bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probing the self‐association, intermolecular contacts, and folding propensity of amelogenin
Authors: Ndao Moise , Dutta Kaushik , Bromley Keith M. , Lakshminarayanan Rajamani , Sun Zhi , Rewari Gita , Moradian‐Oldak Janet , Evans John Spencer 
Published: February 2011

AbstractAmelogenins are an intrinsically disordered protein family that plays a major role in the development of tooth enamel, one of the most highly mineralized materials in nature. Monomeric porcine amelogenin possesses random coil and residual secondary structures, but it is not known which sequence regions would be conformationally attractive to potential enamel matrix targets such as other amelogenins (self‐assembly), other matrix proteins, cell surfaces, or biominerals. To address this further, we investigated recombinant porcine amelogenin (rP172) using “solvent engineering” techniques to simultaneously promote native‐like structure and induce amelogenin oligomerization in a manner that allows identification of intermolecular contacts between amelogenin molecules. We discovered that in the presence of 2,2,2‐trifluoroethanol (TFE) significant folding transitions and stabilization occurred primarily within the N‐ and C‐termini, while the polyproline Type II central domain was largely resistant to conformational transitions. Seven Pro residues (P2, P127, P130, P139, P154, P157, P162) exhibited conformational response to TFE, and this indicates these Pro residues act as folding enhancers in rP172. The remaining Pro residues resisted TFE perturbations and thus act as conformational stabilizers. We also noted that TFE induced rP172 self‐association via the formation of intermolecular contacts involving P4–H6, V19–P33, and E40–T58 regions of the N‐terminus. Collectively, these results confirm that the N‐ and C‐termini of amelogenin are conformationally responsive and represent potential interactive sites for amelogenin–target interactions during enamel matrix mineralization. Conversely, the Pro, Gln central domain is resistant to folding and this may have important functional significance for amelogenin.
Docosahexaenoic acid selectively induces human prostate cancer cell sensitivity to oxidative stress through modulation of NF‐κB
Authors: Cavazos David A. , Price Ramona S. , Apte Shruti S. , deGraffenried Linda A. 
Published: February 2011

AbstractBACKGROUNDOxidative burden is strongly implicated in the pathogenesis of age‐related diseases, including prostate cancer tumor formation. As omega‐3 fatty acids possess known antioxidant properties, we investigated the effects of docosahexaenoic acid (DHA‐22:6n‐3), one component of fish oil, in modulating the effects of oxidative DNA damage in LNCaP and PacMetUT1 human prostate adenocarcinoma cells and in a normal human prostate cell line, PrEC.METHODSCell survival was determined by an inhibition of colony formation assay. DNA double‐strand breaks, NF‐κB subcellular localization and relative survivin expression levels were determined by immunofluorescence and survivin expression levels confirmed by immunoblot assay. Measurement of NF‐κB transcriptional activity was investigated by dual luciferase assay.RESULTSLNCaP and PacMetUT1 cells pretreated with DHA and pulsed with 32 µM H2O2 exhibit decreased survival compared to PrEC. γ‐H2AX foci, indicating DNA double‐strand breaks, were associated with translocation of NF‐κB into the nucleus, whereas exposure to DHA prior to H2O2 treatment prevented NF‐κB translocation. Further, DHA attenuated H2O2‐induced NF‐κB transcriptional activity and diminished expression of the downstream target, survivin.CONCLUSIONSNF‐κB is heavily implicated in promoting prosurvival signaling and may be critical for resistance to the chronic oxidative stress observed in the pathogenesis of prostate cancer. Our studies indicate that exposure of cells to physiologically achievable levels of DHA prior to treatment with H2O2 results in decreased cancer cell survival which is associated with nuclear exclusion of NF‐κB. We therefore propose that DHA selectively sensitizes prostate cancer cells to growth arrest through attenuation of the NF‐κB survival pathway. Prostate 71:1420–1428, 2011. © 2011 Wiley‐Liss, Inc.
hZIP1 zinc transporter down‐regulation in prostate cancer involves the overexpression of ras responsive element binding protein‐1 (RREB‐1)
Authors: Zou Jing , Milon Beatrice C. , Desouki Mohamed M. , Costello Leslie C. , Franklin Renty B. 
Published: February 2011

AbstractBACKGROUNDA marked decrease in the level of zinc is a consistent characteristic of prostate cancer; which results from down‐regulation of ZIP1 zinc transporter. The aim of this study was to determine if RREB‐1 transcription is involved in the down‐regulation of ZIP1 gene expression; and to determine the expression of RREB‐1 in benign and cancerous prostate in situ.METHODSOverexpression and siRNA knock down of RREB‐1 were used to determine the effect of RREB‐1 on hZIP1 abundance in PC‐3 cells. Immunohistochemistry with tissue microarrays (TMAs) and tissue sections was used to determine the levels of RREB‐1 expression in prostate in situ.RESULTSOverexpression of RREB‐1 resulted in a decrease in the abundance of hZIP1 in the plasma membrane of PC‐3 cells; whereas siRNA knock down significantly increased hZIP1 expression. Prostate TMAs and tissue sections showed an inverse relationship between RREB‐1 and hZIP1 staining.CONCLUSIONSRREB‐1 overexpression results in down‐regulation of hZIP1 and contributes to the loss of hZIP1 expression and zinc in prostate cancer. This is an early event in prostate carcinogenesis. Prostate 71:1518–1524, 2011. © 2011 Wiley‐Liss, Inc.
Genetic variation in RNASEL and risk for prostate cancer in a population‐based case–control study
Authors: Fesinmeyer Megan D. , Kwon Erika M. , Fu Rong , Ostrander Elaine A. , Stanford Janet L. 
Published: February 2011

AbstractBACKGROUNDLinkage studies have implicated chromosome 1q24 as a putative locus for hereditary prostate cancer. The RNASEL gene maps to 1q24 and has been associated with prostate cancer risk in multiple family‐based linkage studies. The RNASEL gene product combats viral infection by degrading viral RNA and inducing apoptosis of infected cells. Few studies have evaluated the role of RNASEL variants in unselected or sporadic prostate cancer, or have considered the potential interaction between RNASEL variants and patient characteristics associated with past infection.METHODSTen SNPs in the RNASEL gene were genotyped in 1,308 prostate cancer cases and 1,267 age‐matched controls from prior population‐based, case–control studies. The association between each SNP and haplotype with prostate cancer risk was calculated using logistic regression. Associations stratified by Gleason score were evaluated using polytomous regression. The likelihood ratio test was used to investigate effect modification.RESULTSTwo RNASEL SNPs were associated with overall increases in prostate cancer risk (OR = 1.13 for each variant allele of rs12723593; OR = 1.88 for any variant allele of rs56250729). Risk estimates did not vary substantially by Gleason score, but there was effect modification for the variant allele of rs635261 by history of prostatitis (P = 0.02).CONCLUSIONSThis study identified three RNASEL variants that are associated with risk for prostate cancer. Further research is required to confirm these results and to better understand the potential role RNASEL variants may play in the etiology of sporadic prostate cancer. Prostate 71:1538–1547, 2011. © 2011 Wiley‐Liss, Inc.
SWAP70, actin‐binding protein, function as an oncogene targeting tumor‐suppressive miR‐145 in prostate cancer
Authors: Chiyomaru Takeshi , Tatarano Shuichi , Kawakami Kazumori , Enokida Hideki , Yoshino Hirofumi , Nohata Nijiro , Fuse Miki , Seki Naohiko , Nakagawa Masayuki 
Published: February 2011

AbstractBACKGROUNDMiR‐145 is down‐regulated in various human cancers. We previously demonstrated that some actin‐binding proteins were targeted by several microRNAs (miRNAs), including miR‐145, in bladder and prostate cancer (CaP). The aim of this study is to determine a novel oncogenic gene targeted by miR‐145 by focusing on actin‐binding proteins in CaP.METHODSWe focused on the SWAP switching B‐cell complex 70 kDa subunit (SWAP70), which is an F‐actin binding protein involved in activating B‐cell transformation. A luciferase reporter assay was used to identify the actual binding sites between miR‐145 and SWAP70 mRNA. Cell viability was evaluated by cell proliferation, wound healing, and matrigel invasion assays in si‐SWAP70 transfectants. A total of 75 clinical prostate specimens were subjected to immunohistochemistry of SWAP70.RESULTSMolecular target searches of this miRNA and the luciferase reporter assay showed that SWAP70 was directly regulated by miR‐145. Silencing of SWAP70 studies demonstrated significant inhibitions of cell migration and invasion in CaP cell lines. The SWAP70 positive‐staining was significantly higher in percentage in the CaP than in benign prostate hyperplasia tissue.CONCLUSIONSDown‐regulation of miR‐145 was a frequent event in CaP, and it may have a tumor suppressive function. SWAP70 may be a target of miR‐145, and it might have a potential oncogenic function. The novel molecular networks though which miR‐145 acts, may provide new insights into the underlying molecular mechanisms of CaP. Prostate 71:1559–1567, 2011. © 2011 Wiley‐Liss, Inc.
Gene expression pathways of high grade localized prostate cancer
Authors: Ross Ashley E. , Marchionni Luigi , Vuica‐Ross Milena , Cheadle Chris , Fan Jinshui , Berman David M. , Schaeffer Edward M. 
Published: February 2011

AbstractBACKGROUNDDespite advances in screening and local therapy, prostate cancer remains the second most common cause of cancer related death among American men, with those having high grade disease being at highest risk for prostate cancer mortality. Here we identify the genes and cellular pathways that distinguish high grade from low grade pathologically localized prostate cancer.METHODSCancer cells from low grade (Gleason 3 + 3 = 6) or high grade (4 + 4 = 8) tumors of men with localized disease were isolated by laser capture micro‐dissection. Expression profiling was conducted across 18,344 unique annotated genes and data were analyzed using packages from the R/Bioconductor project to determine differential gene expression and perform gene set enrichment analysis. Publically available expression data was retrieved and analyzed individually in the same manner and in cross platform meta‐analyses.RESULTSSix hundred seventy genes were differentially expressed between Gleason sum 6 and 8 tumors with a false discovery rate of <5% (P < 0.0014) including genes previously shown to mediate prostate cancer survival, proliferation, and metastasis. Functional themes associated with Gleason grade included developmental processes, signal transduction, chemokine and embryonic stem cell pathways with specific enrichment of the androgen receptor, EGFR, TNF‐alpha, and Notch signaling cascades.CONCLUSIONSIn addition to androgen receptor signaling, growth factor, and cytokine mediated pathways are active in clinically localized high grade prostate cancer. The availability of therapeutics that selectively target these pathways encourages the development of clinical trials for their selective use in the neoadjuvant or adjuvant setting in men at high risk for disease progression. Prostate 71:1568–1578, 2011. © 2011 Wiley‐Liss, Inc.
Efficacy of layer treatment with methoprene for control of Rhyzopertha dominica (Coleoptera: Bostrychidae) on wheat, rice and maize
Authors: Athanassiou Christos G , Arthur Frank H , Throne James E 
Published: February 2011

AbstractBACKGROUND: Insect growth regulators are promising alternatives to traditional pesticides in stored grain. The efficacy of the juvenile hormone analogue methoprene was evaluated as a layer treatment in a laboratory experiment for control of Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae) in wheat, rice and maize.RESULTS: Adults of R. dominica were placed in vials containing 33, 26 and 29 g (to a depth of 6.5 cm) of wheat, rice and maize, respectively, that was entirely or partially treated with 1, 5 or 10 mg kg−1 methoprene. In wheat and rice, the layer treatments were not as effective as the whole‐grain treatment, but there was decreased progeny production as the application rate increased. However, on maize the partial treatments were as effective as the whole‐grain treatment at 5 and 10 mg kg−1.CONCLUSIONS: The results suggest that partial layer treatments with methoprene can be used to control R. dominica on maize but may not be effective for control of this species on wheat and rice. Copyright © 2011 Society of Chemical Industry
Impact of Cry3Bb1‐expressing Bt maize on adults of the western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae)
Authors: Meissle Michael , Hellmich Richard L , Romeis Jörg 
Published: February 2011

AbstractBACKGROUND: Genetically engineered maize producing insecticidal Cry3Bb1 protein from Bacillus thuringiensis (Bt) is protected from root damage by corn rootworm larvae. An examination was made to establish whether western corn rootworm (Diabrotica virgifera virgifera) adults are affected by Cry3Bb1‐expressing maize (MON88017) when feeding on above‐ground tissue.RESULTS: In laboratory bioassays, adult D. v. virgifera were fed for 7 weeks with silk, leaves or pollen from Bt maize or the corresponding near‐isoline. Male, but not female, survival was reduced in the Bt‐leaf treatment compared with the control. Female weight was lower when fed Bt maize, and egg production was reduced in the Bt‐silk treatment. ELISA measurements demonstrated that beetles feeding on silk were exposed to higher Cry3Bb1 concentrations than beetles collected from Bt‐maize fields in the United States. In contrast to silk and pollen, feeding on leaves resulted in high mortality and low fecundity. Females feeding on pollen produced more eggs than on silk. C:N ratios indicated that silk does not provide enough nitrogen for optimal egg production.CONCLUSIONS: Direct effects of Cry3Bb1 on adult beetles could explain the observed effects, but varietal differences between Bt and control maize are also possible. The impact of Bt maize on adult populations, however, is likely to be limited. Copyright © 2011 Society of Chemical Industry
Gastrin and cholecystokinin peptide‐based radiopharmaceuticals: an in vivo and in vitro comparison
Authors: Tornesello Anna Lucia , Aurilio Michela , Accardo Antonella , Tarallo Laura , Barbieri Antonio , Arra Claudio , Tesauro Diego , Morelli Giancarlo , Aloj Luigi 
Published: February 2011

AbstractThe development of suitable radioligands for targeting CCK‐2 receptor expressing tumors, such as medullary thyroid carcinoma, is of great clinical interest. In the search for the best CCK‐2R binding peptides, we have synthesized, evaluated and compared the CCK8 peptide (Asp‐Tyr‐Met‐Gly‐Trp‐Met‐Asp‐PheNH2) and two gastrin analogs commonly referred to as MG0 (DGlu‐Glu(5)‐Ala‐Tyr‐Gly‐Trp‐Met‐Asp‐PheNH2) and MG11 (DGlu(1)‐Ala‐Tyr‐Gly‐Trp‐Met‐Asp‐PheNH2). The N‐terminal portion of the three peptide sequences was derivatized by introducing the DTPAGlu or DOTA chelators to allow radiolobeling with 111In(III) and 68Ga(III), respectively. Saturation binding and cellular internalization experiments were performed on A431 cells overexpressing CCK2R (A431‐CCK2R). All compounds showed Kd values in the nM range and were internalized with similar rates in CCK2 receptor overexpressing cells. Biodistribution experiments showed higher specific uptake of both MG0‐based compounds compared to conjugates containing the CCK8 and MG11 peptide sequences. The higher retention levels of MG0‐based peptides were associated with markedly elevated and undesired kidney uptake compared to the other compounds. Current indications suggest that the 5 Glu N‐terminal residues while improving peptide stability and receptor‐mediated tumor uptake cause unacceptably high kidney retention. Although displaying lower absolute tumor uptake values, the DOTA‐coupled CCK8 peptide provided the best tumor to kidney uptake ratio and appears more suitable as lead compound for improvement of radiopharmaceutical properties. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Derivatization of peptides as quaternary ammonium salts for sensitive detection by ESI‐MS
Authors: Cydzik Marzena , Rudowska Magdalena , Stefanowicz Piotr , Szewczuk Zbigniew 
Published: February 2011

AbstractA series of model peptides in the form of quaternary ammonium salts at the N‐terminus was efficiently prepared by the solid‐phase synthesis. Tandem mass spectrometric analysis of the peptide quaternary ammonium derivatives was shown to provide sequence confirmation and enhanced detection. We designed the 2‐(1,4‐diazabicyclo[2.2.2] octylammonium)acetyl quaternary ammonium group which does not suffer from neutral losses during MS/MS experiments. The presented quaternization of 1,4‐diazabicyclo[2.2.2]octane (DABCO) by iodoacetylated peptides is relatively easy and compatible with standard solid‐phase peptide synthesis. This methodology offers a novel sensitive approach to analyze peptides and other compounds. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Probing structural transitions in both structured and disordered proteins using site‐directed spin‐labeling EPR spectroscopy
Authors: Longhi Sonia , Belle Valérie , Fournel André , Guigliarelli Bruno , Carrière Frédéric 
Published: February 2011

AbstractEPR spectroscopy is a technique that specifically detects unpaired electrons. EPR‐sensitive reporter groups (spin labels or spin probes) can be introduced into biological systems via site‐directed spin‐labeling (SDSL). The basic strategy of SDSL involves the introduction of a paramagnetic group at a selected protein site. This is usually accomplished by cysteine‐substitution mutagenesis, followed by covalent modification of the unique sulfydryl group with a selective reagent bearing a nitroxide radical. In this review we briefly describe the theoretical principles of this well‐established approach and illustrate how we successfully applied it to investigate structural transitions in both human pancreatic lipase (HPL), a protein with a well‐defined α/β hydrolase fold, and the intrinsically disorderedC‐terminal domain of the measles virus nucleoprotein (NTAIL) upon addition of ligands and/or protein partners. In both cases, SDSL EPR spectroscopy allowed us to document protein conformational changes at the residue level. The studies herein summarized show that this approach is not only particularly well‐suited to study IDPs that inherently escape atomistic description by X‐ray crystallography but also provides dynamic information on structural transitions occurring within well‐characterized structured proteins for which X‐ray crystallography can only provide snapshots of the initial and final stages. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Chemical synthesis and evaluation of a backbone‐cyclized minimized 2‐helix Z‐domain
Authors: Järver Peter , Mikaelsson Cecilia , Karlström Amelie Eriksson 
Published: February 2011

AbstractThe Z‐molecule is a small, engineered IgG‐binding affinity protein derived from the immunoglobulin‐binding domain B of Staphylococcus aureus protein A. The Z‐domain consists of 58 amino acids forming a well‐defined antiparallel three‐helix structure. Two of the three helices are involved in ligand binding, whereas the third helix provides structural support to the three‐helix bundle. The small size and the stable three‐helix structure are two attractive properties comprised in the Z‐domain, but a further reduction in size of the protein is valuable for several reasons. Reduction in size facilitates synthetic production of any protein‐based molecule, which is beneficial from an economical viewpoint. In addition, a smaller protein is easier to manipulate through chemical modifications. By omitting the third stabilizing helix from the Z‐domain and joining the N‐ and C‐termini by a native peptide bond, the affinity protein obtains the advantageous properties of a smaller scaffold and in addition becomes resistant to exoproteases. We here demonstrate the synthesis and evaluation of a novel cyclic two‐helix Z‐domain. The molecule has retained affinity for its target protein, is resistant to heat treatment, and lacks both N‐ and C‐termini. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Low‐generation asymmetric dendrimers exhibit minimal toxicity and effectively complex DNA
Authors: Shah Neha , Steptoe Raymond J. , Parekh Harendra S. 
Published: February 2011

AbstractConventional dendrimers are spherical symmetrically branched polymers ending with active surface functional groups. Polyamidoamine (PAMAM) dendrimers have been widely studied as gene delivery vectors and have proven effective at delivering DNA to cells in vitro. However, higher‐generation (G4‐G8) PAMAM dendrimers exhibit toxicity due to their high cationic charge density and this has limited their application in vitro and in vivo. Another limitation arises when attempts are made to functionalize spherical dendrimers as targeting moieties cannot be site‐specifically attached. Therefore, we propose that lower‐generation asymmetric dendrimers, which are likely devoid of toxicity and to which site‐specific attachment of targeting ligands can be achieved, would be a viable alternative to currently available dendrimers. We synthesized and characterized a series of peptide‐based asymmetric dendrimers and compared their toxicity profile and ability to condense DNA to spherical PAMAM G1 dendrimers. We show that asymmetric dendrimers are minimally toxic and condense DNA into stable toroids which have been reported necessary for efficient cell transfection. This paves the way for these systems to be conjugated with targeting ligands for gene delivery in vitro and in vivo. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Triplet–triplet energy transfer studies on conformational dynamics in peptides and a protein
Authors: Reiner Andreas 
Published: February 2011

AbstractPeptides and proteins are highly dynamic systems, which can adopt more or less stable conformations. The dynamics of these molecules, particularly those on the nanosecond to tens of microsecond time scale, are difficult to assess with conventional techniques. This review summarizes experiments using TTET, a technique that reports on van der Waals contact formation between a triplet donor and acceptor group, and which is sensitive in this time range. TTET allows to directly measure the chain dynamics of unstructured model peptides, i.e. large‐amplitude fluctuations on the nanosecond time scale. Furthermore, contact formation can be used as irreversible probing reaction to study the kinetics of conformational equilibria. This approach enabled us to measure local α‐helix folding and unfolding in helical peptides, which gave new insight into the equilibrium dynamics of this fundamental secondary structure element. TTET has also been applied to study the dynamics both in the native and unfolded state of a protein, the villin headpiece subdomain. The contact formation kinetics between different positions revealed an unlocking and local unfolding reaction in the native state of this model protein, and gave information about the chain dynamics in the unfolded state ensemble. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.