bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential in vivo amelioration by N‐acetyl‐L‐cysteine of oxidative stress in brain in human double mutant APP/PS‐1 knock‐in mice: Toward therapeutic modulation of mild cognitive impairment
Authors: Huang Quanzhen , Aluise Christopher D. , Joshi Gururaj , Sultana Rukhsana , St. Clair Daret K. , Markesbery William R. , Butterfield D. Allan
Published: June 2010

Alzheimer's disease (AD) is the most prevalent form of dementia among the elderly. Although the underlying cause has yet to be established, numerous data have shown that oxidative stress is implicated in AD as well as in preclinical stages of AD, such as mild cognitive impairment (MCI). The oxidative stress observed in brains of subjects with AD and MCI may be due, either fully or in part, to increased free radicals mediated by amyloid‐β peptide (Aβ). By using double human mutant APP/PS‐1 knock‐in mice as the AD model, the present work demonstrates that the APP/PS‐1 double mutation results in elevated protein oxidation (as indexed by protein carbonyls), protein nitration (as indexed by 3‐nitrotyrosine), as well as lipid peroxidation (as indexed by protein‐bound 4‐hydroxy‐2‐nonenal) in brains of mice aged 9 months and 12 months. APP/PS‐1 mice also exhibited lower levels of brain glutathione peroxidase (GPx) in both age groups studied, whereas glutathione reductase (GR) levels in brain were unaffected by the mutation. The activities of both of these antioxidant enzymes were significantly decreased in APP/PS‐1 mouse brains, whereas the activity of glucose‐6‐phosphate dehydrogenase (G6PDH) was increased relative to controls in both age groups. Levels of peptidyl prolyl isomerase 1 (Pin1) were significantly decreased in APP/PS‐1 mouse brain aged 9 and 12 months. Administration of N‐acetyl‐L‐cysteine (NAC), a glutathione precursor, to APP/PS‐1 mice via drinking water suppressed increased protein oxidation and nitration and also significantly augmented levels and activity of GPx in brain from both age groups. Oral administration of NAC also increased the diminished activity of GR and protected against lipid peroxidation in brains of 9‐month‐old APP/PS‐1 mice only. Pin1 levels, GR levels, and G6PDH activity in brain were unaffected by oral administration of NAC in both age groups. These results are discussed with reference to the therapeutic potential of this brain‐accessible glutathione precursor in the treatment of MCI and AD. © 2010 Wiley‐Liss, Inc.
Climatology of the areal precipitation in Amman/Jordan
Authors: Ghanem Ali Ahmad
Published: June 2010

Data of the rainy seasons from 1956/1957 to 2005/2006 for 11 stations distributed over Amman area were analyzed. They were used to estimate the areal rainfall amount in Amman area; the annual data have a normal distribution with an average of 283.7 mm. The areal rainfall amounts varied from year to year, with a standard deviation (SD) of 72.9 mm and with a variation coefficient of 26%. The analysis of the areal rainfall over a 50‐year period shows a decreasing trend (−0.4 mm/year), but with no statistical significance. The running means show two wet periods (1962/1963–1973/1974 and 1987/1988–1993/1994) and two dry periods that occurred in the beginning and the end of the study period. The amounts of water fall over Amman area ranged from 300 mm3 to 870 mm3. Despite these amounts, Amman suffers from water shortage which needs to be solved. Copyright © 2010 Royal Meteorological Society
A possible mechanism for El Niño‐like warming in response to the future greenhouse warming
Authors: Kug Jong‐Seong , Sooraj K. P. , Jin Fei‐Fei , Ham Yoo‐Geun , Kim Daehyun
Published: June 2010

Using the climate change experiments generated for the Fourth Assessment of the Intergovernmental Panel on Climate Change, a possible mechanism for the El Niño‐like warming in response to the greenhouse warming is suggested. From the coupled global climate model (CGCM) simulations with climate change scenario, it is found that the Bjerknes air–sea coupled process is a dominant contributor to the tropical Pacific response. However, it is revealed that most CGCMs commonly simulate the off‐equatorial maximum of precipitation change. It is suggested here that the off‐equatorial precipitation and the associated equatorial westerlies play a seeding role in triggering an El Niño‐like warming response. Atmospheric GCM (AGCM) experiments show that even uniform sea‐surface temperature (SST) warming leads to off‐equatorial increase in precipitation which brings equatorial westerlies, implying that these non‐uniform (off‐equatorial) responses can play a seeding role for the El Niño‐like warming pattern. Copyright © 2010 Royal Meteorological Society
Ozone mini‐holes over Valencia (Spain) and their influence on the UV erythemal radiation
Authors: Martínez‐Lozano J. A. , Utrillas M. P. , Núñez J. A. , Tamayo J. , Marín M. J. , Esteve A. R. , Cañada J. , Moreno J. C.
Published: June 2010

Low ozone level episodes (also known as mini‐holes) have been analysed over Valencia, Spain, during the period from 1 January 2000 to 31 December 2007. In this study, 24 episodes, lasting 1 or 2 days each, were detected. Most of them can be explained dynamically by the existence of an anticyclone over the Azores, which sends air masses coming from the Caribbean over the Iberian Peninsula. A positive anomaly in the vertical temperature profile in the high troposphere and one negative anomaly in the medium and low stratosphere are also observed in most of the analysed episodes. The total ozone column decrease is accompanied by a rise in the UV erythemal radiation levels. This increase is quantified at 1.29 times the decrease in the total ozone column. This is known as the radiation amplification factor (RAF) of UV erythemal radiation. Copyright © 2010 Royal Meteorological Society
Wind fluctuations over the North Sea
Authors: Vincent Claire L. , Pinson Pierre , Giebela Gregor
Published: June 2010

Climatological patterns in wind speed fluctuations with periods of 1 min to 10 h are analysed using data from a meteorological mast in the Danish North Sea. Fluctuations on these time scales are of particular relevance to the effective management of the power supply from large wind farms. The Hilbert‐Huang transform (HHT) is shown to be an effective tool for analysing long time series of wind speed observations, as it describes the time‐evolving spectral information in the time series. By binning and averaging the time‐evolving spectrum, the average spectral behaviour of the wind speed under a certain class of conditions can be found. Here, the HHT is applied to create conditional spectra which demonstrate patterns in the occurrence of severe wind variability. It is shown that wind fluctuations over the North Sea are more severe for westerly flow than for easterly flow, and that severe fluctuations are often observed in the vicinity of precipitation. The most severe wind fluctuations occur in the autumn and winter seasons, and are slightly more common when the pressure tendency is rising. Further, it is found that the wind is more variable for atmospherically unstable conditions than for stable conditions. Copyright © 2010 Royal Meteorological Society
Accelerated aging of intervertebral discs in a mouse model of progeria
Authors: Vo Nam , Seo Hyoung‐Yeon , Robinson Andria , Sowa Gwendolyn , Bentley Douglas , Taylor Lauren , Studer Rebecca , Usas Arvydas , Huard Johnny , Alber Sean , Watkins Simon C. , Lee Joon , Coehlo Paulo , Wang Dong , Loppini Mattia , Robbins Paul D. , Niedernhofer Laura J. , Kang James
Published: June 2010

Intervertebral disc degeneration (IDD) is a common and debilitating disorder that results in reduced flexibility of the spine, pain, and reduced mobility. Risk factors for IDD include age, genetic predisposition, injury, and other environmental factors such as smoking. Loss of proteoglycans (PGs) contributes to IDD with advancing age. Currently there is a lack of a model for rapid investigation of disc aging and evaluation of therapeutic interventions. Here we examined progression of disc aging in a murine model of a human progeroid syndrome caused by deficiency of the DNA repair endonuclease, ERCC1–XPF (Ercc1−/Δ mice). The ERCC1‐deficient mice showed loss of disc height and degenerative structural changes in their vertebral bodies similar to those reported for old rodents. Compared to their wild‐type littermates, Ercc1−/Δ mice also exhibit other age‐related IDD characteristics, including premature loss of disc PG, reduced matrix PG synthesis, and enhanced apoptosis and cell senescence. Finally, the onset of age‐associated disc pathologies was further accelerated in Ercc1−/Δ mice following chronic treatment with the chemotherapeutic agent mechlorethamine. These results demonstrate that Ercc1−/Δ mice represent an accurate and rapid model of disc aging and provide novel evidence that DNA damage negatively impacts PG synthesis. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1600–1607, 2010
Outcomes following temporal bone resection
Authors: Dean Nichole R. , White Hilliary N. , Carter Dale S. , Desmond Renee A. , Carroll William R. , McGrew Benjamin M. , Rosenthal Eben L.
Published: June 2010

Objectives/Hypothesis:

To evaluate survival outcomes in patients undergoing temporal bone resection.

Study Design:

Retrospective review.

Methods:

From 2002 to 2009 a total of 65 patients underwent temporal bone resection for epithelial (n = 47) and salivary (n = 18) skull base malignancies. Tumor characteristics, defect reconstruction, and postoperative course were assessed. Outcomes measured included disease‐free survival and cancer recurrence.

Results:

The majority of patients presented with recurrent (65%), advanced stage (94%), cutaneous (72%), and squamous cell carcinoma (57%). Thirty‐nine patients had perineural invasion (60%) and required facial nerve resection; 16 (25%) had intracranial extension. Local (n = 6), regional (n = 2), or free flap (n = 46) reconstruction was required in 80% of patients. Free flap donor sites included the anterolateral thigh (31%), radial forearm free flap (19%), rectus (35%), and latissimus (4%). The average hospital stay was 4.9 days (range, 1–28 days). The overall complication rate was 15% and included stroke (n = 4), cerebrospinal fluid leak (n = 2), hematoma formation (n = 1), infection (n = 1), flap loss (n = 1), and postoperative myocardial infarction (n = 1). A total of 22 patients (34%) developed cancer recurrence during the follow‐up period (median, 10 months), 17 (77%) of whom presented with recurrent disease at the time of temporal bone resection. Two‐year disease‐free survival was 68%, and 5‐year disease‐free survival was 50%.

Conclusions:

Aggressive surgical resection and reconstruction is recommended for primary and recurrent skull base malignancies with acceptable morbidity and improved disease‐free survival. Laryngoscope, 2010
Effect of cricopharyngeus muscle surgery on the pharynx
Authors: Allen Jacqui , White Cheryl J. , Leonard Rebecca , Belafsky Peter C.
Published: June 2010

Objectives/Hypothesis:

Cricopharyngeus muscle dysfunction (CPD) ranges from asymptomatic cricopharyngeal bar (CPB) to Zenker's diverticulum. Previous work suggests that CPD can result in dilation and weakening of the pharynx above the obstruction. The purpose of this investigation was to evaluate the ability of surgery on the cricopharyngeus muscle to improve pharyngeal area and strength.

Study Design:

Retrospective case study.

Methods:

Videofluoroscopic swallowing studies of all persons with CPD who underwent cricopharyngeus (CP) intervention followed by routine postoperative fluoroscopic study, between October 1, 1999 and January 1, 2010 were reviewed. Objective measures of pharyngeal area and constriction were obtained from pretreatment and post‐treatment studies. Paired t tests and repeated measures analysis of variance were employed to compare results.

Results:

Fifty‐four patients were included. Pharyngeal constriction and pharyngoesophageal segment (PES) opening improved significantly after intervention (P < .05).Pharyngeal dilation was unchanged (P > .05). PES opening improved more with CP myotomy than with dilation and botulinum toxin.

Conclusions:

Relief of CP obstruction by surgery or dilation improves pharyngeal constriction and PES opening. Dilation of the pharynx possibly related to prolonged outlet obstruction does not improve. CP myotomy appears more effective than dilation or botulinum toxin in relieving obstruction. Laryngoscope, 2010
Fumonisin exposure through maize in complementary foods is inversely associated with linear growth of infants in Tanzania
Authors: Kimanya Martin E. , De Meulenaer Bruno , Roberfroid Dominique , Lachat Carl , Kolsteren Patrick
Published: June 2010

Infants consuming maize‐based foods are at a high risk of exposure to fumonisins. This study explored the association between exposure of fumonisins from maize and growth retardation among infants in Tanzania. Mothers of 215 infants consented for their children to participate in this study. We estimated maize intake for each child by twice conducting a 24 h dietary recall and fumonisins level in the maize, using HPLC. Fumonisins exposure for each child was estimated by combining his/her maize intake and the fumonisins level in the maize. Of the infants, 191 consumed maize. The maize consumed by 131 infants contained fumonisins at levels varying from 21 to 3201 μg/kg. Fumonisins exposure in 26 infants exceeded the provisional maximum tolerable daily intake of 2 μg/kg body weight. At 12 months of age, infants exposed to fumonisins intakes above the provisional maximum tolerable daily intake of 2 μg/kg bodyweight were significantly shorter by 1.3 cm and 328 g lighter. It appears that the exposure to fumonisins is associated with growth retardation. This is the first study to report an association between fumonisins exposures and growth retardation.
Immunological one‐step determination of the central nervous system indicator proteins, neuron‐specific enolase and glial fibrillary acidic protein, in meat products
Authors: Kuczius Thorsten , Böhler Olga , Karch Helge
Published: June 2010

The determination of specific marker proteins is important in the prevention of infections and transmission of disease. Several diagnostic assays have been developed but these are mostly restricted to the detection of single antigens. Thus there is a need for multiplex detection assays for the simultaneous analysis of several disease indicators. Consumer protection against the transmission of prion diseases is ensured by the removal of specified risk material from cattle meat during slaughtering and this is regulated by law. The investigation reported here describes a one‐step determination on immunoblots of the simultaneous detection of two indicator proteins, neuron‐specific enolase and glial fibrillary acidic protein, in tissues of the central nervous system. Although the two proteins run in polyacrylamide gels with similar molecular masses the indicators are differentiated by immunological reactions followed by visualizing the different coloured specific protein bands which develop. The enolase exhibits a brown band, whereas the glial fibrillary acidic protein is red. Immunoblotting has proved to be a suitable assay for multiplex analysis of marker proteins possessing similar molecular weights and is therefore a suitable tool for application in food, veterinary and medical facilities.
Bioavailability of multiple components following acute ingestion of a polyphenol‐rich juice drink
Authors: Borges Gina , Mullen William , Mullan Adam , Lean Michael E. J. , Roberts Susan A. , Crozier Alan
Published: June 2010

A healthy diet involves eating fruit and vegetables on a daily basis, the benefits of which are in part linked to the ingestion of bioactive compounds including polyphenols. As a convenient means of delivering additional polyphenols to the diet, a polyphenol‐rich (P‐R) juice drink was prepared and the bioavailability of its diverse spectrum of constituents investigated. Ten human volunteers followed a low‐flavonoid diet for 2 days before drinking 350 mL of the P‐R beverage. Plasma and urine were collected for 24 h and analyzed by HPLC‐PDA‐MS. The plasma pharmacokinetics and recoveries of urinary metabolites of flavan‐3‐ols, flavanones, dihydrochalcones and 5‐O‐caffeoylquinic acid, both in terms of their identity and quantity, were, in most instances, not markedly different to those reported in other feeding studies with green tea, orange juice, apple cider and coffee. This indicates that the combination of polyphenolic compounds in the P‐R beverage are absorbed and excreted to a similar extent whether fed individually or together in a single beverage. It is concluded that the P‐R beverage can deliver the intended blend of bioavailable polyphenols, which would normally require consumption of several different plant‐derived foods.
Total removal of unwanted harmonic peaks (TruHARP) MRI for single breath‐hold high‐resolution myocardial motion and strain quantification
Authors: Agarwal Harsh K. , Prince Jerry L. , Abd‐Elmoniem Khaled Z.
Published: June 2010

Current MRI methods for myocardial motion and strain quantification have limited resolution because of Fourier space spectral peak interference. Methods have been proposed to remove this interference in order to improve resolution; however, these methods are clinically impractical due to the prolonged imaging times. In this paper, we propose total removal of unwanted harmonic peaks (TruHARP); a myocardial motion and strain quantification methodology that uses a novel single breath‐hold MR image acquisition protocol. In post‐processing, TruHARP separates the spectral peaks in the acquired images, enabling high‐resolution motion and strain quantification. The impact of high resolution on calculated circumferential and radial strains is studied using realistic Monte Carlo simulations, and the improvement in strain maps is demonstrated in six human subjects. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Eigenstrain reconstruction method in linear friction welded aluminium alloy and MMC plates
Authors: Jun Tea‐Sung , Korsunsky Alexander M.
Published: June 2010

In the present paper, we put forward a combined experimental and modelling approach based on the inverse eigenstrain methodology. The approach allows approximate reconstruction of the complete strain/stress state in the entire component. The resulting description is qualitatively different from the raw input data, since it is continuous, complete and consistent (the latter in terms of satisfying equilibrium, compatibility and boundary conditions). This is a significant improvement compared with the experimentally obtained limited knowledge of stress components at a selected number of measurement points, or from simple interpolation between these points. In the current study, the methodology is applied to the interpretation of diffraction strain measurements obtained by neutron and synchrotron X‐ray scattering in linear friction welds between aluminium‐based materials. We introduce a novel approach and present the mathematical framework that allows the eigenstrain reconstruction method (ERM) to be extended so as to provide a rational resolution of the important issue of unstrained lattice parameter (d0) determination. Different implementations of the general inverse eigenstrain principle are considered and compared. Copyright © 2010 John Wiley & Sons, Ltd.
Retinoic acid enhances sensitivity of neuroblastoma cells for imatinib mesylate
Authors: Neumann Ingo , Foell Jürgen L. , Bremer Marianne , Volkmer Ines , Korholz Dieter , Burdach Stefan , Staege Martin S.
Published: June 2010

Background

Retinoids can induce differentiation of neuroblastoma (NB) cells and are in clinical use for the treatment of patients with NB. Despite improvements of standard treatment during the last years, many patients with NB still relapse and new treatment options for these patients are required.

Procedure

We analyzed NB cells after incubation with retinoids by using Affymetrix HG_U133A microarrays, reverse transcription‐polymerase chain reaction (RT‐PCR), and flow cytometry. Sequencing of RT‐PCR products was applied for determination of CD117 mRNA sequences from NB cell lines. In addition, we tested sensitivity of NB cells for the kinase inhibitor imatinib mesylate after treatment with retinoids.

Results

Treatment of NB cells with retinoids induced expression of several genes including the retinoid metabolizing enzymes CYP26A1 and CYP26B1. In addition, we observed up‐regulation of CD117 (KIT), particularly after long‐term treatment with retinoids. Sequencing of CD117 mRNA from NB cell lines revealed heterozygosity for a non‐synonymous single nucleotide polymorphism in SH‐SY5Y NB cells. Up‐regulation of CD117 in NB cells correlated with increased sensitivity for the kinase inhibitor imatinib mesylate.

Conclusions

The combination of retinoids with kinase inhibitors might be worth exploring further for the treatment of NB patients. Pediatr Blood Cancer. 2010;55:464–470. © 2010 Wiley‐Liss, Inc.
Molecular characterization of heat shock proteins 90 (HSP83?) and 70 in tropical strains of Bombyx mori
Authors: Sosalegowda Aparna H. , Kundapur Rajesh R. , Boregowda Manjunatha H.
Published: June 2010

Following the concept of whole organism, we have extracted total protein from the Bombyx mori for the identification and analysis of HSPs. Expression of 90 kDa HSP in first, second and third instars, 84 kDa in fourth instar and 90‐, 84‐, 62‐, 60‐, 52‐ and 33‐kDa HSPs in fifth instar larvae of tropical polyvoltine and bivoltine silkworm strains were obvious. Further, we have combined single and 2‐DE with MALDI‐TOF for analysis of BmHSPs. Ninety kilodalton band excised from 1‐DE gel was identified as HSP83 by MALDI‐TOF‐MS. The immunoblot analysis confirmed the expression of HSP90 in all the instars larvae of B. mori. Heat shock‐induced protein spots were excised from 2‐DE gels for MALDI‐TOF‐MS analysis. The Mascot search results are for HSP68, HSC70‐1 and HSP70Ba in Pure Mysore, and major HSP70Bbb, HSP68, HSC‐3 and HSP83 in NB4D2. Multiple sequence alignment explicit the variations in amino acid sequence between Pure Mysore and NB4D2. Notably, the PMF of spot 2 matched the coding sequence of B. mori and its gene annotation was determined on chromosome 9. With this novel approach, expression of BmHSP90 was confirmed in all the instars and uncovered isoforms of BmHSP70, which provided unequivocal insight to analyze and understand the biological significance in B. mori.
The Deinococcus radiodurans Snf2 intein caught in the act: Detection of the Class 3 intein signature Block F branched intermediate
Authors: Brace Lear E. , Southworth Maurice W. , Tori Kazuo , Cushing Michelle L. , Perler Francine
Published: June 2010

Inteins are the protein equivalent of introns. They are remarkable and robust single turnover enzymes that splice out of precursor proteins during post‐translational maturation of the host protein (extein). The Deinococcus radiodurans Snf2 intein is the second member of the recently discovered Class 3 subfamily of inteins to be characterized. Class 3 inteins have a unique sequence signature: (a) they start with residues other than the standard Class 1 Cys, Ser or Thr, (b) have a noncontiguous, centrally located Trp/Cys/Thr triplet, and (c) all but one have Ser or Thr at the start of the C‐extein instead of the more common Cys. We previously proposed that Class 3 inteins splice by a variation in the standard intein‐mediated protein splicing mechanism that includes a novel initiating step leading to the formation of a previously unrecognized branched intermediate. In this mechanism defined with the Class 3 prototypic Mycobacteriophage Bethlehem DnaB intein, the triplet Cys attacks the peptide bond at the N‐terminal splice junction to form the class specific branched intermediate after which the N‐extein is transferred to the side chain of the Ser, Thr, or Cys at the C‐terminal splice junction to form the standard intein branched intermediate. Analysis of the Deinococcus radiodurans Snf2 intein confirms this splicing mechanism. Moreover, the Class 3 specific Block F branched intermediate was isolated, providing the first direct proof of its existence.
Isgur‐Wise functions and the Lorentz group
Authors: Le Yaouanc A. , Oliver L. , Raynal J.‐C.
Published: June 2010

Bjorken‐like sum rules have proven to be very powerful in constraining the derivatives of the Isgur‐Wise (IW) function. We expose here, adapted to the simpler case of the baryon transition Λb → Λc ℓ ν (j = 0 for the light could), that the reason behind these strong constraints is the general idea that the IW function is expressed in terms of scalar products of states of the light cloud in a Hilbert space, related by Lorentz transformations. This fact leads to strong constraints on their possible shape. Both Lorentz group and the sum rule approaches are equivalent.
Expression and function of ATIP/MTUS1 in human prostate cancer cell lines
Authors: Louis Simon N.S. , Chow Laurie , Rezmann Linda , Krezel Michael A. , Catt Kevin J. , Tikellis Chris , Frauman Albert G. , Louis William J.
Published: June 2010

BACKGROUND

We have previously demonstrated Ang II type 2 (AT2‐) receptor‐mediated inhibition of EGF‐induced prostate cancer cell growth in androgen‐dependent (LNCaP) and independent (PC3) prostate cancer cell lines.

METHODS

To explore the signaling pathways involved in this inhibitory effect, we examined the interaction of the AT2‐receptor with its novel regulatory partner ATIP using real time PCR, over‐expression, siRNA and [3H]thymidine incorporation assays.

RESULTS

The results in human prostate cancer cell lines demonstrate the presence of ATIP in both cell lines examined, and suggest that (i) the AT2‐receptor through an interaction with ATIP mediates an anti‐growth factor effect in both androgen‐dependent and androgen‐independent cell lines; (ii) ATIP expression decreases as the rate of cell growth and androgen‐independence increase; and (iii) EGF may act on cell growth in part by reducing the content of ATIP present in the cells.

CONCLUSIONS

The results support our earlier proposal in normal cell lines that ATIP is an important component of the cellular response to AT2‐receptor activation. The results further suggest that a critical level of ATIP is required to mediate the effect of AT2‐receptor activation to inhibit EGF mediated increases in cell growth. They also suggest that EGF may in part induce cell growth by suppressing the level of ATIP expression. Prostate 70: 1563–1574, 2010. © 2010 Wiley‐Liss, Inc.
Exploring the role of the phospholipid ligand in endothelial protein C receptor: A molecular dynamics study
Authors: Chiappori Federica , Merelli Ivan , Milanesi Luciano , Rovida Ermanna
Published: June 2010

Endothelial protein C receptor (EPCR) is a CD1‐like transmembrane glycoprotein with important regulatory roles in protein C (PC) pathway, enhancing PC's anticoagulant, anti‐inflammatory, and antiapoptotic activities. Similarly to homologous CD1d, EPCR binds a phospholipid [phosphatidylethanolamine (PTY)] in a groove corresponding to the antigen‐presenting site, although it is not clear if lipid exchange can occur in EPCR as in CD1d. The presence of PTY seems essential for PC γ‐carboxyglutamic acid (Gla) domain binding. However, the lipid‐free form of the EPCR has not been characterized. We have investigated the structural role of PTY on EPCR, by multiple molecular dynamics (MD) simulations of ligand bound and unbound forms of the protein. Structural changes, subsequent to ligand removal, led to identification of two stable and folded ligand‐free conformations. Compared with the bound form, unbound structures showed a narrowing of the A′ pocket and a high flexibility of the helices around it, in agreement with CD1d simulation. Thus, a lipid exchange with a mechanism similar to CD1d is proposed. In addition, unbound conformations presented a reduced interaction surface for Gla domain, confirming the role of PTY in establishing the proper EPCR conformation for the interaction with its partner protein. Single MD simulations were also obtained for 29 mutant models with predicted structural stability and impaired binding ability. Ligand affinity calculations, based on linear interaction energy method, showed that substitution‐induced conformational changes affecting helices around the A′ pocket were associated to a reduced binding affinity. Mutants responsible for this effect may represent useful reagents for experimental tests. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Can self‐inhibitory peptides be derived from the interfaces of globular protein–protein interactions?
Authors: London Nir , Raveh Barak , Movshovitz‐Attias Dana , Schueler‐Furman Ora
Published: June 2010

In this study, we assess on a large scale the possibility of deriving self‐inhibitory peptides from protein domains with globular architectures. Such inhibitory peptides would inhibit interactions of their origin domain by mimicking its mode of binding to cognate partners, and could serve as promising leads for rational design of inhibitory drugs. For our large‐scale analysis, we analyzed short linear segments that were cut out of protein interfaces in silico in complex structures of protein–protein docking Benchmark 3.0 and CAPRI targets from rounds 1–19. Our results suggest that more than 50% of these globular interactions are dominated by one short linear segment at the domain interface, which provides more than half of the original interaction energy. Importantly, in many cases the derived peptides show strong energetic preference for their original binding mode independently of the context of their original domain, as we demonstrate by extensive computational peptide docking experiments. As an in depth case study, we computationally design a candidate peptide to inhibit the EphB4–EphrinB2 interaction based on a short peptide derived from the G‐H loop in EphrinB2. Altogether, we provide an elaborate framework for the in silico selection of candidate inhibitory molecules for protein–protein interactions. Such candidate molecules can be readily subjected to wet‐laboratory experiments and provide highly promising starting points for subsequent drug design. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Temperature‐induced transition between polyproline I and II helices: quantitative fitting of hysteresis effects
Authors: Kuemin Michael , Engel Jürgen , Wennemers Helma
Published: June 2010

The conformational properties of the polyproline I (PPI) helix of oligoprolines toward heating were examined. Oligoproline H‐Pro12‐NH2 served as a model which adopts in n‐PrOH a pronounced PPI conformation with all cis amide bonds, whereas a polyproline II (PPII) conformation with all trans amide bonds is predominant in pure aqueous buffer. CD spectroscopic studies revealed that a conformational change from the PPI to the PPII helix takes place upon heating and back to the PPI helix upon cooling. This conformational transition cycle is characterized by a strong hysteresis. With a quantitative fitting of the experimentally observed hysteresis loops by a newly developed iterative integration with different starting conditions, kinetic and thermodynamic parameters for the transition from the PPI to the PPII helical conformation were determined. The transition is as expected for cis–trans isomerizations of amide bonds comparatively slow (k = 0.003 s−1 at 80 °C) and characterized by an activation energy Ea of 81.1 ± 3.6 kJ mol−1. Thermodynamically, the transition from the PPI to the PPII helix is characterized by a positive standard enthalpy (ΔH0 = 33.5 ± 2.1 kJ min−1) and a positive standard entropy (ΔS0 = 102 ± 6.6 J mol−1 K−1). Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.
Inhibitory effect of Thuja orientalis on TNF‐α‐induced vascular inflammation
Authors: Lee Yun Jung , Hwang Sun Mi , Yoon Jung Joo , Lee So Min , Kyung Eun Ho , Kim Jin Sook , Kang Dae Gill , Lee Ho Sub
Published: June 2010

Vascular inflammation is involved in the initiation and progression of vascular diseases including atherosclerosis. While conducting in vitro screening of 600 medicinal plant extracts, an aqueous extract of Thuja orientalis (ATO) was found to exhibit antiinflammatory activity in human umbilical vein endothelial cells (HUVEC). In the current study, the antiinflammatory activity of ATO and possible mechanisms for this were investigated in HUVEC. Preincubation with ATO (20 μg/mL) suppressed tumor necrosis factor‐α (TNF‐α)‐induced expression of adhesion molecules including intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and E‐selectin at both the protein and mRNA levels. ATO also inhibited U937 monocyte adhesion to HUVEC stimulated by TNF‐α. In addition, ATO attenuated TNF‐α‐induced p65 NF‐κB translocation into the nucleus and phosphorylation of IκB‐α. Furthermore, ATO significantly inhibited TNF‐α‐induced intracellular reactive oxygen species (ROS) production. Overall, the present data suggest that ATO can suppress TNF‐α‐induced vascular inflammatory processes, possibly via inhibition of ROS and NF‐κB activation, in HUVEC. Copyright © 2010 John Wiley & Sons, Ltd.
Neuroprotective effect of honokiol and magnolol, compounds from Magnolia officinalis, on beta‐amyloid‐induced toxicity in PC12 cells
Authors: Hoi Chu Peng , Ho Yee Ping , Baum Larry , Chow Albert H. L.
Published: June 2010

Amyloid β peptide (Aβ) induced toxicity is a well‐established pathway of neuronal cell death which might play a role in Alzheimer's disease. In this regard, the toxic effect of Aβ on a cultured Aβ‐sensitive neuronal cell line was used as a primary screening tool for potential anti‐Alzheimer's therapeutic agents. The effects of nine pure compounds (vitamin E, α‐asarone, salidroside, baicolin, magnolol, gastrodin, bilobalide, honokiol and β‐asarone) from selected Chinese herbs on neuronal cell death induced by Aβ in NGF‐differentiated PC12 cells were examined. Only two of the studied compounds, honokiol and magnolol, significantly decreased Aβ‐induced cell death. Further experiments indicated that their neuroprotective effects are possibly mediated through reduced ROS production as well as suppression of intracellular calcium elevation and inhibition of caspase‐3 activity. The results provide for the first time a scientific rationale for the clinical use of honokiol and magnolol in the treatment of Alzheimer's disease. Copyright © 2010 John Wiley & Sons, Ltd.
Dimensional compactification and two‐particle binding
Authors: Delfino A. , Timóteo V. S. , Frederico T. , Tomio Lauro , Cordeiro C. E.
Published: June 2010

The renormalization group equations (RGE) are applied to the study of two‐body singular interactions at the surface of an infinite long cylinder with a radius R. A single scale, independent of R, emerges from the renormalization procedure of removing the ultraviolet momentum divergence of the original interacting Green's function. This single scale implies in a R‐dependent binding energy, which is obtained from the pole of the Green's function. The binding is infinitely large in the limit R = 0, while as R goes to infinity it converges to the well‐ known two‐dimensional (2D) result in flat space. The physical scale is controlled by the energy binding value on the 2D flat surface. By exploring the effect of space dimensions D, from D = 1 to D = 3, in the physics and scales, it is also shown that by decreasing the dimensionality one favors the two‐body binding. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Ab initio multireference singles and doubles configuration interaction study of the low‐energy states of iron mononitride
Authors: de Oliveira Marcos Herrerias , Martins Filho Harley Paiva , Da Motta Neto Joaquim Delphino
Published: June 2010

Low‐lying states of iron mononitride are studied using ab initio multireference singles and doubles configuration interaction (MR‐SDCI) calculations. For each one of the 2Δ, 4Π, 6Σ+, 2Π, 4Δ, 6Π, and 6Δ states the reference wavefunction has been obtained at the complete active space self consistent field (CASSCF) level and relativistic corrections were included. Potential energy curves are presented for all states. Spectroscopic constants have been determined for the 2Δ, 4Π, and 6Σ+ states assuming a Morse‐type potential function using a code written by one of us. For the 2Δ state, the calculated spectroscopic constants are Re = 1.567 Å, ωe = 827 cm−1, and μ = 1.68 D. Rotovibrational analysis suggests that the third vibrational level of the 2Δ state already surpasses the first vibrational levels of the 4Π and 6Σ+ states, what reassures the difficulty in correctly attributing the lines of the experimental spectrum. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Are the anions MeO(CO) (n = 1 and 2) methoxide anion donors in the gas phase? A theoretical investigation
Authors: Wang Tianfang , Eichinger Peter C. H. , Dua Suresh , Bowie John H.
Published: June 2010

The anions CH3O‐–CO and CH3OCO‐–CO are both methoxide anion donors. The processes CH3O‐–CO → CH3O– + CO and CH3OCO—CO → CH3O– + 2CO have ΔG values of +8 and −68 kJ mol−1, respectively, at the CCSD(T)/6‐311++G(2d, 2p)//B3LYP/6‐311++G(2d,2p) level of theory.

The reactions CH3OCOCO → CH3OCO + CO (ΔG = −22 kJ mol−1) and CH3COCH(O–)CO2CH3 → CH3COCH(O–)OCH3 + CO (ΔG = +19 kJ mol−1) proceed directly from the precursor anions via the transition states (CH3OCO…CO2)– and (CH3COCHO…CH3OCO)–, respectively.

Anion CH3COCH(O–)CO2CH3 undergoes methoxide anion transfer and loss of two molecules of CO in the reaction sequence CH3COCH(O–)CO2CH3 → CH3CH(O–)COCO2CH3 → [CH3CHO (CH3OCO‐–CO)] → CH3CH(O–)OCH3 + 2CO (ΔG = +9 kJ mol−1). The hydride ion transfer in the first step is a key feature of the reaction sequence.

Copyright © 2010 John Wiley & Sons, Ltd.
Use of high‐resolution mass spectrometry to investigate a metabolite interference during liquid chromatography/tandem mass spectrometric quantification of a small molecule in toxicokinetic study samples
Authors: Furlong Michael , Bessire Andrew , Song Wei , Huntington Christopher , Groeber Elizabeth
Published: June 2010

During routine liquid chromatography/tandem mass spectrometric (LC/MS/MS) bioanalysis of a small molecule analyte in rat serum samples from a toxicokinetic study, an unexpected interfering peak was observed in the extracted ion chromatogram of the internal standard. No interfering peaks were observed in the extracted ion chromatogram of the analyte. The dose‐dependent peak area response and peak area response versus time profiles of the interfering peak suggested that it might have been related to a metabolite of the dosed compound. Further investigation using high‐resolution mass spectrometry led to unequivocal identification of the interfering peak as anN‐desmethyl metabolite of the parent analyte. High‐resolution mass spectrometry (HRMS) was also used to demonstrate that the interfering response of the metabolite in the multiple reaction monitoring (MRM) channel of the internal standard was due to an isobaric relationship between the13C‐isotope of the metabolite and the internal standard (i.e., common precursor ion mass), coupled with a metabolite product ion with identical mass to the product ion used in the MRM transition of the internal standard. These results emphasize (1) the need to carefully evaluate internal standard candidates with regard to potential interferences from metabolites during LC/MS/MS method development, validation and bioanalysis of small molecule analytes in biological matrices; (2) the value of HRMS as a tool to investigate unexpected interferences encountered during LC/MS/MS analysis of small molecules in biological matrices; and (3) the potential for interference regardless of choice of IS and therefore the importance of conducting assay robustness on incurredin vitroorin vivostudy samples. Copyright © 2010 John Wiley & Sons, Ltd.
Theoretical and experimental study of the achievable separation power in resistive‐glass atmospheric pressure ion mobility spectrometry
Authors: Kwasnik Mark , Fernández Facundo M.
Published: June 2010

We present a detailed investigation of the performance of our previously reported nanoelectrospray high‐resolution resistive‐glass atmospheric pressure drift tube ion mobility spectrometer constructed with monolithic resistive‐glass desolvation and drift regions. Using experimental spectral data and theoretical pulse width and diffusion variables, we compare theoretical and experimental resolving powers achievable under a variety of field strengths and ion gate pulse widths. The effects of instrumental and operational parameters on the resolution achievable in chromatographic terms are also discussed. Following characterization of the separation power of the instrument, experimental spectral peak width data is fitted by a least‐squares procedure to a pre‐existing semi‐empirical model developed to study contributions to peak width other than initial pulse width and diffusional broadening. The model suggests possible contributions to the final measured peak width from electric field inhomogeneity and minor contributions from instrumental parameters such as anode size, anode‐to‐anode grid distance and drift gas flow rate. The model also reveals an unexpected ion gate width dependence on the final measured peak width that we attribute to non‐ideal performance of the Bradbury‐Nielsen ion gate and limitations in the design of our pulsing‐electronics. Copyright © 2010 John Wiley & Sons, Ltd.
Aerial photographic analysis of channel narrowing and vegetation expansion in Canyon De Chelly National Monument, Arizona, USA, 1935–2004
Authors: Cadol D. , Rathburn S. L. , Cooper D. J.
Published: June 2010

Aerial photographs from the past 70 years show narrowing of channels in Canyon de Chelly National Monument, which coincided with the establishment and expansion of woody riparian vegetation, primarily non‐native tamarisk (Tamarix ssp.) and Russian olive (Elaeagnus angustifolia) and native cottonwood (Populus spp.). Rectified air photo sets were used to map the extent of woody riparian vegetation cover in the canyon bottom as well as the channel planform geometry for 6 years: 1935, 1964, 1975, 1981, 1989 and 2004. In 1935, vegetation covered less than 1 per cent of the canyon bottom and the channel was braided and 91 m wide on average. By 2004, the channel in the upper 75% of the canyon had narrowed to a single thread an average of 6.5 m wide and was lined by riparian vegetation, with vegetation covering up to 45% of the canyon bottom in some reaches. A relative timing index was developed that incorporates information from both channel and vegetation area expansion or contraction into a single variable. Vegetation establishment lagged channel narrowing in the upper reaches of the canyons, but narrowing and vegetation establishment occurred simultaneously in the middle and lower reaches. Narrowing progressed downstream through time, and the lowermost reaches remained braided and unincised in 2006. We interpret these patterns to suggest that riparian vegetation is responding to and interacting with changes in the channel morphology of Canyon de Chelly rather than driving channel change. Copyright © 2010 John Wiley & Sons, Ltd.
Establishing spatial trends in water chemistry and stable isotopes (δ15N and δ13C) in the Elwha River prior to dam removal and salmon recolonization
Authors: Duda J. J. , Coe H. J. , Morley S. A. , Kloehn K. K.
Published: June 2010

Two high‐head dams on the Elwha River in Washington State (USA) have changed the migratory patterns of resident and anadromous fish, limiting Pacific salmon to the lower 7.9 km of a river that historically supported large Pacific salmon runs. To document the effects of the dams prior to their removal, we measured carbon and nitrogen stable isotope ratios of primary producers, benthic macroinvertebrates, and fish, and water chemistry above, between and below the dams. We found that δ15N was significantly higher in fish, stoneflies, black flies, periphyton and macroalgae where salmon still have access. Fish and chloroperlid stoneflies were enriched in δ13C, but the values were more variable than in δ15N. For some taxa, there were also differences between the two river sections that lack salmon, suggesting that factors other than marine‐derived nutrients are structuring longitudinal isotopic profiles. Consistent with trophic theory, macroalgae had the lowest δ15N, followed by periphyton, macroinvertebrates and fish, with a range of 6.9, 6.2 and 7.7‰ below, between, and above the dams, respectively. Water chemistry analyses confirmed earlier reports that the river is oligotrophic. Phosphorous levels in the Elwha were lower than those found in other regional rivers, with significant differences among regulated, unregulated and reference sections. The removal of these dams, among the largest of such projects ever attempted, is expected to facilitate the return of salmon and their marine‐derived nutrients (MDN) throughout the watershed, possibly altering the food web structure, nutrient levels and stable isotope values that we documented. Published in 2010 by John Wiley & Sons, Ltd.
Temperature effects in the sputtering of a molecular solid by energetic atomic and cluster projectiles
Authors: Brenes D. A. , Willingham D. , Winograd N. , Postawa Z.
Published: June 2010

Temperature effects in the sputtering of an organic molecule were investigated by subjecting a well defined film of coronene to Au1 and C60 primary ions at 100 and 300 K. Strong field photoionization of the sputtered neutral flux was employed to monitor the change in flight time and kinetic energy distributions of intact and fragmented species. Copyright © 2010 John Wiley & Sons, Ltd.
Retrospective sputter depth profiling using 3D mass spectral imaging
Authors: Zheng Leiliang , Wucher Andreas , Winograd Nicholas
Published: June 2010

A molecular multilayer stack composed of alternating Langmuir‐Blodgett films was analyzed by ToF‐SIMS imaging in combination with intermediate sputter erosion using a focused C60+ cluster ion beam. From the resulting dataset, depth profiles of any desired lateral portion of the analyzed field‐of‐view can be extracted in retrospect, allowing the influence of the gating area on the apparent depth resolution to be assessed. In a similar way, the observed degradation of depth resolution with increasing depth of the analyzed interface can be analyzed in order to determine the ‘intrinsic’ depth resolution of the method. Copyright © 2010 John Wiley & Sons, Ltd.
Modeling the interaction of keV clusters with molecular solids
Authors: Mody Jaydeep D. , Webb Roger P.
Published: June 2010

The use of polyatomic (cluster) ion beams for SIMS has proven to be an efficient method for the characterization of solids. Computer simulation programs such as Molecular Dynamics (MD) are often run to gain an insight into the ion‐solid interactions that take place under these circumstances; however, for simulations to be able to make accurate predictions, a massive amount of computational resources are required to be at hand. These include several months in simulation time and the use of very large targets, not to mention that a single simulation run is a representation of only a single ion trajectory. Thus, MD simulations are invaluable for gaining insight into ion‐solid interactions but are less so for being able to provide information when time constraints are put in place. The work here aims to achieve a prediction model that, when completely functional, will be able to deal with the pressures of the clock. This, we believe, is achievable by employing simpler modeling criteria that are dependant upon aspects of an initial energy deposition profile within the target under irradiation. Copyright © 2010 John Wiley & Sons, Ltd.