bluuebunny/crossref_metadata_2025_split huggingface dataset:
A water soluble parthenolide analog suppresses in vivo tumor growth of two tobacco‐associated cancers, lung and bladder cancer, by targeting NF‐κB and generating reactive oxygen species
Authors: Shanmugam Rajasubramaniam , Kusumanchi Praveen , Appaiah Hitesh , Cheng Liang , Crooks Peter , Neelakantan Sundar , Peat Tyler , Klaunig James , Matthews William , Nakshatri Harikrishna , Sweeney Christopher J. 
Published: July 2010

AbstractDimethylaminoparthenolide (DMAPT) is a water soluble parthenolide analog with preclinical activity in hematologic malignancies. Using non–small lung cancer (NSCLC) cell lines (A549 and H522) and an immortalized human bronchial epithelial cell line (BEAS2B) and TCC cell lines (UMUC‐3, HT‐1197 and HT‐1376) and a bladder papilloma (RT‐4), we aimed to characterize DMAPT's anticancer activity in tobacco‐associated neoplasms. Flow cytometric, electrophoretic mobility gel shift assays (EMSA), and Western blot studies measured generation of reactive oxygen species (ROS), inhibition of NFκB DNA binding, and changes in cell cycle distribution and apoptotic proteins. DMAPT generated ROS with subsequent JNK activation and also decreased NFκB DNA binding and antiapoptotic proteins, TRAF‐2 and XIAP. DMAPT‐induced apoptotic cell death and altered cell cycle distribution with upregulation of p21 and p73 levels in a cell type–dependent manner. DMAPT suppressed cyclin D1 in BEAS2B. DMAPT retained NFκB and cell cycle inhibitory activity in the presence of the tobacco carcinogen nitrosamine ketone, 4(methylnitrosamino)‐1‐(3–pyridyl)‐1‐butanone (NNK). Using a BrdU accumulation assay, 5–20 μM of DMAPT was shown to inhibit cellular proliferation of all cell lines by more than 95%. Oral dosing of DMAPT suppressed in vivo A549 and UMUC‐3 subcutaneous xenograft growth by 54% (p = 0.015) and 63% (p < 0.01), respectively, and A549 lung metastatic volume by 28% (p = 0.043). In total, this data demonstrates DMAPT's novel anticancer properties in both early and late stage tobacco‐associated neoplasms as well as its significant in vivo activity. The data provides support for the conduct of clinical trials in TCC and NSCLC.
Notch as a molecular switch in neural stem cells
Authors: Zhou Zhi‐Dong , Kumari Udhaya , Xiao Zhi‐Cheng , Tan Eng‐King 
Published: July 2010

AbstractNotch signaling pathway, originally discovered in Drosophila, impinges on a wide array of cellular processes including cell proliferation, cell differentiation, and cell apoptosis. Recent accumulating evidences implicated the important roles of Notch signal pathway in different aspects of stem cell biology of neural stem cell (NSC). In vivo and in vitro studies illustrated that Notch signal pathway could promote gliogenesis, inhibit premature neurogenesis, and be involved in self‐renew of NSC. This short review summarizes the roles of the Notch signaling pathway on gliogenesis, neurogenesis, and self‐renew of NSC and their underlying molecular mechanisms. © 2010 IUBMB IUBMB Life, 62(8): 618–623, 2010.
Hypoxia regulates the ferrous iron uptake and reactive oxygen species level via divalent metal transporter 1 (DMT1) Exon1B by hypoxia‐inducible factor‐1
Authors: Wang Dan , Wang Li‐Hong , Zhao Yu , Lu Ya‐Peng , Zhu Li 
Published: July 2010

AbstractHypoxia has been shown to increase the expression of a variety of proteins involved in iron homeostasis, including ceruloplasmin, transferrin, and transferring receptor. Divalent metal transporter 1 (DMT1) is a transmembrane protein that is important in divalent metal ion transport, in particular iron. Although previous studies have provided that DMT1 exon1A is regulated by hypoxia, little is known about the relationship between DMT1 exon1B and hypoxia. Hypoxia‐inducible factor 1 (HIF‐1) is a transcription factor which is stabilized when mammalian cells are subjected to hypoxia. In this study, we have identified a functional hypoxia‐response element (HRE) at position of −327 to −323 (‐ACGTG‐) in DMT1 exon1B promoter using a combination of bioinformatics and biological approaches. Both the total cellular iron and ferrous uptake increased after hypoxia, decreased after DMT1 RNA interference. Reactive oxygen species (ROS) were also changed by +iron responsive element (IRE) DMT1 exon1B overexpression. These findings implicated DMT1 exon1B was a target gene for HIF‐1. Hypoxia might affect cellular iron uptake through regulating the expression of DMT1. When iron was present in excess, cells might be damaged by the ROS production. © 2010 IUBMB IUBMB Life, 62(8): 629–636, 2010.
Calcium channel blocker use and risk of Parkinson's disease
Authors: Simon Kelly Claire , Gao Xiang , Chen Honglei , Schwarzschild Michael A. , Ascherio Alberto 
Published: July 2010

AbstractWe investigated whether the use of calcium channel blockers (CCBs) was associated with a reduced risk of Parkinson's disease (PD) in two large prospective cohorts: the Nurses' Health Study (NHS) and Health Professionals' Follow‐Up Study (HPFS). Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) to assess the association between use of CCBs and risk of PD adjusting for potential confounders. We identified 514 incident cases of PD during follow‐up. No association between baseline use of CCBs (RR = 1.18, 95% CI: 0.73–1.92), frequency of use or duration of use of CCBs and PD risk was observed (P > 0.2 for all). These findings do not support a role for CCBs in providing neuroprotection against development of PD. © 2010 Movement Disorder Society
A proton NMR study on the hydration of normal versus psoriatic stratum corneum: linking distinguishable reservoirs to anatomical structures
Authors: Laule Cornelia , Tahir Sumia , Chia Charmaine L. L. , Vavasour Irene M. , Kitson Neil , MacKay Alex L. 
Published: July 2010

AbstractThe NMR behaviour of normal and psoriatic stratum corneum (SC) was investigated as a function of hydration with the aim of obtaining a better understanding of the role of water in the SC structure. Time domain NMR techniques were employed to identify the signal from water and that from nonaqueous components of the SC, such as lipids and proteins. The signals were investigated as a function of water content. The free induction decay was separated into mobile signal (from water and mobile lipids) and solid signal (from protein and 'solid' lipids). Spin–spin relaxation (T2) measurements further separated the mobile domains within the SC. The results suggested that, when water is added to dry SC, it first enters the corneocytes; then, at a hydration of 0.24–0.33 g H2O/g SC (normal SC) or 0.12–0.24 g H2O/g SC (psoriatic SC), water begins to accumulate in hydrated lipid regions. Water was found to exchange between these two domains on the time scale of a few hundred milliseconds. When compared with normal SC, psoriatic SC had a looser corneocyte structure, a larger mobile lipid component at low hydration and a smaller capacity for corneocyte water. Copyright © 2010 John Wiley & Sons, Ltd.
Determination of the X‐ray structure of the snake venom protein omwaprin by total chemical synthesis and racemic protein crystallography
Authors: Banigan James R. , Mandal Kalyaneswar , Sawaya Michael R. , Thammavongsa Vilasak , Hendrickx Antoni P. A. , Schneewind Olaf , Yeates Todd O. , Kent Stephen B. H. 
Published: July 2010

AbstractThe 50‐residue snake venom protein L‐omwaprin and its enantiomer D‐omwaprin were prepared by total chemical synthesis. Radial diffusion assays were performed against Bacillus megaterium and Bacillus anthracis; both L‐ and D‐omwaprin showed antibacterial activity against B. megaterium. The native protein enantiomer, made of L‐amino acids, failed to crystallize readily. However, when a racemic mixture containing equal amounts of L‐ and D‐omwaprin was used, diffraction quality crystals were obtained. The racemic protein sample crystallized in the centrosymmetric space group P21/c and its structure was determined at atomic resolution (1.33 Å) by a combination of Patterson and direct methods based on the strong scattering from the sulfur atoms in the eight cysteine residues per protein. Racemic crystallography once again proved to be a valuable method for obtaining crystals of recalcitrant proteins and for determining high‐resolution X‐ray structures by direct methods.
Helicity of short E‐R/K peptides
Authors: Sommese Ruth F. , Sivaramakrishnan Sivaraj , Baldwin Robert L. , Spudich James A. 
Published: July 2010

AbstractUnderstanding the secondary structure of peptides is important in protein folding, enzyme function, and peptide‐based drug design. Previous studies of synthetic Ala‐based peptides (>12 a.a.) have demonstrated the role for charged side chain interactions involving Glu/Lys or Glu/Arg spaced three (i, i + 3) or four (i, i + 4) residues apart. The secondary structure of short peptides (<9 a.a.), however, has not been investigated. In this study, the effect of repetitive Glu/Lys or Glu/Arg side chain interactions, giving rise to E‐R/K helices, on the helicity of short peptides was examined using circular dichroism. Short E‐R/K–based peptides show significant helix content. Peptides containing one or more E‐R interactions display greater helicity than those with similar E‐K interactions. Significant helicity is achieved in Arg‐based E‐R/K peptides eight, six, and five amino acids long. In these short peptides, each additional i + 3 and i + 4 salt bridge has substantial contribution to fractional helix content. The E‐R/K peptides exhibit a strongly linear melt curve indicative of noncooperative folding. The significant helicity of these short peptides with predictable dependence on number, position, and type of side chain interactions makes them an important consideration in peptide design.
Non‐3D domain swapped crystal structure of truncated zebrafish alphaA crystallin
Authors: Laganowsky A. , Eisenberg D. 
Published: July 2010

AbstractIn previous work on truncated alpha crystallins (Laganowsky et al., Protein Sci 2010; 19:1031–1043), we determined crystal structures of the alpha crystallin core, a seven beta‐stranded immunoglobulin‐like domain, with its conserved C‐terminal extension. These extensions swap into neighboring cores forming oligomeric assemblies. The extension is palindromic in sequence, binding in either of two directions. Here, we report the crystal structure of a truncated alphaA crystallin (AAC) from zebrafish (Danio rerio) revealing C‐terminal extensions in a non three‐dimensional (3D) domain swapped, “closed” state. The extension is quasi‐palindromic, bound within its own zebrafish core domain, lying in the opposite direction to that of bovine AAC, which is bound within an adjacent core domain (Laganowsky et al., Protein Sci 2010; 19:1031–1043). Our findings establish that the C‐terminal extension of alpha crystallin proteins can be either 3D domain swapped or non‐3D domain swapped. This duality provides another molecular mechanism for alpha crystallin proteins to maintain the polydispersity that is crucial for eye lens transparency.
Oligomerization state and supramolecular structure of the HIV‐1 Vpu protein transmembrane segment in phospholipid bilayers
Authors: Lu Jun‐Xia , Sharpe Simon , Ghirlando Rodolfo , Yau Wai‐Ming , Tycko Robert 
Published: July 2010

AbstractHIV‐1 Vpu is an 81‐residue protein with a single N‐terminal transmembrane (TM) helical segment that is involved in the release of new virions from host cell membranes. Vpu and its TM segment form ion channels in phospholipid bilayers, presumably by oligomerization of TM helices into a pore‐like structure. We describe measurements that provide new constraints on the oligomerization state and supramolecular structure of residues 1–40 of Vpu (Vpu1–40), including analytical ultracentrifugation measurements to investigate oligomerization in detergent micelles, photo‐induced crosslinking experiments to investigate oligomerization in bilayers, and solid‐state nuclear magnetic resonance measurements to obtain constraints on intermolecular contacts between and orientations of TM helices in bilayers. From these data, we develop molecular models for Vpu TM oligomers. The data indicate that a variety of oligomers coexist in phospholipid bilayers, so that a unique supramolecular structure can not be defined. Nonetheless, since oligomers of various sizes have similar intermolecular contacts and orientations, molecular models developed from our data are most likely representative of Vpu TM oligomers that exist in host cell membranes.
Structural and functional characterization of Salmonella enterica serovar Typhimurium YcbL: An unusual Type II glyoxalase
Authors: Stamp Anna L. , Owen Paul , El Omari Kamel , Nichols Charles E. , Lockyer Michael , Lamb Heather K. , Charles Ian G. , Hawkins Alastair R. , Stammers David K. 
Published: July 2010

AbstractYcbL has been annotated as either a metallo‐β‐lactamase or glyoxalase II (GLX2), both members of the zinc metallohydrolase superfamily, that contains many enzymes with a diverse range of activities. Here, we report crystallographic and biochemical data for Salmonella enterica serovar Typhimurium YcbL that establishes it as GLX2, which differs in certain structural and functional properties compared with previously known examples. These features include the insertion of an α‐helix after residue 87 in YcbL and truncation of the C‐terminal domain, which leads to the loss of some recognition determinants for the glutathione substrate. Despite these changes, YcbL has robust GLX2 activity. A further difference is that the YcbL structure contains only a single bound metal ion rather than the dual site normally observed for GLX2s. Activity assays in the presence of various metal ions indicate an increase in activity above basal levels in the presence of manganous and ferrous ions. Thus, YcbL represents a novel member of the GLX2 family.
Calcium channel blocking activity ofMentha longifoliaL. explains its medicinal use in diarrhoea and gut spasm
Authors: Shah Abdul Jabbar , Bhulani Nizar Noorali , Khan Sara Haroon , ur Rehman Najeeb , Gilani Anwarul Hassan 
Published: July 2010

AbstractMentha longifoliahas a reputation in traditional medicine in the indications of diarrhoea and gut spasm. This study was carried out to provide a possible pharmacological basis for its medicinal use in hyperactive gut disorders. In a castor oil induced diarrhoeal model, the crude extract ofMentha longifolia(Ml.Cr), at doses of 100–1000 mg/kg, provided 31–80% protection, similar to loperamide. In isolated rabbit jejunum preparations, Ml.Cr caused inhibition of spontaneous and high K+‐induced contractions, with respective EC50values of 1.80 (1.34–2.24;n= 6–8) and 0.60 mg/mL (0.37–0.85;n= 6–8), which suggests spasmolytic activity, mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pretreatment of the tissue with Ml.Cr (0.3–1 mg/mL) caused a rightward shift in the Ca++concentration–response curves (CRCs), similar to verapamil. Loperamide also inhibited spontaneous and high K+‐induced contractions and shifted the Ca++CRCs to the right. Activity‐directed fractionation revealed that the petroleum spirit fraction was more potent than the parent crude extract and aqueous fraction. These data indicate that the antidiarrhoeal and spasmolytic effects of the crude extract ofMentha longifoliaare mediated through the presence of CCB‐like constituent(s), concentrated in the petroleum spirit fraction and this study provides indirect evidence for its medicinal use in diarrhoea and spasm. Copyright © 2010 John Wiley & Sons, Ltd.
A robust model predictive control algorithm for incrementally conic uncertain/nonlinear systems
Authors: Açıkmeşe Behçet , Carson John M. , Bayard David S. 
Published: July 2010

AbstractThis paper presents a robustly stabilizing model predictive control algorithm for systems with incrementally conic uncertain/nonlinear terms and bounded disturbances. The resulting control input consists of feedforward and feedback components. The feedforward control generates a nominal trajectory from online solution of a finite‐horizon constrained optimal control problem for a nominal system model. The feedback control policy is designed off‐line by utilizing a model of the uncertainty/nonlinearity and establishes invariant ‘state tubes’ around the nominal system trajectories. The entire controller is shown to be robustly stabilizing with a region of attraction composed of the initial states for which the finite‐horizon constrained optimal control problem is feasible for the nominal system. Synthesis of the feedback control policy involves solution of linear matrix inequalities. An illustrative numerical example is provided to demonstrate the control design and the resulting closed‐loop system performance. Copyright © 2010 John Wiley & Sons, Ltd.
Phenylalanine loading in pediatric patients with dopa‐responsive dystonia: revised test protocol and pediatric cutoff values
Authors: Opladen Thomas , Okun Jürgen G. , Burgard Peter , Blau Nenad , Hoffmann Georg F. 
Published: July 2010

AbstractObjectivesThe objectives of this study were to determine the value of phenylalanine (Phe) loading for diagnosing dopa‐responsive dystonia (DRD) in children.MethodsWe investigated orally administered Phe loading tests (100 mg/kg) in seven patients with confirmed DRD and 17 pediatric patients with clinically suspected but excluded DRD. Results of Phe, tyrosine (Tyr), and biopterin from plasma and dried blood spot (DBS) analyses were correlated, and pediatric cutoff values established.ResultsThe peak Phe concentration following a Phe load in the pediatric DRD population is lower than reported in adults. By using adult cutoff values and either Phe/Try ratios or biopterin concentrations only, false positive and false negative results are frequent. Only the combined analysis of the Phe/Tyr ratio and biopterin concentration is reliable in children. In children with DRD, dried blood Phe/Tyr ratio exceeded 4.6 (plasma Phe/Tyr ratio >5.4) after 2 h and biopterin concentration in dried blood remained below 16.2 nmol/L (plasma biopterin <14 nmol/L) 1 h after Phe challenge.ConclusionsPhe loading is a useful tool for diagnosing DRD in children. Test duration can be reduced to only 2 h, and specific pediatric cutoff values need to be applied. Simultaneous measurements of the Phe/Tyr ratio and biopterin in plasma or DBS are essential in pediatric patients.
The effect of expertise on the relation between implicit and explicit attitude measures: An information availability/accessibility perspective
Authors: Czellar Sandor , Luna David 
Published: July 2010

AbstractThree experiments investigate expertise as a moderator of the relationship between implicit and explicit attitude measures. Prior research suggests that greater expertise leads to stronger implicit–explicit relations; however, a cognitive view of expertise can also predict a weaker implicit–explicit relation. Our framework helps to resolve that seeming contradiction on the basis of the availability/accessibility of attributes versus attitudes in explicit attitude measures. We show that object specificity and contextual factors (e.g., instructions and prior evaluations in a survey) differentially affect the availability/accessibility of global attitudes and attribute information for novices versus experts, thus determining how expertise moderates the implicit–explicit relation.
A TRANSITION REGION EXPLOSIVE EVENT OBSERVED IN He ii WITH THE MOSES SOUNDING ROCKET
Authors: Fox J. Lewis , Kankelborg Charles C. , Thomas Roger J. 
Published: July 2010

ABSTRACT
Transition region explosive events (EEs) have been observed with slit spectrographs since at least 1975, most commonly in lines of C iv (1548 Å, 1550 Å) and Si iv (1393 Å, 1402 Å). We report what we believe to be the first observation of a transition region EE in He ii 304 Å. With the Multi-Order Solar EUV Spectrograph (MOSES) sounding rocket, a novel slitless imaging spectrograph, we are able to see the spatial structure of the event. We observe a bright core expelling two jets that are distinctly non-collinear, in directions that are not anti-parallel. The jets have sky-plane velocities of order 75 km s−1 and line-of-sight velocities of +75 km s−1 (blue) and −30 km s−1 (red). The core is a region of high non-thermal Doppler broadening, characteristic of EEs, with maximal broadening 380 km s−1 FWHM. It is possible to resolve the core broadening into red and blue line-of-sight components of maximum Doppler velocities +160 km s−1 and −220 km s−1. The event lasts more than 150 s. Its properties correspond to the larger, long-lived, and more energetic EEs observed in other wavelengths.
Rai1 haploinsufficiency causes reduced Bdnf expression resulting in hyperphagia, obesity and altered fat distribution in mice and humans with no evidence of metabolic syndrome
Authors: Burns Brooke , Schmidt Kristie , Williams Stephen R. , Kim Sun , Girirajan Santhosh , Elsea Sarah H. 
Published: July 2010

Abstract
Smith–Magenis syndrome (SMS) is a genetic disorder caused by haploinsufficiency of the retinoic acid induced 1 (RAI1) gene. In addition to intellectual disabilities, behavioral abnormalities and sleep disturbances, a majority of children with SMS also have significant early-onset obesity. To study the role of RAI1 in obesity, we investigated the growth and obesity phenotype in a mouse model haploinsufficient for Rai1. Data show that Rai1+/− mice are hyperphagic, have an impaired satiety response and have altered abdominal and subcutaneous fat distribution, with Rai1+/− female mice having a higher proportion of abdominal fat when compared with wild-type female mice. Expression analyses revealed that Bdnf (brain-derived neurotrophic factor), a gene previously associated with hyperphagia and obesity, is downregulated in the Rai1+/− mouse hypothalamus, and reporter studies show that RAI1 directly regulates the expression of BDNF. Even though the Rai1+/− mice are significantly obese, serum analyses do not reveal any evidence of metabolic syndrome. Supporting these findings, a caregiver survey revealed that even though a high incidence of abdominal obesity is observed in females with SMS, they did not exhibit a higher incidence of indicators of metabolic syndrome above the general population. We conclude that Rai1 haploinsufficiency represents a single-gene model of obesity with hyperphagia, abnormal fat distribution and altered hypothalamic gene expression associated with satiety, food intake, behavior and obesity. Linking RAI1 and BDNF provides a more thorough understanding of the role of Rai1 in growth and obesity and insight into the complex pathogenicity of obesity, behavior and sex-specific differences in adiposity.