bluuebunny/crossref_metadata_2025 huggingface dataset:
The course of untreated anxiety and depression, and determinants of poor one-year outcome: a one-year cohort study
Authors: van Beljouw Ilse MJ , Verhaak Peter FM , Cuijpers Pim , van Marwijk Harm WJ , Penninx Brenda WJH
Published: October 2010

Background

Little is known about the course and outcome of untreated anxiety and depression in patients with and without a self-perceived need for care. The aim of the present study was to examine the one-year course of untreated anxiety and depression, and to determine predictors of a poor outcome.

Method

Baseline and one-year follow-up data were used of 594 primary care patients with current anxiety or depressive disorders at baseline (established by the Composite Interview Diagnostic Instrument (CIDI)), from the Netherlands Study of Depression and Anxiety (NESDA). Receipt of and need for care were assessed by the Perceived Need for Care Questionnaire (PNCQ).

Results

In depression, treated and untreated patients with a perceived treatment need showed more rapid symptom decline but greater symptom severity at follow-up than untreated patients without a self-perceived mental problem or treatment need. A lower education level, lower income, unemployment, loneliness, less social support, perceived need for care, number of somatic disorders, a comorbid anxiety and depressive disorder and symptom severity at baseline predicted a poorer outcome in both anxiety and depression. When all variables were considered at the same time, only baseline symptom severity appeared to predict a poorer outcome in anxiety. In depression, a poorer outcome was also predicted by more loneliness and a comorbid anxiety and depressive disorder.

Conclusion

In clinical practice, special attention should be paid to exploring the need for care among possible risk groups (e.g. low social economic status, low social support), and support them in making an informed decision on whether or not to seek treatment.
Analysis of binding properties and specificity through identification of the interface forming residues (IFR) for serine proteases in silico docked to different inhibitors
Authors: Ribeiro Cristina , Togawa Roberto C , Neshich Izabella AP , Mazoni Ivan , Mancini Adauto L , Minardi Raquel C de Melo , da Silveira Carlos H , Jardine José G , Santoro Marcelo M , Neshich Goran
Published: October 2010

Background

Enzymes belonging to the same super family of proteins in general operate on variety of substrates and are inhibited by wide selection of inhibitors. In this work our main objective was to expand the scope of studies that consider only the catalytic and binding pocket amino acids while analyzing enzyme specificity and instead, include a wider category which we have named the Interface Forming Residues (IFR). We were motivated to identify those amino acids with decreased accessibility to solvent after docking of different types of inhibitors to sub classes of serine proteases and then create a table (matrix) of all amino acid positions at the interface as well as their respective occupancies. Our goal is to establish a platform for analysis of the relationship between IFR characteristics and binding properties/specificity for bi-molecular complexes.

Results

We propose a novel method for describing binding properties and delineating serine proteases specificity by compiling an exhaustive table of interface forming residues (IFR) for serine proteases and their inhibitors. Currently, the Protein Data Bank (PDB) does not contain all the data that our analysis would require. Therefore, an in silico approach was designed for building corresponding complexes

The IFRs are obtained by "rigid body docking" among 70 structurally aligned, sequence wise non-redundant, serine protease structures with 3 inhibitors: bovine pancreatic trypsin inhibitor (BPTI), ecotine and ovomucoid third domain inhibitor. The table (matrix) of all amino acid positions at the interface and their respective occupancy is created. We also developed a new computational protocol for predicting IFRs for those complexes which were not deciphered experimentally so far, achieving accuracy of at least 0.97.

Conclusions

The serine proteases interfaces prefer polar (including glycine) residues (with some exceptions). Charged residues were found to be uniquely prevalent at the interfaces between the "miscellaneous-virus" subfamily and the three inhibitors. This prompts speculation about how important this difference in IFR characteristics is for maintaining virulence of those organisms.

Our work here provides a unique tool for both structure/function relationship analysis as well as a compilation of indicators detailing how the specificity of various serine proteases may have been achieved and/or could be altered. It also indicates that the interface forming residues which also determine specificity of serine protease subfamily can not be presented in a canonical way but rather as a matrix of alternative populations of amino acids occupying variety of IFR positions.
Imported malaria in an area in southern Madrid, 2005-2008
Authors: Rey Sonia , Zuza Inés , Martínez-Mondéjar Belén , Rubio José M , Merino Francisco J
Published: October 2010

Background

In Spain, malaria cases are mostly due to migrants and travellers returning from endemic areas. The objective of this work was to describe the malaria cases diagnosed at the Severo Ochoa University Hospital (HUSO) in Leganés in the south of the Madrid Region from 2005 to 2008.

Methods

Descriptive retrospective study performed at HUSO. Data sources are registries from the Microbiology Department and malaria cases notified to the Preventive Medicine Department. Analysed parameters were: administrative, demographical, related to the stay at the endemic country, clinical, microbiological diagnosis method, pregnancy, treatment and prophylaxis, co-infections, and days of hospital stay.

Results

Fifty-seven patients diagnosed with malaria were studied. Case distribution per year was 13 in 2005, 15 in 2006, 15 in 2007 and 14 in 2008. Thirty-three patients were female (57.9%) and 24 male (42.1%). Mean age was 27.8 years. Most of the malaria cases were acquired in Nigeria (49.1%) and Equatorial Guinea (32.7%). 29.1% of the patients were immigrants who had arrived recently, and 61.8% acquired malaria when travelling to their countries of origin to visit friends and relatives (VFR). Majority of cases were diagnosed between June and September. Microscopy was positive in 39 cases (68.4%) immunochromatography in 42 (73.7%) and PCR in the 55 cases where performed. Plasmodium falciparum was responsible for 94.7% of the cases. The more frequent symptoms were fever (77.2%), followed by headache and gastrointestinal symptoms (33.3%). Nine cases needed hospital admittance, a pregnant woman, three children, four VFR and an African tourist, but all evolved favourably. Chemoprophylaxis data was known from 55 patients. It was taken correctly in one case (1.8%), in five (9.1%) the prophylaxis was improper while the others 49 (89.1%) cases had not followed any anti-malarial prophylaxis.

Conclusions

Children, pregnant women and the VFR have the highest risk to present severe malaria and to need hospital admittance. Another important risk factor for acquiring malaria is incorrect prophylaxis. The first place for malaria acquisition was Nigeria and the main species causing malaria was P. falciparum.
Review for the generalist: The antinuclear antibody test in children - When to use it and what to do with a positive titer
Authors: Malleson Peter N , Mackinnon Murray J , Sailer-Hoeck Michaela , Spencer Charles H
Published: October 2010

The antinuclear antibody test (ANA) is a much overused test in pediatrics. The ANA does have a role in serologic testing but it should be a very limited one. It is often ordered as a screening test for rheumatic illnesses in a primary care setting. However, since it has low specificity and sensitivity for most rheumatic and musculoskeletal illnesses in children, it should not be ordered as a screening test for non-specific complaints such as musculoskeletal pain. It should only be used as a diagnostic test for children with probable Systemic Lupus Erythematosus (SLE) or Mixed Connective Tissue Disease, (MCTD) and other possible overlap-like illnesses. Such children should have developed definite signs and symptoms of a disease before the ANA is ordered. This review presents data supporting these conclusions and a review of the ANA literature in adults and children.

By limiting ANA testing, primary care providers can avoid needless venipuncture pain, unnecessary referrals, extra medical expenses, and most importantly, significant parental anxieties. It is best not to do the ANA test in most children but if it ordered and is positive in a low titer (<1:640), the results can be ignored if the child is otherwise well and does not have other features of a systemic illness.
Genetic diversity and C2-like subgenogroup strains of enterovirus 71, Taiwan, 2008
Authors: Huang Yuan-Pin , Lin Tsuey-Li , Hsu Li-Ching , Chen Yu-Ju , Tseng Yin-Hsin , Hsu Chiu-Chu , Fan Wen-Bin , Yang Jyh-Yuan , Chang Feng-Yee , Wu Ho-Sheng
Published: October 2010

Background

Human enterovirus 71 (EV-71) is known of having caused numerous outbreaks of hand-foot-mouth disease, and other clinical manifestations globally. In 2008, 989 EV-71 strains were isolated in Taiwan.

Results

In this study, the genetic and antigenic properties of these strains were analyzed and the genetic diversity of EV-71 subgenogroups surfacing in Taiwan was depicted, which includes 3 previously reported subgenogroups of C5, B5, and C4, and one C2-like subgenogroup. Based on the phylogenetic analyses using their complete genome nucleotide sequences and neutralization tests, the C2-like subgenogroup forms a genetically distinct cluster from other subgenogroups, and the antisera show a maximum of 128-fold decrease of neutralization titer against this subgenogroup. In addition, the subgenogroup C4 isolates of 2008 were found quite similar genetically to the Chinese strains that caused outbreaks in recent years and thus they should be carefully watched.

Conclusions

Other than to be the first report describing the existence of C2-like subgenogroup of EV-71 in Taiwan, this article also foresees a potential of subgenogroup C4 outbreaks in Taiwan in the near future.
Lung abscess predicts the surgical outcome in patients with pleural empyema
Authors: Huang Hung-Che , Chen Heng-Chung , Fang Hsin-Yuan , Lin Yi-Chieh , Wu Chin-Yen , Cheng Ching-Yuan
Published: October 2010

Objectives

Most cases of pleural empyema are caused by pulmonary infections, which are usually combined with pneumonia or lung abscess. The mortality of patients with pleural empyema remains high (up to 20%). It also contributes to higher hospital costs and longer hospital stays. We studied pleural empyema with combined lung abscess to determine if abscess was associated with mortality.

Methods

From January 2004 to December 2006, we retrospectively reviewed 259 patients diagnosed with pleural empyema who received thoracscopic decortications of the pleura in a single medical center. We evaluated their clinical data and analyzed their chest computed tomography scans. Outcomes of pleural empyema were compared between groups with and without lung abscess.

Results

Twenty-two pleural empyema patients had lung abscesses. Clinical data showed significantly higher incidences in the lung abscess group of pre-operative leukocytosis, need for an intensive care unit stay and mortality.

Conclusion

Patients with pleural empyema and lung abscess have higher intensive care unit admission rate, higher mortality during 30 days and overall mortality than patients with pleural empyema. The odds ratio of lung abscess is 4.685. Physician shall pay more attention on high risk patient of lung abscess for early detection and management.
“Substitutable” Polymer Brushes: Reactive Poly(methacrylate) Brushes with Exchangeable Alkoxyamine Units in the Side Chain
Authors: Sato Tomoya , Amamoto Yoshifumi , Yamaguchi Hiroki , Otsuka Hideyuki , Takahara Atsushi
Published: October 2010

A reactive polymer brush containing alkoxyamine units in the side chains, when heated with an alkoxyamine-terminated fluorinated nongrafted polymer, gave a grafted copolymer brush by a radical crossover reaction of alkoxyamine units. The fluorinated grafted copolymer brush could be converted back to the parent polymer brush upon treatment with an excess of low-molecular alkoxyamine. The reversible change in the surface properties of the brush was confirmed by X-ray photoelectron spectroscopy and contact angle measurements.
Aggregation of l-Cysteinato Tricobaltate(III) Anions by Lanthanide(III) Cations into Dimensional Structures That are Controlled by Diastereoisomerism and Ionic Size
Authors: Yuan Hou Qun , Igashira-Kamiyama Asako , Konno Takumi
Published: October 2010

Treatment of the ΛLLLΛLLL and ΔLLLΔLLL isomers of K3[Co{Co(l-cys-N,S)3}2] (K3[1], l-cys: l-cysteinate) with Ln(NO3)3 (Ln = La and Yb) in water gave coordination polymers, ΛLLLΛLLL-Ln[1] and ΔLLLΔLLL-Ln[1], respectively, in which [1]3− binds to Ln3+ through carboxylate groups in a 1:1 ratio. It was found that the dimensional structures of Ln[1] are controlled not only by the diastereoisomerism of [1]3− (ΛLLLΛLLL vs. ΔLLLΔLLL) but also by the ionic size of Ln3+ (La3+ vs. Yb3+).
Novel Phenanthroline Derivatives for Electron Transport in Organic Light-emitting Diodes
Authors: Kathirgamanathan Poopathy , Surendrakumar Sivagnanasundram , Ravichandran Seenivasagam , Vanga Raghava Reddy , Antipan-Lara Juan , Ganeshamurugan Subramaniam , Kumaravel Muttulingham , Paramaswara Gnanamoly , Arkley Vincent
Published: October 2010

A series of novel arylvinyl-substituted phenanthroline derivatives have been synthesized and their applications as electron-transporting materials in organic light-emitting diodes (OLED’s) have been investigated. One particular derivative, namely, 2,9-bis(2-thiophen-2-ylvinyl)[1,10]phenanthroline shows significantly lower operating voltage than tris(8-quinolinolato)aluminum(III) (Alq3) and substantially higher lifetime than bathophenanthroline (BPhen).
Validation and Implementation of an Algorithm for Reporting the Automated Absolute Neutrophil Count From Selected Flagged Specimens
Authors: Sireci Anthony N. , Herlitz Leal , Lee Keagan , Bautista Jessica L. , Kratz Alexander
Published: October 2010

Samples that are flagged by automated cell counters and, therefore, require a time-consuming microscopic review cause unacceptable wait times for patients in hematology/oncology clinics. We used a set of 518 samples to validate that 5 flags on Sysmex XE/XT instruments (Sysmex, Kobe, Japan) could safely be ignored when the absolute neutrophil count (ANC) was the primary clinical question. The R2 between automated and manual ANCs was 96.9% for samples triggering non-ANC flags, with 1 clinically significant discrepant sample out of 296 (0.3%). A new test code allowing clinicians to specify “ANC-only” was implemented, and these non-ANC specific flags were disregarded. The new order set was used in 16.3% of patients. Automated reporting of the ANC in selected flagged samples reduced the review rate by 60% and decreased the turnaround time by 100 minutes. This approach to automatically report the ANC in selected flagged specimens in which the ANC is the primary clinical interest safely decreases the turnaround time for many ANC samples.
The Specificity of Immunophenotypic Alterations in Blasts in Nonacute Myeloid Disorders
Authors: Harrington Alexandra , Olteanu Horatiu , Kroft Steven
Published: October 2010

Data regarding flow cytometry (FC) in nonacute myeloid disorders is confounded by variable gating strategies and controls limited to normal bone marrow (BM) samples. Blasts in diagnostic BM samples of myelodysplastic syndromes (MDSs), myeloproliferative neoplasms (MPNs), and chronic myelomonocytic leukemias (CMMLs) were compared with 20 nonneoplastic cytopenias/cytoses (CCs) and negative staging BM samples using 4-color FC. Blasts in 10 of 20 CCs showed immunophenotypic differences vs control samples. Immunophenotypic alterations were identified in 18 of 21 MDSs, 11 of 14 MPNs, and 7 of 7 CMMLs vs control samples and 13 (62%) of 21 MDSs, 7 (50%) of 14 MPNs, and 3 (43%) of 7 CMMLs vs CCs. Neoplastic-specific blast immunophenotypic changes included expression of CD7, CD11b, CD15, CD36, and CD56; CD34 overexpression; HLA-DR variability; lack of CD13 and CD33; underexpression of CD13, CD33, CD45, and HLA-DR; and partial loss of CD13, CD33, CD38, and CD117. In all cases, blasts were CD34+. Several blast immunophenotypic alterations are shared in neoplastic and nonneoplastic BM samples. Approximately 40% to 60% of neoplastic BM samples exhibited aberrancies not seen in reactive BM samples.
Cerebrospinal Fluid Penetration of High-Dose Daptomycin in Suspected Staphylococcus aureus Meningitis
Authors: Riser M Shawn , Bland Christopher M , Rudisill Celeste N , Bookstaver P Brandon
Published: October 2010

Objective:

To report a case of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia with suspected MSSA meningitis treated with high-dose daptomycin assessed with concurrent serum and cerebrospinal fluid (CSF) concentrations.

Case Summary:

A 54-year-old male presented to the emergency department with generalized weakness and presumed health-care–associated pneumonia shown on chest radiograph. Treatment was empirically initiated with vancomycin, levofloxacin, and piperacillin/tazobactam. Blood cultures revealed S. aureus susceptible to oxacillin. Empiric antibiotic treatment was narrowed to nafcillin on day 4. On day 8, the patient developed acute renal failure (serum creatinine 1.9 mg/dL, increased from 1.2 mg/dL the previous day and 0.8 mg/dL on admission). The patient's Glasgow Coma Score was 3, with normal findings shown on computed tomography scan of the head 72 hours following an episode of cardiac arrest on day 10. The patient experienced relapsing MSSA bacteremia on day 9, increasing the suspicion for a central nervous system (CNS) infection. Nafcillin was discontinued and daptomycin 9 mg/kg daily was initiated for suspected meningitis and was continued until the patient's death on day 16. Daptomycin serum and CSF trough concentrations were 11.21 μg/mL and 0.52 μg/mL, respectively, prior to the third dose. Lumbar puncture results were inconclusive and no further blood cultures were positive for MSSA. Creatine kinase levels were normal prior to daptomycin therapy and were not reassessed.

Discussion:

Daptomycin was initiated in our patient secondary to possible nafcillin-induced acute interstitial nephritis and relapsing bacteremia. At a dose of 9 mg/kg, resultant penetration of 5% was higher than in previous reports, more consistent with inflamed meninges.

Conclusions:

High-dose daptomycin may be an alternative option for MSSA bacteremia with or without a CNS source in patients who have failed or cannot tolerate standard therapy. Further clinical evaluation in patients with confirmed meningitis is warranted.
Fatty acid composition of serum phospholipids in cystic fibrosis (CF) patients with or without CF related liver disease
Authors: Van Biervliet Stephanie , Van Biervliet Jean-Pierre , Robberecht Eddy , Christophe Armand
Published: October 2010

Background: In cystic fibrosis (CF), changes in fatty acid (FA) composition of serum phospholipids (PL) and cell membranes can account, in part, for the inflammatory state of the disease. The severity of the genotype is known to correlate with the degree of FA changes. Liver diseases, such as cholestasis and cirrhosis are also known to influence FA status. Until now, there is no data on the influence of CF related liver disease (CFRLD) on the FA status of CF patients. The aim of this study was to evaluate, whether the presence of CFRLD influences FA status.

Methods: A fasting blood sample for the determination of serum vitamin E and PL-FA composition was collected from 79 CF patients with stable pulmonary disease and under good control in our CF centre. Patients with CFRLD (n=13) were compared to CF patients with the same severity of genotype (n=66) but without CFRLD.

Results: The CF patients with CFRLD had lower docosahexaenoic acid (DHA, 22:6n-3) and increased docosatetraenoic acid (22:4n-6). There were no significant differences in the precursors of these FAs.

Conclusions: DHA concentration in patients with CFRLD is decreased more substantially compared with their genotype controls. The presence of CFRLD should be taken into account in future FA studies in CF patients.

Clin Chem Lab Med 2010;48:1751–5.
Helicobacter pylori infection and the severity of gastritis are not associated with iron deficiency in a group of Brazilian patients
Authors: Alvarenga Eliana C. , Montes Ciro G. , Guerrazzi Fábio , Zeitune José M. , Grotto Helena Z.W.
Published: October 2010

Background:
Helicobacter pylori (H. pylori) infection has been associated with iron deficiency anemia. However, results reported in the literature are contradictory. The goal of the present study was to study the possible association between H. pylori infection and iron deficiency in a sample of adults.

Methods: One hundred and fifty individuals were studied (H. pylori-positive n=75; H. pylori-negative n=50). The presence of anemia was determined using red cell indices and reticulocyte hemoglobin content (CHr). Iron status was assessed based on serum iron and ferritin levels. Possible involvement of inflammatory activity in erythropoiesis was investigated by measuring the correlation between C-reactive protein (CRP) and red cell indices and iron status.

Results: There were no significant differences in the hematological or biochemical parameters for the two groups. Iron deficiency was diagnosed in six individuals, but no difference in prevalence was found between the H. pylori-positive and H. pylori-negative groups. A weak but significant inverse correlation was observed between CRP and CHr concentrations and between serum gastrin and CHr in the H. pylori-positive group. These results suggest a reduction in iron availability for reticulocyte hemoglobinization, but insufficient to cause anemia.

Conclusions:
H. pylori infection was not a determining factor for development of iron deficiency in our study population.

Clin Chem Lab Med 2010;48:1809–12.
Non-invasive assessment of liver fibrosis: it is time for laboratory medicine
Authors: Sebastiani Giada , Gkouvatsos Konstantinos , Plebani Mario
Published: October 2010

Chronic liver diseases (CLDs) represent a major cause of morbidity and mortality worldwide. In all etiologies of CLDs, staging of liver fibrosis is essential for both prognosis and management. Until a few years ago, liver biopsy was the only tool for the diagnosis of liver fibrosis in patients with CLDs. However, liver biopsy is an invasive and costly procedure. More recently, various serum biomarkers and laboratory tests have been proposed as surrogates of liver histology. Due to inadequate diagnostic accuracy or to lack of sufficient validation, guidelines still do not recommend them as a substitute for liver biopsy that is still considered the gold standard for the diagnosis of liver fibrosis. Notably, non-invasive serum biomarkers, when combined, may reduce by 50%–80% the number of liver biopsies needed for correctly classifying hepatic fibrosis. However, liver biopsy cannot be avoided completely, but should be used in those cases in which non-invasive methods show poor accuracy. In this view, serum biomarkers and liver biopsy represent a union between laboratory medicine and hepatology.
Gender-specific association of serum uric acid with metabolic syndrome and its components in juvenile obesity
Authors: Krzystek-Korpacka Malgorzata , Patryn Eliza , Kustrzeba-Wojcicka Irena , Chrzanowska Joanna , Gamian Andrzej , Noczynska Anna
Published: October 2010

Background:Hyperuricemia has been implicated in the pathogenesis of obesity and related metabolic abnormalities. Studies on the association between serum uric acid (sUA) and metabolic syndrome (MetS) in juvenile obesity are scant. The effect of gender has not been evaluated.

Methods:sUA (uricase method), anthropometric and biochemical indices were measured in gender-stratified children/adolescents consisting of 113 overweight/obese and 71 lean individuals.

Results:In males, sUA was significantly elevated in overweight as well as obese patients. sUA was strongly associated with obesity indices and reflected sexual development, decreases in high density lipoprotein-cholesterol, and moderately, the number of MetS components. Waist circumference (WC) and Tanner stage explained 40% of sUA variability. Controlling for body mass index (BMI) and other MetS components, sUA was associated with abdominal obesity, explaining 30% of variability in WC. In females, sUA was significantly increased in obesity, high blood pressure (BP), and MetS and corresponded with the number of MetS components, indices of glucose metabolism, triglycerides (TG), and the atherogenecity index. Insulin-resistance (IR) (homeostasis model assessment; HOMA) and high BP explained 29% of sUA variability, whereas sUA, while controlling for BMI, age, and other MetS components, was associated with hypertriglyceridemia, hyperglycemia, high BP, and abdominal obesity. IR mediated the associations with high TG and glucose.

Conclusions:The association between sUA and MetS components in juvenile obesity is gender-specific, with females being related more closely and to more metabolic abnormalities. It may explain why, despite its lower concentrations, sUA is an independent predictor of mortality from all causes and from vascular diseases exclusively in females. Our findings may help in identifying metabolic abnormalities which may possibly be targeted by reducing sUA in males and females.
Evaluation of ovarian cancer biomarkers in subjects with benign asbestos-related pleural diseases
Authors: Park Eun-Kee , Johnson Anthony R. , Yates Deborah H. , Thomas Paul S.
Published: October 2010

Background: Mesothelioma and ovarian cancer have been reported to have a similar pathogenesis, and for this reason it was hypothesized that there may be biomarkers in common and possibly associated with benign pleural diseases caused by asbestos exposure.

Methods: Serum biomarkers including insulin-like growth factor-II (IGF-II), leptin, prolactin and vascular endothelial growth factor (VEGF) were measured in an observational study of subjects with benign asbestos-related pleural diseases (BARPD) (n=24) and healthy subjects with an asbestos exposure history (n=12).

Results: Mean serum IGF-II and VEGF concentration in healthy subjects with a history of asbestos exposure were higher than those with BARPD. Mean serum concentrations of leptin and prolactin showed opposite trends when compared to IGF-II and VEGF concentrations among these groups.

Conclusions: The results suggest that IGF-II and VEGF concentrations are lower in BARPD, similar to studies of ovarian cancer. This finding warrants further investigation with malignant asbestos-related diseases.
Reconstruction of pressure velocities and boundaries of thin layers in thinly-stratified layers
Authors: Karchevsky A. L.
Published: October 2010

The algorithm of reconstruction of pressure velocities in a thinly stratified layer and of the location of the gap points of medium is suggested. The analytic expressions for derivatives of residual functional with respect to the pressure velocities in thin layers and by the coordinate of gap points of medium are obtained. The suggested algorithm is tested by numerical examples.
A Dominant Mutation in a Neuronal Acetylcholine Receptor Subunit Leads to Motor Neuron Degeneration inCaenorhabditis elegans
Authors: Barbagallo Belinda , Prescott Hilary A. , Boyle Patrick , Climer Jason , Francis Michael M.
Published: October 2010

Inappropriate or excessive activation of ionotropic receptors can have dramatic consequences for neuronal function and, in many instances, leads to cell death. InCaenorhabditis elegans, nicotinic acetylcholine receptor (nAChR) subunits are highly expressed in a neural circuit that controls movement. Here, we show that heteromeric nAChRs containing theacr-2subunit are diffusely localized in the processes of excitatory motor neurons and act to modulate motor neuron activity. Excessive signaling through these receptors leads to cell-autonomous degeneration of cholinergic motor neurons and paralysis.C. elegansdouble mutants lacking calreticulin and calnexin—two genes previously implicated in the cellular events leading to necrotic-like cell death (Xu et al. 2001)—are resistant to nAChR-mediated toxicity and possess normal numbers of motor neuron cell bodies. Nonetheless, excess nAChR activation leads to progressive destabilization of the motor neuron processes and, ultimately, paralysis in these animals. Our results provide new evidence that chronic activation of ionotropic receptors can have devastating degenerative effects in neurons and reveal that ion channel-mediated toxicity may have distinct consequences in neuronal cell bodies and processes.
Influence of Phasic and Tonic Dopamine Release on Receptor Activation
Authors: Dreyer Jakob K. , Herrik Kjartan F. , Berg Rune W. , Hounsgaard Jørn D.
Published: October 2010

Tonic and phasic dopamine release is implicated in learning, motivation, and motor functions. However, the relationship between spike patterns in dopaminergic neurons, the extracellular concentration of dopamine, and activation of dopamine receptors remains unresolved. In the present study, we develop a computational model of dopamine signaling that give insight into the relationship between the dynamics of release and occupancy of D1and D2receptors. The model is derived from first principles using experimental data. It has no free parameters and offers unbiased estimation of the boundaries of dopaminergic volume transmission. Bursts primarily increase occupancy of D1receptors, whereas pauses translate into low occupancy of D1and D2receptors. Phasic firing patterns, composed of bursts and pauses, reduce the average D2receptor occupancy and increase average D1receptor occupancy compared with equivalent tonic firing. Receptor occupancy is crucially dependent on synchrony and the balance between tonic and phasic firing modes. Our results provide quantitative insight in the dynamics of volume transmission and complement experimental data obtained with electrophysiology, positron emission tomography, microdialysis, amperometry, and voltammetry.
Distinct Levels of Dopamine Denervation Differentially Alter Striatal Synaptic Plasticity and NMDA Receptor Subunit Composition
Authors: Paillé Vincent , Picconi Barbara , Bagetta Vincenza , Ghiglieri Veronica , Sgobio Carmelo , Di Filippo Massimiliano , Viscomi Maria T. , Giampà Carmela , Fusco Francesca R. , Gardoni Fabrizio , Bernardi Giorgio , Greengard Paul , Di Luca Monica , Calabresi Paolo
Published: October 2010

A correct interplay between dopamine (DA) and glutamate is essential for corticostriatal synaptic plasticity and motor activity. In an experimental model of Parkinson's disease (PD) obtained in rats, the complete depletion of striatal DA, mimicking advanced stages of the disease, results in the loss of both forms of striatal plasticity: long-term potentiation (LTP) and long-term depression (LTD). However, early PD stages are characterized by an incomplete reduction in striatal DA levels. The mechanism by which this incomplete reduction in DA level affects striatal synaptic plasticity and glutamatergic synapses is unknown. Here we present a model of early PD in which a partial denervation, causing mild motor deficits, selectively affects NMDA-dependent LTP but not LTD and dramatically alters NMDA receptor composition in the postsynaptic density. Our findings show that DA decrease influences corticostriatal synaptic plasticity depending on the level of depletion. The use of the TAT2A cell-permeable peptide, as an innovative therapeutic strategy in early PD, rescues physiological NMDA receptor composition, synaptic plasticity, and motor behavior.
The Expression of TAG-1 in Glial Cells Is Sufficient for the Formation of the Juxtaparanodal Complex and the Phenotypic Rescue of Tag-1 Homozygous Mutants in the CNS
Authors: Savvaki Maria , Theodorakis Kostas , Zoupi Lida , Stamatakis Antonis , Tivodar Simona , Kyriacou Kyriacos , Stylianopoulou Fotini , Karagogeos Domna
Published: October 2010

Myelinated fibers are organized into specialized domains that ensure the rapid propagation of action potentials and are characterized by protein complexes underlying axoglial interactions. TAG-1 (Transient Axonal Glycoprotein-1), a cell adhesion molecule of the Ig superfamily, is expressed by neurons as well as by myelinating glia. It is essential for the molecular organization of myelinated fibers as it maintains the integrity of the juxtaparanodal region through its interactions with Caspr2 and the voltage-gated potassium channels (VGKCs) on the axolemma. Since TAG-1 is the only known component of the juxtaparanodal complex expressed by the glial cell, it is important to clarify its role in the molecular organization of juxtaparanodes. For this purpose, we generated transgenic mice that exclusively express TAG-1 in oligodendrocytes and lack endogenous gene expression (Tag-1−/−;plpTg(rTag-1)). Phenotypic analysis clearly demonstrates that glial TAG-1 is sufficient for the proper organization and maintenance of the juxtaparanodal domain in the CNS. Biochemical analysis shows that glial TAG-1 physically interacts with Caspr2 and VGKCs. Ultrastructural and behavioral analysis ofTag-1−/−;plpTg(rTag-1)mice shows that the expression of glial TAG-1 is sufficient to restore the axonal and myelin deficits as well as the behavioral defects observed inTag-1−/−animals. Together, these data highlight the pivotal role of myelinating glia on axonal domain differentiation and organization.
Laminar-Specific Maturation of GABAergic Transmission and Susceptibility to Visual Deprivation Are Related to Endocannabinoid Sensitivity in Mouse Visual Cortex
Authors: Jiang Bin , Sohya Kazuhiro , Sarihi Abdolrahman , Yanagawa Yuchio , Tsumoto Tadaharu
Published: October 2010

The developmental period when neuronal responses are modified by visual experience is reported to start and end earlier in layer 4 than in layer 2/3 of the visual cortex, and the maturation of GABAergic inhibitory circuits is suggested to determine the timing of this period. Here, we examine whether the laminar difference in such timing corresponds to a difference in the time course of the functional maturation of GABAergic synaptic transmission to star pyramidal and pyramidal cells in layers 4 and 2/3, respectively, of the mouse visual cortex and whether the development of the strength of GABAergic transmission is affected by visual deprivation in a laminar-specific manner. Our analysis of developmental changes in inhibitory postsynaptic currents of star pyramidal and pyramidal cells evoked by electrical stimulation of afferents or action potentials of fast-spiking GABAergic neurons revealed that there was a sequential maturation of GABAergic function from layers 4 to 2/3. The maturation of inhibition in layer 4 occurred at postnatal week 3, which preceded by 1 week that of layer 2/3. Visual deprivation by dark rearing arrested the functional development of GABAergic transmission in layer 2/3, whereas dark rearing was not so effective in layer 4. GABAergic synapses in layer 2/3 were sensitive to an agonist for cannabinoid type 1 receptors and not normally matured in receptor knock-out mice, whereas those in layer 4 were not so. These results suggest laminar-specific maturation of inhibition and susceptibility to visual deprivation, which may be related to the laminar difference in sensitivity to endocannabinoids.
PKA-Induced Internalization of Slack KNaChannels Produces Dorsal Root Ganglion Neuron Hyperexcitability
Authors: Nuwer Megan O. , Picchione Kelly E. , Bhattacharjee Arin
Published: October 2010

Inflammatory mediators through the activation of the protein kinase A (PKA) pathway sensitize primary afferent nociceptors to mechanical, thermal, and osmotic stimuli. However, it is unclear which ion conductances are responsible for PKA-induced nociceptor hyperexcitability. We have previously shown the abundant expression of Slack sodium-activated potassium (KNa) channels in nociceptive dorsal root ganglion (DRG) neurons. Here we show using cultured DRG neurons, that of the total potassium current,IK, the KNacurrent is predominantly inhibited by PKA. We demonstrate that PKA modulation of KNachannels does not happen at the level of channel gating but arises from the internal trafficking of Slack channels from DRG membranes. Furthermore, we found that knocking down the Slack subunit by RNA interference causes a loss of firing accommodation analogous to that observed during PKA activation. Our data suggest that the change in nociceptive firing occurring during inflammation is the result of PKA-induced Slack channel trafficking.
The Influence of Natural Scene Dynamics on Auditory Cortical Activity
Authors: Chandrasekaran Chandramouli , Turesson Hjalmar K. , Brown Charles H. , Ghazanfar Asif A.
Published: October 2010

The efficient cortical encoding of natural scenes is essential for guiding adaptive behavior. Because natural scenes and network activity in cortical circuits share similar temporal scales, it is necessary to understand how the temporal structure of natural scenes influences network dynamics in cortical circuits and spiking output. We examined the relationship between the structure of natural acoustic scenes and its impact on network activity [as indexed by local field potentials (LFPs)] and spiking responses in macaque primary auditory cortex. Natural auditory scenes led to a change in the power of the LFP in the 2–9 and 16–30 Hz frequency ranges relative to the ongoing activity. In contrast, ongoing rhythmic activity in the 9–16 Hz range was essentially unaffected by the natural scene. Phase coherence analysis showed that scene-related changes in LFP power were at least partially attributable to the locking of the LFP and spiking activity to the temporal structure in the scene, with locking extending up to 25 Hz for some scenes and cortical sites. Consistent with distributed place and temporal coding schemes, a key predictor of phase locking and power changes was the overlap between the spectral selectivity of a cortical site and the spectral structure of the scene. Finally, during the processing of natural acoustic scenes, spikes were locked to LFP phase at frequencies up to 30 Hz. These results are consistent with an idea that the cortical representation of natural scenes emerges from an interaction between network activity and stimulus dynamics.
Opioid-Induced GABA Potentiation after Chronic Morphine Attenuates the Rewarding Effects of Opioids in the Ventral Tegmental Area
Authors: Madhavan Anuradha , Bonci Antonello , Whistler Jennifer L.
Published: October 2010

GABA transmission in the ventral tegmental area (VTA) is critical for fine tuning the activity of dopamine neurons in response to opioids. However, the precise mechanism by which GABA input shapes opioid reward is poorly understood. We observed a reduction of conditioned place preference for low doses of the opioid [d-Ala2,N-MePhe4, Gly5-ol]-enkephalin (DAMGO) and a switch in the functional effects of μ-opioid receptor modulation of GABA postsynaptic currents in the mouse VTA 1 d after chronic morphine treatment. Specifically, whereas in naive mice DAMGO inhibits GABA postsynaptic currents, GABAergic currents are potentiated by DAMGO after chronic morphine treatment. Importantly, pretreatment with the cAMP signaling inhibitor (R)-adenosine, cyclic 3′,5′-(hydrogenphosphorothioate) triethylammonium both restored DAMGO reward and reversed the DAMGO-mediated potentiation, thereby reestablishing the inhibitory effects of opioids on GABA currents. Thus, a paradoxical bidirectionality in μ-receptor-mediated control of GABA transmission following chronic morphine treatment is a critical mechanism that determines the expression of opioid reward in the VTA.
Medial Dorsal Hypothalamus Mediates the Inhibition of Reward Seeking after Extinction
Authors: Marchant Nathan J. , Furlong Teri M. , McNally Gavan P.
Published: October 2010

Extinction promotes abstinence from drug seeking. Extinction expression is an active process, dependent on infralimbic prefrontal cortex (ilPFC). However, the neurocircuitry mediating extinction expression is unknown. Here we studied the neural mechanisms for expression of extinction of alcoholic beer seeking in rats. We first examined the pattern of activation in prefrontal cortex projections to medial dorsal hypothalamus (MDH) (i.e., perifornical and dorsomedial nuclei) during extinction expression. Double labeling for retrograde tracer cholera toxin B subunit (CTb) and the neuronal activity marker c-Fos revealed significant recruitment of MDH projecting ilPFC neurons during extinction expression. We then studied the causal role of MDH in inhibiting alcoholic beer seeking during extinction expression. MDH infusion of the inhibitory neuropeptide cocaine- and amphetamine-regulated transcript prevented extinction expression, showing that MDH is necessary for extinction expression. Next we examined the pattern of activation in MDH projections to paraventricular thalamus (PVT) during extinction expression. Double labeling for CTb and c-Fos revealed significant recruitment of PVT projecting MDH neurons during extinction expression. We also showed, using triple-label immunofluorescence, that the majority of PVT projecting extinction neurons express prodynorphin, suggesting that actions at κ opioid receptors (KORs) in PVT may be critical for inhibiting alcoholic beer seeking. Consistent with this, infusions of a KOR agonist into PVT prevented reinstatement of alcoholic beer seeking showing that PVT KOR activation is sufficient to inhibit alcoholic beer seeking. Together, these findings identify a role for MDH and its ilPFC afferents and PVT efferents in inhibiting alcoholic beer seeking during extinction expression.
Kognitive Humanoide Robotik: Entwicklungsschritte in Lernen und Verhaltensorganisation
Authors: Goerick Christian , Körner Edgar
Published: October 2010

In diesem Beitrag geben wir einen Überblick über unsere Forschungsarbeiten auf dem Gebiet der humanoiden Robotik mit dem Schwerpunkt auf kognitiven Systemen. Insbesondere betrachten wir eine Serie von Systemen, die wir gemäß unseres hierarchischen inkrementellen Systemansatzes erforscht, realisiert und analysiert haben.
Entwurf und Regelung des Humanoiden Laufroboters Lola
Authors: Buschmann Thomas , Lohmeier Sebastian , Ulbrich Heinz
Published: October 2010

Der Beitrag beschreibt den mechatronischen Entwurf und die Laufregelung des humanoiden Roboters Lola. Seine charakteristischen Merkmale sind die redundante Kinematik, der extreme Leichtbau, Gelenkantriebe mit bürstenlosen Motoren und eine Elektronik-Architektur mit dezentraler Gelenkregelung. Ein Schwerpunkt im Entwurf war die Optimierung der Massenverteilung zur Verbesserung der Systemdynamik. Die Referenztrajektorien werden in Echtzeit berechnet und durch eine stabilisierende Regelung auf Basis hybrider Kraft-/Positionsregelung modifiziert. Das Regelungssystem ermöglicht sowohl schnelles Gehen als auch die für das autonome Gehen erforderliche Anpassung der Laufrichtung und -geschwindigkeit während des Gehens.
DLRs zweihändiger Humanoide Justin: Systementwurf, Integration und Regelung
Authors: Wimböck Thomas , Borst Christoph , Albu-Schäffer Alin , Ott Christian , Schmidt Florian , Fuchs Matthias , Friedl Werner , Eiberger Oliver , Baumann Andreas , Beyer Alexander , Hirzinger Gerd
Published: October 2010

Mit dem mobilen humanoiden Roboter Justin stellt das DLR eine für die feinfühlige Manipulation von Alltagsgegenständen ausgelegte Hardware-Plattform vor. Die Überlegungen und wesentlichen Designentscheidungen für den mechatronischen Entwurf des Systems werden vorgestellt. Weiterhin wird beschrieben wie die vorhandene Sensorik des Systems zur passivitätsbasierten Regelung genutzt werden kann und so dem Roboter eine einstellbare Nachgiebigkeit im Aufgabenraum gegeben werden kann. Dies ermöglicht die feinfühlige Anpassung an unbekannte Umgebungen. Einige beispielhafte Anwendungen und Experimente zeigen, wie diese Eigenschaften die Programmierung solcher komplexer Robotersysteme vereinfachen und sicherer machen können.
Hazard Assessments of Manufactured Nanomaterials
Authors: Morimoto Yasuo , Kobayashi Norihiro , Shinohara Naohide , Myojo Toshihiko , Tanaka Isamu , Nakanishi Junko
Published: October 2010

Hazard Assessments of Manufactured Nanomaterials: Yasuo Morimoto, et al. Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan

Background

It has been difficult to make reliable hazard assessments of manufactured nanomaterials, because the nanomaterials form large agglomerations in both in vitro and in vivo studies.

Objective

In the New Energy and Industrial Technology Development Organization (NEDO) Project of Japan, the physicochemical properties of many manufactured nanomaterials are being measured, and in vitro and in vivo studies are being performed to determine which endpoints are correspond to the hazards and risks of nanomaterials. Focusing on titanium dioxide, fullerenes and carbon nanotubes, we introduce findings made in inhalation and intratracheal installation studies overseas, and together with the findings made in the NEDO project, and also assess the hazards presented by manufactured nanomaterials.

Results and Conclusion

A project by NEDO has succeeded in ensuring the stability of dispersion (nanoscale <100 nm) of manufactured nanomaterials, and is developing hazard assessments of manufactured nanomaterials. In these interim reports, the acceptable exposure concentration of titanium dioxide and fullerene was proposed to be 1.2 mg/m3and 0.8 mg/m3respirable dust in working environment, respectively.
ICE withdraws from ICE Conditions of Contract in favour of NEC3
Authors: Clarke Barry
Published: October 2010

The Institution of Civil Engineers (IEC) decided in July 2010 to withdraw from the 65-year-old ICE Conditions of Contract in favour of the NEC3 suite of contracts it first published in 1993. ICE vice-president Barry Clarke explains why.
Footbridge paper wins top prize in ICE 2010 graduate and student competition
Authors: Blackmore Tony
Published: October 2010

A paper on an innovative opening mechanism for a footbridge won Arup graduate Lee Franck the £1500 top prize in this year's ICE graduate and student papers competition – as well a significant boost to her confidence. ICE's awards executive Tony Blackmore explains the wider benefits.
A1 Wetherby upgrade: lowering the impact of highway engineering
Authors: Metcalfe Wayne
Published: October 2010

The A1 at Wetherby, West Yorkshire has been a notorious bottleneck for many years on the UK's primary north–south route east of the Pennine ridge. A £71 million improvement scheme was completed at the end of 2009, including upgrading the 10 km trunk road to motorway status. This paper focuses on the innovative sequential demolition techniques developed to reduce traffic delays, and explains how a significant reduction in carbon dioxide output was achieved through well-planned and effective reuse of demolition and earthworks materials.