bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ex VivoActivity of Histone Deacetylase Inhibitors against Multidrug-Resistant Clinical Isolates ofPlasmodium falciparumandP. vivax
Authors: Marfurt Jutta , Chalfein Ferryanto , Prayoga Pak , Wabiser Frans , Kenangalem Enny , Piera Kim A. , Fairlie David P. , Tjitra Emiliana , Anstey Nicholas M. , Andrews Kathy T. , Price Ric N. 
Published: December 2010

ABSTRACTHistone acetylation plays an important role in regulating gene transcription and silencing inPlasmodium falciparum. Histone deacetylase (HDAC) inhibitors, particularly those of the hydroxamate class, have been shown to have potentin vitroactivity against drug-resistant and -sensitive laboratory strains ofP. falciparum, raising their potential as a new class of antimalarial compounds. In the current study, stage-specificex vivosusceptibility profiles of representative hydroxamate-based HDAC inhibitors suberoylanilide hydroxamic acid (SAHA), 2-ASA-9, and 2-ASA-14 (2-ASA-9 and 2-ASA-14 are 2-aminosuberic acid-based HDAC inhibitors) were assessed in multidrug-resistant clinical isolates ofP. falciparum(n= 24) andP. vivax(n= 25) from Papua, Indonesia, using a modified schizont maturation assay. Submicromolar concentrations of SAHA, 2-ASA-9, and 2-ASA-14 inhibited the growth of bothP. falciparum(median 50% inhibitory concentrations [IC50s] of 310, 533, and 266 nM) andP. vivax(median IC50s of 170, 503, and 278 nM). Inverse correlation patterns between HDAC inhibitors and chloroquine forP. falciparumand mefloquine forP. vivaxindicate species-specific susceptibility profiles for HDAC inhibitors. These HDAC inhibitors were also found to be potentex vivoagainstP.vivaxschizont maturation, comparable to that inP. falciparum, suggesting that HDAC inhibitors may be promising candidates for antimalarial therapy in geographical locations where both species are endemic. Further studies optimizing the selectivity andin vivoefficacy of HDAC inhibitors inPlasmodiumspp. and defining drug interaction with common antimalarial compounds are warranted to investigate the role of HDAC inhibitors in antimalarial therapy.
Antialarmin Effect of Tick Saliva during the Transmission of Lyme Disease
Authors: Marchal Claire , Schramm Frederic , Kern Aurélie , Luft Benjamin J. , Yang Xiaohua , Schuijt Tim , Hovius Joppe , Jaulhac Benoît , Boulanger Nathalie 
Published: December 2010

ABSTRACTTick saliva has potent immunomodulatory properties. In arthropod-borne diseases, this effect is largely used by microorganisms to increase their pathogenicity and to evade host immune responses. We show that in Lyme borreliosis, tick salivary gland extract and a tick saliva protein, Salp15, inhibitin vitrokeratinocyte inflammation induced byBorrelia burgdorferisensu stricto or by the major outer surface lipoprotein ofBorrelia, OspC. Chemokines (interleukin-8 [IL-8] and monocyte chemoattractant protein 1 [MCP-1]) and several antimicrobial peptides (defensins, cathelicidin, psoriasin, and RNase 7) were downregulated. Interestingly, antimicrobial peptides (AMPs) transiently inhibited bacterial motility but did not kill the organisms when testedin vitro. We conclude that tick saliva affects the chemotactic properties of chemokines and AMPs on immune cells and has an antialarmin effect on human primary keratinocytes. Alarmins are mediators that mobilize and activate antigen-presenting cells. Inhibition of cutaneous innate immunity and of the migration of immune cells to the site of the tick bite ensures a favorable environment forBorrelia.The bacterium can then multiply locally and, subsequently, disseminate to the target organs, including joints, heart, and the central nervous system.
Complete Genome Sequence of
Mycoplasma bovis
Type Strain PG45 (ATCC 25523)
Authors: Wise Kim S. , Calcutt Michael J. , Foecking Mark F. , Röske Kerstin , Madupu Ramana , Methé Barbara A. 
Published: December 2010

ABSTRACT

This complete and fully assembled genome sequence of
Mycoplasma bovis
type strain PG45 is the first available for this species and offers a framework for comparison with additional pathogenic isolates. The single circular chromosome of 1,003,404 bp reveals multiple gene sets and mechanisms involved in variable expression of surface antigens and the incursion of numerous and assorted mobile elements, despite its reduced size.
Polycyclic aromatic hydrocarbon-induced oxidative stress and lipid peroxidation in relation to immunological alteration
Authors: Jeng Hueiwang Anna , Pan Chih-Hong , Diawara Norou , Chang-Chien Guo-Ping , Lin Wen-Yi , Huang Chia-Tsuan , Ho Chi-Kung , Wu Ming-Tsang 
Published: December 2010

ObjectivesWe evaluated the association between exposure to polycyclic aromatic hydrocarbons (PAHs) and immunological measurements using blood samples from coke oven workers exposed to high and low PAH levels.MethodsA population-based cross-sectional study was conducted from 2008–2009 with coke oven workers and steel-rolling workers as the exposed and control groups, respectively. Questionnaires on basic demographic information were administered. Personal breathing zone and urine samples were collected to quantify personal PAH intake and biological response doses. Immunological and cytokine parameters in serum were analysed. Urinary malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were analysed to determine oxidative stress induced by PAHs in relation to altered humoural immunological status.ResultsMean levels of serum immunoglobulin A (IgA) and TNF-α were significantly increased in coke oven workers compared to steel-rolling workers who had no or minimal PAH exposure (p=0.0033 and p<0.0001, respectively). There were no significant differences in mean levels of IL-4 and IL-10 between coke oven workers and steel-rolling workers. Moderate activation of lipid peroxidation and oxidative damage as determined by plasma MDA and 8-OHdG levels were detected simultaneously with significant alterations in IgA and IgE levels. Multiple regression analyses demonstrated that PAHs with high molecular weights >252 (dibenzo(a,h)anthracene, benzo(a)pyrene, benzo(a)anthracene and/or indeno(1,2,3-cd)pyrene) correlated with IgA and IgE levels.ConclusionsThis study showed that coke oven workers with chronic exposure to PAHs may develop immunological alteration. Oxidative stress and lipid peroxidation induced by PAHs may partly explain the alteration in immunological parameters.
DNA Repair Protein Biomarkers Associated with Time to Recurrence in Triple-Negative Breast Cancer
Authors: Alexander Brian M. , Sprott Kam , Farrow D. Allan , Wang XiaoZhe , D'Andrea Alan D. , Schnitt Stuart J. , Collins Laura C. , Weaver David T. , Garber Judy E. 
Published: December 2010

Abstract
Purpose: To evaluate the prognostic utility of immunohistochemical assessment of key proteins in multiple DNA repair pathways in triple-negative breast cancer (TNBC; estrogen receptor negative, progesterone receptor negative, and HER2/neu negative by immunohistochemistry).
Experimental Design: Archived clinically annotated tumor specimens from 112 women with TNBC were immunostained with antibodies against DNA repair proteins and scored using digital image analysis. The cohort was divided into training and test sets for development of a multiantibody model. Scores were combined with clinical data to assess association with outcome.
Results: Low XPF (P = 0.005), pMK2 (P = 0.01), MLH; P = 0.002), and FANCD2 (P = 0.001) were each associated with shorter time to recurrence (TTR) in univariate analysis. A 4-antibody model could segregate high-risk and low-risk groups on the basis of TTR in both the training (relative risk [RR] = 3.52; P = 9.05E-07) and test (RR 2.67; P = 0.019) cohorts.
Conclusions: DNA repair proteins may be useful as prognostic markers in TNBC. Further study in larger, uniformly treated cohorts with additional clinical parameters is warranted. Clin Cancer Res; 16(23); 5796–804. ©2010 AACR.
Seamless Phase I-II Trial Design for Assessing Toxicity and Efficacy for Targeted Agents
Authors: Hoering Antje , LeBlanc Mike , Crowley John 
Published: December 2010

Abstract
Purpose: The premise for phase I trials for cytostatic agents is different from that of cytotoxic agents. For cytostatic agents, toxicity and efficacy do not necessarily increase monotonically with increasing dose levels, but likely plateau after they reach maximal toxicity or efficacy. Here, we propose a phase I-II trial design to assess both toxicity and efficacy to find the best dose as well as a good dose.
Experimental Design: We propose a 2-step dose-finding trial for assessing both toxicity and efficacy for a targeted agent. The 1st step uses a traditional phase I trial design. This step only assesses toxicity and finds the maximal tolerated dose (MTD). For the 2nd step, we propose a modified phase II selection design for 2 or 3 dose levels at and below the MTD to determine efficacy and evaluate each dose level by both efficacy and toxicity.
Results and Conclusion: Simulation studies are done on several combinations of toxicity and efficacy scenarios to assess the operating statistics of our proposed trial design. We then compare our results with a traditional phase I trial followed by a single-arm phase II trial using the same total sample size. The proposed design does better in most cases than a traditional design using the same overall sample size. This design allows assessing a few dose levels more closely for both efficacy and toxicity and provides greater certainty of having correctly determined the best dose level before launching into a large efficacy trial. Clin Cancer Res; 17(4); 1–7. ©2010 AACR.
Quercetin Induces Tumor-Selective Apoptosis through Downregulation of Mcl-1 and Activation of Bax
Authors: Cheng Senping , Gao Ning , Zhang Zhuo , Chen Gang , Budhraja Amit , Ke Zunji , Son Young-ok , Wang Xin , Luo Jia , Shi Xianglin 
Published: December 2010

AbstractPurpose: To investigate the in vivo antitumor efficacy of quercetin in U937 xenografts and the functional roles of Mcl-1 and Bax in quercetin-induced apoptosis in human leukemia.Experimental Design: Leukemia cells were treated with quercetin, after which apoptosis, Mcl-1 expression, and Bax activation and translocation were evaluated. The efficacy of quercetin as well as Mcl-1 expression and Bax activation were investigated in xenografts of U937 cells.Results: Administration of quercetin caused pronounced apoptosis in both transformed and primary leukemia cells but not in normal blood peripheral mononuclear cells. Quercetin-induced apoptosis was accompanied by Mcl-1 downregulation and Bax conformational change and mitochondrial translocation that triggered cytochrome c release. Knockdown of Bax by siRNA reversed quercetin-induced apoptosis and abrogated the activation of caspase and apoptosis. Ectopic expression of Mcl-1 attenuated quercetin-mediated Bax activation, translocation, and cell death. Conversely, interruption of Mcl-1 by siRNA enhanced Bax activation and translocation, as well as lethality induced by quercetin. However, the absence of Bax had no effect on quercetin-mediated Mcl-1 downregulation. Furthermore, in vivo administration of quercetin attenuated tumor growth in U937 xenografts. The TUNEL-positive apoptotic cells in tumor sections increased in quercetin-treated mice as compared with controls. Mcl-1 downregulation and Bax activation were also observed in xenografts.Conclusions: These data suggest that quercetin may be useful for the treatment of leukemia by preferentially inducing apoptosis in leukemia versus normal hematopoietic cells through a process involving Mcl-1 downregulation, which, in turn, potentiates Bax activation and mitochondrial translocation, culminating in apoptosis. Clin Cancer Res; 16(23); 5679–91. ©2010 AACR.
Differential cytotoxic actions of Shiga toxin 1 and Shiga toxin 2 on microvascular and macrovascular endothelial cells
Authors: Bauwens Andreas , Bielaszewska Martina , Kemper Björn , Langehanenberg Patrik , Bally Gert von , Reichelt Rudolf , Mulac Dennis , Humpf Hans-Ulrich , Friedrich Alexander , Kim Kwang , Karch Helge , Müthing Johannes 
Published: December 2010

SummaryShiga toxin (Stx)-mediated injury to vascular endothelial cells in the kidneys, brain and other organs underlies the pathogenesis of haemolytic uraemic syndrome (HUS) caused by enterohaemorrhagic Escherichia coli (EHEC). We present a direct and comprehensive comparison of cellular injury induced by the two major Stx types, Stx1 and Stx2, in human brain microvascular endothelial cells (HBMECs) and EA.hy 926 macro-vascular endothelial cells. Scanning electron microscopy of microcarrier-based cell cultures, digital holographic microscopy of living single cells, and quantitative apoptosis/necrosis assays demonstrate that Stx1 causes both necrosis and apoptosis, whereas Stx2 induces almost exclusively apoptosis in both cell lines. Moreover, microvascular and macrovascular endothelial cells have different susceptibilities to the toxins: EA.hy 926 cells are slightly, but significantly (~ 10 times) more susceptible to Stx1, whereas HBMECs are strikingly (≥ 1,000 times) more susceptible to Stx2. These findings have implications in the pathogenesis of HUS, and suggest the existence of yet to be delineated Stx type-specific mechanisms of endothelial cell injury beyond inhibition of protein bio-synthesis.
β3Adrenergic Stimulation of the Cardiac Na+-K+Pump by Reversal of an Inhibitory Oxidative Modification
Authors: Bundgaard Henning , Liu Chia-Chi , Garcia Alvaro , Hamilton Elisha J. , Huang Yifei , Chia Karin K.M. , Hunyor Stephen N. , Figtree Gemma A. , Rasmussen Helge H. 
Published: December 2010

Background—Inhibition of L-type Ca2+current contributes to negative inotropy of β3adrenergic receptor (β3AR) activation, but effects on other determinants of excitation-contraction coupling are not known. Of these, the Na+-K+pump is of particular interest because of adverse effects attributed to high cardiac myocyte Na+levels and upregulation of the β3AR in heart failure.Methods and Results—We voltage clamped rabbit ventricular myocytes and identified electrogenic Na+-K+pump current (Ip) as the shift in holding current induced by ouabain. The synthetic β3AR agonists BRL37344 and CL316,243 and the natural agonist norepinephrine increasedIp. Pump stimulation was insensitive to the β1/β2AR antagonist nadolol and the protein kinase A inhibitor H-89 but sensitive to the β3AR antagonist L-748,337. Blockade of nitric oxide synthase abolished pump stimulation and an increase in fluorescence of myocytes loaded with a nitric oxide–sensitive dye. Exposure of myocytes to β3AR agonists decreased β1Na+-K+pump subunit glutathionylation, an oxidative modification that causes pump inhibition. The in vivo relevance of this was indicated by an increase in myocardial β1pump subunit glutathionylation with elimination of β3AR–mediated signaling in β3AR−/−mice. The in vivo effect of BRL37344 on contractility of the nonfailing and failing heart in sheep was consistent with a beneficial effect of Na+-K+pump stimulation in heart failure.Conclusions—The β3AR mediates decreased β1subunit glutathionylation and Na+-K+pump stimulation in the heart. Upregulation of the receptor in heart failure may be a beneficial mechanism that facilitates the export of excess Na+.
High-Order Spectral Filter for the Spherical-Surface Limited Area
Authors: Park Ja-Rin , Cheong Hyeong-Bin , Kang Hyun-Gyu 
Published: December 2010

Abstract
A high-order spectral filter for the spherical-surface limited-area domain, either window or sector type, is presented, where the window domain is finite both in longitude and latitude and the sector domain is finite in longitude, but is ranged from Pole to Pole in latitude. The data given in the physical domain are extended to either extended window or sector domain by padding artificial data that are appropriate for spectral decomposition with half-ranged Fourier series. The high-order filter equation of Laplacian operator type was split into first- or second-order spherical elliptic equations as in the global domain high-order spectral filter. Each low-order elliptic equation is discretized using half-ranged Fourier series both in longitudinal and latitudinal direction. Since the domain is of the spherical geometry, the window domain spectral filter consists of full matrices for each zonal wavenumber and thus performs filtering with O(N3) operation for N × N grids. On the other hand, the sector domain filter performs with efficient O(N2 logN) operation for the same grids, because the matrices can be constructed in tridiagonal form.
The error of the filter was analyzed using the eigenfunctions of the filter equation to get insights on data-extension parameters. The limited-area domain filters were tested with localized analytic function and the midlatitude observed data of meteorological variables, and the results were compared to those of the global domain filter. Accuracies of window and sector domain filters were found almost the same, and they turned out to vary with the filter parameters and the location and size of the domain. Application of the limited domain filters to the tropical cyclone initialization scheme showed very close performances to each other for the track and intensity forecasts.
A General Filter for Stretched-Grid Models: Application in Cartesian Geometry
Authors: Surcel Dorina , Laprise René 
Published: December 2010

Global climate models with variable resolution are effective means to represent regional scales over an area of interest while avoiding the nesting issues of limited-area models. The stretched-grid approach provides a dynamical downscaling approach that naturally allows two-way interactions between the regional and global scales of motion. Concentrating the resolution over a subset of the earth’s surface increases computational efficiency and reduces the computational costs compared to global uniform high-resolution models; however, it does not come free of some problems related to the variation of resolution. To address the issues associated with the stretching and anisotropy of the computational grid, a general convolution filter with a flexible response function is developed. The main feature of this filter is to locally remove scales shorter than a user-prescribed spatially varying length scale. The filtering effectiveness and computational efficiency of the filter can be custom tailored by an appropriate compromise between the filtering response and the width of the convolution stencil. This approach has been tested in one- and two-dimensional Cartesian geometry. It is shown that an effective filter can be obtained using a limited spatial stencil for the convolution to reduce computational cost, and that an adjustable spatially variable and nearly isotropic response can be obtained for application on variable grids.
Classification of rice (Oryza satival. japonica nipponbare) immunophilins (FKBPs, CYPs) and expression patterns under water stress
Authors: Ahn Jun Cheul , Kim Dae-Won , You Young Nim , Seok Min Sook , Park Jeong Mee , Hwang Hyunsik , Kim Beom-Gi , Luan Sheng , Park Hong-Seog , Cho Hye Sun 
Published: December 2010

Abstract

Background
FK506 binding proteins (FKBPs) and cyclophilins (CYPs) are abundant and ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) superfamily, which regulate much of metabolism through a chaperone or an isomerization of proline residues during protein folding. They are collectively referred to as immunophilin (IMM), being present in almost all cellular organs. In particular, a number of IMMs relate to environmental stresses.

Results
FKBP and CYP proteins in rice (Oryza sativa cv. Japonica) were identified and classified, and given the appropriate name for each IMM, considering the ortholog-relation with Arabidopsis and Chlamydomonas or molecular weight of the proteins. 29 FKBP and 27 CYP genes can putatively be identified in rice; among them, a number of genes can be putatively classified as orthologs of Arabidopsis IMMs. However, some genes were novel, did not match with those of Arabidopsis and Chlamydomonas, and several genes were paralogs by genetic duplication. Among 56 IMMs in rice, a significant number are regulated by salt and/or desiccation stress. In addition, their expression levels responding to the water-stress have been analyzed in different tissues, and some subcellular IMMs located by means of tagging with GFP protein.

Conclusion
Like other green photosynthetic organisms such as Arabidopsis (23 FKBPs and 29 CYPs) and Chlamydomonas (23 FKBs and 26 CYNs), rice has the highest number of IMM genes among organisms reported so far, suggesting that the numbers relate closely to photosynthesis. Classification of the putative FKBPs and CYPs in rice provides the information about their evolutional/functional significance when comparisons are drawn with the relatively well studied genera, Arabidopsis and Chlamydomonas. In addition, many of the genes upregulated by water stress offer the possibility of manipulating the stress responses in rice.
High yield expression of leptospirosis vaccine candidates LigA and LipL32 in the methylotrophic yeast Pichia pastoris
Authors: Hartwig Daiane D , Oliveira Thaís L , Seixas Fabiana K , Forster Karine M , Rizzi Caroline , Hartleben Cláudia P , McBride Alan JA , Dellagostin Odir A 
Published: December 2010

Abstract

Background
Leptospirosis, a zoonosis caused by Leptospira spp., is recognized as an emergent infectious disease. Due to the lack of adequate diagnostic tools, vaccines are an attractive intervention strategy. Recombinant proteins produced in Escherichia coli have demonstrated promising results, albeit with variable efficacy. Pichia pastoris is an alternative host with several advantages for the production of recombinant proteins.

Results
The vaccine candidates LigANI and LipL32 were cloned and expressed in P. pastoris as secreted proteins. Large-scale expression resulted in a yield of 276 mg/L for LigANI and 285 mg/L for LipL32. The recombinant proteins were glycosylated and were recognized by antibodies present in the sera of patients with severe leptospirosis.

Conclusions
The expression of LigANI and LipL32 in P. pastoris resulted in a significant increase in yield compared to expression in E. coli. In addition, the proteins were secreted, allowing for easy purification, and retained the antigenic characteristics of the native proteins, demonstrating their potential application as subunit vaccine candidates.
Expression of insulin-like 3 (INSL3) and differential splicing of its receptor in the ovary of rhesus macaques
Authors: Hanna Carol B , Yao Shan , Patta Maristela C , Jensen Jeffrey T , Wu Xuemei 
Published: December 2010

Abstract

Background
Although insulin-like 3 (INSL3) has been identified in the gonad of both sexes in many species, there are only limited reports on the distribution of INSL3 and its receptor, relaxin/insulin-like family peptide receptor 2 (RXFP2), in the primate ovary. Since the hormone-receptor pair is believed to play a role in female reproduction, investigating the transcription of INSL3/RXFP2 genes and the spatiotemporal expression of INSL3 in the nonhuman primate may shed light on the functional aspects of the system in humans.

Methods
Database mining, molecular and immunological methods were applied.

Results
One single INSL3 transcript and three novel splice variant transcripts of RXFP2 were identified in the ovary of rhesus macaques. While the full-length RXFP2 transcript is barely detectable in granulosa cells during the periovulatory period, INSL3 transcript and protein are highly abundant in theca cells surrounding antral follicles. Moreover, the INSL3 level in follicular fluid is 3-4 times higher than that in female serum which remains low throughout the menstrual cycle.

Conclusions
The presence of INSL3 and its receptor in the ovary implies a potential role of the ligand-receptor pair in female reproduction in nonhuman primates. However, the existence of multiple splice variants of RXFP2 indicates a very complex nature of the hormone-receptor system.