic effect in previous headaches may be one of the causes of drug abuse.
Growth and Lipid Metabolism in Girls and Young Women with Epilepsy during Pubertal Maturation
Authors: Mikkonen Kirsi , Knip Mikael , Pakarinen Arto J. , Lanning Peter , Isojärvi Jouko I. T. , Vainionpää Leena K.
Published: June 2005

Summary:  Purpose: To assess growth and the serum lipid profile in girls with epilepsy receiving monotherapy at a mean age of 12.6 years and approximately 6 years later.

Methods: A population‐based cohort of 77 girls with epilepsy and 49 healthy controls participated in this follow‐up study including two cross‐sectional evaluations (age range, 8–18.5 years on the first evaluation, and 12.5–25.8 years on the second evaluation). Forty of the patients were initially taking valproate (VPA), 19, carbamazepine (CBZ), and 18, oxcarbazepine (OXC). Growth data were compiled, body mass index (BMI) was calculated, and serum total (TC), and high‐density lipoprotein (HDL‐C) and low‐density lipoprotein (LDL‐C) cholesterol and triglyceride concentrations were analyzed.

Results: Linear growth and final height did not differ between the patients and the controls. At follow‐up, the mean BMI of the patients who were off medication (61%) was similar to that of the controls, whereas the patients initially treated with VPA who were still taking any medication had a higher BMI. On the first evaluation, the patients taking VPA had low serum HDL‐C, and those taking CBZ or OXC had high serum TC and LDL‐C concentrations. At follow‐up, serum lipid levels were similar in the patients off medication and the controls.

Conclusions: Neither epilepsy nor antiepileptic therapy affects linear growth or final height, but they may have unfavorable effects on body weight and serum lipid concentrations. Lipid‐profile impairment seems to be transient if the medication is discontinued. Overweight is common in patients treated with VPA during puberty if epilepsy and medication continue into adulthood.
Retinal Electrophysiological Results in Patients Receiving Lamotrigine Monotherapy
Authors: Arndt Carl F. , Husson Jeremie , Derambure Philippe , Hache Jean Claude , Arnaud Bernard , Defoort‐Dhellemmes Sabine
Published: June 2005

Summary:  Purpose: To evaluate the effects on vision in patients receiving lamotrigine (LTG) monotherapy.

Methods: Twenty‐four consecutive patients taking LTG for partial seizures were referred for a routine ophthalmologic examination including visual acuity testing, tonometry, slit lamp, and fundus examination. Automated kinetic perimetry, electrooculogram (EOG), and electroretinogram were performed after informed consent was obtained.

Results: In 18 patients finally included, the clinical ophthalmologic examination showed no abnormality. Four patients complained of blurring; among them, one patient had a visual field constriction in both eyes, which, however, was of unclear clinical significance (poor compliance) and a reduced light/dark ratio of the electrooculogram. One other patient with blurred vision had a reduced EOG, but the visual field was normal. Two patients had a reduced EOG but no visual symptoms. Considering the whole group of patients receiving LTG therapy, the light/dark ratio of the EOG was reduced in a dose‐dependent fashion (p < 0.0001). The electroretinogram was normal in all patients.

Conclusions: No irreversible visual field impairment in patients treated with LTG was encountered, although a dose‐dependent retinal toxicity may have been present. The exact cellular mechanism of the electrophysiologic changes in patients taking LTG remain to be explained.
Morphologic and Neurochemical Abnormalities in the Auditory Brainstem of the Genetically Epilepsy‐prone Hamster (GPG/Vall)
Authors: Fuentes‐Santamaría Verónica , Cantos Raquel , Alvarado Juan Carlos , García‐Atarés Natividad , López Dolores E.
Published: June 2005

Summary:  Purpose: This study was performed to evaluate whether audiogenic seizures, in a strain of genetically epilepsy‐prone hamsters (GPG/Vall), might be associated with morphologic alterations in the cochlea and auditory brainstem. In addition, we used parvalbumin as a marker of neurons with high levels of activity to examine changes within neurons.

Methods: Cochlear histology as well as parvalbumin immunohistochemistry were performed to assess possible abnormalities in the GPG/Vall hamster. Densitometry also was used to quantify levels of parvalbumin immunostaining within neurons and fibers in auditory nuclei.

Results: In the present study, missing outer hair cells and spiral ganglion cells were observed in the GPG/Vall hamster. In addition, an increase was noted in the size of spiral ganglion cells as well as a decrease in the volume and cell size of the cochlear nucleus (CN), the superior olivary complex nuclei (SOC), and the nuclei of the lateral lemniscus (LL) and the inferior colliculus (IC). These alterations were accompanied by an increase in levels of parvalbumin immunostaining within CN, SOC, and LL neurons, as well as within parvalbumin‐immunostained fibers in the CN and IC.

Conclusions: These data are consistent with a cascade of atrophic changes starting in the cochlea and extending along the auditory brainstem in an animal model of inherited epilepsy. Our data also show an upregulation in parvalbumin immunostaining in the neuropil of the IC that may reflect a protective mechanism to prevent cell death in the afferent sources to this nucleus.
Adenoid cystic carcinoma of maxillary sinus with metastatic hepatocellular carcinoma
Authors: SATAKE NOBUO , YOSHIDA SEIJI , JINNOUCHI OSAMU , SEKITA TAKUMA
Published: June 2005

A case of collision tumor in the left maxillary sinus composed of adenoid cystic carcinoma (ACC) and metastatic hepatocellular carcinoma (HCC) is reported. Radiographic examination revealed masses in the liver and bilateral lung metastases. Histologically, proliferation of tumor cells with resemblance to HCC was observed, in addition to the ACC. For this reason, differential diagnosis between a second primary tumor and metastasis was made. The metastatic lesion immunohistochemically showed positivity for hepatocyte antigen (OCH1E5) and protein induced by vitamin K absence or antagonist II (PIVKA‐II), sustaining the HCC diagnosis. Primary ACC and metastatic HCC in the maxillary sinus are rare, and this may therefore be the first case of maxillary sinus tumor with both these elements.
Pathological and clinical significance of increased intraepithelial lymphocytes (IELs) in small bowel mucosa
Authors: CHANG FUJU , MAHADEVA ULA , DEERE HARRIET
Published: June 2005

Intestinal intraepithelial lymphocytes (IELs) belong to a unique T‐cell population interspersed between epithelial cells of both the small and large intestine. It is becoming increasingly recognised that an increased number of IELs with a normal villous architecture is within the wide spectrum of histological abnormalities observed in coeliac disease. An increased number of IELs is the earliest pathological change following gluten challenge and a high IEL count may be the only sign of gluten sensitivity. Therefore, the finding of a raised IEL count with normal villous architecture is of sufficient clinical importance to be reported in routine small bowel biopsies. However, it is evident that not all small intestinal biopsy specimens showing increased IELs are explained by gluten sensitivity. Increased IELs in small bowel mucosa have also been associated with autoimmune disorders, tropical sprue, food protein intolerance, Helicobacter pylori‐associated gastritis, peptic duodenitis, parasitic and viral infections, as well as the development of intestinal lymphoma. Histological examination of a biopsy specimen of the small bowel remains the diagnostic gold standard for coeliac disease. There will be an ever increasing demand for histological confirmation of gluten sensitivity in patients in whom the classic microscopic appearance of flattened villi may not have fully developed. The more widespread recognition by histopathologists of the pattern of injury manifested by increased numbers of IELs in intestinal biopsy specimens will certainly help in early diagnosis of coeliac disease, lessen diagnostic confusion and influence the modern practice of gastrointestinal tract medicine. This review discusses some of the recent developments in clinical pathology pertaining to increased IELs in small bowel mucosal biopsies.
Carcinosarcoma of the parotid gland: an unusual case with large‐cell neuroendocrine carcinoma and rhabdomyosarcoma
Authors: UEO T. , KAKU N. , KASHIMA K. , DAA T. , KONDO Y. , YOSHIDA K. , SUZUKI M. , YOKOYAMA S.
Published: June 2005

We report a case of carcinosarcoma of the parotid gland in a 72‐year‐old Japanese man. The patient noticed a rapidly enlarging hard mass in the right parotid gland. He underwent radical parotidectomy with cervical lymph node dissection. The resected tumor measured 3.5×4.5 cm and histopathologically showed carcinomatous and sarcomatous components. The carcinomatous component consisted of large‐cell neuroendocrine carcinoma (LCNEC), squamous cell carcinoma and adenocarcinoma not otherwise specified, while the sarcomatous component included spindle cell sarcoma not otherwise specified, so‐called myxosarcoma and rhabdomyosarcoma. The LCNEC component was predominant within the whole tumor. The diagnoses of LCNEC and rhabdomyosarcoma were also confirmed immunohistochemically. With regard to histopathogenesis, based on the lack of histopathological evidence and antecedent history of pleomorphic adenoma, we considered the present case to be de novo, not expleomorphic adenoma.
Effectiveness of periodontal therapy on the severity of cyclosporin A‐induced gingival overgrowth
Authors: Aimetti Mario , Romano Federica , Debernardi Cesare
Published: June 2005

Aim: The purpose of the present study was to evaluate the clinical effects of aetiological periodontal treatment in a group of transplant patients medicated with cyclosporin A (CsA) who exhibited severe gingival overgrowth.

Materials and Methods: Twenty‐one patients received oral hygiene instructions, supra‐ and subgingival scaling and periodontal maintenance therapy and were monitored for 12 months. Full‐mouth plaque score (FMPS), full‐mouth bleeding score (FMBS), periodontal probing depth and degree of gingival overgrowth (Seymour index GO) were recorded at baseline, 6 and 12 months after treatment.

Results: Statistical evaluation revealed that all clinical variables significantly decreased compared with baseline. At baseline 18 out of 21 treated patients (85.71%) exhibited clinically significant overgrowth. Initial GO score of 2.38±1.92 in the anterior sextants and of 1.29±1.59 in the posterior segments were reduced to 0.56±0.83 and to 0.45±0.84 at 12 months (p<0.001). A difference of 1.82 and 0.84 in the severity of treated GO was accompained by a 42% and 34% decrease in FMPS and FMBS, respectively.

Conclusions: Aetiological periodontal treatment and regular maintenance therapy were effective in resolving the inflammation and in eliminating the need for surgical treatment in patients receiving CsA.
Prevalence of periodontal pathogens in Brazilians with aggressive or chronic periodontitis
Authors: Cortelli Jose R. , Cortelli Sheila Cavalca , Jordan Shawn , Haraszthy V. I. , Zambon J. J.
Published: June 2005

Objectives: Previous studies suggest differences between geographically and racially distinct populations in the prevalence of periodontopathic bacteria as well as greater periodontal destruction associated with infection by highly leucotoxic Actinobacillus actinomycetemcomitans. The present study examined these hypotheses in Brazilians with aggressive or chronic periodontitis.

Materials and Methods: Clinical, radiographical, and microbiological assessments were performed on 25 aggressive periodontitis and 178 chronic periodontitis patients including 71 males and 132 females, 15–69 years of age.

Results: The prevalence of Porphyromonas gingivalis was similar to that of other South American populations. The prevalence of A. actinomycetemcomitans and its highly leucotoxic subgroup was higher in Brazilians. Highly leucotoxic A. actinomycetemcomitans was more prevalent in aggressive periodontitis (χ2=27.83) and positively associated with deep pockets (>6 mm, χ2=18.26) and young age (<29 years, χ2=18.68). Greater mean attachment loss was found in subjects with highly leucotoxic A. actinomycetemcomitans than in subjects with minimally leucotoxic (p=0.0029) or subjects not infected (p=0.0001).

Conclusion: These data support the hypothesis of differences between populations in the prevalence of periodontopathic bacteria and of greater attachment loss in sites infected with highly leucotoxic A. actinomycetemcomitans. Detection of highly leucotoxic A. actinomycetemcomitans in children and adolescents may be a useful marker for aggressive periodontitis.
The effect of quitting smoking on chronic periodontitis
Authors: Preshaw P. M. , Heasman L. , Stacey F. , Steen N. , McCracken G. I. , Heasman P. A.
Published: June 2005

Objectives: To evaluate longitudinally the effect of smoking cessation on clinical and radiographic outcomes following non‐surgical treatment in smokers with chronic periodontitis.

Material and Methods: Forty‐nine smokers with chronic periodontitis who wished to quit smoking were recruited. Full‐mouth probing depths, bleeding and plaque data were recorded at baseline, 3, 6 and 12 months. Clinical attachment levels were recorded at target sites and subtraction radiography was used to assess bone density changes. Patients received non‐surgical periodontal therapy during the first 3 months and supportive periodontal care over the remainder of the study. Smoking cessation counselling was provided according to individual need.

Results: After 12 months, of patients with complete data, 10 had continuously quit smoking (20% of the original population), 10 continued smoking and six were oscillators (those patients who quit and then relapsed). There were no differences between the groups following treatment with respect to mean clinical or radiographic parameters. Analysis of probing depth reductions between baseline and month 12, however, and comparing quitters with the other two groups combined, demonstrated a significant difference in favour of quitters (p<0.05). Furthermore, quitters were significantly more likely to demonstrate probing depth reductions 2 and 3 mm than non‐quitters and oscillators (p<0.05).

Conclusion: Quitting smoking has an additional beneficial effect in reducing probing depths following non‐surgical treatment over a 12‐month period.
Short‐term anti‐plaque effect of two chlorhexidine varnishes
Authors: Cosyn Jan , Wyn Iris , De Rouck Tim , Collys Kris , Bottenberg Peter , Matthijs Stefan , Moradi Sabzevar Mehran
Published: June 2005

Background: Chlorhexidine (CHX) varnishes have been mainly used for the prevention of caries in high‐risk populations. Reports regarding their anti‐plaque effect on a clinical level are limited to non‐existing as opposed to their microbiological impact on plaque formation.

Aim: The aim of this preliminary investigation was to evaluate the anti‐plaque effect of two CHX varnishes applied on sound enamel in relation to a positive control, a negative control and to one another.

Methods: Sixteen healthy subjects volunteered for this randomized‐controlled, single‐blind, four‐treatment–four‐period crossover‐designed clinical trial. A 3‐day plaque re‐growth model was used to determine de novo plaque accumulation following CHX rinsing, Cervitec® application, EC40® application and no therapy. The amount of plaque was measured using the Quigley and Hein plaque index and “automatic image analysis” (AIA).

Results and Conclusions: Varnish treatment resulted in significantly higher plaque levels than CHX rinsing irrespective of the varnish that was used (p0.002), implying that the latter is likely to remain the gold standard as an anti‐plaque agent. However, highly significant differences were also found in favour of both varnish systems when compared with no therapy (p<0.001), which indicates that varnish treatment is an effective means of inhibiting plaque formation in a short time span. Cervitec® exhibited slightly, yet significantly, higher plaque levels in comparison with EC40® as determined by AIA (p=0.006). Large‐scale trials with a longer observation period are necessary to substantiate these results.
Protein Sorting to the Storage Vacuoles of Plants: A Critical Appraisal
Authors: Robinson David G. , Oliviusson Peter , Hinz Giselbert
Published: June 2005

The vacuole of plant cells is no longer considered to be a single compartment with multifunctional properties. A lot of evidence now points to the presence of multiple functionally distinct vacuolar compartments, some existing side by side in the same cell. As a consequence, the plant Golgi apparatus is faced with the problem of recognizing proteins destined for lytic and storage vacuoles and segregating them individually from the flow of secretory proteins to the cell surface. In contrast to acid hydrolases, which are sorted by BP‐80‐like receptors at the trans‐Golgi of plant cells, the identification of receptors for storage proteins has in many ways resembled ‘the search for the Holy Grail’. There are several candidates for storage protein receptors, but in no single case is the evidence entirely convincing. Much of the problem lies in the lack of consensus, sorting sequences in the proteins investigated. Other difficulties stem from ‘out‐of‐context’ heterologous expression studies. Evidence is now accumulating for the participation of hydrophobic sequences in inducing the formation of protein aggregates in the early Golgi apparatus, for which classical sorting receptors do not appear to be necessary. This review critically examines the current situation and contrasts the differences between data obtained in situ and data obtained transgenically. It highlights the so‐called ‘dense‐vesicle’ pathway and culminates with a discussion on the hitherto neglected problem of the intracellular transport of storage protein processing enzymes.
Akt Regulates the Subcellular Localization of the Rab27a‐Binding Protein JFC1 by Phosphorylation
Authors: Johnson Jennifer L. , Pacquelet Sandrine , Lane William S. , Eam Boreth , Catz Sergio D.
Published: June 2005

Here, we show that the Rab27a‐binding protein JFC1/Slp1 (synaptotagmin‐like protein) is regulated by Akt‐mediated phosphorylation. Using the phosphatase and tensin homolog‐null LNCaP cells and the phosphatidylinositol 3‐kinase inhibitor LY294002, we show that the phosphorylation of endogenous JFC1 is dependent on the phosphatidylinositol 3‐kinase/Akt pathway. JFC1 was phosphorylated in cells expressing a constitutively active Akt, confirming that it is an Akt substrate in vivo. Direct phosphorylation of JFC1 by Akt was confirmed in vitro. Using microcapillary high‐performance liquid chromatography tandem mass spectrometry, we identified five Akt‐phosphorylation sites in JFC1. By mutagenesis analysis and subsequent immunoprecipitation (IP), we established that Akt phosphorylates JFC1 at serine 241. JFC1 and Rab27a colocalize in the proximity of the plasma membrane in LNCaP cells. The interaction was confirmed by IP analysis and was abolished by the point mutation W83S in JFC1. Phosphorylation did not alter the ability of JFC1 to bind to Rab27a. Instead, phosphorylation by Akt dramatically decreased when JFC1 was bound to Rab27a. Finally, we show that as a consequence of in vivo phosphorylation, JFC1 dissociates from the membrane, promoting JFC1 redistribution to the cytosol. Our results suggest that Akt regulates JFC1/Slp1 function by phosphorylation and may have implications on Rab27a‐containing vesicle secretion.
CeVPS‐27 is an Endosomal Protein Required for the Molting and the Endocytic Trafficking of the Low‐Density Lipoprotein Receptor‐Related Protein 1 in Caenorhabditis elegans
Authors: Roudier Nathalie , Lefebvre Christophe , Legouis Renaud
Published: June 2005

Class E vacuolar protein‐sorting (Vps) proteins were first described in yeast as being involved in receptor‐mediated endocytosis and multivesicular body formation. Inactivation by RNA interference of the class E VPS genes of the nematode Caenorhabditis elegans revealed heterogeneous phenotypes. We have further characterized the role of the essential gene Cevps‐27, ortholog of human hepatocyte growth factor‐regulated tyrosine kinase substrate, during the development of C. elegans. Use of green fluorescent protein fusion constructs and antibody staining revealed that Cevps‐27 localizes to endosomal membranes. It is widely expressed but enriched in epithelial cells. Cevps‐27 mutants presented enlarged endosomal structures and an accumulation of autophagic vesicles as revealed by electron microscopy and the analysis of the autophagic marker LGG‐1. Cevps‐27 animals arrested at L2‐L3 molt with an inability to degrade their old cuticle. This molting phenotype was more severe when Cevps‐27 worms were grown on suboptimal concentrations of cholesterol. Furthermore, defective endocytic trafficking of the low‐density lipoprotein receptor‐related protein 1 (LRP‐1) was also observed in Cevps‐27 mutants. These results indicate that CeVPS‐27 is required for endosomal and autophagic pathways in C. elegans and plays a crucial role in the control of molting through LRP‐1 internalization and cholesterol traffic.
Association of vasopressin 1a receptor levels with a regulatory microsatellite and behavior
Authors: Hammock E. A. D. , Lim M. M. , Nair H. P. , Young L. J.
Published: June 2005

Vasopressin regulates complex behaviors such as anxiety, parenting, social engagement and attachment and aggression in a species‐specific manner. The capacity of vasopressin to modulate these behaviors is thought to depend on the species‐specific distribution patterns of vasopressin 1a receptors (V1aRs) in the brain. There is considerable individual variation in the pattern of V1aR binding in the brains of the prairie vole species, Microtus ochrogaster. We hypothesize that this individual variability in V1aR expression levels is associated with individual variation in a polymorphic microsatellite in the 5′ regulatory region of the prairie vole v1ar gene. Additionally, we hypothesize that individual variation in V1aR expression contributes to individual variation in vasopressin‐dependent behaviors. To test these hypotheses, we first screened 20 adult male prairie voles for behavioral variation using tests that measure anxiety‐related and social behaviors. We then assessed the brains of those animals for V1aR variability with receptor autoradiography and used polymerase chain reaction to genotype the same animals for the length of their 5′ microsatellite polymorphism in the v1ar gene. In this report, we describe the results of this discovery‐based experimental approach to identify potential gene, brain and behavior interrelationships. The analysis reveals that V1aR levels, in some but not all brain regions, are associated with microsatellite length and that V1aR levels in those and other brain regions correlate with anxiety‐related and social behaviors. These results generate novel hypotheses regarding neural control of anxiety‐related and social behaviors and yield insight into potential mechanisms by which non‐coding gene polymorphisms may influence behavioral traits.
FINITE SEMIGROUPS WITH INFINITE IRREDUNDANT IDENTITY BASES
Authors: JACKSON MARCEL
Published: June 2005

We give the first examples of finite semigroups whose identities have infinite irredundant bases.
ALL DISCRETE $\mathcal{RP}$ GROUPS WHOSE GENERATORS HAVE REAL TRACES
Authors: KLIMENKO ELENA , KOPTEVA NATALIA
Published: June 2005

In this paper we give necessary and sufficient conditions for discreteness of a subgroup of PSL(2,ℂ) generated by a hyperbolic element and an elliptic one of odd order with non-orthogonally intersecting axes. Thus we completely determine two-generator non-elementary Kleinian groups without invariant plane with real traces of the generators and their commutator. We also give a list of all parameters that correspond to such groups. An interesting corollary of the result is that the group of the minimal known volume hyperbolic orbifold ℍ3/Γ353 has real parameters.
NEURON DYNAMICS AND CHAOTIC SYNCHRONIZATION
Authors: TITO ARECCHI F.
Published: June 2005

At the borderline between neuroscience and physics of complex phenomena, a new paradigm is under investigation, namely feature binding. This terminology denotes how a large collection of coupled neurons combines external signals with internal memories into new coherent patterns of meaning. An external stimulus spreads over an assembly of coupled neurons, building up a corresponding collective state. Thus, the synchronization of spike trains of many individual neurons is the basis of a coherent perception. Based on recent investigations, a novel conjecture for the dynamics of single neurons and, consequently, for neuron assemblies has been formulated. Homoclinic chaos is proposed as the most suitable way to code information in time by trains of equal spikes occurring at apparently erratic times; a new quantitative indicator, called propensity, is introduced to select the most appropriate neuron model. In order to classify the set of different perceptions, the percept space is given a metric structure by introducing a distance measure between distinct percepts. The distance in percept space is conjugate to the duration of the perception in the sense that an uncertainty relation in percept space is associated with time limited perceptions. (Thus coding of different percepts by synchronized spike trains entails fundamental quantum features. It is conjectured that they are related to the details of the perceptual chain rather than depending on Planck's action.)
ω-3 and ω-6 polyunsaturated fatty acids block HERG channels
Authors: Guizy Miriam , Arias Cristina , David Miren , González Teresa , Valenzuela Carmen
Published: June 2005

Dietary polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, which have been attributed to their availability to modulate Na+, Ca2+, and several K+ channels. However, their effects on human ether-a-go-go-related gene ( HERG) channels are unknown. In this study we have analyzed the effects of arachidonic acid (AA, ω-6) and docosahexaenoic acid (DHA, ω-3) on HERG channels stably expressed in Chinese hamster ovary cells by using the whole cell patch-clamp technique. At 10 μM, AA and DHA blocked HERG channels, at the end of 5-s pulses to −10 mV, to a similar extent (37.7 ± 2.4% vs. 50.2 ± 8.1%, n = 7–10, P > 0.05). 5,6,11,14-Eicosatetrayenoic acid, a nonmetabolizable AA analog, induced effects similar to those of AA on HERG current. Both PUFAs shifted the midpoint of activation curves of HERG channels by −5.1 ± 1.8 mV ( n = 10, P < 0.05) and −11.2 ± 1.1 mV ( n = 7, P < 0.01). Also, AA and DHA shifted the midpoint of inactivation curves by +12.0 ± 3.9 mV ( n = 4; P < 0.05) and +15.8 ± 4.3 mV ( n = 4; P < 0.05), respectively. DHA and AA accelerated the deactivation kinetics and slowed the inactivation kinetics at potentials positive to +40 mV. Block induced by DHA, but not that produced by AA, was higher when measured after applying a pulse to −120 mV (I→O). Finally, both AA and DHA induced a use-dependent inhibition of HERG channels. In summary, block induced by AA and DHA was time, voltage, and use dependent. The results obtained suggest that both PUFAs bind preferentially to the open state of the channel, although an interaction with inactivated HERG channels cannot be ruled out for AA.
Notch-mediated CBF-1/RBP-Jκ-dependent regulation of human vascular smooth muscle cell phenotype in vitro
Authors: Morrow David , Scheller Agnieszka , Birney Yvonne A. , Sweeney Catherine , Guha Shaunta , Cummins Philip M. , Murphy Ronan , Walls Dermot , Redmond Eileen M. , Cahill Paul A.
Published: June 2005

Vascular smooth muscle cell (VSMC) phenotypic modulation is a key factor in vascular pathology. We have investigated the role of Notch receptor signaling in controlling human vascular smooth muscle cell (hVSMC) differentiation in vitro and established a role for cyclic strain-induced changes in Notch signaling in promoting this phenotypic response. The expression of α-actin, calponin, myosin, and smoothelin was examined by performing immunocytochemistry, Western blot analysis, and quantitative real-time PCR in hVSMCs cultured under static conditions after forced overexpression of constitutively active Notch 1 and 3 receptors, inhibition of endogenous Cp-binding factor 1 (CBF-1)/recombination signal sequence-binding protein-Jκ (RBP-Jκ) signaling, and exposure to cyclic strain using a Flexercell Tension Plus unit. Overexpression of constitutively active Notch intracellular (IC) receptors (Notch 1 IC and Notch 3 IC) resulted in a significant downregulation of α-actin, calponin, myosin, and smoothelin expression, an effect that was significantly attenuated after inhibition of Notch-mediated, CBF-1/RBP-Jκ-dependent signaling by coexpression of RPMS-1 (Epstein-Barr virus-encoded gene product) and selective knockdown of basic helix-loop-helix factors [hairy enhancer of split ( HES) gene and Hes-related transcription (Hrt) factors Hrt-1, Hrt-2, and Hrt-3] using targeted small interfering RNA. Cells cultured under conditions of defined equibiaxial cyclic strain (10% strain, 60 cycles/min, 24 h) exhibited a significant reduction in Notch 1 IC and Notch 3 IC expression concomitant with a significant increase in VSMC differentiation marker expression. Moreover, this cyclic strain-induced increase was further enhanced after inhibition of CBF-1/RBP-Jκ-dependent signaling with RPMS-1. These findings suggest that Notch promotes changes in hVSMC phenotype via activation of CBF-1/RBP-Jκ-dependent pathways in vitro and contributes to the phenotypic response of VSMCs to cyclic strain-induced changes in VSMC differentiation.
Role of ubiquitin-proteasome degradation pathway in biogenesis efficiency of β-cell ATP-sensitive potassium channels
Authors: Yan Fei-Fei , Lin Chia-Wei , Cartier Etienne A. , Shyng Show-Ling
Published: June 2005

ATP-sensitive potassium (KATP) channels of pancreatic β-cells mediate glucose-induced insulin secretion by linking glucose metabolism to membrane excitability. The number of plasma membrane KATP channels determines the sensitivity of β-cells to glucose stimulation. The KATP channel is formed in the endoplasmic reticulum (ER) on coassembly of four inwardly rectifying potassium channel Kir6.2 subunits and four sulfonylurea receptor 1 (SUR1) subunits. Little is known about the cellular events that govern the channel's biogenesis efficiency and expression. Recent studies have implicated the ubiquitin-proteasome pathway in modulating surface expression of several ion channels. In this work, we investigated whether the ubiquitin-proteasome pathway plays a role in the biogenesis efficiency and surface expression of KATP channels. We provide evidence that, when expressed in COS cells, both Kir6.2 and SUR1 undergo ER-associated degradation via the ubiquitin-proteasome system. Moreover, treatment of cells with proteasome inhibitors MG132 or lactacystin leads to increased surface expression of KATP channels by increasing the efficiency of channel biogenesis. Importantly, inhibition of proteasome function in a pancreatic β-cell line, INS-1, that express endogenous KATP channels also results in increased channel number at the cell surface, as assessed by surface biotinylation and whole cell patch-clamp recordings. Our results support a role of the ubiquitin-proteasome pathway in the biogenesis efficiency and surface expression of β-cell KATP channels.
Mechanisms Underlying Reorganization of Fractured Tactile Cerebellar Maps After Deafferentation in Developing and Adult Rats
Authors: Shumway Caroly , Morissette Josée , Bower James M.
Published: June 2005

Our previous studies showed that fractured tactile cerebellar maps in rats reorganize after deafferentation during development and in adulthood while maintaining a fractured somatotopy. Several months after deafferentation of the infraorbital branch of the trigeminal nerve, the missing upper lip innervation is replaced in the tactile maps in the granule cell layer of crus IIa. The predominant input into the denervated area is always the upper incisor representation. This study examined whether this reorganization was caused by mechanisms intrinsic to the cerebellum or extrinsic, i.e., occurring in somatosensory structures afferent to the cerebellum. We first compared normal and deafferented maps and found that the expansion of the upper incisor is not caused by a preexisting bias in the strength or abundance of upper incisor input in normal animals. We then mapped tactile representations before and immediately after denervation. We found that the pattern of reorganization observed in the cerebellum several months later is not caused by unmasking of a silent or weaker upper incisor representation. Both results indicate that the reorganization is not a result of subsequent growth or sprouting mechanism within the cerebellum itself. Finally, we compared postlesion maps in the cerebellum and the somatosensory cortex. We found that the upper incisor representation significantly expands in both regions and that this expansion is correlated, suggesting that reorganization in the cerebellum is a passive consequence of reorganization in afferent cerebellar pathways. This result has important developmental and functional implications.
Quantitative Characterization of Disparity Tuning in Ventral Pathway Area V4
Authors: Hinkle David A. , Connor Charles E.
Published: June 2005

We performed a quantitative characterization of binocular disparity-tuning functions in the ventral (object-processing) pathway of the macaque visual cortex. We measured responses of 452 area V4 neurons to stimuli with disparities ranging from −1.0 to +1.0°. Asymmetric Gaussian functions fit the raw data best (median R = 0.90), capturing both the modal components (local peaks in the −1.0 to +1.0° range) and the monotonic components (linear or sigmoidal dependency on disparity) of the tuning patterns. Values derived from the asymmetric Gaussian fits were used to characterize neurons on a modal × monotonic tuning domain. Points along the modal tuning axis correspond to classic tuned excitatory and inhibitory patterns; points along the monotonic axis correspond to classic near and far patterns. The distribution on this domain was continuous, with the majority of neurons exhibiting a mixed modal/monotonic tuning pattern. The distribution in the modal dimension was shifted toward excitatory patterns, consistent with previous results in other areas. The distribution in the monotonic dimension was shifted toward tuning for crossed disparities (corresponding to stimuli nearer than the fixation plane). This could reflect a perceptual emphasis on objects or object parts closer to the observer. We also found that disparity-tuning strength was positively correlated with orientation-tuning strength and color-tuning strength, and negatively correlated with receptive field eccentricity.
Dynamic Spatiotemporal Synaptic Integration in Cortical Neurons: Neuronal Gain, Revisited
Authors: Azouz Rony
Published: June 2005

Gain modulation is a ubiquitous phenomenon in cortical neurons, providing flexibility to operate under changing conditions. The prevailing view is that this modulation reflects a change in the relationship between mean input and output firing rate brought about by variation in neuronal membrane characteristics. An alternative mechanism is proposed for neuronal gain modulation that takes into account the capability of cortical neurons to process spatiotemporal synaptic correlations. Through the use of numerical simulations, it is shown that voltage-gated and leak conductances, membrane potential, noise, and input firing rate modify the sensitivity of cortical neurons to the degree of temporal correlation between their synaptic inputs. These changes are expressed in a change of the temporal window for synaptic integration and the range of input correlation over which response probability is graded. The study also demonstrates that temporal integration depends on the distance between the inputs and that this interplay of space and time is modulated by voltage-gated and leak conductances. Thus, gain modulation may reflect a change in the relationship between spatiotemporal synaptic correlations and output firing probability. It is further proposed that by acting synergistically with the network, dynamic spatiotemporal synaptic integration in cortical neurons may serve a functional role in the formation of dynamic cell assemblies.
Spatial Properties of Central Vestibular Neurons of Monkeys After Bilateral Lateral Canal Nerve Section
Authors: Yakushin Sergei B. , Raphan Theodore , Büttner-Ennever Jean A. , Suzuki Jun-Ichi , Cohen Bernard
Published: June 2005

Thirty-seven neurons were recorded in the superior vestibular nucleus (SVN) of two cynomolgus monkeys 1–2 yr after bilateral lateral canal nerve section to test whether the central neurons had spatially adapted for the loss of lateral canal input. The absence of lateral canal function was verified with eye movement recordings. The relation of unit activity to the vertical canals was determined by oscillating the animals about a horizontal axis with the head in various orientations relative to the axis of rotation. Animals were also oscillated about a vertical axis while upright or tilted in pitch. In the second test, the vertical canals are maximally activated when the animals are tilted back about −50° from the spatial upright and the lateral canals when the animals are tilted forward about 30°. We reasoned that if central compensation occurred, the head orientation at which the response of the vertical canal-related neurons was maximal should be shifted toward the plane of the lateral canals. No lateral canal-related units were found after nerve section, and vertical canal-related units were found only in SVN not in the rostral medial vestibular nucleus. SVN canal-related units were maximally activated when the head was tilted back at −47 ± 17 and −50 ± 12° (means ± SD) in the two animals, close to the predicted orientation of the vertical canals. This indicated that spatial adaptation of vertical canal-related vestibular neurons had not occurred. There were substantial neck and/or otolith-related inputs activating the vertical canal-related neurons in the nerve-sectioned animals, which could have contributed to oculomotor compensation after nerve section.
Existence of solutions for equations involving iterated functional series
Authors: Murugan V , Subrahmanyam PV
Published: June 2005

Theorems on the existence and uniqueness of differentiable solutions for a class of iterated functional series equations are obtained. These extend earlier results due to Zhang.
Convergence theorems for a common fixed point of a finite family of nonself nonexpansive mappings
Authors: Chidume CE , Zegeye Habtu , Shahzad Naseer
Published: June 2005

Let "Equation missing" be a nonempty closed convex subset of a reflexive real Banach space "Equation missing" which has a uniformly Gâteaux differentiable norm. Assume that "Equation missing" is a sunny nonexpansive retract of "Equation missing" with "Equation missing" as the sunny nonexpansive retraction. Let "Equation missing", "Equation missing", be a family of nonexpansive mappings which are weakly inward. Assume that every nonempty closed bounded convex subset of "Equation missing" has the fixed point property for nonexpansive mappings. A strong convergence theorem is proved for a common fixed point of a family of nonexpansive mappings provided that "Equation missing", "Equation missing", satisfy some mild conditions.
On the risk‐adjusted pricing‐methodology‐based valuationof vanilla options and explanation of the volatility smile
Authors: Jandačka Martin , Ševčovič Daniel
Published: June 2005

We analyse a model for pricing derivative securities in the
presence of both transaction costs as well as the risk from a
volatile portfolio. The model is based on the Black‐Scholes
parabolic PDE in which transaction costs are described following
the Hoggard, Whalley, and Wilmott approach. The risk from a volatile portfolio is described by the
variance of the synthesized portfolio. Transaction
costs as well as the volatile portfolio risk depend on the time
lag between two consecutive transactions. Minimizing their sum
yields the optimal length of the hedge interval. In this model,
prices of vanilla options can be computed from a solution to a
fully nonlinear parabolic equation in which a diffusion
coefficient representing volatility nonlinearly depends on the
solution itself giving rise to explaining the volatility smile
analytically. We derive a robust numerical scheme for solving the
governing equation and perform extensive numerical testing of the
model and compare the results to real option market data. Implied
risk and volatility are introduced and computed for large option
datasets. We discuss how they can be used in qualitative and
quantitative analysis of option market data.
Data‐Mining Analysis Suggests an Epigenetic Pathogenesis for Type 2 Diabetes
Authors: Wren Jonathan D. , Garner Harold R.
Published: June 2005

The etiological origin of type 2 diabetes mellitus (T2DM) has long been controversial. The body of literature related to T2DM is vast and varied in focus, making a broad epidemiological perspective
difficult, if not impossible. A data‐mining approach was used to analyze all electronically available scientific literature, over 12 million Medline records, for “objects” such as genes, diseases, phenotypes, and chemical compounds linked to other objects within the T2DM literature but were not themselves within
the T2DM literature. The goal of this analysis was to conduct a comprehensive survey to identify novel factors implicated in the pathology of T2DM by statistically evaluating mutually shared associations. Surprisingly, epigenetic factors were among the highest statistical scores in this analysis, strongly implicating epigenetic changes within the body as causal factors in the pathogenesis of T2DM. Further analysis implicates adipocytes as the potential tissue of origin, and cytokines or cytokine‐like genes as the dysregulated factor(s) responsible for the T2DM phenotype. The analysis provides a wealth of literature supporting this hypothesis, which—if true—represents an important paradigm shift for researchers studying the pathogenesis of T2DM.
Multiclass Cancer Classification by Using Fuzzy Support Vector Machine and Binary Decision Tree With Gene Selection
Authors: Mao Yong , Zhou Xiaobo , Pi Daoying , Sun Youxian , Wong Stephen T. C.
Published: June 2005

We investigate the problems of multiclass cancer classification with gene selection from gene expression data. Two different constructed multiclass classifiers with gene selection are proposed, which are fuzzy support vector machine (FSVM) with gene selection and binary classification tree based on SVM with gene selection. Using F test and recursive feature elimination based on SVM as gene selection methods, binary classification tree based on
SVM with F test, binary classification tree based on SVM with recursive feature elimination based on SVM, and FSVM with recursive feature elimination based on SVM are tested in our experiments. To accelerate computation, preselecting the strongest genes is also used. The proposed techniques are applied to analyze
breast cancer data, small round blue‐cell tumors, and acute leukemia data. Compared to existing multiclass cancer classifiers and binary classification tree based on SVM with F test or binary classification tree based on SVM with recursive feature elimination based on SVM mentioned in this paper, FSVM based on recursive feature elimination based on SVM can find most important genes that affect certain types of cancer with high recognition
accuracy.
Computational, Integrative, and Comparative Methods for the Elucidation of Genetic Coexpression Networks
Authors: Baldwin Nicole E. , Chesler Elissa J. , Kirov Stefan , Langston Michael A. , Snoddy Jay R. , Williams Robert W. , Zhang Bing
Published: June 2005

Gene expression microarray data can be used for the assembly of genetic coexpression network graphs. Using mRNA samples obtained from recombinant inbred Mus musculus strains, it is possible to integrate allelic variation with molecular and higher‐order phenotypes. The depth of quantitative genetic analysis of microarray data can be vastly enhanced utilizing this mouse resource in combination with powerful computational
algorithms, platforms, and data repositories. The resulting network graphs transect many levels of biological scale. This
approach is illustrated with the extraction of cliques of putatively co‐regulated genes and their annotation using gene
ontology analysis and cis‐regulatory element discovery. The causal basis for co‐regulation is detected through the use of quantitative trait locus mapping.
Online Analytical Processing (OLAP): A Fast and Effective Data Mining Tool for Gene Expression Databases
Authors: Alkharouf Nadim W. , Jamison D. Curtis , Matthews Benjamin F.
Published: June 2005

Gene expression databases contain a wealth of information, but current data mining tools are limited in their speed and effectiveness in extracting meaningful biological knowledge from them. Online analytical processing (OLAP) can be used as a supplement to cluster analysis for fast and effective data mining of gene expression databases. We used Analysis Services 2000, a product that ships with SQLServer2000, to construct an OLAP cube that was used to mine a time series experiment designed to identify genes associated with resistance of soybean to the
soybean cyst nematode, a devastating pest of soybean. The data for these experiments is stored in the soybean genomics and microarray database (SGMD). A number of candidate resistance genes and pathways were found. Compared to traditional cluster analysis of gene expression data, OLAP was more effective and faster in finding biologically meaningful information. OLAP is available from a number of vendors and can work with any relational database management system through OLE DB.