bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteome of brain glia: The molecular basis of diverse glial phenotypes
Authors: Jha Mithilesh Kumar , Kim Jae‐Hong , Suk Kyoungho
Published: October 2013

Several different types of nonneuronal glial cells with diverse phenotypes are present in the CNS, and all have distinct indispensible functions. Although glial cells primarily provide neurons with metabolic and structural support in the healthy brain, they may switch phenotype from a “resting” to a “reactive” state in response to pathological insults. Furthermore, this reactive gliosis is an invariant feature of the pathogeneses of CNS maladies. The glial proteome serves as a signature of glial phenotype, and not only executes physiological functions, but also acts as a molecular mediator of the reactive glial phenotype. The glial proteome is also involved in intra‐ and intercellular communications as exemplified by glia–glia and neuron–glia interactions. The utilization of authoritative proteomic tools and the bioinformatic analyses have helped to profile the brain glial proteome and explore the molecular mechanisms of diverse glial phenotypes. Furthermore, technologic innovations have equipped the field of “glioproteomics” with refined tools for studies of the expression, interaction, and function of glial proteins in the healthy and in the diseased CNS. Glioproteomics is expected to contribute to the elucidation of the molecular mechanisms of CNS pathophysiology and to the discovery of biomarkers and theragnostic targets in CNS disorders.
Proteomic snapshot of spearmint (Mentha spicata L.) leaf trichomes: A genuine terpenoid factory
Authors: Champagne Antoine , Boutry Marc
Published: October 2013

Peltate glandular trichomes from Mentha spicata were purified on a Percoll gradient and soluble and membrane proteins were trypsinized and the peptides were separated by nano‐LC fractionation and analyzed by MALDI‐MS/MS. The vast majority of the 1666 proteins identified were housekeeping proteins or involved in the primary metabolism. However, 57 were predicted to be involved in the secondary metabolism. Of these, 21 were involved in the synthesis of phenylpropanoids and phenolics and 32 in terpenoid synthesis. Of the 14 membrane transporters identified, the 11 ATP‐binding cassette transporters provide good material for assessing whether active transport is required for the transfer of monoterpenoid intermediates between cellular compartments and for the secretion of the final products into the subcuticular storage cavity. In conclusion, this proteome analysis of M. spicata peltate trichomes has identified several candidate proteins that might be involved in terpenoid synthesis and transport. The data have been deposited to the ProteomeXchange with identifier PXD000352 (http://proteomecentral.proteomexchange.org/dataset/PXD000352).
Managing sleep disorders in primary care
Authors: Dadabhoy Shahid
Published: October 2013

Our series of Commentaries from the Primary Care Neurology Society (P‐CNS) provide a primary care perspective on neurology articles featured in Progress in Neurology and Psychiatry. Here, Dr Shahid Dadabhoy discusses ‘An update on sleep disorders and their treatment’ (see page 15 of the September October 13 issue).
Chronic mania associated with left hippocampal atrophy
Authors: Chakraborty Nandini , Miramontes Carmen
Published: October 2013

Abnormalities in the hippocampus have been implicated in the pathophysiology of bipolar disorder. Dr Chakraborty and Carmen Miramontes report an atypical presentation of bipolar disorder with chronic mania (lasting more than two years) in a patient with a history of head injury and evidence of left hippocampal atrophy on neuroimaging.
Negative symptoms in schizophrenia: meeting the challenge
Authors: Young Allan , Halari Rozmin , Gray Richard
Published: October 2013

Controlling the positive symptoms in schizophrenia is difficult but current drugs are reasonably effective. Negative symptoms pose much more of a challenge. In this Expert Panel Discussion, chaired by Progress publisher Tim Dean, the participants consider issues and solutions around the management of negative symptoms in schizophrenia, as well as developments for the future.
A radio phone‐in programme for mental health education and promotion
Authors: Laugharne Richard , Shankar Rohit , Dunkley Rosie , Fisher Sarah , Barnett Jonathan
Published: October 2013

There is evidence that mass‐media campaigns can educate the public, influence health behaviour and may reduce stigma. In this article, the authors describe how they initiated a new local radio phone‐in programme covering different mental health problems and evaluated the benefits to members of the public who called the programme.
Designed non‐symmetrical 4,7‐pi‐extended‐2,1,3‐benzothiadiazole derivatives: Synthesis guided by DFT predictions
Authors: Lopes Thiago O. , da Silva Filho Demétrio A. , Lapis Alexandre A. M. , de Oliveira Heibbe C. B. , Neto Brenno A. D.
Published: October 2013

A series of rationally designed, non‐symmetrical, 4,7‐π‐extended‐2,1,3‐benzothidiazole derivatives had their electronic and geometrical properties evaluated by means of DFT calculations. The data obtained from the calculated 2,1,3‐benzothiadiazole (BTD) intermediates allowed the design and synthesis of a final structure bearing a fluorine‐containing aromatic group on one side of the BTD ring and a C≡C spacer linking a long chain‐containing (C8) aromatic group on the other side. This specific molecular architecture is expected to display liquid crystalline behavior. The new designed structure was therefore synthesized in good overall yield using cross‐coupling reactions (Suzuki and Sonogashira reactions). Copyright © 2013 John Wiley & Sons, Ltd.
Synthesis of POSS–polyurethane hybrids using octakis(m‐isoprenyl‐α,α′‐dimethylbenzylisocyanato dimethylsiloxy) octasilsesquioxane (Q8M8TMI) as a crosslinking agent
Authors: Markovic Elda , Nguyen Kim , Clarke Stephen , Constantopoulos Kristina , Matisons Janis , Simon George P.
Published: October 2013

A series of polyurethane hybrid networks have been synthesized using octakis(m‐isoprenyl‐α,α′‐dimethylbenzylisocyanato dimethylsiloxy) octasilsesquioxane (Q8M8TMI) as a crosslinking agent. The formation of the urethane linkages within the polyurethane hybrids was confirmed by photoacoustic FTIR spectroscopy. The TGA and DSC studies demonstrated that the incorporation of the POSS crosslinking agents altered the thermal properties of the polyurethanes, and that this was dependent on the length of the polyethylene glycol chain. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 5038–5045
Copolymerization of norbornene with ω‐alkenylaluminum as a precursor comonomer for introduction of carbonyl moieties
Authors: Lee Jang‐Woo , Jantasee Sasiradee , Jongsomsjit Bunjerd , Tanaka Ryo , Nakayama Yuushou , Shiono Takeshi
Published: October 2013

Norbornene copolymers functionalized with methyl ester group or carboxy group are facilely synthesized by the copolymerization of norbornene and 7‐octenyldiisobutylaluminum (ODIBA) with ansa‐dimethylsilylene(fluorenyl)(t‐butylamido)dimethyltitanium (1) activated by Ph3CB(C6F5)4, and the sequential CO2/methanolysis reactions or CO2/hydrolysis reactions, respectively. The methanolysis and the hydrolysis are simply switched by engaging acidic methanol or acidic aqueous acetone as the quenching/washing solution, respectively. Meanwhile, the increase of ODIBA in the copolymerization abruptly decreases the yield and number–average molecular weight (Mn) of the product. However, the addition of triisobutylaluminum (8 mM) and the use of excess Ph3CB(C6F5)4 (twofold of 0.4 mM of 1) significantly increase the yield, accompanying the increase in the Mn and the narrowing of the molecular weight distribution (Mw/Mn), especially in the case of the use of excess Ph3CB(C6F5)4. The yield (g polymer/g monomers), Mn, and Mw/Mn reach up to 0.82, 341,000, and 1.46, respectively, at a copolymerization condition. The carboxy groups in the norbornene copolymers are controlled in the range of 0–1.8 mol % in high polymer yields with high Mn and narrow Mw/Mn accompanied by the decrease in the contact angle with water from 104° to 89°. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 5085–5090
Synthesis of SET–LRP‐induced galactoglucomannan‐diblock copolymers
Authors: Dax Daniel , Xu Chunlin , Långvik Otto , Hemming Jarl , Backman Peter , Willför Stefan
Published: October 2013

Polysaccharides are biorenewable and biodegradable starting materials for the development of functional materials. The synthesis of a monofunctional macroinitiator for single electron transfer‐living radical polymerization was successfully developed from a wood polysaccharide‐O‐acetyl galactoglucomannan (GGM) using a beforehand synthesized amino‐functional α‐bromoisobutyryl derivative applying reductive amination. The GGM macroinitiator was employed to initiate a controlled radical polymerization of [2‐(methacryloyloxy)ethyl]trimethylammonium chloride (MeDMA), methyl methacrylate (MMA), and N‐isopropylacrylamide (NIPAM) using Cu0/Me6‐Tren as a catalyst. The either charged or amphiphilic GGM‐b‐copolymers with different chain lengths of the synthetic block were successfully synthesized without prior hydrophobization of the GGM chain and dimethyl sulfoxide (DMSO) or DMSO/water mixtures were used as solvents. This novel synthetic approach may find untapped potentials particularly for the development of polysaccharide‐based amphiphilic additives for cosmetics or paints and for the design of novel temperature or pH responsive polymers with such potential applications as in drug delivery systems or in biocomposites. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 5100–5110
A pH‐responsive cyclopolymer having phospho‐ and sulfopropyl pendents in the same repeating unit: Synthesis, characterization, and its application as an antiscalant
Authors: Haladu Shamsuddeen A. , Ali Shaikh A.
Published: October 2013

A new zwitterionic monomer 3‐[diallyl{3‐(diethoxyphosphoryl)propyl}ammonio]propane‐1‐sulfonate has been synthesized and cyclopolymerized to give the corresponding polyzwitterion (±) (PZ) bearing both phosphonate and sulfonate functionalities on each repeating unit. phosphonate ester hydrolysis in PZ gave a pH‐responsive dibasic polyzwitterionic acid (±) (PZA) bearing PO3H2 units. The PZA under pH‐induced transformation was converted into polyzwitterion/anion (± −) (PZAN) and polyzwitterion/dianion (± =) (PZDAN) having respective PO3H− and PO32− units. The polymers′ interesting solubility and viscosity behaviors have been investigated in detail. The apparent protonation constants in salt‐free water and 0.1 M NaCl of the PO32− in (± =) (PZDAN) and PO3H– in (± −) (PZAN) as well as in their corresponding monomeric units have been determined. Evaluation of antiscaling properties of the PZA using supersaturated solution of CaSO4 revealed ≈100% scale inhibition efficiency at a meager concentration of 20 ppm for a duration of 45 h at 40 °C. The PZA has the potential to be used effectively as an antiscalant in reverse osmosis plant. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 5130–5142
Influence of monomer type on miniemulsion polymerization systems stabilized by graphene oxide as sole surfactant
Authors: Che Man S. H. , Mohd Yusof N. Y. , Whittaker Michael R. , Thickett Stuart C. , Zetterlund Per B.
Published: October 2013

Based on a recent report [J. Polym. Sci. Part A. Polym. Chem. 2013, 51, 47–58] whereby we demonstrated the synthesis of polystyrene nanoparticles by miniemulsion polymerization stabilized by graphene oxide (GO) nanosheets as sole surfactant, we hereby report the synthesis of hybrid polymer nanoparticles of several members of the (meth)acrylate family as well as the cross‐linker divinylbenzene via the same approach. The nature of the resultant emulsion is strongly linked to the polarity of the monomer used; monomers with a relatively small polar component (based on Hansen solubility parameters) such as lauryl methacrylate and benzyl methacrylate, in addition to styrene, generate stable emulsions that can be effectively polymerized. Particularly polar monomers (e.g., methyl acrylate and methyl methacrylate) formed kinetically stable emulsions in the presence of GO, however rapid coagulation occurred during polymerization. Electron microscopy analysis reveals the formation of polymer nanoparticles with size distribution between 200 and 1000 nm with roughened surface morphologies, indicative of GO sheets adsorbed at the interface. The results of this work demonstrate the applicability of this synthetic route for specific monomers in the preparation of novel graphene‐based polymeric materials. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 5153–5162
Influence of talc with different particle sizes in melt‐mixed LLDPE/MWCNT composites
Authors: Müller Michael Thomas , Dreyße Janine , Häußler Liane , Krause Beate , Pötschke Petra
Published: October 2013

Linear low‐density polyethylene (LLDPE) was melt‐mixed with multiwalled carbon nanotubes (MWCNTs) and varying amounts of three different kinds of talc (phyllo silicate), each with a different particle size distribution, to examine the effect of these filler combinations with regards to the electrical percolation behavior. The state of the filler dispersion was assessed using transmission light microscopy and electron microscopy. The use of talc as a second filler during the melt mixing of LLDPE/MWCNT composites resulted in an improvement in the dispersion of the MWCNTs and a decrease of the electrical percolation threshold. Talc with lower particle sizes showed a more pronounced effect than talc with larger particle sizes. However, the improvement in dispersion was not reflected in the mechanical properties. Modulus and stress values increase with both, MWCNT and talc addition, but not in a synergistic manner. The crystallization behavior of the composites was studied by differential scanning calorimetry to determine its potential influence on the electrical percolation threshold. It was found that the crystallinity of the matrix increased slightly with the addition of talc but no further increments were observed with the incorporation of the MWCNTs. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1680–1691
Recent advances in polymer network liquid crystal spatial light modulators
Authors: Sun Jie , Wu Shin‐Tson
Published: October 2013

Polymer network liquid crystal (PNLC) spatial light modulators are attractive for display and photonic applications because they can achieve submillisecond response time while keeping a large phase change. However, their on‐state scattering caused by the grain boundary of LC multidomains hinders their applications. In this article, we review recent progress on the development of scattering‐free PNLCs extending from short‐wavelength infrared to visible region by reducing the domain sizes to ∼200 nm through low temperature curing process. To reduce operation voltage, both transmissive and reflective modes, LC material properties (birefringence and dielectric anisotropy), polymer composition and concentration, and pretilt angle effect are analyzed. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014, 52, 183–192
Health and well‐being in adolescent survivors of early childhood cancer: a report from the Childhood Cancer Survivor Study
Authors: Mertens Ann C. , Brand Sarah , Ness Kirsten K. , Li Zhenghong , Mitby Pauline A. , Riley Anne , Patenaude Andrea Farkas , Zeltzer Lonnie
Published: October 2013

Objective

With the growing number of childhood cancer survivors in the US, it is important to assess the well‐being of these individuals, particularly during the transitional phase of adolescence. Data about adolescent survivors' overall health and quality of life will help identify survivor subgroups most in need of targeted attention to successfully transition to adulthood.

Participants and methods

This ancillary study to the Childhood Cancer Survivor Study focused on children 15‐19 years of age who had been diagnosed with cancer before the age of 4 years. A cohort of siblings of pediatric cancer survivors of the same ages served as a comparison sample. Adolescent health was assessed using the Child Health and Illness Profile‐Adolescent Edition (CHIP‐AE) survey.

Results

The teen survey was sent to 444 survivor teens and 189 siblings. Of these, 307(69%) survivors and 97 (51%) siblings completed and returned the survey. The overall health profiles of siblings and survivors were similar. Among survivors, females scored significantly below males on satisfaction, discomfort, and disorders domains. Survivors diagnosed with central nervous system tumors scored less favorably than leukemia survivors in the global domains of satisfaction and disorders.

Conclusion

In general, adolescent survivors fare favorably compared to healthy siblings. However, identification of the subset of pediatric cancer survivors who are more vulnerable to medical and psychosocial disorders in adolescence provides the opportunity for design and implementation of intervention strategies that may improve quality of life. Copyright © 2013 John Wiley & Sons, Ltd.
Polystyrene Surface Modification for Localized Cell Culture Using a Capillary Dielectric Barrier Discharge Atmospheric‐Pressure Microplasma Jet
Authors: Doherty Kyle G. , Oh Jun‐Seok , Unsworth Paul , Bowfield Andrew , Sheridan Carl M. , Weightman Peter , Bradley James W. , Williams Rachel L.
Published: October 2013

This paper reports the spatially resolved surface modification of polystyrene (PS) using an atmospheric‐pressure microplasma jet. Treatment of PS surfaces using a microplasma jet with a 100 µm diameter is investigated using contact angle, XPS, AFM and lens epithelial cell (LEC) growth. Microplasma jet treatment creates a defined reduction in contact angle of approximately 60° in a circular pattern with a diameter of 1.5 mm or more. Spatially resolved XPS analysis demonstrates that a reduction in contact angle is related to an increase in O1s peak intensity. AFM confirms that microplasma jet treatment causes no significant change in surface roughness. LECs are confined to a treated area.
Evolution of Hydrophobicity in Plasma Polymerised 1,7‐Octadiene Films
Authors: Akhavan Behnam , Jarvis Karyn , Majewski Peter
Published: October 2013

1,7‐Octadiene (OD) was plasma polymerised onto silicon wafers and glass slides under a broad range of input specific energies and deposition times to study the hydrophobicity of deposited films. Deposition of plasma polymerised 1,7‐octadiene (ppOD) film resulted in decrease of glass slide surface free energy (SFE) from ≈71 to 44 mJ · m−2. X‐ray photoelectron spectroscopy (XPS) and time of flight secondary ion mass spectroscopy (ToF‐SIMS) results confirmed that this decrease is due to the concealing of polar SiOH groups by non‐polar CxHy functionalities. Atomic force microscopy (AFM) images along with ToF‐SIMS spectra suggested patchy‐like growth of ppOD films in the very early stages of polymerisation. It has been demonstrated that a precise control over the surface hydrophobicity is achieved by simply tuning the plasma polymerisation parameters.
Synthesis, Morphological Control, and Properties of Silver Nanoparticles in Potential Applications
Authors: Shenashen Mohamed A. , El‐Safty Sherif A. , Elshehy Emad A.
Published: October 2013

Nanostructured materials, especially nanoparticles (NPs), of noble metal NPs such as silver (Ag) have been the focus of research in recent decades because of their distinct physical, chemical, and biological properties. These materials have attracted considerable attention because of their potential applications, such as catalysis, biosensing, drug delivery, and nanodevice fabrication. Previous studies on Ag NPs have clearly demonstrated that their electromagnetic, optical, and catalytic properties are strongly influenced by their shape, size, and size distribution, which can be varied by using different synthetic methods, reducing agents, and stabilizers. The valuable optical properties of Ag NPs have allowed for new approaches in sensing and imaging applications, offering a wide range of detection modes, such as colorimetric, scattering, and surface‐enhanced Raman scattering techniques, at extremely low detection limits. Here, an overview of the various chemical, physical, and biological properties of Ag NP fabrication approaches to obtain the various shapes and sizes is presented.
Multiresponsive Block Copolymer‐Modified “Hairy” Gold Nanoparticles for Remote Control of Interfaces
Authors: Shi Yelu , Selin Victor , Wang Yuhao , Sukhishvili Svetlana A.
Published: October 2013

Hybrid gold nanoparticles modified with poly(N‐isopropylacrylamide)‐block‐poly(2‐succinyloxyethyl methacrylate) (PNIPAM‐b‐PSEMA) brushes are synthesized using surface‐initiated atom transfer radical polymerization (SI‐ATRP). The “hairy” particles demonstrate reversible pH‐ and temperature‐controlled changes in size and aggregation state in solution. When adsorbed within a sub‐monolayer at a solid surface, they support reversible changes in surface wettability in response to changes in solution pH, temperature, or illumination by laser light.
Gold‐Coated Iron Oxide Glyconanoparticles for MRI, CT, and US Multimodal Imaging
Authors: Carril Mónica , Fernández Itziar , Rodríguez Juan , García Isabel , Penadés Soledad
Published: October 2013

In the pursuit of novel multimodal nanoprobes, the application of superparamagnetic gold‐coated iron oxide nanoparticles (NPs) of 6 nm as contrast agents in phantoms for X‐ray CT, US, and T2‐weighted MRI is tested. It is hypothesized that the gold coating could increase the contrast of these NPs when irradiated with X‐rays. The impact of the surrounding environment in the attenuation of gold coating is also evaluated by performing the measurements in air or in water to better mimic in vivo conditions. Additionally, it is proved that these NPs can enhance contrast in ultrasound scanning. Furthermore, their magnetite content is a known source of negative contrast in MRI. As expected, for the X‐ray CT phantoms, there is a linear increase of contrast with concentration. Additionally, the attenuation of gold in water is lower than that of the same sample in air, and the rate of attenuation at different voltage varies differently depending on the surrounding media. Interestingly, it is possible to obtain brighter ultrasound images by using these NPs and their ultrasound signal increases with the concentration of the particles. Moreover, and as expected, T2‐weighted MRI images become substantially darker as the concentration of iron increases. The obtained results and their comparative analysis show that these kinds of NPs can effectively be used as contrast agents in MRI, CT, and US. This could be an interesting starting point for future applications as multimodal contrast agents for targeted imaging.
Solidification Behavior of the Hydrazine Nitrate‐Nitroguanidine Eutectic System
Authors: Chen Ling , Li Hua‐Rong , Xu Rui‐Juan , Xiong Ying , Xu Tao , Huang Bo‐Yong , Shu Yuan‐Jie
Published: October 2013

In an attempt to better understand the properties of energetic eutectic materials, the eutectic mixture of hydrazine nitrate (HN) and nitroguanidine (NQ) was prepared by a melt crystallization method. The melting temperature and fusion enthalpy of the pure components and the eutectic were determined using differential scanning calorimetry. The structure of the HN‐NQ title compound was characterized by infrared spectroscopy (IR), X‐ray diffraction (XRD), and scanning electron microscopy. Thermodynamic functions such as excess Gibb’s energy, excess enthalpy, and excess entropy of the title mixture were calculated using activity coefficient data. The intermolecular interactions of different molar ratios of the HN‐NQ eutectic were determined by density functional theory (DFT) methods. The results of the excess thermodynamic functions and computer simulations indicate that the eutectic is not a mechanical mixture. IR spectroscopic and XRD studies confirm that there is some interaction between the components during the formation of the eutectic mixture. Moreover, the microstructure of the eutectic mixture at a molar ratio of 3 : 2 was more uniform than others, which was proved by DFT calculations. The Jackson’s roughness parameter was found to be greater than 2, suggesting a faceted, irregular morphology. These results could pave a way for further investigation of the energetic eutectic system aiming to supersede TNT.
Conformational dynamics is more important than helical propensity for the folding of the all α‐helical protein Im7
Authors: Figueiredo Angelo Miguel , Whittaker Sara B.‐M. , Knowling Stuart E. , Radford Sheena E. , Moore Geoffrey R.
Published: October 2013

Im7 folds via an on‐pathway intermediate that contains three of the four native α‐helices. The missing helix, helix III, is the shortest and its failure to be formed until late in the pathway is related to frustration in the structure. Im7H3M3, a 94‐residue variant of the 87‐residue Im7 in which helix III is the longest of the four native helices, also folds via an intermediate. To investigate the structural basis for this we calculated the frustration in the structure of Im7H3M3 and used NMR to investigate its dynamics. We found that the native state of Im7H3M3 is highly frustrated and in equilibrium with an intermediate state that lacks helix III, similar to Im7. Model‐free analysis identified residues with chemical exchange contributions to their relaxation that aligned with the residues predicted to have highly frustrated interactions, also like Im7. Finally, we determined properties of urea‐denatured Im7H3M3 and identified four clusters of interacting residues that corresponded to the α‐helices of the native protein. In Im7 the cluster sizes were related to the lengths of the α‐helices with cluster III being the smallest but in Im7H3M3 cluster III was also the smallest, despite this region forming the longest helix in the native state. These results suggest that the conformational properties of the urea‐denatured states promote formation of a three‐helix intermediate in which the residues that form helix III remain non‐helical. Thus it appears that features of the native structure are formed early in folding linked to collapse of the unfolded state.
MALDI MS profiling of post‐DRE urine samples highlights the potential of β‐microseminoprotein as a marker for prostatic diseases
Authors: Flatley Brian , Wilmott Karen G. , Malone Peter , Cramer Rainer
Published: October 2013

BACKGROUND

To use spectra acquired by matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry (MS) from pre‐ and post‐digital rectal examination (DRE) urine samples to search for discriminating peaks that can adequately distinguish between benign and malignant prostate conditions, and identify the peaks' underlying biomolecules.

METHODS

Twenty‐five participants with prostate cancer (PCa) and 27 participants with a variety of benign prostatic conditions as confirmed by a 10‐core tissue biopsy were included. Pre‐ and post‐DRE urine samples were prepared for MALDI MS profiling using an automated clean‐up procedure. Following mass spectra collection and processing, peak mass and intensity were extracted and subjected to statistical analysis to identify peaks capable of distinguishing between benign and cancer. Logistic regression was used to combine markers to create a sensitive and specific test.

RESULTS

A peak at m/z 10,760 was identified as β‐microseminoprotein (β‐MSMB) and found to be statistically lower in urine from PCa participants using the peak's average areas. By combining serum prostate‐specific antigen (PSA) levels with MALDI MS‐measured β‐MSMB levels, optimum threshold values obtained from Receiver Operator characteristics curves gave an increased sensitivity of 96% at a specificity of 26%.

CONCLUSIONS

These results demonstrate that with a simple sample clean‐up followed by MALDI MS profiling, significant differences of MSMB abundance were found in post‐DRE urine samples. In combination with PSA serum levels, obtained from a classic clinical assay led to high classification accuracy for PCa in the studied sample set. Our results need to be validated in a larger multicenter prospective randomized clinical trial. Prostate 74:103–111, 2014. © 2013 Wiley Periodicals, Inc.
Using a consensus approach based on the conservation of inter‐residue contacts to rank CAPRI models
Authors: Vangone Anna , Cavallo Luigi , Oliva Romina
Published: October 2013

Herein we propose the use of a consensus approach, CONSRANK, for ranking CAPRI models. CONSRANK relies on the conservation of inter‐residue contacts in the analyzed decoys ensemble. Models are ranked according to their ability to match the most frequently observed contacts. We applied CONSRANK to 19 CAPRI protein–protein targets, covering a wide range of prediction difficulty and involved in a variety of biological functions. CONSRANK results are consistently good, both in terms of native‐like (NL) solutions ranked in the top positions and of values of the Area Under the receiver operating characteristic Curve (AUC). For targets having a percentage of NL solutions above 3%, an excellent performance is found, with AUC values approaching 1. For the difficult target T46, having only 3.4% NL solutions, the number of NL solutions in the top 5 and 10 ranked positions is enriched by a factor 30, and the AUC value is as high as 0.997. AUC values below 0.8 are only found for targets featuring a percentage of NL solutions within 1.1%. Remarkably, a false consensus emerges only in one case, T42, which happens to be an artificial protein, whose assembly details remain uncertain, based on controversial experimental data. We also show that CONSRANK still performs very well on a limited number of models, provided that more than 1 NL solution is included in the ensemble, thus extending its applicability to cases where few dozens of models are available. Proteins 2013; 81:2210‐2220. © 2013 Wiley Periodicals, Inc.
Intrinsically disordered regions in autophagy proteins
Authors: Mei Yang , Su Minfei , Soni Gaurav , Salem Saeed , Colbert Christopher L. , Sinha Sangita C.
Published: October 2013

Autophagy is an essential eukaryotic pathway required for cellular homeostasis. Numerous key autophagy effectors and regulators have been identified, but the mechanism by which they carry out their function in autophagy is not fully understood. Our rigorous bioinformatic analysis shows that the majority of key human autophagy proteins include intrinsically disordered regions (IDRs), which are sequences lacking stable secondary and tertiary structure; suggesting that IDRs play an important, yet hitherto uninvestigated, role in autophagy. Available crystal structures corroborate the absence of structure in some of these predicted IDRs. Regions of orthologs equivalent to the IDRs predicted in the human autophagy proteins are poorly conserved, indicating that these regions may have diverse functions in different homologs. We also show that IDRs predicted in human proteins contain several regions predicted to facilitate protein–protein interactions, and delineate the network of proteins that interact with each predicted IDR‐containing autophagy protein, suggesting that many of these interactions may involve IDRs. Lastly, we experimentally show that a BCL2 homology 3 domain (BH3D), within the key autophagy effector BECN1 is an IDR. This BH3D undergoes a dramatic conformational change from coil to α‐helix upon binding to BCL2s, with the C‐terminal half of this BH3D constituting a binding motif, which serves to anchor the interaction of the BH3D to BCL2s. The information presented here will help inform future in‐depth investigations of the biological role and mechanism of IDRs in autophagy proteins. Proteins 2014; 82:565–578. © 2013 Wiley Periodicals, Inc.
Elastic network normal mode dynamics reveal the GPCR activation mechanism
Authors: Kolan Dikla , Fonar Gennadiy , Samson Abraham O.
Published: October 2013

G‐protein‐coupled receptors (GPCR) are a family of membrane‐embedded metabotropic receptors which translate extracellular ligand binding into an intracellular response. Here, we calculate the motion of several GPCR family members such as the M2 and M3 muscarinic acetylcholine receptors, the A2A adenosine receptor, the β2‐adrenergic receptor, and the CXCR4 chemokine receptor using elastic network normal modes. The normal modes reveal a dilation and a contraction of the GPCR vestibule associated with ligand passage, and activation, respectively. Contraction of the vestibule on the extracellular side is correlated with cavity formation of the G‐protein binding pocket on the intracellular side, which initiates intracellular signaling. Interestingly, the normal modes of rhodopsin do not correlate well with the motion of other GPCR family members. Electrostatic potential calculation of the GPCRs reveal a negatively charged field around the ligand binding site acting as a siphon to draw‐in positively charged ligands on the membrane surface. Altogether, these results expose the GPCR activation mechanism and show how conformational changes on the cell surface side of the receptor are allosterically translated into structural changes on the inside. Proteins 2014; 82:579–586. © 2013 Wiley Periodicals, Inc.
Docking, scoring, and affinity prediction in CAPRI
Authors: Lensink Marc F. , Wodak Shoshana J.
Published: October 2013

We present the fifth evaluation of docking and related scoring methods used in the community‐wide experiment on the Critical Assessment of Predicted Interactions (CAPRI). The evaluation examined predictions submitted for a total of 15 targets in eight CAPRI rounds held during the years 2010–2012. The targets represented one the most diverse set tackled by the CAPRI community so far. They included only 10 “classical” docking and scoring problems. In one of the classical targets, the new challenge was to predict the position of water molecules in the protein–protein interface. The remaining five targets represented other new challenges that involved estimating the relative binding affinity and the effect of point mutations on the stability of designed and natural protein–protein complexes. Although the 10 classical CAPRI targets included two difficult multicomponent systems, and a protein–oligosaccharide complex with which CAPRI participants had little experience, this evaluation indicates that the performance of docking and scoring methods has remained quite robust. More remarkably, we find that automatic docking servers exhibit a significantly improved performance, with some servers now performing on par with predictions done by humans. The performance of CAPRI participants in the new challenges, briefly reviewed here, was mediocre overall, but some groups did relatively well and their approaches suggested ways of improving methods for designing binders and for estimating the free energies of protein assemblies, which should impact the field of protein modeling and design as a whole. Proteins 2013; 81:2082–2095. © 2013 Wiley Periodicals, Inc.
Secondary sugar binding site identified for LecA lectin from Pseudomonas aeruginosa
Authors: Blanchard Bertrand , Imberty Anne , Varrot Annabelle
Published: October 2013

The galactose‐specific lectin LecA from Pseudomonas aeruginosa is a target for the development of new anti‐infectious compounds. Sugar based molecules with anti‐adhesive properties present great potential in the fight against bacterial infection and biofilm formation. LecA is specific for oligosaccharides with terminal α‐galactoside residues and displays strong affinity for melibiose (αGal1‐6Glc) with a Kd of 38.8 µM. The crystal structure of LecA/melibiose complex shows classical calcium‐bridged binding of αGal in the primary binding site but also revealed a secondary sugar binding site with glucose bound. This sugar binding site is in close proximity to the galactose binding one, is independent of calcium and mainly involves interactions with a symmetry‐related protein. This discovery would help to the design of new potent inhibitors targeting both binding sites. Proteins 2014; 82:1060–1065. © 2013 Wiley Periodicals, Inc.
Performance of ZDOCK in CAPRI rounds 20–26
Authors: Vreven Thom , Pierce Brian G. , Hwang Howook , Weng Zhiping
Published: October 2013

We report the performance of our approaches for protein–protein docking and interface analysis in CAPRI Rounds 20–26. At the core of our pipeline was the ZDOCK program for rigid‐body protein–protein docking. We then reranked the ZDOCK predictions using the ZRANK or IRAD scoring functions, pruned and analyzed energy landscapes using clustering, and analyzed the docking results using our interface prediction approach RCF. When possible, we used biological information from the literature to apply constraints to the search space during or after the ZDOCK runs. For approximately half of the standard docking challenges, we made at least one prediction that was acceptable or better. For the scoring challenges, we made acceptable or better predictions for all but one target. This indicates that our scoring functions are generally able to select the correct binding mode. Proteins 2013; 81:2175–2182. © 2013 Wiley Periodicals, Inc.
A novel twist on molecular interactions between thioredoxin and nicotinamide adenine dinucleotide phosphate‐dependent thioredoxin reductase
Authors: Kirkensgaard Kristine G. , Hägglund Per , Shahpiri Azar , Finnie Christine , Henriksen Anette , Svensson Birte
Published: October 2013

The ubiquitous disulfide reductase thioredoxin (Trx) regulates several important biological processes such as seed germination in plants. Oxidized cytosolic Trx is regenerated by nicotinamide adenine dinucleotide phosphate (NADPH)‐dependent thioredoxin reductase (NTR) in a multistep transfer of reducing equivalents from NADPH to Trx via a tightly NTR‐bound flavin. Here, interactions between NTR and Trx are predicted by molecular modelling of the barley NTR:Trx complex (HvNTR2:HvTrxh2) and probed by site directed mutagenesis. Enzyme kinetics analysis reveals mutants in a loop of the flavin adenine dinucleotide (FAD)‐binding domain of HvNTR2 to strongly affect the interaction with Trx. In particular, Trp42 and Met43 play key roles for recognition of the endogenous HvTrxh2. Trx from Arabidopsis thaliana is also efficiently recycled by HvNTR2 but turnover in this case appears to be less dependent on these two residues, suggesting a distinct mode for NTR:Trx recognition. Comparison between the HvNTR2:HvTrxh2 model and the crystal structure of the Escherichia coli NTR:Trx complex reveals major differences in interactions involving the FAD‐ and NADPH‐binding domains as supported by our experiments. Overall, the findings suggest that NTR:Trx interactions in different biological systems are fine‐tuned by multiple intermolecular contacts. Proteins 2014; 82:607–619. © 2013 Wiley Periodicals, Inc.
Prediction and validation of the unexplored RNA‐binding protein atlas of the human proteome
Authors: Zhao Huiying , Yang Yuedong , Janga Sarath Chandra , Kao C. Cheng , Zhou Yaoqi
Published: October 2013

Detecting protein‐RNA interactions is challenging both experimentally and computationally because RNAs are large in number, diverse in cellular location and function, and flexible in structure. As a result, many RNA‐binding proteins (RBPs) remain to be identified. Here, a template‐based, function‐prediction technique SPOT‐Seq for RBPs is applied to human proteome and its result is validated by a recent proteomic experimental discovery of 860 mRNA‐binding proteins (mRBPs). The coverage (or sensitivity) is 42.6% for 1217 known RBPs annotated in the Gene Ontology and 43.6% for 860 newly discovered human mRBPs. Consistent sensitivity indicates the robust performance of SPOT‐Seq for predicting RBPs. More importantly, SPOT‐Seq detects 2418 novel RBPs in human proteome, 291 of which were validated by the newly discovered mRBP set. Among 291 validated novel RBPs, 61 are not homologous to any known RBPs. Successful validation of predicted novel RBPs permits us to further analysis of their phenotypic roles in disease pathways. The dataset of 2418 predicted novel RBPs along with confidence levels and complex structures is available at http://sparks-lab.org (in publications) for experimental confirmations and hypothesis generation. Proteins 2014; 82:640–647. © 2013 Wiley Periodicals, Inc.
Effects of D‐amino acid oxidase inhibition on memory performance and long‐term potentiation in vivo
Authors: Hopkins Seth C. , Campbell Una C. , Heffernan Michele L. R. , Spear Kerry L. , Jeggo Ross D. , Spanswick David C. , Varney Mark A. , Large Thomas H.
Published: October 2013

N‐methyl‐d‐aspartate receptor (NMDAR) activation can initiate changes in synaptic strength, evident as long‐term potentiation (LTP), and is a key molecular correlate of memory formation. Inhibition of d‐amino acid oxidase (DAAO) may increase NMDAR activity by regulating d‐serine concentrations, but which neuronal and behavioral effects are influenced by DAAO inhibition remain elusive. In anesthetized rats, extracellular field excitatory postsynaptic potentials (fEPSPs) were recorded before and after a theta frequency burst stimulation (TBS) of the Schaffer collateral pathway of the CA1 region in the hippocampus. Memory performance was assessed after training with tests of contextual fear conditioning (FC, mice) and novel object recognition (NOR, rats). Oral administration of 3, 10, and 30 mg/kg 4H‐furo[3,2‐b]pyrrole‐5‐carboxylic acid (SUN) produced dose‐related and steady increases of cerebellum d‐serine in rats and mice, indicative of lasting inhibition of central DAAO. SUN administered 2 h prior to training improved contextual fear conditioning in mice and novel object recognition memory in rats when tested 24 h after training. In anesthetized rats, LTP was established proportional to the number of TBS trains. d‐cycloserine (DCS) was used to identify a submaximal level of LTP (5× TBS) that responded to NMDA receptor activation; SUN administered at 10 mg/kg 3–4 h prior to testing similarly increased in vivo LTP levels compared to vehicle control animals. Interestingly, in vivo administration of DCS also increased brain d‐serine concentrations. These results indicate that DAAO inhibition increased NMDAR‐related synaptic plasticity during phases of post training memory consolidation to improve memory performance in hippocampal‐dependent behavioral tests.
Estimating the frequency of Cry1F resistance in field populations of the European corn borer (Lepidoptera: Crambidae)
Authors: Siegfried Blair D , Rangasamy Murugesan , Wang Haichuan , Spencer Terence , Haridas Chirakkal V , Tenhumberg Brigitte , Sumerford Douglas V , Storer Nicholas P
Published: October 2013

BACKGROUND

Transgenic corn hybrids that express toxins from Bacillus thuringiensis (Bt) have suppressed European corn borer populations and reduced the pest status of this insect throughout much of the US corn belt. A major assumption of the high‐dose/refuge strategy proposed for insect resistance management and Bt corn is that the frequency of resistance alleles is low so that resistant pests surviving exposure to Bt corn will be rare.

RESULTS

The frequency of resistance to the Cry1F Bt toxin was estimated using two different screening tools and compared with annual susceptibility monitoring based on diagnostic bioassays and LC50 and EC50 determinations. An F1 screening approach where field‐collected individuals were mated to a resistant laboratory strain and progeny were assayed to determine genotype revealed that resistance alleles could be recovered even during the first year of commercially available Cry1F corn (2003). Estimates of frequency from 2003–2005 and 2006–2008 indicated that, although allele frequency was higher than theoretical assumptions (0.0286 and 0.0253 respectively), there was no indication that the frequency was increasing. Similar estimates in 2008 and 2009 using an F2 screening approach confirmed the presence of non‐rare resistance alleles (frequency ≈ 0.0093 and 0.0142 for 2008 and 2009, respectively). The results of both screening methods were in general agreement with the observed mortality in diagnostic bioassays and LC50 and EC50 determinations.

CONCLUSIONS

These results are consistent with previous modeling results, suggesting that the high‐dose/refuge strategy that is in place for Bt corn may be effective in delaying resistance evolution even when a relatively high frequency of resistance alleles exists. © 2013 Society of Chemical Industry
Structure activity relationships of peptidic analogs of MyoD for the development of Id1 inhibitors as antiproliferative agents
Authors: Hsiao Yu‐Cheng , Yang De‐Len , Hung Hui‐Ling , Lung Feng‐Di T.
Published: October 2013

Id proteins, inhibitors of DNA binding proteins, have highly conserved dimerization motif known as the helix‐loop‐helix (HLH) domain that acts as a negative regulator of basic HLH (bHLH) transcription factors. In signaling pathways, Id proteins play an important role in cellular development, proliferation, and differentiation. The mechanism of Id proteins is to antagonize bHLH proteins, thereby preventing them from binding to DNA and inhibiting transcription of cellular differentiation‐associated genes in cancer. Recently, we reported an inhibitor of Id1, peptide 3C, which showed good affinity to Id1 protein and exhibited inhibitory effects in cancer cells. In this study, Ala (A)‐substituted analogs of peptide 3C were synthesized by SPPS, purified by RP‐HPLC, and characterized by MALDI‐TOF MS. Binding of each peptide to Id1 or Id1‐HLH (the HLH domain of Id1) was monitored by surface plasmon resonance (SPR)‐based biosensor. Biological effect of each peptide in MCF‐7 breast cancer cells was analyzed by MTT cell viability assay. The secondary structure of substituted analogs of peptide 3C was investigated by circular dichroism (CD) spectroscopy. SPR results revealed that A‐substituted analogs of peptide 3C showed weaker binding to Id1 than that of peptide 3C, indicating that the six amino acid residues in the N‐terminal of peptide 3C were all essential for binding to Id1 and the importance of amino acid residue was I2 > Q6 > Y1 > G4 > L5 > E3. In addition, substitution of E3 in peptide 3C with D, Q, and R did not improve the binding potency of peptide 3C. MTT assay demonstrated that neither A‐substituted nor position 3‐substituted analogs of peptide 3C showed increased antiproliferative effect in MCF‐7 cancer cells. CD results indicated that peptide 3C exhibited the highest content of α‐helical structure (39.37%), suggesting that the α‐helical structure may contribute to its binding potency for Id1 and Id1‐HLH. SAR results provided important information for the development of peptidic inhibitors of Id1 as anticancer agents and demonstrated peptide 3C as a promising lead for further modifications. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.