bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Strategies for the Design of Drugs Targeting RNA and RNA — Protein Complexes
Authors: Hermann Thomas
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Metal‐Directed Self‐Assembly
Authors: Constable Edwin C.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Repair and Replication of Oxidized DNA Bases Using Modified Oligodeoxyribonucleotides
Authors: Gasparutto Didier , Bourdat Anne‐Gaelle , D'Ham Cedric , Duarte Victor , Romieu Anthony , Cadet Jean
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Orthogonal Ligation Strategies for Peptide and Protein
Authors: Tam James P. , Yu Qitao , Miao Zhenwei
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Perspective on “Theoretical Interpretation of 1‐2 Asymmetric Induction: The Importance of Antiperiplanarity”
Authors: Houk K. N.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Perspective on “Intermolecular Orbital Theory of the Interactions Between Conjugated Systems.” Part 1. General Theory. Part 2. Thermal and Photochemical Cycloadditions
Authors: Eisenstein Odile
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Perspective on “An Extended Hueckel Theory.” Part 1. Hydrocarbons
Authors: Whangbo Myung‐Hwan
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Perspective on “Quantum Theory Contributions to the Benzene Problem.” Part 1. The Electron Configuration of Benzene and Related Compounds
Authors: Frenking Gernot
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Structure and Dynamics in Metal Carbonyl Clusters: NMR, EXAFS and Crystallographic Studies
Authors: Farrugia Louis J. , Orpen A. Guy
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Physical Methods for a Study of Organophosphorus Chemistry
Authors: Slinn R. N. , Salt M. C.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: High‐Resolution NMR Spectroscopy at High Pressure
Authors: Jonas Jiri
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Regiospecific 4‐O‐Alkylation to Tetronic Acids with Isoureas.
Authors: Schobert Rainer , Siegfried Sven
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Chiral Action at a Distance: Remote Substituent Effects on the Optical Activity of Calyculins A and B.
Authors: Kondru Rama K. , Beratan David N. , Friestad Gregory K. , Smith III Amos B. , Wipf Peter
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis of Heterylphthalonitriles
Authors: Abramov I. G. , Plakhtinskii V. V. , Abramova M. B. , Smirnov A. V. , Krasovskaya G. G.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Design, Synthesis, and in vitro Biological Activity of Benzimidazole‐Based Factor Xa Inhibitors.
Authors: Zhao Zuchun , et al. et al.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis and Characterization of Pyridine‐Based Polyamido‐Polyester Optically Active Macrocycles and Enantiomeric Recognition for D‐ and L‐Amino Acid Methyl Ester Hydrochloride.
Authors: Zhao Hongwu , Hua Wenting
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis and Applications of Chiral Selones
Authors: Silks L. A."Pete" , Wu Ruilian , Dunlap R. Bruce , Odom Jerome D.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: An Oxidative Prins Cyclization Methodology.
Authors: Chen Chuanfeng , Mariano Patrick S.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Physical Adsorption Characterization of Nanoporous Materials
Authors: Thommes M.
Published: June 2010

During recent years, major progress has been made in the understanding of the adsorption, pore condensation and hysteresis behavior of fluids in novel ordered nanoporous materials with well defined pore structure. This has led to major advances in the structural characterization by physical adsorption, also because of the development and availability of advanced theoretical procedures based on statistical mechanics (e.g., density functional theory, molecular simulation) which allows to describe adsorption and phase behavior of fluids in pores on a molecular level. Very recent improvements allow even to take into account surface geometrical in‐homogeneity of the pore walls However, there are still many open questions concerning the structural characterization of more complex porous systems. Important aspects of the major underlying mechanisms associated with the adsorption, pore condensation and hysteresis behavior of fluids in micro‐mesoporous materials are reviewed and their significance for advanced physical adsorption characterization is discussed.
Phase 3 trial of everolimus for metastatic renal cell carcinoma
Authors: Motzer Robert J. , Escudier Bernard , Oudard Stephane , Hutson Thomas E. , Porta Camillo , Bracarda Sergio , Grünwald Viktor , Thompson John A. , Figlin Robert A. , Hollaender Norbert , Kay Andrea , Ravaud Alain ,   for the RECORD‐1 Study Group
Published: June 2010

BACKGROUND:

A phase 3 trial demonstrated superiority at interim analysis for everolimus over placebo in patients with metastatic renal cell carcinoma (mRCC) progressing on vascular endothelial growth factor receptor–tyrosine kinase inhibitors. Final results and analysis of prognostic factors are reported.

METHODS:

Patients with mRCC (N = 416) were randomized (2:1) to everolimus 10 mg/d (n = 277) or placebo (n = 139) plus best supportive care. Progression‐free survival (PFS) and safety were assessed to the end of double‐blind treatment. Mature overall survival (OS) data were analyzed, and prognostic factors for survival were investigated by multivariate analyses. A rank‐preserving structural failure time model estimated the effect on OS, correcting for crossover from placebo to everolimus.

RESULTS:

The median PFS was 4.9 months (everolimus) versus 1.9 months (placebo) (hazard ratio [HR], 0.33; P < .001) by independent central review and 5.5 months (everolimus) versus 1.9 months (placebo) (HR, 0.32; P < .001) by investigators. Serious adverse events with everolimus, independent of causality, in ≥5% of patients included infections (all types, 10%), dyspnea (7%), and fatigue (5%). The median OS was 14.8 months (everolimus) versus 14.4 months (placebo) (HR, 0.87; P = .162), with 80% of patients in the placebo arm crossed over to everolimus. By the rank‐preserving structural failure time model, the survival corrected for crossover was 1.9‐fold longer (95% confidence interval, 0.5‐8.5) with everolimus compared with placebo only. Independent prognostic factors for shorter OS in the study included low performance status, high corrected calcium, low hemoglobin, and prior sunitinib (P < .01).

CONCLUSIONS:

These results established the efficacy and safety of everolimus in patients with mRCC after progression on sunitinib and/or sorafenib. Cancer 2010. © 2010 American Cancer Society.
TGF‐β affects development and differentiation of human natural killer cell subsets
Authors: Allan David S. J. , Rybalov Basya , Awong Génève , Zúñiga‐Pflücker Juan Carlos , Kopcow Hernan D. , Carlyle James R. , Strominger Jack L.
Published: June 2010

Human peripheral blood NK cells may be divided into two main subsets: CD56brightCD16− and CD56dimCD16+. Since TGF‐β is known to influence the development of many leukocyte lineages, its effects on NK cell differentiation either from human CD34+Lin− hematopoietic progenitor/stem cells in vitro or from peripheral blood NK cells were investigated. TGF‐β represses development of NK cells from CD34+ progenitors and inhibits differentiation of CD16+ NK cells. Moreover, TGF‐β also results in conversion of a minor fraction of CD56brightCD16+ cells found in peripheral blood into CD56brightCD16− cells, highlighting a possible role of the former as a developmental intermediate and of TGF‐β in influencing the genesis of NK subsets found in blood.
EAE mediated by a non‐IFN‐γ/non‐IL‐17 pathway
Authors: Kroenke Mark A. , Chensue Stephen W. , Segal Benjamin M.
Published: June 2010

Previous studies have shown that EAE can be elicited by the adoptive transfer of either IFN‐γ‐producing (Th1) or IL‐17‐producing (Th17) myelin‐specific CD4+ T‐cell lines. Paradoxically, mice deficient in either IFN‐γ or IL‐17 remain susceptible to EAE following immunization with myelin antigens in CFA. These observations raise questions about the redundancy of IFN‐γ and IL‐17 in autoimmune demyelinating disease mediated by a diverse, polyclonal population of autoreactive T cells. In this study, we show that an atypical form of EAE, induced in C57BL/6 mice by the adoptive transfer of IFN‐γ‐deficient effector T cells, required IL‐17 signaling for the development of brainstem infiltrates. In contrast, classical EAE, characterized by predominant spinal cord inflammation, occurred in the combined absence of IFN‐γ and IL‐17 signaling, but was dependent on GM‐CSF and CXCR2. Our findings contribute to a growing body of data, indicating that individual cytokines vary in their importance across different models of CNS autoimmunity.
Factors Influencing the Structural and Magnetic Properties of Octahedral Cobalt(II) and Iron(II) Complexes of Terdentate N3 Schiff Base Ligands
Authors: Handel Robyn W. , Willms Holger , Jameson Geoffrey B. , Berry Kevin J. , Moubaraki Boujemaa , Murray Keith S. , Brooker Sally
Published: June 2010

The influence of the length of the linking alkyl spacer and of the presence of either a proton or a methyl group, in four related terdentate N3 Schiff base ligands, on the structures and properties of the resulting iron(II) and cobalt(II) complexes has been investigated. The four ligands were prepared in situ by condensation of 2‐(2‐aminoethyl)pyridine or 2‐(aminomethyl)pyridine with 2‐acetylpyridine (L1 vs. L3) or 2‐formylpyridine (L2 vs. L4). Hence they comprised a mixture of a relatively rigid chelate with a 2‐iminopyridyl moiety, comparable to bipyridine coordination, and a more flexible chelate containing the –(CH2)n– spacer. Four iron(II) complexes, [Fe(L1)2](BF4)2 (1), [Fe(L2)2](BF4)2 (2), [Fe(L3)2](BF4)2 (3), [Fe(L4)2](BF4)2 (4), were obtained whereas only in the case of the two ethylene (i.e. not methylene) spaced ligands could pure cobalt(II) complexes, [Co(L1)2](BF4)2 (5), [Co(L2)2](BF4)2 (6), be obtained. The 1H NMR spectra confirmed that in MeCN 1–4 are diamagnetic whereas 5 and 6 are paramagnetic. X‐ray structure determinations of the ethylene‐linked complexes, 1, 5 and 6, revealed distorted octahedral geometries due to chelate ring restrictions. The M–N distances were typical for high‐spin cobalt(II) (5 and 6) and for low‐spin iron(II) (1). The magnetic data on 5 and 6 are typical of those expected for distorted octahedral high‐spin d7 species; fitting attempts have yielded zero‐field splitting and low symmetry ligand field parameters. A metal‐centred M2+/3+ redox wave and ligand‐based reduction processes were observed for 1–6 in MeCN. The metal‐centred redox potential (Fe: 1 0.59, 2 0.68, 3 0.58, 4 0.70 V; Co: 5 0.03, 6 0.09 V vs. Fc/Fc+) was influenced much more strongly by the presence of the proton vs. methyl group (Fe: shift of 0.09–0.12 V, Co: shift of 0.06 V) than by the bridging methylene vs. ethylene group (Fe: shift of 0.01–0.02 V).
Simple RuCl3‐Catalyzed Amide Synthesis from Alcohols and Amines
Authors: Ghosh Subhash Chandra , Hong Soon Hyeok
Published: June 2010

A catalyst for the direct synthesis of amides from amines and alcohols, generated in situ from the economically attractive and readily available RuCl3, an N‐heterocyclic carbene (NHC), and pyridine, was developed. Of the screened NHC precursors, a less bulky one gave better yields for modestly sterically hindered substrates. In a search for the true catalytic intermediates, Grubbs catalysts were found to be active for the amidation of alcohols under basic conditions, suggesting that an Ru complex supported by an NHC ligand can catalyze the reaction.
Evaluation of UASB/CO2 stripping system for simultaneous removal of organics and calcium in linerboard wastewater
Authors: Lee Yong‐Woo , Choi Jeong‐Yun , Kim Jong‐Oh , Chung Jinwook
Published: June 2010

A combined upflow anaerobic sludge blanket (UASB) and CO2‐stripping system was evaluated for its capacity to simultaneously remove organic compounds and calcium from linerboard mill wastewater. A continuous‐flow UASB has significant potential to remove organic compounds, and its removal efficiency is closely related to volumetric organic loading. After the UASB process, a gradual decrease of pH was observed and CO2‐stripping indicated the formation of acid/methane and carbonate. The high concentration of carbonate that was generated from the elevated pH of the CO2 stripper easily reacted with calcium in the wastewater to form a solid‐phase calcium carbonate. The significant amount of methane that was produced during the UASB process implies that methane‐producing bacteria dominate the microbial composition of the reactor. In the CO2 stripper system, calcium removal and alkalinity consumption rose simultaneously with increasing solution pHs. This result suggests that the combined activity of the UASB reactor and the CO2 stripper system is a powerful tool for removing organic compounds and calcium from linerboard wastewater. Such a system would allow water from the linerboard production process to be reused and be discharged with fewer toxic compounds. © 2010 American Institute of Chemical Engineers Environ Prog, 2011
Pilot‐scale study on ozone‐enhanced catalytic oxidation of waste gas emissions from the pulp and paper industry
Authors: Sahle‐Demessie Endalkachew , Almquist Catherine B. , Devulapelli Venu Gopal
Published: June 2010

Field studies were conducted at Domtar's Kraft pulp and paper mill (Hawesville, KY) for 2 weeks to investigate the treatment of high volume, low concentration (HVLC) waste gas streams using ozone‐enhanced catalytic oxidation technology. The contaminants in the HVLC waste gas from the pulping area of the mill contained mainly methanol (360 ± 80 ppm) and total reduced sulfur compounds [dimethyl sulfide (DMS) (4400 ± 670 ppm) and dimethyl disulfide (150 ± 25 ppm). The catalysts used in the field studies included ViO2/TiO2 and CuO/MoO3/ã‐Al2O3. The results of the field study showed ozone‐to‐sulfur ratios >2, space velocities <1000 h−1, and reaction temperatures ≥250°C are required to achieve >90% destruction of DMS in the HVLC waste gas stream. Ozone‐enhanced catalytic oxidation has key environmental advantages over incineration, including mild operating temperatures and thus, lower energy costs and lower NOx formation. Although the technology appeared to be feasible at the laboratory scale, the field study data revealed that several obstacles must be overcome prior to this technology being implemented at large scale. © 2010 American Institute of Chemical Engineers Environ Prog, 2011
The characteristics and clinical outcome of adult patients with aplastic anemia and abnormal cytogenetics at diagnosis
Authors: Kim Sung‐Yong , Lee Jong‐Wook , Lee Sung‐Eun , Cho Byung‐Sik , Kim Myungshin , Eom Ki‐Seong , Kim Yoo‐Jin , Kim Hee‐Je , Lee Seok , Min Chang‐Ki , Cho Seok‐Goo , Kim Dong‐Wook , Han Kyungja , Min Woo‐Sung
Published: June 2010

The characteristics and clinical outcome of 600 adult patients with aplastic anemia (AA) that had successful cytogenetic studies at the time of diagnosis were retrospectively evaluated. Among these, 572 (95.3%) had normal cytogenetics and 28 (4.7%) had abnormal cytogenetics. The most frequent abnormality was trisomy 8 (n = 15), followed by monosomy 7/deletion of 7q (n = 5), and deletion of 1q (n = 5). There were no statistically significant differences with respect to gender, hepatitis viral infection, paroxysmal nocturnal hemoglobinuria, or severity of disease between the patients in the normal and abnormal cytogenetics groups; however, the patients with abnormal cytogenetics were generally younger than those with normal cytogenetics (P < 0.001). Abnormal cytogenetics was associated with a higher cumulative leukemic transformation rate (P < 0.001) and lower leukemic transformation‐free survival (P = 0.021). Furthermore, abnormal cytogenetics was an independent predictor of a poor response to immunosuppressive therapy (HR = 0.255; 95% CI = 0.077–0.839; P = 0.024). These analyses suggest that patients with AA and abnormal cytogenetics have different clinical characteristics compared to patients with AA and normal cytogenetics. © 2010 Wiley‐Liss, Inc.
Deficiency of electroneutral K+–Cl−cotransporter 3 causes a disruption in impulse propagation along peripheral nerves
Authors: Sun Yuan‐Ting , Lin Thy‐Sheng , Tzeng Shun‐Fen , Delpire Eric , Shen Meng‐Ru
Published: June 2010

Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K+–Cl−cotransporter (KCC) family includes four isoforms (KCC1–4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K+and Cl−with concurrent water flux. Mutation inSLC12A6gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral neuropathy. Nevertheless, the role of KCC3 in nerve function remains a puzzle. In this study, the microscopic examination of KCC isoforms expressed in peripheral nerves showed high expression of KCC2–4 in nodal segments of the axons and in the perinucleus and microvilli of Schwann cells. The KCC inhibitor [[(dihydroindenyl)oxy]alkanoic acid] but not the Na+–K+–2Cl−‐cotransport inhibitor (bumetanide) dose‐dependently suppressed the amplitude and area of compound muscle action potential, indicating the involvement of KCC activity in peripheral nerve conduction. Furthermore, the amplitude and area under the curve were smaller, and the nerve conduction velocity was slower in nerves fromKCC3−/−mice than in nerves from wild‐type mice, while the expression pattern of KCC2 and KCC4 was similar in KCC3 kockout and wild‐type strains.KCC3−/−mice also manifested a prominent motor deficit in the beam‐walking test. This is the first study to demonstrate that the K+–Cl−cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves. © 2010 Wiley‐Liss, Inc.
The effect of allogeneic stem cell transplantation on high risk chronic lymphocytic leukaemia: a single centre retrospective analysis
Authors: Válková V , Schwarz J , Vítek A , Marková M , Pohlreich D , Benešová K , Michalová K , Cetkovský P , Trněný M
Published: June 2010

In recent years, many studies have confirmed that allogeneic stem cell transplantation (allo‐SCT) can provide long‐term disease control and possible cure in selected patients with chronic lymphocytic leukaemia (CLL), including those with a biologically highly unfavourable risk profile. A retrospective analysis of allo‐SCT in 30 patients with CLL whose risk profile was unfavourable and who were treated in the years 2000–2009 was performed. The aim was to compare the results of allo‐SCT by prognostic factors and conditioning type and evaluate the results of unrelated transplantation. The median age was 54 years. Donors were 8 HLA‐matched siblings and 22 unrelated volunteers, 11 of whom were mismatched. Eighteen patients were treated with reduced intensity conditioning. Twelve patients received myeloablative conditioning. Estimated overall survival (OS) at 3 years was 78%, progression‐free survival (PFS) 71%, relapse incidence 10% and non‐relapse mortality (NRM) 16%, respectively, with a median follow‐up of 35 months. According to molecular/cytogenetic characteristics, OS and PFS for the high risk group (17p‐ or 11q‐) were 89 and 77%, respectively, not significantly different from those with standard risk. Graft‐versus‐host disease (GVHD) was associated with greater toxicity; significantly higher NRM for patients with aGVHD (p = 0.04) and worse PFS for patients with cGVHD (p = 0.04). Our results for the refractory disease group (77% responses) indicate that chemoresistance may be overcome by the GVL effect. Transplants from unrelated donors may be considered comparable to those from related donors. Copyright © 2010 John Wiley & Sons, Ltd.
Loss of p14ARF confers resistance to heat shock‐ and oxidative stress‐mediated cell death by upregulating β‐catenin
Authors: Damalas Alexander , Velimezi Georgia , Kalaitzakis Alexander , Liontos Michalis , Papavassiliou Athanasios G. , Gorgoulis Vassilis , Angelidis Charalampos
Published: June 2010

The p14ARF is a key tumor suppressor induced mainly by oncogenic stimuli. Although p14ARF does not seem to respond to DNA damage, there are very few data regarding its role in other forms of stress, such as heat shock (HS) and oxidative stress (OS). Here, we report that suppression of p14ARF increased resistance to cell death when cells were treated with H2O2 or subjected to HS. In this setting, protection from cell death was mediated by elevated levels and activity of β‐catenin, as downregulation of β‐catenin alleviated the protective role of p14ARF silencing. Moreover, Hsp70 was shown to regulate β‐catenin protein levels by interacting with p14ARF, suggesting that Hsp70, p14ARF and β‐catenin form a regulatory network. This novel pathway triggers cell death signals when cells are exposed to HS and OS.
p53 status influences response to tamoxifen but not to fulvestrant in breast cancer cell lines
Authors: Fernandez‐Cuesta Lynnette , Anaganti Suresh , Hainaut Pierre , Olivier Magali
Published: June 2010

Mutations in the tumor suppressor gene TP53 are associated with poor prognosis in breast cancer. This prognostic value may rely in part on the fact that p53 plays a role in the antiproliferative and apoptotic activities of chemotherapy regimens used to treat breast tumors. However, some studies suggested that p53 may also influence response to antihormone treatments. Here we investigate how p53 may affect response to antihormonal treatments, using estrogen‐dependent breast cancer cell‐lines with different p53 status. We show that p53 mutated cells were more resistant to cytotoxic effects of 4‐hydroxy‐tamoxifen (OHT) compared to p53 wild‐type cells. In contrast, p53 status did not significantly impact on response to fulvestrant. p53 mutated cells were also hypersensitive to proliferative effects of estradiol. Interestingly, OHT at doses in the low range had proliferative activities in p53 mutated cells (120–150% proliferation rate under 1 μM OHT treatment in low estrogen conditions). Using gene silencing or specific tyrosine kinase inhibitors, we show that the proliferative effects of OHT were estrogen receptor dependent and could be abrogated by the inhibition of EGFR and/or HER2 kinases. These findings suggest that loss of p53 function may increase cross‐talks between estrogen receptor and EGFR/HER2 pathways, contributing to a proliferative effect of OHT. These results bring new insights into the prognostic role of p53 in breast cancer and into possible mechanisms underlying tamoxifen resistance.
The Proto‐Ribosome: An Ancient Nano‐machine for Peptide Bond Formation
Authors: Davidovich Chen , Belousoff Matthew , Wekselman Itai , Shapira Tal , Krupkin Miri , Zimmerman Ella , Bashan Anat , Yonath Ada
Published: June 2010

The ribosome is a ribozyme whose active site, the peptidyl transferase center (PTC), is situated within a highly conserved universal symmetrical region that connects all ribosomal functional centers involved in amino acid polymerization. The linkage between this elaborate architecture and A‐site tRNA position revealed that the A‐ to P‐site passage of the tRNA 3′ terminus during protein synthesis is performed by a rotary motion, synchronized with the overall tRNA/mRNA sideways movement, and guided by the PTC. This rotary motion leads to suitable stereochemistry for peptide bond formation as well as for substrate‐mediated catalysis. Analysis of the substrate binding modes to ribosomes led to the hypothesis that the ancient ribosome produced single peptide bonds and non‐coded chains, potentially in a similar manner to the modern PTC. Later in evolution, a mechanism, enabling some type of decoding genetic control triggered the emergence of the small ribosomal subunit or part of it. This seems to be the result of the appearance of reaction products that could have evolved after polypeptides capable of enzymatic function were generated sporadically, while an ancient stable RNA fold was converted into an old version of a tRNA molecule. Since in the contemporary ribosome, the symmetry relates only to the backbone fold and nucleotide orientations but not nucleotide sequences, it emphasizes the superiority of functional requirement over sequence conservation, and indicates that the PTC may have evolved by gene fusion or gene duplication.
New predictive model for monitoring bone remodeling
Authors: Bougherara Habiba , Klika Václav , Maršík František , Mařík Ivo A. , Yahia L'Hocine
Published: June 2010

The aim of this article was to present a new thermodynamic‐based model for bone remodeling which is able to predict the functional adaptation of bone in response to changes in both mechanical and biochemical environments. The model was based on chemical kinetics and irreversible thermodynamic principles, in which bone is considered as a self‐organizing system that exchanges matter, energy and entropy with its surroundings. The governing equations of the mathematical model have been numerically solved using Matlab software and implemented in ANSYS software using the Finite Element Method. With the aid of this model, the whole inner structure of bone was elucidated. The current model suggested that bone remodeling was a dynamic process which was driven by mechanical loading, metabolic factors and other external contributions. The model clearly indicated that in the absence of mechanical stimulus, the bone was not completely resorbed and reaches a new steady state after about 50% of bone loss. This finding agreed with previous clinical studies. Furthermore, results of virtual computations of bone density in a composite femur showed the development of a dense cortical bone around the medullary canal and a dense trabeculæ bone between the femoral head and the calcar region of the medial cortex due to compressive stresses. The comparison of the predicted bone density with the structure of the proximal femur obtained from X‐rays and using strain energy density gave credibility to the current model. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
Controlled release of 2, 3 desulfated heparin exerts its anti‐inflammatory activity by effectively inhibiting E‐selectin
Authors: Lakshmi T. S. Ramyaa , Shanmugasundaram N. , Shanmuganathan S. , Karthikeyan K. , Meenakshi J. , Babu Mary
Published: June 2010

Control of inflammation using appropriate anti‐inflammatory agent prevents wound from becoming chronic. Heparin is a heterogeneous mixture of polysaccharide molecules with a mean molecular weight between 12–30 kDa containing 200–300 disaccharide units of glycosaminoglycan chains. Chemical modifications leading to generation of a unique pentasaccharide sequence effectively reduces its anticoagualant activity, while retaining its anti‐inflammmatory property. In this study, Standard heparin was partially desulfated to 2, 3 desulfated heparin (2, 3 DSH) and its anti‐inflammatory property was determined by assessing its ability to prevent static adhesion of leukocytes to endothelium and clotting assay. The effectiveness of 2, 3 DSH to down regulate E‐selectin and key proinflammatory cytokines (IL‐1β and IL‐6) was assessed by western blot and immunocytochemistry. These results were compared with commercially available 2‐Desulfated Heparin (2DSH) and standard heparin (SH). Finally, a controlled delivery system of 2, 3 DSH was designed using chitosan microspheres and collagen as scaffold. Optimal loading of 2, 3 DSH was achieved and the release kinetics were tuned to follow a controlled release pattern. The steady state concentration of 2, 3 DSH was found to be optimal to elicit anti‐inflammatory property and could achieve inhibition of E‐selectin expression while unaffecting the normal clotting cascade. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Chemistry and heterocyclization of dithiobiurea and thioureidoalkylthiourea
Authors: Hassan Alaa A. , El‐Sheref Essmat M.
Published: June 2010

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This review summarizes published data on the behavior and reactions of dithiobiurea and thioureidoalkylthiourea derivatives, which lead to the formation of heterocyclic systems, including methods of preparation in addition to synthesis of imidazolidine, thiazole, thioazolidine, triazolidine, thiadiazine, and spiro compounds. J. Heterocyclic Chem., (2010).
Climatology of Mediterranean cyclones using the ERA‐40 dataset
Authors: Campins Joan , Genovés A. , Picornell M. A. , Jansà A.
Published: June 2010

The generation of cyclone climatologies has recently received a renewed interest. Cyclones are closely related to the climate of certain regions, and thus, their variability is one of the key points in current climate research. The Mediterranean is a region with high density of cyclones, but due to its location and its particular morphology, cyclones are subject to large spatial and seasonal variability. Moreover, some cyclones are related to hazardous weather events, in particular, heavy precipitation and strong winds. Improved knowledge of Mediterranean cyclones would contribute to the improvement of the forecasts of such damaging events. In this study, objective detection and tracking algorithms are used on the ERA‐40 reanalysis to derive a climatology of surface cyclones for the Mediterranean region. The detection algorithm is also applied at various vertical levels, characterizing the three‐dimensional structure of the cyclones, and allowing to derive their vertical thickness. The relatively high spatial resolution, but mainly the long period (45 years) makes the ERA‐40 reanalysis especially suitable for the generation of a cyclone climatology. The aim of this study is twofold. First, a detailed description of the Mediterranean surface cyclones is obtained. This includes the spatial and seasonal variability and some of their main individual features, like the intensity, size, vertical thickness and life cycle. Moreover, some regions with a large cyclogenetic frequency are studied in detail. Second, the results of the present climatology are compared with many other studies. The qualitative comparison indicates a general agreement with most of previous climatologies. However, as a consequence of the ERA‐40 resolution, the comparison with high‐resolution cyclone datasets shows a shortcoming related to the detection of small cyclones. Nevertheless, it is concluded that the current climatology depicts a comprehensive view of the synoptic and sub‐synoptic cyclonic activities in the Mediterranean. Copyright © 2010 Royal Meteorological Society
International broadcast meteorology
Authors: Teather John
Published: June 2010

Broadcast meteorology has undergone a rapid expansion in the past few years and the profession of ‘Broadcast Meteorologist’ is now seen as a serious branch of meteorology. This paper explains how weather forecasts have evolved on television, focusing mainly on the BBC where the author was Director of the BBC Weather Centre for many years. The International Association of Broadcast Meteorology (IABM) has been established to promote weather broadcasting standards across the world and the foundation of this organization is discussed. Copyright © 2010 Royal Meteorological Society
Peptides from Pisum sativum L. enzymatic protein digest with anti‐adhesive activity against Helicobacter pylori: Structure–activity and inhibitory activity against BabA, SabA, HpaA and a fibronectin‐binding adhesin
Authors: Niehues Michael , Euler Marco , Georgi Gilda , Mank Marko , Stahl Bernd , Hensel Andreas
Published: June 2010

Scope: Identification of anti‐adhesive peptides against Helicobacter pylori obtained by enzymatic hydrolysis of seed proteins from Pisum sativum L. (Fabaceae).

Methods and results: Bioassay‐guided fractionation of protein tryptic digest by ultrafiltration, size exclusion chromatography (SEC) and reversed phase chromatography (RPC) were used. Identification of bioactive peptides was achieved by MALDI‐TOF‐MS. Adhesion of H. pylori was monitored by two different assays, using a quantitative in vitro assay on human AGS cells with evaluation of bacterial binding by flow cytometry, beside a semi‐quantitative in situ adhesion assay using FITC‐labelled H. pylori on human stomach tissue sections. From two highly active fractions (F3, F3.3) two anti‐adhesive peptides (S3, S5) were identified. Neither F3 nor S3 or S5 had any cytotoxic effect against H. pylori. By hemagglutination assay and semiquantitative dot blot overlay assay with immobilized ligands it was shown that F3 interacts specifically with H. pylori adhesins BabA, SabA, HpaA and a fibronectin‐binding adhesin, while S3 and S5 inhibit only BabA. It was demonstrated that BabA, usually interacting with carbohydrate motifs such as fucosylated blood group antigens, interacts with the peptide moieties.

Conclusion: Bioactive peptides from pea protein could be applied as functional ingredients for protecting infants and children against infections such as H. pylori.
Functional and proliferative effects of repeated low‐dose oral administration of furan in rat liver
Authors: Mally Angela , Graff Carmen , Schmal Olga , Moro Sabrina , Hamberger Carolin , Schauer Ute M. , Brück Jens , Özden Sibel , Sieber Max , Steger Ulrich , Schrenk Dieter , Hard Gordon C. , Chipman James Kevin , Dekant Wolfgang
Published: June 2010

Scope: Furan, a food contaminant formed during heat processing, induces hepatocellular tumors in rodents and high incidences of cholangiocarcinomas in rats even at the lowest dose (2 mg/kg b.w.) administered. Initial estimates suggested that human intake of furan may be as high as 3.5 μg/kg b.w./day, indicating a relatively narrow margin of exposure. The aim of this study was to establish dose–response data for cytotoxicity, regenerative cell proliferation and secondary oxidative DNA damage in livers of male F344 rats treated with furan at doses ≤2 mg/kg b.w. for 28 days.

Methods and results: No significant signs of hepatotoxicity other than a mild, dose‐dependent increase in serum cholesterol and unconjugated bile acids, and no evidence of oxidative DNA damage were seen. Histopathological alterations and proliferative changes were restricted to subcapsular areas of the left and caudate liver lobes.

Conclusion: Although statistically significant effects were only seen at the 2 mg/kg b.w. dose during the course of our study, a ∼two and ∼threefold increase in 5‐bromo‐2′‐deoxyuridine labeling index was observed at 0.1 and 0.5 mg/kg b.w., respectively, suggesting that chronic exposure to doses even below 2 mg/kg b.w. may cause proliferative changes in rat liver and highlighting the need to assess furan carcinogenicity at lower doses.
TASSER_low‐zsc: An approach to improve structure prediction using lowz‐score–ranked templates
Authors: Pandit Shashi B. , Skolnick Jeffrey
Published: June 2010

In a variety of threading methods, often poorly ranked (lowz‐score) templates have good alignments. Here, a new method,TASSER_low‐zscthat identifies these lowz‐score–ranked templates to improve protein structure prediction accuracy, is described. The approach consists of clustering of threading templates by affinity propagation on the basis of structural similarity (thread_cluster) followed by TASSER modeling, with final models selected by using a TASSER_QA variant. To establish the generality of the approach, templates provided by two threading methods, SP3and SPARKS2, are examined. The SP3and SPARKS2benchmark datasets consist of 351 and 357 medium/hard proteins (those with moderate to poor quality templates and/or alignments) of length ≤250 residues, respectively. For SP3medium and hard targets, usingthread_cluster, the TM‐scores of the best template improve by ∼4 and 9% over the original set (without lowz‐score templates) respectively; after TASSER modeling/refinement and ranking, the best model improves by ∼7 and 9% over the best model generated with the original template set. Moreover,TASSER_low‐zscgenerates 22% (43%) more foldable medium (hard) targets. Similar improvements are observed with low‐ranked templates from SPARKS2. The template clustering approach could be applied to other modeling methods that utilize multiple templates to improve structure prediction. Proteins 2010. © 2010 Wiley‐Liss, Inc.
i‐Patch: Interprotein contact prediction using local network information
Authors: Hamer Rebecca , Luo Qiang , Armitage Judith P. , Reinert Gesine , Deane Charlotte M.
Published: June 2010

Biological processes are commonly controlled by precise protein‐protein interactions. These connections rely on specific amino acids at the binding interfaces. Here we predict the binding residues of such interprotein complexes. We have developed a suite of methods, i‐Patch, which predict the interprotein contact sites by considering the two proteins as a network, with residues as nodes and contacts as edges. i‐Patch starts with two proteins, A and B, which are assumed to interact, but for which the structure of the complex is not available. However, we assume that for each protein, we have a reference structure and a multiple sequence alignment of homologues. i‐Patch then uses the propensities of patches of residues to interact, to predict interprotein contact sites. i‐Patch outperforms several other tested algorithms for prediction of interprotein contact sites. It gives 59% precision with 20% recall on a blind test set of 31 protein pairs. Combining the i‐Patch scores with an existing correlated mutation algorithm, McBASC, using a logistic model gave little improvement. Results from a case study, on bacterial chemotaxis protein complexes, demonstrate that our predictions can identify contact residues, as well as suggesting unknown interfaces in multiprotein complexes. Proteins 2010. © 2010 Wiley‐Liss, Inc.
CAPRI targets T29–T42: Proving ground for new docking procedures
Authors: Eisenstein Miriam , Ben‐Shimon Avraham , Frankenstein Ziv , Kowalsman Noga
Published: June 2010

The critical assessment of protein interactions (CAPRI) experiment provides a unique opportunity for unbiased assessment of docking procedures. The recent CAPRI targets T29–T42 entailed docking of bound, unbound, and modeled structures, presenting a wide range of prediction difficulty. We submitted accurate predictions for targets T40, T41, and T42, a good prediction for T32 and acceptable predictions for T29 and T34. The accuracy of our docking results generally matched the prediction difficulty; hence, docking of modeled proteins produced less accurate results. However, there were interesting exceptions: an accurate prediction was submitted for the dimer of modeled tetratricopeptide repeat (T42) and only an acceptable prediction for the bound/unbound case T29. The ensembles of docking models produced in the scans included an acceptable or better prediction for every target. We show here that our recently developed postscan reevaluation procedure, which tests propensity and solvation measures of the whole interface and the interface core, successfully distinguished these predictions from false docking models. For enzyme–inhibitor targets, we show that the distance of the interface from the enzyme's centroid ranked high native like docking models. Also, for one case we demonstrate that docking of an ensemble of conformers produced by normal modes analysis can improve the accuracy of the prediction. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Application of biasing‐potential replica‐exchange simulations for loop modeling and refinement of proteins in explicit solvent
Authors: Kannan Srinivasaraghavan , Zacharias Martin
Published: June 2010

Comparative or homology modeling of a target protein based on sequence similarity to a protein with known structure is widely used to provide structural models of proteins. Depending on the target‐template similarity these model structures may contain regions of limited structural accuracy. In principle, molecular dynamics (MD) simulations can be used to refine protein model structures and also to model loop regions that connect structurally conserved regions but it is limited by the currently accessible simulation time scales. A recently developed biasing potential replica exchange (BP‐REMD) method was used to refine loops and complete decoy protein structures at atomic resolution including explicit solvent. In standard REMD simulations several replicas of a system are run in parallel at different temperatures allowing exchanges at preset time intervals. In a BP‐REMD simulation replicas are controlled by various levels of a biasing potential to reduce the energy barriers associated with peptide backbone dihedral transitions. The method requires much fewer replicas for efficient sampling compared with T‐REMD. Application of the approach to several protein loops indicated improved conformational sampling of backbone dihedral angle of loop residues compared to conventional MD simulations. BP‐REMD refinement simulations on several test cases starting from decoy structures deviating significantly from the native structure resulted in final structures in much closer agreement with experiment compared to conventional MD simulations. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Structure of the ATP‐binding domain of Plasmodium falciparum Hsp90
Authors: Corbett Kevin D. , Berger James M.
Published: June 2010

Hsp90 is an important cellular chaperone and attractive target for therapeutics against both cancer and infectious organisms. The Hsp90 protein from the parasite Plasmodium falciparum, the causative agent of malaria, is critical for this organism's survival; the anti‐Hsp90 drug geldanamycin is toxic to P. falciparum growth. We have solved the structure of the N‐terminal ATP‐binding domain of P. falciparum Hsp90, which contains a principal drug‐binding pocket, in both apo and ADP‐bound states at 2.3 Å resolution. The structure shows that P. falciparum Hsp90 is highly similar to human Hsp90, and likely binds agents such as geldanamycin in an identical manner. Our results should aid in the structural understanding of Hsp90‐drug interactions in P. falciparum, and provide a scaffold for future drug‐discovery efforts. Proteins 2010; © 2010 Wiley‐Liss, Inc.