bluuebunny/crossref_metadata_2025 huggingface dataset:
Mass spectrometry analysis of the influenza virus
Authors: Downard Kevin M. , Morrissey Bethny , Schwahn Alexander B.
Published: September 2008

The role of mass spectrometry to probe characteristics of the influenza virus, and vaccine and antiviral drugs that target the virus, are reviewed. Genetic and proteomic approaches have been applied which incorporate high resolution mass spectrometry and mass mapping to genotype the virus and establish its evolution in terms of the primary structure of the surface protein antigens. A mass spectrometric immunoassay has been developed and applied to assess the structure and antigenicity of the virus in terms of the hemagglutinin antigen. The quantitation of the hemagglutinin antigen in vaccine preparations has also been conducted that is of importance to their efficacy. Finally, the characterization and quantitation of antiviral drugs against the virus, and their metabolites, have been monitored in blood, serum, and urine. The combined approaches demonstrate the strengths of modern mass spectrometric methods for the characterization of this killer virus. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 28:35–49, 2009 [This article was published online 10 September 2008. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 7 November 2008.]
Electrophysiological correlates of motor conversion disorder
Authors: Liepert Joachim , Hassa Thomas , Tüscher Oliver , Schmidt Roger
Published: September 2008

In patients with a functional (psychogenic) paresis, motor conduction tests are, by definition, normal. We investigated whether these patients exhibit an abnormal motor excitability. Four female patients with a functional paresis of the left upper extremity were studied using transcranial magnetic stimulation (TMS). We investigated motor thresholds, intracortical inhibition and intracortical facilitation at rest. Corticospinal excitability was evaluated by single pulse TMS during rest and during imagination of tonic index finger adductions. Data obtained from the affected first dorsal interosseous muscle were compared with the unaffected hand and with a healthy age‐matched control group. Three patients demonstrated a flaccid paresis, one patient had a psychogenic dystonia. Motor thresholds, short interval intracortical inhibition and intracortical facilitation recorded from the affected side were normal. In healthy subjects, movement imagination produced an increase of corticospinal excitability. In the patients, motor imagery with the affected index finger resulted in a decrease of corticospinal excitability compared to rest, being significantly different from the unaffected side and from the control group. We suggest that suppression of corticospinal excitability during movement imagination is an electrophysiological correlate of the patients' inability to move voluntarily and provides some insight into the pathophysiology of this disorder. © 2008 Movement Disorder Society
Focal childhood‐onset, action induced primary hip dystonia treated with pallidal deep brain stimulation
Authors: Low Hu Liang , Honey Christopher R.
Published: September 2008

Focal proximal lower limb dystonias are rare. Unlike the adult form, focal lower limb dystonias in children usually become generalized. The condition is often unrecognized and the patient often receives orthopedic or psychiatric treatment for years before the diagnosis eventually made. Previously reported cases of isolated lower limb dystonias have been managed nonsurgically. We present a case of a childhood‐onset action‐induced primary hip dystonia that has remained focal even in adulthood and which responded successfully to pallidal deep brain stimulation. Additionally, our results suggest that neurons representing the leg lie within the most ventral aspect of the globus pallidus interna. © 2008 Movement Disorder Society
Bilateral deep brain stimulation of the globus pallidus internus in tardive dystonia
Authors: Sako Wataru , Goto Satoshi , Shimazu Hideki , Murase Nagako , Matsuzaki Kazuhito , Tamura Tetsuya , Mure Hideo , Tomogane Yusuke , Arita Norio , Yoshikawa Hiroo , Nagahiro Shinji , Kaji Ryuji
Published: September 2008

Tardive dystonia is a disabling movement disorder as a consequence of exposure to neuroleptic drugs. We followed 6 patients with medically refractory tardive dystonia treated by bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for 21 ± 18 months. At last follow‐up, the Burke‐Fahn‐Marsden Dystonia Rating Scale (BFMDRS) motor score improved by 86% ± 14%, and the BFMDRS disability score improved by 80% ± 12%. Bilateral GPi‐DBS is a beneficial therapeutic option for the long‐term relief of tardive dystonia. © 2008 Movement Disorder Society
Latest view on the mechanism of action of deep brain stimulation
Authors: Hammond Constance , Ammari Rachida , Bioulac Bernard , Garcia Liliana
Published: September 2008

How does deep brain stimulation (DBS) applied at high frequency (100 Hz and above, HFS) in diverse points of cortico‐basal ganglia thalamo‐cortical loops alleviate symptoms of neurological disorders such as Parkinson's disease, dystonia, and obsessive compulsive disorders? Do the effects of HFS stem solely or even largely from local effects on the stimulated brain structure or are they also mediated by actions of HFS on distal structures? Indeed, HFS as an extracellular stimulation is expected to activate subsets of both afferent and efferent axons, leading to antidromic spikes that collide with ongoing spontaneous ones and orthodromic spikes that evoke synaptic responses in target neurons. The present review suggests that HFS interfere with spontaneous pathological patterns by introducing a regular activity in several nodal points of the network. Therefore, the best site of implantation of the HFS electrode may be in a region where the HFS‐driven activity spreads to most of the identified, dysrhythmic, neuronal populations without causing additional side effects. This should help tackling the most difficult issue namely, how does the regular HFS‐driven activity that dampens the spontaneous pathological one, restore neuronal processing along cortico‐basal ganglia‐thalamo‐cortical loops? © 2008 Movement Disorder Society
Alternate trains of postural muscle vibration promote cyclic body displacement in standing parkinsonian patients
Authors: De Nunzio Alessandro M. , Nardone Antonio , Picco Daniele , Nilsson Jan , Schieppati Marco
Published: September 2008

Patients suffering from Parkinson's disease (PD) have difficulties with control of stance, postural changes, and walking, seemingly depending on problems in central integration of proprioceptive information. We tested the hypothesis that alternate vibration of postural muscles can induce cyclic medio‐lateral or antero‐posterior sway in PD, mimicking that accompanying body progression during walking, thereby favoring the production of locomotor tasks. In 12 standing PD patients and 11 healthy subjects, we applied trains of vibratory stimuli, bilaterally in an alternating paradigm to soleus, tibialis anterior, or paravertebral muscles. The trains of stimuli were delivered at frequencies selected to be above, near, and below the normal walking rhythm. The displacement of the center of foot pressure (CoP) was recorded. In PD, sway area during unperturbed stance was just larger than in healthy subjects; shifts in CoP in response to vibration were preserved, regardless of the vibrated muscle pair; CoP oscillations along medio‐lateral, but not antero‐posterior direction, were coupled to the vibration trains; time to initiate and terminate the postural responses was normal. PD patients correctly integrate and exploit the vibration‐induced proprioceptive inflow to produce body oscillations comparable to those occurring during walking. Vibratory stimulation can be safely and easily employed to provoke rhythmic postural changes in PD. © 2008 Movement Disorder Society
Parkinsonism and dystonia caused by the illicit use of ephedrone—A longitudinal study
Authors: Selikhova Marianna , Fedoryshyn Ljuda , Matviyenko Yuri , Komnatska Irena , Kyrylchuk Marianna , Krolicki Lesrek , Friedman Andrzej , Taylor Andrew , Jäger H. Rolf , Lees Andrew , Sanotsky Yanush
Published: September 2008

A neurological syndrome characterized by levodopa unresponsive bradykinesia, retropulsion with falls backwards, dysarthria, gait disturbance, dystonia, and emotional lability was identified in 13 male opiate addicts following the prolonged intravenous use of ephedrone (methcathinone), a central nervous stimulant prepared from pseudoephedrine, potassium permanganate, and vinegar. The natural history, response to treatment, and clinical features has been studied, and MR and dopamine transporter SPECT brain imaging were carried out. Pubic hair was sampled for manganese. The clinical and radiological picture closely resembled previous reports of chronic manganese poisoning and increased mean manganese level in pubic hair observed for at least 1 year after cessation of ephedrone. Odor identification was intact. Cognitive assessment showed a mild executive dysfunction and a mild depression. DaTSCANs were all normal. The neurological syndrome bears some similarities to PSP but differs from Parkinson's disease. Delayed neurological progression despite discontinuation of ephedrone occurred in one‐third of cases. Ephedrone poisoning should be considered as a possible cause of secondary Parkinsonism in young adults, particularly from Eastern Europe. © 2008 Movement Disorder Society
Structure elucidation and complete NMR spectral assignments of two new sesquiterpene lactone xylosides from Lactuca triangulata
Authors: Michalska Klaudia , Żylewski Marek , Kisiel Wanda
Published: September 2008

Two new sesquiterpene lactone xylosides, derivatives of the guaianolides 9α‐hydroxyleucodin and 9α‐hydroxy‐11,13‐dehydroleucodin, were isolated from roots of Lactuca triangulata. Their structures were established on the basis of 1H and 13C NMR spectra, 2D NMR (HMQC, HMBC, COSY, NOESY) techniques and comparison with the literature data. The compounds represent the first example of sesquiterpene lactone xylosides. Copyright © 2008 John Wiley & Sons, Ltd.
Exploring the healthcare journey of patients with rheumatoid arthritis: A mapping project – implications for practice
Authors: Oliver Susan
Published: September 2008

Objective: Consumers of healthcare can reveal important insights into the personal challenges they experience when negotiating their health needs. The National Rheumatoid Arthritis Society (NRAS) wanted to explore the experiences of those with rheumatoid arthritis (RA) in order to understand the impact on the individual and on healthcare resources and benchmark care against published standards and guidelines.

Methods: A project was designed to explore the experiences of individuals with sero‐positive RA who had been diagnosed for three years or less. Qualitative semi‐structured interviews were used and combined with process mapping to explore the experiences of a purposeful sample of individuals with RA. The information generated was mapped and variances explored. Ethical approval was not required as the data were collected outside the National Health Service.

Results: Twenty‐two participants' stories were mapped. Fifty per cent of participants sought a medical opinion within three weeks of symptom onset and the majority received a disease‐modifying anti‐rheumatic drug within six months from first presenting symptoms. Work‐related issues were highlighted by 13 participants, and seven of these experienced job losses directly attributed to their diagnosis.

Conclusions: This unique mapping approach used qualitative research and process mapping to compare patient experiences against recognized standards and guidelines. These twenty‐two stories reveal important insights into the challenges experienced in negotiating these healthcare journeys and the impact upon the individual as a result of variances in standards of care received. The participants in this study were chiefly self‐motivated, informed and articulate, and did not reflect the broad ethnic, social or cultural diversity in the UK. Limitations must also be considered in relation to perceptions and recall of participants over a three‐year period, as these may have altered over time and illness experience. Copyright © 2008 John Wiley & Sons, Ltd.
Ultrasonographic swelling ratio in the diagnosis of ulnar neuropathy at the elbow
Authors: Yoon Joon Shik , Walker Francis O. , Cartwright Michael S.
Published: September 2008

High‐resolution ultrasound can demonstrate focal nerve enlargement in entrapment neuropathies. We hypothesized that a ratio between the nerve cross‐sectional area at the site of maximal enlargement and at an unaffected site may improve diagnostic accuracy in ulnar neuropathy at the elbow (UNE), when compared to a single measurement at the site of maximal enlargement. Ultrasound was used to measure the cross‐sectional area of the ulnar nerve at three sites in 30 normal, healthy controls and 26 individuals with UNE. In individuals with UNE, the ratio was 2.9:1 when the site of maximal swelling was compared with a distal ulnar nerve site and 2.8:1 when compared with a proximal site. This represented a significant increase compared with the ratio of 1.1:1 for both comparisons in controls (P < 0.0001). This type of ratio may be particularly useful for assessing entrapment in those with polyneuropathy or obesity, both of which can cause diffuse nerve enlargement. Muscle Nerve, 2008
Motor responses of the sternocleidomastoid muscle in patients with amyotrophic lateral sclerosis
Authors: Pinto Susana , de Carvalho Mamede
Published: September 2008

The sternocleidomastoid muscle (SCM) is an accessory inspiratory muscle, but it is not investigated systematically in patients with amyotrophic lateral sclerosis (ALS). We aimed to study the involvement of the SCM and to evaluate the role of the diaphragm and SCM on respiratory tests performed in ALS patients. We studied 45 patients (mean age ± SD: 60.6 ± 13 years). In all patients we evaluated: neck flexion strength; forced vital capacity (FVC); maximal inspiratory pressure (PImax); sniff nasal inspiratory pressure (SNIP); ALS functional scale (ALS‐FRS‐R); SCM and diaphragm compound muscle action potential (CMAP) amplitudes (SCM Ampl and Diaphr Ampl) and latencies (SCM Lat and Diaphr Lat). In ALS patients, SCM Lat is increased and SCM Ampl is smaller in patients with neck weakness. The subgroup of patients with neck weakness had more abnormal respiratory function tests and lower clinical scores. There is a significant correlation between SCM Amp and Diaphr Ampl, FVC, PImax, and SNIP. Hence, there is a parallel loss of motor units in the SCM and diaphragm. On multiple regression analysis both PImax and SNIP are dependent on SCM Ampl and Diaphr Ampl, but FVC is not. PImax and SNIP determination mostly depend on SCM and diaphragm function, but the FVC is also dependent on expiratory muscle function. We conclude that neck weakness is a clinical sign that indicates a poor prognosis, and the SCM CMAP can contribute to respiratory function evaluation in ALS patients. Muscle Nerve, 2008
Decreased muscle atrophy F‐box (MAFbx) expression in regenerating muscle after muscle‐damaging exercise
Authors: Okada Atsushi , Ono Yusuke , Nagatomi Ryoichi , Kishimoto Koshi N. , Itoi Eiji
Published: September 2008

A muscle‐specific ubiquitin ligase, Muscle Atrophy F‐box (MAFbx), is known to mediate the degradation of muscle‐specific transcription factor MyoD in vitro. Its regulation in regenerating skeletal muscle, however, has not been clarified. We looked for evidence of MAFbx downregulation in the course of regeneration after muscle damaging exercise. The soleus and gastrocnemius muscles of mice were subjected to forced eccentric contraction by electrical stimulation to induce muscle damage. The expression of developmental myosin heavy chain (MHCd) suggested that muscle regeneration took place from Day 3 after exercise. mRNA and protein expression of MAFbx decreased on Days 3, 5, and 7, while MyoD protein increased on Days 3, 5, and 7. Although further study is required to establish the causal relationships, downregulation of MAFbx may have reduced MyoD degradation in favor of muscle regeneration. Muscle Nerve, 2008
Complications of needle electromyography: Hematoma risk and correlation with anticoagulation and antiplatelet therapy
Authors: Lynch Stacy L. , Boon Andrea J. , Smith Jay , Harper C. Michel , Tanaka Elisa M.
Published: September 2008

Electromyography (EMG) is considered a relatively safe procedure based primarily on clinical experience. Literature review reveals few reported complications from bleeding or hematoma formation. No evidence‐based guidelines exist for EMG procedures in patients who are taking anticoagulant or antiplatelet medications. The purpose of this study was to determine if patients taking anticoagulant or antiplatelet agents exhibit an increased risk of hematoma formation after routine needle EMG of the tibialis anterior muscle when compared to controls. Study subjects underwent routine needle EMG of the tibialis anterior muscle followed by ultrasound examination to evaluate for the presence of hematoma formation. A mean of 30.8 min elapsed between needle insertion and ultrasound evaluation. A total of 101 patients who were taking warfarin were studied. They had International Normalized Ratio (INR) values at or above 1.5, and two were found to have small, subclinical hematomas. Of 57 patients taking clopidogrel and/or aspirin, 1 was found to have a small, subclinical hematoma. In the control group (51 patients taking neither class of medication), no hematomas were found on ultrasound. This study suggests that hematoma formation from a standard needle EMG is rare. In addition, hematoma formation in our study group of patients on anticoagulant or antiplatelet medications was also uncommon, and no patients with documented hematomas experienced symptoms. These findings should be considered when determining the feasibility of electrodiagnostic evaluation of patients who are taking anticoagulant or antiplatelet medications. Muscle Nerve, 2008
Oculomotor involvement in myotonic dystrophy type 2
Authors: Ajroud‐Driss Senda , Sufit Robert , Siddique Teepu , Hain Timothy C.
Published: September 2008

Oculomotor function has not been studied in patients with myotonic dystrophy type 2 (DM2). We report the presence of rebound nystagmus in seven of eight patients with DM2 in the absence of a structural brainstem or cerebellar lesion. The rebound nystagmus observed in these patients is very suggestive of ocular myotonia, and examination of patients using video‐Frenzel goggles may be a useful method for diagnosing myotonia of the extraocular muscles. Muscle Nerve, 2008
Animal models of sacral neuromodulation for detrusor overactivity
Authors: Vignes Jean‐Rodolphe , Deloire Mathilde , Petry Klaus
Published: September 2008

The recent increase in the use of sacral neuromodulation (SN) for the treatment of detrusor overactivity has coincided with improved knowledge of micturition physiology and technological advances in nerve stimulation. Efficacy of SN treatment and patient satisfaction should continue to progress. Nevertheless, the exact mechanism of the action of this technique remains uncertain. Numerous theories have been proposed to explain the mechanism of action, including stimulation of efferents, or direct effect on the muscle, stimulation of the afferents, induction of spinal plasticity, and modifications of cortical activation. In experimental conditions, to evaluate the effects of electrical stimulation, animal models are generally focused on bladder inflammation or spinalization which both induce detrusor overactivity. Recently, experimental autoimmune encephalomyelitis in rats has proven useful to study bladder dysfunction characterized as both detrursor overactivity or acontractile detrursor. The present article reviews experimental approaches for SN for treatment of detrusor overactivity and provides explanations for the potential acting mechanisms. Neurourol. Urodynam. 28:8–12, 2009. © 2008 Wiley‐Liss, Inc.
High‐order layerwise finite element for the damped free‐vibration response of thick composite and sandwich composite plates
Authors: Plagianakos Theofanis S. , Saravanos Dimitris A.
Published: September 2008

A high‐order layerwise finite element methodology is presented, which enables prediction of the damped dynamic characteristics of thick composite and sandwich composite plates. The through‐thickness displacement field in each discrete layer of the laminate includes quadratic and cubic polynomial distributions of the in‐plane displacements, in addition to the linear approximations assumed by linear layerwise theories. Stiffness, mass and damping matrices are formulated from ply to structural level. Interlaminar shear stress compatibility conditions are imposed on the discrete layer matrices, leading to both size reduction and prediction of interlaminar shear stresses at the laminate interfaces. The C1 continuous finite element implemented yields an element damping matrix in addition to element stiffness and mass matrices. Application cases include thick [0/90/0], [±θ]S and [±θ] composite plates with interlaminar damping layers and sandwich plates with composite faces and foam core. In the latter case, modal frequencies and damping were also experimentally determined and compared with the finite element predictions. Copyright © 2008 John Wiley & Sons, Ltd.
Correlation between rheological, electrical, and microstructure characteristics in polyethylene/aluminum nanocomposites
Authors: Huang Xingyi , Kim Chonung , Ma Zhisen , Jiang Pingkai , Yin Yi , Li Zhe
Published: September 2008

Polyethylene (PE)/aluminum (Al) nanocomposites with various filler contents were prepared by a solution compounding method. We investigated the influence of the surface modification of Al nanoparticles on the microstructure and physical properties of the nanocomposites. The silane coupling agent octyl‐trimethoxysilane was shown to significantly increase interfacial compatibility between the polymer phase and Al nanoparticles. Rheological percolation threshold values were determined by analyzing the improvement in storage modulus at low frequencies depending on the Al loadings. Lower percolation threshold values were obtained for the composites prepared with the original nanoparticles than those prepared with the silane‐modified Al nanoparticles. A strong correlation between the time and concentration dependences of dc conductivity and rheological properties was observed in the different nanocomposite systems. The rheological threshold of the composites is smaller than the percolation threshold of electrical conductivity for both of the nanocomposite systems. The difference in percolation threshold is understood in terms of the smaller particle–particle distance required for electrical conduction when compared with that required to impede polymer mobility. It was directly shown by SEM characterization that the nanoparticle surface modification yielded better filler dispersion, as is consistent with our rheological and electrical analysis. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2143–2154, 2008
Investigation of thermodynamic properties of hyperbranched poly(ester amide) by inverse gas chromatography
Authors: Dritsas G. S. , Karatasos K. , Panayiotou C.
Published: September 2008

Thermodynamic properties of the hyperbranched poly (ester amide) (Hybrane® 1200) were investigated by inverse gas chromatography (IGC) using 19 different solvents as the probes at infinite dilution. Retention data of probes were used for an extensive characterization of the polymer, which includes the determination of the Flory‐Huggins interaction parameter, the weight fraction activity coefficient, the total, partial, and additive solubility parameters. The analysis of the results indicated that the additive value of the solubility parameter is lower than the value obtained from a standard procedure. Furthermore, the solubility parameter decreases with increase of temperature. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2166–2172, 2008
Investigation on nonisothermal crystallization kinetics of the high‐flow nylon 6 by differential scanning calorimetry
Authors: Zhang Fan , Zhou Li , Xiong Yuanqin , Xu Weijian
Published: September 2008

The crystallization kinetics of the high‐flow nylon 6 containing polyamidoamine (PAMAM) dendrimers units in nylon 6 matrix was investigated by differential scanning calorimetry. The Ozawa and Mo equations were used to describe the crystallization kinetics under nonisothermal condition. The values of Avrami exponent m and the cooling crystallization function F(T) were determined from the Ozawa plots, which showed bad linearity, and were divided into three sections depending on different cooling rates. The plots of the m and log F(T) values versus crystallization temperatures were obtained, which indicated that the actual crystallization mechanisms might change with the crystallization temperatures. The high‐flow nylon 6 has higher values of m and log F(T) than those of pure nylon 6, which implied that the high‐flow nylon 6 had more complicated crystallization mechanisms and slower crystallization rate than those of pure nylon 6. The good linearity of the Mo plots verified the success of this combined approach. The activation energies of the high‐flow nylon 6 ranged from 157 to 174 kJ/mol, which were determined by the Kissinger method. The ΔE values were lower than those of pure nylon 6, and the ΔE values were affected by both the generation and the content of PAMAM units in the nylon 6 matrix. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2201–2211, 2008
Chiari I malformation presenting as chronic cough
Authors: Amos Louella B. , Quintero Diana R.
Published: September 2008

We present a 9‐month‐old infant with persistent cough refractory to conventional asthma therapy. An extensive evaluation eventually revealed a Chiari I malformation with syringohydromyelia. His cough resolved one month after surgical decompression, suggesting that brainstem compression from the Chiari malformation directly caused his symptoms. Pediatr Pulmonol. 2008; 43:1040–1042. © 2008 Wiley‐Liss, Inc.
CSF amyloid‐β 1‐38 and 1‐42 in FTD and AD: Biomarker performance critically depends on the detergent accessible fraction
Authors: Bibl Mirko , Lewczuk Piotr , Esselmann Hermann , Mollenhauer Brit , Klafki Hans‐Wolfgang , Welge Volker , Wolf Stefanie , Trenkwalder Claudia , Otto Markus , Kornhuber Johannes , Wiltfang Jens
Published: September 2008

Cerebrospinal fluid (CSF) Aβ1‐38, Aβ1‐40, and Aβ1‐42 were comparatively analyzed by amyloid‐beta SDS‐PAGE with Western immunoblot (Aβ‐SDS‐PAGE/immunoblot), electrochemiluminescence detection and ELISA (MSD/ELISA) in patients with Alzheimer's disease (AD, n = 40), frontotemporal dementia (FTD, n = 30), and other dementias (n = 50) and nondemented disease controls (n = 30). CSF Aβ‐peptide concentrations were higher and selective decreases of CSF Aβ1‐38 in FTD and Aβ1‐42 in AD were more evident as measured after SDS‐denaturizing of samples by Aβ‐SDS‐PAGE/immunoblot. The SDS‐accessible pool of CSF Aβ1‐38 and Aβ1‐42, represented by the individual gain of Aβ‐peptide yield using Aβ‐SDS‐PAGE/immunoblot, was reduced in both FTD and AD. Accordingly, biomarker accuracies of Aβ1‐38 and Aβ1‐42 for detection of FTD and AD, respectively declined as determined by MSD/ELISA. We conclude that a pool of CSF Aβ1‐38 and Aβ1‐42, which shows disease‐specific reductions in FTD and AD, may be bound to carriers and can be released by SDS. Assessing this SDS‐accessible Aβ‐peptide pool may crucially enhance the accuracy of CSF biomarker tests. Identifying disease‐specific binding properties of affected Aβ carriers may elucidate pathogenic aspects and open up a novel field for therapeutic approaches.
Applications of protein microarrays for biomarker discovery
Authors: Ramachandran Niroshan , Srivastava Sanjeeva , LaBaer Joshua
Published: September 2008

The search for new biomarkers for diagnosis, prognosis, and therapeutic monitoring of diseases continues in earnest despite dwindling success at finding novel reliable markers. Some of the current markers in clinical use do not provide optimal sensitivity and specificity, with the prostate cancer antigen (PSA) being one of many such examples. The emergence of proteomic techniques and systems approaches to study disease pathophysiology has rekindled the quest for new biomarkers. In particular the use of protein microarrays has surged as a powerful tool for large‐scale testing of biological samples. Approximately half the reports on protein microarrays have been published in the last two years especially in the area of biomarker discovery. In this review, we will discuss the application of protein microarray technologies that offer unique opportunities to find novel biomarkers.
Insulin receptor expression by human prostate cancers
Authors: Cox Michael E. , Gleave Martin E. , Zakikhani Mahvash , Bell Robert H. , Piura Esther , Vickers Elaine , Cunningham Matthew , Larsson Ola , Fazli Ladan , Pollak Michael
Published: September 2008

BACKGROUND

Although recent laboratory and population studies suggest that prostate cancer may be responsive to insulin, there is a gap in knowledge concerning the expression of insulin receptors on benign or malignant prostate tissue.

METHODS

We immunostained 644 cores on tissue microarrays prepared from 29 prostate tissue samples without malignancies, 78 Gleason grade 3 cancers, 21 Gleason grade 4 cancers and 33 Gleason grade 5 cancers with antibodies against the insulin‐like growth factor I receptor and the insulin receptor.

RESULTS

We observed immunoreactivity with both antibodies, which implies the presence of hybrid receptors as well as IGF‐I receptors and insulin receptors. Insulin receptor staining intensity was significantly (P < 0.001) higher on malignant than benign prostate epithelial cells. Analysis of information from public gene expression databases confirmed that co‐expression of insulin receptor mRNA and IGF‐I receptor mRNA is common in prostate cancer specimens. RT‐PCR methods provided evidence for the presence of mRNA for both IR‐A and IR‐B insulin receptor isoforms.

CONCLUSION

These observations document the presence of insulin receptors on primary human prostate cancers. The findings are relevant not only to ongoing clinical trials of drug candidates that target IGF‐I and/or insulin receptors, but also to the hypothesis that obesity‐associated hyperinsulinemia mediates the adverse effect of obesity on prostate cancer prognosis. Prostate 69: 33–40, 2009. © 2008 Wiley–Liss, Inc.
Model quality assessment using distance constraints from alignments
Authors: Paluszewski Martin , Karplus Kevin
Published: September 2008

Given a set of alternative models for a specific protein sequence, the model quality assessment (MQA) problem asks for an assignment of scores to each model in the set. A good MQA program assigns these scores such that they correlate well with real quality of the models, ideally scoring best that model which is closest to the true structure. In this article, we present a new approach for addressing the MQA problem. It is based on distance constraints extracted from alignments to templates of known structure, and is implemented in the Undertaker program for protein structure prediction. One novel feature is that we extract noncontact constraints as well as contact constraints. We describe how the distance constraint extraction is done and we show how they can be used to address the MQA problem. We have compared our method on CASP7 targets and the results show that our method is at least comparable with the best MQA methods that were assessed at CASP7. We also propose a new evaluation measure, Kendall's τ, that is more interpretable than conventional measures used for evaluating MQA methods (Pearson's r and Spearman's ρ). We show clear examples where Kendall's τ agrees much more with our intuition of a correct MQA, and we therefore propose that Kendall's τ be used for future CASP MQA assessments. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Binding and release of cholesterol in the Osh4 protein of yeast
Authors: Singh Rishi P. , Brooks Bernard R. , Klauda Jeffery B.
Published: September 2008

Sterols have been shown experimentally to bind to the Osh4 protein (a homolog of the oxysterol binding proteins) of Saccharomyces cerevisiae within a binding tunnel, which consists of antiparallel β‐sheets that resemble a β‐barrel and three α‐helices of the N‐terminus. This and other Osh proteins are essential for intracellular transport of sterols and ultimately cell life. Molecular dynamics (MD) simulations are used to study the binding of cholesterol to Osh4 at the atomic level. The structure of the protein is stable during the course of all MD simulations and has little deviation from the experimental crystal structure. The conformational stability of cholesterol within the binding tunnel is aided in part by direct or water‐mediated interactions between the 3‐hydroxyl (3‐OH) group of cholesterol and Trp46, Gln96, Tyr97, Asn165, and/or Gln181 as well as dispersive interactions with Phe42, Leu24, Leu39, Ile167, and Ile203. These residues along with other nonpolar residues in the binding tunnel and lid contribute nearly 75% to the total binding energy. The strongest and most populated interaction is between Gln96 and 3‐OH with a cholesterol/Gln96 interaction energy of −4.5 ± 1.0 kcal/mol. Phe42 has a similar level of attraction to cholesterol with −4.1 ± 0.3 kcal/mol. A MD simulation without the N‐terminus lid that covers the binding tunnel resulted in similar binding conformations and binding energies when compared with simulations with the full‐length protein. Steered MD was used to determine details of the mechanism used by Osh4 to release cholesterol to the cytoplasm. Phe42, Gln96, Asn165, Gln181, Pro211, and Ile206 are found to direct the cholesterol as it exits the binding tunnel as well as Lys109. The mechanism of sterol release is conceptualized as a molecular ladder with the rungs being amino acids or water‐mediated amino acids that interact with 3‐OH. Proteins 2009. Published 2008 Wiley‐Liss, Inc.
In silico analyses of substrate interactions with human serum paraoxonase 1
Authors: Hu Xin , Jiang Xiaohui , Lenz David E. , Cerasoli Douglas M. , Wallqvist Anders
Published: September 2008

Human paraoxonase (HuPON1) is a serum enzyme that exhibits a broad spectrum of hydrolytic activities, including the hydrolysis of various organophosphates, esters, and recently identified lactone substrates. Despite intensive site‐directed mutagenesis and other biological studies, the structural basis for the specificity of substrate interactions of HuPON1 remains elusive. In this study, we apply homology modeling, docking, and molecular dynamic (MD) simulations to probe the binding interactions of HuPON1 with representative substrates. The results suggest that the active site of HuPON1 is characterized by two distinct binding regions: the hydrophobic binding site for arylesters/lactones, and the paraoxon binding site for phosphotriesters. The unique binding modes proposed for each type of substrate reveal a number of key residues governing substrate specificity. The polymorphic residue R/Q192 interacts with the leaving group of paraoxon, suggesting it plays an important role in the proper positioning of this substrate in the active site. MD simulations of the optimal binding complexes show that residue Y71 undergoes an “open‐closed” conformational change upon ligand binding, and forms strong interactions with substrates. Further binding free energy calculations and residual decomposition give a more refined molecular view of the energetics and origin of HuPON1/substrate interactions. These studies provide a theoretical model of substrate binding and specificity associated with wild type and mutant forms of HuPON1, which can be applied in the rational design of HuPON1 variants as bioscavengers with enhanced catalytic activity. Proteins 2008. Published 2008 Wiley‐Liss, Inc.
PIK3CA somatic mutations in breast cancer: Mechanistic insights from Langevin dynamics simulations
Authors: Mankoo Parminder K. , Sukumar Saraswati , Karchin Rachel
Published: September 2008

Somatic mutations in PIK3CA (phosphatidylinositol‐3 kinase, catalytic subunit, alpha isoform) are reported in breast and other human cancers to concentrate at hotspots within its kinase and helical domains. Most of these mutations cause kinase gain of function in vitro and are associated with oncogenicity in vivo. However, little is known about the mechanisms driving tumor development. We have performed computational structural studies on a homology model of wildtype PIK3CA plus recurrent H1047R, H1047L, and P539R mutations, located in the kinase and helical domains, respectively. The time evolution of the structures show that H1047R/L mutants exhibit a larger area of the catalytic cleft between the kinase N‐ and C‐lobes compared with the wildtype that could facilitate the entrance of substrates. This larger area might yield enhanced substrate‐to‐product turnover associated with oncogenicity. In addition, the H1047R/L mutants display increased kinase activation loop mobility, compared with the wildtype. The P539R mutant forms more hydrogen bonds and salt‐bridge interactions than the wildtype, properties that are associated with enhanced thermostability. Mutant‐specific differences in the catalytic cleft and activation loop behavior suggest that structure‐based mutant‐specific inhibitors can be designed for PIK3CA‐positive breast cancers. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Efficiency of a bagasse substrate in a biological bed system for the degradation of glyphosate, malathion and lambda‐cyhalothrin under tropical climate conditions
Authors: de Roffignac Laure , Cattan Philippe , Mailloux Julie , Herzog David , Le Bellec Fabrice
Published: September 2008

BACKGROUND: After the rinsing of spray equipment, the rinsing water contains polluting products. One way to avoid pollution is to bring the rinsing water over a purification system, a biological bed. The system consists of an impermeable tub filled with a biomix substrate that facilitates biodegradation of pesticides. Usually, straw is one component of the biomix. The objective of this study was to assess the efficiency of an unusual substrate, bagasse, a residue of sugar cane, for the degradation of three pesticides, glyphosate, malathion and lambda‐cyhalothrin.

RESULTS: Results showed that more than 99% of malathion and glyphosate were degraded in 6 months. In the biological bed, the DT50 value for malathion was 17 days, for glyphosate 33 days and for lambda‐cyhalothrin 43 days. The degradation rate of aminomethylphosphonic acid (AMPA) residues from the degradation of glyphosate was slower than that of the other pesticides (DT50 69 days). Finally, the innocuousness of the biomix after 6 months of degradation was confirmed by biological tests.

CONCLUSIONS: Although the degradation rates of the three pesticides in the present bagasse‐based system were similar to those under temperate conditions, the degradation conditions were improved by comparison with those in soil under the given tropical conditions. Further benefits of this system are pesticide confinement, to avoid their dispersion in the environment by liquids or solids, and a lower overall cost. Finally, possibilities for optimising the bagasse‐based system (e.g. management of the water content and nature of the biomix) are discussed. Copyright © 2008 Society of Chemical Industry
Toxicity of spiromesifen to the developmental stages of Bemisia tabaci biotype B
Authors: Kontsedalov Svetlana , Gottlieb Yuval , Ishaaya Isaac , Nauen Ralf , Horowitz Rami , Ghanim Murad
Published: September 2008

BACKGROUND: Spiromesifen is a novel insecticidal/acaricidal compound derived from spirocyclic tetronic acids that acts effectively against whiteflies and mites via inhibition of acetyl‐CoA‐carboxylase, a lipid metabolism enzyme. The effects of spiromesifen on the developmental stages of the whitefly Bemisia tabaci (Gennadius) were studied under laboratory conditions to generate baseline action thresholds for field evaluations of the compound.

RESULTS: Adult B. tabaci mortality rate after spiromesifen treatment (5 mg L−1) was 40%. Treatment with 0.5 mg L−1 reduced fecundity per female by more than 80%, and fertility was almost nil. LC50 for eggs was 2.6 mg L−1, and for first instar 0.5 mg L−1. Scanning electron microscopy revealed that eggs laid by treated adult females had an abnormally perforated chorion, and females were unable to complete oviposition. Light and fluorescent microscopy showed significantly smaller eggs following treatment, and smaller, abnormally formed and improperly localized bacteriomes in eggs and nymphs. The number of ovarioles counted in females treated with 5 mg L−1 was significantly reduced. Spiromesifen showed no cross‐resistance with other commonly used insecticides from different chemical groups, and resistance monitoring in Israel showed no development of field resistance to this insecticide after 1 year of use.

CONCLUSION: The strong effect on juvenile stages of B. tabaci with a unique mode of action and the absence of cross‐resistance with major commonly used insecticides from different chemical groups suggest the use of spiromesifen in pest and resistance management programmes. Copyright © 2008 Society of Chemical Industry
Efficient generation of Heisenberg Hamiltonian matrices for VB calculations of potential energy surfaces
Authors: Tokmachev A. M. , Robb M. A.
Published: September 2008

The spin‐Hamiltonian valence bond theory relies upon covalent configurations formed by singly occupied orbitals differing by their spin counterparts. This theory has been proven to be successful in studying potential energy surfaces of the ground and lowest excited states in organic molecules when used as a part of the hybrid molecular mechanics—valence bond method. The method allows one to consider systems with large active spaces formed by n electrons in n orbitals and relies upon a specially proposed graphical unitary group approach. At the same time, the restriction of the equality of the numbers of electrons and orbitals in the active space is too severe: it excludes from the consideration a lot of interesting applications. We can mention here carbocations and systems with heteroatoms. Moreover, the structure of the method makes it difficult to study charge‐transfer excited states because they are formed by ionic configurations. In the present work we tackle these problems by significant extension of the spin‐Hamiltonian approach. We consider (i) more general active space formed by n ± m electrons in n orbitals and (ii) states with the charge transfer. The main problem addressed is the generation of Hamiltonian matrices for these general cases. We propose a scheme combining operators of electron exchange and hopping, generating all nonzero matrix elements step‐by‐step. This scheme provides a very efficient way to generate the Hamiltonians, thus extending the applicability of spin‐Hamiltonian valence bond theory. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009
A simple model for the band structure and D.C. conductivity of an infinite CO···HN chain perpendicular to the protein backbone
Authors: Bende Attila , Bogár Ferenc , Ladik János
Published: September 2008

The1 Hartree–Fock crystal orbital (CO) method in its linear combination of atomic orbitals form was applied to determine the band structure of histone proteins taking 0.041e charge transfer per nucleotide base from the PO groups of poly(guanilic acid) to the arginine, and lysine side chains in histones (see text). Assuming that there are infinite COs, perpendicular to the main chain, formed by the amide groups of one segment of the protein chain bound together by H‐bonds with the CO groups of another segment of the chain, we have calculated the band structure. From this, we have determined the mobility using the deformation potential approximation. Multiplying this with the mobile electron concentration due to the charge transfer between the PO groups of DNA and the positive side chains in histones, we have obtained for the direct current (D.C.) electron conductivity σfib = 1.07 × 10−9 Ω−1 cm for a single fiber and after division by the cross‐section of 9.10 × 10−16 cm2, σspec = 1.18 × 106 Ω−1 cm−1 for the specific conductivity. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009
On the Hamiltonicity Gap and doubly stochastic matrices
Authors: Borkar Vivek S. , Ejov Vladimir , Filar Jerzy A.
Published: September 2008

We consider the Hamiltonian cycle problem embedded in singularly perturbed (controlled) Markov chains. We also consider a functional on the space of stationary policies of the process that consists of the (1,1)‐entry of the fundamental matrices of the Markov chains induced by these policies. We focus on the subset of these policies that induce doubly stochastic probability transition matrices which we refer to as the “doubly stochastic policies.” We show that when the perturbation parameter, ε, is sufficiently small, the minimum of this functional over the space of the doubly stochastic policies is attained at a Hamiltonian cycle, provided that the graph is Hamiltonian. We also show that when the graph is non‐Hamiltonian, the above minimum is strictly greater than that in a Hamiltonian case. We call the size of this difference the “Hamiltonicity Gap” and derive a conservative lower bound for this gap. Our results imply that the Hamiltonian cycle problem is equivalent to the problem of minimizing the variance of the first hitting time of the home node, over doubly stochastic policies. © 2008 Wiley Periodicals, Inc. Random Struct. Alg., 2009
A comparison of changes in secretory immunoglobulin A following a stress‐inducing and stress‐reducing task
Authors: Benham Grant , Nash Michael R. , Baldwin Debora R.
Published: September 2008

Research suggests that the immune system may be adversely affected by chronic stress. There is some evidence that relaxation‐based practices may effect an increase in immune functioning, but recent findings suggest that acute stress may lead to similar increases. Given this, we used a counterbalanced within‐subjects design to directly compare the effects of a stressful mental arithmetic task and a relaxation‐based task on secretory immunoglobulin A (S‐IgA). Thirty participants were seen in small groups of two or three where they were administered both a mental arithmetic (stress) task and a relaxing hypnosis task. Four‐minute timed saliva samples were obtained immediately following the two experimental tasks and following two baseline periods. Results demonstrated that, compared with baseline, S‐IgA concentration and secretion rate were significantly higher following both the relaxation‐based task and stress task. Additionally, our data showed that the increases were short‐lived, decreasing significantly within 8 min following the completion of each task. Our results indicate that both stress‐reducing and stress‐inducing tasks can increase S‐IgA levels, and these results are discussed with reference to the potential differential mechanisms and clinical significance of such changes. Copyright © 2008 John Wiley & Sons, Ltd.
Transport control of shear‐thinning fluids within corrugated microannulus
Authors: Chu Z.Kwang‐Hua , Qin Chen
Published: September 2008

The rheological characteristics and volume flow rates (up to the second order) of shear‐thinning fluids inside the transversely corrugated microannuli were obtained by using the verified fluid model and boundary perturbation method. Our results show that the temperature as well as wavy‐roughness could influence the transport of the shear‐thinning fluids significantly. Meanwhile, the phase shift between the outer and inner walls of microannuli could tune the transport of shear‐thinning fluids significantly when the wavy‐roughness (of the microannuli) is larger enough and the external forcing is small. Our results could be applied to the flow control in biofluidics and microfluidics.