bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of artichoke extract (Cynara scolymusL.) on palmitic‐1‐14C acid oxidation in rats
Authors: Juzyszyn Zygmunt , Czerny Boguslaw , Pawlik Andrzej , Drozdzik Marek
Published: April 2008

Studies on the effect of the artichoke extract (AE) on oxidation of palmitic‐1‐14C acid administered intravenously to rats at a dose 25 and 50 mg/kg bw demonstrated marked enhancement of both14CO2expiration rate and14CO2recovery in the expired air. The extract suppressed accumulation of palmitic‐1‐14C acid in serum lipids and epididymal fat pad tissue as well. The effects of the extract on14CO2expiration rate,14CO2recovery, as well as accumulation of palmitic‐1‐14C acid were dose dependent. Total14CO2recovery in expired air during 60 min was elevated by 17.3% (p< 0.05) and 52.1% (p< 0.001) in rats administered the extract at a dose of 25 and 50 mg/kg, respectively. The rats supplemented with the AE at a dose of 25 and 50 mg/kg bw were characterized by 10.0% (not significant) and 19% (p< 0.05) decrease in14C radioactivity of serum lipids as well as reduction of epididymal fat tissue14C radioactivity by 8.7 and 17.5% (p< 0.05), respectively, in comparison with the control rats. Thus, the results demonstrate that the AE possess stimulatory properties with respect to oxidation of palmitic acid administered to rats, and provide new information on the mechanism of antilipemic activity of the extract associated with activation of lipid oxidation in the organism.
Kinetin enhances in vitro development of parthenogenetic and nuclear transfer porcine embryos
Authors: Won C. , Park S.K. , Cho S.‐G. , Min B.‐M. , Roh S.
Published: April 2008

Culture conditions affect the development of mammalian embryos in vitro. Kinetin belongs to the family of N6‐substituted adenine derivates and promotes cell division, synthesis of DNA repair enzymes, superoxide dismutase activity, and ribosomal RNA transcription. We investigated the effects of kinetin on in vitro development of parthenogenetic and nuclear transfer (NT) porcine embryos. These embryos were cultured with or without kinetin in either BSA‐ or polyvinyl alcohol‐containing medium for 7 days. mRNA expression of three developmentally important genes, HSP70, Glut‐1, and poly[A] polymerase in NT embryos was analyzed. Regardless of kinetin supplementation, the proportion of blastocysts and blastocyst cells were not significantly different in parthenogenetic embryos. However, kinetin supplementation increased expansion and hatching rates in all groups. In somatic cell NT embryos, kinetin increased the proportion of embryos developed to blastocysts from 7.5% to 15.4% in medium supplemented with PVA. However, gene expression levels of HSP70, poly[A] polymerase and Glut‐1 mRNA were not significantly different in NT blastocysts. The present study indicates that kinetin not only improves blastocyst expansion and cell number of parthenogenetic porcine embryos but also enhances NT porcine embryo development in a completely defined culture condition in vitro. Mol. Reprod. Dev. 75: 1701–1709, 2008. © 2008 Wiley‐Liss, Inc.
Studies on the migration in PA6‐OMMT nanocomposites: effect of annealing on migration as evidenced by ARXPS (angle resolved X‐ray photoelectron spectroscopy)
Authors: Huang Nianhua , Lewin Menachem , Tang Yong , Fan Chou , Wang Jianqi
Published: April 2008

The present paper deals with experiments in which the angle resolved X‐ray photoelectron spectroscopy (ARXPS) technique was applied to investigate the phenomenon of migration in polyamide 6 with organically modified montmorillonite (PA6‐OMMT) nanocomposites. This is the first time ARXPS was used, to gain a more detailed insight into the migration process. Curve‐fitting analyses are reported which enable the differentiation between a manual mixture of PA6 with OMMT at room temperature from a nanocomposite structure. The ARXPS technique was applied to annealed samples at 250, 275, and 285°C, for 2 hr, and with three take of angles, α, of 90, 60, and 30°. The depth of the layer investigated is 9 nm in case the sample surface is well defined. By tilting the take‐off angle of the beam‐out electrons one can determine the intensity of the signals at various distances from the surface within the investigated layer. The concentration gradient of the Si signals is observed. The rate of migration is found to be more rapid in the layer closest to the surface. The intensity of the Si signals in the investigated layer is found to be 1.8 to 9.1 times that of the same composite sample at room temperature. This ratio determines the extent of migration. At temperatures higher than 250°C and times of annealing greater than 30 min a decrease in the extent of migration is observed. This decrease is explained by the gradual decomposition of the surfactant and the consequent removal of the polymeric matrix molecules from the migrating exfoliated units, culminating in denuded alumino‐silicate layers. These layers aggregate to noncolloidal microcomposite particles which do not migrate. The concentration of the exfoliated units decreases with consequent decrease in migration. A gradient of decreasing concentration of Si2p signals was observed after various times of annealing, where the gradient becomes more uniform with increase in time. Copyright © 2008 John Wiley & Sons, Ltd.
Potassium diperiodatonickelate‐initiated graft copolymerization of methyl acrylate onto organophilic montmorillonite
Authors: Deng Kuilin , Liu Jing , Zheng Xiangyang , Zhang Yaqin , Jia Na , Tian Hua , Liu Yinghai
Published: April 2008

Using potassium diperiodatonickelate (Ni (IV)) as an efficient initiator, the graft copolymerization of methyl acrylate (MA) onto organophilic montmorillonite (OMMT) was successfully performed in an alkaline medium. Three grafting parameters were systematically evaluated as functions of the temperature, the initiator concentration, reaction time, pH value, and the ratio of MA to OMMT substrate. The structure of the titled graft copolymers (OMMT‐g‐PMA) were confirmed by Fourier transform infrared spectroscopy (FTIR), X‐ray diffraction (XRD), differential scanning calorimetry (DSC), and thermo‐gravimetric analysis (TGA). It was found that Ni (IV) was a highly efficient initiator for graft copolymerization of the MA onto OMMT, i.e., grafting efficiency is as high as 95% and grafting percentage can be facilely controlled within 700% in this study. In addition, the highest grafting efficiency and grafting percentage were obtained when temperature adopted was over 40°C and pH was about 10.3. A single‐electron‐transfer mechanism was proposed to illustrate the formation of radicals and the initiation reaction. Copyright © 2008 John Wiley & Sons, Ltd.
Color tunability in non‐doped single‐layer PLEDs from a carbazole‐based electroluminescent polymer
Authors: Liu Yingliang , Cao Huayu , Xin Yuanrong , Li Jianghui , Chen Zhijian , Gong Qihuang , Cao Shaokui
Published: April 2008

A conjugated polymer with a carbazole moiety, poly(3,6‐divinylene‐N‐octyl‐carbazole‐p‐phenylene), was synthesized by Wittig reaction. The polymer can be dissolved in common organic solvents such as THF, chloroform, etc. Using this polymer as an active layer, single‐layer non‐doped PLEDs with different thicknesses were fabricated by a spin‐coating approach. The results suggested that electroluminescence spectra are changed with the film thickness of the polymer emitter. Fortunately, CIE 1931 coordinate values are moved to the white‐light region only by changing the film thickness. Copyright © 2008 John Wiley & Sons, Ltd.
Microencapsulated ammonium polyphosphate with urea–melamine–formaldehyde shell: preparation, characterization, and its flame retardance in polypropylene
Authors: Wu Kun , Wang Zhengzhou , Hu Yuan
Published: April 2008

Microencapsulated ammonium polyphosphate (MCU‐APP) with urea–melamine–formaldehyde (UMF) resin is prepared by in situ polymerization, and is characterized by FTIR and XPS. The microencapsulation of APP with the UMF resin leads to a decrease in the particle's water solubility. The flame retardant actions of MCU‐APP and APP in PP are studied using limiting oxygen index (LOI) and UL‐94 test, and their thermal stability is evaluated by thermogravimetric analysis. It is found that the LOI value of the PP/MCU‐APP composite is higher than the value of the PP/APP composite. In comparison with the PP/MCU‐APP composites, the LOI values of the PP/MCU‐APP/DPER ternary composites at the same additive loading increase, and UL‐94 ratings of most ternary composites are raised to V‐0. The water‐resistant properties of the PP composites containing APP and MCU‐APP are studied. Moreover, the combustion behavior of the PP composites is investigated by the cone calorimeter. Copyright © 2008 John Wiley & Sons, Ltd.
The proteome of gastric lymph in normal and nematode infected sheep
Authors: Goldfinch Gillian M. , Smith W. David , Imrie Lisa , McLean Kevin , Inglis Neil F. , Pemberton Alan D.
Published: April 2008

Lymph node cannulation allows the collection of lymph draining from a defined anatomical region. Proteomic analysis of that lymph offers a potentially valuable insight into the immunoinflammatory response of that particular region. In this study, ovine gastric lymph has been used to monitor the proteomic changes occurring in the tissue fluid of the abomasum, in response to infection with the parasitic nematode, Teladorsagia circumcincta. Lymph, collected temporally over an experimental infection period, was analysed by means of 2‐DE and subsequent gel analysis using densitometry software. In addition, the composition of the lymphatic proteome was further explored by means of MALDI‐TOF and MS/MS analyses. The concentration of gelsolin, α‐1 β glycoprotein and haemopexin were altered significantly (p<0.05) with infection.
Predicting left ventricular remodeling after a first myocardial infarction by plasma proteome analysis
Authors: Pinet Florence , Beseme Olivia , Cieniewski‐Bernard Caroline , Drobecq Hervé , Jourdain Sabine , Lamblin Nicolas , Amouyel Philippe , Bauters Christophe
Published: April 2008

Recent improvements in therapeutic strategies did not prevent left ventricular remodeling (LVR), which remains a common event (30%) after acute myocardial infarction (AMI). We report the use of a systematic approach, based on comparative proteomics, to select circulating biomarkers that may be associated with LVR. We selected 93 patients enrolled in a prospective study. These patients with anterior wall Q‐wave AMI underwent echocardiographic follow‐up at hospitalization, 3 months and 1 year after AMI. They were divided into three groups (no, low, or high remodeling). Plasma samples of these patients (day 5 of hospitalization) were processed and stored at −80°C within 2 h and analyzed using SELDI‐TOF protein chip technology. This systematic approach allowed to select candidate proteins modulated by LVR: post‐translational variants of α1‐chain of haptoglobin (Hpα1) corresponding to m/z 9493, 9565, and 9623, which were more elevated in remodeling patients. The peak 9493 m/z was shown having a receiving‐operating characteristic (ROC) value of 0.71 between non‐ and remodeling patients. SELDI‐TOF approach may lead to the identification of circulating proteins associated with LVR. Whether these candidate proteins will help to identify patients who are at high risk of heart failure after AMI will have to be tested in future studies.
Enhanced nuclear proteomics
Authors: Barthéléry Miguel , Salli Ugur , Vrana Kent E.
Published: April 2008

Nuclear proteomics provides an opportunity to examine protein effectors that contribute to cellular phenotype. Both the quality and sensitivity of gel‐based nuclear proteomics are limited, however, by the over‐representation of histones in the protein mixture. These highly charged proteins overshadow rare species and interfere with IEF. A nuclear isolation and protein extraction procedure, tested on human embryonic stem cells, is reported that effectively isolates intact nuclei and then depletes the sample of histones by taking advantage of their ability to form an insoluble complex with DNA at lower pH (even under denaturing conditions). Ubiquitous histones and abundant nuclear actin, are depleted up to 99 ± 0.02 and 42 ± 5%, respectively. This technique greatly improves electrofocusing efficacy and nearly doubles the number of detected protein spots. This approach to nuclear protein isolation for 2‐D PAGE opens the door to better investigation of nuclear protein dynamics.
Investigating copper‐regulated protein expression in Menkes fibroblasts using antibody microarrays
Authors: Du Tai , La Fontaine Sharon L. , Abdo Michael , Bellingham Shayne A. , Greenough Mark , Volitakis Irene , Cherny Robert A. , Bush Ashley I. , Hudson Peter J. , Camakaris James , Mercer Julian F. , Crouch Peter J. , Masters Colin L. , Perreau Victoria M. , White Anthony R.
Published: April 2008

Neurodegenerative illnesses are characterized by aberrant metabolism of biometals such as copper (Cu), zinc (Zn) and iron (Fe). However, little is known about the metabolic effects associated with altered metal homeostasis. In this study, we used an in vitro model of altered Cu homeostasis to investigate how Cu regulates cellular protein expression. Human fibroblasts containing a natural deletion mutation of the Menkes (MNK) ATP7A Cu transporter (MNK deleted) were compared to fibroblasts overexpressing ATP7A (MNK transfected). Cultures of MNK‐transfected (Low‐Cu) cells exhibited 95% less intracellular Cu than MNK‐deleted (High‐Cu) cells. Comparative proteomic analysis of the two cell‐lines was performed using antibody microarrays, and significant differential protein expression was observed between Low‐Cu and High‐Cu cell‐lines. Western blot analysis confirmed the altered protein expression of Ku80, nexilin, L‐caldesmon, MAP4, Inhibitor 2 and DNA topoisomerase I. The top 50 altered proteins were analysed using the software program Pathway Studio (Ariadne Genomics) and revealed a significant over‐representation of proteins involved in DNA repair and maintenance. Further analysis confirmed that expression of the DNA repair protein Ku80 was dependent on cellular Cu homeostasis and that Low‐Cu levels in fibroblasts resulted in elevated susceptibility to DNA oxidation.
A simple and inexpensive on‐column frit fabrication method for fused‐silica capillaries for increased capacity and versatility in LC‐MS/MS applications
Authors: Wang Ling‐Chi , Okitsu Cindy Yen , Kochounian Harold , Rodriguez Anthony , Hsieh Chih‐Lin , Zandi Ebrahim
Published: April 2008

A modified sol–gel method for a one‐step on‐column frit preparation for fused‐silica capillaries and its utility for peptide separation in LC‐MS/MS is described. This method is inexpensive, reproducible, and does not require specialized equipments. Because the frit fabrication process does not damage polyimide coating, the frit‐fabricated column can be tightly connected on‐line for high pressure LC. These columns can replace any capillary liquid transfer tubing without any specialized connections up‐stream of a spray tip column. Therefore multiple columns with different phases can be connected in series for one‐ or multiple‐dimensional chromatography.
Applications in Brain Proteomics: 8th HUPO Brain Proteome Project Workshop 7 October 2007, Seoul, Korea
Authors: Hamacher Michael , Stephan Christian , Hardt Tanja , Eisenacher Martin , Henkel Andreas , Wiltfang Jens , Jimenez Connie R. , Park Young Mok , Marcus Katrin , Meyer Helmut E.
Published: April 2008

What are the current approaches in brain proteomics? Can we combine different, but complementary study designs to obtain better results concerning brain diseases? What are the neuro‐hotspots, especially in Korea? These were some of the questions the participants of the 8th HUPO Brain Proteome Project Workshop tried to answer prior to the 6th HUPO World Congress in Seoul, Korea. Around 100 scientists came together during the afternoon of 7 October, 2007, to discuss and to catch up on the latest results and strategies concerning Huntington's disease, glioblastoma and standardization.
Clinical assessment of the cancer diagnostic value of prostatic zinc: A comprehensive needle‐biopsy study
Authors: Cortesi M. , Fridman E. , Volkov A. , Shilstein S. Sh. , Chechik R. , Breskin A. , Vartsky D. , Kleinman N. , Kogan G. , Moriel E. , Gladysh V. , Huszar M. , Ramon J. , Raviv G.
Published: April 2008

Background

The correlation between Zinc concentration in the prostate's peripheral zone to the onset or presence of malignant process needs to be evaluated in detail.

Methods

Zinc concentration was measured in ∼1–4 mm3 segments of fresh needle‐biopsy cores, with X‐ray fluorescence, and correlated with the histological findings of these tissue segments.

Results

Local Zinc concentration is correlated with the presence of cancer (PCa); the higher the Gleason score the greater the Local Zinc depletion. The Zinc value averaged over the entire extracted tissue is specific only to Gleason score 8–9 PCa. The results refer to patients avoiding Zinc‐rich supplements since those show elevated prostatic Zinc concentration in identified cancer tissue. A computer simulation analysis of randomly located 0.03–3.3 cm3 lesions, with particular Gleason score and the measured Local Zinc concentration, revealed a potential diagnostic approach definitely superior to PSA, with sensitivity to the tumor grade and with excellent detection capability for Gleason score >6. Further clinical studies have been designed, both on full prostates after radical prostatectomy as well as on biopsy cores at higher resolution, to establish the accuracy of the method for Gleason score = 6.

Conclusions

The PCa diagnostic potential of Local Zinc concentration is confirmed and there is indication that the amount of Zinc depletion could be used as a measure of the Gleason score of the tumor. Local Zinc concentration mapping has the potential to improve patient selection for biopsy, biopsy site selection and local therapy (e.g., Cryotherapy, Brachytherapy) site selection. Prostate 68:994–1006, 2008. © 2008 Wiley‐Liss, Inc.
Functional annotation by sequence‐weighted structure alignments: Statistical analysis and case studies from the Protein 3000 structural genomics project in Japan
Authors: Standley Daron M. , Toh Hiroyuki , Nakamura Haruki
Published: April 2008

A method to functionally annotate structural genomics targets, based on a novel structural alignment scoring function, is proposed. In the proposed score, position‐specific scoring matrices are used to weight structurally aligned residue pairs to highlight evolutionarily conserved motifs. The functional form of the score is first optimized for discriminating domains belonging to the same Pfam family from domains belonging to different families but the same CATH or SCOP superfamily. In the optimization stage, we consider four standard weighting functions as well as our own, the “maximum substitution probability,” and combinations of these functions. The optimized score achieves an area of 0.87 under the receiver‐operating characteristic curve with respect to identifying Pfam families within a sequence‐unique benchmark set of domain pairs. Confidence measures are then derived from the benchmark distribution of true‐positive scores. The alignment method is next applied to the task of functionally annotating 230 query proteins released to the public as part of the Protein 3000 structural genomics project in Japan. Of these queries, 78 were found to align to templates with the same Pfam family as the query or had sequence identities ≥30%. Another 49 queries were found to match more distantly related templates. Within this group, the template predicted by our method to be the closest functional relative was often not the most structurally similar. Several nontrivial cases are discussed in detail. Finally, 103 queries matched templates at the fold level, but not the family or superfamily level, and remain functionally uncharacterized. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Refinement of noncalorimetric determination of the change in heat capacity, ΔCp, of protein unfolding and validation across a wide temperature range
Authors: Talla‐Singh Deepika , Stites Wesley E.
Published: April 2008

The change in heat capacity, ΔCp, on protein unfolding has been usually determined by calorimetry. A noncalorimetric method which employs the Gibbs‐Helmholtz relationship to determine ΔCp has seen some use. Generally, in this method the free energy change on unfolding of the protein is determined at a variety of temperatures and the temperature at which ΔG is zero, Tm, and change in enthalpy at Tm are determined by thermal denaturation and ΔCp is then calculated using the Gibbs‐Helmholtz equation. We show here that an abbreviated method with stability determinations at just two temperatures gives values of ΔCp consistent with values from free energy change on unfolding determination at a much wider range of temperatures. Further, even the free energy change on unfolding from a single solvent denaturation at the proper temperature, when coupled with the melting temperature, Tm, and the van't Hoff enthalpy, ΔHvH, from a thermal denaturation, gives a reasonable estimate of ΔCp, albeit with greater uncertainty than solvent denaturations at two temperatures. We also find that nonlinear regression of the Gibbs‐Helmholtz equation as a function of stability and temperature while simultaneously fitting ΔCp, Tm, and ΔHvH gives values for the last two parameters that are in excellent agreement with experimental values. Proteins 2008. © 2008 Wiley‐Liss, Inc.
The complex structure of calmodulin bound to a calcineurin peptide
Authors: Ye Qilu , Wang Hailong , Zheng Jimin , Wei Qun , Jia Zongchao
Published: April 2008

The activity of the protein phosphatase calcineurin (CN) is regulated by an autoinhibition mechanism wherein several domains from its catalytic A subunit, including the calmodulin binding domain (CaMBD), block access to its active site. Upon binding of Ca2+ and calmodulin (Ca2+/CaM) to CaMBD, the autoinhibitory domains dissociate from the catalytic groove, thus activating the enzyme. To date, the structure of the CN/CaM/Ca2+ complex has not been determined in its entirety. Previously, we determined the structure of a fusion protein consisting of CaM and a 25‐residue peptide taken from the CaMBD, joined by a 5‐glycine linker. This structure revealed a novel CaM binding motif. However, the presence of the extraneous glycine linker cast doubt on the authenticity of this structure as an accurate representation of CN/CaM binding in vivo. Thus, here, we have determined the crystal structure of CaM complexed with the 25‐residue CaMBD peptide without the glycine linker at a resolution of 2.1 Å. The structure is essentially identical to the fusion construction which displays CaM bound to the CaMBD peptide as a dimer with an open, elongated conformation. The N‐lobe from one molecule and C‐lobe from another encompass and bind the CaMBD peptide. Thus, it validates the existence of this novel CaM binding motif. Our experiments suggest that the dimeric CaM/CaMBD complex exists in solution, which is unambiguously validated using a carefully‐designed CaM‐sepharose pull‐down experiment. We discuss structural features that produce this novel binding motif, including the role of the CaMBD peptide residues Arg‐408, Val‐409, and Phe‐410, which work to provide rigidity to the otherwise flexible central CaM helix joining the N‐ and C‐lobes, ultimately keeping these lobes apart and forcing “head‐to‐tail” dimerization to attain the requisite N‐ and C‐lobe pairing for CaMBD binding. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Structure determination of discoidin II from Dictyostelium discoideum and carbohydrate binding properties of the lectin domain
Authors: Aragão Karoline Saboia , Satre Michel , Imberty Anne , Varrot Annabelle
Published: April 2008

The social amoeba Dictyostelium discoideum adopts a cohesive stage upon starvation and then produces Discoidin I and II, two proteins able to bind galactose and N‐acetyl‐galactosamine. The N‐terminal domain or discoidin domain (DS) is widely distributed in eukaryotes where it plays a role in extracellular matrix binding while the C‐terminal domain displays sequence similarities to invertebrate lectins. We present the first X‐ray structures of the wild‐type and recombinant Discoidin II in unliganded state and in complex with monosaccharides. The protein forms a homotrimer which presents two binding surfaces situated on the opposite boundaries of the structure. The binding sites of the N‐terminal domain contain PEG molecules that could mimics binding of natural ligand. The C‐terminal lectin domain interactions with N‐acetyl‐D‐galactosamine and methyl‐β‐galactoside are described. The carbohydrate binding sites are located at the interface between monomers. Specificity for galacto configuration can be rationalized since the axial O4 hydroxyl group is involved in several hydrogen bonds with protein side chains. Titration microcalorimetry allowed characterization of affinity and demonstrated the enthalpy‐driven character of the interaction. Those results highlight the structural differentiation of the DS domain involved in many cell‐adhesion processes from the lectin activity of Dictyostelium discoidins. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Temperature‐dependent downhill unfolding of ubiquitin. II. Modeling the free energy surface
Authors: Chung Hoi Sung , Tokmakoff Andrei
Published: April 2008

To provide evidence for the interpretation of temperature‐dependent unfolding kinetics and the downhill unfolding scenario presented in the accompanying experimental article (Part I), the free energy surface of ubiquitin unfolding is calculated using statistical mechanical models of the Muñoz‐Eaton (ME) form. The models allow only two states for each amino acid residue, folded or unfolded, and permutations of these states generate an ensemble of microstates. One‐dimensional free energy curves are calculated using the number of folded residues as a reaction coordinate. The proposed sequential unfolding of ubiquitin's β‐sheet is tested by mapping the free energy onto two reaction coordinates inspired by the experiment as follows: the number of folded residues in ubiquitin's stable β‐strands I and II and those of the less stable strands III–V. Although the original ME model successfully captures folding features of zipper‐like one‐dimensional folders, it misses important tertiary interactions between residues that are far from each other in primary sequence. To take tertiary contacts into account, partially folded microstates based on a spherical growth model are included in the calculation and compared with the original model. By calculating the folding probability of each residue for a given point on the free energy surface, the unfolding pathway of ubiquitin is visualized. At low temperature, thermal unfolding occurs along a sequential unfolding pathway as follows: disruption of the β‐strands III–V followed by unfolding of the strands I and II. At high temperature, multiple unfolding routes are formed. The heterogeneity of the transition state explains the global nonexponential unfolding observed in the T‐jump experiment at high temperature. The calculation also reports a high stability for the α‐helix of ubiquitin. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Temperature‐dependent downhill unfolding of ubiquitin. I. Nanosecond‐to‐millisecond resolved nonlinear infrared spectroscopy
Authors: Chung Hoi Sung , Tokmakoff Andrei
Published: April 2008

Transient thermal unfolding of ubiquitin is investigated using nonlinear infrared spectroscopy after a nanosecond laser temperature jump (T‐jump). The abrupt change in the unfolding free energy surface and the ns time resolution allow us to observe a fast response on ns to μs time‐scales, which we attribute to downhill unfolding, before a cross‐over to ms kinetics. The downhill unfolding by a sub‐population of folded proteins is induced through a shift of the barrier toward the native state. By adjusting the T‐jump width, the effect of the initial (Ti) and final (Tf) temperature on the unfolding dynamics can be separated. From the amplitude of the fast downhill unfolding, the fractional population prepared at the unfolding transition state is obtained. This population increases with both Ti and with Tf. A two‐state kinetic analysis of the ms refolding provides thermodynamic information about the barrier height. By a combination of the fast and slow unfolding and folding parameters, a quasi‐two‐state kinetic analysis is performed to calculate the time‐dependent population changes of the folded state. This calculation coincides with the experimentally obtained population changes at low temperature but deviations are found in the T‐jump from 67 to 78°C. Using temperature‐dependent barrier height changes, a temperature Φ value analysis is performed. The result shows a decreasing trend of ΦT with temperature, which indicates an increase of the heterogeneity of the transition state. We conclude that ubiquitin unfolds along a well‐defined pathway at low temperature which expands with increasing temperature to include multiple routes. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Using a strategy based on the concept of convergent evolution to identify residue substitutions responsible for thermal adaptation
Authors: Lin Yeong‐Shin
Published: April 2008

Factors that are related to thermostability of proteins have been extensively studied in recent years, especially by comparing thermophiles and mesophiles. However, most of them are global characters. It is still not clear how to identify specific residues or fragments which may be more relevant to protein thermostability. Moreover, some of the differences among the thermophiles and mesophiles may be due to phylogenetic differences instead of thermal adaptation. To resolve these problems, I adopted a strategy to identify residue substitutions evolved convergently in thermophiles or mesophiles. These residues may therefore be responsible for thermal adaptation. Four classes of genomes were utilized in this study, including thermophilic archaea, mesophilic archaea, thermophilic bacteria, and mesophilic bacteria. For most clusters of orthologous groups (COGs) with sequences from all of these four classes of genomes, I can identify specific residues or fragments that may potentially be responsible for thermal adaptation. Functional or structural constraints (represented as sequence conservation) were suggested to have higher impact on thermal adaption than secondary structure or solvent accessibility does. I further compared thermophilic archaea and mesophilic bacteria, and found that the most diverged fragments may not necessarily correspond to the thermostability‐determining ones. The usual approach to compare thermophiles and mesophiles without considering phylogenetic relationships may roughly identify sequence features contributing to thermostability; however, to specifically identify residue substitutions responsible for thermal adaptation, one should take sequence evolution into consideration. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Brucea javanica fruit induces cytotoxicity and apoptosis in pancreatic adenocarcinoma cell lines
Authors: Lau Sin Ting , Lin Zhi‐Xiu , Zhao Ming , Leung Po Sing
Published: April 2008

Brucea javanica fruit is thought to have anticancer properties in Chinese medicine and its extract has been shown to possess antiproliferative and pro‐apoptotic activities on human carcinoma cells. In the present study we demonstrated for the first time that Fructus Bruceae extract exhibited cytotoxic effects on the three pancreatic adenocarcinoma cell lines, PANC‐1, SW1990 and CAPAN‐1; the effects were comparable to those exhibited by camptothecin in our culture system. In addition, Fructus Bruceae extract induced fragmentation of genomic DNA, as evidenced by Hoechst staining and the cell death detection ELISAPLUS assay. Western blot analysis further showed down‐regulation of pro‐caspase 3 protein expression, indicating that the observed cytotoxic effects of the extract were associated with induction of apoptosis. These findings are not only significant in the development of traditional Chinese medicine as an alternative treatment for pancreatic cancer, but also in the elucidation of the potential mechanism(s) of Fructus Bruceae extract in cancer therapy. Copyright © 2008 John Wiley & Sons, Ltd.
Antifungal activity of Heterothalamus alienus metabolites
Authors: Pacciaroni Adriana del V. , de los Angeles Gette María , Derita Marcos , Ariza‐Espinar Luis , Gil Roberto R. , Zacchino Susana A. , Silva Gloria L.
Published: April 2008

The chemical study of Heterothalamus alienus gave rutin, spathulenol (1), (1R,7S)‐germacra‐4(15),5,10(14)‐trien‐1β‐ol (2), sakuranetin (3), padmatin 3‐acetate (4), (2R,3R)‐dihydroquercetin‐7,3′,4′‐trimethyl ether (5), (2R,3R)‐dihydroquercetin‐7,4′‐dimethyl ether (6), (2R,3R)‐3‐acetoxy‐5,7,4′‐trihydroxyflavanone (7), as the main components of an antifungal extract of the aerial parts of the plant. Compound 2 showed moderate activity, with Epidermophyton floccosum being the most susceptible species (MIC = 100 µg/mL); compound 3 showed the best antifungal behavior having a broad spectrum of action and the lowest MICs. This flavanone along with flavanolol 5 showed very good activity against standardized (MIC = 31.2 µg/mL) as well as clinical isolates of Trichophyton rubrum and T. mentagrophytes (MIC ranges 31.2–62.5 µg/mL and 31.2–125 µg/mL, respectively) and demonstrated not only fungistatic but also fungicide properties. Flavanolol 6 was active against all the dermatophytes tested with MICs of 62.5–250 µg/mL. Rutin, spathulenol (1) and the 3‐acetylated flavanones 4 and 7 were inactive or marginally active against the fungal panel. Copyright © 2008 John Wiley & Sons, Ltd.
Liquorice‐induced hypokalaemia and water retention in the absence of hypertension
Authors: Francini‐Pesenti F. , Puato M. , Piccoli A. , Brocadello F.
Published: April 2008

This is a case report of a woman who showed headache, weakness, upper‐limb edema and a generalized convulsive seizure after chronic ingestion of liquorice. She was taking oral contraceptives which can predispose to liquorice toxicity. Plasma potassium, aldosterone, renin activity and albumin were below the normal level. The abdominal echography and computerized tomography scan demonstrated a perihepatic and perisplenic thin liquid layer with liquid collection in the pelvis. The bioelectrical impedance suggested a hyperhydration state. After stopping the liquorice, the laboratory and bioelectrical values normalized and clinical upper‐limb edema and the liquid in the abdomen disappeared in a few days. Copyright © 2008 John Wiley & Sons, Ltd.
Keto‐enol tautomerism in linear and cyclic β‐diketones: A DFT study in vacuo and in solution
Authors: Alagona Giuliano , Ghio Caterina
Published: April 2008

DFT geometry optimizations have been performed at the B3LYP/6‐31G* level in the gas phase and at the IEF‐PCM/B3LYP/6‐31G* level in tetrahydrofuran (THF) and aqueous solutions using scaled radii for the diketo and ketoenol forms of acetylacetone and cyclohexanedione. To evaluate basis set effects, starting from the aforementioned minima, the 6‐311++G** optimized structures have been obtained. A number of complexes of both systems including one explicit water molecule have been considered up to the B3LYP/6‐311++G** level, for cyclohexanedione taking into account the B3LYP/6‐31G* basis set superposition errors as well. The diketo–ketoenol interconversion mechanisms have been investigated at the B3LYP/6‐31G* level in vacuo. Interestingly, the geometric constraint due to the presence of the ring facilitates the description of the reaction mechanism in cyclohexanedione. Despite the very different flexibility of the two systems that in the case of acetylacetone prevents a straightforward interconversion of the diketo to the most stable of its ketoenol forms, both reactions occur with a very high barrier (about 62–63 kcal/mol), unaffected by continuum solvents, that decreases by 2.5–3.5 kcal/mol after the inclusion of thermal corrections. The barriers are almost halved, becoming ∼31–35 kcal/mol, for the addition of a single water molecule according to various model reaction paths. Thermal corrections are limited (0.8–1.6 kcal/mol) for those adducts. The formation of a 1,1‐diol, explored in the case of acetylacetone, might facilitate the obtainment of the most stable diketo conformation, featuring the carbonyl groups in distinct orientations. Inclusion of dispersion and basis set effects via the G2MP2 protocol does not alter the relative stability of both system tautomers. In contrast, the G2MP2 interconversion barriers for the isolated systems in vacuo are close to the B3LYP ones, whereas they turn out to be somewhat higher than the free energy‐based B3LYP barriers in the presence of a catalytic water molecule. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008
Quantum‐based models of charge‐dependent potential energy surfaces: Three‐state models
Authors: Valone Steven M. , Li Jiabo , Jindal Saryu
Published: April 2008

Quantum‐based models of how potential energies depend on charge are developed from a three‐state model, at the level of neglecting state‐to‐state overlap. The energy as a function of charge is defined as proposed previously (Valone and Atlas, J Chem Phys 2004, 120, 7262). With this definition, addition of a third state smooths the derivatives of the energy model with respect to charge at integer values of charge that are in the interior of the allowed charge range. These derivatives are related to the chemical potential. At the dissociation limit, this model converges to established limits. Another dependence is proposed that uses two different charges simultaneously. The concepts are illustrated, with calculations on an OH molecule. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008
Revisiting the foundations of quantum theory of atoms in molecules (QTAIM): The variational procedure and the zero‐flux conditions
Authors: Nasertayoob Payam , Shahbazian Shant
Published: April 2008

A rigorous mathematical procedure is proposed in order to employ the variational apparatus in “Quantum theory of atoms in molecules.” This mathematical procedure is free from the previously reported mathematical obstacles. Although it is possible to apply the Schrödinger's variational procedure to derive the putative net zero‐flux condition, no claim has been made to derive the equation of motion (Schrödinger equation) from subsystem variational procedure. In this regard, the problem of admissible and general neighborhoods and their relevance to the subsystem variational procedure has been discussed thoroughly in this article. In the end, a brief discussion has been offered to emphasize the difference between the net and local zero‐flux conditions with particular emphasize on its logical consequences. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008
Koopmans' approximation applied in atoms and diatomic molecules using the diffusion quantum Monte Carlo method
Authors: Delfino Angelotti Wagner Fernando , Streit Lívia , Luiz Da Fonseca André , Custodio Rogério
Published: April 2008

Koopmans' theorem was applied to generate trial wave functions for ions from neutral systems and further applied in the determination of vertical ionization energies using the diffusion quantum Monte Carlo (DQMC) method. The results for successive and conventional ionization energies for atoms and diatomic molecules using the Slater minimum basis set with polarization wave functions indicate that DQMC provides a significant quantity of relaxation and electronic correlation effects. The conventional ionizations for core electrons calculated with DQMC for atoms and diatomic molecules yielded an average deviation of around 2–3 eV from the experimental results, which is excellent when compared with a deviation of around 17 eV estimated from Koopmans' theorem. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008
The Tyranny of Small Steps: a reoccurring behaviour in management
Authors: Haraldsson Hörður V. , Sverdrup Harald U. , Belyazid Salim , Holmqvist Johan , Gramstad Robin C. J.
Published: April 2008

The Tyranny of Small Steps (TYST) behaviour has been investigated. Explained through a systemic perspective, the behaviour TYST is an unwanted change to a system through a series of small activities that may be independent from one another. These activities are small enough not to be detected by the ‘surveillance’ within the system, but significant enough to encroach upon the ‘tolerance zone’ of the system and compromise integrity of the system. TYST is an unintentional process that is experienced within the system and made possible by the lack of transparency between an overarching level and a local level where the encroachment is taking place. The Örby case study illustrates a real life manifestation of the TYST behaviour in management and planning. The TYST illustrates the necessity for total transparency in any systems in order to avoid unintended consequence. The TYST process may be regarded as a part of wide range of complex systems but depending on the conditions, it can remain dormant, and only become active when the conditions for lack of transparency are fulfilled. Copyright © 2008 John Wiley & Sons, Ltd.
Systems science and complexity: some proposals for future development
Authors: Leleur Steen
Published: April 2008

In this paper some new, conceptual ideas referred to as a complexity orientation are presented on the basis of systemic planning (SP), which has been developed as a proactive, multi‐methodology approach for complex planning tasks. Specifically, the complexity orientation is compared to other systems science research orientations represented by the following labels: functionalist, interpretive, emancipatory and postmodern. After presentation and discussion of the research orientation framework, SP is compared to other current systems and management practice. Finally, the potential of a complexity orientation is treated more generally and also with a focus on its epistemological interpretation, which is carried out with a special emphasis on the work of Luhmann. General findings of the paper are that a complexity orientation ought to complement the other four research orientations to serve as a methodological platform for management practice and that Luhmann's theories ought to be addressed by the systems community as a potential for informing further development of systems science and thinking. Copyright © 2008 John Wiley & Sons, Ltd.
Is management science or art?
Authors: Gao Fei
Published: April 2008

In this paper I have drawn a brief picture to map the nature of management in modern high‐tech organizations from the viewpoint of critical systems thinking. First, I point out the difference between science and art. Then, following Jackson's classification of different systems approaches such as modernism and postmodernism, I connect modernism with objectivism and collective subjectivism, and postmodernism with individual subjectivism. Through clarifying three ways of knowing/understanding the world and introducing a new knowledge systems model of modern high‐tech corporations, I argue that in the knowledge age, management is both a science and an art. Objects under consideration belonging to different parts of reality require different approaches to deal with. The purpose of this article is to give a brief explanation of why management is both a science and an art, and to inspire further debate and discussion on the essence of management among academics and practitioners. Copyright © 2008 John Wiley & Sons, Ltd.
A theoretical framework for a structuration model of social issues in software development in information systems
Authors: Loureiro‐Koechlin Cecilia
Published: April 2008

This study looks at how human and social issues affect software developers' work and the software they produce. It focuses on the development of software to support information systems, and therefore positions software development as an activity within Information Systems Development. Although some research in IS and software development address human and social issues they do so by considering either business organisations or software development environments separately but do not connect both contexts together. This research tries to build this connection through a model of social issues in software development. The model was generated from data collected from an interpretive online ethnography of virtual communities of software developers. The model of social issues complements Orlikowski's structurational model of enactment of technologies‐in‐practice and suggests that human and social issues that affect the production of software emerge from three different contexts: software development environment, software development practices and complex business organisations. Copyright © 2008 John Wiley & Sons, Ltd.
Prenatal ultrasound detection of facial clefts: a prospective study of 49 314 deliveries in a non‐selected population in Norway
Authors: Offerdal K. , Jebens N. , Syvertsen T. , Blaas H.‐G. K. , Johansen O. J. , Eik‐Nes S. H.
Published: April 2008

Objectives

To evaluate prenatal detection of facial clefts by ultrasound examination in a large non‐selected population, and to study trends in detection rates over 18 years, as well as the prevalence of isolated cases and those with associated anomalies.

Methods

This prospective follow‐up study from January 1987 to December 2004 was divided into two 9‐year periods. The study included all registered cases of prenatally or postnatally diagnosed facial clefts in a non‐selected population in Norway.

Results

A total of 101 fetuses or newborns with facial clefts in a population of 49 314 deliveries were registered. The distribution of clefts was: 25 (25%) cleft lip, 52 (51%) cleft lip and palate, and 24 (24%) cleft palate (CP). No CP was detected prenatally. Cleft lip with or without cleft palate (CL(P)) was detected prenatally in 35/77 (45%) cases, with a significant increase in the detection rate from 34% to 58% between the two 9‐year periods (P = 0.03). Over the whole study period CL(P) was detected at a median of 19 + 2 gestational weeks, with no change over time; altogether 24/35 (69%) cases were detected at the routine second‐trimester ultrasound examination. Thirty‐three of 77 (43%) cases of CL(P) and 14/24 (58%) cases of CP had associated anomalies; 12/101 (12%) had chromosomal aberrations. In 18/101 (18%) the clefts were part of a syndrome or sequence.

Conclusions

The detection rate for CL(P) improved significantly over time. Detection of CL(P) is important because nearly half the cases have associated anomalies. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.
Faith‐based organizing for youth: One organization's district campaign for small schools policy
Authors: Snyder Ron
Published: April 2008

Oakland Community Organizations (OCO) has worked for over ten years to improve educational opportunities in low‐income neighborhoods in Oakland, California. The work of thousands of parent, teacher, youth, and community leaders has resulted in the formation of nearly fifty new small schools and more than ten charters, creating settings for individualized learning environments and the opportunity for quality choices for many of Oakland's low‐income families. In this article, OCO's executive director, Ron Snyder, outlines a four‐phase organizing process undertaken by OCO, based on a set of organizing principles that have sustained community‐led education reform despite constant changes in the political and school district environment: the centrality of love (self‐interest) as a motivator for advocacy; the importance of quality research and powerful ideas (vision) as alternatives to the status quo; application of a model that creates a common structure, language, and experience to sustain leaders; the need for institutional and network power to apply leverage; the flexibility to seize opportunity when the window is open; and faithfulness to the object of our love: our children.