bluuebunny/crossref_metadata_2025 huggingface dataset:
Nerve conduction studies in Charcot–Marie–Tooth disease in a cohort from Turkey
Authors: Deymeer Feza , Matur Zeliha , Poyraz Muruvvet , Battaloglu Esra , Oflazer‐Serdaroglu Piraye , Parman Yesim
Published: March 2011

Introduction:

In the demyelinating form of Charcot–Marie–Tooth disease, median motor conduction velocity (MCV) was noted to be around 20 m/s in peripheral myelin protein 22 (PMP22) duplications, in contrast to higher MCVs in connexin 32 gene (Cx32) mutations and lower MCVs in the demyelinating form of myelin protein zero gene (MPZ) mutations.

Methods:

Nerve conduction studies were performed in 64 families with both common and rare mutations.

Results:

Mean MCV of the median nerve was 20 ± 5 m/s in PMP22 duplications, 34 ± 6 m/s in Cx32 mutations, 20 ± 9 m/s in KIAA1985 (SH3TC2) mutations, and 11 ± 8 m/s in MPZ mutations. Conduction was generally uniform; however, conduction blocks were present in 1 patient each with the MPZ mutation and PMP22 duplication, both with unusual phenotypes.

Conclusion:

Our results confirm those of the other investigators. Electrophysiological results of the rare KIAA1985 (SH3TC2) mutation reveal that their MCVs span a broad range and that conduction is uniform. Muscle Nerve, 2011
Altered corticospinal transmission to the hand after maximum voluntary efforts
Authors: Giesebrecht Sabine , Martin Peter G. , Gandevia Simon C. , Taylor Janet L.
Published: March 2011

Introduction: After maximal voluntary contractions (MVCs), responses to corticospinal tract stimulation change differently in arm and leg muscles. This study we examined responses in the first dorsal interosseous muscle (FDI). Methods: Stimulation of the corticospinal tract at the cervicomedullary motor evoked potentials in FDI. Stimuli were delivered before and after 10‐s and 1‐min MVCs. The reproducibility of changes in the cervicomedullary motor evoked potentials (CMEPs) was investigated. F‐waves tested motoneuron excitability. Results: After the MVCs, the CMEP area was initially variable. By ∽1 min after 10‐s and 1‐min MVCs, CMEPs in relaxed muscle decreased to 63 ± 15% and 52 ± 32%, respectively, of control and remained depressed for ∽10 min. Responses evoked 2 days apart varied between subjects but not between days. After 10‐s MVCs, F‐waves were reduced at rest. During weak contraction, CMEPs but not F‐waves were depressed. Conclusions: Our results suggest that contraction produces changes at the corticomotoneuronal synapses to FDI. In addition, motoneuron excitability is reduced. Muscle Nerve, 2011
Value of distal compound muscle action potential duration prolongation in acute inflammatory demyelinating polyneuropathy: A European perspective
Authors: Rajabally Yusuf A. , Nicolas Guillaume
Published: March 2011

Introduction: The value of distal compound muscle action potential duration (DCMAPD) has not been widely studied in acute inflammatory demyelinating polyneuropathy (AIDP) with electromyography (EMG) equipment at low‐cut filter settings <10 Hz, as used in Europe. Methods: We retrospectively reviewed the records of 40 patients with AIDP and 40 controls with axonal neuropathy, from Leicester, UK, and Angers, France. Results: The best combination of sensitivity/specificity for AIDP using DCMAPD prolongation in any one nerve was offered by cut‐offs from two other studies (sensitivity: 90% and 87.5%, respectively; specificity: 92.5% for both). Independent DCMAPD prolongation in any one nerve was better than, or equivalent to, other criteria. Conclusions: DCMAPD prolongation in any one nerve, at cut‐offs suggested by prior studies, represents a sensitive and specific marker to aid/simplify electrodiagnosis of AIDP in patients studied with EMG equipment with low‐cut filter settings of <10 Hz. Muscle Nerve, 2011
Effect of knee position on quadriceps muscle force steadiness and activation strategies
Authors: Krishnan Chandramouli , Allen Eric J. , Williams Glenn N.
Published: March 2011

Introduction: In this study we investigated the effect of knee position on quadriceps force steadiness and activation strategies. Methods: Quadriceps force steadiness was evaluated in 22 volunteers at two knee positions by testing their ability to regulate submaximal force. Muscle activation strategies were studied in both time and frequency domains using surface electromyography. Results: Quadriceps force fluctuations and the associated agonist and antagonist activity were significantly higher at 90° than at 30° of flexion (P < 0.05). The quadriceps median frequency recorded at 30° was significantly higher than at 90° of flexion (P < 0.05). Regression analyses revealed that force steadiness was related to quadriceps activation and median frequency (P < 0.001), but not to hamstring coactivation (P > 0.05). Conclusions: The results indicate that knee position significantly affects quadriceps force steadiness and activation strategies. This finding may have important implications for designing a force control testing protocol and interpreting test results. Muscle Nerve, 2011
Differential susceptibility of muscles to myotonia and force impairment in a mouse model of myotonic dystrophy
Authors: Moyer Michelle , Berger Dara S. , Ladd Andrea N. , Van Lunteren Erik
Published: March 2011

Introduction:

Myotonic dystrophy, or dystrophia myotonica (DM), is characterized by prominent muscle wasting and weakness as well as delayed muscle relaxation resulting from persistent electrical discharges.

Methods:

We hypothesized heterogeneity among muscles in degree of weakness and myotonia in an expanded [(CUG)250] repeats transgenic (HSALR) mouse DM model. Muscle contraction was compared among diaphragm, extensor digitorum longus (EDL), and soleus muscles.

Results:

Myotonia was found only in EDL, as manifested by longer late‐relaxation time and elevated myotonic index. EDL, but not the other two muscles, had impaired force over a wide range of stimulation frequencies. During fatigue‐inducing stimulation, DM EDL muscle force per cross‐sectional area was significantly impaired during 25‐Hz stimulation, whereas there were no differences in fatigue response for DM diaphragm or soleus.

Conclusion:

In an expanded repeats model of DM the EDL is more susceptible to myotonia and force impairment than muscles with lower proportions of fast‐twitch fibers. Muscle Nerve, 2011
Sleep hypoventilation syndrome and respiratory failure due to multifocal motor neuropathy with conduction block
Authors: Kyriakides Theodoros , Papacostas Savvas , Papanicolaou Eleni , Bagdades Evis , Papathanasiou Eleftherios S.
Published: March 2011

Sleep hypoventilation syndrome and respiratory failure have been reported in association with a diverse spectrum of neuromuscular disorders. We report a patient with multifocal motor neuropathy with conduction block who presented with sleep hypoventilation, presumably due to bilateral phrenic neuropathy and was initially diagnosed to have obstructive sleep apnea syndrome. Once the correct diagnosis was made the patient was treated successfully with a combination of regular immunoglobulin and bilevel nocturnal ventilation. Delay in the administration of intravenous immunoglobulin resulted in respiratory failure. Muscle Nerve, 2011
Unconfined seepage analysis in earth dams using smoothed fixed grid finite element method
Authors: Kazemzadeh‐Parsi Mohammad Javad , Daneshmand Farhang
Published: March 2011

One major difficulty in seepage analyses is finding the position of phreatic surface which is unknown at the beginning of solution and must be determined in an iterative process. The objective of the present study is to develop a novel non‐boundary‐fitted mesh finite‐element method capable of solving the unconfined seepage problem in domains with arbitrary geometry and continuously varied permeability. A new non‐boundary‐fitted finite element method named as smoothed fixed grid finite element method (SFGFEM) is used to simplify the solution of variable domain problem of unconfined seepage. The gradient smoothing technique, in which the area integrals are transformed into the line integrals around edges of smoothing cells, is used to obtain the element matrices. The solution process starts with an initial guess for the unknown boundary and SFGFEM is used to approximate the field variable. The boundary shape is then modified to eventually satisfy nonlinear boundary condition in an iterative process. Some numerical examples are solved to evaluate the applicability of the proposed method and the results are compared with those available in the literature. Copyright © 2011 John Wiley & Sons, Ltd.
3D subsidence analyses above gas reservoirs accounting for an unconventional plasticity model
Authors: Salomoni Valentina A. , Fincato Riccardo
Published: March 2011

The coupled hydro‐mechanical state in soils coming from consolidation/subsidence processes and undergoing plasticity phenomena is here evaluated by means of the subloading surface model. The most important feature of this theory is the abolition of the distinction between the elastic and plastic domains, as it happens in the conventional elastoplastic models. This means that plastic deformations are generated whenever there is a change in stress and a smoother elastoplastic transition is produced. The plasticity algorithm has been implemented in the PLASCON3D FE code, coupling hydro‐thermo‐mechanical fields within a saturated (locally partially saturated) porous medium subjected to external loads and water/gas withdrawals from deep layers (aquifers/reservoirs). The 3D model has been first calibrated and validated against examples taken from the literature, and then subsidence analyses at regional scales due to gas extractions have been developed to predict the evolution of settlements and pore pressure in soils for long‐term scenarios. Copyright © 2011 John Wiley & Sons, Ltd.
PNE versus 1st stage tined lead procedure: A direct comparison to select the most sensitive test method to identify patients suitable for sacral neuromodulation therapy
Authors: Leong Randall K. , De Wachter Stefan G.G. , Nieman F.H.M. , de Bie Rob A. , van Kerrebroeck Philip E.V.
Published: March 2011

Aims

To compare the patient's response rate to the Percutaneous Nerve Evaluation test (PNE) and the 1st stage tined‐lead placement test (FSTLP) for sacral neuromodulation therapy (SNM).

Methods

Single center study on patients with refractory idiopathic overactive bladder syndrome (OAB) or non‐obstructive urinary retention, screened with both PNE and FSTLP. Patients were followed prospectively and their response rate based on bladder diary after PNE was compared to that after FSTLP. More than 50% improvement in at least two relevant urinary symptoms was considered a positive response. A Wilcoxon paired test was done to compare the rates of the two screening options and logistic regression to determine possible associations. A follow‐up was conducted to determine the long‐term failure rate.

Results

One hundred patients were included (82 female, 69 OAB). The mean age was 55 years (SD 13). The positive response rate on PNE was 47%. FSTLP showed a 69% positive response rate, which was negatively related to age. The 22% gain in positive response was statistically significant (P < 0.001) and positively associated with female gender and younger age. All 69 patients with a positive response to FSTLP received SNM treatment. Failure rate after an average of 2 years was 2.9%.

Conclusions

This study suggests that FSTLP may be a more sensitive screening method than PNE to identify patients eligible for SNM therapy, warranting randomized trials. Neurourol. Urodynam. 30:1249–1252, 2011. © 2011 Wiley‐Liss, Inc.
Green tea drinking is inversely associated with urinary incontinence in middle‐aged and older women
Authors: Hirayama Fumi , Lee Andy H.
Published: March 2011

Aims

To investigate the association between green tea consumption and urinary incontinence among middle‐aged and older women.

Methods

Three hundred community‐dwelling women aged 40–75 years were recruited in middle and southern Japan. A validated food frequency questionnaire was administered face‐to‐face to obtain information on dietary intake and habitual tea and coffee consumption. Urinary incontinence status was ascertained using the International Consultation on Incontinence Questionnaire‐Short Form.

Results

The prevalence of urinary incontinence was 27.5% among 298 eligible participants. The 82 women who leaked urine tended to drink less green tea (daily mean intake 622, SD 554 ml) than others without the condition (daily mean intake 757, SD 571 ml), P = 0.04. Relative to non‐drinkers, the adjusted odds ratios of urinary incontinence were 0.37 (95% CI 0.15–0.91) for drinking more than 700 ml and 0.34 (95% CI 0.13–0.88) for drinking 4 or more cups daily. The corresponding dose–response relationships for these quantity (P = 0.04) and frequency (P = 0.01) of intake were significant. However, association with black tea, oolong tea and coffee consumption was not evident.

Conclusions

The findings suggested an inverse association between urinary incontinence and habitual green tea consumption in middle‐aged and older women. Neurourol. Urodynam. 30:1262–1265, 2011. © 2011 Wiley‐Liss, Inc.
Is there an association between female urinary incontinence and decreased genital sensation?
Authors: Lowenstein Lior , Gruenwald Ilan , Itskovitz‐Eldor Joseph , Gartman Irena , Vardi Yoram
Published: March 2011

Aim

To explore the relationship between urinary incontinence and genital sensory functioning in females with sexual dysfunction disorders.

Methods

A retrospective consecutive chart review was conducted for all women who were referred to our tertiary female urology clinic with a primary complaint of sexual dysfunction between October 1999 and January 2009. Our study sample included 177 women, all of whom underwent a thorough clinical evaluation. Urinary incontinence was diagnosed based on clinical history and physical examination by a urogynecologist. The Genital Thermal and Vibratory Sensory Analyzer (GSA) was used for sensory testing in the genital area. Independent t‐test and multivariate linear regression were used for statistical analysis.

Results

Of the 177 study patients (median age 34, range 18–68), 63 (36%) had urinary incontinence. Women with urinary incontinence were found to be less sensitive to warm, cold, and vibratory thresholds at both the anterior and the posterior vaginal wall and the clitoral area (P < 0.05).

Conclusions

Women with urinary incontinence and sexual dysfunction are less sensitive to all sensory testing in the genital region than women with sexual dysfunction alone. This relationship may be attributable to afferent nerve damage and the critical role it may play in the etiology of urinary incontinence. Neurourol. Urodynam. 30:1291–1294, 2011. © 2011 Wiley‐Liss, Inc.
Neuromodulation of bladder activity by stimulation of feline pudendal nerve using a transdermal amplitude modulated signal (TAMS)
Authors: Shen Bing , Roppolo James R. , Subbaroyan Jeyakumar , DiUbaldi Anthony , Wahlgren Steve , de Groat William C. , Tai Changfeng
Published: March 2011

Aim: To develop a non‐invasive neuromodulation method to regulate bladder activity.

Methods: Neuromodulation of bladder activity was investigated in felines with an intact spinal cord under α‐chloralose anesthesia using a transcutaneous stimulation method with surface electrodes attached to the skin area between the base of the tail and the sciatic notch.

Results: The bladder could be either inhibited or excited depending on stimulation frequency and bladder volume. With the bladder distended to induce large amplitude rhythmic isovolumetric bladder contractions, stimulation at a frequency between 5 and 7 Hz significantly suppressed the contractions. Stimulation applied during a cystometrogram (CMG) also increased bladder capacity by 44.3 ± 10.8%. At a frequency between 20 and 40 Hz the inhibitory effect on rhythmic bladder contractions was weak and did not increase bladder capacity during CMG. At low bladder volumes ranging between 60% and 100% of the bladder capacity 20 Hz stimulation‐induced small amplitude (21.2 ± 14.6 cmH2O) bladder contractions. However, stimulation at 20 Hz induced large amplitude (111.7 ± 22.2 cmH2O) bladder contractions at a bladder volume about 100–110% of the bladder capacity after the rhythmic bladder contractions were completely inhibited by the inhibitory 5 Hz stimulation.

Conclusions: Both inhibitory and excitatory effects on bladder activity can be obtained in cats using the non‐invasive neural stimulation approach. This pre‐clinical study warrants a further clinical trial to investigate the possibility of using this non‐invasive stimulation method to treat incontinence or urinary retention. Neurourol. Urodynam. 30: 1686–1694, 2011. © 2011 Wiley Periodicals, Inc.
The roles of fascins in health and disease
Authors: Hashimoto Yosuke , Kim Dae Joong , Adams Josephine C
Published: March 2011

Fascins are actin‐binding proteins that cross‐link filamentous actin into tightly packed parallel bundles. These bundles are important for the organization and morphology of an extremely diverse set of sub‐cellular structures that include dynamic and stable cell‐surface protrusions, stress fibres, and the specialized actin bundles of photoreceptor and stereocilia cells. In this review, we discuss the fascin gene family and its evolution, the actin‐bundling activity of fascins and the molecular pathways by which it is regulated, and the role of the diverse actin/fascin structures in normal cellular processes. We discuss the mechanisms by which fascins contribute to disease pathologies, especially cancer, where fascin‐1 is emerging as a novel therapeutic target in carcinoma metastasis. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Transition from cylindroma to spiradenoma in CYLD‐defective tumours is associated with reduced DKK2 expression
Authors: Rajan Neil , Burn John , Langtry James , Sieber‐Blum Maya , Lord Christopher J , Ashworth Alan
Published: March 2011

Patients carrying heterozygous germline truncating mutations in the CYLD gene develop multiple primary hair follicle‐related tumours. A highly patterned tumour, termed cylindroma, and a highly disorganized tumour, termed spiradenoma, may both develop in the same patient. Furthermore, histological features of both tumour types have been described within the same tumour specimen. We used three‐dimensional computer‐aided reconstruction of these tumours to demonstrate contiguous growth of cylindromas into spiradenomas, thus suggesting a transition between the two tumour types. To explore factors that may influence cutaneous tumour patterning, genome‐wide transcriptomic analysis of 32 CYLD‐defective tumours was performed. Overexpression of the Wnt/β‐catenin signalling pathway was observed relative to normal perilesional tissue. Morphometric analysis was used to investigate the relationship between Wnt pathway‐related gene expression and tumour organization. This revealed an association between reduced Dickkopf 2 (DKK2—a negative regulator of the Wnt/β‐catenin signalling pathway) expression and loss of tumour patterning. Reduced DKK2 expression was associated with methylation of the DKK2 gene promoter in the majority of tumour samples assayed. RNA interference‐mediated silencing of DKK2 expression in cylindroma primary cell cultures caused an increase in colony formation, cell viability, and anchorage‐independent growth. Using these data, we propose a model where epigenetic programming may influence tumour patterning in patients with CYLD mutations. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Insulin‐like growth factor‐1 receptor inhibition overcomes gefitinib resistance in mucinous lung adenocarcinoma
Authors: Hurbin Amandine , Wislez Marie , Busser Benoît , Antoine Martine , Tenaud Corine , Rabbe Nathalie , Dufort Sandrine , de Fraipont Florence , Moro‐Sibilot Denis , Cadranel Jacques , Coll Jean‐Luc , Brambilla Elisabeth
Published: March 2011

The appropriate selection of patients is a major challenge in the treatment of non‐small cell lung cancer (NSCLC) with epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs). Prospective trials in adenocarcinoma demonstrated that the mucinous subtype presents a poorer outcome under EGFR‐TKI treatment than the non‐mucinous subtype. Our aim was to determine the molecular characteristics associated with resistance to EGFR‐TKIs in mucinous and non‐mucinous adenocarcinoma. Eighty adenocarcinoma samples, including 34 tumours from patients treated with gefitinib in a phase II clinical trial (IFCT0401), were classified as mucinous (n = 32) or non‐mucinous (n = 48) adenocarcinoma. We demonstrated that four biological markers were differentially expressed between the two subtypes: mucinous tumours that overexpressed IGF1R (p < 0.0001) and amphiregulin (p = 0.004) with a tendency for more frequent KRAS mutations, in contrast to non‐mucinous tumours that overexpressed EGFR (p < 0.0001) and TTF‐1 (p < 0.0001) with more frequent EGFR mutations (p = 0.037). Higher IGF1R (p = 0.02) and lower TTF‐1 (p = 0.02) expression was associated with disease progression under gefitinib treatment. We observed in vitro cross‐talk between EGFR and IGF1R signalling pathways in gefitinib‐resistant H358 mucinous cells. Anti‐amphiregulin siRNAs and anti‐IGF1R treatments sensitized the H358 cells to gefitinib‐induced apoptosis with additive effects, suggesting that these treatments could overcome the resistance of mucinous tumours to EGFR‐TKIs, including those with KRAS mutation. Our results highlighted that mucinous and non‐mucinous adenocarcinoma subtypes are different entities with different therapeutic responses to EGFR‐TKIs. These data will foster the development of therapeutic strategies for treating adenocarcinoma with mucinous component. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles
Authors: Muralidhar Balaji , Winder David , Murray Matthew , Palmer Roger , Barbosa‐Morais Nuno , Saini Harpreet , Roberts Ian , Pett Mark , Coleman Nicholas
Published: March 2011

Although gain of chromosome 5p is one of the most frequent DNA copy‐number imbalances in cervical squamous cell carcinoma (SCC), the genes that drive its selection remain poorly understood. In a previous cross‐sectional clinical study, we showed that the microRNA processor Drosha (located on chromosome 5p) demonstrates frequent copy‐number gain and overexpression in cervical SCC, associated with altered microRNA profiles. Here, we have conducted gene depletion/overexpression experiments to demonstrate the functional significance of up‐regulated Drosha in cervical SCC cells. Drosha depletion by RNA interference (RNAi) produced significant, specific reductions in cell motility/invasiveness in vitro, with a silent RNAi‐resistant Drosha mutation providing phenotype rescue. Unsupervised hierarchical clustering following global profiling of 319 microRNAs in 18 cervical SCC cell line specimens generated two groups according to Drosha expression levels. Altering Drosha levels in individual SCC lines changed the group into which the cells clustered, with gene depletion effects being rescued by the RNAi‐resistant mutation. Forty‐five microRNAs showed significant differential expression between the groups, including four of 14 that were differentially expressed in association with Drosha levels in clinical samples. miR‐31 up‐regulation in Drosha‐overexpressing samples/cell lines was the highest‐ranked change (by adjusted p value) in both analyses, an observation validated by northern blotting. These functional data support the role of Drosha as an oncogene in cervical SCC, by affecting expression of cancer‐associated microRNAs that have the potential to regulate numerous protein‐coding genes. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Prenatal BACs‐on‐Beads™: a new technology for rapid detection of aneuploidies and microdeletions in prenatal diagnosis
Authors: Vialard F. , Simoni G. , Aboura A. , De Toffol S. , Molina Gomes D. , Marcato L. , Serero S. , Clement P. , Bouhanna P. , Rouleau E. , Grimi B. , Selva J. , Gaetani E. , Maggi F. , Joseph A. , Benzacken B. , Grati F. R.
Published: March 2011

Objective

Molecular cytogenetic techniques on uncultured prenatal samples are the sole tests applied in some countries in cases with advanced maternal age (AMA) or increased risk after prenatal screening. Moreover, there is a trend to perform invasive prenatal diagnosis (PD) during the first trimester before ultrasound manifestations, so new rapid and reliable assays are necessary to investigate microdeletions not detectable with the conventional karyotype. We report the validation study of the prenatal bacterial artificial chromosomes‐on‐Beads™(BoBs™; CE‐IVD), a bead‐based multiplex assay detecting chromosomes 13, 18, 21, X/Y aneuploidies and nine microdeletion regions having an overall detection rate of 1/1700.

Method

We retrospectively studied 408 selected samples and prospectively tested 212 consecutive samples ascertained for conventional karyotyping.

Results

We did not find false‐positive results. Triploidies were not detected. Maternal cell contamination of male samples up to 90% was unmasked inspecting gonosome profiles. Mosaic conditions at 20 to 30% were revealed. Failures were due to low amount of DNA.

Conclusion

Prenatal BoBs™is a robust technology for the investigation of fetuses with normal karyotype with or without sonographic abnormalities. Running in parallel with the karyotype analysis, it can be proposed instead of rapid FISH or QF‐PCR providing rapid results on common aneuploidies and additional information regarding the microdeletion syndromes. Copyright © 2011 John Wiley & Sons, Ltd.
How microbial proteomics got started
Authors: Neidhardt Frederick C.
Published: March 2011

Publication in 1975 by Patrick O'Farrell of a procedure to separate the proteins of Escherichia coli in a two‐dimensional array on polyacrylamide gels marked the birth of the field now called proteomics. Although O'Farrell's contribution was soon to have wide ranging effects on research in many fields, the initial impact was greatest in the arena of whole cell physiology. Refinements and amplification of the original procedure, including improved standardization and reproducibility of gel patterns, introduction of techniques to measure the quantity of protein in individual spots, and biochemical identification of the protein spots, afforded investigators the ability to explore for the first time the integrated working of control circuits in the living cell. From O'Farrell's contribution has grown the rich array of techniques currently employed and still being developed in the diverse field of microbial proteomics.
Mining quorum sensing regulated proteins – Role of bacterial cell‐to‐cell communication in global gene regulation as assessed by proteomics
Authors: Eberl Leo , Riedel Katharina
Published: March 2011

Many bacteria utilize cell‐to‐cell communication systems that rely on small diffusible signal molecules to monitor the size of their population in a process known as quorum sensing (QS). QS plays a central role in coordinating genes that are generally mediating prokaryotic interactions with its eukaryotic host. In pathogens, this form of gene regulation is, for instance, believed to ensure that the cells remain invisible to the immune system until the pathogen has reached a critical population density sufficient to overwhelm host defenses and to establish an infection. This review summarizes proteome analyses to identify QS‐regulated proteins focussing on Gram‐negative bacteria interacting with their eukaryotic hosts either as symbionts or as pathogens. In most studies, the power of comparative 2‐D PAGE coupled to MS analysis has been employed to recognize and identify QS‐controlled proteins. The high number of QS‐regulated proteins in the majority of the investigated species strongly supports the importance of QS as global regulatory system and suggests that it also operates via post‐transcriptional mechanisms. As QS has been proven to be a central regulator for the expression of pathogenic traits and biofilm formation in various opportunistic pathogens, it represents a highly attractive target for the development of novel antibacterial drugs. Proteomics has also been exploited to validate the target specificity of natural and synthetic QS inhibitors that have a great potential as alternative therapeutics for the treatment of bacterial infections.
Polymer thermal and acoustic properties using heterodyne detected transient grating technique
Authors: Amirkhani Masoud , Taschin Andrea , Cucini Riccardo , Bartolini Paolo , Leporini Dino , Torre Renato
Published: March 2011

We investigated the acoustic and thermal features of a polymeric system by a heterodyne detected transient grating technique. We studied two polymers characterized by different molecular weights. Transient grating experiments could reveal a reliable series of information on sound velocity, acoustic damping time, and thermal diffusion of the polymers. The temperature and molecular weight dependence of the polymer acoustic and thermal properties are reported. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011
Surface Modification of COC Microfluidic Devices: A Comparative Study of Nitrogen Plasma Treatment and its Advantages Over Argon and Oxygen Plasma Treatments
Authors: Roy Sunanda , Yue Chee Yoon
Published: March 2011

Control of surface properties is very important in high performance microfluidic devices because appropriate functionalization of the surface of the microchannel helps to minimize adsorption of certain analytes thus improving its performance. In this regard, both the argon and oxygen plasma techniques have been used to improve the adaption of polymer surfaces to biological environments. However, the less common nitrogen plasma technique has not been used for surface modification of cyclic olefin copolymer (COC) in microfluidic applications. This paper presents a comparative study between the argon, oxygen, and nitrogen plasma treatments with the aim to identify the most suitable process for the development of a smart, disposable chip for the Bio‐MEMS application. The chemical and morphological changes of the plasma modified COC surfaces were characterized using X‐ray photoelectron spectroscopy, atomic force microscopy, and water contact angle measurements. The effect of plasma treatment on the strength of thermally bonded lap‐shear specimens was studied. The influence of plasma treatment on the integrity of thermally sealed microdevices was assessed using burst pressure tests. The plasma treatments had a significant impact on the electroosmosis flow mobility in the microchannels. The hemocompatibility of the various plasma‐modified COC surfaces was determined using the static platelets adhesion experiment. It was shown that the nitrogen plasma treatment was more effective than the argon and oxygen treatments for the modification of COC based microfluidic devices.

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Diagnosis of subclinical and clinical acute T‐cell‐mediated rejection in renal transplant patients by urinary proteome analysis
Authors: Metzger Jochen , Chatzikyrkou Christos , Broecker Verena , Schiffer Eric , Jaensch Lothar , Iphoefer Alexander , Mengel Michael , Mullen William , Mischak Harald , Haller Hermann , Gwinner Wilfried
Published: March 2011

Purpose: Noninvasive diagnosis of acute renal allograft rejection may be advantageous compared with the allograft biopsy.

Experimental design: In this study, a multi‐marker classification model for rejection was defined on a training set of 39 allograft patients by statistical comparison of capillary electrophoresis mass spectrometry (CE‐MS) peptide spectra in urine samples from 16 cases with subclinical acute T‐cell‐mediated tubulointerstitial rejection and 23 nonrejection controls.

Results: Application of the rejection model to a blinded validation set (n=64) resulted in an AUC value of 0.91 (95% CI: 0.82–0.97, p=0.0001). In total, 16 out of 18 subclinical and 10 out of 10 clinical rejections (BANFF grades Ia/Ib), and 28 out of 36 controls without rejection were correctly classified. Acute tubular injury in the biopsies or concomitant urinary tract infection did not interfere with CE‐MS‐based diagnosis. Sequence information of identified altered collagen α(I) and α (III) chain fragments in rejection samples suggested an involvement of matrix metalloproteinase‐8 (MMP‐8). Biopsy stainings revealed matrix metalloproteinase‐8 exclusively in neutrophils located within peritubular capillaries and sparsely, in the tubulointerstitium during rejection.

Conclusions and clinical relevance: The established marker set contains peptides related to tubulointerstitial infiltration seen in acute rejection. The set of urinary peptide markers will be used for early diagnosis of acute kidney allograft rejection marker in a multicenter phase III prospective study.
Exploring sequence requirements for C3/C4 carboxylate recognition in the Pseudomonas aeruginosa cephalosporinase: Insights into plasticity of the AmpC β‐lactamase
Authors: Drawz Sarah M. , Taracila Magdalena , Caselli Emilia , Prati Fabio , Bonomo Robert A.
Published: March 2011

In Pseudomonas aeruginosa, the chromosomally encoded class C cephalosporinase (AmpC β‐lactamase) is often responsible for high‐level resistance to β‐lactam antibiotics. Despite years of study of these important β‐lactamases, knowledge regarding how amino acid sequence dictates function of the AmpC Pseudomonas‐derived cephalosporinase (PDC) remains scarce. Insights into structure‐function relationships are crucial to the design of both β‐lactams and high‐affinity inhibitors. In order to understand how PDC recognizes the C3/C4 carboxylate of β‐lactams, we first examined a molecular model of a P. aeruginosa AmpC β‐lactamase, PDC‐3, in complex with a boronate inhibitor that possesses a side chain that mimics the thiazolidine/dihydrothiazine ring and the C3/C4 carboxylate characteristic of β‐lactam substrates. We next tested the hypothesis generated by our model, i.e. that more than one amino acid residue is involved in recognition of the C3/C4 β‐lactam carboxylate, and engineered alanine variants at three putative carboxylate binding amino acids. Antimicrobial susceptibility testing showed that the PDC‐3 β‐lactamase maintains a high level of activity despite the substitution of C3/C4 β‐lactam carboxylate recognition residues. Enzyme kinetics were determined for a panel of nine penicillin and cephalosporin analog boronates synthesized as active site probes of the PDC‐3 enzyme and the Arg349Ala variant. Our examination of the PDC‐3 active site revealed that more than one residue could serve to interact with the C3/C4 carboxylate of the β‐lactam. This functional versatility has implications for novel drug design, protein evolution, and resistance profile of this enzyme.
Structural biology of gram‐positive bacterial adhesins
Authors: Vengadesan Krishnan , Narayana Sthanam V. L.
Published: March 2011

The structural biology of Gram‐positive cell surface adhesins is an emerging field of research, whereas Gram‐negative pilus assembly and anchoring have been extensively investigated and are well understood. Gram‐positive surface proteins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) and individual proteins that assemble into long, hair‐like organelles known as pili have similar features at the primary sequence level as well as at the tertiary structural level. Some of these conserved features are essential for their transportation from the cytoplasm and for cell wall anchoring. More importantly, the MSCRAMMs and the individual pilins are assembled with building blocks that are variants of structural modules used for human immunoglobulins. MSCRAMMs target the host's extracellular matrix proteins, such as collagen, fibrinogen, and fibronectin, and they have received considerable attention from structural biologists in the last decade, who have primarily been interested in understanding their interactions with host tissue. The recent focus is on the newly discovered pili of Gram‐positive bacteria, and in this review, we highlight the advances in understanding of the individual pilus constituents and their associations and stress the similarities between the individual pilins and surface proteins.
NMR reveals novel mechanisms of protein activity regulation
Authors: Kalodimos Charalampos G.
Published: March 2011

NMR spectroscopy is one of the most powerful tools for the characterization of biomolecular systems. A unique aspect of NMR is its capacity to provide an integrated insight into both the structure and intrinsic dynamics of biomolecules. In addition, NMR can provide site‐resolved information about the conformation entropy of binding, as well as about energetically excited conformational states. Recent advances have enabled the application of NMR for the characterization of supramolecular systems. A summary of mechanisms underpinning protein activity regulation revealed by the application of NMR spectroscopy in a number of biological systems studied in the lab is provided.
A career pathway in protein folding: From model peptides to postreductionist protein science
Authors: Gierasch Lila M.
Published: March 2011

This review discusses the inherent challenge of linking “reductionist” approaches to decipher the information encoded in protein sequences with burgeoning efforts to explore protein folding in native environments—“postreductionist” approaches. Because the invitation to write this article came as a result of my selection to receive the 2010 Dorothy Hodgkin Award of the Protein Society, I use examples from my own work to illustrate the evolution from the reductionist to the postreductionist perspective. I am incredibly honored to receive the Hodgkin Award, but I want to emphasize that it is the combined effort, creativity, and talent of many students, postdoctoral fellows, and collaborators over several years that has led to any accomplishments on which this selection is based. Moreover, I do not claim to have unique insight into the topics discussed here; but this writing opportunity allows me to illustrate some threads in the evolution of protein folding research with my own experiences and to point out to those embarking on careers how the twists and turns in anyone's scientific path are influenced and enriched by the scientific context of our research. The path my own career has taken thus far has been shaped by the timing of discoveries in the field of protein science; together with our contemporaries, we become part of a knowledge evolution. In my own case, this has been an epoch of great discovery in protein folding and I feel very fortunate to have participated in it.
An alternative view of the proposed alternative activities of hemopexin
Authors: Mauk Marcia R. , Smith Ann , Grant Mauk A.
Published: March 2011

Hemopexin is a plasma protein that plays a well‐established biological role in sequestering heme that is released into the plasma from hemoglobin and myoglobin as the result of intravascular or extravascular hemolysis as well as from skeletal muscle trauma or neuromuscular disease. In recent years, a variety of additional biological activities have been attributed to hemopexin, for example, hyaluronidase activity, serine protease activity, pro‐inflammatory and anti‐inflammatory activity as well as suppression of lymphocyte necrosis, inhibition of cellular adhesion, and binding of divalent metal ions. This review examines the challenges involved in the purification of hemopexin from plasma and in the recombinant expression of hemopexin and evaluates the questions that these challenges and the characteristics of hemopexin raise concerning the validity of many of the new activities proposed for this protein. As well, an homology model of the three‐dimensional structure of human hemopexin is used to reveal that the protein lacks the catalytic triad that is characteristic of many serine proteases but that hemopexin possesses two highly exposed Arg‐Gly‐Glu sequences that may promote interaction with cell surfaces.
Quantum flavor oscillations extended to the Dirac theory
Authors: Bernardini A.E. , Guzzo M.M. , Nishi C.C.
Published: March 2011

Flavor oscillations by itself and its coupling with chiral oscillations and/or spin‐flipping are the most relevant quantum phenomena of neutrino physics. This report deals with the quantum theory of flavor oscillations in vacuum, extended to fermionic particles in the several subtle aspects of the first quantization and second quantization theories. At first, the basic controversies regarding quantum‐mechanical derivations of the flavor conversion formulas are reviewed based on the internal wave packet (IWP) framework. In this scenario, the use of the Dirac equation is required for a satisfactory evolution of fermionic mass‐eigenstates since in the standard treatment of oscillations the mass‐eigenstates are implicitly assumed to be scalars and, consequently, the spinorial form of neutrino wave functions is not included in the calculations. Within first quantized theories, besides flavor oscillations, chiral oscillations automatically appear when we set the dynamic equations for a fermionic Dirac‐type particle. It is also observed that there is no constraint between chiral oscillations, when it takes place in vacuum, and the process of spin‐flipping related to the helicity quantum number, which does not take place in vacuum. The left‐handed chiral nature of created and detected neutrinos can be implemented in the first quantized Dirac theory in presence of mixing; the probability loss due to the changing of initially left‐handed neutrinos to the undetected right‐handed neutrinos can be obtained in analytic form. These modifications introduce correction factors proportional to mν2/Eν2 that are very difficult to be quantified by the current phenomenological analysis. All these effects can also be identified when the non‐minimal coupling with an external (electro)magnetic field in the neutrino interacting Lagrangian is taken into account. In the context of a causal relativistic theory of a free particle, one of the two effects should be present in flavor oscillations: (a) rapid oscillations or (b) initial flavor violation. Concerning second quantized approaches, a simple second quantized treatment exhibits a tiny but inevitable initial flavor violation without the possibility of rapid oscillations. Such effect is a consequence of an intrinsically indefinite but approximately well defined neutrino flavor. Within a realistic calculation in pion decay, including the quantum field treatment of the creation process with finite decay width, it is possible to quantify such violation. The violation effects are shown to be much larger than loop induced lepton flavor violation processes, already present in the standard model in the presence of massive neutrinos with mixing. For the implicitly assumed fermionic nature of the Dirac theory, the conclusions of this report lead to lessons concerning flavor mixing, chiral oscillations, interference between positive and negative frequency components of Dirac equation solutions, and the field formulation of quantum oscillations.
Charged dilatonic black holes and their transport properties
Authors: Goutéraux B. , Kim B.S. , Meyer R.
Published: March 2011

We briefly explain the consistency conditions imposed on the effective holographic theories, which are parameterized by two real exponents (γ,δ) that control the IR dynamics. The general scaling of DC resistivity with temperature at low temperature and AC conductivity at low frequency across the whole (γ,δ) plane are explained. There is a codimension‐one region where the DC resistivity is linear in the temperature. For massive carriers, it is shown that when the scalar operator is not the dilaton, the DC resistivity scales as the heat capacity (and entropy) for (2+1)‐dimensional systems. Regions are identified where the theory at finite density is a Mott‐like insulator. This contribution is based on (C. Charmousis, et al. J. High Energy Phys. 1011, 151 (2010)) [1] with emphasis on the transport properties of charged dilatonic black holes with potential.
Free energy of ABJM theory
Authors: Smedbäck M.
Published: March 2011

The free energy of ABJM theory has previously been computed in the strong and weak coupling limits. In this note, we report on results for the computation of the first non‐vanishing quantum correction to the free energy, from the field theory side. The correction can be expressed in terms of a thermal mass for the scalar fields. This mass vanishes to 1‐loop order, but there is a non‐vanishing result to 2‐loop order. Hence, the leading correction to the free energy is non‐analytic in the 't Hooft coupling constant λ. The reason is that the infrared divergences necessitate a resummation of ring diagrams and a related reorganization of perturbation theory, in which already the leading correction receives contributions from all orders in λ. These results suggest that the free energy interpolates smoothly between weak and strong coupling.
String vacua with massive boson‐fermion degeneracy and non‐singular cosmology
Authors: Florakis I.
Published: March 2011

We discuss marginal deformations of string vacua with Massive boson‐fermion Degeneracy Symmetry (MSDS), in connection to the cosmological evolution of the Universe from an early non‐geometrical era. In particular, we discuss recent results on the stringy mechanism that resolves both Hagedorn divergences and the Initial Singularity problem.
A resilience assessment framework for infrastructure and economic systems: Quantitative and qualitative resilience analysis of petrochemical supply chains to a hurricane
Authors: Vugrin Eric D. , Warren Drake E. , Ehlen Mark A.
Published: March 2011

In recent years, the nation has recognized that critical infrastructure protection should consider not only the prevention of disruptive events but also the processes that infrastructure systems undergo to maintain functionality following disruptions. This more comprehensive approach has been termed critical infrastructure resilience. Given the occurrence of a particular disruptive event, the resilience of a system to that event is the system's ability to reduce efficiently both the magnitude and duration of the deviation from targeted system performance levels. Under the direction of the U. S. Department of Homeland Security's Science and Technology Directorate, Sandia National Laboratories has developed a comprehensive resilience assessment framework for evaluating the resilience of infrastructure and economic systems. The framework includes a quantitative methodology that measures resilience costs that result from a disruption to infrastructure function. The framework also includes a qualitative analysis methodology that assesses system characteristics affecting resilience to provide insight and direction for potential improvements. This article describes the resilience assessment framework and demonstrates the utility of the assessment framework through application to two hypothetical scenarios involving the disruption of a petrochemical supply chain by hurricanes. © 2011 American Institute of Chemical Engineers Process Saf Prog, 2011