bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of medicines in malaria control and elimination
Authors: Warsame Marian , Olumese Peter , Mendis Kamini
Published: January 2010

Antimalarial medicines constitute important tools to cure and prevent malaria infections, thereby averting death and disability; their role in reducing the transmission of malaria is becoming increasingly important. Effective medicines that are currently available include artemisinin‐based combination therapies (ACTs) for uncomplicated malaria, parenteral and rectal formulations of artemisinin derivatives and quinine injectables for severe malaria, and primaquine as an anti‐relapse agent. These medicines are not optimal, however, owing to safety considerations in specific risk groups, complex regimens, and less than optimal formulations. The efficacy of antimalarial medicines including currently used ACTs is threatened by parasite resistance. Resistance to artemisinins has recently been identified at the Cambodia–Thailand border. Intermittent preventive treatment is constrained by the lack of a replacement for sulfadoxine‐pyrimethamine. Despite increasing financial support to procure medicines, access to medicines by populations at risk of malaria, particularly in African countries, remains poor. This is largely due to weak health systems that are unable to deliver quality diagnostics and medicines through an efficient supply chain system, close at hand to the sick patient, especially in remote rural areas. Health systems are also challenged by incorrect prescribing practices in the informal and often unregulated private sector (an important provider of medicines for malaria) and the proliferation of counterfeit and substandard medicines. The provision of a more equitable access to life‐saving medicines requires no less than a steady drug development pipeline for new medicines tailored to meet the challenging conditions in endemic countries, ideally single dose, highly effective against both disease and relapse‐causing parasites and infective forms, extremely safe and with a long shelf life, and made available at affordable prices. Drug Dev Res 71: 4–11, 2010. © 2010 Wiley‐Liss, Inc.
Neutral effects of the novel analgesic tapentadol on cardiac repolarization due to mixed ion channel inhibitory activities
Authors: Schneider J. , Jahnel U. , Linz K.
Published: January 2010

Tapentadol is a novel analgesic with µ‐opioid receptor agonistic and norepinephrine reuptake inhibiting activities at submicromolar concentrations. Given that inhibition of cardiac potassium currents by noncardiovascular pharmaceuticals is a critical issue in drug development, the potential effects of tapentadol on myocardial repolarization were evaluated. Tapentadol concentration‐dependently inhibited hERG‐related currents in CHO cells with 250 and 750 times lower potency than haloperidol and sertindole. In electrically stimulated guinea pig papillary muscles, tapentadol at 10 and 100 µM shortened the action potential duration at 30% of repolarization (APD30) and APD90. Maximum effects (100 µM) were more pronounced on APD30than on APD90. In contrast, the hERG inhibitor,d,l‐sotalol concentration‐dependently (1–100 nM) prolonged APD90without affecting APD30. In isolated, perfused, spontaneously beating guinea pig hearts, volume‐conducted ECGs revealed that tapentadol reduced heart rate (HR) and prolonged uncorrected QT time, but did not affect HR‐corrected QTc time. The hERG inhibitor, dofetilide (0.01 and 0.1 µM) reduced HR and prolonged QT and QTc time. PR time was prolonged by tapentadol but not by dofetilide. Intravenous infusion of tapentadol (3, 6, 9mg/kg) in conscious dogs led to suprapharmacological plasma concentrations of up to 12 µM (2,531 ng/ml). QT time decreased in tapentadol‐treated dogs in parallel to an increase in HR, whereas HR‐corrected QTc time was not affected. In conclusion, the in vitro effects of tapentadol suggest mixed ion channel activities on potassium, calcium, and sodium channels at supra‐pharmacological concentrations. These activities may be neutralizing, resulting in lack of a net effect of tapentadol on cardiac repolarization. Drug Dev Res 1–12, 2010  © 2010 Wiley‐Liss, Inc.
Assessing quality of diabetes care and its variation in Aboriginal community health centres in Australia
Authors: Si Damin , Bailie Ross , Dowden Michelle , Kennedy Catherine , Cox Rhonda , O'Donoghue Lynette , Liddle Helen , Kwedza Ru , Connors Christine , Thompson Sandra , Burke Hugh , Brown Alex , Weeramanthri Tarun
Published: January 2010

Background

Examining variation in diabetes care across regions/organizations provides insight into underlying factors related to quality of care. The aims of this study were to assess quality of diabetes care and its variation among Aboriginal community health centres in Australia, and to estimate partitioning of variation attributable to health centre and individual patient characteristics.

Methods

During 2005–2009, clinical medical audits were conducted in 62 Aboriginal community health centres from four states/territories. Main outcome measures include adherence to guidelines‐scheduled processes of diabetes care, treatment and medication adjustment, and control of HbA1c, blood pressure, total cholesterol and albumin/creatinine ratio (ACR).

Results

Wide variation was observed across different categories of diabetes care measures and across centres: (1) overall adherence to delivery of services averaged 57% (range 22–83% across centres); (2) medication adjustment rates after elevated HbA1c: 26% (0–72%); and (3) proportions of patients with HbA$_{\rm {1c}} < 7\%:27\%$ (0–55%); with blood pressure < 130/80 mmHg: 36%(0–59%). Health centre level characteristics accounted for 36% of the total variation in adherence to process measures, and 3–11% of the total variation in patient intermediate outcomes; the remaining, substantial amount of variation in each measure was attributable to patient level characteristics.

Conclusions

Deficiencies in a range of quality of care measures provide multiple opportunities for improvement. The majority of variation in quality of diabetes care appears to be attributable to patient level characteristics. Further understanding of factors affecting variation in the care of individuals should assist clinicians, managers and policy makers to develop strategies to improve quality of diabetes care in Aboriginal communities. Copyright © 2010 John Wiley & Sons, Ltd.
An Oxide‐Centered Trinuclear Manganese(III) Compound with a Bulky Phenol‐Pyrazolate Ligand
Authors: Viciano‐Chumillas Marta , Tanase Stefania , Roubeau Olivier , Teat Simon J. , de Jongh L. Jos , Reedijk Jan
Published: January 2010

A new oxide‐centered trinuclear manganese(III) compound with the formula [Mn3(μ3‐O)(naphpz)3(O2CMe)(MeOH)2]n (1) {H2naphpz = 2‐[1H‐pyrazol‐5(3)‐yl]naphthalen‐1‐ol} has been synthesized and characterized. Three bulky doubly deprotonated phenol‐pyrazole ligands are coordinated to the three manganese(III) ions with a μ3‐oxide bridge in the same plane. Methanol and acetate ligands are at the apical positions of the manganese(III) ions. The trinuclear units are bridged by acetate ligands in the anti‐anti mode, leading to the formation of 1‐D chains. Temperature‐dependent magnetic susceptibility studies indicate the presence of overall antiferromagnetic interactions with magnetic exchange constants of J1 ≈ –1.9 and J2 ≈ –5.5 cm–1 and g = 1.91. Weak antiferromagnetic interactions (zJ′ = –0.37 cm–1) between the trinuclear units in the 1‐D chain (and between the chains) in compound 1 are present.
Rapid and General Protocol towards Catalyst‐Free Friedel–Crafts C‐Alkylation of Indoles in Water Assisted by Microwave Irradiation
Authors: De Rosa Margherita , Soriente Annunziata
Published: January 2010

An efficient and simplified protocol for uncatalyzed Friedel–Crafts alkylation of indoles using microwave irradiation in water is described. A series of functionalized indole derivatives has been synthesized in very short times with moderate to good yields. The combination of microwave irradiation and superheated water offers significant advantages over conventional methods, such as higher selectivities, simplicity, shorter reaction times, and no need for a catalyst.
An improvement to linear‐elastic procedures for seismic performance assessment
Authors: Günay Mehmet Selim , Sucuoğlu Halûk
Published: January 2010

An improved linear‐elastic analysis procedure is developed in this paper as a simple approximate method for displacement‐based seismic assessment of the existing buildings. The procedure is mainly based on reducing the stiffness of structural members that are expected to respond in the inelastic range in a single global iteration step. Modal spectral displacement demands are determined from the equal displacement rule. Response predictions obtained from the proposed procedure are evaluated comparatively by using the results of benchmark nonlinear response history analysis, and both the conventional and the multi‐mode pushover analyses. In comparative evaluations, a twelve‐story RC plane frame and a six‐story unsymmetrical‐plan RC frame are employed by using 91 ground motion components. It is observed that the proposed procedure estimates the flexural deformation demands in deformation‐controlled members and the shear forces in force‐controlled members with reasonable accuracy. Copyright © 2010 John Wiley & Sons, Ltd.
Fire effluent component yields from room‐scale fire tests
Authors: Gann Richard G. , Averill Jason D. , Johnsson Erik L. , Nyden Marc R. , Peacock Richard D.
Published: January 2010

Estimation of the time available for escape (ASET) in the event of a fire is a principal component in fire hazard or risk assessment. Valid data on the yields of toxic smoke components from bench‐scale apparatus is essential to accurate ASET calculations. This paper presents a methodology for obtaining pre‐flashover and post‐flashover toxicant yields from room‐scale fire tests. The data are to be used for comparison with bench‐scale data for the same combustibles: a sofa, bookcases, and electric power cable. Each was burned in a room with a long adjacent corridor. The yields of CO2, CO, HCl, HCN, and soot were determined. Other toxicants (NO2, formaldehyde, and acrolein), whose concentrations were below the detection limits, were of limited importance relative to the detected toxicants. The uncertainty values were comparable to those estimated for calculations used to determine ASET and were sufficiently small to determine whether a bench‐scale apparatus is producing results that are similar to the real‐scale results here. The use of Fourier transform infrared spectroscopy was useful for obtaining toxicant concentration data; however, its operation and interpretation are not routine. The losses of CO, HCN, and HCl along the corridor were dependent on the combustible. Copyright © 2009 John Wiley & Sons, Ltd.
Hedgehog Signaling Is Critical for Normal Liver Regeneration After Partial Hepatectomy in Mice
Authors: Ochoa Begoña , Syn Wing-Kin , Delgado Igotz , Karaca Gamze F. , Jung Youngmi , Wang Jiangbo , Zubiaga Ana M. , Fresnedo Olatz , Omenetti Alessia , Zdanowicz Marzena , Choi Steve S. , Diehl Anna Mae
Published: January 2010

Distinct mechanisms are believed to regulate growth of the liver during fetal development and after injury in adults, because the former relies on progenitors and the latter generally involves replication of mature hepatocytes. However, chronic liver injury in adults increases production of Hedgehog (Hh) ligands, developmental morphogens that control progenitor cell fate and orchestrate various aspects of tissue construction during embryogenesis. This raises the possibility that similar Hh-dependent mechanisms also might regulate adult liver regeneration. The current analysis of murine liver regeneration after 70% partial hepatectomy (PH), an established model of adult liver regeneration, demonstrated that PH induced production of Hh ligands and activated Hh signaling in liver cells. Treatment with a specific Hh signaling inhibitor interfered with several key components of normal liver regeneration, significantly inhibiting progenitor responses, matrix remodeling, proliferation of hepatocytes and ductular cells, and restoration of liver mass. These global inhibitory effects on liver regeneration dramatically reduced survival after PH.

Conclusion:

Mechanisms that mediate liver organogenesis, such as Hh pathway activation, are retained and promote reconstruction of adult livers after injury. Hepatology 2010
Stress‐induced dynamic routing of hippocampal connectivity: A hypothesis
Authors: Segal Menahem , Richter‐Levin Gal , Maggio Nicola
Published: January 2010

Recent observations have caused a drastic shift in the conception of the hippocampus as a homogeneous structure that subserves cognitive functions, either spatial maps or short term episodic memory, to a structure that is associated with both cognitive and emotional functions. In fact, the assignment of cognitive functions to the hippocampus is restricted to its dorsal sector. In contrast, the ventral hippocampus (VH) appears to be associated with control of behavioral inhibition, stress and emotional memory, but not with strictly cognitive functions. Curiously, the VH but not the dorsal hippocampus (DH) is associated with the development of affective disorders. In line with these collective observations, we and others have found that the ability to evoke a sustained long term potentiation (LTP), a cellular correlate of learning and memory, is much lower in the VH compared to the DH. Strikingly, acute stress as well as direct exposure to corticosterone affect DH and VH in an opposite manner; causing facilitation of LTP in the VH and its suppression in the DH. This double dissociative action results from activation of different steroid receptor species in the DH and VH. Since the DH and VH differ in efferent connectivity, and since the strength of LTP can be considered as an indicator of strength of synaptic connectivity, these results suggest that stress regulates the routes by which the hippocampus is functionally linked to the rest of the brain such that under stress, the ventral route to the amygdala is enabled while the dorsal route to the neocortex is suppressed. This selective routing may underlie the complex outcome of stress on hippocampal and amygdala physiology and behavior. © 2009 Wiley‐Liss, Inc.
BDNF is required for the induction of a presynaptic component of the functional conversion of silent synapses
Authors: Cabezas Carolina , Buño Washington
Published: January 2010

Long‐term potentiation (LTP) has received attention because of its proposed role in learning and memory. Despite substantial effort the pre‐ or postsynaptic expression site of LTP remains unsettled. It has been proposed that LTP is expressed postsynaptically through the functional conversion of “silent synapses.” We had shown that Schaffer collateral (SC) silent and “functional synapses,” which lack and express AMPA receptors, respectively exhibit distinct transmitter release properties. Therefore the functional conversion of silent synapses with LTP should be associated with presynaptic modifications. We now show that the pairing‐induced LTP at SC synapses is mediated by combined pre‐ and postsynaptic modifications involving the postsynaptic emergence of an AMPA response coupled with an enhanced glutamate release. BDNF replicates the changes associated with this LTP by activating TrkBRs, suggesting that the neurotrophin is required for the coordinated changes on both sides of the synaptic cleft. © 2010 Wiley‐Liss, Inc.
Discrimination of normal from pre‐malignant cervical tissue by Raman mapping of de‐paraffinized histological tissue sections
Authors: Tan Khay M. , Herrington C. Simon , Brown Christian T. A.
Published: January 2010

The authors present Raman cluster mapping of de‐paraffinized normal cervical tissue and demonstrate the ability of this approach to differentiate between normal squamous epithelium and cervical intraepithelial neoplasia (CIN). Multivariate analysis was performed by hierarchical cluster analysis (HCA) of the Raman spectra associated with the different tissue types and Raman maps were generated using the resultant clusters. Using normal cervical tissue, squamous epithelium and the epithelial‐stromal interface, a muscular artery and endocervical glands were successfully mapped. Analysis of a tissue section containing a cervical intraepithelial neoplasia (CIN) grade 2 lesion adjacent to normal squamous epithelium demonstrated that the CIN lesion clustered predominantly with the basal epithelial cells of normal epithelium and allowed visual discrimination of these areas using the Raman map. These findings suggest that Raman mapping has the potential to provide images that are useful for disease diagnosis. In particular, the discrimination between normal cervical squamous epithelium and CIN is of relevance to cervical screening pathology. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantitative proteome analysis of multidrug resistance in human ovarian cancer cell line
Authors: Li Sang‐Lin , Ye Feng , Cai Wei‐Jun , Hu Huai‐Dong , Hu Peng , Ren Hong , Zhu Fu‐Fan , Zhang Da‐Zhi
Published: January 2010

In order to understand the molecular mechanisms of multidrug resistance (MDR) in ovarian cancer, we employed the proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by LC‐MS/MS, using the cisplatin‐resistant COC1/DDP cell line and its parental COC1 cell line as a model. A total number of 28 proteins differentially expressed were identified, and then the differential expression levels of partially identified proteins were confirmed by Western blot analysis and/or real‐time RT‐PCR. Furthermore, the association of PKM2 and HSPD1, two differentially expressed proteins, with MDR were analyzed, and the results showed that they could contribute considerably to the cisplatin resistance in ovarian cancer cell. The differential expression proteins could be classified into eight categories based on their functions, that is, calcium binding proteins, chaperones, extracellular matrix, proteins involved in drug detoxification or repair of DNA damage, metabolic enzymes, transcription factor, proteins related to cellular structure and proteins relative to signal transduction. These data will be valuable for further study of the mechanisms of MDR in the ovarian cancer. J. Cell. Biochem. 109: 625–633, 2010. © 2010 Wiley‐Liss, Inc.
The cancer‐related Runx2 protein enhances cell growth and responses to androgen and TGFβ in prostate cancer cells
Authors: van der Deen Margaretha , Akech Jacqueline , Wang Tao , FitzGerald Thomas J. , Altieri Dario C. , Languino Lucia R. , Lian Jane B. , van Wijnen Andre J. , Stein Janet L. , Stein Gary S.
Published: January 2010

Prostate cancer cells often metastasize to bone where osteolytic lesions are formed. Runx2 is an essential transcription factor for bone formation and suppresses cell growth in normal osteoblasts but may function as an oncogenic factor in solid tumors (e.g., breast, prostate). Here, we addressed whether Runx2 is linked to steroid hormone and growth factor signaling, which controls prostate cancer cell growth. Protein expression profiling of prostate cell lines (i.e., PC3, LNCaP, RWPE) treated with 5α‐dihydrotestosterone (DHT) or tumor growth factor β (TGFβ) revealed modulations in selected cyclins, cyclin‐dependent kinases (CDKs), and CDK inhibitors that are generally consistent with mitogenic responses. Endogenous elevation of Runx2 and diminished p57 protein levels in PC3 cells are associated with faster proliferation in vitro and development of larger tumors upon xenografting these cells in bone in vivo. To examine whether TGFβ or DHT signaling modulates the transcriptional activity of Runx2 and vice versa, we performed luciferase reporter assays. In PC3 cells that express TGFβRII, TGFβ and Runx2 synergize to increase transcription of synthetic promoters. In LNCaP cells that are DHT responsive, Runx2 stimulates the androgen receptor (AR) responsive expression of the prostate‐specific marker PSA, perhaps facilitated by formation of a complex with AR. Our data suggest that Runx2 is mechanistically linked to TGFβ and androgen responsive pathways that support prostate cancer cell growth. J. Cell. Biochem. 109: 828–837, 2010. © 2010 Wiley‐Liss, Inc.
Pathology and biology associated with the fragile FHIT gene and gene product
Authors: Saldivar Joshua C. , Shibata Hidetaka , Huebner Kay
Published: January 2010

More than 12 years and >800 scientific publications after the discovery of the first gene at a chromosome fragile site, the FHIT gene at FRA3B, there are still questions to pursue concerning the selective advantage conferred to cells by loss of expression of FHIT, the most frequent target of allele deletion in precancerous lesions and cancers. These questions are considered in light of recent investigations of genetic and epigenetic alterations to the locus and in a retrospective consideration of biological roles of the Fhit protein discovered through functional studies. J. Cell. Biochem. 109: 858–865, 2010. © 2010 Wiley‐Liss, Inc.
JAK–STAT is restrained by Notch to control cell proliferation of the Drosophila intestinal stem cells
Authors: Liu Wei , Singh Shree Ram , Hou Steven X.
Published: January 2010

The Drosophila midgut epithelium undergoes continuous regeneration that is sustained by multipotent intestinal stem cells (ISCs) underneath. Notch signaling has dual functions to control ISC behavior: it slows down the ISC proliferation and drives the activated ISCs into different differentiation pathways at a dose‐dependent manner. Here we identified a molecular mechanism to unite these two contradictory functions. We found JAK–STAT signaling controls ISC proliferation and this ability is negatively regulated by Notch at least through a transcriptional control of the JAK–STAT signaling ligand, unpaired (upd). This study provides insight into how stem cells, under steady conditions, balance the processes of proliferation and differentiation to maintain the stable cellular composition of a healthy tissue. J. Cell. Biochem. 109: 992–999, 2010. © 2010 Wiley‐Liss, Inc.
A first‐principles study on the existence and structures of the lighter alkaline‐earth pernitrides
Authors: Wessel Michael , Dronskowski Richard
Published: January 2010

The lighter alkaline‐earth pernitrides BeN2, MgN and CaN2 have been structurally predicted by a series of density‐functional (GGA/PBE/PAW) electronic‐structure calculations. Despite their crystal chemistry clearly pointing towards the formulation M2+N22− with an NN distance of 1.26 Å, all phases turn out as metallic compounds which are exothermic with respect to the elements. The M2+ coordination numbers are a simple function of the cationic radius. The bulk moduli are about three times smaller than those of the noble‐metal pernitrides, a consequence of the smaller anionic charge in the former phases. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Hydrogen uptake capacity of C2H4Sc and its ions: A density functional study
Authors: Wadnerkar Nitin , Kalamse Vijayanand , Chaudhari Ajay
Published: January 2010

We report the gravimetric hydrogen uptake capacity of C2H4Sc complex and isoelectronic ions using Density Functional Theory. We predict that C2H4Sc+ can bind maximum seven hydrogen molecules in dihydrogen form giving gravimetric uptake capacity of 16.2 wt %, larger by about 2 and 4 wt % than the neutral and anion, respectively. We also found that the interaction of hydrogen molecules with C2H4Sc+ ion is characteristically different than that with neutral and anion. Vibrational spectroscopic study reveals that C2H4Sc and isoelectronic ions are quantum mechanically stable with their characteristic change in respective identified mode. The large gravimetric H2 uptake capacity of C2H4Sc+ is well above the target specified by Department of Energy (DOE) by 2015. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
A model study of the efficiency of the Asp–His–Ser triad
Authors: Lankau Timm , Yu Chin‐Hui
Published: January 2010

The observation of the Asp–His–Ser triad (Asp: aspartate, His: histidine, Ser: serine) triad both in mammalian and bacterial proteases suggests a special efficiency. A series of B3LYP/D95*(d,p) calculations on various [X–HβY]− dyads (as part of the [X–HβY–HαAc]− model triad, HAc: acetic acid) made from eight different anions X− and 15 different coupling elements HβY was done to analyze the molecular origin of this efficiency. The X− anion acts merely as an electron density donor independent of its chemical nature, and the evolutionary selection of Asp for the catalytic triad therefore seems to be caused by the pH of the triads environment. As the linking proton Hβ moves from Y− to X−, electron density is effectively moved from X− to Y− thereby increasing the proton affinity (PA) of the [X–HY]− dyad, which finally leads to the deprotonization of the HAc molecule. The degree to which the position of Hα controls the PA is dominatly determined by the coupling element HY. The model calculations indicate that 4‐methyl‐1H‐imidazole (HMim) is a very efficient coupling element, which suggest that the evolutionary convergence to the Asp–His–Ser is not only controlled by the ready availability of the imidazole motive in His but also by its high efficiency. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
DFT study of the full catalytic cycle for the propene hydroformylation catalyzed by a heterobimetallic HPt(SnCl3)(PH3)2 model catalyst
Authors: da Silva Júlio C. S. , Dias Roberta P. , de Almeida Wagner B. , Rocha Willian R.
Published: January 2010

DFT calculations were carried out to study the full catalytic cycle for the hydroformylation of propene, catalyzed by the heterobimetallic model catalyst trans‐Pt(H)(PH3)2(SnCl3). Before the study of the full catalytic cycle, the performance of six pure GGA, one GGA with inclusion of dispersion corrections, four hybrid‐GGA, and three meta‐GGA exchange correlation functional to describe a model reaction promoted by Pt‐Sn catalyst were assessed. It is shown that the BP86 and GPW91 functionals, using extended basis set, provides reliable energetic results when compared with the CCSD(T) calculations. All intermediates and transition states along the elementary steps of the entire catalytic cycle were located and the energies involved in the catalytic cycle calculated using BP86 functional. The solvent effects along the entire catalytic cycle were evaluated using the polarizable continuum model. In contrast with the rhodium catalysts, the regioselectivity of the hydroformylation is set at the carbonylation step. The hydrogenolysis is the rate determining step of the entire cycle, with the activation energy of ∼21 kcal mol−1 in agreement with the experimental value of ∼25 kcal mol−1. The trans effect of the SnCl ligand seems to be pronounced only in the first step of the catalytic cycle, facilitating the insertion of the olefin into the PtH bond trans to it. The analysis of the stationary points obtained along each elementary step of the catalytic cycle is carried out separately and discussed. The BP86/cc‐pVTZ/SBKJC results shows that the pathway leading to the linear aldehyde is preferred, being in agreement with the experimental findings. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Resveratrol enhances perforin expression and NK cell cytotoxicity through NKG2D‐dependent pathways
Authors: Lu Chia‐Chen , Chen Jan‐Kan
Published: January 2010

In a previous report, we showed that the in vivo cytotoxic activity of the natural killer (NK) cells isolated from resveratrol‐pretreated rats is significantly enhanced compared with that of the non‐pretreated rats; however, the underlying mechanism remains unclear. In the present study, we use cultured NK92 cell line to examine the possible signaling pathways underlying the resveratrol‐induced activation. Using cultured K562, HepG2, and A549 cells as targets, we show that resveratrol pretreatment increases NK cell cytotoxicity in a dose‐dependent manner. The enhanced cytotoxic effect is accompanied by increases in JNK and ERK‐1/2 MAP kinase activity and perforin expression. Moreover, the expression of NKG2D, an upstream signaling molecule of the MAP kinases pathway, is also enhanced. Resveratrol‐enhanced perforin expression and cytotoxic activity are effectively inhibited by pretreatment with the inhibitors of JNK (SP600125), ERK‐1/2 (PD98059), or by siRNAs against JNK‐1 and ERK‐2. However, the inhibitors or siRNA to p38 exhibits no effect. Since IL‐2 has been shown to induce NKG2D expression and perforin release, we therefore, examined whether IL‐2 and resveratrol act in parallel. We show that IL‐2 also stimulates perforin expression, however, when treated together with resveratrol, they exhibit no additive effect. The results suggest that in NK92 cells, resveratrol may act via a similar or overlapping pathway as that of IL‐2, to enhance perforin expression and cytotoxic activity. Data presented strongly indicate that resveratrol act via NKG2D‐dependent JNK and ERK‐1/2 pathways. J. Cell. Physiol. 223: 343–351, 2010. © 2010 Wiley‐Liss, Inc.
FAK activation is required for TNF‐α‐induced IL‐6 production in myoblasts
Authors: Tseng Wen‐Pei , Su Chen‐Ming , Tang Chih‐Hsin
Published: January 2010

Tumor necrosis factor‐α (TNF‐α) is a pleiotropic cytokine produced by activated macrophages. IL‐6 is a multifunctional cytokine that plays a central role in both innate and acquired immune responses. We investigated the signaling pathway involved in IL‐6 production stimulated by TNF‐α in cultured myoblasts. TNF‐α caused concentration‐dependent increases in IL‐6 production. TNF‐α‐mediated IL‐6 production was attenuated by focal adhesion kinase (FAK) mutant and siRNA. Pretreatment with phosphatidylinositol 3‐kinase inhibitor (PI3K; Ly294002 and wortmannin), Akt inhibitor, NF‐κB inhibitor (pyrrolidine dithiocarbamate, PDTC), and IκB protease inhibitor (L‐1‐tosylamido‐2‐phenyl phenylethyl chloromethyl ketone, TPCK) also inhibited the potentiating action of TNF‐α. TNF‐α increased the FAK, PI3K, and Akt phosphorylation. Stimulation of myoblasts with TNF‐α activated IκB kinase α/β (IKKα/β), IκBα phosphorylation, p65 phosphorylation, and κB‐luciferase activity. TNF‐α mediated an increase of κB‐luciferase activity which was inhibited by Ly294002, wortmannin, Akt inhibitor, PDTC and TPCK or FAK, PI3K, and Akt mutant. Our results suggest that TNF‐α increased IL‐6 production in myoblasts via the FAK/PI3K/Akt and NF‐κB signaling pathway. J. Cell. Physiol. 223: 389–396, 2010. © 2010 Wiley‐Liss, Inc.
Quercetin suppresses HeLa cell viability via AMPK‐induced HSP70 and EGFR down‐regulation
Authors: Jung Jin Hee , Lee Jeong Ok , Kim Ji Hae , Lee Soo Kyung , You Ga Young , Park Sun Hwa , Park Ji Man , Kim Eung‐Kyun , Suh Pann‐Ghill , An Jin Kyung , Kim Hyeon Soo
Published: January 2010

Quercetin, an anti‐oxidant flavonoid that is widely distributed in the plant kingdom, has been suggested to have chemopreventive effects on cancer cells, although the mechanism is not completely understood. In this study, we found that quercetin increased the phosphorylation of AMP‐activated protein kinase (AMPK) and downstream acetyl‐CoA carboxylase (ACC) and suppressed the viability of HeLa cells. AICAR, an AMPK activator, and quercetin down‐regulated heat shock protein (HSP)70 and increased the activity of the pro‐apoptotic effector, caspase 3. Knock‐down of AMPK blocked quercetin‐mediated HSP70 down‐regulation. Moreover, knock‐down of HSP70 enhanced quercetin‐mediated caspase 3 activation. Furthermore, quercetin sustained epidermal growth factor receptor (EGFR) activation by suppressing the phosphatases, PP2a and SHP‐2. Finally, quercetin increased the interaction between EGFR and Cbl, and also induced the tyrosine phosphorylation of Cbl. Together, these results suggest that quercetin may have anti‐tumor effects on HeLa cells via AMPK‐induced HSP70 and down‐regulation of EGFR. J. Cell. Physiol. 223: 408–414, 2010. © 2010 Wiley‐Liss, Inc.
Enhanced lipoplex‐mediated gene expression in mesenchymal stem cells using reiterated nuclear localization sequence peptides
Authors: Hoare Melissa , Greiser Udo , Schu Sabine , Mashayekhi Kaveh , Aydogan Emrah , Murphy Mary , Barry Frank , Ritter Thomas , O'Brien Timothy
Published: January 2010

Background

Mesenchymal stem cells (MSC) are widely regarded as a promising tool for cellular therapy applications, and genetic modification by safe, liposome‐based vectors may enhance their therapeutic potential.

Methods

The present study describes the use of a cationic lipid vector (Lipofectamine 2000™) to deliver genes to MSC isolated from a number of species in vitro and determined the characteristics of this vector system in terms of dose, toxicity and the time course of expression. In addition, the optimal use of a nuclear localization sequence (NLS) to enhance gene expression was explored.

Results

Lipofection of human MSC did not adversely affect their ability to differentiate into osteogenic‐ and adipogenic lineages. Although human and rat MSC were found to take up lipoplexes with relative efficiency, lower levels of gene expression were detected in rabbit MSC, demonstrating a crucial effect of species. Peptides containing reiterated motifs of NLS were found to significantly improve on the level of transgene expression. Optimal gene delivery was observed when a three‐fold reiterated NLS sequence was included in the liposome formulation.

Conclusions

Thus, nonviral gene delivery to MSC is feasible with efficiency being species dependent and can be enhanced by use of a three‐fold reiterated NLS. Copyright © 2010 John Wiley & Sons, Ltd.
On Ks,t minors in (s+t)‐chromatic graphs
Authors: Kostochka A. V.
Published: January 2010

Let K denote the graph obtained from the complete graph Ks+t by deleting the edges of some Kt‐subgraph. We prove that for each fixed s and sufficiently large t, every graph with chromatic number s+t has a K minor. © 2010 Wiley Periodicals, Inc. J Graph Theory 65: 343–350, 2010
Caste, livelihoods and livestock: An exploration of the uptake of livestock vaccination adoption among poor farmers in India
Authors: Heffernan Claire , Thomson Kim , Nielsen Louise
Published: January 2010

The study explores the uptake of livestock vaccination among poor farming communities in Tamil Nadu State, India by revisiting innovation diffusion theory. Overall, 601 farmers participated in the study. We found the adoption of particular vaccines was strongly influenced by socio‐cultural grouping i.e. caste, rather than other factors such as income, age, education‐level or gender. Adoption was also related to specific knowledge frames regarding disease causality, rather than any wider ethno‐veterinary beliefs. Thus, the adoption of livestock vaccination is unlikely to improve without knowledge transfer activities, which acknowledge both social divisions and local epistemologies regarding animal health. Copyright © 2010 John Wiley & Sons, Ltd.
Phylogenetic diversity of alkaline protease‐producing psychrotrophic bacteria from glacier and cold environments of Lahaul and Spiti, India
Authors: Salwan Richa , Gulati Arvind , Kasana Ramesh Chand
Published: January 2010

The diversity of proteolytic bacteria associated with a glacier and cold environment soils from three different locations in Lahaul and Spiti, India was investigated. Two hundred seventeen bacterial strains were isolated in pure culture. Subsequently these strains were screened for protease‐production and one hundred nine showed protease production. From these protease producing psychrotrophic bacteria twenty showing high enzyme production at low temperature and alkaline pH were characterized and identified. The 16S rRNA phylogenetic analysis revealed that none of the strains showed 100% identity with the validly published species of various genera. Isolates belonged to three classes i.e. Actinobacteria, Gammaproteobacteria and Alphaproteobacteria, and were affiliated with the genera Acinetobacter, Arthrobacter, Mycoplana, Pseudomonas, Pseudoxanthomonas, Serratia and Stenotrophomonas. The optimal growth temperature ranged from 10 to 28 °C and interestingly, high levels of enzyme productions were measured at growth temperatures between 15 and 25 °C, for most of the isolates in plate assay. Most of the isolates were found to produce at least two other hydrolytic enzymes along with protease. The crude protease from one strain was active over broad range of temperature and pH with optima at 30 °C and 7.5, respectively. The protease activity was enhanced by Ca2+, dithiothreitol and β‐mercaptoethanol. While Na+, Hg2+, Zn2+, Mn2+, phenylmethanesulfonyl fluoride and ethylenediaminetetraacetic acid did not showed much effect on protease activity. The results enrich our knowledge on the psychrotrophic bacterial diversity and biogeographic distribution of enzyme producing bacteria in western Himalaya. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Cloning and characterization of poly(3‐hydroxybutyrate) biosynthesis genes from Pseudomonas sp. USM 4‐55
Authors: Tan Yifen , Neo Pei‐Chin , Najimudin Nazalan , Sudesh Kumar , Muhammad Tengku Sifzizul Tengku , Othman Ahmad Sofiman , Samian Razip
Published: January 2010

Pseudomonas sp. USM 4‐55 is a locally isolated bacterium that possesses the ability to produce polyhydroxyalkanoates (PHA) consisting of both poly(3‐hydroxybutyrate) [P(3HB)] homopolymer and medium‐chain length (mcl) monomers (6 to 14 carbon atoms) when sugars or fatty acids are utilized as the sole carbon source. In this study, the P(3HB) biosynthesis operon carrying the phbCPs P(3HB) synthase was successfully cloned and sequenced using a homologous probe. Three open reading frames encoding NADPH‐dependent acetoacetyl‐coenzyme A reductase (PhbBPs), β‐ketothiolase (PhbAPs) and P(3HB) synthase (PhbCPs) were found in the phb operon. The genetic organization of phb operon showed a putative promoter region, followed by phbBPs‐phbAPs‐phbCPs. phbRPswhich encoded a putative transcriptional activator was located in the opposite orientation, upstream of phbBACPs. Heterologous expression of pGEM″ABex harboring phbCPs in Escherichia coli JM109 resulted in P(3HB) accumulation of up to 40% of dry cell weight (DCW). (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Characterization of ACC deaminase gene in Pseudomonas entomophila strain PS‐PJH isolated from the rhizosphere soil
Authors: Kamala‐Kannan Seralathan , Lee Kui‐Jae , Park Seung‐Moon , Chae Jong‐Chan , Yun Bong‐Sik , Lee Yong Hoon , Park Yool‐Jin , Oh Byung‐Taek
Published: January 2010

The enzyme 1‐aminocyclopropane‐1‐carboxylate (ACC) deaminase cleaves the ethylene precursor ACC into α‐ketobutyrate and ammonia. The decreased level of ethylene allows the plant to be more resistant to a wide environmental stress including plant pathogens. In the present study, we characterized the ACC deaminase activity of a Pseudomonas entomophila strain PS‐PJH isolated from the red pepper rhizosphere region of red pepper grown at Jinan, Korea. The isolate produced 23.8 ± 0.4 μmol of α‐ketobutyrate/mg of protein/h during ACC deamination under in vitro conditions. Polymerase chain reaction for acdS gene showed that the isolated P. entomophila strain PS‐PJH carry sequences similar to the known acdS genes. Results of the multiple sequence alignment revealed >99% identity (nucleotide and amino acid) with acdS gene of Pseudomonas putida strains AM15 and UW4. The isolated bacteria promoted 43.3 and 34.1% of growth in Raphanus sativus and Lactuca sativa plants, respectively. Based on the 16S–23S internal transcribed spacer region sequences, the isolate was identified as P. entomophila. To the best of our knowledge this is the first study to report the acdS gene in P. entomophila. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The toxicity of lead to Desulfovibrio desulfuricans G20 in the presence of goethite and quartz
Authors: Sani Rajesh K. , Rastogi Gurdeep , Moberly James G. , Dohnalkova Alice , Ginn Timothy R. , Spycher Nicolas , Shende Rajesh V. , Peyton Brent M.
Published: January 2010

An aqueous mixture of goethite, quartz, and lead chloride (PbCl2) was treated with the sulfate‐reducing bacterium, Desulfovibrio desulfuricans G20 (D. desulfuricans G20), in a medium specifically designed to assess metal toxicity. In the presence of 26 μM of soluble Pb, together with the goethite and quartz, D. desulfuricans G20 grew after a lag time of 5 days compared to 2 days in Pb‐, goethite‐, and quartz‐free treatments. In the absence of goethite and quartz, however, with 26 μM soluble Pb, no measurable growth was observed. Results showed that D. desulfuricans G20 first removed Pb from solutions then growth began resulting in black precipitates of Pb and iron sulfides. Transmission electron microscopic analyses of thin sections of D. desulfuricans G20 treated with 10 μM PbCl2 in goethite‐ and quartz‐free treatment showed the presence of a dense deposit of lead sulfide precipitates both in the periplasm and cytoplasm. However, thin sections of D. desulfuricans G20 treated with goethite, quartz, and PbCl2 (26 μM soluble Pb) showed the presence of a dense deposit of iron sulfide precipitates both in the periplasm and cytoplasm. Energy‐dispersive X‐ray spectroscopy, selected area electron diffraction patterns, or X‐ray diffraction analyses confirmed the structure of precipitated Pb inside the cell as galena (PbS) in goethite‐ and quartz‐free treatments, and iron sulfides in treatments with goethite, quartz, and PbCl2. Overall results suggest that even at the same soluble Pb concentration (26 μM), in the presence of goethite and quartz, apparent Pb toxicity to D. desulfuricans G20 decreased significantly. Further, accumulation of lead/iron sulfides inside D. desulfuricans G20 cells depended on the presence of goethite and quartz. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Characteristics of metastasis in the breast from extramammary malignancies
Authors: Lee Se Kyung , Kim Wan Wook , Kim Sung Hoon , Hur Sung Mo , Kim Sangmin , Choi Jae Hyuck , Cho Eun Yoon , Han Soo Yeon , Hahn Boo‐Kyung , Choe Jun‐Ho , Kim Jung‐Han , Kim Jee Soo , Lee Jeong Eon , Nam Seok Jin , Yang Jung‐Hyun
Published: January 2010

Background and Objective

Breast metastasis from extramammary neoplasm is rare. We present the cases of metastasis to the breast after review of results in one institute and we want to show the difference of previous report.

Methods

The surgical and pathology databases of Samsung Medical Center from November 1994 to March 2009 were investigated to identify all patients with a diagnosis of metastasis to the breast.

Results

Thirty‐three patients with breast metastases from extramammary neoplasm were studied. Gastric carcinoma was most common metastatic origin in this study. There were four cases with microcalcifications in their metastatic lesions. This is the first report of microcalcification of metastatic lesions to the breast from hepatocellular carcinoma and gastric cancer.

Conclusions

Pathologic examination and considering known clinical history may be helpful to differentiate the primary breast cancer and metastatic cancer. Metastasis to the breast from an extramammary neoplasm usually indicates disseminated metastatic disease and a poor prognosis. An accurate diagnosis of breast metastases, differentiating primary from metastatic breast carcinoma, is important for proper management. J. Surg. Oncol. 2010;101:137–140. © 2010 Wiley‐Liss, Inc.
Controlling the histological margin for non‐melanoma skin cancer conveniently using a double‐bladed scalpel
Authors: Aoyagi Satoru , Hata Hiroo , Homma Erina , Shimizu Hiroshi
Published: January 2010

Background

In some countries, intraoperative histological evaluation to control the surgical margin for non‐melanoma skin cancer is widely used instead of Mohs micrographic surgery. Nevertheless, this evaluation by frozen section analysis is usually limited to suspicious areas.

Objectives

To evaluate the efficacy of double‐bladed scalpel for intraoperative histological margin control for non‐melanoma skin cancers.

Methods

Between 2005 and 2009, 10 basal cell carcinomas and 5 squamous cell carcinomas were underwent complete histological margin control in which a double‐bladed scalpel was used during the surgery at the Hokkaido University Hospital in Japan.

Results

The mean number of re‐excisions required for complete tumor resection was 1.4 times. Nine (60%) of the 15 patients obtained histological clearance of all surgical margins at the first re‐excision. The mean size of total surgical margin was 6.1 mm (range: 2–12 mm). The median time from the first tumor excision to reconstruction was 124 min. No local recurrences have been reported.

Conclusions

This method may be used as an alternative for complete histological margin control at many hospitals where it is difficult to perform Mohs micrographic surgery. J. Surg. Oncol. 2010;101:175–179. © 2010 Wiley‐Liss, Inc.
Posterior decompression and stabilization, and surgical vertebroplasty with the vertebral body stenting for metastatic vertebral and epidural cauda equina compression
Authors: Mavrogenis Andreas F. , Papadopoulos Elias C. , Starantzis Konstantinos , Korres Demetrios S. , Papagelopoulos Panayiotis J.
Published: January 2010

We present the technique of combined posterior decompression and spinal instrumentation, and surgical (open) vertebroplasty using a novel system called vertebral body stenting (VBS) during a single session in a patient with metastatic vertebral and epidural cauda equina compression. J. Surg. Oncol. 2010; 101:253–258. © 2010 Wiley‐Liss, Inc.
Can children catch up in growth after living donor liver transplantation?
Authors: El Moghazy Walid Mohamed , Ogura Yasuhiro , Harada Kouji , Koizumi Akio , Uemoto Shinji
Published: January 2010

Several studies have shown improved growth after liver transplantation, but long-term follow-up data have been lacking. This study was aimed at evaluating the ability of children to catch up in height after living donor liver transplantation (LDLT) and at clarifying factors affecting growth. Growth was assessed by serial height measurements performed during follow-up. Standardized height scores (z scores) were calculated for each patient preoperatively (at the baseline) and at 1, 2, 3, 5, 10, and 15 years after LDLT. The risk potential of several preoperative and postoperative variables was evaluated. A total of 237 patients, including 159 females (67.1%), met the inclusion criteria. The mean age at the time of transplant was 3.89 ± 0.28 years. The mean z score was −1.70 ± 0.09, whereas the baseline height deficit was −6.50 ± 0.39 cm. After LDLT, the z score improved significantly and reached −0.64 ± 0.14 by the end of the first year. The best height improvement was seen after 10 years (−0.33 ± 0.16). However, significant growth retardation remained at 15 years (−0.47 ± 0.17). Height showed 3 distinct phases after transplantation: a growth spurt, a plateau phase, and a late declining phase. Univariate and multivariate analyses showed that children under 2 years and those with the most growth retardation at the time of LDLT achieved the best height gain in the first year. Late growth retardation was related to the baseline z score, ABO-incompatible grafts, and graft dysfunction. In conclusion, children have the potential ability to catch up in growth to normal levels after LDLT; they can show impressive height gains in the first year followed by protracted improvement over 10 years and then late growth retardation. Young age is a determinant for early height gain, whereas ABO-incompatible grafts and graft dysfunction are determinants for late growth retardation. In contrast, the baseline z score is a determinant for both.